Cosmetic Dermatology: Products and Procedures - PDF Free Download (2024)

Cosmetic Dermatology Products and Procedures

Cosmetic Dermatology Products and Procedures E D I T E D BY

Zoe Diana Draelos MD Consulting Professor Department of Dermatology Duke University School of Medicine Durham, North Carolina USA

A John Wiley & Sons, Ltd., Publication

This edition first published 2010 © by Blackwell Publishing Ltd Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical and Medical business to form Wiley-Blackwell. Registered office: John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Editorial offices: 9600 Garsington Road, Oxford, OX4 2DQ, UK The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 111 River Street, Hoboken, NJ 07030-5774, USA For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by physicians for any particular patient. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging-in-Publication Data Cosmetic dermatology : products and procedures / edited by Zoe Diana Draelos. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4051-8635-3 (hardcover : alk. paper) 1. Skin–Care and hygiene. 2. Cosmetics. 3. Dermatology. I. Draelos, Zoe Kececioglu. [DNLM: 1. Cosmetics. 2. Dermatologic Agents. 3. Cosmetic Techniques. 4. Skin Care– methods. QV 60 C8346 2009] RL87.C68 2009 646.7′2–dc22 2009031482 ISBN: 9781405186353 A catalogue record for this book is available from the British Library. Set in 9 on 12 pt Meridien by Toppan Best-set Premedia Limited Printed and bound in Singapore 1



Contributors, viii

Section II Hygiene Products, 75

Foreword, xiv Jeffrey S. Dover

Part One Cleansers, 77

Introduction: Definition of Cosmetic Dermatology, xv Zoe D. Draelos

10 Bar cleansers, 77 Anthony W. Johnson and K.P. Ananthapadmanabhan

Section I Basic Concepts, 1 Part One Skin Physiology Pertinent to Cosmetic Dermatology, 3 1 Epidermal barrier, 3 Sreekumar Pillai, Marc Cornell, and Christian Oresajo 2 Photoaging, 13 Murad Alam and Jillian Havey 3 Self-perceived sensitive skin, 22 Olivier de Lacharrière 4 Pigmentation and skin of color, 27 Chesahna Kindred and Rebat M. Halder 5 Sensitive skin and the somatosensory system, 38 Francis McGlone and David Reilly 6 Novel, compelling non-invasive techniques for evaluating cosmetic products, 47 Thomas J. Stephens, Christian Oresajo, Robert Goodman, Margarita Yatskayer, and Paul Kavanaugh 7 Contact dermatitis and topical agents, 55 David E. Cohen and Aieska de Souza Part Two Delivery of Cosmetic Skin Actives, 62

11 Personal cleansers: body washes, 88 Keith Ertel and Heather Focht 12 Facial cleansers and cleansing cloths, 95 Erik Hasenoehrl 13 Non-foaming and low-foaming cleansers, 102 Duncan Aust 14 Liquid hand cleansers and sanitizers, 106 Duane Charbonneau 15 Shampoos for normal scalp hygiene and dandruff, 115 James R. Schwartz, Marcela Valenzuela, and Sanjeev Midha Part Two Moisturizers, 123 16 Facial moisturizers, 123 Yohini Appa 17 Hand and foot moisturizers, 130 Teresa M. Weber, Andrea M. Schoelermann, Ute Breitenbach, Ulrich Scherdin, and Alexandra Kowcz 18 Sunless tanning products, 139 Angelike Galdi, Peter Foltis, and Christian Oresajo 19 Sunscreens, 144 Dominique Moyal, Angelike Galdi, and Christian Oresajo Part Three Personal Care Products, 150

8 Percutaneous delivery of cosmetic actives to the skin, 62 Marc Cornell, Sreekumar Pillai, and Christian Oresajo

20 Antiperspirants and deodorants, 150 Eric S. Abrutyn

9 Creams, lotions, and ointments, 71 Irwin Palefsky

21 Blade shaving, 156 Keith Ertel and Gillian McFeat



Section III Adornment, 165 Part One Colored Facial Cosmetics, 167

38 Retinoids, 309 Olivier Sorg, Gürkan Kaya, Behrooz Kasraee, and Jean H. Saurat

22 Facial foundation, 167 Sylvie Guichard and Véronique Roulier

39 Topical vitamins, 319 Donald L. Bissett

23 Camouflage techniques, 176 Anne Bouloc

40 Clinical uses of hydroxyacids, 327 Barbara Green, Eugene J. Van Scott, and Ruey Yu

24 Lips and lipsticks, 184 Catherine Heusèle, Hervé Cantin, and Frédéric Bonté

41 The contribution of dietary nutrients and supplements to skin health, 335 Helen Knaggs, Steve Wood, Doug Burke, and Jan Lephart

25 Eye cosmetics, 190 Sarah A. Vickery, Peter Wyatt, and John Gilley Part Two Nail Cosmetics, 197 26 Nail physiology and grooming, 197 Phoebe Rich and Heh Shin R. Kwak 27 Colored nail cosmetics and hardeners, 206 Paul H. Bryson and Sunil J. Sirdesai 28 Cosmetic prostheses as artificial nail enhancements, 215 Douglas Schoon Part Three Hair Cosmetics, 222 29 Hair physiology and grooming, 222 Maria Hordinsky, Ana Paula Avancini Caramori, and Jeff D. Donovan

Part Two Injectable Antiaging Techniques, 342 42 Botulinum toxins, 342 Joel L. Cohen and Scott R. Freeman 43 Hyaluronic acid fillers, 352 Mark S. Nestor 44 Calcium hydroxylapatite for soft tissue augmentation, 356 Stephen Mandy 45 Skin fillers, 361 Neil Sadick, Misbah H. Khan, and Babar K. Rao 46 Polylactic acid fillers, 373 Kenneth R. Beer Part Three Resurfacing Techniques, 377

30 Hair dyes, 227 Frauke Neuser and Harald Schlatter

47 Superficial chemical peels, 377 M. Amanda Jacobs and Randall Roenigk

31 Permanent hair waving, 236 Annette Schwan-Jonczyk and Gerhard Sendelbach

48 Medium depth chemical peels, 384 Gary D. Monheit and Jens J. Thiele

32 Hair straightening, 248 Harold Bryant, Felicia Dixon, Angela Ellington, and Crystal Porter

49 CO2 laser resurfacing: confluent and fractionated, 393 Mitchel P. Goldman

33 Hair styling – technology and formulations, 256 Thomas Krause, Rene Rust, and Dianna C. Kenneally

Section IV Antiaging, 267

50 Non-ablative resurfacing, 409 David J. Goldberg and Katie Rossy 51 Microdermabrasion, 418 Pearl Grimes 52 Dermabrasion, 426 Christopher Harmon and Chad Prather

Part One Cosmeceuticals, 269 34 Botanicals, 269 Carl Thornfeldt 35 Antioxidants and anti-inflammatories, 281 Bryan B. Fuller 36 Peptides and proteins, 292 Karl Lintner 37 Cellular growth factors, 302 Richard E. Fitzpatrick and Rahul C. Mehta


Part Four Skin Modulation Techniques, 432 53 Laser-assisted hair removal, 432 Keyvan Nouri, Voraphol Vejjabhinanta, Nidhi Avashia, and Rawat Charoensawad 54 Radiofrequency devices, 439 Vic Narurkar 55 LED photomodulation for reversal of photoaging and reduction of inflammation, 444 Robert Weiss, Roy Geronemus, David McDaniel, and Corinne Granger

Contents Part Five Skin Contouring Techniques, 450 56 Liposuction: manual, mechanical, and laser assisted, 450 Emily Tierney and C. William Hanke 57 Liposuction of the neck, 463 Kimberly J. Butterwick 58 Hand recontouring with calcium hydroxylapatite, 473 Kenneth L. Edelson Part Six Implementation of Cosmetic Dermatology into Therapeutics, 480

60 Over-the-counter acne treatments, 488 Emmy M. Graber and Diane Thiboutot 61 Rosacea regimens, 495 Joseph Bikowski 62 Eczema regimens, 502 Zoe D. Draelos 63 Psoriasis regimens, 507 Steven R. Feldman and Lindsay C. Strowd Index, 514

59 Antiaging regimens, 480 Karen E. Burke



Eric S. Abrutyn

Donald L. Bissett

MS Founder TPC2 Advisors Ltd. Inc. Chiriqui, Republic of Panama

PhD Beth Jewell-Motz Procter & Gamble Co. Sharon Woods Technical Center Cincinnati, OH, USA

Murad Alam

MD, MSCI Associate Professor of Dermatology and Otolaryngology Chief of Cutaneous and Aesthetic Surgery Department of Dermatology Feinberg School of Medicine Northwestern University Chicago, IL, USA

K.P. Ananthapadmanabhan


Senior Principal Scientist Unilever HPC R&D Trumbull, CT, USA

Yohini Appa

PhD Senior Director of Scientific Affairs, Johnson & Johnson New Brunswick, NJ, USA

Duncan Aust

PhD Senior Vice President of Research and Development DFB Branded Pharmaceuticals Fort Worth, TX, USA

Nidhi Avashia

MD Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami, FL, USA

Kenneth R. Beer

MD, PA Palm Beach Esthetic, Dermatology & Laser Center West Palm Beach, FL, USA and Clinical Voluntary Assistant Professor of Dermatology University of Miami Miami, FL, USA

Frédéric Bonté

PhD Director of Scientific Communication LVMH Recherche Saint Jean de Braye, France

Anne Bouloc

MD, PhD Vichy International Medical Director Cosmetique Active International Asnières, France

Ute Breitenbach


Beiersdorf AG Hamburg, Germany

Harold Bryant

PhD Assistant Vice President L’Oréal Institute for Ethnic Hair and Skin Research Chicago, IL, USA

Paul H. Bryson

PhD Director of Research and Development OPI Products Inc. North Hollywood Los Angeles, CA, USA

Doug Burke

PhD Senior Scientist Phamanex Global Research and Development Provo, UT, USA

Karen E. Burke

MD, PhD Assistant Clinical Professor, Dermatology The Mount Sinai Medical Center Rivercourt New York, NY, USA

Joseph Bikowski

MD, FAAD Clinical Assistant Professor, Dermatology Ohio State University Columbus, OH, USA and Bikowski Skin Care Center Sewickley, PA, USA


Kimberly J. Butterwick

MD Dermatology/Cosmetic Laser Associates of La Jolla, Inc. San Diego, CA, USA


Hervé Cantin

Zoe D. Draelos

LVMH Recherche Saint Jean de Braye, France

Ana Paula Avancini Caramori

MD Department of Dermatology Complexo Hospitalar Santa Casa de Porto Alegre Porto Alegre, Brazil

Duane Charbonneau


Global Microbiology Procter & Gamble Co. Health Sciences Institute Mason, OH, USA

Rawat Charoensawad


Director, Rawat Clinic and Clinical Consultant, Biophile Training Center Bangkok, Thailand

David E. Cohen,

MD, MPH Vice Chairman for Clinical Affairs Director of Allergic, Occupational, and Environmental Dermatology New York University School of Medicine Department of Dermatology New York, NY, USA

Joel L. Cohen

MD About Skin Dermatology Englewood, CO, USA and Department of Dermatology University of Colorado Englewood, CO, USA

Marc Cornell Director L’Oréal Research Clark, NJ, USA

Felicia Dixon

PhD Manager L’Oréal Institute for Ethnic Hair and Skin Research Chicago, IL, USA

Jeff C. Donovan


Division of Dermatology University of Toronto Toronto, Canada

Jeffrey S. Dover

MD, FRCPC, FRCP (Glasgow) Associate Clinical Professor of Dermatology Yale University School of Medicine, Adjunct Professor of Dermatology Dartmouth Medical School, SkinCare Physicians Chestnut Hill, MA, USA

MD Consulting Professor Department of Dermatology Duke University School of Medicine Durham, NC, USA

Kenneth L. Edelson

MD, FAACS Clinical Instructor, Department of Dermatology Mount Sinai School of Medicine Attending Physician, Dermatology, The Mount Sinai Hospital New York, NY, USA and Private Practice Cosmetic, Dermatologic and Laser Surgery New York, NY, USA

Angela Ellington Assistant Vice President L’Oréal Institute for Ethnic Hair and Skin Research Chicago, IL, USA

Keith Ertel

MS, PhD Principal Scientist Procter & Gamble Co. Cincinnati, OH, USA

Steven R. Feldman

MD, PhD Center for Dermatology Research Departments of Dermatology, Pathology, and Public Health Sciences Wake Forest University School of Medicine Winston-Salem, NC, USA

Richard E. Fitzpatrick

MD Founder, Chair, Scientific Advisory Board SkinMedica, Inc. Carlsbad, CA, USA and Associate Clinical Professor Division of Dermatology UCSD School of Medicine San Diego, CA, USA

Heather Focht


Section Head Procter & Gamble Co. Cincinnati, OH, USA

Peter Foltis

MS Director of Scientific Affairs and Skin Care L’Oréal USA Clark, NJ, USA

Scott R. Freeman

MD Dermatology Resident University of Colorado at Denver and Health Sciences Center Denver, CO, USA



Bryan B. Fuller

PhD Founder, CEO Therametics and Adjunct Professor of Biochemistry and Molecular Biology University of Oklahoma Health Sciences Center Oklahoma City, OK, USA

Angelike Galdi


L’Oréal USA Clark, NJ, USA

Pearl Grimes

MD Director Vitiligo and Pigmentation Institute of Southern California Los Angeles, CA, USA and Clinical Professor Division of Dermatology David Geffen School of Medicine University of California–Los Angeles Los Angeles, CA, USA

Sylvie Guichard Roy Geronemus

MD Laser & Skin Surgery Center of New York New York, NY, USA and New York University Medical Center New York, NY, USA

John Gilley Principal Researcher Procter & Gamble Cosmetics Hunt Valley, MD, USA

David J. Goldberg

MD Clinical Professor and Director of Laser Research Department of Dermatology at the Mount Sinai School of Medicine New York, NY, USA and Director, Skin Laser & Surgery Specialists of New York and New Jersey New York, NY, USA

Mitchel P. Goldman

MD Volunteer Clinical Professor of Dermatology/Medicine University of California, San Diego and Dermatology/Cosmetic Dermatology Associates of La Jolla, Inc. San Diego, CA, USA

Robert Goodman Thomas J. Stephens & Associates Inc. Dallas Research Center Carrollton, TX, USA

Emmy M. Graber


SkinCare Physicians Chestnut Hill, MA, USA

Corinne Granger MD Director of Instrumental Cosmetics L’Oréal Research Asnières, France

Make Up Scientific Communication Director L’Oréal Recherche Chevilly-Larue, France

Rebat M. Halder

MD Professor and Chair Department of Dermatology Howard University College of Medicine Washington, DC, USA

C. William Hanke

MD, MPH, FACP Professor of Dermatology University of Iowa Carver College of Medicine Iowa City, IA, USA and Clinical Professor of Otolaryngology-Head and Neck Surgery Indiana University School of Medicine Indianapolis, IN, USA

Christopher Harmon

MD Total Skin and Beauty Dermatology Center Birmingham, AL, USA

Erik Hasenoehrl

PhD Procter & Gamble Co. Ivorydale Technical Center Cincinnati, OH, USA

Jillian Havey Department of Dermatology Feinberg School of Medicine Northwestern University Chicago, IL, USA

Catherine Heusèle LVMH Recherche Saint Jean de Braye, France

Maria Hordinsky Barbara A. Green

RPh, MS VP Clinical Affairs, NeoStrata Company, Inc. Princeton, NJ, USA

MD Professor and Chair Department of Dermatology University of Minnesota Minneapolis, MN, USA

M. Amanda Jacobs Senior Associate Consultant Department of Dermatology Mayo Clinic Rochester, MN, USA




Anthony W. Johnson


Jan Lephart

Director, Skin Clinical Science Unilever HPC R&D Trumbull, CT, USA

Senior Director Nu Skin Global Research & Development Provo, UT, USA

Behrooz Kasraee

Karl Lintner

MD Department of Dermatology Geneva University Hospital Geneva, Switzerland

MSc, PhD Technical Advisor Enterprise Technology/Sederma SAS Le Perray en Yvelines Cedex, France

Paul Kavanaugh

MS Thomas J. Stephens & Associates Inc. Dallas Research Center Carrollton, TX, USA

Gürkan Kaya

MD, PhD Department of Dermatology Geneva University Hospital Geneva, Switzerland

Stephen Mandy

MD Volunteer Professor of Dermatology University of Miami Miami, FL, USA and Private Practice Miami Beach, FL, USA

David McDaniel Dianna C. Kenneally


Principal Scientist Procter & Gamble Co. Mason, OH, USA

Misbah H. Khan

MD Fellow, Procedural Dermatology Northwestern University and Northwestern Memorial Hospital Chicago, IL, USA

Chesahna Kindred

MD Laser Skin & Vein Center of Virginia Virginia Beach, VA, USA and Eastern Virginia Medical School Virginia Beach, VA, USA

Gillian McFeat

PhD Gillette Reading Innovation Centre Procter & Gamble Co. Reading, UK


Clinical Research Fellow Department of Dermatology Howard University College of Medicine Washington, DC, USA

Francis McGlone

PhD Perception and Behaviour Group Unilever Research & Development Wirral, UK

Rahul C. Mehta Helen Knaggs


Vice President Nu Skin Global Research and Development Provo, UT, USA


Senior Scientific Director SkinMedica, Inc. Carlsbad, CA, USA

Sanjeev Midha Alexandra Kowcz


VP, US R&D Beiersdorf Inc. Wilton, CT, USA

PhD Principal Scientist Procter & Gamble Beauty Science Cincinnati, OH, USA

Gary D. Monheit Thomas Krause


Polymer Chemist Wella/Procter & Gamble Service GmbH Upstream Design Styling Darmstadt, Germany

Heh Shin R. Kwak

Dominique Moyal



L’Oréal Recherche Asnières, France

Knott Street Dermatology 301 NW Knott Street Portland, OR, USA

Olivier de Lacharrière

MD Total Skin & Beauty Dermatology Center, PC, and Clinical Associate Professor Departments of Dermatology and Ophthamology University of Alabama at Birmingham Birmingham, AL, USA


L’Oréal Recherche Clichy, France



Vic Narurkar

MD, FAAD Director Bay Area Laser Institute San Francisco, CA, USA and University of California Davis Medical School Sacramento, CA, USA

Babar K. Rao

MD Chair Department of Dermatology University of Medicine and Dentistry New Jersey Robert-Wood Johnson Medical School Somerset, NJ, USA

David Reilly Mark S. Nestor


Director Center for Cosmetic Enhancement Aventura, FL, USA and Voluntary Associate Professor of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami, FL, USA

Frauke Neuser


Principal Scientist Procter & Gamble Technical Centres Ltd Rusham Park, Whitehall Lane Egham Surrey, UK

Keyvan Nouri

MD Professor of Dermatology and Otolaryngology Director of Mohs, Dermatologic and Laser Surgery Director of Surgical Training Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami, FL, USA


One Discover Colworth Park Sharnbrook Bedford, UK

Phoebe Rich

MD Oregon Dermatology and Research Center Portland, OR, USA

Randall Roenigk

MD Robert H. Kieckhefer Professor, Chair Department of Dermatology Mayo Clinic Rochester, MN, USA

Katie Rossy

MD New York Medical College New York, NY, USA

Véronique Roulier Make Up Development Director L’Oréal Recherche Chevilly-Larue, France

Rene Rust

Assistant Vice President L’Oréal USA Clark, NJ, USA

PhD Senior Scientist, Hair and Scalp Care Wella/Procter & Gamble Service GmbH Darmstadt, Germany

Irwin Palefsky

Neil Sadick

Christian Oresajo


CEO Cosmetech Laboratories Inc. Fairfield, NJ, USA

Sreekumar Pillai

PhD Associate Principal Scientist L’Oréal Research Clark, NJ, USA

Crystal Porter

PhD Manager L’Oréal Institute for Ethnic Hair and Skin Research Chicago, IL, USA

Chad Prather

MD Total Skin and Beauty Dermatology Center Birmingham, AL, USA

MD, FAAD, FAACS, FACPh Clinical Professor Weill Cornell Medical College New York, NY, USA and Sadick Dermatology New York, NY, USA

Jean H. Saurat

MD Department of Dermatology Geneva University Hospital Geneva, Switzerland

Ulrich Scherdin


Beiersdorf AG Hamburg, Germany

Andrea M. Schoelermann


Beiersdorf AG Hamburg, Germany

Harald Schlatter

PhD Principal Toxicologist Procter & Gamble German Innovation Centre Darmstadt, Germany



Douglas Schoon

Emily Tierney

Schoon Scientific and Regulatory Consulting, LLC Dana Point, CA, USA

Annette Schwan-Jonczyk


Wella/Procter & Gamble Service GmbH Global Hair Methods Darmstadt, Germany

James R. Schwartz


Research Fellow Procter & Gamble Beauty Science Cincinnati, OH, USA

Gerhard Sendelbach

PhD Wella/Procter & Gamble Service GmbH Global Hair Methods Darmstadt, Germany

PhD Mohr Surgery and Procedural Dermatology Fellow Laser and Skin Surgery Center of Indiana Carmel, IN, USA and Department of Dermatology Boston University School of Medicine Boston, MA, USA

Marcela Valenzuela

PhD Senior Scientist Procter & Gamble Beauty Science Cincinnati, OH, USA

Eugene J. Van Scott


Private Practice Abington, PA, USA

Voraphol Vejjabhinanta Sunil J. Sirdesai

PhD Co-Director of Research and Development OPI Products Inc. North Hollywood Los Angeles, CA, USA

Olivier Sorg

PhD Department of Dermatology Geneva University Hospital Geneva, Switzerland

Aieska de Souza

MD, MSc New York University School of Medicine Department of Dermatology New York, NY, USA

Thomas J. Stephens

PhD Thomas J. Stephens & Associates Inc. Dallas Research Center Carrollton, TX, USA

Lindsay C. Strowd

MD Center for Dermatology Research Department of Dermatology Wake Forest University School of Medicine Medical Center Boulevard Winston-Salem, NC, USA

Diane Thiboutot

MD Pennsylvania State University College of Medicine Milton S. Hershey Medical Center Hershey, PA, USA

Jens J. Thiele

MD, PhD Dermatology Specialist, Inc. Oceanside, CA, USA

Carl Thornfeldt CTDerm, PC Fruitland, ID, USA and Episciences, Inc. Boise, ID, USA

MD Clinical instructor Suphannahong Dermatology Institute Bangkok, Thailand and Mohs, Dermatologic and Laser Surgery Fellow Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami, FL, USA

Sarah A. Vickery

PhD Principal Scientist Procter & Gamble Cosmetics Hunt Valley, MD, USA

Teresa M. Weber

PhD Director, Clinical and Scientific Affairs Beiersdorf Inc. Wilton, CT, USA

Robert Weiss

MD Maryland Laser Skin & Vein Institute Hunt Valley, MD, USA and Johns Hopkins University School of Medicine Baltimore, MD, USA

Steve Wood

PhD Director Phamanex Global Research and Development Provo, UT, USA

Peter Wyatt Senior Engineer Procter & Gamble Cosmetics Hunt Valley, MD, USA

Margarita Yatskayer


L’Oréal Research USA Clark, NJ, USA


Ruey J. Yu

PhD, OMD Private Practice Chalfont, PA, USA



Dermatology began as a medical specialty but over the last half century it has evolved to combine medical and surgical aspects of skin care. Mohs skin cancer surgery was the catalyst that propelled dermatology to become a more procedurally based specialty. The combination of an aging population, economic prosperity, and technological breakthroughs have revolutionized cosmetic aspects of dermatology in the past few years. Recent minimally invasive approaches have enhanced our ability to prevent and reverse the signs of photoaging in our patients. Dermatologists have pioneered medications, technologies, and devices in the burgeoning field of cosmetic surgery. Cutaneous lasers, light, and energy sources, the use of botulinum exotoxin, soft tissue augmentation, minimally invasive leg vein treatments, chemical peels, hair transplants, and dilute anesthesia liposuction have all been either developed or improved by dermatologists. Many scientific papers, reviews and textbooks have been published to help disseminate this new knowledge. Recently it has become abundantly clear that unless photoaging is treated with effective skin care and photoprotection, cosmetic surgical procedures will not have their optimal outcome. Cosmeceuticals are integral to this process but, while some rigorous studies exist, much of the knowledge surrounding cosmeceuticals is hearsay and non-data based marketing information. Given increasing requests by our patients for guidance on the use of cosmeceuticals, understanding this body of information is essential to the practicing dermatologist. In Cosmetic Dermatology: Products and Procedures, Zoe Draelos has compiled a truly comprehensive book that addresses the broad nature of the subspecialty. Unlike prior texts on the


subject she has included all the essential topics of skin health. The concept is one that has been long awaited and will be embraced by our dermatologic colleagues and other health care professionals who participate in the diagnosis, and treatment of the skin. No one is better suited to edit a textbook of this scope than Dr. Zoe Draelos. She is an international authority on Cosmetic Dermatology and she has been instrumental in advancing the field of cosmeceuticals by her extensive research, writing, and teachings. This text brings together experts from industry, manufacturing, research, and dermatology and highlights the best from each of these fields. Doctor Draelos has divided the book into four different segments. The book opens with Basic Concepts, which includes physiology pertinent to cosmetic dermatology, and delivery of cosmetic skin actives. This section is followed by Hygiene Products, which include cleansers, moisturizers, and personal care products. The section on Adornment includes colored facial products, nail cosmetics, and hair cosmetics. The book concludes with a section on Antiaging, which includes cosmeceuticals, injectable antiaging techniques, resurfacing techniques, and skin modulation techniques. You will enjoy dipping into individual chapters or sections depending on your desires, but a full read of the book from start to finish will no doubt enhance your knowledge base and prepare you for the full spectrum of cosmetic dermatology patients. Enjoy. Jeffrey S. Dover August 2009

Introduction: Definition of Cosmetic Dermatology

This text is intended to function as a compendium on the field of cosmetic dermatology. Cosmetic dermatology knowledge draws on the insight of the bench researcher, the innovation of the manufacturer, the formulation expertise of the cosmetic chemist, the art of the dermatologic surgeon, and the experience of the clinical dermatologist. These knowledge bases heretofore have been presented in separate textbooks written for specific audiences. This approach to information archival does not provide for the synthesis of knowledge required to advance the science of cosmetic dermatology. The book begins with a discussion of basic concepts relating to skin physiology. The areas of skin physiology that are relevant to cosmetic dermatology include skin barrier, photoaging, sensitive skin, pigmentation issues, and sensory perceptions. All cosmetic products impact the skin barrier, it is to be hoped in a positive manner, to improve skin health. Failure of the skin to function optimally results in photoaging, sensitive skin, and pigmentation abnormalities. Damage to the skin is ultimately perceived as sensory anomalies. Skin damage can be accelerated by products that induce contact dermatitis. While the dermatologist can assess skin health visually, non-invasive methods are valuable to confirm observations or to detect slight changes in skin health that are imperceptible to the human eye. An important part of cosmetic dermatology products is the manner in which they are presented to the skin surface. Delivery systems are key to product efficacy and include creams, ointments, aerosols, powders, and nanoparticles. Once delivered to the skin surface, those substances designed to modify the skin must penetrate with aid of penetration enhancers to ensure percutaneous delivery. The most useful manner to evaluate products used in cosmetic dermatology is by category. The book is organized by product, based on the order in which they are used as part of a daily routine. The first daily activity is cleansing to ensure proper hygiene. A variety of cleansers are available to maintain the biofilm to include bars, liquids, nonfoaming, and antibacterial varieties. They can be applied with the hands or with the aid of an implement. Specialized products to cleanse the hair are shampoos, which may be useful in prevention of scalp disease. Following cleansing, the next step is typically moisturization. There are unique moisturizers for the face, hands, and feet. Extensions of moisturizers that contain other active

ingredients include sunscreens. Other products with a unique hygiene purpose include antiperspirants and shaving products. This completes the list of major products used to hygiene and skincare purposes. The book then turns to colored products for adorning the body. These include colored facial cosmetics, namely facial foundations, lipsticks, and eye cosmetics. It is the artistic use of these cosmetics that can provide camouflaging for skin abnormalities of contour and color. Adornment can also be applied to the nails, in the forms of nail cosmetics and prostheses, and to the hair, in the form of hair dyes, permanent waves, and hair straightening. From adornment, the book addresses the burgeoning category of cosmeceuticals. Cosmeceuticals can be divided into the broad categories of botanicals, antioxidants, antiinflammatories, peptides and proteins, cellular growth factors, retinoids, exfoliants, and nutraceuticals. These agents aim to improve the appearance of aging skin through topical applications, but injectable products for rejuvenation are an equally important category in cosmetic dermatology. Injectables can be categorized as neurotoxins and fillers (hyaluronic acid, hydroxyapatite, collagen, and polylactic acid). Finally, the surgical area of cosmetic dermatology must be address in terms of resurfacing techniques, skin modulation techniques, and skin contouring techniques. Resurfacing can be accomplished chemically with superficial and medium depth chemical peels or physically with microdermabrasion and dermabrasion. The newest area of resurfacing involves the use of lasers, both ablative and non-ablative. Other rejuvenative devices than collagen and pigmentation include intense pulsed light, radiofrequency, and diodes. These techniques can be combined with liposuction of the body and face to recontour the adipose tissue underlying the skin. The book closes with a discussion of how cosmetic dermatology can be implemented as part of a treatment regimen for aging skin, acne, rosacea, psoriasis, and eczema. In order to allow effective synthesis of the wide range of information included in this text, each chapter has been organized with a template to create a standardized presentation. The chapters open with basic concepts pertinent to each area. From these key points, the authors have developed their information to define the topic, discuss unique attributes, advantages and disadvantages, and indications.


Introduction It is my hope that this book will provide a standard textbook for the broad field of cosmetic dermatology. In the past, cosmetic dermatology has been considered a medical and surgical afterthought in dermatology residency programs and continuing medical education sessions. Perhaps this was in part because of the lack of a textbook defining the knowl-


edge base. This is no longer the case. Cosmetic dermatology has become a field unto itself. Zoe D. Draelos May 2009

Section I Basic Concepts

Part 1: Skin Physiology Pertinent to Cosmetic Dermatology Chapter 1: Epidermal barrier Sreekumar Pillai, Marc Cornell, and Christian Oresajo L’Oréal Research, Clark, NJ, USA

BAS I C CONCEPTS • The outer surface of the skin, the epidermis, along with its outermost layer, the stratum corneum, forms the epidermal barrier. • The stratum corneum is a structurally heterogeneous tissue composed of non-nucleated, flat, protein-enriched corneocytes and lipid-enriched intercellular domains. • The roles of the skin barrier include preventing microbes from entering the skin, protecting from environmental toxins, maintaining skin hydration, and diffusing oxidative stress. • Delivery technologies such as lipid systems, nanoparticles, microcapsules, polymers, and films can improve the barrier properties of the skin.

Introduction Skin is the interface between the body and the environment. There are three major compartments of the skin: the epidermis, the dermis, and the hypodermis. Epidermis is the outermost structure and it is a multilayered, epithelial tissue divided into several layers. The outermost structure of the epidermis is the stratum corneum (SC) which forms the epidermal permeability barrier that prevents the loss of water and electrolytes. Other protective or barrier roles for the epidermis include: immune defense, UV protection, and protection from oxidative damage. Changes in the epidermal barrier caused by environmental factors, age, or other conditions can alter the appearance as well as the functions of the skin. Understanding the structure and function of the SC and the epidermal barrier is vital because it is the key to healthy skin and its associated social ramifications.

Structural components of the epidermal barrier The outer surface of the skin, the epidermis, mostly consists of epidermal cells, known as keratinocytes, which are arranged in several stratified layers – the basal cell layer, the

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

spinous cell layer and the granular cell layer – whose differentiation eventually produces the SC. Unlike other layers, the SC is made of anucleated cells called corneocytes which are derived from keratinocytes. The SC forms the major protective barrier of the skin, the epidermal permeability barrier. Figure 1.1 shows the different layers of the epidermis and the components that form the epidermal barrier. The SC is a structurally heterogeneous tissue composed of non-nucleated, flat, protein-enriched corneocytes and lipidenriched intercellular domains [1]. The lipids for barrier function are synthesized in the keratinocytes of the nucleated epidermal layers, stored in the lamellar bodies, and extruded into the intercellular spaces during the transition from the stratum granulosum to the SC forming a system of continuous membrane bilayers [1,2]. In addition to the lipids, other components such as melanins, proteins of the SC and epidermis, free amino acids and other small molecules also have important roles in the protective barrier of the skin. A list of the different structural as well as functional components of the SC is shown in Table 1.1.

Corneocytes Corneocytes are formed by the terminal differentiation of the keratinocytes from the granular layer of the epidermis. The epidermis is comprised of 70% water, as are most tissues, yet the SC is comprised of only 15% water. Alongside this change in water content the keratinocyte nuclei and virtually all the subcellular organelles begin to disappear in the granular cell layer leaving a proteineous core containing keratins, other structural proteins, free amino acids and amino acid



Skin Physiology

Keratohyalin and lamellar granules of the stratum granulosum

Stratum corneum Stratum granulosum

Desmosomes Stratum spinosum

Melanocyte Langerhans cell

Stratum basale

Dermis Figure 1.1 Diagram of the epidermis indicating the different layers of the epidermis and other structural components of the epidermal barrier.

Table 1.1 Structural and functional components of the stratum corneum. Components





Topmost layer of epidermis


Resiliency of SC

Outer surface of the SC

Cornified envelope precursor proteins

Structural proteins that are cross-linked to form CE

Outer surface of SC


Permeability barrier of skin

Granular cells of epidermis

SC interfacial lipids

Permeability barrier of skin

Lipid bilayers between SC

Lipid–protein cross-links

Scaffold for corneocytes

Between SC and lipid bi-layers

Desmosomes and corneodesmosomes

Intercellular adhesion and provide shear resistance

Between keratinocytes and corneocytes

Keratohyalin granules

Formation of keratin “bundles” and NMF precursor proteins

Stratum granulosum


Water holding capacity of SC

Within SC

pH and calcium gradients

Provides differentiation signals and LG secretion signals

All through epidermis

Specialized enzymes (lipases, glycosidases, proteases)

Processing and maturation of SC lipids, desquamation

Within LG and all through epidermis

Melanin granules and “dust”

UV protection of skin

Produced by melanocytes of basal layer, melanin “dust” in SC

CE, cornified envelope; LG, lamellar granules; NMF, natural moisturizing factor; SC, stratum corneum.


1. Epidermal barrier derivatives, and melanin particles which persist throughout the SC. From an oval or polyhedral shape of the viable cells in the spinous layers, the keratinocyte starts to flatten off in the granular cell layer and then assumes a spindle shape and finally becomes a flat corneocyte. The corneocyte itself develops a tough, chemically resistant protein band at the periphery of the cell, called the cornified cell envelope, formed from cross-linked cytoskeletal proteins [3].

teins. The molecular structure of these components suggests that the glutamine and serine residues of CE envelope proteins such as loricrin and involucrin are covalently linked to the omega hydroxyl ceramides [8]. In addition, other free fatty acids (FFA) and ceramides (Cer), may also form protein cross-links on the extracellular side of the CE, providing the scaffold for the corneocytes to the lipid membrane of the SC.

Proteins of the cornified envelope

Desmosomes and corneodesmosomes

The cornified envelope (CE) contains highly cross-linked proteins formed from special precursor proteins synthesized in the granular cell layer, particularly involucrin, loricrin, and cornifin. In addition to these major protein components, several other minor unique proteins are also cross-linked to the cornified envelope. These include proteins with specific functions such as calcium binding proteins, antimicrobial and immune functional proteins, proteins that provide structural integrity to SC by binding to lipids and desmosomes, and protease inhibitors. The cross-linking is promoted by the enzyme transglutaminase which is detectable histochemically in the granular cell layer and lower segments of the stratum corneum. The γ-glutamyl link that results from transglutaminase activity is extremely chemically resistant and this provides the cohesivity and resiliency to the SC.

Desmosomes are specialized cell structures that provide cell– cell adhesion (Figure 1.1). They help to resist shearing forces and are present in simple and stratified squamous epithelia as in human epidermis. Desmosomes are molecular complexes of cell adhesion proteins and linking proteins that attach the cell surface adhesion proteins to intracellular keratin cytoskeletal filaments proteins. Some of the specialized proteins present in desmosomes are cadherins, calcium binding proteins, desmogleins, and desmocollins. Cross-linking of other additional proteins such as envoplakins and periplakins further stabilizes desmosomes. Corneodesmosomes are remnants of the desmosomal structures that provide the attachment sites between corneocytes and cohesiveness for the corneocytes in the SC. Corneodesmosomes have to be degraded by specialized proteases and glycosidases, mainly serine proteases, for the skin to shed in a process called desquamation [9].

Lamellar granules and inter-corneocyte lipids Lamellar granules or bodies (LG or LB) are specialized lipidcarrying vesicles formed in suprabasal keratinocytes, destined for delivery of the lipids in the interface between the corneocytes. These lipids form the essential component of the epidermal permeability barrier and provide the “mortar” into which the corneocyte “bricks” are laid for the permeability barrier formation. When the granular keratinocytes mature to the SC, specific enzymes within the LB process the lipids, releasing the non-polar epidermal permeability barrier lipids, namely, cholesterol, free fatty acids and ceramides, from their polar precursors – phospholipids, glucosyl ceramides, and cholesteryl sulfate, respectively. These enzymes include: lipases, phospholipases, sphingomyelinases, glucosyl ceramidases, and sterol sulfatases [4,5]. The lipids fuse together in the SC to form a continuous bi-layer. It is these lipids, along with the corneocytes, that constitute the bulk of the water barrier property of the SC [6,7].

Keratohyalin granules Keratohyalin granules are irregularly shaped granules present in the granular cells of the epidermis, thus providing these cells their granular appearance (Figure 1.1). These organelles contains abundant amount of keratins “bundled” together by a variety of other proteins, most important of which is filaggrin (filament aggregating protein). An important role of this protein, in addition to bundling of the major structural protein, keratin of the epidermis, is to provide the natural moisturizing factor (NMF) for the SC. Filaggrin contains all the amino acids that are present in the NMF. Filaggrin, under appropriate conditions, is dephosphorylated and proteolytically digested during the process when granular cells mature into corneocytes. The amino acids from filaggrin are further converted to the NMF components by enzymatic processing and are retained inside the corneocytes as components of NMF [4,9].

Lipid–protein cross-links at the cornified envelope LG are enriched in a specific lipid unique to the keratinizing epithelia such as the human epidermis. This lipid (a ceramide) has a very long chain omega-hydroxy fatty acid moiety with linoleic acid linked to the omega hydroxyl group in ester form. This lipid is processed within the SC to release the omega hydroxyl ceramide that becomes crosslinked to the amino groups of the cornified envelope pro-

Functions of epidermal barrier Water evaporation barrier (epidermal permeability barrier) Perhaps the most studied and the most important function of the SC is the formation of the epidermal permeability barrier [1,4,10]. The SC limits the transcutaneous movement



Skin Physiology

of water and electrolytes, a function that is essential for terrestrial survival. Lipids, particularly ceramides, cholesterol, and FFA, together form lamellar membranes in the extracellular spaces of the SC which limit the loss of water and electrolytes. Corneocytes are embedded in this lipid-enriched matrix, and the cornified envelope, which surrounds corneocytes, provides a scaffold necessary for the organization of the lamellar membranes. Extensive research, mainly by Peter Elias’ group has elucidated the structure, properties, and the regulation of the skin barrier by integrated mechanisms [5,7,11]. Barrier disruption triggers a cascade of biochemical processes leading to rapid repair of the epidermal barrier. These steps include increased keratinocyte proliferation and differentiation, increased production of corneocytes, and production, processing, and secretion of barrier lipids, ultimately leading to the repair of the epidermal permeability barrier. These events are described in more detail in the barrier homeostasis section below. A list of the different functions of human epidermis is shown in Table 1.2.

Mechanical barrier Cornified envelope provides mechanical strength and rigidity to the epidermis, thereby protecting the host from injury. Specialized protein precursors and their modified amino acid cross-links provide the mechanical strength to the SC. One such protein, trichohyalin, is a multifunctional crossbridging protein that forms intra- and inter-protein crosslinks between cell envelope structure and cytoplasmic keratin filament network [12]. Special enzymes called trans-

Table 1.2 Barrier functions of the epidermis. Function

Localization/components involved

Water and electrolyte permeability barrier

SC/corneocyte proteins and extracellular lipids

Mechanical barrier

SC/corneocytes, cornified envelope

Microbial barrier/immune function

SC/lipid components/viable epidermis



Protection from environmental toxins/drugs

SC/corneocytes, cornified envelope


SC, epidermis/proteases and glycosidases

UV barrier

SC/melanins of SC/epidermis

Oxidative stress barrier

SC, epidermis/antioxidants

NMF, natural moisturizing factor; SC, stratum corneum.


glutaminases, some present exclusively in the epidermis (transglutaminase 3), catalyze this cross-linking reaction. In addition, adjacent corneocytes are linked by corneodesmosomes, and many of the lipids of the SC barrier are also chemically cross-linked to the cornified envelope. All these chemical links provide the mechanical strength and rigidity to the SC.

Antimicrobial barrier and immune protection The epidermal barrier acts as a physical barrier to pathogenic organisms that attempt to penetrate the skin from the outside environment. Secretions such as sebum and sweat and their acid pH provide antimicrobial properties to skin. Innate immune function of keratinocytes and other immune cells of the epidermis such as Langerhans cells and phagocytes provide additional immune protection in skin. Epidermis also generates a spectrum of antimicrobial lipids, peptides, nucleic acids, proteases, and chemical signals that together forms the antimicrobial barrier (Table 1.3). The antimicrobial peptides are comprised of highly conserved, small, cysteine rich, cationic proteins that are expressed in large amounts in skin. Desquamation, which causes the outward movement of corneocytes and their sloughing off at the surface, also serves as a built-in mechanism inhibiting pathogens from colonizing the skin.

NMF and skin hydration and moisturization NMF is a collection of water-soluble compounds that are found in the stratum corneum (Table 1.4). These compounds compose approximately 20–30% of the dry weight of the

Table 1.3 Antimicrobial components of epidermis and stratum corneum. Component

Class of compound


Free fatty acids


Stratum corneum

Glucosyl ceramides


Stratum corneum



Stratum corneum



Stratum corneum










RNAse 7

Nucleic acid


Low pH


Stratum corneum

“Toll-like” receptors

Protein signaling molecules




Stratum corneum and epidermis

1. Epidermal barrier

Table 1.4 Approximate composition of skin natural moisturizing factor. Components

Percentage levels

Amino acids and their salts (over a dozen)


Pyrrolidine carboxylic acid sodium salt, urocanic acid, ornithine, citruline (derived from filaggrin hydrolysis products)






Glucosamine, creatinine, ammonia, uric acid


Cations (sodium, calcium, potassium) Anions (phosphates, chlorides)

10–11 6–7



Citrate, formate


corneocyte. Many of the components of NMF are derived from the hydrolysis of filaggrin, a histidine- and glutaminerich basic protein of the keratohyalin granule. The SC hydration level controls the protease that hydrolyzes filaggrin and histidase that converts histidine to urocanic acid. As NMF is water soluble and can easily be washed away from the SC, the lipid layer surrounding the corneocyte helps seal the corneocyte to prevent loss of NMF. In addition to preventing water loss from the organism, the SC also acts to provide hydration and moisturization to skin. NMF components absorb and hold water allowing the outermost layers of the SC to stay hydrated despite exposure to the harsh external environment. Glycerol, a major component of the NMF, is an important humectant present in skin which contributes skin hydration. Glycerol is produced locally within the SC by the hydrolysis of triglycerides by lipases, but also taken up into the epidermis from the circulation by specific receptors present in the epidermis called aquaporins [13]. Other humectants in the NMF include urea, sodium and potassium lactates, and pyrrolidine carboxylic acid (PCA) [9].

Protection from environmental toxins and topical drug penetration The SC also has the important task of preventing toxic substances and topically applied drugs from penetrating the skin. The SC acts as a protective wrap because of the highly resilient and cross-linked protein coat of the corneocytes and the lipid-enriched intercellular domains. Pharmacologists and topical or “transdermal” drug developers are interested in increasing SC permeation of drugs into the skin. The multiple route(s) of penetration of drugs into the skin can be via hair follicles, interfollicular sites, or by penetration

through corneocytes and lipid bilayer membranes of the SC [10]. The molecular weight, solubility, and molecular configuration of the toxins and drugs greatly influence the rate of penetration. Different chemical compounds adopt different pathways for skin penetration.

Desquamation and the role of proteolytic enzymes The process by which individual corneocytes are sloughed off from the top of the SC is called desquamation. Normal desquamation is required to maintain the homeostasis of the epidermis. Corneocyte to corneocyte cohesion is controlled by the intercellular lipids as well as the corneodesmosomes that bind the corneocytes together. The presence of specialized proteolytic enzymes and glycosidases in the SC help in cleavage of desmosomal bonds resulting in release of corneocytes [9]. In addition, the SC also contains protease inhibitors that keep these proteases in check and the balance of protease–protease inhibitors have a regulatory role in the control of the desquamatory process. The desquamatory process is also highly regulated by the epidermal barrier function. The SC contains three families of proteases (serine, cysteine, and aspartate proteases), including the epidermalspecific serine proteases (SP), kallikrein-5 (SC tryptic enzyme [SCTE]), and kallikrein-7 (SC chymotryptic enzyme), as well as at least two cysteine proteases, including the SC thiol protease (SCTP), and at least one aspartate protease, cathepsin D. All these proteases have specific roles in the desquamatory process at different layers of the epidermis.

Melanin and the UV barrier Although melanin is not typically considered a functional component of the epidermal barrier, its role in the protection of the skin from UV radiation is indisputable. Melanins are formed in specialized dendritic cells called melanocytes in the basal layers of the epidermis. The melanin produced is transferred into keratinocytes in the basal and spinous layers. There are two types of melanins, depending on the composition and the color. The darker eumelanin is most protective to UV than the lighter, high sulfur-containing pheomelanin. The keratinocytes carry the melanins through the granular layer and into the SC layer of the epidermis. The melanin “dust” present in the SC is structurally different from the organized melanin granules found in the viable deeper layers of the epidermis. The content and composition of melanins also change in SC depending on sun exposure and skin type of the individual. Solar UV radiation is very damaging to proteins, lipids, and nucleic acids and causes oxidative damage to these macromolecules. The SC absorbs some UV energy but it is the melanin particles inside the corneocytes that provide the most protection. Darker skin (higher eumelanin content) is significantly more resistant to the damaging effects of UV on DNA than lighter skin. In addition, UV-induced apoptosis



Skin Physiology

(cell death that results in removal of damaged cells) is significantly greater in darker skin. This combination of decreased DNA damage and more efficient removal of UVdamaged cells plays a critical part in the decreased photocarcinogenesis seen in individuals with darker skin [14]. In addition to melanin, trans-urocanic acid (tUCA), a product of histidine deamination produced in the SC, also acts as an endogenous sunscreen and protects skin from UV damage.

a controlled manner by degradation of desmosomal constituent proteins by the SC proteases. The protease activities are under the control of protease inhibitors which are colocalized with the proteases within the SC. In addition, the activation cascade of the SC proteases is also controlled by the barrier requirement. Lipids and lipid precursors such as cholesterol sulfate also regulate desquamation by controlling the activities of the SC proteases [21].

Corneocyte maturation Oxidative stress barrier The SC has been recognized as the main cutaneous oxidation target of UV and other atmospheric oxidants such as pollutants and cigarette smoke. UVA radiation, in addition to damaging the DNA of fibroblasts, also indirectly causes oxidative stress damage of epidermal keratinocytes. The oxidation of lipids and carbonylation of proteins of the SC lead to disruption of epidermal barrier and poor skin condition [15]. In addition to its effects on SC, UV also initiates and activates a complex cascade of biochemical reactions within the epidermis, causing depletion of cellular antioxidants and antioxidant enzymes such as superoxide dismutase (SOD) and catalase. Acute and chronic exposure to UV has been associated with depletion of SOD and catalase in the skin of hairless mice [16]. This lack of antioxidant protection further causes DNA damage, formation of thymine dimers, activation of proinflammatory cytokines and neuroendocrine mediators, leading to inflammation and free radical generation [17]. Skin naturally uses antioxidants to protect itself from photodamage. UV depletes antioxidants from outer SC. A gradient in the antioxidant levels (alfa-tocopherol, vitamin C, glutathione, and urate) with the lowest concentrations in the outer layers and a steep increase in the deeper layers of the SC protects it from oxidative stress [18]. Depletion of antioxidant protection leads to UV-induced barrier abnormalities. Topical application of antioxidants would support these physiologic mechanisms and restore a healthy skin barrier [19,20].

Regulation of barrier homeostasis The epidermal barrier is constantly challenged by environmental and physiologic factors. Because a fully functional epidermal barrier is required for terrestrial life to exist, barrier homeostasis is tightly regulated by a variety of mechanisms.

Desquamation Integral components of the barrier, corneocytes, and the intercellular lipid bilayers are constantly synthesized and secreted by the keratinocytes during the process of terminal differentiation. The continuous renewal process is balanced by desquamation which removes individual corneocytes in


Terminal differentiation of keratinocytes to mature corneocytes is controlled by calcium, hormonal factors, and by desquamation. High calcium levels in the outer nucleated layers of epidermis stimulate specific protein synthesis and activate the enzymes that induce the formation of corneocytes. A variety of hormones and cytokines control keratinocyte terminal differentiation, thereby regulating barrier formation. Many of the regulators of these hormones are lipids or lipid intermediates which are synthesized by the epidermal keratinocytes for the barrier function, thereby exerting control of barrier homeostasis by affecting the corneocyte maturation. For example, the activators and/or ligands for the nuclear hormone receptors (e.g. peroxisome proliferation activator receptor [PPAR] and vitamin D receptor) that influence keratinocyte terminal differentiation are endogenous lipids synthesized by keratinocytes.

Lipid synthesis Epidermal lipids, the integral components of the permeability barrier, are synthesized and secreted by the keratinocytes in the stratum granulosum after processing and packaging into the LB. Epidermis is a very active site of lipid synthesis under basal conditions and especially under conditions when the barrier is disrupted. Epidermis synthesizes ceramides, cholesterol, and FFA (a major component of phospholipids and ceramides). These three lipid classes are required in equimolar distribution for proper barrier function. The synthesis, processing, and secretion of these lipid classes are under strict control by the permeability barrier requirements. For example, under conditions of barrier disruption, rapid and immediate secretion by already packaged LB occurs as well as transcriptional and translational increases in key enzymes required for new synthesis of these lipids to take place. In addition, many of the hormonal regulators of corneocyte maturation are lipids or lipid intermediates synthesized by the epidermis. SC lipid synthesis and lipid content are also altered with various skin conditions such as inflammation and winter xerosis [22,23].

Environmental and physiologic factors Barrier homeostasis is under control of environmental factors such as humidity variations. High humidity (increased

1. Epidermal barrier SC hydration) downregulates barrier competence (as assessed by barrier recovery after disruption) whereas low humidity enhances barrier homeostasis. Physiologic factors can also have influence on barrier function. High stress (chronic as well as acute) increases corticosteroid levels and causes disruption of barrier homeostasis. Conditions that cause skin inflammation can stimulate the secretion of inflammatory cytokines such as interleukins, induce epidermal hyperplasia, cause impaired differentiation, and disrupt epidermal barrier functions.

Hormones Barrier homeostasis and SC integrity, lipid synthesis is all under the control of different hormones, cytokines, and calcium. Nuclear hormone receptors for both well-known ligands, such as thyroid hormones, retinoic acid, and vitamin D, and “liporeceptors” whose ligands are endogenous lipids control barrier homeostasis. These liporeceptors include peroxisome proliferator activator receptor (PPAR alfa, beta, and gamma) and liver X receptor (LXR). The activators for these receptors are endogenous lipids and lipid intermediates or metabolites such as certain FFA, leukotrienes, prostanoids, and oxygenated sterols. These hormones, mediated by their receptors, control barrier at the level of epidermal cell maturation (corneocyte formation), transcriptional regulation of terminal differentiation proteins and enzymes required for lipid processing, lipid transport, and secretion into LB [5].

pH and calcium Outermost SC pH is maintained in the acidic range, typically in the range 4.5–5.0, by a variety of different mechanisms. This acidity is maintained by formation of FFA from phospholipids; sodium proton exchangers in the SC and by the conversion of histidine of the NMF to urocanic acid by histidase enzyme in the SC. In addition, lactic acid, a major component of the NMF, has a major role in maintaining the acid pH of the SC. Maintenance of an acidic pH in the SC is important for the integrity and cohesion of the SC as well as the maintenance of the normal skin microflora. The growth of normal skin microflora is supported by acidic pH while a more neutral pH supports pathogenic microbes’ invasion of the skin. This acidic pH is optimal for processing of precursor lipids to mature barrier forming lipids and for initiating the desquamatory process. The desquamatory proteases present in the outer SC such as the thiol proteases and cathepsins are more active in the acidic pH, whereas the SCCE and SCTE present in the lower SC are more active at neutral pH. When the pH gradient is disrupted, desquamation is decreased resulting in dry scaly skin and disrupted barrier function. In the normal epidermis, there is a characteristic intraepidermal calcium gradient, with peak concentrations of

calcium in the granular layer and decreasing all the way up to the SC [24]. The calcium gradient regulates barrier properties by controlling the maturation of the corneocytes, regulating the enzymes that process lipids and by modulating the desquamatory process. Calcium stimulates a variety of processes including the formation and secretion of LB, differentiation of keratinocytes, formation of cornified envelope precursor proteins, and cross-linking of these proteins by the calcium inducible enzyme transglutaminase. Specifically, high levels of calcium stimulate the expression of proteins required for keratinocyte differentiation, including key structural proteins of the cornified envelope, such as loricrin, involucrin, and the enzyme, transglutaminase 1, which catalyzes the cross-linking of these proteins into a rigid structure.

Coordinated regulation of multiple barrier functions Co-localization of many of the barrier functions allows regulation of the functions of the epidermal barrier to be coordinated. For example, epidermal permeability barrier, antimicrobial barrier, mechanical protective barrier, and UV barrier are all co-localized in the SC. A disruption of one function can lead to multiple barrier disruptions, and therefore multiple barrier functions are coordinately regulated [5]. Disruption of the permeability barrier leads to activation of the cytokine cascade (increased levels of primary cytokines, interleukin-1, and tumor necrosis factor-alfa) which in turn activates the synthesis of antimicrobial peptides of the SC. Additionally, the cytokines and growth factors released during barrier disruption lead to corneocyte maturation, thereby strengthening the mechanical and protective barrier of the skin. Hydration of the skin itself controls barrier function by regulating the activities of the desquamatory proteases (high humidity decreases barrier function and stimulates desquamation). In addition, humidity levels control filaggrin hydrolysis which releases the free amino acids that form the NMF (histidine, glutamine arginine, and their by-products) and trans-urocanic acid (deamination of histidine) which serves as a UV barrier.

Methods for studying barrier structure and function Physical methods SC integrity and desquamation can be measured using tape stripping methods. Under dry skin conditions, when the barrier is compromised, corneocytes do not separate singly but as “clumps.” This can be quantified by using special tapes and visualizing the corneocytes removed by light microscopy. Another harsher tape-stripping method involves stripping of the SC using cyanoacrylate glue. These physical methods provide a clue to the binding forces that hold the



Skin Physiology

corneocyte together. The efficacy of treatment with skin moisturizers or emollients that improve skin hydration and reduce scaling can be quantitated using these methods.

Instrumental methods The flux of water vapor through the skin (transepidermal water loss [TEWL]) can be determined using an evaporimeter [25]. This instrument contains two water sensors mounted vertically in a chamber one above the other. When placed on the skin in a stable ambient environment the difference in water vapor values between the two sensors is a measure of the flow of water coming from the skin (TEWL). There are several commercially available evaporimeters (e.g. Tewameter® [Courage & Khazaka, Köln, Germany]), which are widely used in clinical practice as well as in investigative skin biology. Recovery of the epidermal barrier (TEWL) after disruption using physical methods (e.g. tape strips) or chemical methods (organic solvent washing) provides valuable information on epidermal barrier properties [26]. Skin hydration can be measured using the Corneometer® (Courage & Khazaka, Köln, Germany). The measurement is based on capacitance of a dielectric medium. Any change in the dielectric constant caused by skin surface hydration variation alters the capacitance of a precision measuring capacitor. The measurement can detect even the slightest changes in hydration level. Another important recent development in skin capacitance methodology is the SkinChip® (L’Oreal, Paris, France). Skin capacitance imaging of skin surface can be obtained using the SkinChip. This method provides information on skin microrelief, level of SC hydration, and sweat gland activity. SkinChip technology can be used to quantify regional variation in skin, skin changes with age, effects of hydrating formulations, surfactant effects on corneocytes, acne, and skin pore characteristics [27]. Several other recently developed methods for measuring epidermal thickness such as confocal microscopy, dermatoechography, and dermatoscopy can provide valuable information on skin morphology and barrier abnormalities [28]. Other more sophisticated (although not easily portable) instrumentation techniques such as ultrasound, optical coherence tomography, and magnetic resonance imaging (MRI) can provide useful information on internal structures of SC and/or epidermis and its improvements with treatment. MRI has been successfully used to evaluate skin hydration and water behavior in aging skin [29].

Biologic methods Ultrastructural details of SC and the intercellular spaces of the SC can be visualized using transmission electron microscopy of thin vertical sections and freeze–fracture replicas, field emission scanning electron microscopy, and immunofluorescence confocal laser scanning microscopy [30]. The ultrastructural details of the lipid bi-layers within the SC can


be visualized by electron microscopy after fixation using ruthenium tetroxide. The existence of corneodesmosomes in the SC, and their importance in desquamation, can be measured by scanning electron microscopy of skin surface replicas. The constituent cells of the SC, the corneocytes, can be visualized and quantitated by scraping the skin surface or by use of a detergent solution. The suspension so obtained can be analyzed by microscopy, biochemical or immunologic techniques. Punch or shaved biopsy techniques can be combined with immunohistochemistry using specific SC and/or epidermis specific antibodies to quantify the SC quality. Specific antibodies for keratinocyte differentiation specific proteins, desmosomal proteins, or specific proteases can provide information on skin barrier properties.

Relevance of skin barrier to cosmetic product development Topical products that influence barrier functions The human skin is constantly exposed to a hostile environment: changes in relative humidity, extremes of temperature, environmental toxins, and daily topically applied products. Daily exposure to soaps and other household chemicals can compromise skin barrier properties and cause unhealthy skin conditions. Prolonged exposure to surfactants removes the epidermal barrier lipids and enhances desquamation leading to impaired barrier properties [4,10]. Allergic reactions to topical products can result in allergic or irritant contact dermatitis, resulting in itchy and scaly skin and skin redness leading to barrier perturbations.

Cosmetics that restore skin barrier properties Water is the most important plasticizer of SC. Cracking and fissuring of skin develops as SC hydration declines below a critical threshold. Skin moisturization is a property of the outer SC (also known as stratum disjunctum) as corneocytes of the lower SC (stratum compactum) are hydrated by the body fluids. “Moisturizers” are substances that when applied to skin add water and/or retains water in the SC. The NMF components present in the outer SC act as humectants, absorb moisture from the atmosphere, and are sensitive to humidity of the atmosphere. The amino acids and their metabolites, along with other inorganic and organic osmolytes such as urea, lactic acid, taurine, and glycerol act as humectants within the outer SC. Secretions from sebaceous glands on the surface of the skin also act as emollients and contribute to skin hydration. A lack of any of these components can contribute to dry scaly skin. Topical application of all of the above components can act as humectants, and can relieve dry skin condition and improve skin moisturization

1. Epidermal barrier and barrier properties. Film-forming polysaccharide materials such as hyaluronic acid binds and retains water and helps to keep skin supple and soft. In addition to humectants, emollients such as petroleum jelly, hydrocarbon oils and waxes, mineral and silicone oils, and paraffin wax provide an occlusive barrier to the skin, preventing excessive moisture loss from the skin surface. Topically applied barrier compatible lipids also contribute to skin moisturization and improved skin conditions. Chronologically aged skin exhibits delayed recovery rates after defined barrier insults, with decreased epidermal lipid synthesis. Application of a mixture of cholesterol, ceramides, and essential/non-essential FFAs in an equimolar ratio was shown to lead to normal barrier recovery, and a 3 : 1 : 1 : 1 ratio of these four ingredients demonstrated accelerated barrier recovery [31]. Topical application of antioxidants and anti-inflammatory agents also protects skin from UV-induced skin damage by providing protection from oxidative damage to skin proteins and lipids [19,20].

Skin irritation from cosmetics Thousands of ingredients are used by the cosmetic industry. These include pure compounds, mixtures, plant extracts, oils and waxes, surfactants, detergents, preservatives, and polymers. Although all the ingredients used by the cosmetic industry are tested for safety, some consumers may still experience reactions to some of them. Most common reactions are irritant contact reactions while allergic contact reactions are less common. Irritant reactions tend to be more rapid and cause mild discomfort and redness and scaling of skin. Allergic reactions can be delayed, more persistent, and sometimes severe. Ingredients previously considered safe can be irritating in a different formulation because of increased penetration into skin. More than 50% of the general population perceives their skin as sensitive. It is believed that the perception of sensitive skin is, at least in part, related to skin barrier function. People with impaired barrier function may experience higher irritation to a particular ingredient because of its increased penetration into deeper layers of the skin.

Conclusions and future trends Major advances have been made in the last several decades in understanding the complexity and functions of the SC. Extensive research by several groups has elucidated the metabolically active role of SC and characterized the major components within it and their importance in providing protection from the external environment. New insights into the molecular control mechanisms of desquamation, lipid processing, barrier function, and antimicrobial protection have been elucidated in the last decade.

Knowledge of other less well-known epithelial organelles such as intercellular junctions, tight junctions, and gap junctions and their role in barrier function in the skin is being elucidated. Intermolecular links that connect intercellular lipids with the corneocytes of the SC and their crucial role for maintaining barrier function is an area being actively researched. New knowledge of the corneocyte envelope structure and the physical state of the intercellular lipid crystallinity and their interrelationship would lead to development of new lipid actives for improving SC moisturization and for treatment of skin barrier disorders. Further research in the cellular signaling events that control the communication between SC and the viable epidermis will shed more light on barrier homeostasis mechanisms. Novel delivery systems have an increasingly important role in the development of effective skin care products. Delivery technologies such as lipid systems, nanoparticles, microcapsules, polymers, and films are being pursued not only as vehicles for delivering cosmetic actives through skin, but also for improving barrier properties of the skin. Undoubtedly, skin care and cosmetic companies will exploit this new knowledge in developing novel and more efficacious products for strengthening the epidermal barrier and to improve and enhance the functional and aesthetic properties of the human skin.

References 1 Elias PM. (1983) Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 80, 44s–9s. 2 Menon GK, Feingold KR, Elias PM. (1992) Lamellar body secretory response to barrier disruption. J Invest Dermatol 98, 279–89. 3 Downing DT. (1992) Lipid and protein structures in the permeability barrier of mammalian epidermis. J Lipid Res 33, 301–13. 4 Rawlings AV, Matts PJ. (2005) Stratum corneum moisturization at the molecular level: an update in relation to the dry skin cycle. J Invest Dermatol 124, 1099–11. 5 Elias PM. (2005) Stratum corneum defensive functions: an integrated view. J Invest Dermatol 125, 183–200. 6 Elias PM. (1996) Stratum corneum architecture, metabolic activity and interactivity with subjacent cell layers. Exp Dermatol 5, 191–201. 7 Elias PM, Feingold KR. (1992) Lipids and the epidermal water barrier: metabolism, regulation, and pathophysiology. Semin Dermatol 11, 176–82. 8 Uchida Y, Holleran WM. (2008) Omega-O-acylceramide, a lipid essential for mammalian survival. J Dermatol Sci 51, 77–87. 9 Harding CR, Watkinson A, Rawlings AV, Scott IR. (2000) Dry skin, moisturization and corneodesmolysis. Int J Cosmet Sci 22, 21–52. 10 Schaefer H, Redelmeier TE, eds. (1996) Skin Barrier: Principles of Percutaneous Absorption. Karger, Basel. 11 Elias PM, Menon GK. (1991) Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 24, 1–26.



Skin Physiology

12 Steinert PM, Parry DA, Marekov LN. (2003) Trichohyalin mechanically strengthens the hair follicle: multiple crossbridging roles in the inner root shealth. J Biol Chem 278, 41409–19. 13 Choi EH, Man M-Q, Wang F, Zhang X, Brown BE, Feingold KR, et al. (2005) Is endogenous glycerol a determinant of stratum corneum hydration in humans? J Invest Dermatol 125, 288–93. 14 Yamaguchi Y, Takahashi K, Zmudzka BZ, Kornhauser A, Miller SA, Tadokoro T, et al. (2006) Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis. FASEB J 20, 1486–8. 15 Sander CS, Chang H, Salzmann S, Muller CSL, EkanayakeMudiyanselage S, Elsner P, et al. (2002) Photoaging is associated with protein oxidation in human skin in vivo. J Invest Dermatol 118, 618–25. 16 Pence BC, Naylor MF. (1990) Effects of single-dose UV radiation on skin SOD, catalase and xanthine oxidase in hairless mice. J Invest Dermatol 95, 213–6. 17 Pillai S, Oresajo C, Hayward J. (2005) UV radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammationinduced matrix degradation. Int J Cosmet Sci 27, 17–34. 18 Weber SU, Thiele JJ, Cross CE, Packer L. (1999) Vitamin C, uric acid, and glutathione gradients in murine stratum corneum and their susceptibility to ozone exposure. J Invest Dermatol 113, 1128–32. 19 Lopez-Torres M, Thiele JJ, Shindo Y, Han D, Packer L. (1998) Topical application of alpha-tocopherol modulates the antioxidant network and diminishes UV-induced oxidative damage in murine skin. Br J Dermatol 138, 207–15. 20 Pinnell SR. (2003) Cutaneous photodamage, oxidative stress, and topical antioxidant protection. J Am Acad Dermatol 48, 1–19.


21 Madison KC. (2003) Barrier function of the skin: “la raison d’etre” of the epidermis. J Invest Dermatol 121, 231–41. 22 Chatenay F, Corcuff P, Saint-Leger D, Leveque JL. (1990) Alterations in the composition of human stratum corneum lipids induced by inflammation. Photodermatol Photoimmunol Photomed 7, 119–22. 23 Saint-Leger D, Francois AM, Leveque JL, Stoudemayer TJ, Kligman AM, Grove G. (1999) Stratum corneum lipids in skin xerosis. Dermatologica 178, 151–5. 24 Menon GK, Grayson S, Elias PM. (1985) Ionic calcium reservoirs in mammalian epidermis: ultrastructural localization by ioncapture cytochemistry. J Invest Dermatol 84, 508–12. 25 Nilsson GE. (1977) Measurement of water exchange through the skin. Med Biol Eng Comput 15, 209. 26 Pinnagoda J, Tupker RA. (1995) Measurement of the transepidermal water loss. In: Serup J, Jemec GBE, eds. Handbook of Non-Invasive Methods and the Skin. Boca Raton, FL: CRC Press, pp. 173–8. 27 Leveque JL, Querleux B. (2003) SkinChip, a new tool for investigating the skin surface in vivo. Skin Res Technol 9, 343–7. 28 Corcuff P, Gonnord G, Pierard GE, Leveque JL. (1996) In vivo confocal microsocopy of human skin: a new design for cosmetology and dermatology. Scanning 18, 351–5. 29 Richard S, Querleux B, Bittoun J, Jolivet O, Idy-Peretti I, de Lacharriere O, et al. (1993) Characterization of skin in vivo by high resolution magnetic resonance imaging: water behavior and age-related effects. J Invest Dermatol 100, 705–9. 30 Corcuff P, Fiat F, Minondo AM. (2001) Ultrastructure of human stratum coreum. Skin Pharmacol Appl Skin Physiol 1, 4–9. 31 Zettersten EM, Ghadially R, Feingold KR, Crumrine D, Elias PM. (1997) Optimal ratios of topical stratum corneum lipids improve barrier recovery in chronologically aged skin. J Am Acad Dermatol 37, 403–8.

Chapter 2: Photoaging Murad Alam and Jillian Havey Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

BAS I C CONCEPTS • UV radiation damages human skin connective tissue through several interdependent, but distinct, processes. • The normal dermal matrix is maintained through signaling transduction pathways, transcription factors, cell surface receptors, and enzymatic reactions. • UV radiation produces reactive oxygen species which inhibit procollagen production, degrade collagen, and damage fibroblasts.

Introduction Skin, the largest human organ, is chronically exposed to UV radiation from the sun. Thinning of the ozone layer, which increases UV transmittance to the Earth, has heightened awareness of the potential injurious skin effects of exposure to UV radiation: photoaging, sunburn, immunosuppression, and carcinogenesis. Photoaging, the most common form of skin damage caused by UV exposure, produces damage to connective tissue, melanocytes, and the microvasculture [1]. Recent advances in understanding photoaging in human skin have identified the physical manifestations, histologic characteristics, and molecular mechanisms of UV exposure.

Definition Photoaging is the leading form of skin damage caused by sun exposure, occurring more frequently than skin cancer. Chronic UV exposure results in premature skin aging, termed cutaneous photoaging, which is marked by fine and coarse wrinkling of the skin, dyspigmentation, sallow color, textural changes, loss of elasticity, and premalignant actinic keratoses. Most of these clinical signs are caused by dermal alterations. Pigmentary disorders such as seborrheic keratoses, lentigines, and diffuse hyperpigmentation are characteristic of epidermal changes [2]. These physical characteristics are confirmed histologically by epidermal thinning and disorganization of the dermal connective tissue (see p. 14). Loss of connective tissue inter-

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

stitial collagen fibrils and accumulation of disorganized connective tissue elastin leads to solar elastosis, a condition characteristic of photoaged skin [3]. Similar alterations in the cellular component and the extracellular matrix of the connective tissue of photoaged skin may affect superficial capillaries, causing surface telangiectasias [4].

Physiology Photoaged versus chronically aged skin Skin, like all other organs, ages over time. Aging can be defined as intrinsic and extrinsic. Intrinsic aging is a hallmark of human chronologic aging and occurs in both sunexposed and non-sun-exposed skin. Extrinsic aging, on the contrary, is affected by exposure to environmental factors such as UV radiation. While sun-protected chronically aged skin and photoaged chronically aged skin share common characteristics, many of the physical characteristics of skin that decline with age show an accelerated decline with photoaging [5]. Compared with photodamaged skin, sunprotected skin is characterized by dryness, fine wrinkles, skin atrophy, hom*ogeneous pigmentation, and seborrheic keratoses [6]. Extrinsically aged skin, on the contrary, is characterized by roughness, dryness, both fine and coarse wrinkles, atrophy, uneven pigmentation, and superficial vascular abnormalities (e.g. telangiectasias) [6]. It is important to note that these attributes are not absolute and can vary according to Fitzpatrick skin type classification and history of sun exposure. While the pathophysiology of photoaged and photoprotected skin differ, the histologic features of these two entities are distinct. In photo-protected skin, a thin epidermis is present with an intact stratum corneum, the dermoepidermal junction and the dermis are flattened, and dermal fibroblasts produce less collagen. In photoaged skin,



Skin Physiology

the thickness of the epidermis can either increase or decrease, corresponding to areas of keratinocyte atypia. The dermoepidermal junction is atrophied in appearance and the basal membrane thickness is increased, reflecting basal keratinocyte damage. Changes in the dermis of photoaged skin can vary based on the amount of acquired UV damage. Solar elastosis is the most prominent histologic feature of photoaged skin. The quantity of elastin in the dermis decreases in chronically aged skin, but in UV-exposed skin, elastin increases in proportion to the amount of UV exposure [7,8]. Accumulated elastic fibers occupy areas in the dermal compartment previously inhabited by collagen fibers [9]. This altered elastin deposition is manifest clinically as wrinkles and yellow discoloration of the skin. Another feature of photoaged skin is collagen fibril disorganization. Mature collagen fibers, which constitute the bulk of the skin’s connective tissue, are degenerated and replaced by collagen with a basophilic appearance, termed basophilic degeneration. Additional photoaged skin characteristics include an increase in the deposition of glycosaminoglycans and dermal extracellular matrix proteins [10,11]. In fact, the overall cell population in photodamaged skin increases, leading to hyperplastic fibroblast proliferation and infiltration of inflammatory substrates that cause chronic inflammation (heliodermatitis) [12]. Changes in the microvasculature also occur, as is clinically manifested in surface telangiectasias and other vascular abnormalities.


Photobiology In order to fully understand the molecular mechanisms responsible for photoaging in human skin, an awareness of the UV spectrum is crucial. The UV spectrum is divided into three main components: UVC (270–290 nm), UVB (290– 320 nm), and UVA (320–400 nm). While UVC radiation is filtered by ozone and atmospheric moisture, and consequently never reaches the Earth, UVA and UVB rays do reach the terrestrial surface. Although the ratio of UVA to UVB rays is 20 : 1 [13] and UVB is greatest during the summer months, both forms of radiation have acute and chronic effects on human skin. Photoaging is the superposition of UVA and UVB radiation on intrinsic aging. In order to exert biologic effects on human skin, both categories of UV rays must be absorbed by chromophores in the skin. Depending on the wavelength absorbed, UV light interacts with different skin cells at different depths (Figure 2.1). More specifically, energy from UVB rays is mostly absorbed by the epidermis and affects epidermal cells such as the keratinocytes, whereas energy from UVA rays affects both epidermal keratinocytes and the deeper dermal fibroblasts. The absorbed energy is converted into varying chemical reactions that cause histologic and clinical changes in the skin. UVA absorption by chromophores mostly acts indirectly by transferring energy to oxygen to generate reactive oxygen species (ROS), which subsequently causes several effects such as transcription factor activation, lipid peroxidation, and DNA-strand breaks. On the contrary, UVB has a more direct effect on the absorb-



Keratinocytes AP-1 NF-κB

ROS Dermis


MMP and mtDNA


Figure 2.1 Ultraviolet light interacts with different skin cells at different depths. More specifically, energy from UVB rays is mostly absorbed by the epidermis and affects epidermal cells such as the keratinocytes. Energy from UVA rays affects both epidermal keratinocytes and the deeper dermal fibroblasts. AP-1, activator protein 1; NF-κB, nuclear factor κB; MMP, matrix metalloproteinase; mtDNA, mitochondrial DNA; ROS, reactive oxygen species. (Reproduced by permission of: Blackwell Publishing. This figure was published in: Berneburg M, Plettenberg H, Krutmann J. (2000) Photoaging in human skin. Photodermatol Photoimmunol Photomed 16, figure 1, p. 240.)

2. Photoaging ing chromophores and causes cross-linking of adjacent DNA pyrimidines and other DNA-related damage [14]. Approximately 50% of UV-induced photodamage is from the formation of free radicals, while mechanisms such as direct cellular injury account for the remainder of UV effects [15].

Cutaneous microvasculature Intrinsically aged skin and photodamaged skin share similar cutaneous vasculature characteristics, such as decreased cutaneous temperature, pallor, decreased cutaneous vessel size, reduced erythema, reduced cutaneous nutritional supply, and reduced cutaneous vascular responsiveness [16– 18]. However, there are also significant differences in the microvasculature of chronologic sun-protected versus photoaged skin. Studies have reported that the blood vessels in photoaged skin are obliterated and the overall horizontal architecture of the vascular plexuses is disrupted [19]. In contrast to photodamaged skin, intrinsically aged skin does not display a greatly disturbed pattern of horizontal vasculature. Additionally, while cutaneous vessel size has been reported to decrease with age in both scenarios, only photoaged skin exhibits a large reduction in the number of dermal vessels. This reduction is especially highlighted in the upper dermal connective tissue, where it is hypothesized that chronic UV-induced degradation of elastic and collagen fibers is no longer able to provide the physical support required for normal cutaneous vessel maintenance [16]. Furthermore, preliminary studies have reported that the effects of exposure to acute UV radiation differ from chronic exposure. Recent studies have implied that a single exposure to UVB radiation induces skin angiogenesis in human skin in vivo [20,21]. The epidermis-derived vascular endothelial growth factor (VEGF) is an angiogenic factor that is significantly upregulated with UV exposure in keratinocytes in vitro and in human skin in vivo. Chung and Eun [16] have demonstrated that, compared to low VEGF expression in non-UV-irradiated control skin, epidermal VEGF expression increased significantly on days 2 and 3 post-UV-irradiation, consequently inducing cutaneous angiogenesis. Therefore, acute UV exposure has been shown to induce angiogenesis. However, chronic UV-exposed photodamaged skin exhibits a significant reduction in the number of cutaneous blood vessels. The reasons for this discrepancy between the effects of acute and chronic UV exposure on angiogenesis in vivo are still under investigation.

damages human skin by at least two interdependent mechanisms: 1 Photochemical generation of ROS; and 2 Activation of cutaneous signal transduction pathways. These molecular processes and their underlying components are described in detail below. Before these processes are highlighted, however, the structure and function of collagen must be understood.

Collagen Type I collagen accounts for greater than 90% of the protein in the human skin, with type III collagen accounting for a smaller fraction (10%). The unique physical characteristics of collagen fibers are essential for providing strength, structural integrity, and resilience to the skin. Dermal fibroblasts synthesize individual collagen polypeptide chains as precursor molecules called procollagen. These procollagen building blocks are assembled into larger collagen fibers through enzymatic cross-linking and form the three-dimensional dermal network mainly made of collagen types I and III. This intermolecular covalant cross-linking step is essential for maintenance and structural integrity of large collagen fibers, especially type I collagen. Natural breakdown of type I collagen is a slow process and occurs through enzymatic degradation [22]. Dermal collagen has a half-life of greater than 1 year [22], and this slow rate of type I collagen turnover allows for disorganization and fragmentation of collagen which impair its functions. In fact, fragmentation and dispersion of collagen fibers is a feature of photodamaged skin that is clinically manifest in the changes associated with photodamaged human skin. The regulation of collagen production is an important mechanism to understand before discussing how this process is impaired. In general, collagen gene expression is regulated by the cytokine, transforming growth factor β (TGF-β), and the transcription factor, activator protein (AP-1), in human skin fibroblasts. When TGF-βs bind to their cell surface receptors (TβRI and TβRII), transcription factors Smad2 and Smad3 are activated, combine with Smad4, and enter the nucleus, where they regulate type I procollagen production. AP-1 has an opposing effect and inhibits collagen gene transcription by either direct suppression of gene transcription or obstructing the Smad complex from binding to the TGF-β target gene (Figure 2.2) [23]. Therefore, in the absence of any inhibiting factors, the TGF-β/Smad signaling pathway results in a net increase in procollagen production.

How does UV irradiation stimulate photoaging?

Molecular mechanisms of photoaging During the last few years substantial progress has been made in exposing the molecular mechanisms accountable for photoaging in human skin. One major theoretical advance that has been elucidated by this work is that UV irradiation

UV irradiation stimulates photoaging through several molecular mechanisms, discussed in detail below.

Reactive oxygen species Approximately 50% of UV-induced photodamage is from the formation of free radicals, while mechanisms such as



Skin Physiology complex. This, in turn, reduces TGF-β target gene expression, such as expression of type I procollagen [27].


UV-induced matrix metalloproteinases stimulate collagen degradation

Smad 2,3 Smad 7 TβR I/II


Smad 2,3 Smad 4


Smad 2,3

Smad 4 AP-1


Smad 2,3

Smad 4

TGF-β target gene


Figure 2.2 The regulation of procollagen production: the TGF-β/Smad signaling pathway. AP-1, activator protein 1; TβR, TGF-β receptor; TGF-β, transforming growth factor β. (Reproduced by permission of: Elsevier Ltd. This figure was published in: Kang S, Fisher G, Voorhees JJ. (2001) Photoaging pathogenesis, prevention, and treatment. Clin Geriatric Med 17(4), figure 1, p. 645.)

direct cellular injury account for the remainder of UV effects [15]. Proposed in 1954, the free radical theory of aging suggests that aging is a result of reactions caused by excessive amounts of free radicals, which contain one or more unpaired electrons [24]. Generation of ROS occurs during normal chronologic aging and when human skin is exposed to UV light in photoaging [25]. ROS mediate deleterious post-translational effects on aging skin through direct chemical modifications to mitochondrial DNA (mtDNA), cell lipids, deoxyribonucleic acids (DNA), and dermal matrix proteins, including collagens. In fact, a 4977 base-pair deletion of mtDNA was recently found in dermal human fibroblast cells. This deletion is induced by UVA via ROS and is a marker of UVA photodamage [26].

UV radiation inhibits procollagen production: TGF-β/Smad signaling pathway UV light inhibits procollagen production through two signaling pathways: downregulation of TβRII and inhibition of target gene transcription by AP-1. UV radiation has been reported to disrupt the skin collagen matrix through the TGF-β/Smad pathway [1]. More specifically, UV radiation downregulates the TGF-β type II receptor (TβRII) and results in a 90% reduction of TGF-β cell surface binding, consequently reducing downstream activation of the Smad 2, 3, 4 complex and type I procollagen transcription. Additionally, UV radiation activates AP-1, which binds factors that are part of the procollagen type I transcriptional


It has been demonstrated that UV irradiation affects the post-translational modification of dermal matrix proteins (through ROS) and also downregulates the transcription of these same proteins (through the TGF-β/Smad signaling pathway). UVA and UVB light also induces a wide variety of matrix metalloproteinases (MMPs) [28]. As their name suggests, MMPs degrade dermal matrix proteins, specifically collagens, through enzymatic activity. UV-induced MMP-1 initiates cleavage of type I and III dermal collagen, followed by further degradation by MMP-3 and MMP-9. Recall that type I collagen fibrils are stabilized by covalent cross-links. When undergoing degradation by MMPs, collagen molecules can remain cross-linked within the dermal collagen matrix, thereby impairing the structural integrity of the dermis. In the absence of perfect repair mechanisms, MMP-mediated collagen damage can accrue with each UV exposure. This type of collective damage to the dermal matrix collagen is hypothesized to have a direct effect on the physical characteristics of photodamaged skin [14]. In addition to UV induction of MMPs, transcription factors may cause MMP activation. It has been reported that within hours of UV exposure, the transcription factors AP-1 and NF-κB are activated which, in turn, stimulate transcription of MMPs (Figure 2.3) [29].

Fibroblasts regulate their own collagen synthesis Fibroblasts have evolved to regulate their output of extracellular matrix proteins (including collagen) based on internal mechanical tension [30]. Type I collagen fibrils in the dermis serve as mechanical stabilizers and attachment sites for fibroblasts in sun-protected skin. Surface integrins on the fibroblasts attach to collagen and internal actin– myosin microfilaments provide mechanical resistance by pulling on the intact collagen. In response to this created tension, intracellular scaffolding composed of intermediate filaments and microtubules pushes outward to causing fibroblasts to stretch. This stretch is an essential cue for normal collagen and MMP production by fibroblasts (Figure 2.4) [30]. This mechanical tension model is different in photoaged human skin. Fibroblast–integrin attachments are lost, which prevents collagen fragments from binding to fibroblasts. Collagen–fibroblast binding is crucial for maintenance of normal mechanical stability. When mechanical tension is reduced, as in photoaged skin, fibroblasts collapse, which causes decreased procollagen production and increased collagenase (COLase) production [30]. Collagen is continually lost as this cycle repeats itself.

2. Photoaging




FB Figure 2.3 Model depicting the effects of UV irradiation on epidermal keratinocytes (KC) and dermal fibroblasts (FB). AP-1, activator protein 1; MMP, matrix metalloproteinase. (Reproduced by permission of: Fisher GJ, et al. Mechanisms of photoaging and chronological skin aging. Arch Dermatol 2002; 138: figure 1 p. 1463. Copyright 2002, American Medical Association. All Rights reserved.)

Growth factor Cytokine receptors

Growth factor Cytokine receptors

Signal transduction cascade

Signal transduction cascade



Procollagen MMP promoters promoters nucleus



AP-1 MMP promoters


Dermal matrix breakdown Imperfect repair



Intact collagen Cross-links

Photoprotected or young skin


Figure 2.4 Fibroblasts have evolved to regulate their output of collagen based on internal mechanical tension. Model depicting the effects of mechanical tension on procollagen production in (a) sun-protected human skin versus (b) photodamaged human skin. (Reproduced by permission of: Fisher GJ, Varani J, Voorhees, JJ. Looking older. Arch Dermatol 2008; 144(5), figure 2, p. 669. Copyright 2008, American Medical Association. All rights reserved.)

(a) Stretched fibroblast Collagen fragments

Photoaged or aged skin


(b) Collapsed fibroblast



Skin Physiology

Ethnic skin: photoaging All races are susceptible to photoaging. However, people with Fitzpatrick skin phototypes IV–VI are less susceptible to the deleterious effects of UV irradiation than people with a lower Fitzpatrick skin type classification. This phenomenon is most likely a result of the protective role of melanin [31]. Studies reporting ethnic skin photoaging are few and far between. However, for the purposes of this discussion, characteristics of photoaging in different ethnic skin categories are briefly highlighted. In one of the first studies comparing UV absorption amongst different skin types, Kaidbey et al. [32] compared the photoprotective properties of African-American skin with Caucasian skin exposed to UVB irradiation. It was known that only 10% of the total UVB rays penetrated the dermis. However, the mean UVB transmission into the dermis by African-American dermis (5.7%) was found to be significantly less than for Caucasian dermis (29.4%). Similar experiments were performed with UVA irradiation. Although only 50% of the total UVA exposure penetrates into the papillary dermis, UVA transmission into AfricanAmerican dermis was 17.5% compared to 55% for white epidermis [32]. The physiologic reason behind this difference in black and white skin lies at the site of UV filtration. The malpighian layer (basal cell layer) of African-American skin is the main site of UV filtration, while the stratum corneum absorbs most UV rays in white skin. The malpighian layer of African-American skin removes twice as much UVB radiation as the overlying statum corneum, thus mitigating the deleterious effects of UV rays in the underlying dermis [33]. In African-Americans, photoaging may not be clinically apparent until the fifth or sixth decade of life and is more common in individuals with a lighter complexion [34]. The features of photoaging in this ethnic skin group manifest as signs of laxity in the malar fat pads sagging toward the nasolabial folds [35]. In patients of Hispanic and European descent, photoaging occurs in the same frequency as Caucasians and clinical signs are primarily wrinkling rather than pigmentary alterations. The skin of East and South-East Asian patients, on the contrary, mainly exhibits pigmentary alterations (seborrheic keratoses, hyperpigmentation, actinic lentigines, sun-induced melasma) and minimal wrinkling as a result of photoaging [36,37]. Finally, very few studies have reported on the signs of photoaging in South Asian (Pakistanis, Indians) skin. UV-induced hyperpigmentation, dermatosis papulosa nigra, and seborrheic keratosis are noted [38]. Despite all of these differences, it is important to note that the number of melanocytes per unit area of skin does not vary across ethnicities. Instead, it is the relative amount of melanin packaged into melanocytes that accounts for the


physiologic differences between Caucasian skin and ethnic skin [39].

Prevention Although the effects of the sun’s rays appear daunting, there are some ways to avoid the deleterious effects of photoaging. Avoiding photoaging can often prove to be more costeffective than trying to reverse the signs of photoaging after they have manifested.

Primary prevention Sun protection UV rays are especially prevalent during the hours of 10AM– 4PM and sun protection should be encouraged during this time. Sun protection can be offered to patients in the form of sunscreens, sun-protective clothing, and/or sun avoidance. Sun-protective clothing includes any hats, sunglasses, or clothing that would help block the sun’s rays. Photoprotective clothing is given a UV protection factor (UPF) rating, which is a measurement of the amount of irradiation that can be transmitted through a specific type of fabric. A UPF of 40–50 is recommended by most dermatologists, as it transmits less than 2.6% of UV irradiation [5]. Traditionally, sunscreens contain one or more chemical filters – those that physically block, reflect, or scatter specific photons of UV irradiation and those that absorb specific UV photons. UVA sunblocks contain the inorganic particulates titanium dioxide or zinc oxide, while UVA-absorbing suncreens contain terephthalylidene dicamphor sulfonic acid or avobenzene. UVB-absorbing sunscreens can contain salicylates, cinnamates, p-aminobenzoic acid, or a combination of these [40]. The US Food and Drug Administration (FDA) recommended dose of sunscreen application is 2 mg/cm2 [41]. The sun protection factor (SPF) is an international laboratory measure used to assess the efficacy of sunscreens. The SPF can range from 1 to over 80 and indicates the time that a person can be exposed to UVB rays before getting sunburn with sunscreen application relative to the time a person can be exposed without sunscreen. SPF levels are determined by the minimal amount of UV irradiation that can cause UVBstimulated erythema and/or pain. The effectiveness of a particular sunscreen depends on several factors, including the initial amount applied, amount reapplied, skin type of the user, amount of sunscreen the skin has absorbed, and the activities of the user (e.g. swimming, sweating). The sun protection factor is an inadequate determination of skin damage because it does not account for UVA rays. Although UVA rays have an important role in photoaging, their effects are not physically evident as erythema or pain, as are UVB rays. Therefore, it has been suggested that SPF may be an imperfect guide to the ability of a particular sun-

2. Photoaging UV

Skin angiogenesis VEGF TSP

Acute effects

ECM degradation Collagen MMPs

Inflammation Figure 2.5 Model depicting the acute and chronic effects of UV irradiation on skin angiogenesis and extracellular matrix (ECM) degradation in human skin. MMP, matrix metalloproteinase; TSP, thrombospondin-1 (ECM protein; inhibitor of angiogenesis in epithelial tissues); VEGF, vascular endothelial growth factor. (Reproduced by permission of: Blackwell Publishing. This figure was published in: Chung JH, Eun HC. (2007) Angiogenesis in skin aging and photoaging. J Dermatol 34, figure 1, p. 596.)

Worse environment for normal vasculature Photoaged human skin ECM (collagen fibers, elastic fibers) Dermal vasculature

Chronic effects

screen to shield against photoaging [5]. As a result, combination UVA–UVB sunscreens have been developed and are recommended to protect the human skin from both types of irradiation.

Aged and photoaged human skin ECM (collagen fibers, elastic fibers) Dermal vasculature Retinoic acid

Secondary prevention Retinoids A large number of studies have reported that topical application of 0.025–0.1% all-trans retinoic acid (tRA) improves photoaging in human skin [42,43]. Results vary based on treatment duration and applied tRA dose. Although there have been a variety of clinical trials on the topic, the molecular mechanisms by which tRA acts are still waiting to be discovered. Retinoic acids have been used in an ex post facto manner to reverse the signs of photodamage and in a preventative fashion to avoid photoaging. More specifically, tRA has been shown to induce type I and III procollagen gene expression in photoaged skin [44]. It has been observed that topical tRA induces TGF-β in human skin [45], which stimulates the production of type I and III procollagen. In addition, tRA has been used in a preventive fashion to avert UV-induced angiogenesis. Kim et al. [20] demonstrated that topical application of retinoic acid before UV exposure inhibited UV-induced angiogenesis and increases in blood vessel density. In general, extracellular signal-related kinases (ERKs, or classic MAP kinases) positively regulate epidermally derived VEGF. VEGF stimulates angiogenesis upon UV induction. Retinoic acid inhibits ERKs, which can potentially lead to downregulation of VEGF expression, UV-induced angiogenesis, and angiogenesis-associated photoaging (Figures 2.5 and 2.6) [16]. Finally, tRA has been reported to prevent UV-stimulated MMP expression. The transcription factor, c-Jun, is a key

ECM degradation Collagen MMPs

Skin angiogenesis VEGF Vascularization

Better environment for normal vasculature

Improve skin aging Figure 2.6 Model depicting the effect of topical retinoids on photoaged human skin. ECM, extracellular matrix; MMP, matrix metalloproteinase; VEGF, vascular endothelial growth factor. (Reproduced by permission of: Blackwell Publishing. This figure was published in: Chung J, Eun HC. (2007) Angiogenesis in skin aging and photoaging. J Dermatol 34, figure 5, p. 599.)

component in forming the AP-1 complex. Recall that the AP-1 complex both inhibits types I and III procollagen and stimulates transcription of MMPs. Retinoic acid blocks the accumulation of c-Jun protein, consequently inhibiting the formation of the AP-1 complex and dermal matrixassociated degradation [46].

Antioxidants It is important to highlight briefly the role of antioxidants in the reduction of photoaging. In vitro studies have



Skin Physiology

discovered a large number of antioxidants that either forestall or reverse the clinical signs of photodamage caused by ROS. In vivo studies investigating these same antioxidants are ongoing. One such antioxidant, vitamin C, has been shown to mitigate photodamaged keratinocyte formation and erythema post-UV-irradiation [47].

Inherent defense mechanisms Although science has developed exogenous mechanisms to prevent and reverse the clinical signs of photoaging, the human skin possesses endogenous machinery built to protect the skin from UV-induced damage. These inherent defense mechanisms include, but are not limited to, increased epidermal thickness, melanin distribution, DNA repair mechanisms and apoptosis of sunburned keratinocytes, MMP tissue inhibitors, and antioxidants [5,32,48–50].

Failure of prevention: immunosuppression Although photoaging is the most prevalent form of skin damage, local and systemic immunosuppression, leading to skin carcinoma, can result from overexposure to the sun’s rays. This immunosuppression is mediated by a combination of DNA damage, epidermal Langerhans’ cell depletion, and altered cytokine expression [51,52].

Conclusions The pathophysiology of photoaging derives from the ability of UV irradiation to exploit established molecular mechanisms which have evolved to maintain the internal milieu of human skin connective tissue. Disruption of the normal skin architecture does not occur through one pathway, but rather is the culmination of several interdependent, but distinct, processes that have gone awry. The integrity of the normal dermal matrix is maintained through signaling transduction pathways, transcription factors, cell surface receptors, and enzymatic reactions that are intertangled and communicate with one another. When UV irradiation is introduced into this homeostatic picture, deleterious effects can be implemented. Production of ROS, inhibition of procollagen production, collagen degradation, and fibroblast collapse are only a few known processes amongst the medley of mechanisms still waiting to be discovered that contribute to photoaging. Although human skin is equipped with inherent mechanisms to protect against photoaging and methods of prevention and therapeutics are widely available, these alternatives are not absolute and do not necessarily guarantee a perfect escape from the sun’s UV irradiation. With each passing day, scientists continue to discover


novel cutaneous molecular mechanisms affected by UV irradiation and, consequently, search for new solutions to photodamage.

References 1 Quan T, He T, Kang S, Voorhees JJ, Fisher GJ. (2004) Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-beta type II receptor/Smad signaling. Am J Pathol 165, 741–51. 2 Gilchrest B, Rogers G. (1993) Photoaging. In: Lim H, Soter N, eds. Clinical Photomedicine. New York: Marcel Dekker, pp. 95–111. 3 Kang S, Fisher GJ, Voorhees JJ. (2001) Photoaging: pathogenesis, prevention, and treatment. Clin Geriatr Med 17, 643–59. 4 Weiss RA, Weiss MA, Beasley KL. (2002) Rejuvenation of photoaged skin: 5 years results with intense pulsed light of the face, neck, and chest. Dermatol Surg 28, 1115–9. 5 Rabe JH et al. (2006) Photoaging: mechanisms and repair. J Am Acad Dermatol 55, 1–19. 6 Rokhsar CK, Lee S, Fitzpatrick RE. (2005) Review of photorejuvenation: devices, cosmeceuticals, or both? Dermatol Surg 31, 1166–78; discussion 1178. 7 Bernstein E, Brown DB, Urbach F, Forbes D, Del Monaco M, Wu M, et al. (1995) Ultraviolet radiation activates the human elastin promoter in transgenic mice: a novel in vivo and in vitro model of cutaneous photoaging. J Invest Dermatol 105, 269–73. 8 Lewis KG, Bercovitch L, Dill SW, Robinson-Bostom L. (2004) Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes. J Am Acad Dermatol 51, 1–21. 9 El-Domyati M, Attia S, Saleh F, Brown D, Birk DE, Gasparro F, et al. (2002) Intrinsic aging vs photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Exp Dermatol 11, 398–405. 10 Mitchell R. (1967) Chronic solar elastosis: a light and electron microscopic study of the dermis. J Invest Dermatol 48, 203–20. 11 Smith JG Jr, Davidson EA, Sams WM Jr, Clark RD. (1962) Alterations in human dermal connective tissue with age and chronic sun damage. J Invest Dermatol 39, 347–50. 12 Lavker R, Kligman A. (1988) Chronic heliodermatitis: a morphologic evaluation of chronic actinic damage with emphasis on the role of mast cells. J Invest Dermatol 90, 325–30. 13 Urbach F. (1992) Ultraviolet A transmission by modern sunscreens: Is there a real risk? Photodermatol Photoimmunol Photomed 9, 237–41. 14 Fisher G, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S, et al. (2002) Mechanisms of photoaging and chronological skin aging. Arch Dermatol 138, 1462–70. 15 Bernstein EF, Brown DB, Schwartz MD, Kaidbey K, Ksenzenko SM. (2004) The polyhydrxy acid gluconolactone protects against ultraviolet radiation in an in vitro model of cutaneous photoaging. Dermatol Surg 30, 189–96. 16 Chung JH, Eun HC. (2007) Angiogenesis in skin aging and photoaging. J Dermatol 34, 593–600. 17 Chung JH, Yano K, Lee MK, Youn CS, Seo JY, Kim KH, et al. (2002) Differential effects of photoaging vs intrinsic aging on the vascularization of human skin. Arch Dermatol 138, 1437–42. 18 Kelly RI, Pearse R, Bull RH, Leveque JL, de Riqal J, Mortimer PS. (1995) The effects of aging on the cutaneous microvasculature. J Am Acad Dermatol 33, 749–56.

2. Photoaging 19 Kligman AM. (1979) Perspectives and problems in cutaneous gerontology. J Invest Dermatol 73, 39–46. 20 Kim MS, Kim YK, Eun HC, Cho KH, Chung JH. (2006) All-trans retinoic acid antagonizes UV-induced VEGF production and angiogenesis via the inhibition of ERK activation in human skin keratinocytes. J Invest Dermatol 126, 2697–706. 21 Yano K, Kadova K, Kajiya K, Hong YK, Detmar M. (2005) Ultraviolet B irradiation of human skin induces an angiogenic switch that is mediated by upregulation of vascular endothelial growth factor and by downregulation of thrombospondin-1. Br J Dermatol 152, 115–21. 22 Verzijl N, DeGroot J, Thorpe S. (2000) Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 275, 39027–31. 23 Massague J. (1998) TGF-β signal transduction. Annu Rev Biochem 67, 753–91. 24 Herman D. (1998) Expanding functional life span. Exp Geriatr Ontol 33, 95–112. 25 Sohal R, Weindruch R. (1996) Oxidative stress, caloric restriction and aging. Science 273, 59–63. 26 Berneburg M, Plettenberg H, Medve-Konig K, Pfahlberg A, Gers-Barlaq H, Gefeler O, et al. (2004) Induction of the photoaging-associated mitochondrial common deletion in vivo in normal human skin. J Invest Dermatol 122, 1277–83. 27 Karin M, Liu ZG, Zandi E. (1997) AP-1 function and regulation. Curr Opin Cell Biol 9, 240–6. 28 Berneburg M, Plettenberg H, Krutmann J. (2000) Photoaging of human skin. Photodermatol Photoimmunol Photomed 16, 239–44. 29 Fisher G, Wang ZQ, Datta SC, Varani J, Kang S, Voorhees JJ. (1997) Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med 337, 1419–28. 30 Fisher GJ, Varani J, Voorhees JJ. (2008) Looking older: fibroblast collapse and therapeutic implications. Arch Dermatol 144, 666–72. 31 Pathak M. (1974) The role of natural photoprotective agents in human skin. In: Fitzpatrick T, Pathak M, eds. Sunlight and Man. Toyko: University of Toyko Press. 32 Kaidbey KH, Agin PP, Sayre RM, Kligman AM. (1979) Photoprotection by melanin: a comparison of black and Caucasian skin. J Am Acad Dermatol 1, 249–60. 33 Munavalli GS, Weiss RA, Halder RM. (2005) Photoaging and nonablative photorejuvenation in ethnic skin. Dermatol Surg 31, 1250–60; discussion 1261. 34 Taylor SC. (2002) Skin of color: biology, structure, function, and implications for dermatologic disease. J Am Acad Dermatol 46 (Suppl 2), S41–62. 35 Matory W. (1998) Skin care. In: Matory W, ed. Ethnic Considerations in Facial Aesthetic Surgery. Philadelphia: LippincottRaven, p. 100. 36 Chung JH, Lee SH, Youn CS, Park BJ, Kim KH, Park KC, et al. (2001) Cutaneous photodamage in Koreans: influence of sex, sun exposure, smoking, and skin color. Arch Dermatol 137, 1043–51. 37 Goh SH. (1990) The treatment of visible signs of senescence: the Asian experience. Br J Dermatol 122 (Suppl 35), 105–9. 38 Valia R, Ed. (1994) Textbook and Atlas of Dermatology. Bombay: Bhalani Publishing House.

39 Szabo G, Gerald AB, Pathak MA, Fitzpatrick TB. (1969) Racial differences in the fate of melanosomes in human epidermis. Nature 222, 1081–2. 40 Seite S, Colige A, Piquemal-Vivenot P, Montastier C, Fourtanier A, Lapiere C, et al. (2000) A full-UV spectrum absorbing daily use cream protects human skin against biological changes occurring in photoaging. Photodermatol Photoimmunol Photomed 16, 147–55. 41 Bowen D. (1998) Sep00/090600/c000573_10_Attachment_F.pdf. 42 Griffiths CE, Kang S, Ellis CN, Kim KJ, Finkel LJ, Ortiz-Ferrer LC, et al. (1995) Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation: a double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams. Arch Dermatol 131, 1037–44. 43 Kang S, Voorhees JJ. (1998) Photoaging therapy with topical tretinoin: an evidence-based analysis. J Am Acad Dermatol 39, S55–61. 44 Griffiths CE, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ. (1993) Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 329, 530–5. 45 Kim HJ, Bogdan NJ, D’Agostaro LJ, Gold LI, Bryce GF. (1992) Effect of topical retinoic acids on the levels of collagen mRNA during the repair of UVB-induced dermal damage in the hairless mouse and the possible role of TGF-beta as a mediator. J Invest Dermatol 98, 359–63. 46 Fisher GJ, Talwar HS, Lin J, Lin P, McPhillips F, Wang Z, et al. (1998) Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. J Clin Invest 101, 1432–40. 47 Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM, MonteiroRiviere NA, et al. (2003) UV photoprotection by combination topical antioxidants vitamin C and vitamin E. J Am Acad Dermatol 48, 866–74. 48 Huang LC, Clarkin KC, Wahl GM. (1996) Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest. Proc Natl Acad Sci U S A 93, 4827–32. 49 Oh JH, Chung AS, Steinbrenner H, Sies H, Brenneisen P. (2004) Thioredoxin secreted upon ultraviolet A irradiation modulates activities of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in human dermal fibroblasts. Arch Biochem Biophys 423, 218–26. 50 Soter N. (1995) Sunburn and suntan: immediate manifestations of photodamage. In: Gilchrest B, ed. Photodamage. Cambridge, MA: Blackwell Science, pp. 12–25. 51 Vink AA, Moodycliffe AM, Shreedhar V, Ullrich SE, Roza L, Yarosh DB, et al. (1997) The inhibition of antigen-presenting activity of dendritic cells resulting from UV irradiation of murine skin is restored by in vitro photorepair of cyclobutane pyrimidine dimers. Proc Natl Acad Sci U S A 94, 5255–60. 52 Toews GB, Bergstresser PR, Streilein JW. (1980) Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB. J Immunol 124, 445–53.


Chapter 3: Self-perceived sensitive skin Olivier de Lacharrière L’Oréal Recherche, Clichy, France

BAS I C CONCE P T S • Sensitive skin is a term used by individuals who perceive their skin as being more intolerant or reactive than the general population. • Sensitive skin is clinically characterized by subjective, sensorial signs: facial discomfort with stinging, burning, and itching. • The clinical signs of sensitive skin appear in specific conditions, provoked by reactivity factors: environmental factors: wind, sun, cold weather, fast changes in temperature; topical factors: hard water, cosmetics; internal factors: life stress, menstruation, or spicy or hot foods.


Clinical features

Sensitive skin is a clinical syndrome, first described in the 1960s by Thiers [1]. A protocol for clinical evaluation of sensitive skin using lactic acid sting testing was first introduced in the 1970s by Frosch and Kligman [2]. Subsequent to that, interest in the field of sensitive skin exploded based on “subjective discomfort, namely, delayed stinging from topical agents applied to the skin.” In spite of the contrary opinion expressed by Maibach et al. [3] at the end of the 1980s, that “the plausibility of the concept of the sensitive skin evokes discussion and often amusem*nt because of the variance of the number of opinions compared with the amount of data, at least until recently,” significant progress has been made on sensitive skin research in recent years. Based on current opinion, sensitive skin is now well accepted as a clinical syndrome. Based on consumer complaints, it is clear that sensitive skin is a term used by individuals who perceive their skin as being more intolerant or reactive than the general population. Consequently, sensitive skin could be defined as a hyperreactive skin, characterized by exaggerated sensorial reaction to environmental or topical factors, including hard water and cosmetics. Consequently, instead of “sensitive skin,” it is better to call this syndrome “self-perceived sensitive skin” (SPSS). In the last decade, some new understanding on the mechanisms of sensitive skin, involving sensitive epidermal nerves has been emphasized [4].

Clinical signs and provocative factor

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


Sensitive skin is clinically characterized by subjective, sensorial signs: facial discomfort with stinging, burning, and itching. SPSS is more frequent in young women, and decreases with age. The clinical signs of sensitive skin appear in specific conditions, provoked by reactivity factors: • Environmental factors: wind, sun, cold weather, fast changes in temperature; • Topical factors: hard water, cosmetics; • Internal factors: life stress, menstruation, or spicy or hot foods.

Clinical subgroups Although the distribution of sensitive skin occurs throughout the population, multivariate analysis shows that several subgroups could be defined [4,5], according to the severity of sensitive skin and to the provocative factors: 1 Severe sensitive skin; 2 Sensitive skin to environment; 3 Sensitive skin to topical factors.

Severe sensitive skin Severe sensitive skin demonstrates very high facial skin reactivity to all kinds of factors: topical, environmental including atmospheric pollution and also internal factors such as stress and tiredness. Severe sensitive skin could present as “crisis phases” occurring for several days or weeks. During these phases, known as “status cosmeticus,” the skin becomes intolerant to all applied products, even products that are usually very well tolerated by the consumer [6].

3. Self-perceived sensitive skin

Sensitive skin to topical factors Around 25% of women have sensitive skin to topical factors. In this subgroup of sensitive skin, the provocative factor is the application of a product on the skin. It is important to underline that the intolerance observed appears immediately or in the minutes following application, sometimes from the first application.

Table 3.1 List of tested allergens on self-perceived sensitive skin and non-self-perceived sensitive skin subjects. (From [4] and [9].) Diazolidinyl urea





Ethylene diamine

Balsam of Peru


Sensitive skin to environmental factors Around 15–20% of women have sensitive skin to environmental factors such as heat, rapid changes in temperature, or wind.

Benzoic acid

Glyceryl monothioglycolate


Ammonium thioglycolate

Parabens mix


Diathesis factors

Ammonium persulfate


In most cases of sensitive skin, the skin hyperreactivity is constitutional. Thiers [1], who was the first to describe this syndrome, has suggested that diathesis features could exist. We also found that a familiar history of sensitive skin exists. Sensitive skin is more frequently found in subjects with fair complexion, and/or redness on the cheekbones [7,8]. Severe dry skin could be as affected as severe oily skin by skin hyperreactivity. Acquired skin hyperreactivity could mimic the signs observed during sensitive skin syndrome. This acquired “sensitive skin,” characterized by a temporary decrease of the threshold of sensorial reactivity of the skin, could be linked to topical irritants improperly applied such as retinoids or hydroxy-acids. In these cases, it is possible that skin that is usually “non-reactive” becomes “reactive” for a period of time. The presence of active facial dermatitis such as seborrheic dermatitis or rosacea could also lower the threshold of skin reactivity. However, although an outbreak of facial atopic dermatitis increases skin reactivity, it is incorrect to consider all sensitive skin as atopic skin.


Fragance mix

Sensitive skin and immuno-allergologic pattern An important point about sensitive skin comes from controversial opinions that exist regarding allergic status [5,7]. To explore this, skin patch test reactivity was studied in 152 female adult volunteers [9]. Eighty-eight declared themselves as having sensitive skin, and 64 as having nonsensitive skin. A series of 44 different topical ingredients known to be potential allergens were applied to the back under Finn Chambers (Table 3.1). The patches were removed after 47 hours and the reactions read after 1 hour and 2 days. For each ingredient, the incidence of positive reactions was compared between the two populations, using the χ2 test. Positive reactions were recorded for 19 out of the 44 tested compounds. No significant difference in the incidence of positive reactions was found between sensitive and non-sensitive skin subjects for any of the patch-tested ingredients. Currently, sensitive skin must not be considered as a syndrome linked to an immuno-allergologic pattern.

Wool alcohols

Diagnosis Provocative tests The diagnosis of SPSS must be based on clinical signs, which are neurosensorial (i.e. subjective). In fact, facial stinging, burning, and itching are clinical signs directly felt by the subject but not seen by the observer. It corresponds to the concept of “invisible dermatoses” [10], as is also the case for all sensorial signs encountered in dermatology (e.g. itching, pain). Pertinent clinical questionnaires are probably the best tools to diagnose this syndrome. Provocative tests could be of help. The lactic acid stinging test was first described by Frosch and Kligman [2,11]. A solution of 10% lactic acid is applied to a nasolabial fold and the provoked stinging feeling is quantified. Generally, the stinging is measured every minute for 5 minutes on a scale from 0 to 3. The lactic acid reaction is compared with the other nasolabial fold where a control solution (saline solution) is applied. The test discriminates between “stingers” and “non-stingers,” but does not affect the discrimination between sensitive skin and non-sensitive skin subjects [12]. In our opinion, the lactic acid stinging test is of interest to assess efficacy of products, but not for diagnostic purposes. Considering the clinical signs linked to SPSS (stinging, burning, itching), we have hypothesized that the main player is the sensitive epidermal nerve, C-fibers [13]. According to this physiologic hypothesis, we have proposed to test the skin reactivity by using capsaicin [14], an irritant compound extracted from red pepper which acts on vanilloid receptors of the nociceptive C-fibres and provokes the release of neuropeptides as substance P and calcitonin generelated peptide (CGRP) [15,16].



Skin Physiology

Capsaicin cream (0.075%) was applied at the angle of the jaw over an area of 4 cm2. The neurosensorial signs (stinging, burning, and itching [SBI]) were assessed at 3, 5, 10, 15 and 20 minutes according to a scale score (0, 1, 2, 3). The sum of the scores gives the global SBI score. The results we obtained on two groups of subjects clearly showed that the sensitive skin subjects’ (n = 64) reactions were significantly higher than the non-sensitive subjects (n = 88) (Figure 3.1). The capsaicin test allows one to discriminate quite well between SPSS subjects and non-SPSS subjects. On the same population sample, we compared the scores obtained with the capsaicin test with those from the lactic acid stinging test. The results are presented in Table 3.2. With capsaicin, the scores showed a better correlation to the SPSS than those recorded with lactic acid. Furthermore, there is a real relationship between the severity of the sensitive skin and the response to the capsaicin test. The higher the severity of SPSS, the higher the capsaicin score.

Sensitive skin and populations Epidemiologic data The prevalence of SPSS is estimated at 51–56% in Europe, USA, and Japan [8,17–20]. Willis et al. [8] published an epidemiologic study in the UK on sensitive skin where 2058 people (up to 18 years of age) were investigated. Of those who reposonded, 51% of the women and 38% of the men declared themselves to have sensitive skin. In the San Francisco area, the reported prevalence of SPSS in four ethnic groups (African-American, Asian, EuroAmerican, and Hispanic Central American) is 52% [19]. No significant difference of prevalence in each group was found: 52% of African-Americans had sensitive skin, 51% of Asians, 50% of Euro-Americans, and 54% of South Americans. Yang et al. [21] studied the sensitive skin in four cities of China: Beijing and Harbin (northern cities), Chengdu and Suzhou (southern cities). Two thousand Chinese women, aged 18–75 years, were included. The global prevalence of sensitive skin was 36%. The prevalence decreases with age (47% at 21–25 years; 20.8% at 51–55 years).

Global discomfort (stinging + burning + itching) 2.5

Clinical features

Mean score


Although the comparison of groups living in San Francisco (African-Americans, Asians, Euro-Americans, and Hispanics) gave the same prevalence of sensitive skin (52%), some differences (10) were observed for factors of skin reactivity and, to a lesser extent, its clinical symptoms. EuroAmericans were characterized by higher skin reactivity to the wind and tended to be less reactive to cosmetics. African-Americans presented less skin reactivity to most environmental factors and a lower frequency of recurring facial redness. Asians appeared to have greater skin reactivity to sudden changes in temperature, to the wind, and also to spicy foods. They tended to experience itching more frequently. In addition, the frequency of skin reactivity to alcoholic beverages was significantly lower in the African-

1.5 1.0 0.5 Sensitive skin (n = 88) Non-sensitive skin (n = 64)

0 0


10 5 Time (minutes)



Figure 3.1 Stinging, burning, and itching (SBI) score with capsaicin test on self-perceived sensitive skin and non-self-perceived sensitive skin subjects. Scores are significantly different at each experimental time (p < 0.01). (From [4] and [14].)

Table 3.2 (a) Stinging and itching scores with capsaicin test according to the different selfassessed level of self-perceived sensitive skin. (From [4].) Non-sensitive (n = 64)

Sensitive (n = 88)





(n = 42)

(n = 39)

(n = 7)


2.6 ± 0.6

3 ± 0.6

4.3 ± 0.6

5 ± 0.6

p < 0.02


0.6 ± 0.4

1.6 ± 0.4

2 ± 0.4

2.9 ± 0.4

p < 0.02


3. Self-perceived sensitive skin

Table 3.2 (b) Stinging scores during lactic acid stinging test according to the different self-assessed level of self-perceived sensitive skin. (From [4].)

skin, suggesting a direct involvement of epidermal sensitive nerves in skin reactivity.

Specific brain activation on sensitive skin subjects Non-sensitive (n = 64)

2 ± 0.3

Sensitive (n = 88)





(n = 42)

(n = 39)

(n = 7)

2 ± 0.2

3.3 ± 0.3

3 ± 0.3

p < 0.001

p < 0.001

p < 0.01

American and Hispanic sensitive groups and higher in the Asian group. In China, Yang et al. [21] have reported that sensitive skin was strongly reactive to environmental factors, but not to cosmetic use. A significantly higher prevalence (55.8%) of sensitive skin was found in Chengdu (Sichuan), where the food is very spicy. By studying the link between chili consumption and sensitive skin prevalence, it has been confirmed that sensitive skin was strongly linked to spicy food intake.

Physiologic mechanisms involved in selfperceived sensitive skin Barrier function and sensitive skin It is currently believed that sensitive skin is linked to the skin barrier alteration which could explain the increase in skin reactivity to physical or chemical factors. In fact, transepidermal water loss (TEWL) has been reported to be increased in subjects with sensitive skin [18]. In addition, an increase in TEWL has also been reported in the “lactic acid stingers” subjects [12]. The alteration of the skin barrier function is certainly involved in the physiology of some patterns of sensitive skin, but it is not unequivocal.

Epidermal sensitive nerves and sensitive skin In the last decade, additional evidence has been discovered implicating the key role for sensitive nerves in the physiologic mechanisms involved in sensitive skin. The neurosensorial signs of the pattern of capsaicin reactivity of sensitive skin suggest a neurogenic origin [14]. Recent data that emphasize the role of C-fibres in the itching process must also be considered [13]. It is observed that there is a decrease with age in the epidermal sensitive nerve density on the face [22]. It should also be noticed that there is a similar decrease in the facial skin reactivity to capsaicin and in the prevalence of sensitive

To investigate the possible involvement of the central nervous system (CNS) in SPSS patterns, we measured cerebral responses to cutaneous provocative tests in sensitive and in non-sensitive skin subjects using functional magnetic resonance imaging (fMRI) [23]. According to their responses to validated clinical questions about their skin reactivity, subjects were divided into two balanced groups: severe SPSS and non-SPSS subjects. Event-related fMRI was used to measure cerebral activation induced by split-face application of lactic acid and of its vehicle (control). In sensitive skin subjects, prefrontal and cingulate activity was significantly higher demonstrating a CNS involvement in sensitive skin physiologic pathways.

Conclusions Sensitive skin is a syndrome observed all over the world. The key clinical features of sensitive skin are neurosensorial signs, mainly provoked by climatic factors, or by topical applications usually well-tolerated on skin. The hypothesis of the neurogenic origin of sensitive skin is becoming more and more predominant. 1 Sensitive skin subjects demonstrate a significantly higher skin hyperreactivity to capsaicin which specifically stimulates the C-fibers. 2 With age, as sensitive skin is decreasing, facial sensitive epidermal nerve density is also decreasing. 3 Spicy food (rich in capsaicin) increases the prevalence of sensitive skin. 4 The results obtained with fMRI show that sensitive skin subjects demonstrate a specific pattern on cerebral activation, with a higher brain activity for sensitive skin subjects in prefrontal and cingulated areas.

References 1 Thiers H. (1986) Peau sensible. In: H. Thiers. Les Cosmétiques, 2nd edn. Paris: Masson, pp. 266–8. 2 Frosch PJ, Kligman AM. (1977) A method of appraising the stinging capacity of topically applied substances. J Soc Cosmet Chem 28, 197–209. 3 Maibach HI, Lammintausta K, Berardesca E, Freeman S. (1989) Tendancy to irritation: sensitive skin. J Am Acad Dermatol 21, 833–5. 4 De Lacharrière O. (2006) Sensitive skin: a neurological perspective. 24th IFSCC, Osaka, October 2006. 5 Francomano M, Bertoni L, Seidenari S. (2000) Sensitive skin as a subclinical expression of contact allergy to nickel sulfate. Contact Dermatitis 42, 169–70. 6 Fisher AA. (1990) Part I: “Status cosmeticus”: a cosmetic intolerance syndrome. Cutis 46, 109–11016.



Skin Physiology

7 De Lacharriere O, Jourdain R, Bastien P, Garrigue JL. (2001) Sensitive skin is not a subclinical expression of contact allergy. Contact Dermatitis 44, 131–2. 8 Willis CM, Shaw S, De Lacharriere O, Baverel M, Reiche L, Jourdain R, et al. (2001) Sensitive skin: an epidemiological study. Br J Dermatol 145, 258–63. 9 Jourdain R, De Lacharrière O, Shaw S, Reiche L, Willis C, Bastien P, et al. (2002) Does allergy to cosmetics explain sensitive skin? Ann Dermatol Venereol 129, 1S11–77. 10 Kligman AM. (1991) The invisible dermatoses. Arch Dermatol 127, 1375–82. 11 Frosch P, Kligman AM. (1996) An improved procedure for conducting lactic acid stinging test on facial skin. J Soc Cosmet Chem 47, 1–11. 12 Seidenari S, Francomano M, Mantovani L. (1998) Baseline biophysical parameters in subjects with sensitive skin. Contact Dermatitis 38, 311–5. 13 Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjörk HE. (1997) Specific C-receptors for itch in human skin. J Neurosci 17, 8003–8. 14 de Lacharrière O, Reiche L, Montastier C, et al. (1997) Skin reaction to capsaicin: a new way for the understanding of sensitive skin. Australas J Dermatol 38(Suppl 2), 288. 15 Magnusson BM, Koskinen LO. (1996) Effects of topical application of capsaicin to human skin: a comparison of effects evaluated by visual assessment, sensation registration, skin blood flow




18 19





and cutaneous impedance measurements. Acta Derm Venereol 76, 29–32. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816–24. Johnson AW, Page DJ. (1995) Making sense of sensitive skin. Proceedings of the 18th IFSCC Congress, Yokohama, Japan 1995. Morizot F, Le Fur I, Tschachler E. (1998) Sensitive skin: definition, prevalence and possible causes. Cosm Toil 113, 59–66. Jourdain R, De Lacharriere O, Bastien P, Maibach HI. (2002) Ethnic variations in self-perceived sensitive skin: epidemiological survey. Contact Dermatitis 46, 162–9. Morizot F, Le Fur I, Numagami K, Guinot C, Lopez S, Tagami H, et al., eds. Self-reported sensitive skin: a study on 120 healthy Japanese women. 22nd IFSCC, Edinburgh, September 2002. Yang FZ, De Lacharriere O, Lian S, Yang ZL, Li L, Zhou W, et al. (2002) Sensitive skin: specific features in Chinese skin: a clinical study on 2,000 Chinese women. Ann Dermatol Venereol 129, 1S11–77. Besne I, Descombes C, Breton L. (2002) Effect of age and anatomical site on density innervation in human epidermis. Arch Dermatol 138, 1445–50. Querleux B, Dauchot K, Jourdain R, Bastien P, Bittoun J, Anton JL, et al. (2008) Neural basis of sensitive skin: an fRMI study. Skin Res Technol 1, 1–8.

Chapter 4: Pigmentation and skin of color Chesahna Kindred and Rebat M. Halder Howard University College of Medicine, Washington, DC, USA

BAS I C CONCEPTS • Differences in the structure, function, and physiology of the hair and skin in individuals of skin of color are important in understanding the structural and physiologic variations that exist and influence disease presentations. • Melanin, the major determinant of skin color, absorbs UV light and blocks free radical generation, protecting the skin from sun damage and aging. • UV irradiation of keratinocytes induces pigmentation by the upregulation of melanogenic enzymes, DNA damage that induces melanogenesis, increased melanosome transfer to keratinocytes, and increased melanocyte dendricity. • Racial differences in hair include the hair type, shape, and bulb.

Introduction The demographics of the USA reflect a dynamic mixture of people of various ethnic and racial groups. Currently, one in three residents in the USA is a person of skin of color [1]. Persons of skin of color include Africans, African-Americans, Afro-Caribbeans, Asians, Latinos (Hispanics), Native Americans, Middle Easterners, and Mediterraneans. The term “black” as in black skin refers to individuals with African ancestry, including Africans, African-Americans, and Afro-Caribbeans. Subgroups exist within each ethnoracial group. The differences in the structure, function, and physiology of the hair and skin in individuals of skin of color are important in understanding the structural and physiologic variations that exist and influence disease presentations. Pigmentation is especially important in patients of skin of color because pigmentary disorder is the most common reason for a visit to a dermatologist in this group [2].

Melanocytes Melanin, the major determinant of skin color, absorbs UV light and blocks free radical generation, protecting the skin from sun damage and aging. Melanocytes, the cells that produce melanin, synthesize melanin in special organelles, melanosomes. Melanin-filled melanosomes are transferred from one melanocyte to 30–35 adjacent keratinocytes in the basal layer [3]. The number of melanocytes also decreases with age. Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

There is more than one type of melanin: eumelanin, a dark brown–black pigment; and pheomelanin, a yellow– reddish pigment. Eumelanin is deposited in ellipsoidal melanosomes which contain a fibrillar internal structure. Synthesis of eumelanin increases after UV exposure (tanning). Pheomelanin has a higher sulfur content than eumelanin because of the sulfur-containing amino acid cysteine. Pheomelanin is synthesized in spherical melanosomes and is associated with microvesicles [4]. Although not obvious to the naked eye, most melanin pigments of the hair, skin and, eyes are combinations of eumelanin and pheomelanin [5]. It is generally believed that genetics determine the constitutive levels of pheomelanin and eumelanin. Eumelanin is more important in determining the degree of pigmentation than pheomelanin. Eumelanin, and not pheomelanin, increases with visual pigmentation [5]. Lighter melanocytes have higher pheomelanin content than dark melanocytes. In one study [5], white persons had the least amount of eumelanin, Asian Indians had more, and AfricanAmericans had the highest. Of note, adult melanocytes contain significantly more pheomelanin than cultured neonatal melanocytes. Melanosomes also differ among different races. In black persons they are mostly in the basal layer, but those of white persons are mostly in the stratum corneum. This is evident in the site of UV filtration: the basal and spinous layers in blacks and the stratum corneum in white persons. Of note, the epidermis of black skin rarely shows atrophied areas [6]. In black skin, melanocytes contain more than 200 melanosomes. The melanosomes are 0.5–0.8 mm in diameter, do not have a limiting membrane, are stuck closely together, and are individually distributed throughout the epidermis. In white skin, the melanocytes contain less than 20 melanosomes. The melanosomes are 0.3–0.5 mm in



Skin Physiology

diameter, associated with a limiting membrane, and distributed in clusters with spaces between them. The melanosomes of lighter skin degrade faster than that of dark skin. As a result, there is less melanin content in the upper layers of the stratum corneum. Thus, the melanocytes in black skin are larger, more active in making melanin, and the melanosomes are packaged, distributed, and broken down differently from in white skin. There is also a difference in melanosomes between individuals within the same race but with varying degrees of pigmentation. Despite greater melanin content in darker skins, there is no evidence of major differences in the number of melanocytes [7]. Also, dark Caucasian skin resembles the melanosome distribution observed in black skin [8]. Black persons with dark skin have large, nonaggregated melanosomes and those with lighter skin have a combination of large non-aggregated and smaller aggregated melanosomes [9]. White persons with darker skin have non-aggregated melanosomes when exposed to sunlight and white persons with lighter skin have aggregated melanosomes when not exposed to sunlight [7,8,10]. The steps of melanogenesis are as follows. The enzyme tyrosinase hydroxylates tyrosine to dihydroxyphenylalanin (DOPA) and oxidizes DOPA to dopaquinone. Dopaquinone then undergoes one of two pathways. If dopaquinone binds to cysteine, the oxidation of cysteinyldopa produces pheomelanin. In the absence of cysteine, dopaquinone spontaneously converts to dopachrome. Dopachrome is then decarboxylated or tautomerized to eventually yield eumelanin. Melanosomal P-protein is involved in the acidification of the melanosome in melanogenesis [11]. Finally, the tyrosinase activity (not simply the amount of the tyrosinase protein) and cysteine concentration determine the eumelanin–pheomelanin content [5]. Tyrosinase and tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2) are upregulated when α-melanocyte-stimulating hormone (α-MSH) or adrenocorticotropin binds to melanocortin-1 receptor (MC1R), a transmembrane receptor located on melanocytes [11–14]. The MC1R loss-offunction mutation increases sensitivity to UV-induced DNA damage. Gene expression of tyrosinase is similar between black and white persons, but other related genes are expressed differently. The MSH cell surface receptor gene for melanosomal P-protein is expressed differently between races. This gene may regulate tyrosinase, TRP-1, and TRP-2 [5]. In addition to the MC1R, protease-activated receptor 2 (PAR-2) is another important receptor that regulates epidermal cells and affect pigmentation [15]. PAR-2 is expressed on many cells and several different organs. Accordingly, the receptor is involved in several physiologic processes, including growth and development, mitogenesis, injury responses, and cutaneous pigmentation. In the skin, PAR-2 is expressed


in the keratinocytes of the basal, spinous, and granular layers of the epidermis, endothelial cells, hair follicles, myeoepithelial cells of sweat glands, and dermal dendritic-like cells [16,17]. PAR-2 is a seven transmembrane domain G-protein-coupled receptor which undergoes activation via proteolytic cleavage of the NH2 terminus which acts as a tethered ligand which then activates the receptor (autoactivation). PAR-2 activating protease (PAR-2-AP), endothelial cellreleased trypsin, mast cell-released trypsin and chymase, and SLIGKV all irreversibly activate PAR-2 while serine protease inhibitors interferes with the activation of the receptor [18–20]. SLIGKV and trypsin activate PAR-2 to use a Rhodependent signaling pathway to induce melanosomal phagocytosis by keratinocytes. The result is an increase in pigmentation to the same degree as UV radiation [17–21]. Serine proteases are regulatory proteins involved in tumor growth, inflammation, tissue repair, and apoptosis in various tissues [17]. In the skin, serine protease inhibitors prevent the keratinocytes from phagocytosing melanosomes from the presenting dendritic tip of the melanocyte. This leads to a dose-dependent depigmentation without irritation or adverse events. PAR-2 also has a proinflammatory affect in the skin [17]. The activation of PAR-2 expressed on endothelial cells by tryptase, trypsin, or PAR-2-AP leads to an increase in proinflammatory cytokines interleukin 6 (IL-6) and IL-8 and also stimulates NF-κB, an intracellular proinflammatory regulator [18]. Mast cells interact with endothelial cells to regulate inflammatory responses, angiogenesis, and wound healing, and PAR-2 has a regulatory role in this cell–cell interaction [17,18]. UV irradiation of keratinocytes induces pigmentation in several ways: upregulation of melanogenic enzymes, DNA damage that induces melanogenesis, increased melanosome transfer to keratinocytes and increased melanocyte dendricity. UV radiation (UVR) increases the secretion of proteases by keratinocytes in a dose-dependent manner. Specifically, UVR directly increases the expression of PAR-2 de novo, upregulates proteases that activate PAR-2, and activates dermal mast cell degranulation [21]. Data on whether PAR-2 is expressed differently in skin of color compared to white skin are needed. One study did find differences in skin phototypes I, II, and III [21]. UVR increases the expression of PAR-2 in the skin and activated PAR-2 stimulates pigmentation. This study found that the response of PAR-2 to UVR is an important determinant of one’s ability to tan. In the non-irradiated skin, PAR-2 expression was confined to the basal layer and just above the basal layer. Irradiated skin showed de novo PAR-2 expression in the entire epidermis or upper twothirds of the epidermis. Skin phototype I had a delayed upregulation of PAR-2 expression compared to phototypes II and III.

4. Pigmentation and skin of color

Dyspigmentation After cutaneous trauma or inflammation, melanocytes can react with normal, increased, or decreased melanin production; all of which are normal biologic responses. Increased and decreased production results in postinflammatory hyperpigmentation or hypopigmentation. Postinflammatory hyperpigmentation (PIH) is an increase in melanin production and/or an abnormal distribution of melanin resulting from inflammatory cutaneous disorders or irritation from topical medications [22,23]. Examples include acne, allergic contact dermatitis, lichen planus, bullous pemphigoid, herpes zoster, and treatment with topical retinoids. Often, the PIH resulting from acne is more distressing to darker skinned individuals than the initial acute lesion. The color of the hyperpigmentation in PIH depends on the location of the melanin. Melanin in the epidermis appears brown, while melanin in the dermis appears blue-gray. Wood’s lamp examination distinguishes the location of the melanin: the epidermal component is enhanced and the dermal component becomes unapparent [24]. Postinflammatory hypopigmentation shares the same triggers as PIH but instead results from decreased melanin production with clinically apparent light areas [23]. The Wood’s lamp examination does not accentuate hypopigmentation in postinflammatory hypopigmentation; it is useful for depigmented disorders such as vitiligo and piebaldism. The pathogenesis of PIH and postinflammatory hypopigmentation are unknown. It is likely that an inflammatory process in the skin stimulates keratinocytes, melanocytes, and inflammatory cells to release cytokines and inflammatory mediators that lead to the hyperpigmentation or hypopigmentation. The cytokines and inflammatory mediators include leukotriene (LT), prostaglandins (PG), and thromboxane (TXB) [25]. Specifically for PIH, in vitro studies revealed that LT-C4, LT-D4, PG-E2, and TXB-2 stimulate human melanocyte enlargement and dendrocyte proliferation. LT-C4 also increases tyrosinase activity and mitogenic activity of melanocytes. Transforming growth factor-α and LT-C4 stimulate movement of melanocytes. In postinflammatory hypopigmentation, the pathogenesis likely involves inflammatory mediators inducing melanocyte cell-surface expression of intercellular adhesion molecule 1 (ICAM-1) which may lead to leukocyte–melanocyte attachments that inadvertently destroy melanocytes. These inflammatory mediators include interferon-gamma, tumor necrosis factor α (TNF-α), TNF-β, IL-6, and IL-7.

Natural sun protective factor in skin of color It is clear that those who fall within Fitzpatrick skin phototypes IV–VI are less susceptible to photoaging; this is most

likely due to of the photoprotective role of melanin [26,27]. The epidermis of black skin has a protective factor (PF) for UVB of 13.4 and that of white skin is 3.4 [28]. The mean UVB transmission by black epidermis is 5.7% compared to 29.4% for white epidermis. The PF for UVA in black epidermis is 5.7 and in white epidermis is 1.8 [28]. The mean UVA transmission by black epidermis is 17.5% and 55.5% for white epidermis. Hence, 3–4 times more UVA reaches the upper dermis of white persons than that of black persons. The main site of UV filtration in white skin is the stratum corneum, whereas in black skin it is the basal layer [28]. The malphigian layer of black skin removes twice as much UVB radiation as the stratum corneum [29]. It is possible that even greater removal of UVA occurs in black skin basal layers [29]. While the above characteristics of natural sun protective factor were studied in black skin, they can probably be extrapolated to most persons of skin photoypes IV–VI.

Skin of color Epidermis The epidermal layer of skin is made up of five different layers: stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum. The stratum basale (also termed the basal layer) is the germinative layer of the epidermis. The time required for a cell to transition from the basal layer through the other epidermal layers to the stratum corneum is 24–40 days. The morphology and structure of the epidermis is very similar among different races, although a few differences do exist.

Stratum corneum The stratum corneum, the most superficial layer, is the layer responsible for preventing water loss and providing mechanical protection. The cells of the stratum corneum, the corneocytes, are flat cells measuring 50 μm across and 1 μm thick. The corneocytes are arranged in layers; the number of layers varies with anatomic site and race. There are no differences between races in corneocyte surface area, which has a mean size of 900 μm [2,30]. The stratum corneum of black skin is more compact than that of white skin. While the mean thickness of the stratum corneum is the same in black and white skin, black skin contains 20 cell layers while white skin contains 16. The answer to whether or not there are racial differences in spontaneous desquamation is inconclusive [29–31]. Parameters for skin barrier function (stratum corneum hydration, sebum secretion, erythema, and laser Doppler flowmetry) are similar, even after an objective epicutaneous test with sodium lauryl sulfate [32].



Skin Physiology

Transepidermal water loss Transepidermal water loss (TEWL) is the amount of water vapor loss from the skin, excluding sweat. TEWL increases with the temperature of the skin. Concrete evidence regarding the difference in TEWL between different races has yet to be established. Aside from TEWL, hydration is also a characteristic of skin. One of the ways to measure hydration, or water content, is conductance. Conductance, the opposite of resistance, is increased in hydrated skin because hydrated skin is more sensitive to the electrical field [33]. Skin conductance is higher in black persons and Hispanics than white persons [33]. Lipid content in black skin is higher than that of white skin [34]. However, black skin is more prone to dryness, suggesting that a difference in lipid content has a role. This includes the ratio of ceramide : cholesterol : fatty acids, the type of ceramides, and the type of sphingosine backbone. One study suggests that the degree of pigmentation influences lipid differences [35]. Pigmentation affects skin dryness. Skin dryness is greater on sun-exposed (dorsal arm) sites for lighter skin, such as Caucasian and Chinese skin, than sites that are primarily out of the sun (ventral arm) [36]. There is no difference in skin dryness between sites for darker skin, such as AfricanAmericans and Mexicans. For adults less than 51 years of age, skin dryness does not change as a function of ethnicity (African-American, Caucasian, Chinese, and Mexican) for sun-exposed sites and sites that are not primarily sunexposed. For those 51 years of age and older, skin dryness is higher for African-Americans and Caucasians than for Chinese and Mexicans. As a function of age, skin dryness in African-American skin increases 4% on the dorsal site and 3% on the ventral site; in Caucasian skin, it increases 11% on the dorsal site and 10% on the ventral site. All of the above findings suggest that sun exposure can dry the skin and that melanin provides protection.

Skin reactivity Mast cells Sueki et al. [37] studied the mast cells of four AfricanAmerican men and four white men (mean age 29 years) by evaluating punch biopsies of the buttocks with electron microscopy, with the following results. The mast cells of black skin contained larger granules (the authors attributed this to the fusion of granules). Black skin also had 15% more parallel-linear striations and 30% less curved lamellae in mast cells. Tryptase reactivity was localized preferentially over the parallel-linear striations and partially over the dark amorphous subregions within granules of mast cells from black skin, whereas it was confined to the peripheral area of granules, including curved lamellae, in white skin. Cathepsin G reactivity was more intense over the electrondense amorphous areas in both groups, while parallel-linear striations in black skin and curved lamellae in white skin were negative.


Patch test antigens Contact dermatit* Irritant contact dermatitis (ICD) is the most common form of dermatitis and loosely defined as non-specific damage to the skin after exposure to an irritant. The various clinical manifestations are influenced by the concentration of chemicals, duration of exposure, temperature, humidity, and anatomic location, and other factors. Acute contact dermatitis presents with the classic findings of localized superficial erythema, edema, and chemosis. Cumulative contact dermatitis presents with similar findings, but with repeated exposure of a less potent irritant [38]. The susceptibility to ICD differs between black and white skin [39]. The structural differences in stratum corneum of black skin (e.g. compact stratum corneum, low ceramide levels) are credited with decreasing the susceptibility to irritants. Reflectance confocal microscopy (RCM) is an imaging tool that permits real-time qualitative and quantitative study of human skin; when used with a near-infrared laser beam, one can create “virtual sections” of live tissue with high resolution, almost comparable with routine histology. Measuring skin reactivity to chemical irritants with RCM and TEWL reveal that white skin had more severe clinical reactions than black skin. The pigmentation in darker skin can make the assessment of erythema difficult and interfere with identification of subclinical degrees of irritancy. Even without clinical evidence of irritation, RCM and histology reveal parakeratosis, spongiosis, perivascular inflammatory infiltrate, and microvesicle formation. Mean TEWL after exposure to irritants is greater for white skin than for black skin. This supports the concept that the stratum corneum of black skin enhances barrier function and resistance to irritants. There are no differences between white persons and African-Americans in objective and subjective parameters of skin such as dryness, inflammation, overall irritation, burning, stinging, and itching [40]. Acute contact dermatitis with exudation, vesiculation, or frank bullae formation is a more common reaction in white skin whereas dyspigmentation and lichenification is more common in black skin [41]. The response to irritation in Caucasian and AfricanAmerican skin differs in the degree of severity. Caucasian skin has a lower threshold for cutaneous irritation than African-American skin [42]. Caucasian skin also has more severe stratum corneum disruption, parakeratosis, and detached corneocytes. Both groups have the same degree of intra-epidermal spongiosis epidermal (granular and spinous layer) vesicle formation. The variability in human skin irritation responses sometimes creates difficulty in assessing the differences in skin reactivity between human subpopulations. There are conflicting results in studies comparing the sensitivity to irritants in Asian skin with that in Caucasian skin [32,43–46].

4. Pigmentation and skin of color

Dermis The dermis lies deep to the epidermis and is divided into two layers: the papillary and reticular dermis. The papillary dermis is tightly connected to the epidermis via the basem*nt membrane at the dermoepidermal junction. The papillary dermis extends into the epidermis with finger-like projections, hence the name “papillary.” The reticular dermis is a relatively avascular, dense, collagenous structure that also contains elastic tissue and glycosaminoglycans. The dermis is made up of collagen fibers, elastic fibers, and an interfibrillar gel of glycosaminoglycans, salt, and water. Collagen makes up 77% of the fat-free dry weight of skin and provides tensile strength. Collagen types I, II, V, and VI are found in the dermis. The elastic fiber network is interwoven between the collagen bundles. There are differences between the dermis of white and black skin. The dermis of white skin is thinner and less compact than that of black skin [47]. In white skin, the papillary and reticular layers of the dermis are more distinct, contain larger collagen fiber bundles, and the fiber fragments are sparse. The dermis of black skin contains closely stacked, smaller collagen fiber bundles with a surrounding ground substance. The fiber fragments are more prominent in black skin than in white skin. While the quantity is similar in both black and white skin, the size of melanophages is larger in black skin. Also, the number of fibroblasts and lymphatic vessels are greater in black skin. The fibroblasts are larger, have more biosynthetic organelles, and are more multinucleated in black skin [6]. The lymphatic vessels are dilated and empty with surrounding elastic fibers [47]. No racial differences in the epidermal nerve fiber network have been observed using laser-scanning confocal microscopy, suggesting that there is no difference in sensory perception between races, as suggested by capsaicin response to C-fiber activation [48]. Skin extensibility is how stretchable the skin is. Elastic recovery is the time required for the skin to return to its

original state after releasing the stretched skin. Skin elasticity is elastic recovery divided by extensibility. Studies that investigated skin extensibility, elastic recovery, and skin elasticity between races yield conflicting results [31,49]. It is likely that elastic recovery and extensibility vary by anatomic site, race, and age.

Intrinsic skin aging in ethnic skin The majority of literature regarding facial aging features Caucasian patients. Facial aging is result of the combination of photodamage, fat atrophy, gravitational soft tissue redistribution, and bone remodeling. Figure 4.1 demonstrates the morphologic changes of the face caused by aging. The onset of morphologic aging appears in the upper face during the thirties and gradually progresses to the lower face and neck over the next several decades [50]. Early signs of facial aging occur in the periorbital region. In the late thirties, brow ptosis, upper eyelid skin laxity, and descent of the lateral portion of the eyebrow (“hooding”) lead to excess skin of the upper eyelids. During the midforties, “bags” under the eyes result from weakening of the inferior orbital septum and prolapse of the underlying intraorbital fat. Lower eyelid fat prolapse may occur as early as the second decade in those with a familial predisposition. Photodamage produces periocular and brow rhytides [50]. Brow ptosis in African-Americans appears to occur to a lesser degree and in the forties opposed to the thirties compared to that in whites [51]. Prolapse of the lacrimal gland may masquerade as lateral upper eyelid fullness in AfricanAmericans [52]. For Hispanics, the brow facial soft tissues sag at an earlier age [53]. In Asians, the descent of thick juxtabrow tissues in the lateral orbit coupled with the absences of a supratarsal fold may create a prematurely tired eye [50]. The midface show signs of aging during the forties. The malar soft tissue adjacent to the inferior orbital rim descends, accumulating as fullness along the nasolabial fold. The malar

Facial expression lines

Figure 4.1 Morphologic signs of aging. (Adapted from figure by Cindy Luu. From Harris MO. (2006) Intrinsic skin aging in pigmented races. In: Halder RM, ed. Dermatology and Dermatological Therapy of Pigmented Skins. Taylor & Francis Group, pp. 197–209.)

High brow

Low brow

Prominent upper eyelid crease

Excess upper eyelid skin

Full lips

Prominent fat pockets Lower lid hollowing ‘dark circles’ Low cheek Prominent nasolabial fold

Smooth jawline


High protuberant cheek Soft nasolabial fold

Fat accumulation



Skin Physiology

soft tissue atrophy and ptosis result in periorbital hollowing and tear trough deformity. Early aging is evident in individuals of African, Asian, and Hispanic origin in the midface region more so than the upper or lower regions. Signs include tear trough deformity, infraorbital hollowing, malar fat ptosis, nasojugal groove prominence, and deepening of the nasolabial fold. This predisposition to midface aging is likely the result of the relationship of the eyes to the infraorbital rim, basic midface skeletal morphology, and skin thickness [50]. The soft tissue of the lower face is supported in a youthful anatomic position by a series of retaining ligaments within the superficial musculo-aponeurotic system (SMAS) [54]. The SMAS is a discrete fascial layer that envolps the face and forms the basis for resuspending sagging facial tissues [14]. The SMAS fascia envelope maintains tension on facial muscles and offsets soft tissue sagging. In the late thirties, gradual ptosis of the SMAS and skin elastosis sets the stage for jowl formation. Accumulation of submandibular fat and a sagging submandibular gland may have a role in interrupting the smooth contour of a youthful jaw line. Changes in the lower face lead to changes in the neck because the SMAS is anatomically continuous with the platysma muscle. Sagging of the SMAS–platysma unit and submandibular fat redistribution gradually blunts the junction between the jaw and neck. A “double chin” appears at any age as a result of cervicomental laxity with excess submental fat deposits. During the fifties, diastasis and hypertrophy of the anterior edge of the platysma muscle may produce vertical banding in the cervicomental area. During the sixth, seventh, and eighth decades, progressive soft tissue atrophy and bony remodeling of the maxilla and mandible create a relative excess of sagging skin, further exaggerating facial aging. Jowling is a sign of lower facial aging in black persons [50]. In some cases, a bony chin underprojection make create excess localized submental fatty deposits despite a smoothly contoured jaw line. However, in Asians, jowl formation may result from fat accumulation in the buccal space [50]. The “double chin” is more common in Caucasians under 40 years of age than Asians of the same age group, but more common in Asians over 40 years of age because of redundant cervical skin [55].

Extrinsic aging (photoaging) of ethnic skin Sunlight is a major factor for the appearance of premature aging, independent of facial wrinkling, skin color, and skin elasticity. By the late forties, individuals with greater sun exposure appear older than those with less sun exposure. However, the perceived age of individuals in their late twenties is unaffected by sun exposure. Solar exposure greatly increases the total wrinkle length by the late forties. The extent of dermal degenerative change seen by the late forties correlates with premature aging. There is a high correlation between perceived age and facial wrinkles; perceived age


and elastosis; and perceived age and the quantity of collagen. The grenz zone is a subepidermal band of normal dermis consisting of normal collagen fibers and thought to be a site of continual dermal repair. The grenz zone becomes visually apparent only after there is sufficient elastotic damage. With progressive elastosis, the grenz zone beomces thinner [56].

Histopathology Epidermis The absolute number of Langerhans cells vary from person to person but chronic sun exposure decreases their number or depletes them [57]. The severely sun-damaged skin has many vacuolated cells in the spinous layer, excessively vacuolated basal keratinocytes and melnanocytes, cellular atypia, and loss of cellular polarity. Apoptosis in the basal layer is increased. A faulty stratum lucidum and horny layer result from intracellur vesicles in the cells of the basal and spinous layers (sunburn cells), apoptosis, and dyskeratosis. There is focal necrobiosis in the epidermis and dermis in sun-exposed skin. While histologic findings of photoaging in white sunexposed skin include a distorted, swollen, and distinctly cellular stratum lucidum, the stratum lucidum of AfricanAmerican sun-exposed skin remains compact and unaltered [6]. The stratum lucidum in black skin is not altered by sunlight exposure [6]. With age, the dermoepidermal junction becomes flattened with multiple zones of basal lamina and anchoring fibril reduplication. Microfibrils in the papillary dermis become more irregularly oriented. Compact elastic fibers show cystic changes and separation of skeleton fibers with age. The area occupied by the superficial vascular plexus in specimens of equal epidermal surface length decreases from the infant to young adult (21–29 years) to adult (39–52 years) age groups, then increased in the elderly adult (73–75 years) age group [58]. With the exception of the vascularity in the elderly adult group, the above features are similar to those seen in aging white skin, and suggest that chronologic aging in white and black skin is similar. Oxytalan fibers are found in the papillary dermis of sun-exposed skin of white individuals in their twenties and early thirties but disappear in the forties. In black skin, the oxytalan fibers are still found in the dermis of individuals in their fifties. No solar elastosis is seen in specimens of black sun-exposed skin. Older black subjects have an increased number and thickness of elastic fibers that separate the collagenous fiber layer in the reticular dermis. The single-stranded elastic fibers in individuals <50 years of age resemble braids in those >50 years of age. Finally, the sun-exposed skin of a 45-year-old lightcomplexioned black female shared the same amount and distribution of elastic fibers as those in white sun-exposed skin [6]. The grenz zone consists of small fibers oriented horizontally and replaces the papillary dermis. When elastotic mate-

4. Pigmentation and skin of color rial accumulates in the dermis, it crowds out all the collagenous fibers, which are resorbed. As the elastic material is resorbed, wisps of collagenous fibers form in its place. Widely spaced, larger collagenous fiber bundles lie between the waning elastotic masses. The total volume of the dermis gradually diminishes as the spaces between the remaining collagenous and elastic fibers are reduced. When the epidermis rests directly on top of the horizontally oriented, medium-sized collagenous fiber bundles of the intermediate dermis, the dermis lacks a papillary and grenz zone and the dermis cannot sufficiently support the epidermis. As a result, the shrinking dermis crinkles and small wrinkles form. This may be the reason for the absence of a structural basis in secondary wrinkles and may explain why wrinkles flatten out when fluids are injected into the skin or when edema occurs [57]. Photoaging in skin of color has variable presentations. Wrinkling is not as common a manifestation of photoaging in black persons, South Asians, or darker complexioned Hispanics as in white persons because of the photoprotective effects of melanin. All racial groups are eventually subjected to photoaging. Within most racial groups, the lighter complexioned individuals show evidence of photodamaged skin. Caucasian skin has an earlier onset and greater skin wrinkling and sagging signs than darker skin types. Visual photoaging assessments reveal that white skin has more severe fine lines, rhytides, laxity, and overall photodamage than African-American skin [41]. Photoaging is uncommon in black persons but is more often seen in African-Americans than in Africans or AfroCaribbeans. The reason may be the heterogeneous mixture of African, Caucasian, and Native American ancestry often seen in African-Americans. In African-Americans, photoaging appears primarily in lighter complexioned individuals and may not be apparent until the late fifth or sixth decades of life [59]. Photoaging in this group appears as fine wrinkling and mottled pigmentation. In spite of the photoprotective effects of melanin, persons of skin of color are still prone to photoaging, but the reason is not completely known. Infrared radiation may also contribute to photodamage. There is evidence that chronic exposure to natural or artificial heat sources can lead to histologic changes resembling that of UV-induced changes, such as elastosis and carcinoma [60]. The pigmentary manifestations of photoaging common in skin of color include seborrheic keratoses, actinic lentigi-

nes, mottled hyperpigmentation, and solar-induced facial melasma [61]. However, African-American skin has greater dyspigmentation, with increased hyperpigmentation and uneveness of skin tone [40].

Hair There are two types of hair fibers: terminal and vellus. Terminal hair is found on the scalp and trunk. Vellus hair is fine and shorter and softer than terminal hair. The hair fiber grows from the epithelial follicle, which is an invagin*tion of the epidermis from which the hair shaft develops via mitotic activity and into which sebaceous glands open. The hair follicle is one of the most proliferative cell types in the body and undergoes growth cycles. The cycles include anagen (active growth), catagen (regression), and telogen (rest). Each follicle follows a growth pattern independent of the rest. The hair follicle is lined by a cellular inner and outer root sheath of epidermal origin and is invested with a fibrous sheath derived from the dermis. Each hair fiber is made up of an outer cortex and a central medulla. Enclosing the hair shaft is a layer of overlapping keratinized scales, the hair cuticle that serves as protective layers. Racial differences in hair include the hair type, shape, and bulb. There are four types of hair: helical, spiral, straight, and wavy. The spectrum of curliness is displayed in Figure 4.2. The vast majority of black persons have spiral hair [62]. The hair of black persons are naturally more brittle and more susceptible to breakage and spontaneous knotting than that of white persons. The kinky form of black hair, the weak intercellular cohesion between cortical cells, and the specific hair grooming practices among black persons account for the accentuation of these findings [62]. The shape of the hair is different between races: black hair has an elliptical shape, Asian hair is round-shaped straight hair, and Caucasian hair is intermediate [63,64]. The bulb determines the shape of the hair shaft, indicating a genetic difference in hair follicle structure [30]. The cross-section of black hair has a longer major axis, a flattened elliptical shape, and curved follicles. Asian hair has the largest cross-sectional area and Western European hair has the smallest [64,65]. Black persons have fewer elastic fibers anchoring the hair follicles to the dermis than white subjects. Melanosomes were in the outer root sheath and in the bulb of vellus hairs in black, but not in

Figure 4.2 The spectrum of curliness in human hair. (This figure was published in: Loussouarn G, Garcel A, Lozano I, Collaudin C, Porter Crystal, Panhard S, et al. (2007) Worldwide diversity of hair curliness: a new method of assessment. Int J Dermatol 46 (Suppl 1), 2–6.)



Skin Physiology is completely straight and the Caucasian hair form is intermediate [65]. Mesocortical, orthocortical, and paracortical cells are the three cell types in the hair cortex. In straight hair, mesocortical cells predominate [66]. In wavy hair, the orthocortical and mesocortical cells are interlaced around paracortical cells. In tightly curled hair, the mesocortex disappears, making orthocortical cells the majority. Distinct cortical cells express the acidic hair keratin hHa8. Figure 4.3 displays the distribution of hHa8 cells in straight, wavy, and tightly curled hair. Straight hair has a patchy but hom*oge-

white persons. Black hair also has more pigment and on microscopy has larger melanin granules than hair from light-skinned and Asian individuals. Similarities between white and black hair include: cuticle thickness, scale size and shape, and cortical cells [65]. While the curly nature of black hair is believed to result from the shape of the hair follicle [65], new research shows that the curliness of hair correlates with the distribution of cortical cells independent of ethnoracial origin [66]. Black hair follicles have a helical form, whereas the Asian follicle








Figure 4.3 hHa8 hair keratin distribution in hair follicles. hHa8 pattern in (a) straight, (b) wavy, and (c) curly hair longitudinal sections. hHa8 pattern in (d) straight and (e) curly hair cross-sections. (From Thibaut et al. (2007) Human hair keratin network and curvature. Int J Dermatol 46 (Suppl 1), 7–10.)


4. Pigmentation and skin of color nous pattern of positively charged hHa8 cells surrounding a core of negatively charged cells. As the degree of curl decreases, the hHa8 pattern becomes asymmetric, independent of ethnic origin. In tightly curled hair, hHa8 accumulates on the concave side of the hair fiber and the medulla compartment disappears. There are no differences in keratin types between hair from different races and no differences in amino acid composition of hair from different races [67]. Among Caucasian, Asian, and Africans, there are no differences in the intimate structures of fibers, whereas geometry, mechanical properties, and water swelling differed according to ethnic origin [68]. One study [69] in 1941 did find variation in the levels of some amino acids between black and white hair. Black subjects had significantly greater levels of tyrosine, phenylalanine, and ammonia in the hair, but were deficient in serine and threonine. The morphologic features of African hair were examined using the transmission and scanning electron microscopic (SEM) techniques in an unpublished study. The cuticle cells of African hair were compared with those of Caucasian hair. Two different electronic density layers were shown. The denser exocuticle is derived from the aggregation of protein granules that first appear when the scale cells leave the bulb region. The endocuticle is derived from the zone that contains the nucleus and cellular organites. The cuticle of Caucasian hair is usually 6–8 layers thick and constant in the hair perimeter, covering the entire length of each fiber. However, black hair has variable thickness; the ends of the minor axis of fibers are 6–8 layers thick, and the thickness diminishes to 1–2 layers at the ends of the major axis. The weakened endocuticle is subject to numerous fractures (Handjur C, Fiat, Huart M, Tang D, Leory F, unpublished data).

References 1 US Census Bureau. (2008) Older and More Diverse Nation by Midcentury. US Census Bureau News. August 14, 2008 online at: archives/population/010048.html. Accessed November 12, 2008. 2 Halder RM, Nandedkar MA, Neal KW. (2003) Pigmentary disorders in ethnic skin. Dermatol Clin 21, 617–28. 3 Fitzpatrick TB, Szabo G. (1959) The melanocytes: cytology and cytochemistry. J Invest Dermatol 32, 197–209. 4 Jimbow K, Oikawa O, Sugiyama S, Takeuchi T. (1979) Comparison of eumelanogenesis and pheomelanogenesis in retinal and follicular melanocytes: role of vesiculo-globular bodies in melanosome differentiation. J Invest Dermatol 73, 278–84. 5 Wakamatsu K, Kavanagh R, Kadekaro AL, Terzieva S, Sturm RA, Leachman S, et al. (2006) Diversity of pigmentation in cultured human melanocytes is due to differences in the type as well as quantity of melanin. Pigment Cell Res 19, 154–62.

6 Montagna W, Carlisle K. (1991) The architecture of black and white facial skin. J Am Acad Dermatol 24, 929–37. 7 Taylor SC. (2002) Skin of color; biology, structure, function, implications for dermatologic disease. J Am Acad Dermatol 46, S41–62. 8 Toda K, Fatnak MK, Parrish A, Fitzpatrick TB. (1972) Alteration of racial differences in melanosome distribution in human epidermis after exporsure to ultraviolet light. Nat New Biol 236, 143–4. 9 Olson RL, Gaylor J, Evertt MA. (1973) Skin color, melanin, and erythema. Arch Dermatol 108, 541–4. 10 Jimbow M, Jimbow K. (1989) Pigmentary disorders in Oriental skin. Clin Dermatol 7, 11–27. 11 Abdel-Malek Z, Swope VB, Suzuki I, Akcali C, Harriger MD, Boyce ST, et al. (1995) Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides. Proc Natl Acad Sci U S A 92, 1789–93. 12 Sturm RA, Teasdale RD, Box NF. (2001) Human pigmentation genes: identification, structure and consequences of pylymorphic variation. Gene 277, 49–62. 13 Rees JL. (2003) Genetics of hair and skin color. Annu Rev Genet 37, 67–90. 14 Suzuki I, Cone RD, Im S, Nordlund J, Abdel-Malek ZA. (1996) Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology 137, 1627–33. 15 Hou L, Kapas S, Cruchley AT, Macey MG, Harriott P, Chinni C, et al. (1998) Immunolocalization of protease-activated receptor-2 in skin: receptor activation stimulates interleukin-8 secretion by keratinocytes in vitro. Immunology 94, 356–62. 16 Steinhoff M, Neisius U, Ikoma A, Fartasch M, Heyer Gisela, Skov PS, et al. (2003) Proteinase-activated receptor-1 mediates itch: a novel pathway for pruritus in human skin. J Neurosci 23, 6176–80. 17 Shpacovitch VM, Brzoska T, Buddenkotte J, Stroh C, Sommerhoff CP, Ansel JC, et al. (2002) Agonists of proteinase-activated receptor 2 induce cytokine release and activation of nuclear transcription factor κB in human dermal microvascular endothelial cells. J Invest Dermtol 118, 380–5. 18 Seiberg M, Paine C, Sharlow E, Andrade-Gordon P, Constanzo M, Eisinger M, et al. (2000) Inhibition of melanosome transfer results in skin lightening. J Invest Dermatol 115, 162–7. 19 Nystedt S, Ramakrishnan V, Sundelin J. (1996) The proteinaseactivated receptor 2 is induced by inflammatory mediators in human endothelial cells: comparison with the thrombin receptor. J Biol Chem 271, 14910–5. 20 Bohm SK, Kong W, Bromme D, Smeekens SP, Anderson DC, Connolly A, et al. (1996) Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem J 314, 1009–16. 21 Scott G, Deng A, Rodriguez-Burford C, Seiberg M, Han R, Babiarz L, et al. (2001) Protease-activated receptor 2, a receptor involved in melanosome transfer, is upregulated in human skin by ultraviolet irradiation. J Invest Dermatol 117, 1412–20. 22 Gilchrest BA. (1977) Localization of melanin pigmentation in skin with Wood’s lamp. Br J Dermatol 96, 245–7. 23 Morelli JG, Norris DA. (1993) Influence of inflammatory mediators and cytokines on human melanocyte function (Review). J Invest Dermatol 100 (2 Suppl), 191S–5S.



Skin Physiology

24 Grover R, Morgan BDG. (1996) Management of hypopigmentation following burn injury. Burns 22, 727–30. 25 Johnston GA, Svukabd KS, McLelland J. (1998) Melasma of the arms associated with hormone replacement therapy (letter). Br J Dermatol 139, 932. 26 Pathak MA, Fitzpatrick TB. (1974) The role of natural photoprotective agents in human skin. In: Fitzpatrick TB, Pathak MA, Harber LC, Seiji M, Kukita A, eds. Sunlight and Man. Tokyo: University of Tokyo Press, pp. 725–50. 27 Kligman AM. (1974) Solar elastosis in relation to pigmentation. In: Fitzpatrick TB, Pathak MA, Harber LC, Seiji M, Kukita A, eds. Sunlight and Man. Tokyo: University of Tokyo Press, pp. 157–63. 28 Kaidbey KH, Agin PP, Sayre RM, Kligman AM. (1979) Photoprotection by melanin: a comparison of black and Caucasian skin. J Am Acad Dermatol 1, 249–60. 29 Manuskiatti W, Schwindt DA, Maibach HI. (1998) Influence of age, anatomic site and race on skin roughness and scaliness. Dermatology 196, 401–7. 30 Courcuff P, Lotte C, Rougier A, Maibach HI. (1991) Racial differences in corneocytes: a comparison between black, white, and Oriental skin. Acta Dermatol Venereol 71, 146–8. 31 Warrier AG, Kligman AM, Harper RA, Bowman J, Wickett RR. (1996) A comparison of black and white skin using noninvasive methods. J Soc Cosmet Chem 47, 229–40. 32 Aramaki J, Kawana S, Effendy I, Happle R, Löffler H. (2002) Differences of skin irritation between Japanse and European women. Br J Dermatol 146, 1052–6. 33 Triebskorn A, Gloor M. (1993) Noninvasive methods for the determination of skin hydration. In: Forsch PJ, Kligman AM, eds. Noninvasive Methods for the Quantification of Skin Functions. Berlin; New York (NY): Springer-Verlag, pp. 42–55. 34 La Ruche G, Cesarini JP. (1992) Histology and physiology of black skin. Ann Dermatovenereologica 119, 567–74. 35 Reed JT, Ghadially R, Elias MM. (1995) Skin type but neither race nor gender, influence epidermal permeability barrier function. Arch Dermatol 131, 1134–8. 36 Diridollou S, de Rigal J, Querleux B, Leroy F, Holloway Barbosa V. (2007) Comparative study of the hydration of the stratum corneum between four ethnic groups: influence of age. Int J Dermatol 46 (Suppl 1), 11–4. 37 Sueki H, Whitaker-Menezes D, Kligman AM. (2001) Structural diversity of mast cell granules in black and white skin. Br J Dermatol 144, 85–93. 38 Modjtahedi SP, Maibach HI. (2002) Ethnicity as a possible endogenous factor in irritant contact dermatitis: comparing the irritant response amoung Caucasians, blacks, and Asians. Contact Dermatitis 47, 272–8. 39 Hicks SP, Swindells KJ, Middelkamp-Hup MA, Sifakis MA, González E, González S. (2003) Confocal histopathology of irritant contact dermatitis in vivo and the impact of skin color (black vs white). J Am Acad Dermatol 48, 727–34. 40 Grimes P, Edison BL, Green BA, Wildnauer RH. (2004) Evaluation of inherent differences between african american and white skin surface properties using subjective and objective measures. Cutis 73, 392–6. 41 Berardesca F, Maibach H. (1996) Racial differences in skin pathophysiology. J Am Acad Dermatol 34, 667–72.


42 Galindo, GR, Mayer JA, Slymen D, Almaguer DD, Clapp E, et al. (2007) Sun sensitivity in 5 US ethnoracial groups. Cutis 80, 25–30. 43 Robinson MK. (2002) Population differences in acute skin irritation responses. Race, sex, age, sensitive skin and repeart subject comparisons. Contact Dermatitis 46, 86–93. 44 Foy V, Weinkauf R, Whittle E, Basketter DA. (2001) Ethnic variation in the skin irritation response. Contact Dermatitis 45, 346–9. 45 Robinson MK. (2000) Racial differences in acute and cumulative skin irritation responses between Caucasian and Asian populations. Contact Dermatitis 42, 134–43. 46 Tadaki T, Watanabe M, Kumasaka K, Tanita Y, Kato T, Tagami H, et al. (1993) The effect of tretinoin on the photodamaged skin of the Japanese. Tohoku J Exp Med 169, 131–9. 47 Montagna W, Giusseppe P, Kenney JA. (1993) The structure of black skin. In: Montagna W, Giusseppe P, Kenney JA, eds. Black Skin Structure and Function. Academic Press, pp. 37–49. 48 Reilly DM, Ferdinando D, Johnston C, Shaw C, Buchanan KD, Green MR. (1997) The epidermal nerve fiber network: characterization of nerve fibers in human skin by confocal microscopy and assessment of racial variations. Br J Dermatol 137, 163–70. 49 Berardesca E, Rigal J, Leveque JL, et al. (1991) In vivo biophysical characterization of skin physiological differences in races. Dermatologica 182, 89–93. 50 Harris MO. (2006) Intrinsic skin aging in pigmented races. In: Halder RM, ed. Dermatology and Dermatological Therapy of Pigmented Skins. Taylor & Francis Group, pp. 197–209. 51 Matory WE. (1998) Aging in people of color. In: Matory WE, ed. Ethnic Considerations in Facial Aesthetic Surgery. Philadelphia: Lippincott-Raven, 151–70. 52 Bosniak SL, Zillkha MC. (1999) Cosmetic Blepharoplasty and Facial Rejuvenation. New York: Lippincott-Raven. 53 Ramirez OM. (1998) Facial surgery in the Hispano-American patient. In: Matory WE, ed. Ethnic Considerations in Facial Aesthetic Surgery. Philadelphia: Lippincott-Raven, pp. 307–20. 54 Stuzin JM, Baker TJ, Gordon HL. (1992) The relationship of the superficial and deep facial fascias: relevance to rhytidectomy and aging. Plast Reconstr Surg 89, 441–9. 55 Shirakable Y. (1988) The Oriental aging face: an evaluation of adecade of experience with the triangular SMAS flap technique. Aesthetic Plast Surg 12, 25–32. 56 Warren R, Garstein V, Kligman AM, Montagna W, Allendorf RA, Ridder GM. (1991) Age, sunlight, and facial skin: a histologic and quantitative study. J Am Acad Dermatol 25, 751–60. 57 Montagna W, Kirchner S, Carlisle K. (1989) Histology of sundamaged human skin. J Am Acad Dermatol 12, 907–18. 58 Herzberg AJ, Dinehart SM. (1989) Chronologic aging in black skin. Am J Dermatopathol 11, 319–28. 59 Halder RM. (1998) The role of retinoids in the management of cutaneous conditions in blacks. J Am Acad Dermatol 39 (Part 3), S98–103. 60 Kligman LH. (1982) Intensification of ultraviolet-induced dermal damage by infrared radiation. Arch Dermatol 272, 229–38. 61 Halder RM, Richards GM. (2006) Photoaging in pigmented skins. In: Halder RM, ed. Dermatology and Dermatological Therapy of Pigmented Skins. Taylor & Francis Group, pp. 211–20.

4. Pigmentation and skin of color 62 Halder RM. (1983) Hair and scalp disorders in blacks. Cutis 32, 378–80. 63 Bernard BA. (2003) Hair shape of curly hair. J Am Acad Dermatol 48 (6 Suppl), S120–6. 64 Vernall DO. (1961) Study of the size and shape of hair from four races of men. Am J Phys Anthropol 19, 345. 65 Brooks O, Lewis A. (1983) Treatment regimens for “styled” black hair. Cosmet Toiletries 98, 59–68. 66 Thibaut S, Barbarat P, Leroy F, Bernard BA. (2007) Human hair keratin network and curvature. Int J Dermatol 46 (Suppl 1), 7–10.

67 Gold RJ, Scriver CG. (1971) The amino acid composition of hair from different racial origins. Clin Chim Acta 33, 465–6. 68 Franbourg A, Hallegot P, Baltenneck F, Toutain C, Leroy F. (2003) Current research on ethnic hair. J Am Acad Dermatol 48 (6 Suppl), S115–9. 69 Menkart J, Wolfram L, Mao I. (1966) Causacian hair, Negro hair and wool: similarities and differences. J Soc Cosmet Chem 17, 769–87.


Chapter 5: Sensitive skin and the somatosensory system Francis McGlone1 and David Reilly2 1 2

Perception and Behaviour Group, Unilever Research & Development, Wirral, UK One Discover, Colworth Park, Sharnbrook, Bedford, UK

BAS I C CONCE P T S • The primary sensory modality subserving the body senses is collectively described as the somatosensory system, and comprises all those peripheral afferent nerve fibers, and specialized receptors, subserving cutaneous, and proprioceptive sensitivity. • Individuals with sensitive skin demonstrate heightened reactivity of the somatosensory system. • A separate set of neurons mediates itch and pain. The afferent neurons responsible for histamine-induced itch in humans are unmyelinated C-fibers. • Low threshold mechanoreceptors are responsible for the sensation of touch, a wide range of receptor systems code for temperature, and as the skin’s integrity is critical for survival, there are an even larger number of sensory receptors and nerves that warn us of damage to the skin – the pain and itch systems.

Introduction The primary sensory modality subserving the body senses is collectively described as the somatosensory system, and comprises all those peripheral afferent nerve fibers, and specialized receptors, subserving cutaneous and proprioceptive sensitivity. The latter processes information about limb position and muscle forces which the central nervous system uses to monitor and control limb movements and, via elegant feedback and feedforward mechanisms, ensure that a planned action or movement is executed fluently. This chapter focuses on sensory inputs arising from the skin surface – cutaneous sensibility – and describes the neurobiologic processes that enable the skin to “sense.” Skin sensations are multimodal and are classically described as sensing the three submodalities of touch, temperature, and pain. We also consider the growing evidence for a fourth submodality, present only in hairy skin, which is preferentially activated by slowly moving, low force, mechanical stimuli. This brief introduction to somatosensation starts with the discriminative touch system. Sensation enters the periphery via sensory axons that have their cell bodies sitting just outside the spinal cord in the dorsal root ganglia, with one ganglion for each spinal nerve root. Neurons are the building blocks of the nervous system and somatosensory neurons are unique in that, unlike most neurons, the electrical signal does not pass through the cell body but the cell body sits off to one side, without dendrites. The signal passes directly

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


from the distal axon process to the proximal process which enters the dorsal half of the spinal cord, and immediately turns up the spinal cord forming a white matter column, the dorsal columns, which relay information to the first brain relay nucleus in the medulla. These axons are called the primary afferents, because they are the same axons that carry the signal into the spinal cord. Sensory input from the face does not enter the spinal cord, but instead enters the brainstem via the trigeminal nerve (one of the cranial nerves). Just as with inputs from the body, there are three modalities of touch, temperature, and pain, with each modality having different receptors traveling along different tracts projecting to different targets in the brainstem. Once the pathways synapse in the brainstem, they join the pathways from the body on their way up to the thalamus and higher cortical structures. Sensory information arising from the skin is represented in the brain in the primary and secondary somatosensory cortex, where the contralateral body surfaces are mapped in each hemisphere.

Peripheral nervous system The skin is the most extensive and versatile organ of the body and in a fully grown adult covers a surface area approaching 2 m2. This surface is far more than a just a passive barrier. It contains in excess of 2 million sweat glands and 5 million hairs that may be either fine vellous types covering all surfaces, apart from the soles of the feet and the palms of the hands (glabrous skin), or over 100 000 of the coarser type found on the scalp. Evidence is also emerging that non-glabrous skin contains a system of nerves that code specifically for the pleasant properties of touch. Skin consists

5. Sensitive skin of an outer, waterproof, stratified squamous epithelium of ectodermal origin – the epidermis – plus an inner, thicker, supporting layer of connective tissue of mesodermal origin – the dermis. The thickness of this layer varies from 0.5 mm over the eyelid to >5.0 mm over the palm and sole of the foot.

Touch Of the three “classic” submodalities of the somatosensory system, discriminative touch subserves the perception of pressure, vibration, and texture and relies upon four different receptors in the digit skin: 1 Meissner corpuscles; 2 Pacinian corpuscles; 3 Merkel disks; and 4 Ruffini endings. These are collectively known as low threshold mechanoreceptors (LTMs), a class of cutaneous receptors that are specialized to transduce mechanical forces impinging the skin into nerve impulses. The first two are classified as fast adapting (FA) as they only respond to the initial and final contact of a mechanical stimulus on the skin, and the second two are classified as slowly adapting (SA) as they continue firing during a constant mechanical stimulus. A further classification relates to the LTM’s receptive field (RF; i.e. the surface area of skin to which they are sensitive). The RF is determined by the LTM’s anatomic location within the skin, with those near the surface at the dermal– epidermal boundary, Meissner corpuscles and Merkel disks, having small RFs, and those lying deeper within the dermis, Pacinian corpuscles and Ruffini endings, having large RFs (Figure 5.1).

Psychophysical procedures have been traditionally employed to study the sense of touch where differing frequencies of vibrotactile stimulation are used to quantify the response properties of this sensory system. Von Bekesy [1] was the first to use vibratory stimuli as an extension of his research interests in audition. In a typical experiment participants were asked to respond with a simple button-press when they could just detect the presence of a vibration presented to a digit, within one of two time periods. This two alternative force choice paradigm (2-AFC) provides a threshold-tuning curve, the slopes of which provide information about a particular class of LTM’s response properties. Bolanowski et al. [2] proposed that there are four distinct psychophysical channels mediating tactile perception in the glabrous skin of the hand. Each psychophysically determined channel is represented by one of the four anatomic end organs and nerve fiber subtypes, with frequencies in the 40–500 Hz range providing a sense of “vibration,” transmitted by Pacinian corpuscles (PC channel or FAI); Meissner corpuscles being responsible for the sense of “flutter” in the 2–40 Hz range (NPI channel or FAII); the sense of “pressure” being mediated by Merkel disks in the 0.4–2.0 Hz range (NPIII or SAI); and Ruffini end organs producing a “buzzing” sensation in the 100–500 Hz range (NPII or SAII). Neurophysiologic studies have, by and large, supported this model, but there is still some way to go to link the anatomy with perception (Table 5.1). There have been relatively few studies of tactile sensitivity on hairy skin, the cat being the animal of choice for most of these studies. Mechanoreceptive afferents (Aβ fibers) have been described that are analogous to those found in human

Table 5.1 Main characteristics of primary sensory afferents innervating human skin. Class


Axonal diameter (μm)

Conduction velocity (m s−1)

Proprioceptors from muscles and tendons



Low threshold mechanoreceptors



Cold, noxious, thermal



Noxious, heat, thermal




Light stroking, gentle touch




Autonomic, sweat glands, vasculature







Stratum corneum Stratum lucldum Stratum granulosum Melanocyte Stratum splnosum Stratum granulosum Lamina basilaris Melssner’s corpuscle Merkel’s disks

Epidermis Cuticle Scarf skin Stratum mucosum

Pars papillris or Papillary dermis (loose connective tissue) Dermal nerve networks Ruffint endings

Dermis Cuticle True skin

Pars reticularis or Reticular dermis dense connective tissue) Pacinian corpuscles Stratum subsutaneum Tela subcutanea Muscle, ligament, or bone Eccrine gland


Halr shaft

Melanocyte Erector pilorum muscle

Sebaceous gland

Tactile pad Stratum corneum Stratum lucldum Stratum granulosum Stratum splnosum

Epidermis Cuticle Scarf skin

Stratum granulosum Lamina basilaris Blood vessels Pars papillris or Papillary dermis (loose connective tissue) Ruffint endings Dermal nerve networks

Hair follicle network

Apocrine gland

Blood vessels

Eccrine gland

Dermis Cuticle True skin

Pars reticularis or Reticular dermis dense connective tissue)

Pacinian corpuscles Stratum subsutaneum Tela subcutanea Muscle, ligament, or bone

(b) Figure 5.1 A cross-sectional perspective of (a) glabrous and (b) hairy skin. (This figure was published with permission of the artist, R.T. Verrillo.)

5. Sensitive skin glabrous skin (FAI, FAII, SAI, SAII), and Essick and Edin [3] have described sensory fibers with these properties in human facial skin. The relationship between these sensory fibers and tactile perception is still uncertain. Sensory axons are classified according to their degree of myelination, the fatty sheath that surrounds the nerve fiber. The degree of myelination determines the speed with which the axon can conduct nerve impulses and hence the nerves conduction velocity. The largest and fastest axons are called Aα and include some of the proprioceptive neurons, such as the muscle stretch receptors. The second largest group, called Aβ, includes all of the discriminative touch receptors being described here. Pain and temperature include the third and fourth groups, Aδ and C-fibers. Electrophysiologic studies on single peripheral nerve fibers innervating the human hand have provided a generally accepted model of touch that relates the four anatomically defined types of cutaneous or subcutaneous sense organs to their neural response patterns [4]. The technique they employed is called microneurograpahy and involves inserting a fine tungsten microelectrode, tip diameter <5 μm, through the skin of the wrist and into the underlying median nerve which innervates the thumb and first two digits (Figure 5.2).

Temperature The cutaneous somatosensory system detects changes in ambient temperature over an impressive range, initiated

when thermal stimuli that differ from a homeostatic setpoint excite temperature specific sensory nerves in the skin, and relay this information to the spinal cord and brain. It is important to recognize that these nerves code for temperature change, not absolute temperature, as a thermometer does. The system does not have specialized receptor end organs such as those found with LTMs but uses free nerve endings throughout skin to sense changes in temperature. Within the innocuous thermal sensing range there are two populations of thermosensory fibers, one that respond to warmth (warm receptors) and one that responds to cold (cold receptors), and include fibers from the Aδ and C range. Specific cutaneous cold and warm receptors have been defined as slowly conducting units that exhibit a steady-state discharge at constant skin temperature and a dynamic response to temperature changes [5,6]. Cold-specific and warm-specific receptors can be distinguished from nociceptors that respond to noxious low and high temperatures (<20 °C and >45 °C) [7,8], and also from thermosensitive mechanoreceptors [5,9]. Standard medical textbooks describe the cutaneous cold sense in humans as being mediated by myelinated A-fibers with CVs in the range 12–30 m s−1 [10], but recent work concludes that either human cold-specific afferent fibers are incompletely myelinated “BC” fibers, or else there are C as well as A cold fibers, with the C-fiber group contributing little to sensation (Figure 5.3) [11]. The free nerve endings for cold-sensitive or warmsensitive nerve fibers are located just beneath the skin

Adaptation Fast, no static responses

Slow, static response present

Edge sensitive

Edge sensitive

Small, sharp borders


(43%) Meissner


(25%) Merkel

Large, obscure borders


Innervation density

Receptive fields


Sensitive to lateral skin stretch FAII

(13%) Pacini Golgi–Mazzoni

Figure 5.2 The four types of low threshold mechanoreceptors in human glabrous skin are depicted. The four panels in the center show the nerve firing responses to a ramp and hold indentation and the frequency of occurrence (%) and putative morphologic correlate. The black dots in the left panel show the receptive fields of type I (top) and type II (bottom)


(19%) Ruffini

afferents. The right panel shows the average density of type I (top) and type II (bottom) afferents with darker area depicting higher densities. (From Westling GK. (1986) Sensori-motor mechanisms during precision grip in man. Umea University medical dissertation. New Series 171, Umea, Sweden.)



Skin Physiology

35˚C 31˚C (a)


35˚C 31˚C (b) Figure 5.3 Resting discharge of a C cold fiber at room temperature [11]. (a) The resting discharge is suppressed by warming of the receptive field (RF) from 31 °C to 35 °C. (b) From a holding temperature of 35 °C, at which the unit is silent, activity is initiated by cooling the RF to 31 °C. (Time bar: 5 s.)

surface. The terminals of an individual temperature-sensitive fiber do not branch profusely or widely. Rather, the endings of each fiber form a small, discretely sensitive point, which is separate from the sensitive points of neighboring fibers. The total area of skin occupied by the receptor endings of a single temperature-sensitive nerve fiber is relatively small (approximately 1 mm in diameter), with the density of these thermosensitive points varying in different body regions. In most areas of the body there are 3–10 times as many cold-sensitive points as warm-sensitive points. It is well established from physiologic and psychologic testing that warm-sensitive and cold-sensitive fibers are distinctively different from one another in both structure and function.

Pain Here we consider a system of peripheral sensory nerves that innervate all cutaneous structures and whose sole purpose is to protect the skin against potential or actual damage. These primary afferents include Aδ and C-fibers which respond selectively and linearly to levels of thermal, mechanical, and chemical intensity/strength that are tissue-threatening. This encoding mechanism is termed nociception and describes the sensory process detecting any overt, or impending, tissue damage. The term pain describes the perception of irritation, stinging, burning, soreness, or painful sensations arising from the skin. It is important to recognize that the perception of pain not only depends on nociceptor input, but also on other processes and pathways giving information about emotional or contextual components. Pain is therefore described in terms of an “experience” rather than just a simple sensation. There are again submodalties within the


nociceptive system (Aδ and C) subserving nociception. Aδ fibers are thin (1–5 μm), poorly myelinated axons of mechanical nociceptors, thermal receptors, and mechanoreceptors with axon potential conduction velocities of approximately 12 m s−1. C-fibers are very thin (<1 μm) unmyelinated slowly conducting axons of <1 m s−1. Mechanical nociceptors are in the Aδ range and possess receptive fields distributed as 5–20 small sensitive spots over an area approximately 2–3 mm in diameter. In many cases activation of these spots depends upon stimuli intense enough to produce tissue damage, such as a pinprick. Aδ units with a short latency response to intense thermal stimulation in the range 40– 50 °C have been described as well as other units excited by heat after a long latency – usually with thresholds in excess of 50 °C. Over 50% of the unmyelinated axons (C-fibers) of a peripheral nerve respond, not only to intense mechanical stimulation, but also to heat and noxious chemicals, and are therefore classified as polymodal nociceptors [12] or C-mechano-heat (CMH) nociceptors [13]. Receptive fields consist of single zones with distinct borders and in this respect they differ from Aδ nociceptors that have multipoint fields. Innervation densities are high and responses have been reported to a number of irritant chemicals such as dilute acids, histamine, bradykinin, and capsaicin. Following inflammation some units can acquire responsiveness to stimuli to which they were previously unresponsive. Recruitment of these “silent nociceptors” implies spatial summation to the nociceptive afferent barrage at central levels, and may therefore contribute to primary hyperalgesia after chemical irritation and to secondary hyperalgesia as a consequence of central sensitization. Nociceptors do not show the kinds of adaptation response found with rapidly adapting LTMs (i.e. they fire continuously to tissue damage), but pain sensation may come and go and pain may be felt in the absence of any nociceptor discharge. They rely on chemical mediators around the nerve ending which are released from nerve terminals and skin cells in response to tissue damage. The axon terminals of nociceptive axons possess no specialized end organ structure and for that reason are referred to as free nerve endings. This absence of any encapsulation renders them sensitive to chemical agents, both intrinsic and extrinsic, and inflammatory mediators released at a site of injury can initiate or modulate activity in surrounding nociceptors over an area of several millimeters leading to two kinds of sensory responses termed hyperalgesia – the phenomenon of increased sensitivity of damaged areas to painful stimuli. Primary hyperalgesia occurs within the damaged area; secondary hyperalgesia occurs in undamaged tissues surrounding this area. One further sensation mediated by afferent C-fibers is that of itch. The sensation of itch has, in the past, been thought to be generated by the weak activation of pain nerves, but

5. Sensitive skin with the recent finding of primary afferent neurons in humans [14] and spinal projection neurons in cats [15], which have response properties that match those subjectively experienced after histamine application to the skin, it is now recognized that separate sets of neurons mediate itch and pain, and that the afferent neurons responsible for histamine-induced itch in humans are unmyelinated C-fibers. Until relatively recently it was thought that histamine was the final common mediator of itch, but clinical observations where itch can be induced mechanically, or is not found with an accompanying flare reaction, cannot be explained by histamine-sensitive pruriceptors leading to evidence for the existence of histamine-independent types of itch nerves [16] in which itch is generated without a flare reaction by cowhage spicules. As with the existence of multiple types of pain afferents, different classes of itch nerves are also likely to account for the various experiences of itch reported by patients [17].

bonding behaviors – pleasant touch [22]. If pain is elicited via sensory C- and Aδ-fibers then it is reasonable to speculate that the same system may be alternatively modulated to deliver a sensation of pleasure. A study employing the pan-neuronal marker PGP9.5 and confocal laser microscopy has identified a population of free nerve endings in the epidermis that may be the putative anatomic substrate for this submodality [23].

Sympathetic nerves Although this chapter deals with sensory aspects of skin innervation it is important to acknowledge the role of a class of efferent (motor) nerves that innervate various skin structures: (a) blood vessels; (b) cutaneous glands; and (c) unstriated muscle in the skin (e.g. the erectors of the hairs). In sensitive skin conditions, and some painful neuropathic states, sympathetic nerves have a role in exacerbating inflammation and irritation (for review see Roosterman et al. [24]).

Pleasure In recent years a growing body of evidence has been accumulating, from anatomic, psychophysical, electrophysiologic, and neuroimaging studies, that a further submodality of afferent, slowly conducting, unmyelinated C-fibers exists in human hairy skin that are neither nociceptive nor pruritic, but that respond preferentially to low force, slowly moving mechanical stimuli. These nerve fibers have been classified as C-tactile afferents (CT-afferents) and were first described by Nordin [18] and Johansson et al. [19]. Evidence of a more general distribution of CT-afferents have subsequently been found in the arm and the leg, but never in glabrous skin sites such as the palms of the hands or the soles of the feet [20]. It is well known that mechanoreceptive innervation of the skin of many mammals is subserved by A and C afferents but until the observations of Nordin and Vallbo C-mechanoreceptive afferents in human skin appeared to be lacking entirely. The functional role of CT-afferents is not fully known, but their neurophysiologic response properties, fiber class, and slow conduction velocities preclude their role in any rapid mechanical discriminative or cognitive tasks, and point to a more limbic function, particularly the emotional aspects of tactile perception [21]. However, the central neural identification of low-threshold C mechanoreceptors, responding specifically to light touch, and the assignment of a functional role in human skin has only recently been achieved. In a study on a unique patient lacking large myelinated Abfibers, it was discovered that activation of CT-afferents produced a faint sensation of pleasant touch, and functional neuroimaging showed activation in the insular cortex but no activation the primary sensory cortex, identifying CTafferents as a system for limbic touch that might underlie emotional, hormonal, and affiliative responses to skin–skin contacts between individuals engaged in grooming and

The central projections The submodalties of skin sensory receptors and nerves that convey information to the brain about mechanical, thermal, and painful stimulation of the skin are grouped into three different pathways in the spinal cord and project to different target areas in the brain. They differ in their receptors, pathways, and targets, and also in the level of decussation (crossing over) within the CNS. Most sensory systems en route to the cerebral cortex decussate at some point, as projections are mapped contralaterally. The discriminative touch system crosses in the medulla, where the spinal cord joins the brain, the pain system crosses at the point of entry into the spinal cord.

Spinal cord All the primary sensory neurons have their cell bodies situated outside the spinal cord in the dorsal root ganglion, there being one ganglion for every spinal nerve root. Tactile primary afferents, or first order neurons, immediately turn up the spinal cord towards the brain, ascending in the dorsal white matter and forming the dorsal columns. In a cross-section of the spinal cord at cervical levels, two separate tracts can be seen: the midline tracts comprise the gracile fasciculus conveying information from the lower half of the body (legs and trunk), and the outer tracts comprise the cuneate fasciculus conveying information from the upper half of the body (arms and trunk). At the medulla, situated at the top of spinal cord, the primary tactile afferents make their first synapse with second order neurons where fibers from each tract synapses in a nucleus of the same name – the gracile fasciculus axons synapse in the gracile nucleus, and the cuneate axons synapse in the cuneate



Skin Physiology

nucleus. The neurons receiving the synapse provide the secondary afferents and cross immediately to form a new tract on the contralateral side of the brainstem – the medial lemniscus – which ascends through the brainstem to the next relay station in the midbrain, the thalamus. As with the tactile system, pain and thermal primary afferents synapse ipsilaterally and then the secondary afferents cross, but the crossings occur at different levels. Pain and temperature afferents enter the dorsal horn of the spinal and synapse within one or two segments, forming the Lissauer tract as they do so. The dorsal horn is a radially laminar structure. The two types of pain fibers, C and Aδ, enter different layers of the dorsal horn. Aδ fibers enter the posterior marginalis and the nucleus proprius, and synapse on a second set of neurons. These are the secondary afferents which will relay the signal to the thalamus. The secondary afferents from both layers cross to the opposite side of the spinal cord and ascend in the spinothalamic tract. The C-fibers enter the substantia gelatinosa and synapse, but they do not synapse on secondary afferents. Instead they synapse on interneurons – neurons that do not project out of the immediate area but relay the signal to the secondary afferents in either the posterior marginalis or the nucleus proprius. The spinothalamic tract ascends the entire length of the cord and the entire brainstem and by the time it reaches the midbrain appears to be continuous with the medial lemniscus. These tracts enter the thalamus together. It is important to note that although the bulk of afferent input adheres to the plan outlined above there is a degree of mixing that goes on between the tracts. We have concentrated on somatosensory inputs from the body thus far, but as facial skin is often the source of sensitive reactions to topical applications, its peripheral and central anatomy and neurophysiology is briefly summarized here. The trigeminal nerve innervates all facial skin structures (including the oral mucosa) and, just as with the spinal afferents, these neurons have their cell bodies outside of the CNS in the trigeminal ganglion with their proximal processes entering the brainstem. Just as in the spinal cord, the three modalities of touch, temperature, and pain have different receptors in the facial skin, travel along different tracts, and have different targets in the brainstem – the trigeminal nucleus – a relatively large structure that extends from the midbrain to the medulla. The large diameter (Aβ) fibers enter directly into the main sensory nucleus of the trigeminal and, as with the somatosensory neurons of the body, synapse and then decussate, the secondary afferents joining the medial lemniscus as it projects to the thalamus. The small diameter fibers conveying pain and temperature enter midbrain with the main Vth cranial nerve, but then descend down the brainstem to the caudal medulla where they synapse and cross. These descending axons form a tract, the spinal tract of V, and


synapse in the spinal nucleus of V, so called because it reaches as far down as the upper cervical spinal cord. The spinal nucleus of V comprises three regions along its length: the subnucleus oralis, the subnucleus interpolaris, and the subnucleus caudalis. The secondary afferents from the subnucleus caudalis cross to the opposite side and join the spinothalamic tract where the somatosensory information from the face joins that from the body, entering the thalamus in a separate nucleus, the ventroposterior medial (VPM) nucleus.

Brain The third order thalamocortical afferents (from thalamus to cortex) travel up through the internal capsule to reach the primary somatosensory cortex, located in the post-central gyrus, a fold of cortex just posterior to the central sulcus (Figure 5.4a). The thalamocortical afferents convey all of the signals, whether from the ventroposterior lateral (VPL) or VPM nucleus, to primary somatosensory cortex where the sensory information from all body surfaces is mapped in a somatotopic (body-mapped) manner [25], with the legs represented medially, at the top of the head, and the face represented laterally (Figure 5.4b). Within the cortex there are thought to be eight separate areas primarily subserving somatosensation: primary somatosensory cortex, SI, comprised of four subregions (2, 1, 3a and 3b); secondary somatosensory cortex, SII, located along the superior bank of the lateral sulcus [26]; the insular cortex; and the posterior parietal cortex, areas 5 and 7b (Figure 5.5). As with studies of the peripheral nervous system, outlined above, the technique of microneurography has again been employed, in this case to study the relationship between skin sensory nerves and their central projections, as evidenced by the use of concurrent functional magnetic resonance imaging (fMRI). Microstimulation of individual LTM afferents, projecting to RFs on the digit, produces robust, focal, and orderly (somatotopic) hemodynamic (BOLD) responses in both primary and secondary somatosensory cortices [27]. It is expected that this technique will permit the study of many different topics in somatosensory neurophysiology, such as sampling from FA and SA mechanoreceptors and C-fibers with neighboring or overlapping RFs on the skin, quantifying their spatial and temporal profiles in response to electrical chemical and/or mechanical stimulation of the skin areas they innervate, as well as perceptual responses to microstimulation. Finally, the forward projections from these primary somatosensory areas to limbic and prefrontal structures has been studied with fMRI in order to understand the affective representations of skin stimulation for both pain and pleasure [28] and it is hoped that studies of this nature will help us to understand better the emotional aspects of both negative and positive skin sensations.

Leg Arm



Cortex Medulla

Spinal cord


W H rist Li and Rin ttle Mi g Ind ddle ex Thu mb Eye No Fa se ce Up per lip Lips

Somatosensory cortex of left hemisphere of brain

Dorsal column nucleus

Lower lip Teeth, gums and

Cell body of sensory nerve

Tongue ynx al Phar min bdo a a Intr

Finger of right hand

Primary afferent fiber


arm Fore Elbow Arm Shoulders Head k Nec k Trun Hip

5. Sensitive skin

Leg Foot Toes Genitals



Figure 5.4 (a) Outline of the somatosensory pathways from the digit tip to primary somatosensory cortex, via the dorsal column nuclei and the thalamus. (b) Penfield’s somatosensory homunculus. Note the relative overrepresentation of the hands and lips, and the relative underrepresentation of the trunk and arms.

Conclusions Central sulcus Intraparietal sulcus

7 3,1,2




Lateral sulcus Figure 5.5 Cortical areas subserving somatosensation. Primary somatosensory cortex is located in the posterior bank of the central sulcus and the posterior gyrus and comprises areas 2, 1, 3a and 3b, secondary somatosensory cortex is located in the upper bank of the lateral sulcus with two further somatosensory regions in the posterior parietal cortex, areas 5 and 7b.

In this chapter we describe the neural architecture of the skin senses, where it has been shown that the skin surfaces we groom when applying cosmetic agents are receptive to a wide variety of physicochemical forms of stimulation. Low threshold mechanoreceptors are responsible for the sensation of touch, a wide range of receptor systems code for temperature, and, as the skin’s integrity is critical for survival, there are an even larger number of sensory receptors and nerves that warn us of damage to the skin – the pain and itch systems. In addition to this “classic” description of the skin senses, we also provide recent evidence for the existence of another skin receptor system which shares many of the same characteristics as the pain system with one important distinction – this system of sensory nerves is excited by low force, slowly moving tactile stimulation – such as that employed when grooming the body surfaces. This C-fiber-based system of peripheral cutaneous sensory nerves is therefore serving both a protective and hedonic role in body grooming behaviors.



Skin Physiology

References 1 von Bekesy G. (1939) Uber die Vibrationsempfindung. [On the vibration sense.] Akust Z 4, 315–34. 2 Bolanowski SJ, Gescheider GA, Verrillo RT, Checkosky CM. (1988) Four channels mediate the mechanical aspects of touch. J Acoust Soc Am 84, 1680–94. 3 Essick GK, Edin BB. (1995) Receptor encoding of moving tactile stimuli in humans: the mean response of individual lowthreshold mechanoreceptors to motion across the receptive field. J Neurosci 15, 848–64. 4 Valbo AB, Johansson RS. (1978) The tactile sensory innervation of the glabrous skin of the human hand. In: Gordon G, ed. Active Touch. New York: Pergammon, pp. 29–54. 5 Hensel H, Boman KKA. (1960) Afferent impulses in cutaneous sensory nerves in human subjects. J Neurophysiol 23, 564–78. 6 Hensel H. (1973) Cutaneous thermoreceptors. In: Iggo A, ed. Somatosensory System. Berlin: Springer-Verlag, pp. 79–110. 7 Torebjörk H. (1976) A new method for classification of C-unit activity in intact human skin nerves. In: Bonica JJ, Albe-Fessard D, eds. Advances in Pain Research and Therapy. New York: Raven, pp. 29–34. 8 Campero M, Serra J, Ochoa, JL. (1966) C-polymodal nociceptors activated by noxious low temperature in human skin. J Physiol 497, 565–72. 9 Konietzny F. (1984) Peripheral neural correlates of temperature sensations in man. Hum Neurobiol 3, 21–32. 10 Darian-Smith I. (1984) Thermal sensibility. In: Darian-Smith I, ed. Handbook of Physiology, Vol. 3, Sensory Processes. Bethesda, MD: American Physiological Society, pp. 879–913. 11 Campero M, Serra J, Bostock H, Ochoa JL. (2001) Slowly conducting afferents activated by innocuous low temperature in human skin. J Physiol 535, 855–65. 12 Bessou M, Perl ER. (1969) Response of cutaneous sensory units with unmyelinated fibres to noxious stimuli. J Neurophysiol 32, 1025–43. 13 Campbell JN, Raja SN, Cohen RH, Manning DC, Khan AA, Meyer RA. (1989) Peripheral neural mechanisms of nociception. In: Wall PD, Melzack R. eds. Textbook of Pain. Edinburgh: Churchill Livingstone, pp. 22–45. 14 Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjörk HE. (1997) Specific C-receptors for itch in human skin. J Neurosci 17, 8003–8. 15 Andrew D, Craig AD. (2001) Spinothalamic lamina 1 neurons selectively sensitive to histamine: a central neural pathway for itch. Nat Neurosci 4, 72–7.


16 Ikoma A, Handwerker H, Miyachi Y, Schmelz M. (2005) Electrically evoked itch in humans. Pain 113, 148–54. 17 Yosipovitch G, Goon ATJ, Wee J, Chan YH, Zucker I, Goh CL. (2002) Itch characteristics in Chinese patients with atopic dermatitis using a new questionnaire for the assessment of pruritus. Int J Dermatol 41, 212–6. 18 Nordin M. (1990) Low threshold mechanoreceptive and nociceptive units with unmyelinated (C) fibres in the human supraorbital nerve. J Physiol 426, 229–40. 19 Johansson RS, Trulsson M, Olsson KA, Westberg KG. (1988) Mechanoreceptor activity from the human face and oral mucosa. Exp Brain Res 72, 204–8. 20 Valbo AB, Hagbarth K-E, Torebjork HE, Wallin BG. (1979) Somatosensory, proprioceptive and sympathetic activity in human peripheral nerves. Physiol Rev 59, 919–57. 21 Essick G, James A, McGlone FP. (1999) Psychophysical assessment of the affective components of non-painful touch. Neuroreport 10, 2083–7. 22 Olausson H, Lamarre Y, Backlund H, Morin C, Wallin BG, Starck S, et al. (2002) Unmyelinated tactile afferents signal touch and project to the insular cortex. Nat Neurosci 5, 900–4. 23 Reilly DM, Ferdinando D, Johnston C, Shaw C, Buchanan KD, Green M. (1997) The epidermal nerve fibre network: characterization of nerve fibres in human skin by confocal microscopy and assessment of racial variations. Br J Dermatol 137, 163–70. 24 Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M. (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86, 1309–79. 25 Maldjian JA, Gotschalk A, Patel RS, Detre, JA, Alsop DC. (1999) The sensory somatotopic map of the human hand demonstrated at 4T. Neuroimage 10, 55–62. 26 Maeda K, Kakigi R, Hoshiyama M, Koyama S. (1999) Topography of the secondary somatosensory cortex in humans: a magentoencephalographic study. Neuroreport 10, 301–6. 27 Trulsson M, Francis ST, Kelly EF, Westling G, Bowtell R, McGlone FP. (2001) Cortical responses to single mechanoreceptive afferent microstimulation revealed with fMRI. Neuroimage 13, 613–22. 28 Rolls E, O’Doherty J, Kringelbach M, Francis S, Bowtell R, McGlone F. (2003) Representation of pleasant and painful touch in the human orbitofrontal cortex. Cereb Cortex 10, 284–94.

Chapter 6: Novel, compelling, non-invasive techniques for evaluating cosmetic products Thomas J. Stephens,1 Christian Oresajo,2 Robert Goodman,1 Margarita Yatskayer,2 and Paul Kavanaugh1 1 2

Thomas J. Stephens & Associates Inc., Dallas Research Center, Carrollton, TX, USA L’Oréal Research USA, Clark, NJ, USA

BAS I C CONCEPTS • Skin care products must be studied for safety and efficacy. • Non-invasive techniques were developed to assess the skin without a biopsy. • Non-invasive techniques are used to evaluate visual appearance, moisturization, barrier integrity, oiliness, elasticity, firmness, erythema, and skin color. • New photography techniques have been developed to detect changes in wrinkling of the face.

Introduction Clinical trials for substantiation of cosmetic claims should be designed with good scientific rigor. In 1999, Rizer et al. [1] described an integrated, multidimensional approach for achieving this goal. The multistep process consisted of the following: careful subject selection, subject self-assessment of product performance, clinical grading, documentation photography, non-invasive bioengineering methods, and statistical analysis. Recently, the use of digital photography combined with image analysis has provided clinical investigators with a powerful new tool for quantifying improvements in wrinkles, hyperpigmentation, pore size, skin tone, and other dermatologic conditions. Unlike past years, in which photographs of subjects were used solely to document clinical changes, use of photographs of subjects has moved beyond simple study documentation. This chapter introduces dermatologists, cosmetic surgeons, and clinical researchers to the cost-effective, non-invasive methods for substantiating cosmetic claims. It includes an overview of commonly used, non-invasive methods in cosmetic studies and a description of various types of highresolution digital photography and their application for evaluating changes in skin.

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

Supporting cosmetic claims with bio-instrumentation Most scientists would agree that the use of non-invasive methods is an objective way for generating quantitative data about a product’s performance on skin. Does this mean that data from non-invasive instruments provide conclusive evidence to support a cosmetic claim? Consider a topical lotion formulated to improve the appearance of facial wrinkles and moisturize skin. Now imagine that it is your responsibility to substantiate these claims in a clinical study using available non-invasive methods. Undoubtedly, you would choose proven methods such as replica profilometry to assess wrinkle changes and the Skicon™ (IBS Ltd., Tokyo, Japan) or Corneometer® (Courage & Khazaka Electronic GmbH, Köln, Germany) to assess changes in skin hydration. Would favorable data from both of these techniques provide conclusive evidence to support the claims? The answer may surprise you. In many cases, non-invasive methods are more useful in providing indirect lines of evidence to support a cosmetic claim. In clinical research this is called a secondary endpoint. A primary endpoint refers to the most meaningful result in a clinical trial. In the example above, the primary endpoints would be a visible improvement in the appearance of wrinkles and reduction in the signs and symptoms of dry skin while the secondary endpoints would be improvements in wrinkle depth and high skin hydration values. The fact that many non-invasive methods are secondary endpoints does not diminish their importance in clinical research. Non-invasive methods often provide valuable information about the mechanism of action of a cosmetic



Skin Physiology

ingredient or cosmetic product on skin and a more reliable method to quantify improvements in skin. The use of colorimetry, a combination of digital photography and image analysis, is a much better method to quantify changes in skin erythema than by clinical examination, even though the human eye is very sensitive to color shifts. This technique is more fully described at the end of this chapter.

Commonly used non-invasive methods in cosmetic studies Approximately 90% or more of the cosmetic studies performed today are designed to support claims relating to improvements of fine lines or wrinkles, uneven skin pigmentation associated with sun exposure and/or hormonal changes, enlarged pores, skin radiance, skin roughness, skin tone, and skin dryness. Table 6.1 provides a listing of commonly used, non-invasive techniques that are used to help support these specific claims. For the reader who would like to learn more about these techniques or other non-invasive methods, there are a number of excellent books and articles available in the chapter’s reference list [2–8]. Ideally, an investigator would like to see agreement between the clinical grading, non-invasive bio-instrumentation measurements and subject self-perception questionnaires. Occasionally, investigators obtain good concordance between clinical grading and self-perception questionnaires, but discordance with the non-invasive technique.

Table 6.1 Commonly used bio-instruments and non-invasive procedures. Name


NOVA Meter






TEWA Meter

Skin barrier function assessment

Derma Lab

Skin barrier function assessment


Firmness and elasticity


Skin tone, erythema, skin lightening, brightness


Skin tone, erythema, skin lightening


Oiliness (sebum)




Scaling, exfoliation, and cell renewal

Silicone Replica Impressions

Skin texture, wrinkling


Let us return to the example of the topical product designed to improve the appearance of wrinkles. It is not uncommon to see visible improvements in wrinkles during clinical grading while failing to detect the improvements using silicone replica profilometry. The discordance is not a result of grader error, but of limitation of the replica impressions to fully detect changes over the entire periocular area. Replica impressions are usually taken by spreading the unpolymerized replica material a few millimeters from the corner of the eye with the subject’s eyes closed. This is necessary in order to prevent the replica material from running into the eye itself. If the grader makes his or her judgment based on the appearance of wrinkling in the areas adjacent to the corner of the eye as well as the area under the eye with the subject’s eyes open, there is chance the grader might see improvements in wrinkling that might not be detected by the replica impression. Additionally, having the eyes closed while the impression is being taken can occasionally result in situations in which the subject squints, resulting in deeper, more pronounced wrinkles. The end result is a replica impression that detects more or deeper wrinkles. An alternative method, Raking Light Optical Profilometry (RLOP), which provides a newer, more novel approach for analyzing changes in wrinkling, is discussed below. The advantage of this technique is that the subject’s eyes are open and the wrinkling appears in the same way as viewed by the clinical grader.

Application of digital photography as a non-invasive technique for assessing skin The challenge for clinical documentation photography is twofold: to choose the best photographic technique relative to the aims of the study and to maximize consistency of the imaging at each clinic visit throughout the trial. The key to successful photography in clinical trials is the application of standardization, which includes the control subject’s positioning, dress, lighting conditions, depth of field, background, and facial expression from visit to visit. The goal is to have images that accurately show treatment effects for use in medical and scientific journals. There is no place for misrepresenting clinical outcomes by changing viewing angles, altering lighting conditions, or having the subject apply facial makeup after using a product [9,10]. The first step to successful photography is to create the appropriate lighting and other photographic techniques specific to the skin conditions of interest in the clinical study. A study involving a product designed to reduce the appearance of fine lines and wrinkles demands significantly different lighting than would trials involving acne, photodamaged skin, skin dryness or flakiness, scars, wound healing, postinflammatory hyperpigmentation (PIH), or pseudofolliculitis

6. Evaluating cosmetic products barbae. In order to ensure a high degree of color consistency in photographic technique, the photographer should include color standard chips in each documentation image. Typically, these standards include small reference chips of white, 18% reflectance gray, black, red, green, and blue, as well as a millimeter scale for size confirmation. In addition, a more comprehensive color chart such as a ColorChecker® (X-Rite America Inc., Grand Rapids, MI, USA) should be photographed under the exact standard lighting immediately before starting each photo visit. Equally crucial is the careful and detailed recording of all aspects of lighting, camera, and lens settings in order to achieve maximum consistency of documentation photographs. Photographing each different photographic set-up provides more certainty that photographs at subsequent sessions are identical to the images made at baseline visit. Prior to photography, all makeup and jewelry must be removed, and hair kept clear of the subject’s face by use of a neutral-color headband. Clothing should be covered by a gray or black cloth drape to prevent errors caused by color reflected from colored clothing. At each subsequent visit in the study, it is necessary to display the baseline image on the computer monitor for side-by-side comparison with that visit’s photograph. Subject position, size, color, and lighting can thus be checked to make sure that changes in the skin are brought about by product effect, and are not artifacts caused by careless photographic technique. When the study is over, the sequence of images should look similar to a time-lapse video, with the only difference from one image to another being changes in the condition of the subject’s skin. At Stephens & Associates, Inc. we have

designed fully equipped photographic studios within our clinics so that subjects can be photographed under standardized conditions from visit to visit (Figure 6.1). These studios are manned by experienced medical photographers who have been trained in the basic science of conducting a clinical trial. While it is not possible for many clinics to have fully equipped studios with medical photographers in their office, there are other off-the-shelf alternatives which will allow them to control the quality of the images in clinical research. The VISIA, VISIA CR and VISIA CR2 are standardized camera systems that have been designed for use in clinical research. VISIA systems can be operated by individuals with little to no experience in photography. VISIA systems are composed of an oval-shaped plastic shell containing a digital camera and lighting system. Subject positioning is controlled by forehead and chin rests. VISIA contains proprietary software called VISIA Complexion Analysis Software System. The VISIA software system, developed by Procter and Gamble, counts the number of spots, pores, wrinkles, porphyrins, UV spots, red areas, and brown areas on the face of subjects. The VISIA CR® (Canfield Scientific Inc., Fairfield, NJ, USA) system has an advantage over the VISIA system in that quality of the images are usually better, because the VISIA CR system is equipped with higher resolution cameras than the standard or first generation VISIA system. At the time of writing, the Complexion Analysis Software (Figure 6.2) is not available on the VISIA CR or VISIA CR 2. A simpler software, using the Canfield RBx system, is currently compatible with the VISIA CR machines. Images taken with either system must be exported from the

Figure 6.1 An example of a Stephens & Associates, Inc. photographic studio. The studio is equipped for taking photographs using standard lighting, parallel and polarized lighting, cross polarized lighting and raking light.

Figure 6.2 An example of the data reporting for the VISIA Complexion Analysis Software.



Skin Physiology

camera for more detailed image analysis of spots, lines, wrinkles, pores, and color changes. VISIA systems, while easy to use, have limitations in certain situations. The chin and head rests are sometimes too small for individuals with large faces, resulting in “jammed in” appearance. Additionally, it is difficult to see skin details such as acne lesions or PIH marks on images taken of subjects with Fitzpatrick skin types V and VI because of the close proximity of the subject’s face to the camera and lighting system. Unlike viewing software provided by Nikon and Canon, VISIA does not allow images to be displayed from previous treatment visits and the baseline visit for a side-by-side image comparison. Therefore, it is difficult to make sure the head position and facial expressions are the same in all photographs.

Review of terminology in clinical photography Individuals incorporating digital photography into a clinical trial are often faced with the difficult task of understating the vocabulary used by staff at clinical research organizations (CROs). This section provides a concise description of commonly used terms and techniques in clinical photography.

Visible light photography This refers to images made with unfiltered full-spectrum (white) light. It is the most common type of photography used in clinical trials. Proper positioning of the strobe flashes is a critical step for capturing various skin conditions in cosmetic clinical trials. Clinical studies involving evenness of color and skin tone require a more generalized, evenly distributed, visible lighting method while the imaging of fine lines, wrinkles, under eye bags, skin texture, and scaling is best achieved by placing the flashes in an off-axis direction. Off-axis lighting refers to lighting that is placed somewhat above and to the side to create small shadows and highlights on the skin thereby giving a three-dimensional quality to the image. Once the lighting conditions have been optimized, it is imperative that the photographer use documentation notes, setup photographs, light metering and color charts to prevent lighting changes from visit to visit.

Polarized photography This involves the placement of linear polarizing filters on both the lighting flash head(s) and in front of the lens of the digital camera. This allows the documentation of skin in two different ways [11]. The parallel-polarized lighting technique accentuates the reflection of light from the skin and tends to obscure fine


topical detail because of strong reflections from the lighting source(s). Parallel-polarized light minimizes subsurface details, such as erythema and pigmentation, while allowing for enhanced viewing of the surface features of the skin, such as sweat, oily skin, and pores. The cross-polarized lighting technique involves fixing the transmission axis of the lens polarizer 90 ° to the axis of the lighting polarizer. This virtually eliminates the reflection of light (glare) from the surface of the skin and accentuates the appearance of inflammation from acne lesions, erythema, rosacea, and telangiectasia. Photodamaged skin becomes somewhat more apparent and some subsurface vascular features are made visible. Cross-polarized photography is useful for evaluating products designed to mitigate the appearance of dyschromic lesions, erythema, acne, and PIH resulting from acne. This technique is highly recommended for acne studies [12]. Examples of a parallel-polarized lighting technique and cross-polarized lighting technique can be found in Figure 6.3.

UV reflectance photography This is a technique designed to highlight or enhance hyperpigmentation on the face. This is accomplished through filtering a flash source to only allow UV light to pass on to the subject’s skin allowing visualization of subsurface melanin distribution. Figure 6.4 shows before and after UV reflectance photographs of a subject treated with a skin lightening product. A UV-blocking filter is placed in front of the lens of the digital camera. Note the improvement in the appearance and distribution of mottled and diffuse hyperpigmentation in the photograph on the right.

UV fluorescence photography This is primarily used to visualize the locations of Propionibacterium acnes in the pores of subjects with acne. Porphyrins produced by P. acnes exhibit an orange–red fluorescence under UVA light. Excitation of P. acnes on skin is achieved using a xenon flash lamp equipped with an UVA bandpass filter. The resulting fluorescence can be recorded using a high-resolution digital camera equipped with an UV barrier filter. An example of this technique can be found in Figure 6.5. Researchers have reported that UV fluorescence photography is a reliable, fast, and easy screening technique to demonstrate the suppressive effect of topical antibacterial agents on P. acnes [13]. Investigators need to be aware of a problem that can occur with using this technique to monitor P. acnes on the face. Many soaps, cosmetics, or sunscreen products contain quenching agents that can interfere with the accuracy of this imaging process. This can lead to an erroneous conclusion about the elimination of P. acnes from the face.

6. Evaluating cosmetic products

Figure 6.3 Examples of a parallelpolarized lighting technique (a) and cross-polarized lighting technique (b).



Figure 6.4 Before and after UV reflectance photographs of a subject treated with a skin lightening product. (a) Ultraviolet reflectance at baseline. (b) Ultraviolet reflectance at 12 weeks.



Digital fluorescence photography has other applications in dermatologic research. The technique can be used to detect salicylic acid in the skin and follicles of subjects participating in claim studies, as well as follow the migration of sunscreen products over the surface of face. Following the migration of sunscreen products over the surface can help explain why some sunscreen products find their way into the eyes producing stinging, burning, and ocular discomfort. Guide photographs refer to photographs taken of mock subjects before the clinical trial begins to provide the sponsor and investigator with choices of techniques to best capture the dermatologic condition being studied. The chosen image becomes the guide, or standard, for photographing all subjects in the trial.

Use of RLOP to detect improvements in periocular fine lines and wrinkles Optical profilometry refers to a technique in which photographic images of silicone rubber impressions taken of facial skin can be analyzed for changes in lines and wrinkles. Grove et al. [14] reported that optical profilometry provides an element of objectivity that can complement clinical assessment in the study of agents that are useful for treating photodamaged skin. While no one would argue that optical profilometry is a time proven method for assessing textural changes, preparing quality silicone replicas can be quite challenging even



Skin Physiology

Figure 6.5 Ultraviolet fluorescence technique.

for veteran clinicians. Common problems include replica ring positioning errors, air bubbles in the replica impression, and controlling the polymerization process. Slight variations in temperature, humidity, and body temperature can produce unsuitable replica impressions. In an effort to reduce the frustration level associated with preparing silicone replicas, we began investigations into using high-resolution digital photographs for quantifying changes in fine line and wrinkles on the face. Off-axial lighting, a common lighting technique used for clinical photography, could be used to create small shadows and highlights that could help define the surface texture of skin. Flash lighting can be placed above and at a 45 ° angle to the side of the face to create a three-dimensional effect of texture in a two-dimensional plane. The raw image files can be analyzed for fine lines and wrinkles on the face. The term to describe this technique is RLOP. RLOP is designed to detect the number, length, width, and depth of horizontal wrinkles in the crow’s feet area (coarse wrinkles) and the under eye area (fine lines). Wrinkles appear as dark lines on grayscale images. Deeper wrinkles appear darker because less light is present at the base of the wrinkle. An irregularly shaped area of interest is selected in the crow’s feet area to avoid capturing the eyebrows or hairline, and a rectangular area of interest is used under the eye. Image Pro® v6 software (Media Cybernetics, Bethesda, MD, USA) is used for the analysis. A horizontal edge filter is used to locate the wrinkles and exclude any dark objects caused by hyperpigmentation or scars. Once the wrinkles are identified with the edge filter they are measured for size (length, width, and area) and grayscale density (where


0 = black) on the original grayscale image. Once the data are collected a paired t-test is used to check for significant changes from baseline or between groups. As part of the validation process, RLOP has been included in several photoaging trials of cosmetic products involving several hundred subjects. The effectiveness of the products was evaluated using visual grading, digital photography with RLOP, bio-instrumentation, and subject self-assessment. The duration of these trials were typically 8 weeks, with clinic visits at 2, 4, and 8 weeks (Figure 6.6). RLOP technology complements and supports the results of clinical grading of fine line and wrinkles. RLOP appears to have several advantages over traditional optical profilometry. These advantages include: • RLOP can be performed on multiple sites on the face using a single digital photograph. • RLOP technology allows for precise location of the area of interest in each digital photograph through imaging software. • Digital images can be archived electronically for an indefinite period of time. • Results are expressed in meaningful units and endpoints. • The area of interest is significantly larger than can be captured in a replica impression. • RLOP can measure the full length of a wrinkle unlike traditional optical profilometry which limits the measured area to the size of the replica impression.

A non-invasive method for assessing the antioxidant protection of topical formulations in humans It is well documented that the addition of antioxidants such as vitamins C, E, and A to skin care formulation can be beneficial in preventing and minimizing skin damage associated with UV light [15–17]. Manufacturers often face a difficult task when formulating with antioxidants, because they are easily destroyed or altered by oxidation which can occur during product manufacturing, filling, or storage. To address these concerns, Pinnell and colleagues developed a human antioxidant assay which assesses the potential of topical antioxidants to enter into the skin and provide adequate protection against UV damage generated by a solar simulator. Antioxidants provide protection from UVRinduced damage by diminishing or blocking the formation of reactive oxygen species which is clinically manifested by erythema [17]. The technique involves the open applications of antioxidant products and a vehicle control to the demarcated areas on the lower back of subjects for four consecutive days. On day 3 the minimal erythema dose (MED) is determined for

6. Evaluating cosmetic products




(d) Figure 6.6 Before and after photographs using Raking Light Optical Profilometry. Top row: Digital photographs from a trial of a subject before (a) and 8 weeks after (b) treatment. Note the improvement in the appearance of wrinkling under the eye. Bottom row: Photographs shows the area of interest (AOI) in red. (c) Baseline. (d) Eight weeks after. The AOIs were precisely located in each digital image by using anatomic landmarks as anchors.

each subject. This is the dose of UV light that produces slight redness on fair-skinned individuals. On day 4, the demarcated sites treated with the antioxidant product, vehicle control, and an untreated site receive solar-simulated UV irritation of 1–5X MED at 1X MED intervals. On day 5, digital images are taken and the investigator has the option of collecting punch biopsies at the treatment sites and analyzing the tissues for multiple bio-markers such as thymine dimers, interleukins, metaloproteins, Langerhans cells (CD1a), p53, and sunburn cells [13,14]. Figure 6.7 shows a pattern of UV responses for a site treated with an antioxidant and a site treated with a vehicle control. Using macro-programs written in Image Pro software, it is possible to determine accurately the a* (degree of redness according to the CIE color standard) of each spot

and to calculate a protection factor for the antioxidant product relative to vehicle control treated site (Table 6.2). Using this technique, Pinnell and associates have been able to formulate a third generation antioxidant product that provides protection against the damaging effects of UV light. The formulation containing 15% ascorbic acid, 1% alfatocopherol, and 0.5% ferulic acid was found to be effective in reducing thymine dimers known to be associated with skin cancer [18,19].

Conclusions Photography and other non-invasive techniques are important to assess the efficacy and safety of cosmetic products.


Skin Physiology




Test material






Table 6.2 Results of theorectical antioxidant protection factor calculations. Increase from unexposed (adjusted for MED) No treatment (control)

Protection factor (%)






Vehicle control



MED, minimal erythema dose.

Often, the non-invasive assessments provide confirmation of the expert grader assessments. It is reassuring to see consistency within the data set to confirm a positive effect of cosmetics and skin care products. This validation technique is necessary to truly evaluate products. This chapter presents several cutaneous research tools.

References 1 Rizer RL, Sigler ML, Miller DL. (1999) Evaluating performance benefits of conditioning formulations on human skin. In: Schueller R, Romanowski P, eds. Conditioning Agents for Hair and Skin. pp. 345–51. 2 Berardesca E. (1997) EEMCO guidance for the assessment of stratum corneum hydration: electrical methods. Skin Res Technol 3, 126–32. 3 Elsner P, Barel AO, Berardesca B, Gabard B, Serup J. (1998) Skin Bioengineering. Basel; New York: Karger. 4 Flosh PJ, Kligman AM. (1993) Non-Invasive Methods for the Quantification of Skin Functions. Springler-Verlag. 5 Serup J, Jemec GBE. (1995) Handbook of Non-Invasive Method and the Skin. Boca Raton, FL: CRC Press. 6 Elsner P, Berardecsa E, Wilhelm KP, Maibach HI. (2006) Bioengineering of the Skin: Skin Biomechanics. Boca Raton, FL: CRC Press.



Figure 6.7 Pattern of UV responses for a site treated with an antioxidant and a site treated with a vehicle control.

7 Elsner P, Berardesca E, Wilhelm KP. (2006) Bioengineering of the Skin: Skin Imaging and Analysis, 2nd edn. Informaword. 8 Elsner P, Berardecsa E, Wilhelm KP, Maibach HI. (1995) Bioengineering of the Skin: Methods and Instrumentation. Taylor & Francis. 9 Stack LB, Storrow AB, Morris MA, Patton DR. (1999) Handbook of Medical7 Photography Philadelphia, PA: Hanley & Belfus, pp. 15–20. 10 Ratner D, Thomas CO, Bickers D. (1999) The use of digital photography in dermatology. J Am Acad Dermatol 41, 749–56. 11 Phillips SB, Kollias N, Gillies R, Muccini A, Drake LA. (1997) Polarized light photography enhances visualization of inflammatory lesions of acne vulgaris. J Am Acad Dermatol 37, 948–52. 12 Rizova E, Kligman A. (2001) New photograqphic technique for clinical evalution of acne. J Eur Acad Dermatol Venereol 15 (Suppl 3), 13–8. 13 Pagnoni A, Kilgman AM, Kollias N, Goldberg S, Stoudemeyer T. (1999) Digital fluorescence photography can assess the suppressive effect of benzoyl peroxide on Propionibacterium acnes. J Am Acad Dermatol 41, 710–6. 14 Grove GL, Grove MJ, Leyden JJ. (1989) Optical profilometry: an objective method for quantification of facial wrinkles. J Am Acad Dermatol 21, 631–7. 15 Rabe JH, Mamelak AJ, EcElgunn JS, Morrison WL, Sauder DN. (2006) Photoaging: mechanisms and repair. J Am Acad Dermatol 55, 1–19. 16 Dreher F, Denig N, Gabard B, Schwindt Da, Maibach MI. (1999) Effect of topical antioxidants on UV-induced erythema formation when administered after exposure. Dermatology 198, 52–5. 17 Pinnell, SR (2003). Cutaneous photodamage, oxidative stress and topical antioxidant protection. J Am Acad Dermatol 48(1), 1–19. 18 Murray JC, Burch JA, Streilein RD, Iannacchione MA, Hall RP, Pinnell SR. (2008) atopical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. J Am Acad Dermatol 59, 418–25. 19 Oresajo C, Stephens T, Hino PD, Law RM, Yatskayer M, Foltis P, et al. (2008) Protective effects of a topiocal antioxidant mixture containing vitamin C, and phloretin against ultraviolet-induced photodamage in human skin. J Cosmet Dermatol 7, 290–7.

Chapter 7: Contact dermatitis and topical agents David E. Cohen and Aieska de Souza New York University School of Medicine Department of Dermatology, New York, NY, USA

BAS I C CONCEPTS • Hypersensitivity reactions can occur in response to topical agents. • Adverse reactions can be characterized by irritant contact dermatitis and allergtic contact dermatitis. • Patch testing is a reliable method for determining the etiology of adverse reactions to topical products. • Treatment of hypersensitivity reactions involves prompt recognition with identification and withdrawal of the offending agent.

Introduction Topical cosmetic medications, cosmeceuticals, and minimally invasive procedures have always had an important role in dermatologic practice, but recent advances have led to a tremendous expansion in the repertory of treatment modalities available. In addition, the use of over-the-counter cosmetics is rising worldwide, along with potential exposure to irritants and allergenic substances [1]. Adverse skin reactions to cosmetics include irritant contact dermatitis, allergic contact dermatitis, contact urticaria, and foreign body reactions [2]. The clinician should be able to diagnose these cases, prescribe the correct treatment, and – most importantly – identify the causative agent. Most of these reactions are treatable without sequelae once the offending agent is identified and avoided [2]. Approximately 15 million Americans have been diagnosed with contact dermatitis [2]. The US Food and Drug Administration (FDA) regulations on cosmetics are based in two important laws: the Federal Food, Drug, and Cosmetic Act (FD&C) which prohibits the marketing of adulterated or misbranded cosmetics, and the Fair Packaging and Labeling Act (FPLA) which states that improperly labeled or deceptively packaged products are subject to regulatory action [3]. Ingredient labeling is mandatory in the USA and Europe, and compounds are listed in descending order of amount using the nomenclature format of the International Cosmetic Ingredient Dictionary [4,5]. However, with the exception of color additives, cosmetic products and ingredients are not subjected to FDA premarket approval and manufacturers’ reporting of adverse reactions is a voluntary process [3]. In order to review the safety of the cosmetic ingredients, the

Cosmetic, Toiletries and Fragrance Association (CTFA) sponsors the Cosmetic Ingredient Review (CIR). Reactions to cosmetics can manifest in a wide range of clinical signs, therefore it is important for the clinician to be familiar with the diversity of those presentations to enable prompt diagnosis and treatment.

Hypersensitivity reactions: pathophysiology and clinical presentations Irritant contact dermatitis Most skin reactions to cosmetics are classified as irritant contact dermatitis [4]. Irritant contact dermatitis is caused by endogenous and environmental elements and it is defined as local inflammation that is not initially mediated by the immune system. Predisposing factors for the development of irritant dermatitis included the presence of a less effective stratum corneum, either from anatomic conditions (face, eyelids) or secondary to endogenous disorders, such as atopic dermatitis. The severity of the dermatitis depends on the amount and strength of the agent, and length and frequency of exposure. Repetitive exposures even to mild agents, such as soaps and detergents, will often result in irritant dermatitis. In addition, harsh scrubbing with mechanical assistance (brushes, synthetic sponges, or cosmetics containing microabrasive spheres) increases the risk for irritation. Psychiatric disorders, leading to compulsive repetitive behaviors of self-cleaning and handwashing, can sometimes be overlooked and a complete patient history must include cleaning habits, occupation, and a detailed list of all products used on both a daily and occasional basis.

Allergic contact dermatitis Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

Allergic dermatitis constitutes at least 10–20% of all cases of contact dermatitis and represents a true delayed-type (type IV) immune reaction. Previous exposure and sensitization



Skin Physiology

to the agent is necessary [2]. Chemical agents act as haptens, which are small electrophilic molecules that bind to carrier proteins and penetrate into the skin. HLA-DR or class II antigens act as the binding site in the surface of the antigenpresenting cells (APCs). These epidermal dentritic cells digest the allergen complex and display the antigenic site on their cell surfaces for presentation to T lymphocytes. If the individual has the genetic susceptibility to that allergen, clonal proliferation of T cells starts with the production of cytokines, further stimulating migration of inflammatory cells and keratinocyte proliferation. Clinical distinction between irritant and allergic dermatitis can be challenging because both conditions manifest as eczematous reactions, ranging from mild erythema and scale with minimal itch to vesicular, bullous, and indurated plaques that are highly pruritic. Furthermore, the two conditions can be superimposed, because an irritated and broken epidermal barrier can facilitate the absorption of haptens and elicit an immune response in susceptible individuals.

healing and foreign body reaction. Acute inflammation is characterized by the presence of neutrophils, mast cell degranulation, and fibrinogen adsorption. The degree of the inflammation is highly dependent upon the injury produced, the site of injection, the material used, and the extent of the provisional matrix formed. The acute phase generally resolves within 1 week, and can be followed by chronic phase inflammatory response, which is characterized by the presence of monocytes, lymphocytes, and plasma cells. After resolution of acute and chronic phases of inflammation, a granulation tissue can be identified, rich in macrophages and fibroblasts which act to produce neovascularization and new healing tissue [6]. Prolonged duration of the inflammatory phase (i.e. longer than 3 weeks) should prompt an investigation to rule out complications, such as infection, allergic reaction, gel migration, abscesses formation, or granulomatous reaction. Foreign body granulomatous reactions with deleterious consequences have been previously described with the use of silicon, bovine collagen, hyaluronic acid, and other fillers [2,7–10].

Contact urticaria Contact urticaria syndrome is divided into immunologic and non-immunologic subtypes. Non-immunologic contact urticaria is the most common form and occurs in the absence of previous exposure. Localized wheals appear within 30–60 minutes after exposure and are not followed by systemic symptoms. Allergic contact urticaria is an immediate-type (type I) hypersensitivity reaction and occurs in sensitized individuals within minutes to hours following the exposure to the allergen. The binding between allergens and immunoglobulin E (IgE) triggers mast cell degranulation and consequent release of inflammatory products, such as histamine, prostaglandins, leukotrienes, and cytokines. As a consequence, individuals experience erythema, swelling, and pruritus which may be localized (wheals and fares) or generalized (angioedema, conjunctivitis, bronchoconstriction, hypotension). Severe reactions may be fatal.

Foreign body reactions Gel fillers are a group of exogenous substances used for soft tissue augmentation. Their mechanism of action is the addition of volume per se once injected and also the production of a collagen matrix. Fillers are supposed to be inert materials but the degree of the response elicited varies according to the material and the technique used, as well as the host immunologic pattern of reaction. The normal initial host response to foreign body implantation is the formation of a blood-based matrix on and around the biomaterial, called the provisional matrix. The tissue injury may also lead to activation of the innate immune response and thrombus formation. The provisional matrix is rich in mitogens, chemoattractants, growth factors, and cytokines, proving an excellent medium both for wound


Common allergens Irritants In the clinical setting, irritant substances are used for the purpose of selectively destroying the damaged superficial layers of the skin, and the depth of penetration is correlated with the agent used, concentration, and time of exposure. Examples of “peeling” agents include retinoic, glycolic, and salicylic acids, resorcinol, trichloroacetic acid, and phenol. Undesirable irritant reactions are commonly seen with daily use of topical retinoids, leading to erythema and fine scaling, which tend to improve with time. A wide variety of substances may act as irritants when sufficient exposure in time and/or concentration is ensured (Table 7.1). Mechanical, chemical, and environmental factors can act alone or in combination to produce irritation in the skin. Mechanical factors include cosmetic procedures (shaving, waxing, laser therapy, dermoabrasion), habits (excessive rubbing of the skin with soaps, scrubs, usage of tight clothes or shoes, intense exercise), occupational exposure (latex gloves, microtrauma of the skin). Wet work (i.e. exposure of the skin to liquid), use of occlusive gloves for longer than 2 hours per day or frequent hand cleaning is one of the most common and important skin irritants [11]. Professions at risk include hairdressers, healthcare workers, and food handlers. Almost all chemicals have the potential to cause skin irritation. The list of the chemical compounds capable of producing irritation of the skin is extensive and largely dependent on the concentration, volume, and time of exposure. Some substances are considered universal irritants, for example, strong acids (hydrofluoric, hydrochloric, sulfuric,

7. Contact dermatitis and topical agents

Table 7.1 List of common skin irritants: mechanic, chemical, and environmental factors known to cause skin irritation. The agents can act alone or in combination to produce contact dermatitis, therefore recognition of all factors involved is crucial for proper management of patients. Mechanic



Shaving, waxing, laser treatment


Excessive heat or sun exposure, sunburn



Food allergies

Rubbing of the skin (e.g. when using a soap or scrubbing)

Surfactants (cocamidopropyl betaine*)

Saunas and jacuzzis (chlorine*)

Friction and/or occlusion (tight clothes, certain fabrics: wool, synthetic fibers)

Chemical peelings

Extreme cold and windburn

Latex gloves



Intense exercise

Fragrances and color additives (musk*)

Dry air


Preservatives (formaldehydes releasing substances: Quaternium 15*, imidazolidinyl urea, DMDM Hydantoin)

Hot and/or prolonged showers


Sunscreens (para-aminobenzoic acid*)

Spicy foods, peppers, condiments

Wet work

Bleaches and whitening agents


* Most common chemical compounds involved.

nitric acids) and strong caustics (sodium hydroxide, potassium hydroxide) produce severe burns even in brief and small exposures. Solvents, including alcohol, turpentine, ketones, and xylene, remove lipids from the skin, producing direct irritation and allowing other irritants, such as soap and water, to produce more damage on the exposed skin. Inappropriate skin cleansing with solvents to remove grease, paints, or oils is a common cause of skin irritation. Soaps are alkali substances and may produce irritation by disrupting the skin barrier; in contrast, cleansing agents with a pH of approximately 5.5 and alcohol-based hand-cleansing gels are less aggressive and should be preferred for sensitive skin. Environmental elements may render the skin more susceptible to cutaneous irritants, and include dry air, extremes of temperature (cold, heat), or important weather variations. Food allergies may cause urticarial reactions; spicy foods and condiments may cause lip and perioral irritant dermatitis. Prolonged exposure to water can cause maceration and desiccation of the skin. Acneiform eruptions refer to the presence of comedones, papules, pustules, and nodular cysts. Follicular plugging has been noticed secondary to the use of isopropyl myristate, an emollient and lubricant used in shaving lotions, shampoos, oils, and deodorants. Sodium lauryl sulfate (SLS) is a surfactant found in many topical medications, particularly for acne, and is a classic experimental cutaneous irritant. Pustular eruptions secondary to SLS have also been described. Bergamot oil (5-methoxypsoralen) induced phototoxic reactions in the past and it has subsequently been removed from the formulations of cosmetics. Photosensitivity reactions caused by topical retinoid preparations are common

and patients should be advised to use sunscreens and avoid sun exposure during treatment. Subjective irritation, described as a tingling, burning, stinging, or itching sensation without visible skin alteration is commonly observed with topical medications. Propylene glycol, hydroxy acids, and ethanol are capable of eliciting sensory irritation in susceptible individuals. Commonly used medications such as benzoic acid, azelaic acid, lactic acid, benzoil peroxide, mequinol, and tretinoin may have sensory irritation as a side effect. Sorbic acid is an organic compound used as a preservative in concentrations up to 0.2% in foods, cosmetics, and drugs. Subjective irritation has been demonstrated with 0.5% sorbic acid and to 1% benzoic acid in susceptible individuals [12]. “Sensitive skin” or cosmetic intolerance syndrome is a condition of cutaneous hyperreactivity secondary to substances that are not defined as irritants [13]. The condition encompasses a complex combination of objective and subjective irritative symptoms and may coexist with hidden allergic processes, urticarial reactions, and/or photodermatitis. Endogenous causes include seborrheic dermatitis, psoriasis, rosacea/perioral dermatitis, atopic dermatitis, and body dysmorphobia. Elimination of all cosmetic products for a prolonged period of time (6–12 months) followed by slow reintroduction (a new products every 2–3 weeks) is helpful when managing these cases.

Contact urticaria Cinnamic acid is a white crystalline substance, slightly soluble in water, which is obtained from oil of cinnamon, or from balsams such as storax. Its primary use is in the



Skin Physiology

manufacturing of the methyl, ethyl, and benzyl esters for the perfume industry, producing the “honey, fruit” odor. Type I non-immunologic reactions can be triggered by fragrances that contain cinnamic acid and cinnamal. Immunologic type I reactions can be triggered in susceptible individuals by parabens (preservatives), henna, and ammonium persulfate (oxidizing agent), leading to systemic symptoms and potentially fatal reactions [4]. Contact urticaria to latex is triggered by exposure to the proteins derived from Hevea brasiliensis tree. Risk factors include the presence of spina bifida, genitourinary tract abnormalities, previous contact to latex (from multiple surgical procedures, or occupational exposure) hand dermatitis, atopy, and specific food allergies (avocado, banana, chestnut, potato, tomato, kiwi, pineapple, papaya, eggplant, melon, passion fruit, mango, wheat, and cherimoya).

Allergic reactions Fragrances Allergic reactions to fragrances affect at least 1% of the population. The distribution of the eruption can be restricted to the areas of application (face, neck, hands, axillae) or it can present as generalized dermatitis. Products containing scents are ubiquitous and include cosmetics and toiletries, cleansers, and household goods. Common sensitizers are balsam of Peru, cinnamal, fragrance mix (eugenol, isoeugenol, oak moss absolute, geraniol, cinnamal, alfa-amyl cinnamic aldehyde, hydroxycitronellal and cinnamic alcohol), and colophony. Patch testing to 26 fragrances was performed as a multicenter project in the European Union to further identify possible additional allergens and prevent adverse reactions by proper labeling of cosmetic products [14]. The compounds considered important allergens were defined as group I substances: tree moss, HMPCC (hydroxymethylpentylcyclohexene carboxaldehyde), oak moss, hydroxycitronellal, isoeugenol, cinnamic aldehyde, and farnesol. Group II included substances clearly allergenic, but less relevant regarding sensitization frequency: cinnamic alcohol, citral, citronellol, geraniol, eugenol, coumarin, lilial, amyl-cinnamic alcohol, and benzyl cinnamate. Rarely, substances in group III were sensitizers: benzyl alcohol, linalool, methylheptin carbonate, alfa-amyl-cinnamic aldehyde, alfa-hexylcinnamic aldehyde, limonene, benzyl salicylate, gammamethylionon, benzyl benzoate, and anisyl alcohol [14]. Allergic reactions to Myroxylon pereira (balsam of Peru) have been correlated to scattered generalized dermatitis. Widespread involvement might also suggest a systemic exposure, and oral ingestion of balsam of Peru has been correlated with hand eczema [15].

Preservatives Preservatives are low molecular weight, biologically active compounds that prevent product contamination by micro-


organisms, or degradation. The recent growing replacement of organic solvents and mineral oils to water-based products in the cosmetic industry has increased the need of preservatives. Distribution of the allergic rash includes face, neck, hands, axillae, or generalized. Common sensitizers include formaldehyde and formaldehyde releasers, thiomerosal, Kathon CG, parabens, glutaraldehyde, DMD-hydantoin, quaternium-15 and are widely present in water-containing products (e.g. shampoos, cosmetics, metalworking fluids, and soaps). Formaldehyde allergy is common and is mostly caused by formaldehyde-releasing biocides in cosmetics, toiletries, and other products. In a recent review of 81 formaldehydeallergic patients, allergic reaction to at least one of the 12 formaldehyde-releasing substances were detected in 79% of the cases and isolated reactions to releasers were rare [16]. Formaldehyde allergy is also reported as a common cause of occupational contact dermatitis and the professions at risk include hairdressers, healthcare workers, painters, photographers, housekeeping personnel, metalworkers, masseurs, and workers dealing with creams, liquid soaps, and detergents [16].

Cleansing agents These are applied to remove sebum, desquamated cells, sweat, and microorganisms. Washout products are briefly in contact with the skin, therefore few cases of allergy have been reported. Allergens include surfactants (cocamidopropyl betaine), preservatives (methylchloroisothiozolinone), antimiocrobials (PCMX), and fragrances.

Moisturizers Moisturizers inhibit transepidermal water loss by occlusion, and are composed of a mixture of substances such as petrolatum, lanolin, lanolin derivates, and fatty alcohols. Stasis dermatitis can be a predisposing factor for allergic contact dermatitis to lanolin. Self-tanning agents have become increasingly popular and are sold separately or in conjunction with moisturizers. Such agents may cause allergic contact reactions when dihydroxyacetone degrades to form formaldehyde, formic acid, and acetic acid.

Hydroquinone Hydroquinone is a whitening agent present in up to 2% in over-the-counter creams and 4% in prescription bleaching creams. Irritant and allergic reactions, hypopigmentation and hyperpigmentation, and exogenous ochronosis are known side effects [17].

Shampoos and conditioners Shampoos contain a combination of cleansing agents and surfactants that act to remove sebum, scales, and microorganisms from the hair and scalp. Conditioner agents neutralize static charge and soften the hair. Common ingredients

7. Contact dermatitis and topical agents are moisturizers, oils, surfactants, lubricants, preservatives, and fragrances. Allergic reactions are uncommon because of the limited amount of time the substance is in contact with the skin, however, cocamidopropyl betaine (surfactant), formaldehyde, methylchloroisothiazolone and methylisothiazolone (preservatives) have been reported as causative agents of allergic contact dermatitis.

Hair dyes and bleaches Hair dyes are classified in semi-permanent and permanent. Semi-permanent dyes are derivates from nitroanilines, nitrophenylenediamines, and nitroaminophenols which use low molecular weight elements that penetrate the hair cuticle. Permanent dyes act by the means of primary intermediates (p-phenylenediamine [PPD] or p-aminophenol) which are oxidized by hydrogen peroxide and react with different couplers to produce a wide range of colours. Once oxidized to para-benzo-quinone diamine, PPD is no longer allergenic [18]. A few exceptions include circ*mstances in which unreacted PPD remains in the skin, for instance with inadequate mixture of ingredients with the use of homemade coloring kits or poor rinsing. Distribution is on the hairline, scalp, face, and photo distributed. Consort dermatitis is defined as the presence of the allergic eruption in the partner of the subject using the allergenic substance. It has been described for cosmetics, including PPD [18]. Temporary henna tattooing and hair dying are common practices. Henna is a natural product derived from the leaves of Lawsonia inermis and rarely causes hypersensitivity reaction. The addition of PPD to henna causes contact sensitization to black henna and reported reactions include mild eczema to bullous reactions with scarring and pigmentation alterations [19]. Hair bleaches include hydrogen peroxide solutions that oxidize melanin and ammonium persulfate, a very strong oxidizing agent and a radical initiator, which can be used as a booster supplement in hair dyes. Type I and IV hypersensitivity reactions may arise from the use of ammonium persulfate.

Permanents Permanents use mercaptans to cleave disufide bonds in hair; neutralizers are then added to reshape the configuration. Neutralizers contain hydrogen peroxide, bromates, perbromates, percarbromates, or sodium borate perhydrate. Ammonium thioglycolate, also known as perm salt, is a cleaving agent and if applied improperly can cause extensive hair damage and acute contact irritant dermatitis. Glycerol monothioglycolate (GMTG, “acid” permanents) can cause allergic contact dermatitis. Storrs [20] demonstrated positive allergic reactions to GMTG in concentrations as low as 0.25%, even when it was tested through glove fabric; however, household-weight neoprene gloves were proven to be protective.

Nail products Nail polish and hardener contains nitrocellulose, resins, plasticizers, solvents and diluents, colors, and suspending agents. Most adverse reactions are secondary to tolysamide formaldehyde resin (toluene sulfonamide/formaldehyde resin). The dermatitis tends to affect places commonly reached by the fingers (e.g. face, eyelids, sides of the neck, mouth), sparing the hands and fingers. Nail elongation materials contain acrylics (ethy acrylate, 2-hydroxy ethyl acrylate, ethylene glycol dimethacrylate, ethyl cyanoacrylate, and triethylene glycol diacrylate) all previously reported as allergens.

Local anesthetics Anesthetic agents can be divided in two groups: esters (benzocaine, tetracaine, and procaine) and amide derivates (lidocaine, mepivacaine, bupivacaine, etidocaine, and prilocaine). Cases of eczematous dermatitis have been reported secondary to the use of topical ester agents and rarely secondary to amide derivates. Contact sensitization to 2.5% lidocaine and 2.5% prilocaine emulsion (EMLA, Astra Zeneca Pharmaceuticals LP, Wilmington, DE, USA) is rare, and additional uncommon side effects reported include purpuric eruption, rash, redness, itching, and edema [2]. True IgE-mediated reactions to injectable anesthetics correspond to less than 1% of all adverse events. Although rare, such reactions may present as life-threatening events and prompt recognition of the symptoms and adequate management is imperative. In contrast, delayed-type reactions manifest within 12–48 hours and present as acute dermatitis (erythema, papules, vesicles and itching) [2,21]. The most common systemic adverse reactions to injectable anesthetics are psychosomatic responses, or exaggerated responses to epinephrine present in many products, caused by anxiety and vasovagal reflex. Patients may present with dyspnea, hyperventilation, and sympathetic responses, such as tachypnea, tachycardia, hypertension, and diaphoresis. Vasovagal syncope and peripheral paresthesias may also occur. Systemic toxicity occurs when excessive dosage is administered and manifest as light-headedness, tremors, restlessness, seizures, and depressed myocardial contractility. Methemoglobulinemia is an idiosyncratic reaction reported with local injectable anesthetics [21].

Topical corticosteroids Non-halogenated topical steroids (hydrocortisone, budesonide) are the most common corticosteroids correlated with allergic reactions. Patients at risk are those with stasis dermatitis and chronic leg ulcers, followed by those with hand eczema, atopic dermatitis, anogenital, foot, and facial dermatitis. Patch testing with tixocortol pivalate and budesonide is useful to identify allergy to hydrocortisone and other steroids molecules that may cross-react [22].



Skin Physiology


Occupational hand eczema

Botulinum toxin is a highly potent neurotoxin that inhibits acetylcholine release at the neuromuscular junction, blocking neuromuscular transmission and reversibly paralyzing striated muscle. Allergic reactions are rare and include generalized pruritus, psoriasiform eruption, urticaria, and erythema multiforme-type reactions [2,23]. Fillers can be classified as hom*ogenous (polymer gels) and combination gels, which differ not only in composition, but also in duration of effect, tissue interaction properties, and type of adverse reactions evoked. hom*ogenous gels are the most commonly used and are subdivided into degradable (hyaluronic acid and collagen) and non-degradable gels (polyacrylamide and silicone). Degradable polymer gels resemble the elements commonly found in the tissues, therefore are degraded by naturally occurring enzymes, located in the extracellular matrix and/or within macrophages [8]. Hence, fibrous response generated by these hydrophilic gels is minimal. Although generally considered safe, affordable, and ease to use, degradable gels are not permanent, and rare complications include allergic reactions, transient swelling, and cystic swelling [2,7]. Collagen fillers are substances derived from bovine collagen, which become non-allergenic after enzymatic digestion with pepsin. Formulations available on the market are collagen I (Zyderm I and II, INAMED Corporation, Santa Barbara, CA, USA) or cross-linked collagen (Zyplast, INAMED Corporation, Santa Barbara, CA, USA). Transient swelling and erythema are the most common reactions and tend to resolve a few days after the procedure. Hypersensitivity allergic reactions involve localized humoral and cellular inflammatory processes. Such reactions can persist up to 1 year after the procedure and are strongly correlated with the presence of antibovine collagen antibodies, hence prophylactic testing of individuals is recommended. Silicone is the term applied to describe the medical group of compounds derived from silicone-containing synthetics. Polydimethylsiloxanes are the most commonly substances used and contain silicon, oxygen, and methane [9]. The silicon gel is hydrophobic and once introduced in the tissues it is dispersed in vacuoles or droplets, which may be absorbed by macrophages and foreign body giant cells. The cells may then migrate to the reticuloendothelial system and/or evoke a local foreign body reaction in the surrounding tissue. Phagocytes enter and transverse the gel, followed by gradual replacement with connective tissue [8]. Adverse reactions to soft tissue augmentation include bacterial infections, abscesses, local inflammation, discoloration, ulceration, migration, and formation of silicon-type granulomas [2,8]. Deep-seated panniculitis can present early as a tingling sensation followed by local edema [8]. Late signs include the presence of a solid, painless tumefaction, with or without facial disfigurement and facial nerve paralysis [10].

Occupational hand eczema among hairdressers is a significant health problem and common sensitizers include hair dyes, ammonium persulfate, preservatives, amphoteric surfactants, fragrances, and glycerol thioglycolate. The use of gloves, mild soaps, and moisturizing creams alleviate the condition but severe refractory cases may require definitive interruption of the occupational activity. Gloves worn as protection may also constitute a source of allergens for hand dermatitis in hairdressers and healthcare professionals.


Diagnosis Diagnostic evaluation of patients with hypersensitivity reactions should be directed towards identifying the causative agent. Prick tests and radio allergo-sorbent tests (RASTs) are available for detection of IgE antibodies against specific allergens, therefore indicated for patients with some type I hypersensitivity reactions. Allergy to bovine collagen can be detected by intradermal challenge. The screening test is recommended for all cases prior to the procedure and consists of an intradermal injection of 0.1 mL of the filler substance in the volar forearm, with evaluation of the reaction within 48–72 hours. A positive test is defined as induration, erythema, tenderness, or swelling that persists or occurs longer than 6 hours after the injection. Positive subjects must be excluded from the procedure. A second test is recommended for non-reactive subjects to lower the chances of treatment-associated adverse reactions. The test should be performed within 2 weeks after the initial exam, in the contralateral forearm or periphery of the face [2]. Patch-testing is required to diagnose delayed type IV allergic reactions. Epicutaneous application of standardized concentrations of allergen chemicals on flat metal chambers are followed by occlusion and removal in 48 hours. The skin reaction is then graded and a second reading is performed in 1–5 days. The presence of induration, erythema, and/or vesicles denotes a positive reaction.

Treatment Treatment is based on identifying the offending agent and lifetime avoidance. Type I reactions required blockage of histamine receptors. Severe anaphylactic reactions require immediate hospitalization for assessment of cardiorespiratory status and intravenous fluids, subcutaneous epinephrine, systemic steroids, and antihistaminic medication. Mild forms of contact allergic dermatitis are readily treatable with avoidance of the offending agent. Topical steroids can be prescribed for a short period of time to hasten the process, whereas serious reactions may require addition of systemic immunosuppressant medication.

7. Contact dermatitis and topical agents

Conclusions Cosmetic products are widely used and reactions to those products are commonly seen in daily dermatologic practice. Prompt recognition with identification and withdraw of the offending agent are key elements for successful management of such reactions.

References 1 Berne B, Tammela M, Färm G, Inerot A, Lindberg M. (2008) Can the reporting of adverse skin reactions to cosmetics be improved? A prospective clinical study using a structured protocol. Contact Dermatitis 58, 223–7. 2 Cohen DE, Kaufmann JM. (2003) Hypersensitivity reactions to products and devices in plastic surgery. Facial Plast Surg Clin North Am 11, 253–65. 3 US Food and Drug Administration. (2005) FDA authority over cosmetics. CFSAN/Office of Cosmetics and Colors; 2005 [updated March 3, 2005; cited September 6, 2008]. Available from: http://∼dms/cos-206.html 4 Engasser PG, Maibach HI. (2003) Cosmetics and skin care in dermatologic practice. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI. Fitzpatrick’s Dermatology in General Medicine, 6th edn. New York: McGraw-Hill, pp. 2369–79. 5 Cosmetic, Toiletry and Fragrance Association (CTFA). (2008) International Cosmetic Ingredient Dictionary and Handbook, 12th edn. Washington, DC: CTFA. 6 Anderson JM, Rodriguez A, Chang DT. (2008) Foreign body reaction to biomaterials. Semin Immunol 20, 86–100. 7 Cohen JL. (2008) Understanding, avoiding, and managing dermal filler complications. Dermatol Surg 34, S92–9. 8 Christensen L. (2007) Normal and pathologic tissue reactions to soft tissue gel fillers. Dermatol Surg 33, S168–75. 9 Chasan PE. (2007) The history of injectable silicon fluids for soft-tissue augmentation. Plast Reconstr Surg 120, 2034–40. 10 Poveda R, Bagán JV, Murillo J, Jiménez Y. (2006) Granulomatous facial reaction to injected cosmetic fillers: a presentation of five cases. Med Oral Patol Oral Cir Bucal 11, E1–5.

11 Jungbauer FH, Lensen GJ, Groothoff JW, Coenraads PJ. (2004). Exposure of the hands to wet work in nurses. Contact Dermatitis 50, 225–9. 12 Lammintausta K, Maibach HI, Wilson D. (1988) Mechanisms of subjective (sensory) irritation: propensity to non-immunologic contact urticaria and objective irritation in stingers. Derm Beruf Umwelt 36, 45–9. 13 Primavera G, Berardesca E. (2005) Sensitive skin: mechanisms and diagnosis. Int J Cosmet Sci 27, 1–10. 14 Schnuch A, Uter W, Geier J, Lessmann H, Frosch PJ. (2007) Sensitization to 26 fragrances to be labelled according to current European regulation: results of the IVDK and review of the literature. Contact Dermatitis 57, 1–10. 15 Zug KA, Rietschel RL, Warshaw EM, Belsito DV, Taylor JS, Maibach HI, et al. (2008) The value of patch testing patients with a scattered generalized distribution of dermatitis: retrospective cross-sectional analyses of North American Contact Dermatitis Group data, 2001 to 2004. J Am Acad Dermatol 59, 426–31. 16 Aalto-Korte K, Kuuliala O, Suuronen K, Alanko K. (2008) Occupational contact allergy to formaldehyde and formaldehyde releasers. Contact Dermatitis 59, 280–9. 17 Draelos ZD. (2007) Skin lightening preparations and the hydroquinone controversy. Dermatol Ther 20, 308–13. 18 Veysey EC, Burge S, Cooper S. (2007) Consort contact dermatitis to paraphenylenediamine, with an unusual clinical presentation of tumid plaques. Contact Dermatitis 56, 366–7. 19 Evans CC, Fleming JD. (2008) Images in clinical medicine: allergic contact dermatitis from a henna tattoo. N Engl J Med 7, 627. 20 Storrs FJ. (1984) Permanent wave contact dermatitis: contact allergy to glyceryl monothioglycolate. J Am Acad Dermatol 11, 74–85. 21 Phillips JF, Yates AB, Deshazo RD. (2007) Approach to patients with suspected hypersensitivity to local anesthetics. Am J Med Sci 334, 190–6. 22 English JS. (2000) Corticosteroid-induced contact dermatitis: a pragmatic approach. Clin Exp Dermatol 25, 261–4. 23 Brueggemann N, Doegnitz L, Harms L, Moser A, Hagenah JM. (1008) Skin reactions after intramuscular injection of Botulinum toxin A: a rare side effect. J Neurol Neurosurg Psychiatry 79, 231–2.


Part 2: Delivery of Cosmetic Skin Actives Chapter 8: Percutaneous delivery of cosmetic actives to the skin Marc Cornell, Sreekumar Pillai, and Christian Oresajo L’Oréal Research, Clark, NJ, USA

BAS I C CONCE P T S • Percutaneous delivery is the penetration of substances into the skin. • The goal of effective percutaneous delivery is to provide an effective amount of an active to the skin target site and thereby optimize efficacy while minimizing side effects. • The main barrier of the active permeation through the skin is the stratum corneum. The active must cross this skin barrier and permeate transepidermally to be delivered to the target site. • Molecules with a molecular weight of less than 500 Daltons penetrate the skin better than molecules with a larger molecular weight. The net charge of a molecule is important in enhancing penetration.

Introduction Recent developments in new technologies combined with new knowledge in skin biology have advanced innovations in skin availability of actives and novel methods of substance delivery. The goal of this chapter is to review new advances in delivery of actives to the skin and the effects of penetration enhancers. An understanding of the structure of the skin is very important in managing active delivery.

The basics The goal of percutaneous delivery is to provide an effective amount of an active to the skin target site and thereby optimize efficacy while minimizing side effects. This can be achieved by an understanding of the skin’s complex structure and by relying on physical and chemical parameters of vehicles applied to the skin.

Skin physiology There are defined compartments and biologic structures within the skin that provide opportunities to deliver actives (Figure 8.1). Within these compartments there are many

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


chemical and biologic processes at work that may alter a given active or the physiology of skin target. The main barrier of active permeation through the skin is the stratum corneum. The active must cross this skin barrier and permeate transepidermally to be delivered to the target site, and the penetration can be moderated by the secretion activity of the appendages. This structure is located at the outermost layer of the epidermis [1]. This transepidermal route can be further subdivided into transcellular and intercellular routes [2]. Delivery of hydrophilic substances can be achieved through sweat gland route; however, this is also minimal in total volume. Therefore, the principal pathway for skin penetration of actives is the transepidermal route (route 1 in Figure 8.1).

Active composition One of the first steps in understanding the phenomenon of active delivery is to completely characterize the active that is intended for delivery to the skin. There are well-known physical and chemical parameters that are specific to all chemical compounds. The essentials for characterization of actives are typically described in the literature or can be measured in the laboratory. This includes the active’s molecular weight, dissociation constant (pK), solubility, and octanol/water [O/W] partition coefficient (log P). These parameters, along with a thorough understanding of the net ionic charge (cationic, anionic, and amphoteric) of the active will help in understanding its penetration profile. As general rule, molecules with a molecular weight of less than 500 Da penetrate the skin better than molecules with

8. Percutaneous delivery



1 Increasing drug diffusion in the skin; 2 Increasing drug solubility in the skin; and/or 3 Increasing the degree of saturation of the drug in the formulation [4]. Equation (1) aids in identifying the ideal parameters for the diffusion of the active across the skin. The influence of solubility and partition coefficient on diffusion across the stratum corneum has been extensively studied in the literature [5].


Vehicle effect Delivery of actives from emulsions Figure 8.1 Possible pathways for a penetrant to cross the skin barrier. (1) across the intact horny layer; (2) through the hair follicles with the associated sebaceous glands; or (3) via the sweat glands. (This figure was published in: Daniels R. Strategies for skin penetration enhancement. Skin Care Forum 37,

a larger molecular weight. It is also known that the net charge of a molecule is important in enhancing penetration. An un-ionized molecule penetrates the skin better than an ionized molecule. A thorough understanding of the relationship between the dissociation constant and formulation pH is critical. In many cases it is advantageous to keep the pH of a formulation near the pK of the active molecule in an attempt to enhance penetration. When looking at the partition coefficient, molecules showing intermediate partition coefficients (log P O/W of 1–3) have adequate solubility within the lipid domains of the stratum corneum to permit diffusion through this domain while still having sufficient hydrophilic nature to allow partitioning into the viable tissues of the epidermis [3].

Fick’s law The permeation of active across the stratum corneum is a passive process, which can be approximated by Fick’s first law: J=

DK (C) L

(equation 8.1)

This defines steady-state flux (J) is related to the diffusion coefficient (D) of the active in the stratum corneum over a diffusional path length or membrane thickness (L), the partition coefficient (K) between the stratum corneum and the vehicle, and the applied drug concentration (C) which is assumed to be constant. Novel formulation strategies allow for manipulation of the partition coefficient (K) and concentration (C). Skin penetration can be enhanced by the following strategies:

The key for evaluation of the vehicle effect is to understand the dynamics between the vehicle and the active. Based on the physical and chemical nature of the active there are specific formulation strategies that can be designed to enhance delivery of actives. The primary vector for topical delivery of actives is a semisolid ointment or emulsion base. The main reason for selection of this dosage form is convenience and cosmetic elegance. Emulsions are convenient because they typically have two phases (hydrophilic and hydrophobic). The biphasic nature allows for placement of actives based on solubility and stability. This allows the formulator to bring lipophilic and hydrophilic actives into the dosage form while maintaining the optimized stability profile. The effect of the type of vehicle has been well described in the literature [6]. Numerous references are available for altering the delivery of actives from various emulsion forms (O/W, W/O, multiple emulsions, and nano-emulsions).

Formulation strategies A basic formulation has many components. Table 8.1 provides an overview of these formula components and also provides a brief summary of the anticipated effect on active delivery. Some of these chemical functions are more clearly defined below in discussion on chemical penetration enhancers. The ability of vehicles to deliver actives is tied to an understanding of diffusion of actives through various skin compartments (epidermal and dermal). Diffusion of actives across the skin is a passive process. Compounds with low solubility and affinity for the hydrophilic and lipophilic components of the stratum corneum would theoretically partition at a slow rate. These difficulties may be overcome by adding a chemical adjunct to the delivery system that would promote partitioning into the stratum corneum. Partitioning of actives from the dosage form is highly dependent on the relative solubility of the active in the components of the delivery system and in the stratum corneum. Thus, the formulation of the vehicle may markedly influence the degree



Delivery of Cosmetic Skin Actives

Table 8.1 Formulation components. Ingredient

Chemical function

Effect on delivery






Fluidizes stratum corneum, alters permeability of stratum cornuem

Propylene glycol


Alter permeability of stratum corneum Alter vehicle stratum corneum partition coefficient



Emulsion particle size reduction, active solubilizer


Skin conditioner, active carrier

Alter stratum corneum permeability Alter vehicle stratum corneum partition coefficient

Delivery system

Protect/target actives

Targeted/enhanced active penetration

of penetration of the active. Percutaneous absorption involves the following sequences: • Partitioning of the molecule into the stratum corneum from the applied vehicle phase; • Molecular diffusion through the stratum corneum; • Partitioning from the stratum corneum into the viable epidermis; and • Diffusion through the epidermis and upper dermis and capillary uptake [7]. One of the most effective formulation techniques to boost active penetration is supersaturation. This chemical process happens when an active’s maximum concentration in solution is exceeded by the use of solvents or co-solvents. This type of solution state can happen during the evaporation of an emulsion on the skin. As water evaporates from a cream rubbed on the skin a superconcentrate depot of active forms on the skin. This creates a diffusional concentration gradient across the stratum corneum. One can attempt to boost this effect even further in the formulation by slightly exceeding the maximum solubility of the active in the formula using co-solvents. Supersaturation is an effective technique but the disadvantage is that active recrystallization can take place in this highly concentrated solution state. There are crystallization inhibitors that can be added to supersaturated solution but many experimental data need to be collected on this type of formulation strategy. Eutectic blends are formulation techniques that can enhance penetration of actives. The melting point of an active influences solubility and hence skin penetration. According to solution theory, the lower the melting point, the greater the solubility of a material in a given solvent, including skin lipids. The melting point can be lowered by


formation of a eutectic mixture. This mixture of two components which, at a certain ratio, inhibits the crystalline process of each other such that the melting point of the two components in the mixture is less than that of each component alone. In all cases, the melting point of the active is depressed to around or below skin temperature thereby enhancing solubility. This technique has been used to enhance the penetration of ibuprofen through the skin [8]. Manipulation of the vehicle skin partition coefficient of a formulation can be used as an overall formulation strategy to boost penetration of actives. This can be done by altering the solubility of the active in the vehicle via selection of different excipients. This change in the solubility parameter (δ) of the excipients can be tuned so that the active is more soluble in the stratum corneum than in the vehicle. Hence the diffusional gradient is altered towards the skin and thereby enhancing penetration. It has been shown that a solvent capable of shifting the solubility parameter (δ) of the skin closer to that of the activate will active flux rate [9]. Another strategy is to add a penetration enhancer that alters the membrane permeability of the skin. This strategy is discussed in more detail below. Skin occlusion can increase stratum corneum hydration, and hence influence percutaneous absorption by altering partitioning between the surface chemical and the skin because of the increasing presence of water, swelling corneocytes, and possibly altering the intercellular lipid phase organization, also by increasing the skin surface temperature, and increasing blood flow [10]. The ultimate goal of penetration enhancement is to target the active in the stratum corneum and/or epidermis without allowing for systemic absorption. This remains the biggest

8. Percutaneous delivery challenge for active penetration enhancement and it is one of the keys for targeted active delivery.

available that propel an abrasive against the skin thereby stripping away the stratum corneum.

Penetration enhancers

Penetration enhancement vectors

In this section, the influence of penetration enhancers on the diffusion coefficient and solubility of the active in the stratum corneum is evaluated. The use of topically applied chemical agents (surfactants, solvents, emollients) is a wellknown technique to modify the stratum corneum and also modify the chemical potential of selected actives. Collectively, these materials can be referred to as penetration enhancers (PEs). Based on the chemical structure, PEs can be categorized into several groups such as fatty acids, fatty alcohols, terpene fatty acid esters, and pyrrolidone derivatives [11]. PEs commonly used in skin care products have well-known safety profiles but their ability to enhance penetration of an active is challenging because of the manifold ingredients used in many formulations.

There are customized carriers (vectors) for delivery of actives to the skin. These vectors are a type of vehicle that allow for enhanced penetration via their small size and unique physical chemical composition. These vectors are known as submicron delivery systems (SDS). Discussion focuses on liposomes, niosomes, lipid particles, and nanocapsules.

Solvents A number of solvents (e.g. ethanol, propylene glycol, Transcutol® [Gattefossé, Saint-Priest, France] and N-methyl pyrrolidone) increase permeant partitioning into and solubility within the stratum corneum, hence increasing KP in Fick’s equation (equation 1). Ethanol was the first penetration enhancer co-solvent incorporated into transdermal systems [12]. Synergistic effects between enhancers (e.g. Azone® [PI Chemicals, Shanghai, China], fatty acids) and more polar co-solvents (e.g. ethanol, propylene glycol) have also been reported suggesting that the latter facilitates the solubilization of the former within the stratum corneum, thus amplifying the lipid-modulating effect. Similarly, solvents such as Transcutol are proposed to act by improving solubility within the membrane rather than by increasing diffusion. Another solvent, dimethylsulfoxide (DMSO), by contrast, is relatively aggressive and induces significant structural perturbations such as keratin denaturation and the solubilization of membrane components [13].

Physical enhancers In addition to the chemical penetration enhancers discussed above, there is another class of penetration enhancers known as physical penetration enhancers. These materials stand between chemical enhancers and penetration enhancer devices. This unique classification is because in most cases the materials are particles of chemical origin (polyethylene, salt, sugar, aluminum oxide) but require physical energy to exert an action on the skin. These materials are used to physically débride or excoriate the stratum corneum by abrasive action. This is typically done by rubbing the particles by hand on the skin. New high-tech devices are now

Liposomes Liposomes are colloidal particles formed as concentric biomolecular layers that are capable of encapsulating actives. The lipid bilayer structure of liposomes mimics the barrier properties of biomembranes, and therefore they offer the potential of examining the behavior of membranes of a known composition. Thus, by altering the lipid composition of the bilayer or the material incorporated, it is possible to establish differences in membrane properties. Liposomes store water-soluble substances inside like biologic cells. The phospholipids forming these liposomes enhance the penetration of the encapsulated active agents into the stratum corneum [14]. There is debate on liposome formulations and their mode of action regarding penetration enhancement. Variation in performance may be caused by the variation in formulation and method of manufacture used to prepare this delivery form. Several factors such as size, lamellarity (unilamellar vs. multilamellar), lipid composition, charge on the liposomal surface, mode of application, and total lipid concentration have been proven to influence deposition into the deeper skin layers. It is reported by several authors that the high elasticity of liposome vesicles could result in enhanced transport across the skin as compared to vesicles with rigid membranes. Liposomes have a heterogeneous lipid composition with several coexisting domains exhibiting different fluidity characteristics in the bi-layers. This property can be used to enhance the penetration of entrapped actives into the skin. It is supposed that once in contact with skin, some budding of liposomal membrane might occur. This could cause a mixing of the liposome bi-layer with intracellular lipids in the stratum corneum which may change the hydration conditions and thereby the structure of lipid lamellae. This may enhance the permeation of the lipophilic active into the stratum corneum and ease the diffusion of hydrophilic actives into the interlamellar spaces [15].

Niosomes Niosomes are formed by blending non-ionic surfactants of the alkyl or dialkyl polyglycerol ether class and cholesterol



Delivery of Cosmetic Skin Actives

with subsequent hydration in aqueous media. These vesicles can be prepared using a number of manufacturing processes: ether injection, membrane extrusion, microfluidization, and sonication. Niosomes have an infrastructure consisting of hydrophilic, amphiphilic, and lipophilic moieties together and as a result can accommodate active molecules with a wide range of solubilities. They can be expected to target the active to its desired site of action and/or to control its release [16]. Niosomes are similar to liposomes in that they both have a bi-layer structure and their final form depends on the method of manufacture. There are structural similarities between niosomes and liposomes but niosomes do not contain phospholipids. This provides niosomes with a better stability profile because of improved oxidative stability.

Nanocapsules can be formed by preparing a lipophilic core surrounded by a thin wall of a polymeric material prepared by anionic polymerization of an alkylcyanoacrylate monomer. These very safe types of system have been proposed as vesicular colloidal polymeric drug carriers. Nanocapsules have the ability to enhance penetration but they can also control delivery of actives to the skin. In a recent study, indomethacin was nano-encapsulated for topical use. This study compared cumulative release of indomethacin dispersed in gel base with indomethacin nano-encapsulated and indomethacin nano-encapsulated in a gel. The highest delivery was achieved with the nanoencapsulated indomethacin (Figure 8.2).

Solid lipid nanoparticles

Devices for penetration enhancement

Solid lipid nanoparticles (SLNP) were developed at the beginning of the 1990s as an alternative carrier system to emulsions, liposomes, and polymeric nanoparticles. SLNP have the advantage of requiring no solvents for production processing and of relatively low cost for the excipients. SLNP represents a particle system that can be produced with an established technique of high-pressure hom*ogenization allowing production on an industrial scale. This method also protects the incorporated drug against chemical degradation as there is little or no access for water to enter the inner area core of the lipid particle [17]. Lipid particles can be used as penetration enhancers of encapsulated actives through the skin because of their excellent occlusive and hydrating properties. SLNP have recently been investigated as carriers for enhanced skin delivery of sunscreens, vitamins A and E, triptolide, and glucocorticoids [18].


Cumulative amount of indomethacin permeated (μg/cm2)

Nanocapsules are a type of submicron delivery system (SDS). This technology can segregate and protect sensitive materials and also control the release of actives. The more obvious opportunity for penetration enhancement of actives is because of their small size (20–1000 nm in diameter).

Ultrasound waves Ultrasound waves are sound waves that are above the audible limit (>20 kH). During ultrasound treatment the skin is exposed to mechanical and thermal energy which can alter the skin barrier property. Thermal and non-thermal characteristics of high-frequency sound waves can enhance the diffusion of topically applied actives. Heating from ultrasound increases the kinetic energy of the molecules in the



PNBCA nanocapsules in pH 7.4 phosphate buffer (I)


PNBCA nanocapsules in PLF-127 gel (II)


25% w/w PLF-127 gel (III)

0 0


Devices for enhancing skin penetration of actives are at the leading edge of skincare technology. When utilizing devices for enhanced penetration of actives it is imperative to look into the regulatory classification of these instruments. The FDA has several guidelines and requirements for medical devices (510K). The 510K regulatory classification is important for safety and efficacy of any consumer device product and an understanding of the regulatory landscape in this area is essential. Four device technologies are reviewed. They range from moderately invasive to mildly invasive in terms of effect on the skin. In all cases, the goal is to reversibly alter the skin barrier function by physical or electroenergetic means.


4 Time (hours)



Figure 8.2 Cumulative amount of indomethicin (initial loading 0.5% w/v) per unit area, permeating through excised rat skin when released from PNBCA nanocapsule dispersion in pH 7.4 phosphate buffer, PNBCA nanocapsule dispersion in Pluronic F-127 gel and 25% w/w Pluronic F-127 gel. Each value is the mean ± SE of four determinations. (This figure was published in: Miyazaki S, Takahashi A, Kubo W, Bachynsky J, Löbenberg R. (2003) Poly n-butylcyanoacrylate (PNBCA) nanocapsules as a carrier for NSAIDs: in vitro release and in vivo skin penetration. J Pharm Pharmaceut Sci 6, 238–45.)

8. Percutaneous delivery active and in the cell membrane. These physiologic changes enhance the opportunity for active molecules to diffuse through the stratum corneum to the capillary network in the papillary dermis. The mechanical characteristics of the sound wave also enhance active diffusion by oscillating the cells at high speed, changing the resting potential of the cell membrane and potentially disrupting the cell membrane of some of the cells in the area [19]. A recent study on the use of ultrasound and topical skin lightening agents showed the effect of high-frequency ultrasound together with a gel containing skin-lightening agents (ascorbyl glucoside and niacinamide) on facial hyperpigmentation in vivo in Japanese women [20].

Patches Delivery patches have been available for some time. One of the first applications of patch technology was in a transdermal motion sickness (scopolamine) patch. There are commercial products that provide actives in a patch formula. They utilize adhesive technology or a rate-limiting porous

Figure 8.3 Solid microneedles fabricated out of silicon, polymer, and metal, imaged by scanning electron microscopy. (a) Silicon microneedle (150 μm tall) from a 400-needle array etched out of a silicon substrate. (b) Section of an array containing 160 000 silicon microneedles (25 μm tall). (c) Metal microneedle (120 μm tall) from a 400-needle array made by electrodepositing onto a polymeric mold. (d–f) Biodegradable polymer microneedles with beveled tips from 100-needle arrays made by filling polymeric molds. (d) Flat-bevel tip made of polylactic acid (400 μm tall). (e) Curved-bevel tip made of polyglycolic acid (600 μm tall). (f) Curved-bevel tip with a groove etched along the full length of the needle made of polyglycolic acid (400 μm tall). (This figure was published in: McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, et al. (2003) Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci U S A 100, 13755–13760.)

membrane to target and localize the actives. Some common patch applications are directed towards reduction of age spots or dark circles under the eye. The key delivery enhancement for patches is a combination of localized delivery and occlusion.

Microneedles Another type of delivery device is the microneedle. Microneedles are similar to traditional needles, but are fabricated at the micro size. They are generally 1 μm in diameter and range 1–100 μm in length (Figure 8.3). The very first microneedle systems consisted of a reservoir and a range of projections (microneedles 50–100 mm long) extending from the reservoir, which penetrated the stratum corneum and epidermis to deliver the active. The microneedle delivery system is not based on diffusion as in other transdermal drug delivery products but based on the temporary mechanical disruption of the skin and the placement of the active within the epidermis, where it can more readily reach its site of action. Microneedles have been fabricated









Delivery of Cosmetic Skin Actives

with various materials such as metals, silicon, silicon dioxide, polymers, glass, and other materials. There are already patents granted for these types of moderately invasive delivery system [21].

Iontophoresis Iontophoresis is a technology that has been brought to the cosmetic industry via the pharmaceutical development field. Iontophoresis passes a small direct current through an active-containing electrode placed in contact with the skin, with a grounding electrode to complete the circuit. Three important mechanisms enhance transport: 1 The driving electrode repels oppositely charged species; 2 The electric current increases skin permeability; and 3 Electro-osmosis moves uncharged molecules and large polar peptides [22]. There are limitations related to this technique. The active ingredient must be water-soluble, ionic, and with a molecular weight below 5000 Da. Even with all of these limitations, reported data show that the drug delivery effectiveness can be increased by one-third through iontophoresis [23].

In vitro and in vivo delivery assessment A key in any evaluation assessment of skin bioavailability of actives is a quantitative measurement of activity by in vitro and in vivo methods. In early development phases in vitro methods provide a quick, reproducible way to identify promising formulations for next phase development studies. There are different techniques for evaluating percutaneous absorption of actives.

Franz cell A well-known technique for measuring in vitro skin permeation is the Franz cell apparatus (Figure 8.4). The test apparatus and technique have been well documented for use within the pharmaceutical and cosmetic industries [24]. The technique utilizes a sampling cell which contains a

Cell cap

solution reservoir and a sampling port, the top portion of the Franz cell is covered with a biologic membrane or skin substitute. The formulation is added to the top of the cell and periodic samples are taken from the cell reservoir and assays are plotted versus time to develop a time–penetration profile.

Tape stripping Tape stripping is a technique used for in vivo active penetration evaluation. In this procedure, penetration of the active is estimated from the amount recovered in the stratum corneum by adhesive tape stripping at a fixed time point following application [25]. This technique is also recognized by FDA as a viable screening option for dermatologic evaluation [26].

Microdialysis During the last decade, microdialysis has been shown to be a promising technique for the assessment of in vivo and ex vivo cutaneous delivery of actives. The technique is based on the passive diffusion of compounds down a concentration gradient across a semi-permeable membrane forming a thin hollow “tube” (typically, a few tenths of a millimeters in diameter), which – at least, in theory – functionally represents a permeable blood vessel (Figure 8.5.). Two kinds of probe are in common use: linear and concentric.

Confocal Raman microspectroscopy Confocal Raman microspectroscopy (CRS) is a new, noninvasive technique which can be used for in vivo skin penetration evaluation. This technique combines Raman spectroscopy with confocal microscopy. CRS is a nondestructive and rapid technique that allows information to be obtained from deep layers under the skin surface, giving the possibility of a real-time tracking of the drug in the skin layers. The specific Raman signature of the active agent enables its identification within the skin [27]. There is a range of techniques of in vitro and in vivo evaluation for following penetration of actives through the skin.

Sampling port

Cell clamp

Water jacket Cell body

Figure 8.4 The Franz diffusion chamber.


8. Percutaneous delivery Microdialysis pump Perfusate


Application site Figure 8.5 The microdialysis apparatus for the evaluation of penetration through the human skin barrier. (This figure was published in: Schnetz E, Fartasch M. (2001) Microdialysis for the evaluation of penetration through the human skin barrier: a promising tool for future research? Eur J Pharm Sci 12, 165–74.)

Stratum corneum Viable epidermis Dermis



Diffuson of solutes into the perfusate

Table 8.2 Methods to assess drug penetration into and/or across the skin. (From Herkenne C, et al. (2008) In vivo methods for the assessment of topical drug bioavailability. Pharm Res 25, 87–103.) Method


Measurement site

Temporal resolution

Technical simplicity

In vitro

Diffusion cell


Transport into and across skin



In vivo: non- or minimally invasive

Tape stripping


Stratum corneum




Stratum corneum





Upper skin




Q (free)

Dermis (or subdermis)









Extracellular fluid








Skin (depth)


In vivo: invasive

Q, quantity of drug; A, pharmacological activity of drug; L, drug localization.

Some are more invasive than others and some are more predictive across various dosage forms utilized on the skin. In Table 8.2 a summary chart shows a good comparison of the techniques based on strengths and weaknesses.

Conclusions and future trends There are many formulation options available for delivering actives to targets within the skin. Understanding the skin and its interaction with various actives allows the chemist to select delivery options that provide safe and effective properties. A good understanding of the physicochemical parameters of the active and the desired skin target are needed before deciding on a particular delivery option. Human studies are the “gold standard” against which all methods for measuring percutaneous absorption should be judged. The conduct of human volunteer experiments is well regulated. Study protocols and accompanying toxicologic data must be submitted to an ethics committee for approval [28].

Next generation delivery technologies are being developed and in some cases are already on the way to the market. Researchers from device and skincare companies are already in collaboration to bring combinations of devices and actives to the field of cosmetic dermatology. The approach can vary from non-invasive LEDs all the way to more invasive, laser-based enhanced penetration of actives. There are many home-use devices coming to the market today. These advances in delivery technology will likely culminate in a commercially available topical product that has its efficacy boosted by some type of chemical or physical delivery device as demonstrated in the delivery of estradiol using either a delivery vesicle (ultra-deformable liposomes) or a device (iontophoresis) [29].

References 1 Chien YW. (1992) Novel Drug Delivery Systems, 2nd edn. New York: Marcel Dekker Inc., p. 303. 2 Barry BW. (1987) Penetration enhancers in pharmacology and the skin. In: Shroot B, Schaefer H, eds. Skin Pharmaco*kinetics. Basel: Karger; Vol. 1, pp. 121–37.



Delivery of Cosmetic Skin Actives

3 Heather A, Benson E. (2005) Current drug delivery, penetration enhancement techniques. Curr Drug Deliv 2, 23–33. 4 Moser K, Kriwet K, Naik A, Kalia YN, Guy RH. (2001) Passive skin penetration enhancement and its quantification in vitro. Eur J Pharm Biopharm 52, 103–12. 5 Katz M, Poulsen BJ. (1971) Absorption of drugs through the skin. In: Brodie BB, Gilette J, eds. Handbook of Experimental Pharmacology. Berlin: Springer Verlag, pp. 103–74. 6 Forster T, Jackwerth B, Pittermann W, Rybinski WM, Schmitt M. (1997) Properties of emulsions: structure and skin penetration. Cosmet Toiletries 112, 73–82. 7 Albery WJ, Hadgraft J. (1979) Percutaneous absorption: theoretical description. Pharm Pharmacol 31, 129–39. 8 Stott PW, Williams AC, Barry BW. (1998) Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen. J Control Release 50, 297–308. 9 Sloan KB, ed. (1992) Prodrugs, Topical and Ocular Drug Delivery Sloan. New York: Marcel Dekker, pp. 179–220. 10 Bucks D, Guy R, Maibach HI. (1991) Effects of occlusion. In: Bronaugh RL, Maibach HI, eds. In Vitro Percutaneous Absorption: Principles, Fundamentals, and Applications. Boca Raton: CRC Press, pp. 85–114. 11 Osborne DW, Henke JJ. (1997) Skin penetration enhancers. Pharm Technol November, 58–66. 12 Walters KA. (1988) Penetration enhancer techniques. In: Hadgraft J, Guy RH, eds. Transdermal Drug Delivery. New York: Marcel Dekker, pp. 197–246. 13 Harrison E, Watkinson AC, Green DM, Hadgraft J, Brain K. (1996) The relative effect of Azone and Transcutol on permeant diffusivity and solubility in human stratum corneum. Pharm Res 13, 542–6. 14 Abeer A, Elzainy W, Gu X, Estelle F, Simons R, Simons KJ. (2003) Hydroxyzine from topical phospholipid liposomal formulations: evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model. AAPS PharmSci 5, 1–8. 15 Cevc G, Blume G. (1992) Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta 1104, 226–32. 16 Baillie AJ, Florence AT, Hume LR, Rogerson A, Muirhead GT. (1985) The preparation and properties of niosomes-non-ionic surfactant vesicles. J Pharm Pharmacol 37, 863–8.


17 Kreuter J. (1994) Nanoparticles. In: Kreuter J, ed. Colloidal Drug Delivery Systems. New York: Marcel Dekker, pp. 219–342. 18 Müller RH, Mäder K, Gohla S. (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery: a review of the state of the art. Eur J Pharm Biopharm 50, 161–77. 19 Dinno MA, Crum LA, Wu J. (1989) The effect of therapeutic ultrasound on the electrophysiologic parameters of frog skin. Med Biol 25, 461–70. 20 Hakozaki T, Takiwaki H, Miyamot K, Sato Y, Arase S. (2006) Ultrasound enhanced skin-lightening effect of vitamin C and niacinamide. Skin Res Technol 12, 105–13. 21 Yuzhakov VV, Gartstein V, Owens GD. (2003) US Patent 6565532. Micro needle apparatus semi-permanent subcutaneous makeup. 22 Barry BW. (2001) Is transdermal drug delivery research still important today? Drug Discov Today 6, 967–71. 23 Yao N, Gnaegy M, Haas C. (2004) Iontophoresis transdermal drug delivery and its design. Pharmaceut Form Quality 6, 42–4. 24 COLIPA Guidelines for Percutaneous Absorption/Penetration. (1997) European Cosmetic, Toiletry and Perfumery Association. 25 Rougier A, Dupuis D, Lotte C. (1989) Stripping method for measuring percutaneous absorption in vivo. In: Bronaugh RL, Maibach HI, eds. Percutaneous Absorption: Mechanisms, Methodology, Drug Delivery, 2nd edn. New York: Marcel Dekker, pp. 415–34. 26 Shah VP, Flynn GL, Yacobi A, Maibach HI, Bon C, Fleischer NM, et al. (1998) Bioequivalence of topical dermatological dosage forms: methods of evaluation of bioequivalence. Pharm Res 15, 167–71. 27 Tfayli A, Piot O, Pitre F, Manfait M. (2007) Follow-up of drug permeation through excised human skin with confocal Raman microspectroscopy. Eur Biophys J 36, 1049–58. 28 World Health Organization (WHO). (1982) World Medical Association: Proposed International Guidelines for Research Involving Human Subjects. Geneva: WHO, p. 88. 29 Essa A, Bonner MC, Barry BW. (2002) Iontophoretic estradiol skin delivery and tritium exchange: ultradeformable liposomes. Int J Pharm 240, 55–66.

Chapter 9: Creams, lotions, and ointments Irwin Palefsky Cosmetech Laboratories Inc., Fairfield, NJ, USA

BAS I C CONCEPTS • Creams, lotions, and ointments are both vehicles and delivery systems for dermatologic products. • Creams and lotions are emulsions, which are colloidal dispersions comprising two immiscible liquids (e.g. oil and water), one of which is dispersed as droplets representing the internal or discontinuous phase within the other external phase. • Ointments are semi-solid preparations used topically for protective emollient effects or as vehicles for the local administration of medicaments. • Ointments are mixtures of fats, waxes, animal and plant oils, and solid and liquid hydrocarbons.

Introduction This chapter examines creams, lotions, and ointments as both vehicles and delivery systems for dermatologic products. Creams, lotions, and ointments have a unique composition that can alter the ability of ingredients to reach the skin surface while also influencing product esthetics. The construction of the cream or ointment is an important determining factor in patient compliance, because if patients do not like the feel, smell, or color of a dermatologic they will not properly follow directions for its use.

Definition of creams, lotions, and ointments Creams and lotions Creams and lotions are classified as emulsions. There are several different types of emulsions that function as a vehicle and delivery system for cosmetic and drug materials. The classic definition of an emulsion is a colloidal dispersion comprising two immiscible liquids (e.g. oil and water), one of which is dispersed as droplets representing the internal or discontinuous phase within the other external phase [1]. All emulsions require the inclusion of an emulsifier or dispersing agent responsible for keeping the two immiscible phases together for an extended period of time. All emulsions are unstable and will eventually separate into two or more phases.

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

Emulsions can be classified as a cream or lotion. There are no legal definition differences between a cream and a lotion. The determination of what constitutes a cream or lotion emulsion is determined by viscosity. If an emulsion can be poured from a bottle or pumped from a jar, it is labeled a lotion. If the emulsion requires a jar or a tube for dispensing and does not readily flow, it is labeled a cream. The term emulsion will be used for the remainder of this chapter to indicate a cream or lotion. The other important part of the definition of an emulsion is based on the materials that comprise the internal phase and the materials that comprise the external or continuous phase. The two categories of emulsions are oil-in-water (O/W) and water-in-oil (W/O). The names describe the composition of the emulsion (Figure 9.1). Emulsions can also be described by their emulsifier type as anionic, cationic, and non-ionic. This terminology refers to the ionic charge, or lack of charge, on the emulsifier system. Emulsions have also been developed that are based on polymeric emulsifiers and liquid crystal emulsifiers. These emulsions are different from traditional emulsions, because the two phases are held together by different mechanisms. Sophisticated emulsion technology is beyond the scope of this chapter; however, additional information can be found in Bloch [1].

Ointments Ointments can be defined as semi-solid preparations used topically for protective emollient effects or as vehicles for the local administration of medicaments. They are mixtures of fats, waxes, animal and plant oils, and solid and liquid hydrocarbons [2]. Ointments are traditionally anhydrous bases, meaning they do not contain water, and therefore pose fewer microbial contamination issues than emulsions, which is a distinct advantage. In addition, because ointments



Delivery of Cosmetic Skin Actives

Table 9.2 A typical “non-ionic” oil-in-water emulsion base. Ingredients


% weight/weight

Deionized water

External phase vehicle





Disodium EDTA

Chelating agent


Butylene glycol



Water phase

Water in oil

Oil in water

Figure 9.1 Different emulsion types. (This figure is from “Emulsions” presentation from Cognis Corp. August 2004.)

Table 9.1 Generic composition of a typical oil-in-water emulsion.

Oil phase Cetearyl alcohol (and) ceteaeth-20





Silicone emollient


% (weight/weight)

Water phase Deionized water



Silicone emollient




Caprylic/capric triglyceride

Organic emollient



0.05–0.5 1.25


Glyceryl stearate (and) PEG100 stearate


Water-soluble emulsifier†

Triethanolamine (99%)

Neutralizing agent and pH adjuster







Water-soluble emollient


Chelating agent

0.05–0.20 The pH of this cream would be 5.5–6.5. The viscosity would be approximately 15 000–25 000 centipoise.

Oil phase Emollient system – oils, esters, silicones, etc.


Oil-soluble emulsifiers


Composition of creams and ointment

“Active ingredients”

As required by regulations

Oil-in-water creams

Oil-soluble antioxidants


Fragrance/essential oil, etc.


The most popular type of emulsion used in skin care products and cosmeceuticals is oil-in-water (O/W). A generic composition for an O/W emulsion is presented in Table 9.1 [3]. Each of the ingredient classes are discussed in detail to aid in the understanding of O/W formulations. A typical “non-ionic” oil-in-water emulsion composition is shown in Table 9.2.


As required



pH adjustments

As required

* Preservatives are frequently added in two places in the formulation. † May also be added into the oil phase.

are anhydrous in nature, they tend to be more waterresistant than emulsions. However, ointments have less esthetic appeal for skin care and dermatology products as they are frequently described as oily, waxy, greasy, sticky, tacky, and heavy. Ointments are used more commonly for the delivery of medications than for skin care products because of their undesirable esthetics.


Emulsifiers Emulsifiers are important to keep the oil and water ingredients miscible. The choice of emulsifier will also determine the emulsion pH and effect the application and stability of the emulsion, as well as the delivery of materials into the skin. Emulsifiers can damage the skin barrier by emulsifying the sebum and intercellular lipids. This has led to the need to develop “skin friendly emulsifiers.” These emulsifiers do not adversely affect the barrier properties of the skin and in some cases even help maintain barrier properties. Because the route of delivery into the skin is primarily through the lipid layer, which constitutes the mortar in the “brick and

9. Creams, lotions, and ointments mortar” model of the skin, the selection of an emulsifier can determine whether the disruption of the lipid layer. Liquid crystal forming emulsifiers are being used more frequently because they maintain the skin barrier. These emulsifiers function like the phospholipids and ceramides found in the skin and therefore do not disrupt barrier function because of their skin lipid compatibility. A popular liquid crystal forming emulsifier is lecithin or hydrogenated lecithin [4]. Another recent trend is the use of emulsifiers as part of the emollient system in the product. Emollients are substances that make the skin feel smooth and soft, which is important to consumer acceptability. The most popular of this emulsifier type are “cationic” emulsifiers, which possess a net positive charge. The skin has a net negative charge because of its amino acid composition. A positively charged emulsifier will be attached to the skin and remain on the skin because of electrostatic attraction. Examples of these emulsifiers are behentrimonium methosulfate and dicetyldimonium chloride. Cationic emulsifiers are also very effective when there is a need to formulate low pH emulsions (less than pH 4.5) as cationic emulsifiers are very stable in low pH environments.

Emollients The choice of emollient or combination of emollients will have a dramatic effect on the feel, application, and delivery of the active to the skin. Matching solubility of active with the oil phase has a big effect in determining the material to be used. Matching the solubility parameter of an organic sunscreen to the solubility parameter of the oil phase has a significant effect on the sunscreen performance. The emollient category has been greatly expanded because of the increased use of silicones and the increasing number of “natural” emollients. The selection of emollient combinations is where art and science are combined. Selecting the right combination which provides the proper initial, middle, and end feel is one of the biggest challenges affecting the successful development of a cream. Concepts such as “cascading effect” describe this type of change which occurs as you apply an emollient system.

Active ingredients Examples of active ingredients are sunscreen materials (e.g. octinoxate, titanium dioxide, avobenzone), antiacne actives (i.e. salicylic acid, benzoyl peroxide), skin lighteners (hydroquinone), etc.

Humectants The humectant, usually a glycol or polyol, will have an effect on “skin cushion” and can also be part of the solvent system for an active ingredient. Glycols, such as propylene glycol and butylene glycol, are very good solvents for salicylic acid (an FDA approved over-the-counter active ingredient used

to treat acne) and are frequently used for this purpose in an emulsion system. In addition, they also function to help with freeze–thaw stability.

Thickeners The thickener(s) are used to control the viscosity and the rheology of the emulsion and can also help in maintaining the stability or product integrity of the emulsion, especially at elevated temperatures. Even in W/O creams thickeners are used for viscosity control. The viscosity of a cream is primarily determined by the thickener used and the viscosity of the external phase. The choice of thickeners, to a large extent, depends upon the compatibility of the thickener with the rest of the ingredients in the formulation, the pH of the formulation, and the desired feel that is trying to be achieved. The predominant thickeners used in O/W emulsions are acrylic-based polymers. The most popular materials are carbomers and its derivatives. Carbomers are a cross-linked polyacrylate polymer and their derivatives which are high molecular weight hom*opolymer and co-polymers of acrylic acid cross-linked with a polyalkenyl polyether [4]. These polymeric thickeners are very effective in stabilizing emulsions at elevated temperatures. (In W/O emulsions the predominant thickeners for the external phase are waxes – natural or synthetic.)

Water-in-oil creams The composition of a W/O emulsion may not look much different on paper than an O/W emulsion except that the emulsifier system would be different and would be designed to make a W/O emulsion. The ratio of the two phases is not an indication of the type of emulsion. There are many O/W emulsions in which the oil phase may be at a higher persentage than the water phase and in a W/O emulsion the water phase is frequently at a higher percentage than the oil phase.

Ointments There are different types of ointments. The traditional type of ointment contains very high levels of petrolatum as this material is a very good water-resistant film former and serves as very effective delivery system for drug actives on the skin. An example of a traditional petrolatum-based ointment is shown in Table 9.3. In reviewing this formulation you will notice that there is no antimicrobial preservative present. Some ointment formulations put in low levels of antimicrobial preservatives for added protection during consumer use, but anhydrous ointments are hostile environments for bacteria and are generally “self-preserving.” The use of an oil-soluble emulsifier helps with the application properties of the ointment as well as the ability to wash it off the skin. Recently, there has been an increased interest in “natural ointments” – ointments that do not use petrochemicals (i.e.



Delivery of Cosmetic Skin Actives

Table 9.3 An example of a traditional petrolatum-based ointment. Ingredients

% (weight/weight)

White petrolatum USP




Natural and/or synthetic waxes


Oil-soluble emulsifier


“Drug actives”

As required



Fragrance/essential oils


Skin feel modifiers


Table 9.4 A typical “natural ointment” composition. Ingredients

% (weight/weight)

Soy bean oil (and) hydrogenated cottonseed oil




Natural waxes


Oil vegetable-soluble emulsifier


“Drug actives”

As required

Natural antioxidants


Natural fragrance/essential oils


Natural skin feel modifiers


petrolatum) and are primarily based on plant-derived materials. The primary difference is in the use of the material that replaces petrolatum in the formulation. There are a number of hydrogenated oil/wax mixtures that are offered and used as “natural petrolatums.” A typical “natural ointment” composition is shown in Table 9.4). “Natural ointments” generally do not have the same unctuous, heavy feel that petrolatum-based ointments have and they usually do not leave as much residual feel on the skin. As with petrolatum-based ointments, little or no antimicrobial preservative is needed because of the anhydrous nature of the ointment. However, antioxidants are a very important components, as these “natural oil-based” ointments have a tendency to turn color and go rancid (similar to what you would see in a vegetable oil) without adequate protection.


While the number of different ingredients that can be used in an emulsion or an ointment can sometimes seem overwhelming, once you break down the product into the attributes and benefits and esthetics that are desired, the choices become less daunting.

Cream and ointment stability Once the formulations have been put together and evaluated, the next step is stability testing. This testing is carried out to determine what happens to the product once it is on the market. The ideal test would be to store the product at ambient temperature for 2–3 years and observe any changes that may occur in product integrity and determine the stability of the active ingredient(s) that are present. Because this timeframe is not practical, accelerated stability testing is conducted to predict the long-term stability of the product. For most emulsions, this testing involves storage of the finished product at 5 °C, 25 °C (RT), and 40 °C and sometimes at 50 °C. Stability at 40 °C is traditionally carried out for 3 months [1]. This testing is accepted by the US FDA for expiration dating until a full 2–3 year study is complete. Its purpose is not to ascertain product integrity but to establish the stability of the drug actives in the product. Elevated temperature testing (40 °C for 3 months) is conducted so that a determination can be made in a reasonable amount of time as to the integrity and stability of the product and to allow the product to be marketed in a reasonable amount of time from the completion of formulation development.

Conclusions The development of the final formulation is a combination of art and science, and both have an important role in the use of the product by the patient or consumer. Once the type of formulation is determined, the ingredients have been selected, the formulation developed, and the appropriate safety, efficacy, preservative and stability testing completed, the product is ready to introduce to the market.

References 1 Block LH. (1996) Pharmaceutical emulsions and microemulsions; emulsions and microemulsion characteristics and attributes. In: Lieberman HA, Rieger MM, Banker GS, eds. Pharmaceutical Dosage Forms: Disperse Systems, Vol. 2. New York: Marcel Dekker, pp. 47, 94–5. 2 Biology on Line; Dictionary-O-Ointments 2008. 3 “Emulsions” presentation from Cognis Corporation, August 2004. 4, Carbopol Rheology Modifiers.

Section II Hygiene Products

Part 1: Cleansers Chapter 10: Bar cleansers Anthony W. Johnson and K.P. Ananthapadmanabhan Unilever HPC R&D, Trumbull, CT, USA

BAS I C CONCEPTS • There are two basic types of cleansing bar – soap bars and synthetic detergent bars. • Like all surfactant-based products, cleansing bars can be harsh or mild to skin. • Mild cleansing bars have a key role in fundamental skin care. • Mild cleansing bars have positive benefits for patients with skin diseases.

Introduction Cleansing bars – historical perspective Anecdotally, soap was discovered by prehistoric man, noticing a waxy reside in the ashes of an evening camp fire around a burnt piece of animal carcass. The waxy material was soap. Potash from the ashes (KOH) had hydrolyzed triglyceride from animal fat to produce potassium soap and glycerol. Actual historical records show soap-like materials in use by Sumerians in 2500 BC and there are references to soap in Greek and Roman records and by the Celts in northern Europe. As European civilizations emerged from the Dark Ages in the 9th and 10th centuries soap making was well established and centered in Marseilles (France), Savona (Italy), and Castilla (Spain). In those days soap was a luxury affordable only by the very rich. Mass manufacture of soap started in the 19th century and was well established by the turn of the century with individually wrapped and branded bars. Synthetic detergents emerged in the 20th century, primarily for fabric washing products. While there are many types of synthetic detergent, very few are suitable for making cleansing bars. It is difficult to make a solid product that is able to retain a solid form during multiple encounters with water and at the same time able to resist cracking, crumbling, and hardening when drying between uses. Soap is ideal for making bars but that is not to say that some of the early soap bars did not dry out and develop cracks

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

or become soft and mushy in humid environments. Modern manufacturers are able to formulate soap bars to control the physical behavior in use and when drying between uses. Soap-based bars continue to dominate the cleansing bar market around the world, but synthetic detergent bars are gaining an increasing share of market (30% of bars sold in the USA). The wide range of soap bars available in the skin marketplace today might suggest a wide range of functionality but this is not the case. To develop new claims and gain shelf space in big supermarkets, manufacturers create variants by minor modifications of their basic bar types – the functional properties of soap bar variants are usually very similar – they all lather and they all clean.

Formulation technology of cleansing bars Cleansing bars are made of surfactants that are solid at room temperature and readily soluble in water. While there are scores of commercially available surfactants only two, alkyl carboxylate (soap) and acyl isethionate (syndet), are used on a large scale for manufacture of cleansing bars (Figure 10.1). These two surfactant types are quite different, leading to different sensory experiences for the consumer and also differences in their interactions with skin. Soap and syndet have in common that they have the physical properties required to be processed into bars that can withstand the challenges of use in the home. As bars they must have a consistent performance – they must lather easily when new but just as readily as the bar is used up over a period of weeks or months. They should produce lather quickly and easily and should not feel gritty in use. The rate of wear should be optimum, neither too fast nor too slow. They must



Cleansers O-

Sodium acyl isethionate (syndet) S



O O O Sodium alkyl carboxylate (soap) O- Na+ O Figure 10.1 Schematic representation of the molecular structures of soap (sodium alkyl carboxylate) and syndet (sodium acyl isethionate) showing the difference in head group structure and size.

fatted soap. Basic soaps are blends of medium chain length fatty acid sodium salts (Figure 10.1). Superfatted soaps are similar but with additional fatty acid. There are other categories of soap bars based on the use of specialist ingredients: transparent bars, antibacterial bars, and deodorant bars. There are large numbers of specialist bars that are simply soap containing a wide range of colors, fragrances, and emotive ingredients such as vitamins, aloe, chamomile, and other natural extracts. The emotive ingredients in specialist bars are there to appeal to the senses and emotions with no real expectation that they have any detectable benefit for the skin.

Basic soap dry quickly after use but must not crack; they should not break apart if dropped, and should not absorb water and become mushy in a humid environment, like a bathroom. There are not many surfactants that can satisfy this list of seemingly simple practical requirements. Broadly speaking, there are two types of manufacturing process for making cleansing bars: (a) a continuous process of milling, extrusion, and stamping; and (b) a batch process of melt casting.

Continuous processing The continuous process starts with synthesis of the basic surfactant, alkyl carboxylate, and then processing this as a solid through various steps during which other ingredients are added until the final composition is attained. After milling and mixing steps to ensure hom*ogeneity, the compounded soap it is extruded as a continuous bar which is chopped and stamped into the individual bar shape of the final product. The technical demands of the continuous process impose constraints on composition and ingredient addition – but it is the fastest and cheapest way to make a cleansing bar.

Soap is the sodium salt of a fatty acid. As the salts of weak acids, soaps form alkaline solutions as they dissociate in water. The pH of soap is typically in the pH range 9–11. This is not sufficient to be overtly irritating to skin but is sufficiently high to negatively impact the pH-dependent processes of the stratum corneum which has a natural pH of around 5.5. The fatty acids used in soap making are natural, derived from animal or plant sources, with the most common chain lengths in the range C12 (e.g. coconut fatty acid) to C18 (e.g. tallow/rendered animal fat). C12–14 soaps are soluble and lather easily. C16–18 soaps are less soluble but good for forming solid bars. The plant oils used in soap making are mostly triglycerides and when treated with lye and/or caustic soda they hydrolyze to the fatty acid sodium salts (soap) and glycerol.

Superfatted soap bars Simple soaps are good cleansers but also drying to skin. Less drying soaps are made by adjusting the soap making process to leave an excess of free fatty acid in the final soap composition (superfatted soaps). This excess fatty acid reduces the lipid stripping and drying effects of a soap bar to a small extent. Beauty soaps are typically superfatted soaps.

Batch processing

Transparent soaps

The essence of the melt cast approach is to make the surfactant and add any desired ingredients to form a hot liquid melt which is poured into individual bar size casts and allowed to set as it cools. This is a much more expensive process but allows for a wider range of additional ingredients in the product formulation. The continuous process is used for most of the mass market bars and the melt cast process for specialist bars often sold in boutiques, custom outlets, and department stores.

There are several types of transparent or semi-transparent soap bars. The earliest was a rosin glycerin soap bar developed by Andrew Pears in 1789. The ingredients of Pears patented transparent soap were sodium palmitate, natural rosin, glycerine, water, C12 soap, rosemary extract, thyme extract, and fragrance. The Pears soap of today is made by essentially the same process, which involves dissolving the raw soap and other ingredients in alcohol, pouring into moulds followed by up to 3 months of evaporation and drying. A different type of transparent bar was introduced in 1955 by Neutrogena based on a patented formulation invented by a Belgian cosmetic chemist, Edmond Fromont. His novel formulation was based on triethanolamine soap (in other words, soap where the neutralizing cation is triethanolamine

Soap bars There are several major compositional types of soap bar with distinct bar properties and in use behaviors – speed and type of lather, rate of use up, aroma, skin compatibility, tendency for mush, etc. Most bars are either basic or super-


10. Bar cleansers instead of the usual sodium). The ingredients of the Neutrogena bar are triethanolamine stearate, C12–18 soaps, glycerine, water, and a range of minor ingredients including a little lanolin derivative and fragrance. Triethanolamine forms acid soaps so the pH of the Neutrogena bar at pH 8–9 is lower than a regular soap with sodium as the cation.

US cleansing bars % total market (volume) Syndet 1 Soap 1 Soap 2 Soap 3 Soap/Syndet Soap 4 Syndet 2 Syndet 3 Soap 5 Private label Syndet 4 Soap 6

Antibacterial and deodorant soap bars Medicated or antibacterial soaps are a large subcategory of the bar soap market. These products are basic soaps containing one of a limited number of approved antibacterial agents. Some of these products are positioned as deodorant soap to inhibit the odor-producing bacteria of the axilla. Washing with any soap is effective for removing and killing the bacteria on skin and the value and contribution of added antibacterial agents is controversial. However, there are a variety of tests developed to assess the effectiveness of antibacterial soaps and there is no doubt that there is some deposition of the antibacterial agents on skin during washing and this is expected to reduce the effectiveness of any residual bacteria and to reduce colonization by other microbes.

US syndet cleansing bars (% of syndet segment)

Bar 1 Bar 2 Bar 3 Bar 4* Bar 5* * Less than 0.1% market share – too low to register

Non-soap detergent bars – syndet bars Because soap is cheap and easy to manufacture the cleansing bar market has remained predominantly soap bars. However, there has been one non-soap bar technology that has achieved a significant place in the US market over the last 50 years and is now extending its reach to other regions of the world. This product, introduced to the US market in 1957 as the Dove bar, is based on patented acyl isethionate as the surfactant component in combination with stearic acid which has a dual function of providing the physical characteristics for forming a stable bar and also acting as a significant skin protecting and moisturizing ingredient. The high level of stearic acid in the Dove bar is the basis of the one-quarter moisturizing cream in the product. When the patents for this novel technology ran out, several other acyl isethionate bars were introduced in the USA market including Caress, Olay, Cetaphil, and Aveeno.

Market overview There are hundreds of cleansing bars on the market but relatively few that are widely sold. Most of the cleansing bar market is supplied by a small number of manufacturers and a limited number of brands. Figure 10.2 shows the segmentation of the US market for soap and syndet cleansing bars.

Preservatives It is of interest that soap bars and syndet bars are self-preserved in the sense that they provide a hostile environment for microorganisms and do not need to contain a preservative to maintain product quality.

US cleansing bar segmentation % total market (volume)

Syndet Soap

Figure 10.2 Segmentation of cleansing bar market (based on average data for 2006, 2007, and 2008). The charts show shares (volume) for leading soaps and syndet bars. Brands not identified. Brands and their market shares vary somewhat year to year and may vary considerably over time.

Impact of cleansing bars on skin structure and function Washing with soap removes dirt and grime from skin and is very effective for removing germs and preventing the spread of infection. There is an appreciation that some soaps are harsh and others mild, but washing with soap is so routine and commonplace that most people give no thought to the cleansing process or its impact on skin. This is a mistake.




Research over the last few years has revealed several mechanisms by which soap interacts with skin structures to adversely affect normal functioning. It is now clear that mild cleansing has significant benefits for both diseased and healthy skin. Mild cleansing can reduce the symptoms of common skin conditions such as eczema, acne, and rosacea and can enhance the attractiveness of normal skin.

Surfactant interaction with the skin–stratum corneum As described in other chapters of this book, the outer layer of skin, the stratum corneum, is a very effective barrier to the penetration of microorganisms and chemicals unless compromised by damage, disease, or a intrinsic weakness caused by one of the genetic variations now known to impact the functioning of the stratum corneum. Whatever the normal state of the stratum corneum for an individual, the most challenging (i.e. potentially damaging) environmental factor, apart from industrial exposure to solvents and other harsh chemicals, is cleansing. And yet cleansing is a key element of good everyday skincare and there is much variation in the damaging potential of different cleansing products including cleansing bars. Understanding how cleansing products impact skin and knowing the mildest cleansing product technologies is a basic requirement for achieving fundamental skin care.

further cleansing or even simply by contact with water. This process explains the paradox that water is often a major factor for causing dry skin. Effects on the key lipid structures of the stratum corneum add to the damage caused by soap– protein interactions and exacerbate the development of skin dryness – remembering that dry skin is not simply a lack of moisture but a disturbance of normal stratum corneum function with retention and accumulation of superficial corneocytes. The build up of corneocytes at the skin surface is responsible for many symptoms associated with “dry” skin – scaling, flaking, roughness, dull appearance (due to light scattering), tightness, loss of resilience/flexibility/elasticity, and ultimately cracking and irritation. All soaps have the ability to induce dry and irritated skin and these effects are most evident in challenging environmental condition – cold or hot temperatures with low humidity, excessive exposure to solar UV radiation, and prolonged exposure to wind. The drying potential of soap varies according to composition such as the balance between soluble (C12–14) and less soluble chain lengths (C16–18) of the fatty acids most commonly used to make soap – the higher the soluble component the more drying the soap. Superfatted soaps are a little milder than simple soaps, and triethanolamine soap and glycerol bars the mildest of the commonly available soap bars.

Soap bar interactions with the stratum corneum

Synthetic detergent bar interactions with the stratum corneum

The properties of soap that make it an effective cleanser also determine that it can be drying and irritating to skin. The high charge density of the carboxyl head group of the soap molecule promotes strong protein binding which is good for cleansing but bad for skin. Soap binds strongly to stratum corneum proteins and disturbs the water-holding mechanisms of the corneocytes. Soaps also denature stratum corneum enzymes essential for corneocytes maturation and desquamation. The result is an accumulation of corneocytes at the skin surface and the characteristic scaly, flaky, roughness associated with dry skin. In addition to damaging proteins, soap and other cleansers can disrupt and strip out the lipid bi-layers of the stratum corneum. The bipolar structure of the soap molecule is similar to the bipolar structure of the three major lipid types that make up the lipid bi-layers of the stratum corneum (fatty acids, cholesterol, and ceramides). Soap disrupts the bi-layer structure of these lipids in the stratum corneum and thereby reduces the effectiveness of the stratum corneum water barrier. Transepidermal water loss (TEWL) is increased through the leaky barrier. Also, disruption of the structured lipid matrix around stratum corneum cells (corneocytes) allows the highly soluble components of the skin’s natural moisturizing factor (NMF), contained in the protein matrix of the corneocytes, to leach out. Leaching is increased by

Synthetic detergent bars (syndet bars) have been available on the US market for 50 years and represent a clear technologic difference from soap-based cleansing bars. Nearly all common synthetic detergent bars are based on an anionic surfactant, acyl isethionate. At the time of writing (2008) these bars account for 40% of the cleansing bars sold in the USA. Alkyl glycerol ether sulfonate (AGES) and monoalkyl phosphate (MAPS) are two of a small number of other synthetic detergents that have been tried for manufacture of cleansing bars but none of these have been successful in the US market. Ironically, because syndet bars are shaped like soap bars and used for cleansing just like a soap bar, most people believe that synthetic detergent bars are just another variety of soap. Most consumers are unaware that there is a fundamental compositional difference between soap and syndet bars that impacts their interactions with skin such that syndet bars are milder than soap bars during cleansing. There is a greater difference between soap and syndet cleansing in terms of healthy and attractive skin than most people realize. It is important for healthcare professionals and dermatologists to appreciate the difference between soap and syndet bars because studies show the difference in mildness is very relevant for their patient groups (see studies described below).


10. Bar cleansers Soap (alkyl carboxylate) and syndet (acyl isethionate) are both anionic surfactants and like all anionic surfactants they interact with skin proteins and skin lipids. But because of the difference in head group physical chemistry soap interactions are more intense leading to a higher potential for inducing dryness and irritation. The carboxylate head group is compact, leading to a high charge density that facilitates binding and denaturation of proteins. By contrast, the isethionate head group is large and diffuse, producing a low charge density and less ability to interact with proteins (Figure 10.1) A second and most important factor contributing to the mildness of the isethionate syndet bar is the ability to formulate acyl isethionate with high levels of stearic acid without losing the ability to lather. In fact, the lather is more dense and creamy than the lather of a typical soap bar. The stearic acid component of the isethionate syndet bar acts as a moisturizing cream and deposits on skin during cleansing, adding to the relative mildness of these types of bar.

Superfatting is, in principle, a similar way to reduce the harshness of plain soap but the results are much more modest because the initial harshness of soap is higher than syndet and the upper limit of practical superfatting is closer to 10% compared to the 20–25% fatty acid that can be formulated in an isethionate bar. Another difference between soap and syndet bars is pH. Soap has an alkaline pH typically around pH 10–11 whereas isethionate/stearic acid bars are close to pH neutral with a pH of a little over 7. The pH of glycerol bars is in the range pH 8–9. These differences in pH have an effect on the interaction of cleansing bars with the stratum corneum. Skin proteins swell markedly if the cleanser pH is highly alkaline (pH >8). Optical coherence tomography (OCT) pictures of stratum corneum after exposure to acidic, neutral, and alkaline pH conditions and the corresponding swelling show that there is significantly higher swelling in alkaline pH solutions (Figure 10.3). Strongly binding detergent molecules can increase the swelling further.

pH 4

pH 6.5

pH 10 Figure 10.3 Swelling of the stratum corneum in different pH buffer solutions. (a) Optical coherence tomography (OCT) images of ex vivo skin treated with different buffer solutions. The arrows show the position and thickness of the stratum corneum. (b) The bar chart provides a graphic representation of the same difference.

Average stratum corneum swelling (μm)

100 80 60

* *

40 20 0

pH 4

pH 6.5 Buffer

pH 10

* Different from pH 10 P<0.05 (a)





High pH also has an impact on stratum corneum lipids. An alkaline pH can ionize fatty acids in the lipid bi-layers making them more like “soap” molecules and destabilizing the highly organized structure of the bi-layers. These factors contribute to the differences in mildness of soap and syndet bars. Environmental scanning electron microscopy pictures of the skin surface and the corresponding transmission electron microscopy images of the proteinlipid ultrastructure of human skin washed under exaggerated conditions (nine repeat washes) with a syndet and a soap bar are seen in Figure 10.4. It is evident from the micrographs that the syndet bar washed sample exhibits wellpreserved cells with intact proteins and lipids compared with the soap washed sample.

Studies comparing mildness properties of soap and syndet cleansing bars Many consumers are not aware of the differences in drying and irritation potential between soap bars and synthetic detergent bars. In practice, most cleansing products are not drying to an extent that is readily perceivable and under normal conditions of use cleansing bars seldom produce


irritation and inflammation. However, in other circ*mstances, particularly drying environmental conditions or with compromised diseased skin, some cleansing bars can cause severe dryness and irritation. Why is this? Under normal conditions it is likely that the skin is superficially and temporarily dried by most cleansers but is rapidly able to restore its ability to hold moisture and maintain healthy functioning. However, under challenging environmental conditions, particularly the harsh cold winters of Canada and the northern USA and the hot dry summers of the central plains and western desert areas of the USA, recovery after washing is likely less rapid. Without supplemental moisturization from the cleansing product or a skin cream or lotion applied after washing, a vicious cycle of damage and inadequate recovery is quickly established, leading initially to dry skin but quickly progressing to deeper damage with fissuring of the stratum corneum (cracking), deeper penetration of the surfactant, frank irritation, and ultimately full-thickness cracking of the stratum corneum leading to chapping and bleeding. This may sound extreme but anyone with a tendency to develop dry skin will recognize this scenario of raid deterioration to more severe irritation when the weather is drying – particularly for handwashing.




Soap bar

Syndet bar (TEM)


Soap bar

Syndet bar

Figure 10.4 Environmental scanning electron micrographs (ESEM) and transmission electron micrographs (TEM) images of human skin washed with water, soap, and a syndet bar (9 repeat washes). Water washed and mild syndet bar washed skin shows well-preserved lipids and plumped (hydrated) corneocytes. By contrast, images of harsh soap-washed skin show significant removal of lipids and damage to proteins.


10. Bar cleansers The first practical demonstration that syndet bars are fundamentally less damaging to skin than soap bars was a study published by Frosh and Kligman [1]. Using a new and simple method, the soap chamber test, they examined the skin irritation potential of all the cleansing bars they could purchase locally in Philadelphia at that time. One bar stood out as exceptionally mild compared with the rest of the marketplace (17 other bars tested) and this was a patented alkyl isethionate bar called Dove. Now that the Dove patent has expired a number of manufacturers sell similar isethionate syndet bars. The difference in relative mildness of soap and isethionate/stearic acid syndet bars is easily demonstrated in the standard wash and rinse tests used by manufacturers of cleansing products. The forearm controlled application test (FCAT) and leg controlled application test (LCAT) are 5-day repeat washing tests. Skin condition is evaluated daily by a variety of techniques including visual dryness, superficial and deeper hydration measured instrumentally, TEWL to

assess barrier performance, and erythema to assess irritation. Typical results obtained by comparing soap and syndet cleansers in a FCAT test are shown in Figure 10.5. An increase in stratum corneum dryness has a negative effect on the mechanical properties of the corneum. Changes in stratum corneum elasticity/stiffness measured in a standard clinical test after washing with soap and syndet bars are shown Figure 10.6. While soap washing increases skin stiffness markedly, the milder syndet bar maintains the original skin condition. Such effects are magnified further under low humidity and winter conditions and can lead to microcracks in the stratum corneum and increased water loss, plus increased vulnerability to penetration of external chemicals into skin. Concern is sometimes expressed that industry standard tests are exaggerated and do not reflect real consumer experience. The evidence accumulated by manufacturers and published in peer-reviewed journals demonstrates that effects in standard tests are indeed predictive of what can be

Visual dryness

Corneometer 5





Mean change from baseline

Mean change from baseline


* 0 –5 –10 –15 –20

* Syndet less dryness than all soaps (P<0.05)


(syndet soap differences P<0.05)

(b) TEWL

Skicon 0

8 6 4


2 0

* Syndet sig. less barrier impairment

Mean change from baseline

Mean change from baseline



Syndet Soap 1 Soap 2 Soap 3 Soap 4 TeaSoap




than soaps 1, 2, 3, 4 (P<0.05)


* Syndet hydrating, soaps drying

* Syndet sig. less drying than soaps 1, 2, 3, 4 (P<0.05)


Figure 10.5 Skin changes after 5 days of twice daily washing with soaps and syndet using the forearm controlled application test (FCAT) method. (a) Visual dryness; (b) transepidermal water loss (TEWL) – skin moisture barrier; (c) Corneometer – stratum corneum hydration; (d) Skicon – superficial stratum corneum hydration.


Change in stiffness (rheometer)




Practical implications of mild cleansing for patients with common skin disease


2.0 1.5 1.0 0.5 Syndet

0 –0.5 0


3.5 Days



Figure 10.6 Changes in skin mechanical properties (stiffness) after 5 days of twice daily washing with soap and syndet using the FCAT method. Soap washing induced a progressive increase in stratum corneum stiffness as measured using a linear skin rheometer whereas the syndet bar did not induce stiffness.

5-day controlled arm wash test

Less dry

Day 7 score minus baseline

5 day change from baseline

Less dry





2–7 day normal use for daily face wash





More dry

More dry Soap


Figure 10.7 Skin dryness induced by soap and syndet bars in a 5-day controlled arm wash test compared to dryness induced by 2–7 days of normal use once daily for facial cleansing. Arm wash test carried out on the same subjects as the 7-day facial wash test. Most soap users were unable to continue soap use for a full week. Most syndet users were able to complete a full week of daily face washing – dryness scores are based on assessments made on day 7 for the whole panel.

experienced in normal use under realistic but challenging environmental conditions. Figure 10.7 shows results of a study where women used soap or syndet for face washing for a week during the Canadian winter. They were not allowed to use a facial moisturizer during the study. Under the cold drying conditions of this study the soap users rapidly experienced intense drying and soreness whereas the syndet users were mostly able to tolerate the withdrawal of their normal after-wash moisturizer for a week.


The studies described in this section [2,3] were based on a simple hypothesis that switching patients with common skin diseases from their current soap bar cleanser to a milder syndet bar cleanser would minimize symptoms and generally help in managing their skin condition. The patient groups studied were atopic dermatitis, acne, and rosacea. The results show that patient symptoms were reduced and general skin quality improved.

Benefits of mild cleansing for adults and children with mild atopic dermatitis A total of 50 patients with mild atopic dermatitis were enrolled for a 4-week double-blind study carried out under the supervision of a certified dermatologist. One group of 25 patients (19 adults and 6 children <15 years) used a marketed syndet cleansing bar instead of their normal cleansing bar for showering during the 4 weeks of the study. A second group of 25 patients (17 adults and 8 children) used a different syndet bar based on the same acyl isethionate cleansing system. Eczema severity was measured at baseline and 4 weeks using the eczema area severity index (EASI) clinical assessment system. Other evaluations at these times were dermatologist assessment of non-lesional skin, hydration by conductance meter, and patient self-assessment by questionnaire. Results indicated good compatibility with the syndet bar as a substitute for patient’s usual bar cleanser for both adults and children. In addition, it was observed that the severity of eczematous lesions reduced with both bars, general skin condition was improved, and hydration was maintained. The main results are shown in Figure 10.8.

Benefits of mild cleansing for acne and rosacea patients In one study, a group of 50 patients with moderate acne and using topical acne medications (benzamycin or benzamycin/ differin) were split into two treatment cells (25 patients per cell) and instructed to use either a syndet bar or a soap bar for 4 weeks in place of their normal cleansing bar. Patient skin condition was assessed at baseline and after 4 weeks of use. Although the clinical differences between soap and syndet in this test were not statistically significant, there was a clear trend that patients using soap experienced worsening of measures relating to skin compatibility and irritation during the 4-week period of the study and little or no change in patients using the syndet bar (Figure 10.9). A similar protocol was used in a study of rosacea patients. Seventy patients were enrolled and divided into two subgroups for a 4-week study period. Evaluations were per-

10. Bar cleansers Dermatologist clinical evaluation EASI (Eczema Area/Severity Index)

Group mean EASI

2.5 2.0




Day 0 Day 28

1.0 0.5 0

Syndet bar A

Syndet bar B

* Day 28 eczema area/severity score sig. less than day 0 score (P<0.02) Patient self assessment of change in skin condition from day 0 to day 28 Decreases from baseline Symptom

Change from day 0

Increases from baseline Attribute

Bar A Bar B Dryness Itching Irritation Tightness Tingling

-1.5 -1.3 -1.1 -0.9 -0.7

-2.1 -2.8 -2.7 -1.3 -1.4

Change from day 0 Bar A Bar B

Complexion Smoothness Softness Appearance

0.2 0.7 0.4 1.3

1.3 2.7 2.8 2.3

Red numbers - sig. diff from baseline at day 28 (P<0.05)

Figure 10.8 Changes in dermatologist and patient assessment of skin condition after 4 weeks’ daily use of syndet cleansing bars by adult and child (7–15 years) patients with atopic dermatitis (AD). A total of 25 patients used bar A and 25 used bar B. The patients were patients with chronic AD stabilized using a variety of treatment regimens which they continued during the trial. The bars were similar in composition with the same acyl isethionate synthetic surfactant system and different ratios of emollients.

formed at baseline and at 4 weeks. The results show a similar trend in favor of using the syndet bar (Figure 10.9). The studies described above indicate a benefit of syndet bars for patients with disease compromised skin. Other studies have shown that use of syndet bars is helpful for skin that is compromised by treatments used to reduce the signs of photodamage such as retinoid therapy or chemical peels.

liquid cleansing products. This is most pronounced in the developed markets of North America and Europe. Like many market trends this change is brought about by changes in consumer needs, habits, and attitudes. Cleansing liquids have become the product of choice for the shower, liquid soaps are increasingly used for hand cleansing, and quick foaming liquids, creams, and wipes have largely replaced soap bars for facial cleansing. Nevertheless, there is little doubt that cleansing bars will remain a universal household product for many years to come. This chapter describes the negative effects for skin associated with cleansing and provides evidence that there are real benefits for patients and consumers generally to use the mildest bar cleansers available. It has long been recognized that environmental factors facilitate the drying, irritating actions of surfactants and that people differ in their susceptibility to these effects. Only recently has it become evident that genetic variations are direct drivers of individual variations in susceptibility to develop dry and sensitive skin. It appears that loss-of-function mutations in the filaggrin gene are relatively common in humans and are the cause of mild and severe forms of ichthyosis vulgaris and atopic dermatitis. The insight that filaggrin gene mutations and variations lead to a compromised barrier that predisposes to dry skin is changing how scientists and professionals think about dry skin and healthy skin functioning. Some people have a good barrier but others are much more susceptible to environmental challenges – including cleansing. Gene profiling is not yet a routine diagnostic procedure but susceptibility to develop dry skin is a strong indication of a compromised barrier and the need for mild cleansing to prevent surfactant-induced exacerbation of a poor barrier. The future will see new and more precise diagnostic tests enabling dermatologists and healthcare professionals to more readily identify consumers and patients who have less than optimal stratum corneum functioning. In parallel, the need to identify mild products and good cleansing practice will come into sharper focus. It will be interesting to see if the future consumer product trend is a rebalancing from soap bars to milder syndet bars or if the trend will be a more direct move from bars to liquid cleansers. Most likely the market will develop in both directions – milder bars and more use of liquid cleansers.

Conclusions The future of cleansing bars Bar soaps have been the most common product for skin cleansing for so long that most people never give them a second thought. However, since the late 1990s there has been a slow but steady decline in soap bar sales in favor of

Cleansing is a basic human need and cleansing bars are the universal way to satisfy this need. Liquid products may be gaining in popularity but it will be decades before bars become redundant, if ever. Cleansing is a challenge to skin for everyone, but for patients with skin problems the choice of cleansing product




Change in acne symptoms – dermatologist assessed

0.3 Soap bar Syndet bar

s Ti gh tn es

Itc hi ng

in gi ng St


Bu rn in g

ne s ry D


el in g



he m


Chane day 0 to day 28



Trend differences (day 28 not statistically significantly different from day 0)

Change in rosacea symptoms – dermatologist assessed

ne ht Ti g

ng hi Itc

ng gi in St


Soap bar Syndet bar












in g

he yt





Chane day 0 to day 28


Trend differences (day 28 not statistically significantly different from day 0)

is the difference between exacerbation and minimization of symptoms. There is ample evidence in the literature that syndet bars are milder than soap-based bars and better for patients with common dermatologic conditions such as atopic dermatitis, eczema, acne, and rosacea. Not everyone needs to use a syndet bar but many consumers and patients currently using soap bars could experience a practical benefit by switching to syndet bar.

References 1 Frosch PJ, Kligman AM. (1979) The soap chamber test: a new method for assessing the irritancy of soaps. J Am Acad Dermatol 1, 35–41. 2 Current Stratum Corneum Research. (2004) Optimizing barrier function through fundamental skin care. Dermatol Ther 17(1), 1–68. [A full issue of the journal (9 papers) dedicated to the biology of the stratum corneum barrier and the impact of cleansing and moisturizing products.] 3 Subramanyan K. (2004) Role of mild cleansing in the management of patient skin. Dermatol Ther 17(1), 26–34. [Specific paper dealing with the clinical studies.]


Figure 10.9 Dermatologist assessed changes in skin condition of patients with mild to moderate acne or mild to moderate rosacea after 4 weeks’ use of soap or syndet bar for daily cleansing. In the acne study were 50 patients using topical benzamycin or benzamycin plus differin. In the rosacea study were 70 patients using topical metronidazole. The syndet bar was acyl isethionate synthetic surfactant and the soap bar was a standard 80/20 soap.

Further reading Ananthapadmanabhan KP, Lips A, Vincent C, Meyer F, Caso S, Johnson A, et al. (2003) pH-induced alterations in stratum corneum properties. Int J Cosmet Sci 25, 103–112. Ananthapadmanabhan KP, Subramanyan K, Rattinger GB. (2002) Moisturizing cleansers. In: Leyden JJ, Rawlings AV, eds. Skin Moisturization. New York: Marcel Decker, pp. 405–32. Ertel K, Keswick B, Bryant P. (1995) A forearm controlled application technique for estimating the relative mildness of personal cleansing products. J Soc Cosmet Chem 46, 67–76. Imokawa G. (1997) Surfactant mildness. In: Rieger MM, Rhein LD, eds. Surfactants in Cosmetics. New York: Marcel Dekker, pp. 427–71. Johnson AW. (2004) Overview. Fundamental skin care: protecting the barrier. Dermatol Ther 17, 213–22. Matts PJ. (2002) Understanding and measuring the optics that drive visual perception of skin appeareance. In: Marks R, Leveque JL, Voegeli R, eds. The Essential Stratum Corneum. London: Martin Dunitz, p. 333. Matts PJ, Goodyer E. (1998) A new instrument to measure the mechanical properties of human stratum corneum in vivo. J Cosmet Sci 49, 321–33.

10. Bar cleansers Meyers CL, Thorn-Lesson D, Subramanyan K. (2004) In vivo confocal fluorescence of skin surface: a novel approach to study effect of products on stratum corneum. J Am Acad Dermatol 50, 130. Misra M, Ananthapadmanabhan KP, Hoyberg K, et al. (1997) Correlation between surfactant-induced ultrastructural changes in epidermis and transepidermal water loss. J Soc Cosmet Chem 48, 219–34. Murahata RI, Aronson MP, Sharko PT, et al. (1997) Cleansing bars for face and body: in search of mildness. In: Rieger MM, Rhein LD, eds. Surfactants in Cosmetics. New York: Marcel Dekker, pp. 427–71. Nicholl G, Murahata R, Grove G, Barrows J, Sharko P. (1995) The relative sensitivity of two arm-wash methods for evaluating the mildness of personal washing products. J Soc Cosmet Chem 46, 129–40.

Prottey C, Ferguson T. (1975) Factors which determine the skin irritation potential of soaps and detergents. J Soc Cosmet 26, 29–46. Rawlings AV, Harding CR. (2002) Moisturization and the skin barrier. Dermatol Ther 17, 43–8. Rawlings AW, Watkinson A, Rogers J, et al. (1994) Abnormalities in stratum corneum structure, lipid composition, and desmosome degradation in soap-induced winter zerosis. J Soc Cosmet Chem 45, 203–20. Strube D, Koontz S, Murahata R, et al. (1989) The flex wash test: a method for evaluating the mildness of personal washing products. J Soc Cosmet Chem 40, 297–306. Wihelm KP, Wolff HH, Maibach HI. (1994) Effects of surfactants on skin hydration. In: Elsner P, Berardesca E, Maibach HI, eds. Bioengineering of the Skin: Water and the Stratum Corneum. Boca Raton, FL: CRC Press, pp. 257–74.


Chapter 11: Personal cleansers: Body washes Keith Ertel and Heather Focht Procter & Gamble Co, Cincinnati, OH, USA

BAS I C CONCE P T S • Dry skin on the body is a particular issue for most consumers. Leave-on lotion application is not always viewed as a convenient intervention, so relief is sought from alternative sources such as moisturizing personal cleansing products. • Body washes are a relatively new introduction into the armamentarium of personal cleansing products and their use is growing rapidly, particularly in developed countries. • Body washes present unique formulation challenges and benefit opportunities compared to traditional cleansing bar forms. • There are several distinct types of body washes. Of these, moisturizing body washes represent the greatest departure from traditional personal cleaners, having the potential to improve dry skin condition. • Moisturizing body washes vary widely in terms of their skin effects (i.e. their ability to mitigate dryness). A product must deposit an effective amount of benefit agent on the skin during the wash–rinse process. Understanding the basis for a product’s designation as “moisturizing” is key.

Background Cleansing to remove soils from the skin’s surface is a basic human need that serves both a cosmetic and a health function. While cleansing needs for the face receives considerable attention and few question the logic of specialized facial cleansers, cleansing needs for the body are often given little thought, the assumption being that any personal cleanser will suffice. This view is somewhat surprising given that body skin accounts for more than 90% of the body’s total surface area and, as we will show, consumers have diverse needs and expectations from a body cleanser. Water alone cannot effectively remove all soils from the skin and surfactant-based materials have been the cleansing aids of choice throughout recorded history. Soap was among the first cleansing aids and some of the earliest references to soap preparation are found in Sumerian and Egyptian writings, although legend holds that the article we know as soap originated by chance at Mount Sapo in Ancient Rome when fat and wood ash from sacrifices were mixed with rainwater. Regardless of its origin, soap was the cleansing aid of choice and remained largely unchanged for centuries. The next real step-change in personal cleanser technology occurred around the time of World War I, when the first non-soap surfactant was introduced. However, bars continued as the predominant form for body cleansing and it was

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


not until the latter part of the 20th century that liquid personal cleansing products for the body (i.e. body washes) were introduced and began to gain a foothold in some regions. Body washes are generally less messy in use than bars (e.g. no soap mush), are more hygienic, and offer greater potential to deliver skin benefits, including dry skin improvement. However, body washes can be less convenient to transport and are generally more expensive on a per use basis than commodity cleansing bars. As a result, body wash adoption tends to reflect countries’ economic development status.

Types of body washes Body washes currently available in the market generally fall into three distinct categories. Regular body washes are products whose primary function is to provide skin cleansing. As such, they are typically based on a relatively simple chassis, although fragrance is sometimes used to define product character or to provide a higher order benefit (e.g. lavender scent may be used to produce a calming effect during use). Moisturizing body washes are intended to provide a dry skin improvement in addition to performing the base skin cleansing function. However, there are different ways to define dry skin improvement for moisturizing body washes. In some cases a product’s benefit is judged relative to another (drying) personal cleanser and “improvement” amounts to producing less dryness than the benchmark. In other cases a product’s benefit is judged relative to an untreated control and “improvement” reflects the effect of the product relative to the condition of untreated skin. Thus, moisturizing body

11. Body washes washes can provide markedly different levels of dry skin improvement depending on the criterion used to judge their performance. Finally, there are products that fall into a broad category best described as specialty body washes. These are extensions of regular and moisturizing body washes that contain ingredients intended to provide additional function or benefit. Examples include products that contain beads or other grit material (e.g. pulverized fruit seeds) to provide exfoliation and an enhanced dry skin benefit, and products that contain menthol or other sensates to provide a “cooling” or “tingling” sensation to the skin.

Major formula components of body washes Water Unlike their cleansing bar counterparts, body wash formulas contain a high percentage of water. This situation is a double-edged sword. On the one hand, eliminating the need to form materials into a bar that will hold its shape while maintaining good performance and wear characteristics removes a number of formulation constraints, and this introduces the possibility of incorporating relatively high levels of non-cleanser materials (e.g. benefit agents) into the formulation. On the other hand, the aqueous milieu present in liquid cleansers and body washes introduces issues not present in bars. For example, many benefit agents are lipophilic in nature and an improperly formulated liquid cleaner may exhibit phase separation or creaming, not unlike the separation of oil and water phases that occurs in some salad dressings. Chemical stability is also a consideration; the greater mobility afforded by a liquid environment increases the likelihood of molecular interactions, and water itself can participate in decomposition reactions (e.g. hydrolysis). An aqueous environment also increases the potential for microbial contamination. Thus, formulating a liquid cleanser or body wash presents a number of unique challenges, particularly if the product is intended to perform a function beyond simple cleansing such as delivering a benefit agent to the skin.

Surfactants Surfactants are the workhorse ingredient in any personal cleansing product. Water is capable of removing some soils from the skin; however, sebum and many of the soils acquired on the skin through incidental contact or purposeful application (e.g. topical medicaments) are lipophilic in nature and are not effectively removed from the skin’s surface by water alone. Surfactants, or surface-active agents, have a dual nature; part of a surfactant molecule’s structure is lipophilic and part of it is hydrophilic. This structural duality allows surfactant molecules to localize at the interface between water and lipophilic soils and lower the inter-

facial tension to help remove the soil. Further, surfactants allow water to more effectively wet the skin’s surface and to solubilize lipopilic soils after removal, which prevents the soils from redepositing on the skin during rinsing. Surfactants are also responsible for the formation of bubbles and lather, which most consumers view as necessary for effective cleansing. As with cleansing bars, the surfactants used in liquid personal cleansers and body washes fall into two primary groups: soaps and non-soaps, also known as synthetic detergents or syndets. Soap is chemically the alkali salt of a fatty acid formed by reacting fatty acid with a strong base, a process known as saponification. The fatty acids used in soap manufacture are derived from animal (e.g. tallow) or plant sources (e.g. coconut or palm kernel oil). These sources differ in their distribution of fatty acid chain lengths, which determines properties such as skin compatibility and lather. Soap’s properties are also affected by external factors such as water hardness; soaps are generally more irritating and lather and rinse more poorly in hard water. Some specialty body washes contain soaps derived from “natural” fatty acid sources such as coconut or soybean oil; these products will behave similarly to products containing soaps derived from traditional fatty acid sources. Syndets, which are derived from petroleum, were developed to overcome shortcomings associated with soaps (e.g. the influence of water hardness on performance) and to expand the pool of available raw materials used in manufacture. Syndets vary widely in terms of their chemical structure, physicochemical properties, and performance characteristics, including skin compatibility. Syndets are not necessarily less irritating than soaps. Sodium lauryl sulfate is an example; many dermatologists view alkyl sulfates as model skin irritants. Most body washes are based on syndet surfactant systems, and because syndets have a wide range of performance characteristics, most body washes combine several surfactant types to achieve specific performance to the finished product. For example, alkyl sulfates, while having relatively poor skin compatibility, lather well. Combining an alkyl sulfate with an amphoteric surfactant such as cocamidopropyl betaine can improve both lather and skin compatibility. Thus, formulating a body wash with syndets involves choosing surfactants to optimize performance and aesthetics, balanced with cost considerations.

Skin benefit agents Some body washes contain ingredients that are intended to provide skin benefits beyond simple cleansing. Dry skin, which is a pervasive dermatologic issue, is one of the most common benefit targets for body washes. Not surprisingly, moisturizing ingredients such as petrolatum, various oils, shea butter, or glycerin, which are found in leave-on moisturizers, are often used in moisturizing body washes. However, simply including a moisturizing ingredient in a




rinse-off product is not sufficient; the product must deposit an effective amount of the material on skin during the cleansing and rinsing process. As noted earlier, standards for judging moisturizing efficacy differ. Clinical testing shows that moisturizing body washes vary widely in their ability to provide a dry skin benefit, and that some may actually worsen dryness and irritation. In addition to moisturizing ingredients to improve dry skin, body washes may also contain particulates such as beads or pulverized fruit seeds to aid exfoliation. A particulate’s size, surface morphology (i.e. smooth or rough), and in-use concentration will determine its ability to provide this benefit. Finally, body washes may contain ingredients that are intended to protect from or to reduce the effects of environmental insults. As with moisturizing ingredients, an efficacious amount of these materials must remain on skin after washing and rinsing.

Other ingredients Body wash formulas contain additional ingredients that act as formulation and stability aids. The addition of polymers and salt alter a product’s viscosity, which can modify performance characteristics or improve physical stability. Feel modifiers such as silicones are sometimes used to improve the in-use tactile properties of body washes that deposit lipophilic benefit agents on skin. Chelating agents such as ethylenediamenetetraacetic acid (EDTA) and antioxidants such as butylated hydroxytoluene (BHT) and are added to improve chemical stability, and buffering a body wash formula to a specific pH value can help inhibit microbial growth and improve the product’s chemical and physical stability. Color and fragrance are an important part of the in-use experience for many body washes. Colors are US Food, Drug, and Cosmetic Act (FD&C) approved dyes and are usually present in relatively low amounts, so the likelihood of experiencing an issue with a body wash product because of dye is low. Fragrances are also usually present in relatively low amounts, although the apparent concentration may seem higher as a result of “bloom” that results from lathering a body wash on a mesh cleansing puff, the recommended application procedure for many of these products. The incidence of issues with modern fragrances is low. Some body washes incorporate natural oils to impart fragrance but these products are not necessarily without potential issues because some of these natural materials can cause sensitization.

In-use performance considerations for body washes Cleansing ability The mechanical action associated with applying a personal cleanser to the body helps to loosen and remove some soils,


but surfactants are the primary agents responsible for aiding soil removal, particularly lipophilic soils. However, surfactants and the cleansing products based on them differ in their abilities to remove sebum and lipophilic soils [1]. These cleansing performance differences are a greater consideration in body washes than in bars because of the relatively lower surfactant concentrations present in the former compared with the latter. Because lipophilic soils present the greatest cleansing challenge, oil-based makeup materials are often used as model soils in tests intended to measure cleansing efficiency. These materials are poorly removed from the skin by water alone and their inherent color makes them easy to detect visually or instrumentally and measure on the skin’s surface. To test the cleaning efficiency of various methods of skin cleansing, we conducted a study comparing a moisturizing petrolatum-depositing body wash, a syndet detergent bar, and water for cleansing ability. A commercial oil-based makeup product served as a model soil and was applied to discrete treatment sites on the volar forearms of light-skinned females. The makeup was allowed to dry for 15 minutes and baseline colorimeter (L*) values were recorded at each site. Lather was generated from each cleansing product in a controlled manner and applied to a randomly assigned site for 10 seconds with gloved fingers. Sites were rinsed with warm water for 15 seconds, allowed to air dry for 30 minutes then chromameter measurements were repeated. Data were analyzed by a mixed-model procedure. The results show that water has little effect on removing the model soil from the skin and while the makeup used in this study is perhaps an extreme challenge, it nonetheless exemplifies why personal cleansing products are needed for soil removal. Not surprisingly, both personal cleansing products removed a significantly greater amount of the model soil than did water (P < 0.01), but the petrolatum-depositing body wash showed significantly greater makeup removal (i.e. cleansing efficiency) than the syndet bar (mean ΔL* values of 5.2 and 3.2, respectively; P < 0.02). Thus, this study shows that a petrolatum-depositing body wash can clean efficiently and demonstrates that consumers are not restricted to the traditional bar form for their skin cleansing needs.

Consumer understanding and need for moisturizing body washes Patients with dry skin that accompanies a dermatologic condition often require a high level of skin moisturization and may be willing to tolerate poor moisturizer product aesthetics (e.g. skin feel) to obtain relief. A recent habits and practices study among a group of 558 adult females demonstrates that a consideration of consumers’ varied moisturization needs and their desired product aesthetics must be made in

11. Body washes order to create products that improve patient compliance. These participants answered questions that provided a range of information about their needs for body moisturization and their expectations for a moisturizing personal cleansing product (i.e. body wash). Dry skin was a source of discomfort for a majority of participants; 62% said they were “very bothered” or “bothered” by discomfort due to dry skin, while 20% said they were “not bothered” by discomfort due to dry skin. Dry skin also drove these consumers to apply leave-on moisturizers; 68% said they “strongly agreed” or “agreed” that they needed to use a moisturizer every day because of their dry skin, while only 16% “disagreed” that their dry skin necessitated daily moisturizer application. With regard to moisturizing cleanser needs, 97% of the participants stated that they want more moisturization from their personal cleansing product. The needs fell into three groups that aligned with self-perceived body skin type. Women in one group (very dry skin, 32% of the population) want a body wash product that delivers a high level of moisturization and a substantial skin feel; women in a second group (dry skin, 35% of the population) want a body wash product that delivers a moderate level of moisturization and a somewhat perceivable skin feel; and women in a third group (combination skin, 22% of the population) want a body wash that provides a low level of moisturization, rapid absorption of the moisturizing agent, and no residual skin feel. This study is just one example of work conducted to understand female consumers’ needs and expectations with regard to dry skin and moisturization. Traditionally, the needs and expectations of their male counterparts were at best little studied and poorly understood, or at worst assumed to be the same as those of females. To gain insights into male consumers’ needs we conducted a habits and practices study among an adult panel representative of the US adult population comprising 303 males and 313 females. As in the study above, participants responded to a series of questions related to attitudes towards body skin condition, body skin care habits and practices, and attitudes towards various cosmetic interventions. This consumer research showed a strong contrast between the sexes in terms of their usage of products to care for their body skin. Males were on the whole less likely to use a treatment on their body than were females. However, dry skin ranked high on the list of body skin care needs for both sexes. Moisturizer application was identified as the best treatment for dry skin, but males were less likely to apply moisturizer to their bodies than were females because of a perceived time constraint. Skin-feel parameters were also more important to males than females; males wanted to feel clean, not sticky or greasy. Surprisingly, the study results indicate that males are more likely to seek help from a dermatologist for their dry skin than females.

Moisturization from body washes Dry skin on the body is a finding in many dermatologic conditions and the results presented in the previous section show that even in the absence of frank skin disease dry skin ranks as one of the most common body skin complaints for both sexes. Skin that is dry can itch, and flaking on “problem” areas such as legs, knees, and elbows is aesthetically unpleasing and can negatively impact self-confidence. Dry skin worsens with age, and low relative humidity, certain medications, and excessive hot water exposure are among the factors that can exacerbate dry skin. Personal cleansing products are also frequently cited as agents that cause or worsen dry skin via removal of essential skin lipids following excessive cleansing or cleansing with “harsh” surfactants. Dry skin signals that there is an insufficient level of moisture in the stratum corneum. Dermatologists often recommend application of leave-on moisturizers to relieve symptoms and to provide an environment in which the skin can repair stratum corneum damage associated with dry skin. However, surveys show that a high percentage of dermatologists believe that their (female) patients do not moisturize as recommended, a lack of convenience being cited as the primary reason for the perceived non-compliance. This pattern is consistent with the results found in our consumer habits and practices research. Coupling moisturization with an existing habit such as showering can improve compliance but, as noted earlier, there are different ways to define a moisturization or dry skin improvement benefit, and simply including a moisturizing ingredient in a body wash formula does not guarantee that it will deposit on skin or remain in a sufficient amount after rinsing to provide a benefit. We conducted a leg wash clinical study using the industry standard method (leg controlled application test) comparing the dry skin improvement efficacy of a water control and three marketed moisturizing body wash products [2]. Treatment sites on the legs were washed in a controlled manner once daily for 7 days with the randomly assigned treatments. Expert visual scores and instrumental measurements collected at baseline and study end were used to assess the change in dry skin condition produced by the treatments. Expert scoring shows a range of skin effects from these moisturizing products (Figure 11.1). Two of the body washes delivered significant (P < 0.05) improvement in dry skin relative to the water control, while one of the products had little effect on visible dry skin. Skin capacitance measurements showed the former body washes improved stratum corneum hydration (P < 0.05), while the latter reduced stratum corneum hydration relative to the control (P < 0.05), i.e. it dried the skin. Expert erythema scoring and transepidemal water loss (TEWL) showed a similar pattern; two of the body wash products improved skin condition relative to control, while the third significantly (P < 0.05) increased erythema and TEWL. This highlights the importance of





1.5 B

1.0 A



0 –0.5





Greater improvement

Visual dryness improvement (Mean change ± SEM)


Moisturizing body wash #1 Moisturizing body wash #2 Moisturizing body wash #3 Control Letters show P ≤ 0.05 groupings at each evaluation

3 hours post-wash

understanding how products that are labeled as “moisturizing” perform clinically whenever possible. Simply recommending that a patient should use a moisturizing body wash may not produce an optimal benefit, and the wrong product recommendation could actually worsen skin condition. The consumer research presented in the previous section also highlights the need for personal cleansing products that deliver different levels of moisturization and different use aesthetics. Many personal cleansers are available in versions that ostensibly are designed for different skin needs, but such products often involve relatively minor changes in formulation and performance. Body washes, because of the greater formulation flexibility they offer, provide an opportunity to develop product versions that offer different levels of performance to meet specific needs. For example, the habits and practices study conducted among females identified three primary consumer groups in terms of body skin moisturization and body wash performance needs. Various body wash products have been created that offer differences in moisturizer level and dry skin improvement benefit across versions in order to meet these needs.

Who will benefit from using body washes? The body wash is a relatively new-to-market personal cleanser form that will initially appeal to users with practical concerns or to users seeking experiential benefits such as better lather and in-use scent intensity, which are often greater than a bar can deliver. Where body washes really distinguish themselves from traditional bar forms, however, is in their ability to provide higher order skin benefits. As we have shown, some body washes can provide a marked skin moisturization benefit that can affect not only the quantity but also the morphology of dry skin flakes (Figure 11.2). A large segment of the population can benefit from using this type of personal cleansing product. However, the following are two examples of conditions that may derive a particular benefit from a moisturizing body wash.


Figure 11.1 Expert dryness scores after 7 days of once-daily washing with marketed body wash products. The results show marked differences in the products’ abilities to provide a dry skin improvement (i.e. a skin moisturization benefit).

Ashy skin African-Americans and other dark-skinned individuals frequently suffer from ashy skin, a condition in which the skin’s surface appears grayish or chalky as a result of excessive dryness. The condition is often exacerbated by soap bar use which is common among this population. Moisturizers or other oils can provide temporary relief but, as discussed earlier, convenience often limits willingness to use leave-on products. Petrolatum is an effective moisturizer but neat application to the skin is limited by both convenience and esthetics. However, a petrolatum-depositing body wash may circumvent these issues while still delivering a skin benefit. To test this hypothesis, we conducted a study among a group of 83 African-American females who normally applied a leave-on moisturizer to relieve their ashy skin [3]. Subjects used a randomly assigned syndet bar or a moisturizing petrolatum-depositing body wash product for daily home showering for a 4-week period. Endpoint evaluations showed that the body wash produced significantly greater dermatologist-scored dry skin improvement and subject satisfaction for items such as ashy skin improvement and reducing itchy/tight feeling. Perhaps most importantly, subjects assigned to the petrolatum-depositing body wash noted marked improvement in their level of satisfaction with the appearance of their leg skin, their level of confidence in letting others see their legs, and in feeling good about themselves because of the appearance of their leg skin (Figure 11.3). These results indicate that proper personal cleanser choice can not only improve the physical symptoms of dry skin but also impact how users feel about themselves.

Atopic dermatitis Atopic dermatitis is a chronically relapsing skin disorder that currently affects an estimated 10% of children and adults in the Western Hemisphere and whose incidence is growing worldwide. Symptoms include xerosis, skin hyperirritability, inflammation, and pruritus. Personal cleansing products are viewed as a triggering factor for atopic dermatitis and dermatologists frequently recommend that their patients avoid

11. Body washes Subject 17: Baseline

Subject 3: Baseline

Subject 13: Baseline

Subject 17: Endpoint

Subject 3: Endpoint

Subject 13: Endpoint


(b) Figure 11.2 Scanning electron microscope (SEM) photomicrographs of skin flakes adhering to tape strips taken from subjects’ legs before (a) and after (b) using a petrolatum-depositing body wash for 3 weeks. Baseline samples show numerous large, thick, dry skin flakes; endpoint samples show fewer and thinner flakes.

'I am satisfied with the appearance of my leg skin' 3


–1 –2

1 0 –1 –2




2 Mean rating (SEM)

P < 0.01

2 Mean rating (SEM)

Mean rating (SEM)


3 P < 0.01

P < 0.01



'Based on the appearance of my leg skin, I feel good about myself'

'I am confident in letting others see my legs'

1 Syndet bar Body wash

0 –1 –2






Figure 11.3 Responses to psychosocial questions answered by African-American subjects before and after using a syndet bar or petrolatum-depositing body wash for 4 weeks. Items were rated on a +3 (strongly agree) to −3 (strongly disagree) scale. Ratings were not significantly different at baseline (P ≥ 0.48); endpoint ratings given subjects assigned to use the body wash were significantly better than those given by subjects assigned to use the syndet bar (P < 0.01).




harsh cleansers. Therapy typically involves application of a prescription topical corticosteroid, using a mild cleanser for bathing or showering, and applying a moisturizer within 3 minutes of the bath or shower to seal in moisture [4]. The latter suggests that a moisturizing body wash may be ideally suited as a therapeutic adjunct in atopic dermatitis. We conducted two studies among subjects undergoing treatment for mild to moderate active atopic dermatitis to examine the effect of using a moisturizing petrolatumdepositing body wash for cleansing. In both studies a moisturizing syndet bar, which is often recommended to patients undergoing therapy, was used as a control. In one study both cleansers were paired with 0.1% triamcinolone acetonide cream. Subjects applied the topical corticosteroid as directed and used their assigned personal cleanser for daily showering. After 4 weeks SCORAD for subjects who used the moisturizing body wash was significantly (P < 0.01) lower than for subject who used the bar. Subjects using the body wash also noted significantly (P < 0.01) greater improvement in skin dryness and itching. The second study again involved subjects with mild to moderate active atopic dermatitis, but in this case subjects assigned to use the petrolatum-containing moisturizing body wash were prescribed a medium potency topical corticosteroid, while subjects assigned to use the moisturizing syndet bar were prescribed a standard high potency topical corticosteroid [5]. At study end the dermatologist investigator judged that subjects assigned to cleanse with the petrolatum-containing moisturizing body wash showed a significantly (P < 0.01) greater incidence of disease clearing than did subjects who used the syndet bar. The greater therapeutic response observed in the body wash group is important, but so is the fact that it was achieved using a lower potency topical corticosteroid, which can potentially reduce cost and the risk of steroid-related side effects. Subjects in the moisturizing body wash group also rated their skin condition better for a number of parameters related to their atopic condition. The results from both these


studies indicate that therapeutic response in atopic dermatitis is influenced by personal cleanser choice and again highlight the importance of personal cleansing product choice when treating skin disease.

Conclusions Body washes represent a new possibility in personal cleansing products, not only because of their ability to provide effective cleansing and deliver an improved in-use experience (e.g. lather amount, rinse feel, scent display) compared with bar cleanser forms, but also because they have a potential to improve skin condition by mitigating dry skin. Moisturizing body washes are in a position to meet a key consumer need for both men and women – dry skin improvement on the body. However, delivering a skin benefit from a rinse-off product is challenging and the product must leave an effective amount of benefit agent on the skin after washing and rinsing. Not surprisingly, moisturizing body washes vary widely in their ability to deliver a benefit and recommenders must understand these differences when evaluating moisturizing body wash products.

References 1 Bechor R, Zlotogorski A, Dikstein S. (1988) Effect of soaps and detergents on the pH and casual lipid levels of the skin surface. J Appl Cosmetol 6, 123–8. 2 Ertel KD, Neumann PB, Hartwig PM, Rains GY, Keswick BH. (1999) Leg wash protocol to assess the skin mositurization potential of personal cleansing products. Int J Cosmet Sci 21, 383–97. 3 Grimes PE. (2001) Double-blind study of a body wash containing petrolatum for relief of ashy, dry skin in African American women. Cosmet Dermatol 14, 25–7. 4 Hanifin J, Chan SC. (1996) Diagnosis and treatment of atopic dermatitis. Dermatol Ther 1, 9–18. 5 Draelos ZD, Ertel K, Hartwig P, Rains G. (2004) The effect of two skin cleansing systems on moderate xerotic eczema. J Am Acad Dermatol 50, 883–8.

Chapter 12: Facial cleansers and cleansing cloths Erik Hasenoehrl Procter & Gamble Co., Ivorydale Technical Center, Cincinnati, OH, USA

BAS I C CONCEPTS • The four goals of facial cleansing are: (1) to clean skin, removing surface dirt and all make-up; (2) to provide a basic level of exfoliation; (3) to remove potentially harmful microorganisms (bacteria); and (4) to cause minimal damage to the epidermis and stratum corneum. • Cleansing can occur by three means: (1) cleansing by chemistry; (2) cleansing by physical action; and (3) in many cases, cleansing by a combination of both chemistry and physical action. • Chemical cleansing occurs via surfactants categorized into four primary groups: cationic, anionic, amphoteric, and non-ionic. • Facial cleansers can be categorized as follows: lathering cleansers, emollient cleansers, milks, scrubs, toners, dry lathering cleansing cloths, and wet cleansing cloths.

Introduction Facial cleansing is not only a means to remove dead skin, dirt, sebaceous oil, and cosmetics, but also a first step in an overall skincare routine, preparing skin for moisturizers and other treatments. Facial cleansing also has an important role, well beyond skincare, in psychological well-being, helping to provide a ritualistic sense of renewal and rejuvenation [1]. Many cleansing technologies – ranging from water to a traditional bar of soap – are available to meet the facial cleansing needs of different skin types and soil loads. This chapter provides an overview of the many specialty facial cleanser technologies available, discusses technologies best suited to each skin type and cleansing need, and provides an in-depth understanding of substrate-based facial cleansers, which represent the newest technology available for facial cleansing.

History Facial cleansing is observed in the animal kingdom and existed well before hom*o sapiens inhabited Earth. Early facial cleansing consisted primarily of a quick splash or rinse of the face with cold water. In fact, this habit can still be observed in the animal kingdom today among many primates [2].

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

The first recorded use of facial cleansing utilizing more than water was among the Ancient Egyptians in 10 000 BC [3]. Egyptians were heavy users of makeups made from a base of metallic ores which contained natural dyes for color; this mixture was then painted onto the face. In this period, Early Egyptians typically bathed and removed makeup in a river. Their cleansers consisted of animal fat mixed with lime and perfume, and were similar to some of the homemade natural soaps in use today. Facial cleansing and body cleansing were done with the same soap. More recently, over the past 20 years, specialty facial cleansers have become quite mainstream, a result of an explosion in cleansing technology which has led to a multitude of high-quality, relatively low-cost cleansers. Most of the technical development have focused on three primary areas: 1 Better removal of exfoliated skin, dirt, soil, excess sebaceous oil, and makeup; 2 Synthetic surfactants that induce less skin barrier damage and are thus less likely to dry skin; and 3 Incorporation of cleansing chemistry onto cleansing cloths. Patients tend to take more care with cleaning and maintaining their face than the rest of their bodies. As such, consumer product companies have developed many different technologies and cleansing forms that benefit different facial skin types, cleansing rituals, and soil loads. Because there is such a broad array of cleansing forms, specialty facial cleansers has become a very fragmented category of products, which utilize more different technologies than most other cleaning applications. Although a wide range of products is available, these products share four common traits:




1 To clean skin (removing surface dirt and all make-up); 2 To provide a basic level of exfoliation; 3 To remove potentially harmful microorganisms (bacteria); and 4 To cause minimal damage to the epidermis and stratum corneum. Additionally, facial cleansers are required to remove a myriad of chemicals and biologic materials, ranging from the latest waterproof makeup to excess skin oils and upper layers of stratum corneum.

Function It is well understood that the use of harsh surfactants and/ or overwashing skin can result in overremoval or distortion of stratum corneum and intercellular lipids, which can lead to reduced skin barrier function [4]. While the wide array of facial cleanser technologies all provide basic levels of skin cleansing, they all clean skin slightly differently. The mechanisms by which cleansing is accomplished can be grouped into three main categories: 1 Cleansing by chemistry; 2 Cleansing by physical action; and 3 In many cases, cleansing by a combination of both chemistry and physical action.

Chemistry of cleansing Two classes of chemicals are used in facial cleansers and are responsible for the cleaning effect: surfactants and solvents. Both of these types of chemicals interact with dirt, soil, and skin to remove unwanted material. Surfactants and solvents work via two different chemical mechanisms to effect removal of these materials. Understanding these mechanistic differences provides dermatologists with the insight needed to prescribe a cleansing regimen based on individual patient needs.

Surfactants Surfactants or “surface acting agents” are usually organic compounds that are amphiphilic, meaning they contain both hydrophilic groups and hydrophobic groups. The combination of both hydrophilic and hydrophobic groups uniquely makes surfactants soluble in both oil and water. Surfactants work by reducing the interfacial tension (the energy that keeps water and oil separated) between oil and water by being adsorbed at the oil–water interface. Once adsorbed at the interface, cleaning surfactants assemble into a low-energy aggregate called a micelle. Surfactant needs to be present at high enough concentration to form a micelle, a level called the critical micelle concentration (CMC), which is also the minimum surfactant concentration required to clean sebaceous oil, cosmetics, etc. When micelles form


in water, their tails form a core that encapsulates an oil droplet, and their (ionic/polar) heads form an outer shell that maintains contact with water. This process is called emulsification. Surfactants clean skin by emulsifying oily components on the surface of skin with water. Once emulsified, the oil can be easily rinsed from skin during the post wash or rinse process. The stronger the surfactant, the more hydrophobic material removed, the greater the potential skin damage from excessive removal of naturally occurring skin lipids, and the greater the ensuing compromise of optimal skin barrier function, therefore correct and careful formulation of these surfactants is required to ensure proper mildness. Recently marketed products show that with careful formulation very strong surfactants such as sodium laurel sulfate (SLS) can be well tolerated by skin. All surfactant-based cleansers require water and generally include a rinsing step. They are best suited to removal of oily residue. Unfortunately, two problems have been associated with cleansing with surfactants (one real and one largely folklore). First, because of their powerful cleansing action, overuse may completely eliminate the protective lipid barrier on the surface of skin, resulting in irritation and dryness. Second, for years consumers have heard negative stories regarding the alkaline (pH around 9) nature of these products. Wrongly assuming that because skin pH is about 5, washing with these high pH surfactants can lead to an increase in skin pH. Recent data suggest that the skin’s natural buffering capacity is more than adequate to eliminate any unwarranted impact of the pH of these products. Classic surfactants used in facial cleansers are categorized into four primary groups: cationic, anionic, amphoteric, and non-ionic. 1 Cationic surfactants used alone are generally poorly tolerated, and are now rarely used in skincare products without carful formulation into coaceravate systems. 2 Anionic surfactants, such as linear alkyl sulfates, consist of molecules with a negatively charged “head” and a long hydrophobic “tail.” Anionic surfactants are widely used because of their good lathering and detergent properties. 3 Amphoteric surfactants, such as the betaines and alkylamino acids, are well tolerated, lather well, and are used in facial cleansers. 4 Non-ionic surfactants, such as polyglucosides, consist of overall uncharged molecules. They are very mild (tolerated better than anionic, cationic surfactants on skin), but do not lather particularly well. Some surfactants are harsh to the skin while others are very mild. Because of the wide variety of available surfactants, not all surfactant-based cleansers are the same. It is important for patients to use products that best fit their skin type. Today, most cleansers use synthetic surfactants.

12. Facial cleansers and cleansing cloths

Solvents A solvent is a liquid that dissolves a solid or another liquid into a hom*ogeneous solution. Solvent-based systems clean skin by dissolving natural sebaceous oil and external oils applied to skin via cosmetics and similar materials. Solvents work under the chemical premise that “like dissolves like.” Solvents can be classified broadly into two categories: polar and non-polar. Typical non-polar solvents used in facial cleansing, such as mineral oil or petrolatum, are from the oil family, whereas typical polar solvents used in cleansing, such as isopropyl alcohol and ethanol, are from the alcohol family. Solvent-based cleansers are usually not used in conjunction with water; rather, they are applied and then “wiped” off with a tissue or cotton ball. Solvent-based cleansers should be chosen carefully on the basis of cleansing need. Non-polar solvents work well for removing oil-based makeups and cosmetics but have little effect on water-based formulations. Similarly, alcohol-based systems work well on water-based makeups. It is also important to note that alcohol-based systems can dry skin, a benefit for younger consumers with acne-prone skin but a potential disadvantage for older consumers and those with dry skin. However, oil-based products can leave a greasy or oily residue, which is beneficial for consumers with dry skin, but undesirable for those with normal to oily skin types. Choosing a solvent-based cleanser based on skin type is critical.

Physical cleaning An alternative to chemical cleansing is physical cleaning of skin. Essentially, physics, primarily in the form of friction, has an important role in cleansing. In facial cleansing, friction is generated primarily by the direct interaction of a washcloth, tissue, cotton ball, or cleansing cloth and the surface of skin. Friction works to help dislodge soils, as well as increase the interaction of chemical cleaning agents (surfactants and solvents) with soils. The role of friction is covered in more detail in the section on substrate cleansers.

Types of facial cleansers Seven primary and popular forms of facial cleansers exist (other rarely used forms exist but are not covered in this chapter). These cleansers can be categorized as follows: lathering cleansers; emollient cleansers; milks; scrubs; toners; dry lathering cleansing cloths and wet cleansing cloths. Each form is described in detail below. A summary of cleansers, technologies, and uses can be seen in Table 12.1.

Lathering cleansers While lathering cleansers constitute one broad classification, they all have one unique characteristic that separates them

from all other cleansing forms – they all generate lather when used in the cleansing process. Typically, these cleansers are formulated with a surfactant level greater than the CMC such that excess surfactant can incorporate air and form lather. Additionally, these cleaners contain surfactants that have short hydrophobic chains; shorter chains enable faster and higher levels of lather. Most lathering cleansers sold today utilize synthetic surfactants that have been especially designed to be mild to skin. These synthetic surfactants have little interaction with skin lipids and therefore produce substantially less skin damage than naturally derived surfactants. However, this quality also compromises to a small extent their capability to remove oil-soluble makeups. Many classes of surfactants are used in facial cleansers; two common ones include sarcosinates and betaines [5]. Even formulations with newer surfactants tend to exhibit some skin barrier damage in clinical studies. Thus, lathering cleansers are generally warranted for patients with normal to oily skin or those who are removing a high cosmetic load (makeup, lipstick, or other cosmetic load). Interestingly, there is a strong consumer bias towards lathering cleansers because high levels of lather provide a very strong signal to consumers that the cleanser is working. Lathering cleansers clean through the chemical process of emulsification, this simply means that the cleanser emulsifies dirt and oils, by suspending or emulsifying materials, thus permitting them to be removed from skin during the rinse process. Many formulators of lathering cleanser products have tried to incorporate skin conditioning technologies that enable deposition of skin conditioners onto skin. Unfortunately, these technologies have generally been less successful at providing skin benefit ingredients than other cleansing forms.

Emollient cleansers Emollient cleansers are a milder alternative to lather cleansers. Although they clean via emulsification, they do not form lather in the presence of water. Surprisingly, however, they do form a structure that suspends dirt and makeup within formulation. Typically, these cleansers provide a very high level of soil removal without drying the skin to the same degree as lathering cleansers. Emollient cleansers generally consist of a special formulation of lathering surfactants in which either lathering is suppressed by an oil (e.g. mineral oil) or the surfactant forms a complex with another charged molecule to inhibit the formation of the air–water interface necessary to provide lather. Clinically, emollient cleansers are generally less harsh on skin than lathering cleansers. However, consumers sometimes complain that emollient cleansers leave a residual film on skin that does not satisfy some cleansing expectations. Typically, these cleansers are best suited to those patients with high cleansing needs who also have dry skin.




Scrubs Facial scrubs are a subset of emollient cleansers. They generally contain small particles of natural or polymeric ingredients. Scrubs are intended to provide a deep cleansing experience including a higher level of skin exfoliation from abrasion with the particles. A non-exhaustive list of natural scrub particles includes seeds of many fruits (e.g. peach, apple, apricot), nut shells (e.g. almond, walnut), grains (e.g. oats, wheat), and sandlewood. Synthetic scrub particles include polyethylene or polypropylene beads. Because of their abrasive nature, patients with sensitive skin may not want to use these as their daily use cleanser; for those with sensitive skin they should be used once or twice a week in addition to normal cleansing routines.

Cleansing milks Milks are a form of cleaner that is generally not used in conjunction with water. Because they are not used in conjunction with a water rinse, cleansing milks are ideal for depositing beneficial agents, such as humectants, petrolatum, vitamins, and desquamatory ingredients, onto the skin. These cleansers are a good choice for cleaning dry or other diseased skin. One drawback is that the residual ingredients left on skin can make skin feel as though cleansing is incomplete. Milks work by dissolving, as opposed to emulsifying, oils and dirt. Typically, they are applied like a lotion and then wiped off with a tissue, cotton ball, or towel.

Toners Toners are a class of facial cleansers formulated to clean skin and shrink pores. This class of cleanser utilizes solvency as the primary mode of cleaning. Toners are usually applied with a physical substrate, such as cotton balls, tissues, or wash cloths; however, some newer toners can be sprayed on and wiped off. In most cases, toners are used in the absence of water. Toner formulations generally utilize alcohol as the solvent of choice and some level of humectants. Toners usually exist in three strengths: 1 Mild: 0–10% alcohol, refresher; 2 Medium: 10–20% alcohol, tonic; and 3 Strong: 20–60% alcohol, astringent. More recently, some companies have developed two-phase toners, which consist of a solvent and an immiscible oil formulated to provide astringent benefits while minimizing the dry skin feeling. Typical uses of toners are makeup removal and pore cleaning associated with acne care. Toners are popular with teenagers and young adults because of the perceived acne benefits and pore tightening associated with this technology.

Substrate cleansers Over the years, facial cleansers have evolved from traditional bar soaps, to milder synthetic detergents, and, most recently, to cleansing cloths (disposable substrates such as a


non-woven material) pretreated with active cleansing and conditioning ingredients. Introduced in the early 2000s, substrate-based cleansers are a relatively new addition to the cleansing technologies available to dermatologists and consumers. These cleansers combine low levels of mild detergents with conditioning ingredients to provide state-of-the-art cleansing and exfoliation with unprecedented mildness [6]. Further, cleansing cloths can be designed to meet the specific needs of different skin types. The substrates used in cleansing cloths generally consist of natural fibers (e.g. cotton); synthetic fibers (e.g. rayon, polyester terphalate [PET] or polypropylene); or a blend of one or more of these fibers. Depending upon the fibers used and the non-woven manufacturing process, the substrate texture can be tailored to meet differing expectations from very soft to rough, meaning that different exfoliation levels can be delivered to the consumer. Technology introduced in 2007 further improves exfoliation and cleansing capabilities by printing a polymer on the surface of a non-woven cloth. The mechanism by which cleansing is accomplished with a cloth is different from that with the liquid cleansers described above. In the case of substrate cleansers, cleaning is driven by a combination of physics (friction from interaction with cloth and skin) and chemistry (either emulsification or dissolution). This combined action offers several key advantages for product formulation and use. Because of the form itself, the cloth can contain a low level of surfactants. Further, utilizing multiple cleansing mechanisms allows formulators the flexibility to customize formulations that contain smaller amounts of chemical ingredients. As a result, substrate-based cleansers can be formulated with as little as 25% of the surfactant used in traditional liquid cleansers (P&G Beauty, Cincinnati, OH, USA, Comparison of surfactant level in Olay Foaming Face Wash, and Olay Daily Facials; unpublished data). For the patient, use of products with combined cleaning mechanisms results in much cleaner skin. Also, lower surfactant levels translate to less skin damage. (True when directly comparing skin damage versus surfactant level of identical surfactants. Surfactant type alone has a large impact on skin damage and must be considered as well as surfactant level when recommending a cleanser.) Another key trait of substrate cleansing cloths is that dirt, makeup, and oil are picked up by and contained within the cloth. The visible dirt and oils on the cloth provide a subtle clue to patients that the cleansing step is complete, reducing overcleansing, another contributor to skin damage. Despite the low level of surfactants in substrate cleansers, these products can still generate a generous lather via the cloth structure, which incorporates air as the lather is generated. The low levels of mild detergent combined with the ability to deposit conditioning agents directly onto the skin result in improvement in the skin’s overall condition beyond

12. Facial cleansers and cleansing cloths basic cleansing. Finally, the different cloth textures allow individualized, but gentle, exfoliation which removes skin flakes for a more even skin surface. This combination of benefits can eliminate the need for other specialty cleansing products such as toners and exfoliators. Two popular forms of substrate-based cleansers exist today: 1 Dry cleansing cloths; and 2 Wet cleansing cloths. The mechanism by which cleansing is accomplished with a cloth is different from that with the liquid cleansers described above. In the case of substrate cleansers, cleaning is driven by a combination of chemistry (either emulsification or dissolution) and physics (friction from interaction with cloth and skin). This combined action offers several key advantages for product formulation and use. Utilizing multiple cleansing mechanisms allows formulators the flexibility to customize formulations that contain lower levels of chemical ingredients. As a result, substrate-based cleansers can be formulated with as little as 25% of the surfactant used in traditional liquid cleansers [7]. For the patient, use of products with combined cleaning mechanisms results in much cleaner skin. Also, lower surfactant levels translate to less skin damage. Another key trait of substrate cleansing cloths is that dirt, makeup, and oil are picked up by and contained within the cloth. The visible dirt and oils on the cloth provide a subtle clue to patients that the cleansing step is complete, reducing overcleansing, another contributor to skin damage.

Daily Facials is one example in which the cleansing surfactant, skin conditioner, and fragrance are applied separately and to different zones of a cloth. This permits the product to deposit conditioning ingredients directly onto skin during the washing procedure, thus delivering unprecedented conditioning benefits from a lathering cleanser. In fact, cleansing cloths are the only specialty cleansing technology that is proven to provide the cleanest skin and improve skin barrier function. Studies have shown that separate addition of petrolatum onto a cleansing cloth provided unparalleled hydration and transepidermal water loss (TEWL) benefits and resulted in a smoother skin surface, a more compact stratum corneum, and well-defined lipid bilayers at the surface of the stratum corneum [8].

Wet cleansing cloths Wet cleansing cloths are traditionally manufactured and shipped to the consumer in their wet state. They originated from disposable wipes technology that was initially developed for removal of excrement and other soils from babies during diaper changes. Wet cloths are used without additional water in both the cleaning and rinsing (wiping off) rituals. Wet cloths are generally of the non-lathering variety and as such can be used as a “wipe-off” product, as opposed to being rinsed with water. The advantage of wet cloths is that small amounts of beneficial ingredients, such as humectants and lipids, are left behind on the skin. This property makes wet wipes one of the most effective cleansing products for patients with dry skin.

Dry lathering cleansing cloths In early 2000, the advent of daily cleansing cloths ushered in the next generation of facial cleansers. Dry cleansing cloths consist of lathering surfactants that have been incorporated in the manufacturing process onto a disposable wash cloth. The patient is instructed to wet the cloth at the sink with warm water and rub to generate lather. Therefore, these products provide a rich, creamy lather like one would find in the lathering cleansers described earlier. Additionally, many of these products contain and deposit on to stratum corneum moisturizing ingredients such as petrolatum and glycerin. These products became an instant success because they combine multiple skin care benefits into one product: 1 High level of cleansing; 2 High level of exfoliation; 3 Minimal reduction in skin barrier function; 4 Rich lather; and 5 In the case of at least one product, significant moisturization [6]. A unique advantage of dry cleansing cloth technology is that the product can be manufactured so that different ingredients can be placed in different “zones” on a cloth. This simple approach enables skilled formulators to use ingredients that are not compatible in a liquid cleanser. Olay

Guide to selecting facial cleansers Recommending a facial cleansing regimen can be a daunting task given the multitude of cleansing forms available. To choose the most appropriate cleanser, physicians should consider skin type, skin problems, and any skin allergies. The following section provides a short reference guide and tools to help in selection of cleansers based on patient skin type, cleansing need, and preference. The selection guide is broken into three parts or strategies: 1 Selection based on skin type; 2 Selection based on cleansing form; and 3 Selection based on skin problems.

Selection based on skin type The first step in selecting a facial cleanser is to assess the patient’s skin type and to categorize it as dry, oily, or normal. Once skin type has been determined, assess the skin for any problems, such as acne, excessive flakiness, and dryness. Table 12.1 systematically lists the main facial cleansers covered in this chapter, and highlights the key characteristics of each cleanser and the best cleanser for each skin type.




Table 12.1 Cleanser technology and skin types. Type of facial cleanser

Primary cleaning mechanism

Key characteristics

Primary recommended skin type

Liquid lathering cleansers


Forms lather when wet


Emollient cleansers






Non-lathering, particulates provide exfoliation benefit

Dry, flakey



High conditioning, generally not used with water

Dry skin



Low viscosity liquid, pore tightening

Oily/young Acne prone

Dry cleansing cloths

Emulsification and physical removal

Provides multiple benefits: cleansing, conditioning, exfoliating, toning

All skin types

Wet cleansing cloths

Dissolution and physical removal

Provides multiple benefits: cleansing, conditioning, exfoliating, toning. Generally not used with water

Dry skin

Cleansing (sebaceous oil)


Cleanser form

Dry cleansing cloth


Toner Wet cleansing cloth Milk Milk

Toner Lathering (alcohol-based) cleanser Dry wipe Wet wipe




Figure 12.2 Products for the removal of excess sebaceous oil.

No substrate

Emollient Scrub Lathering Lathering

Non lathering

Figure 12.1 One of the main cleansing ritual preferences: no substrate/ substrate and lathering/non-lathering.

Selection based on cleanser form or cleansing ritual The second strategy for selecting facial cleansers is to first assess a patient’s cleansing ritual preference. Figure 12.1 depicts one of the main cleansing ritual preferences: no substrate/substrate and lathering/non-lathering. To use this approach most effectively, first, identify the quadrant of Figure 12.1 that best describes the patient’s ritual preference, and then use Table 12.1 to select a facial cleanser that best matches the patient’s skin type. This may be the best


approach to selecting a cleanser is when compliance with skincare is critical.

Selection based on skin problems In many cases, cleanser selection may be somewhat subjective. The following figures provide a hierarchy of the primary benefits associated with facial cleansers ranked by cleanser type. The benefits described in this section are cleaning excess sebaceous oil, cleaning dirt and makeup loads, exfoliation, and mildness to skin. Considering these benefits when prescribing a cleansing routine may prove useful in providing a cleanser that fully meets patient expectation and needs.

Cleaning excess sebaceous oil Removal of excess sebaceous oil is a significant concern of teens and young adults. Cleansing of sebaceous oil is best accomplished with either lathering products that emulsify the oils or toners that are specifically formulated to solubilize sebaceous oil. These products and can also give users a sense of control over oily skin by providing pore tightening benefits (Figure 12.2).

12. Facial cleansers and cleansing cloths

Cleaning dirt and makeup One of the primary benefits of a facial cleanser is removal of high makeup loads and dirt. By a wide margin, dirt and makeup removal is best performed by substrate cleansers. The high cleansing capability of these cleansers is brought about by their capability to provide both physical and chemical cleaning, in addition to the substrates’ ability to trap and hold dirt and oil within their fibers (Figure 12.3).

Exfoliation: removing dry, dead skin cells When high exfoliation is required, because of aging or for other reasons, products that provide physical cleansing are an appropriate choice because they also provide the highest level of exfoliation. Exfoliation is brought about by physical abrasion, which removes the top layers of skin. As a side note, most cleansers provide low to insignificant levels of exfoliation; thus, if exfoliation is the main skin need, a substrate-based cleanser is highly recommended (Figure 12.4).

Cleanser mildness For much of facial cleansing history, cleanser mildness was a significant concern. Now, with new surfactant and cleansing technologies, most specialty facial cleansers (with the exception of toners) provide close to neutral or better mildness. Figure 12.5 ranks cleansing forms for skin for patients for whom dry skin is a key complaint.

Cleansing (makeup) Toner (for nonwaterproof makeup)




Lathering cleanser

Dry wipe Wet wipe



Figure 12.3 Products for the removal of dirt and makeup.

Exfoliation Milk

Lathering cleanser

Wet wipe Scrub

Dry wipe

Emollient Toner Low


Figure 12.4 Products for the removal of dry, dead skin cells.

Mildness/conditioning Dry wipe

Toner Scrub


Wet wipe

Lathering cleanser Milk Low


Figure 12.5 Products for patients for whom dry skin is a key complaint.


Conclusions Many different facial cleansing forms exist today. All can be categorized on the basis of three factors: 1 The type of chemistry used, either surfactant or solvent based; 2 Whether or not the cleansing form creates lather; and 3 Whether or not the cleansing form incorporates physical cleansing as well as chemical cleansing. All of these facial cleansing forms provide the basic level of cleansing required to maintain healthy skin; however, different skin types benefit from different cleansing forms, and patient preference drives usage and compliance. The future of the facial cleansing category is bright. Significant innovation is expected to continue for the foreseeable future, particularly in substrate cleanser applications and formulations for removing the new and more durable makeups and mascaras that are entering the market. Technical development will continue to focus on low damage to skin and improved delivery of specially directed skin ingredients during the cleansing process.

1 Zhong C-B, Liljenquist K. (2006) Washing away your sins: threatened morality and physical cleansing. Science 313(5792), 1451–2. 2 Bolles RC. (1960) Grooming behavior in the rat. J Comp Physiol Psychol 53, 306–10. 3 Nicholson PT, Shaw I. (2000) Ancient Egyptian Materials and Technology. Cambridge UK: Cambridge University Press. 4 Ananthapadmanabhan KP, Moore DJ, Subramanyan K, Misra M, Meyer F. (2004) Cleansing without compromise: the impact of cleansers on the skin barrier and the technology of mild cleansing. Dermatol Ther 17, 16–25. 5 Paye M, Barel AO, Howard I. (2006) Handbook of Cosmetic Science and Technology, 2nd edn. Informa Health Care. 6 Kinderdine S, et al. (2004) The evolution of facial cleansing: substrate cleansers provide mildness benefits of leading soap and syndet. P&G Beauty Science poster presentation, 62nd Annual Meeting of the American Academy of Dermatology, February 6–11, 2004. 7 McAtee D, et al. (2001) US patent 6280757 8-28-2001 8 Coffindaffer T, et al. (2004) Assessment of leading facial skin cleansers by microscopic evaluation of the stratum corneum. P&G Beauty Science poster presentation, 62nd Annual Meeting of the American Academy of Dermatology, February 6–11, 2004.


Chapter 13: Non-foaming and low-foaming cleansers Duncan Aust DFB Branded Pharmaceuticals, Fort Worth, TX, USA

BAS I C CONCE P T S • Effective cleansing can be achieved without foam production. • Non-foaming and low-foaming cleansers are appropriate for all skin types. • Mild surfactants are key to minimizing barrier damage. • Non-foaming and low-foaming cleansers are typically water-based.

Introduction The effective and appropriate use of a suitable skincare regimen is critical to maintaining healthy skin. This cleansing regimen becomes more important in dermatologic disease, where an inappropriate skin care regimen can impede positive treatment outcomes [1]. Cleansing is the first step in managing any dermatologic disease and the right choice of cleanser can have a considerable impact on treatment success. The earliest cleansers were used by the Babylonians around 2200 BC. The Egyptians subsequently combined animal and vegetable oils with alkaline salts to create soaplike substances. Cleansers then evolved to contain salts of fatty acids derived by reacting fat with lye in a process known as saponification, which marked the beginning of currently available foaming soap-based cleansing systems. Non-foaming cleansers were developed in the 2nd century in the form of cold creams and milks. The Greek physician Galen is considered the father of cold cream, because he combined olive oil, beeswax, water, and rose petals. More modern formulations also add borax. There are now many different classes of cleansers; however, this chapter focuses on non-foaming and low-foaming cleansers. It outlines the different types of non-foaming cleansers and how they vary from their regular foaming, liquid, or bar counterparts. It also outlines the most logical choice of non-foaming or low-foaming cleansers for certain skin types and discusses the merits of various cleanser formats.

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


Types of non-foaming and low-foaming cleansers Many consumers mistakenly believe foaming or lathering is a requirement for effective cleansing. However, what is not broadly understood is the fact that, even in the absence of foaming, cleansing can still occur. This is the fundamental premise upon which non-foaming and low-foaming cleansers are based. There are two primary classes of non-foaming and lowfoaming cleansers: aqueous or water-based formulations, which may or may not require water for cleansing, and a second class of waterless cleansers. The majority of nonfoaming and low-foaming cleansers are water-based formulations containing several ingredients: water, surfactants, moisturizers, stabilizing agents, preservatives, fragrances, and dyes (Table 13.1). Key to the efficacy of these aqueousbased cleanser formulations are three primary ingredients; water, surfactants, and humectants.

Surfactants The most important ingredient in the majority of cleansing systems is the surfactant. A surfactant is a chemical that stabilizes mixtures of oil and water by reducing the surface tension at the interface between the oil and water molecules and enhances the formation of foam and its colloidal stability. Surfactants perform two functions in a cleanser. First, they stabilize the cleanser formulation by allowing the oil phase and water phase to coexist in a stable system. Without surfactants, it would be impossible create single-phase formulations. Second, and most importantly, surfactants are required to meet the performance requirements of the cleanser. Surfactants can generally be divided into five classes: anionic, amphoteric (zwitteronic), cationic, non-ionic, and

13. Non-foaming and low-foaming cleansers

Table 13.1 Types of non-foaming and low-foaming cleansers. Cleanser types

Physical forms

Key ingredients



Surfactants, water, foam boosters, humectants, preservatives Surfactants, waxes, binders, filers


Low foaming


Body washes

Surfactants, water, foam boosters, humectants, preservatives, dyes

Lotions Gels

Surfactants, water, humectants, preservatives Surfactants, water, humectants, preservatives


Surfactants, water, humectants, preservatives

Cold creams Waterless cleansers

Water, oil, wax, surfactants Solvent/alcohol, water, surfactant

Thin lotion/milks

Water, moisturizers, oils, surfactants, solvents, preservatives Oil, water, solvent/alcohol, dyes

Two phase

polymeric surfactants. The anionics are characterized by their good foaming and cleansing abilities, but can be too irritating for the skin. As a result, anionics are combined with milder surfactants or conditioning agents. Non-ionics and polymerics tend to be the mildest surfactants and are used in “gentle” cleansing systems. Traditional cationics can be irritating, but new classes have been introduced, rivaling the performance of the non-ionics. The final class, amphoterics, are also mild but this property can differ with pH. Over the last 40+ years, there has been an effort to develop “gentler acting” surfactants, hence the large number of nonionic surfactants currently available. The non-ionic surfactants are the basis for a new group of low-foaming, reduced irritation cleansers and may be combined with the polymeric or amphoteric classes. Examples of mild surfactants and surfactants with low irritation include sulfoacetates, acyl sarcosinates, amphoproprionates, alkanolamides, alkylglucosides, and the original mild surfactant cocamidopropyl betaine.

Low foam production A major drawback of most mild synthetic surfactant systems is poor lather performance. Generally, the longer the carbon backbone of the surfactant, the less irritating the molecule. However, this mildness is often obtained at the expense of effective cleansing and lathering. In fact, many modern cleansers supplement their formulations with “foam boosters” simply to enhance the appearance of foam. These additional ingredients are not required for cleansing, have no cleansing properties, and are there solely to meet consumer expectations. A careful balance is required between mildness and lather.

Mildness The potential for irritation can be reduced by appropriately matching surfactants. For example, sodium lauryl sulfate (SLS), an anionic surfactant with a high index of irritation, has been shown to elicit less irritation when combined with sodium laureth sulfate (SLES) [2]. Balancing the level of surfactants in the formulation to ensure effective cleansing while not having a detrimental effect on skin barrier lipids and proteins is important. Other ingredients can be added to the cleanser formulations to mitigate any detrimental effects. Some of the milder cleansers contain humectants, such as glycerin, to attract water to the skin. Other humectants, such as butylene glycol or propylene glycol, have been used but are less favored than glycerin. Hyaluronic acid, which has the capacity to bind many times its own weight in water, is very expensive and seldom used. The use of humectants in low-foaming and non-foaming cleansers is now commonplace in high end products. In addition to humectants, other skin barrier building ingredients can be used. For example, ceramides and plant extracts with reported antioxidant, anti-irritant properties can be used. However, it is challenging to ensure that these ingredients are delivered to the skin in a cleanser that is rinsed away. Utilizing controlled or sustained release systems can increase ingredient delivery. One example of a controlled release delivery system employed in a cleanser system is the use of a multivesicular emulsion. This emulsion is composed of multilamellar particles, which allow for the sustained release of substances such as ceramides, glycerin, and hyaluronic acid [3]. The mildness of a cleanser is dependent upon many important factors, most notably the choice of other




Table 13.2 Principal cleanser types. Cleanser types



Skin type best suited


Gentle Non-drying Low levels of surfactants

Limited cleansing ability for oily types Limited rinsibility with cold creams Can leave behind residue

Dry to normal

Low foaming

Gentle Non-drying

Limited cleansing ability for oily types

Dry to normal

Easy to remove Low levels of surfactants Bar

Excellent cleansing ability

Can strip barrier of essential oils and lipids Drying Can raise pH of skin Primarily composed of anionic surfactants


Foaming liquid

Good cleansing ability Easy to remove

Can strip barrier of essential oils and lipids

Normal to oily

ingredients in the formulation and the product’s pH [4,5]. Two of the most irritating classes of ingredients used in formulations are fragrances and preservatives. Often the combination of fragrances and high levels of surfactants gives way to a high irritation index. Several studies have correlated a product’s poor performance in patch testing experiments to the combined effects of surfactants and allergens [6,7]. Because of these effects, mild cleanser products are fragrance free; however, preservatives remain a necessary part of the formulator’s arsenal to ensure the products remain free from microbial contamination.

waxes, sterols, monoglycerides, diglycerides, and phospholipids. Lipid-free cleansers have the advantage of not depositing any lipid-like materials on the skin surface. They balance their cleansing and moisturizing ability. In lipid-free cleansers, moisturization is performed by replacing sebum with synthetic oils along with the addition of humectants, such as glycerin. While good for normal to oily skin, lipid-free cleansers may not be the ideal choice for dry skin. Table 13.2 highlights the principal cleanser types: bar, foaming liquid, non-foaming, and low-foaming (regular and lipid free).

Waterless cleansers

Mechanisms of cleansing

Other means of skin cleansing not involving traditional surfactants is with the use of solvents to dissolve oils and sebum. These waterless facial cleansers are aqueous-based alcoholic preparations, typically containing diluted isopropyl alcohol and a small amount of surfactant. Sebum is soluble in alcohol and glycol-based solvents. These cleansers are convenient to use without access to water, and can be effective in patients with very oily skin; however, long-term usage may be harmful to the skin barrier. Other alternative cleansing systems include two-phase systems, where the oil and water–solvent phase do not mix in the formulation and remain as two distinct layers. These systems are mixed by shaking prior to use. They have the advantage of low surfactant concentrations but do not have broad consumer acceptability.

Lipid-free cleansers A new class of cleansers for normal to oily skin is referred to as a lipid-free cleanser. Lipids are defined broadly as fatsoluble, naturally occurring molecules, such as fats, oils,


In the case of the non-foaming cleansers, especially cold creams, the primary mode of action is dependent on the formulation’s ability to bind sebum, dirt, bacteria, and dead skin cells. Cold cream formulations are water-in-oil emulsions (W/O) where the external phase of the emulsion is the hydrophobic or oily component and the water is partitioned as small droplets in the internal phase. It is because of the external oil phase that cold creams bind well to sebum, dirt, and cosmetics with easy removal by wiping. Certain lighter lotions or milks also work along a similar principle, although they differ from cold creams because they are primarily oil-in-water (O/W) emulsions. Upon application to the skin surface, the oil phase droplets “seek out” sebum on the surface of the skin, entrapping it, and facilitating its removal with gentle wiping or water rinsing. These lighter lotions also differ from cold cream by containing some classic surfactants. The surfactants are used to maintain a stable emulsion with an internal oil phase and external aqueous phase, but do not provide any foaming

13. Non-foaming and low-foaming cleansers capability. These cleansers have limited cleansing ability and are not the most effective class of cleansers for oily skin, but work well on dry to normal skin.

Cleansing skin barrier damage The cutaneous effects of surfactants are dependent upon the type, duration of exposure, and concentration [8,9]. Many different surfactants affect the stratum corneum, or outer layer of the epidermis, causing dryness, damage to the barrier function of the skin, irritation, itching, and redness [10]. Surfactants interact with various components of the stratum corneum, including proteins and lipids. Interaction occurs with corneocytes or protein complexes made of threads of keratin, as well as with lipids. In the case of the corneocytes, the surfactants bind to these proteins allowing them to swell and making it possible for other ingredients in the formulation to penetrate into the lower layers of the skin where they can cause itching and irritation. The irritation properties of surfactants have been demonstrated to be related to the mechanisms by which surfactants interact with the stratum corneum [11]. As for lipids, the interaction of surfactants with lipids in the stratum corneum is still not fully understood. Surfactants may get between the lipid bilayers causing increased permeability and even disruption of the bilayer [12]. Surfactants can also cause damage to the lipid structures themselves. Surfactants reduce the amount of lipids in the skin and disrupt skin barrier function by removing these lipids as the cleanser is used. It is not always the surfactants themselves that result in irritation, but other ingredients contained in the formulations (e.g. fragrances and preservatives). The surfactant effect on barrier function opens a pathway for the damaging effects of other ingredients. Obviously, compromising the skin barrier is best avoided as a compromised barrier has been correlated with skin disease including, psoriasis, atopic dermatitis, and other ichthyoses [13].

Conclusions In conclusion, the advantages of non-foaming and lowfoaming cleansers are mildness. The disadvantages are

related to little foaming capability, but this should not be perceived by the consumer as representing ineffective cleansing. Cleansers that leave a “squeaky clean” feel to the skin surface and produce abundant foam may not be the best choice in patients with sensitive skin needs. Nonfoaming and low-foaming cleansers achieve a delicate balance between skin cleansing and tolerability.

References 1 Draelos ZD. (2005) Concepts in skin care maintenance. Cutis 76 (6 Suppl), 19–25. 2 Effendy I, Maibach HI. (1994) Surfactants and experienmental irritant contact dermatitis. Contact Dermatitis 33, 217. 3 Coria Laboratories, LTD. Products. Available from: URL:http:// Accessed September 2, 2008. 4 Ananthapadmanabhan KP, Moore DJ, Subramanyan K, Misra M, Meyer F. (2004) Cleansing without compromise: the impact of cleansers on the skin barrier and the technology of mild cleansing. Dermatol Ther 17 (Suppl 1), 16–25. 5 Kuehl BL, Fyfe KS, Shear NH. (2003) Cutaneous cleansers. Skin Therapy Lett 8, 1–4. 6 Agner T, Johansen JD, Overgaard L, Volund A, Basketter D, Menne T. (2002) Combined effects of irritants and allergens: synergistic effects of nickel and sodium lauryl sulphate in nickelsensitized individuals. Contact Dermatitis 47, 21–6. 7 Pedersen LK, Haslund P, Johansen JD, Held E, Volund A, Agner T. (2004) Influence of a detergent on skin response to methyldibromoglutaronitrile in sensitized individuals. Contact Dermatitis 50, 1–5. 8 Loffler H, Happle R. (2003) Profile of irritant patch testing with detergents: sodium lauryl sulfate, sodium laureth sulfate, and alkyl polyglucoside. Contact Dermatitis 48, 26–32. 9 Slotosch CM, Kampf G, Loffler H. (2007) Effects of disinfectants and detergents on skin irritation. Contact Dermatitis 57, 235–41. 10 Dykes P. (1998) Surfactants and the skin. Int J Cosmet Sci 20, 53–61. 11 Wilhelm KP, Cua BC, Wolff HW, Maibach HI. (1993) Surfactantinduced stratum corneum hydration in vivo: prediction of the irritation potential of anionic surfactants. J Invest Dermatol 101, 310–5. 12 Walters KA, Bialik W, Brain KR. (1993) The effects of surfactants on penetration across the skin. Int J Cosmet Sci 15, 260–70. 13 Marstein S, Jellum E, Eldjarn L. (1973) The concentration of pyroglutamic acid (2-pyrrolidone-5-carboxylic acid) in normal and psoriatic epidermis, determined on a microgram scale by gas chromatography. Clin Chim Acta 49, 389–95.


Chapter 14: Liquid hand cleansers and sanitizers Duane Charbonneau Procter & Gamble Co., Health Sciences Institute, Mason, OH, USA

BAS I C CONCE P T S • The hands are a common site for microbial contamination. • Hand cleansers and sanitizers are designed to reduce transient microbes on the skin surface with the intent of reducing the spread of infectious disease. • Hand cleansing products include liquid soaps with antimicrobial agents, alcohol-based hand sanitizers as well as non-alcoholbased hand sanitizers. • Hand hygiene technologies have decreased nosocomial infections. • Hands with damaged skin harbor more transient organisms than hands with healthy skin.

Introduction Hand washes and hand sanitizers are designed to reduce transient microbes on the skin with the intent of reducing the spread of infectious disease. This class of products includes liquid soaps; liquid soaps with antimicrobial agents, alcohol-based hand sanitizers as well as non-alcohol-based hand sanitizers. Over the past 20 years there has been an increasing concern regarding infectious disease within the community and hospital. In the USA, deaths from infectious disease are ranked sixth among all deaths according to statistics published by the Centers for Disease Control and Prevention. Nosocomial infections are one of the most frequent and severe complications of hospitalization. Nosocomial infections are the fourth leading cause of death in Canada and account for approximately 100 000 deaths annually in the USA [1,2]. These statistics are extremely sobering in light of all the advances made in modern medicine today. Several mitigating factors are responsible for the rising numbers of infection rates within the community as well as the hospital setting. First, is the changing nature and ranges of pathogens to which individuals within the community and hospital are exposed. Pathogens such as rotavirus, Campylobacter, Legionella, SARS, Escherichia coli O157 (E. coli), and norovirus were not commonplace prior to 1980. Additionally, methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile were largely considered hospital problems. Today, community-acquired MRSA

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


(CA-MRSA), norovirus, and new more virulent strains of C. difficile (02) are circulating within the general populous. Second, there are cultural changes that have a role in this increased infection burden, such as reduced hospital stays, in home care for elderly, ease of travel, and a large population of immunocompromised individuals. Third is the diminished research aimed at the identification of new antibiotics. It is no longer economically feasible for pharmaceutical companies to develop and register novel antibiotic technologies. This situation is further exacerbated by the increasing development of antibiotic resistance among common pathogenic microorganisms. With all of these issues, the mechanisms of dealing with infectious disease for the future must fall on prevention strategies in place of treatment regimes. Because hand contact has a crucial role in the transmission of infectious agents, it is imperative that consumers and hospitals have effective hand hygiene technologies.

Hand microbiota Microbes that inhabit the hand are generally divided into two categories: transient and resident flora (Figure 14.1). The transient flora is microbes that inadvertently become attached to the hands following touching of contaminated surfaces; for example, a raw food item, or, as in the case of healthcare workers, an infected wound or body fluid. Several studies have documented the potential of this transfer of transient flora from hands to other parts of the body within an individual or alternatively between individuals. The classic example is the work by Hendley and Gwaltney [3] which demonstrated the importance of hand-to-hand transmission of the common cold virus.

14. Liquid hand cleansers and sanitizers

Figure 14.1 The common flora of the hand. Transient flora are those microorganisms that are picked up from the environment. Resident flora are the microorganisms that routinely inhabit the skin.

Table 14.1 Constituents of the hand resident flora. Organism Acinetobacter baumannii Acinetobacter johnsonii Acinetobacter lwoffi Corynebacterium spp. Enterobacter agglomerans Enterobacter cloacae Klebsiella pneumoniae

microbes are as essential to the health of the skin as the gut microorganisms are to overall health of the individual [4]. The resident flora provides positive health benefits by inhibition of pathogens, immune modulation, and improving the integrity of the skin barrier. Although the resident skin flora usually has an essential role in protecting the host, under certain circ*mstances the resident flora can be pathogenic itself. For example, Staphylococcus epidermidis, an important member of the resident skin flora, is also a common pathogen associated with wound infections. Further, it is estimated that approximately 32% of the population carries the common pathogen Staphylococcus aureus as a member of the skin resident flora [4]. It would appear that frequent exposure to certain transient microbes may lead to them becoming established as a constituent of the resident flora. For example, studies have shown that nurses performing similar tasks within a hospital will have some similarities among their resident flora; while those assigned to different tasks will have different constituents within their resident flora [5,6]. Furthermore, it has recently been shown that homemakers often carrier bacteria within their resident hand flora that are identical to those environmental isolates identified within the home [7]. In terms of hand hygiene, the majority of hand soaps as well as hand sanitizers are primarily targeted toward reducing the level of transient bacteria and viruses on hands. Some products provide only immediate activity (e.g. alcohol hand sanitizers), whereas others provide immediate and residual protection benefits (e.g. triclosan-containing hand sanitizers). Residual protection provides benefits in between product usage preventing re-establishment of transient flora.

Propionibacterium acnes Pseudomonas aeruginosa Staphylococcus aureus Staphylococcus epidermidis Staphylococcus warneri Streptococcus mitis Streptococcus pyogenes

The resident flora of the hand is defined as the complex community of microbes that consistently inhabit the hand and routinely are not washed off with non-medicated soaps. A summary of the bacteria that have been reported to be isolated as resident flora is presented in Table 14.1. Unfortunately, few studies have been undertaken to clearly define the role that these microbes have in health and disease. However, it is speculated that the resident skin

Hand hygiene Since the mid 1800s with the ground breaking work by Professor Ignaz Semmelweis demonstrating a reduction in puerperal sepsis following the institution of hand hygiene protocols, the concept of hand hygiene as means of infection control has been well accepted. In the late 1970s–1980s our understanding that the part hands play in the transmission of bacterial and viral pathogens including the common cold have become well documented [8,9]. Today, hand washing using soap and water or hand antisepsis using hand sanitizer products is the cornerstone of many infection control programs. Hand washing and hand antisepsis guidelines were published by the Association for Professionals in Infection Control (APIC) in 1988 and updated in 1995 [10]. The most recent updates were published in 2002 by the Hygiene Task Force composed of members of APIC, Center(s) for Disease Control (CDC), Healthcare Infection Control practices




Advisory Committee (HICPAC), Society for Healthcare Epidemiology of America (SHEA), and Infectious Diseases Society of America (IDSA) [11]. Since 1995 these various guidelines recognize the utility of hand washing with antimicrobial containing soap as well as the use of waterless hand sanitizers. The Food and Drug Administration’s (FDA) Food Code contains specific hand hygiene guidance for retail and food service workers describing when, where, and how to wash and sanitize hands. Hand sanitizers, meeting specific criteria described in section 2-301.16 of the Food Code, may be used after proper hand washing in retail and food service [12].

Hand hygiene compliance The importance of hand washing is well understood by professional and non-professionals; unfortunately, observational studies that measure compliance based on these standards are, at best, disappointing. Hand hygiene compliance studies estimate that healthcare workers are 40% compliant and food service workers are 30% compliant with standard guidelines [13,14]. A recent observational study demonstrated that fewer than 50% of hospital healthcare workers were observed to wash their hands after toileting [15]. Within the general population, observational studies have clearly demonstrated a gender difference among hand washing compliance. A large American Society for Microbiology study demonstrated that 88% of women and only 66% of men wash their hands after visiting the toilet. Other studies have shown that hand washing compliance is inversely proportional to education levels, indicating that the understanding of guidelines is not the issue [16]. Because hand washing compliance is low there is a need for hand sanitizers, especially those with persistent benefit, to be included in hand hygiene strategies.

The most effective mean wash time is considered to be 15–20 seconds, but observational studies on subjects within healthcare and community settings indicate that the average hand wash time lasts less than 8 seconds. This would imply that as currently practiced the removal of transient microorganisms from the hands is suspect at best. Quantitative studies within a community setting have substantiated this hypothesis. A study conducted by Larson et al. [17] in homemakers measured mean colony-forming units count of 5.72 before washing and 5.69 after. These results indicated that the hand washing technique as practiced was ineffective. A final factor for consideration is that of pH. The low pH of the hands has a crucial role in the innate antimicrobial hostility of the hand surface. The pH of the hands is approximately 4–5 routinely; however, the alkalinity of soaps can result in an increase in the skin pH [18]. This poses a concern because some of the antibacterial characteristics of skin are minimized. In one report, pH increased 0.6 to 1.8 units after hand washing with plain soap and then gradually declined to baseline levels over a period of 45 minutes to 2 hours [18]. Recently, a hand sanitizer has been introduced that provides antibacterial efficacy using triclosan formulated into a low pH matrix. This product maintains the low pH of the hand surface for hours. This imparts not only an immediate antimicrobial benefit but a persistent one as well [19]. Several studies have demonstrated that damaged hands harbor more transient microorganisms than healthy hands [20]. Repeated hand washing with soap and water removes the protective lipid layer which is followed by transepidermal water loss and cutaneous signs of redness, scaling, and possibly dermatitis. The use of alcohol-based hand sanitizers can also lead to dehydration of the skin as well as lipid removal and skin damage which may lead to increased colonization by transient flora. Recent investigations have shown that only subjects with healthy skin achieved appropriate levels of decontamination with plain soap and water [20]. Thus, individuals with damaged hands will require more robust antimicrobial formulations.

Hand washing techniques Hand washing when done properly is considered to be the gold standard for removing transient pathogenic bacteria from the hands. The best accepted hand washing protocol established by the CDC is described below.

Proper hand washing with soap and water • Wet your hands with warm, running water and apply liquid soap or use clean bar soap. Lather well. Rub your hands vigorously together for at least 15–20 seconds. • Scrub all surfaces, including the backs of your hands, wrists, between your fingers and under your fingernails. • Rinse well. • Dry your hands with a clean or disposable towel. • Use a towel to turn off the faucet.


Measurements of efficacy Studies demonstrating the efficacy of antimicrobial hand soaps and sanitizers toward removal of transient microbes can be divided into three categories: 1 In vitro potency and spectrum of activity; 2 In vivo models with artificial inoculate; and 3 Clinical studies demonstrating efficacy.

In vitro measurements In terms of the in vitro measures of efficacy, classic microbiologic protocols of minimum inhibitory concentration (MIC) and time kill studies are usually conducted with bacteria and viruses of interest. The relevance of these in vitro

14. Liquid hand cleansers and sanitizers measurements for products of this nature has been a debate within the research community for decades. The primary information garnered from these studies only provides insights into the potency and spectrum of activity of a formulation within the test laboratory setting. Investigators have also relied on artificial substrates to model removal of transient flora from hands. In these model systems either pig skin or an alternative skin substrate mimic is utilized to model the hand. Bacteria or viruses are inoculated onto the substrate prior to treatment. Measurements of microbial reductions are made following the treatment and efficacy is calculated by comparison with either an untreated control or placebo. Recently, some researchers are using similar models to assess the residual benefits of these formulations. The waterless alcohol-based hand sanitizer technologies have little to no residual benefit versus the triclosan-containing low pH hand sanitizers which provide immediate as well as residual benefit (2008 Nonprescription Medicines Academy).

In vivo models with artificial inoculate mimic transient flora Both in Europe and the USA, there are efficacy standards for antimicrobial soaps and hand sanitizers. In both geographic regions, the tests necessary to fulfill these regulatory requirements involve artificially inoculating subject’s hands with large inoculums of indicator bacteria. This is followed by treatment, neutralization of the active ingredient, and enumeration of remaining viable bacteria. The methods most widely accepted in Europe are EN 1499 for antimicrobial hand soaps and EN 1500 for leave-on hand sanitizers. In both of these test protocols, 12–15 subjects wash their hands with a plain soap and water. The hands are then contaminated by having the subject immerse their hands half-way to metacarpals in a 24-hour broth culture of a non-pathogenic strain of E. coli. Following drying, bacterial recovery is achieved by kneading the fingertips and palms separately into 10 mL Trypticase soy broth plus neutralizers. The hands are removed, disinfected, and again contaminated. The treatments are then applied for 30–60 seconds either with or without a rinsing step depending on product type (rinse-off or leave-on). Post-treatment bacteria are recovered as described above. Extracted bacteria are enumerated using traditional microbiologic plating techniques. In these European tests, efficacy is determined versus internal standards. For EN 1499, antimicrobial hand soaps must provide a superior log reduction to that achieved using a plain soap (sapo kalinus) following a 60-second treatment. When evaluating leave-on products such as hand sanitizers with EN 1500 procedures, the product must deliver a benefit not less than that observed with a 60second application of 60% 2-propanol. In the USA, antimicrobial soaps and sanitizers are regulated by the FDA’s Tentative Final Monograph for Healthcare

Antiseptic Drug Products (FR 1994). The standard method used to evaluate formulations is the American Society of Testing and Materials E 1174. In this test, subjects refrain from utilizing any antimicrobial products for 1 week prior to the start of the study (“washout period”). At the initiation of the study, the subjects perform a cleansing wash to eliminate any residual transient bacteria. The subjects’ hands are then contaminated with 4.5–5.0 mL of a 24-hour broth culture of either a non-pathogenic E. coli or Serratia marcescens. Bacteria are then recovered by separately placing each hand into a glove containing 75 mL sampling solution plus neutralizers. The hand is massaged for 1 minute and bacteria are enumerated using traditional microbiologic plating techniques. This enumeration serves as the baseline measurement. The subjects then perform another cleansing wash and are reinoculated. Following this reinoculation the treatment is applied as described by the manufacture for either an antimicrobial soap or leave-on hand sanitizer. After the treatment is completed the bacteria are again recovered from the hands using the glove method and this is called Test Wash 1. This is followed by another cleansing wash. Once this cleansing wash is complete a cycle of inoculation followed by treatment is performed 10 consecutive times and bacteria are recovered at the 10th cycle. In this protocol, there is no internal standard. The success criteria are determined by log reduction versus the baseline measurement. In Wash 1, a product must achieve a minimum of a 2-log reduction, and at Wash 10, the product must deliver a 3-log reduction versus baseline.

Methodology concerns There is a great deal of critique of these standard methods. First and foremost, these European and US protocols utilize treatment times and typically volumes of product that are far outside of the norm. In the case of the ASTM E1174, there is concern that bacteria are sampled from areas of the hands not involved in transmission such as the back of the hands. An additional concern is the appropriateness of these inocula to the real world situation. In the natural setting, transient bacteria would rarely be present without being incorporated into a soil matrix. To address this issue, investigators have developed methodologies that incorporate the use of a soil matrix such as chicken or hamburger in place of marker bacterial organisms and focused attention is paid to the palms of the hands [21,22]. In the presence of a greasy soil matrix such as chicken, the alcohol-based hand sanitizers lack appreciable efficacy, whereas those containing more potent antimicrobial actives such as triclosan and benzalkonium chloride demonstrate a higher level of effectiveness (Figure 14.2). In addition to these standardized methodologies, other protocols designed to mimic transient flora have been presented within the literature. The most utilized method is commonly referred to as the fingerpad method [23]. In this







Figure 14.2 Effects of different hand sanitizers on greasy soil. Bacterial growth has been colorized. (a) Untreated. (b) Triclosan-based. (c) Alcohol-based.

method, subjects who have previously refrained from using antimicrobial products have their fingerpads contaminated with either bacteria or viruses. The fingerpads are then treated with test product and the bacteria or viruses are enumerated. Recently, authors have utilized this test to evaluate the residual activity of a hand sanitizer. In this test the fingerpad was treated with the sanitizer and subsequently challenged with bacteria 3 hours later [19]. This study demonstrated that the hand sanitizer provided protection from microbial challenge for up to 3 hours post application. Other models have also been described in the literature with the aim of assessing residual antimicrobial activity as well as transfer of microbial agents. One such method involves the ability of antiseptic hand products to interrupt the transfer of microorganisms from fingerpads to hard surfaces under controlled pressures [24].

Resident flora For consumer or common healthcare, antimicrobial hand soaps and hand sanitizers various methods have been developed to look at the impact of these products on the resident flora. One commonly used method is the Cade test which measures the impact of several washes over a period of 5 days [25]. This test, like the Health Care Personnel Handwash test, begins with a washout period. This is followed by a 5-day baseline period and samples are collected over 2 days to control for day-to-day variations. Following this baseline, subjects are instructed to use the product multiple times daily. Subjects are sampled for 2 days during the treatment phase. Efficacy is determined by comparisons between the baseline and treatment phases. The antimicrobial efficacy of surgical hand antiseptics is determined according to a European standard (prEN 12791) and a US standard (TFM). The two methods differ in several ways as shown in Table 14.2. Because of these differences, Kampf et al. [26] have stressed the need to evaluate potential products using both


Table 14.2 US and European standard methods. Difference

US method

prEN 12791

Product application

Hands and lower forearm

Hands only

Number of applications

11 over 5 days

Single application

Sampling times

0, 3, 6 hours post-application

0, 3 hours post-application

Sample method

Glove juice

Fingertip sampling

Success criteria

Absolute bacterial reduction

Non-inferiority to reference standard

methodologies to assure efficacy. Overall, the model systems described above have been very helpful for the determination of efficacy for various antimicrobial hand soaps and hand sanitizers. However, it must be pointed out that these models are not always indicative of efficacy under real use conditions.

Effectiveness of hand hygiene in the community setting Unfortunately, clinical trials of hand hygiene regimes are complex and expensive to execute. Community intervention studies have been limited in scope and have delivered mixed and sometimes inconclusive results. Comprehensive reviews of these studies have resulted in less than favorable outcomes in terms of the quality and the conclusions derived [27]. Reduction in gastrointestinal illnesses associated with handwashing have ranged from −10% to 57%. Unfortunately, only three out of the five studies that evaluated gastrointestinal illness produced statistical significance. In these three

14. Liquid hand cleansers and sanitizers studies, the magnitude of the impact was approximately 50% reduction in the incidence of illness. The impact of hand hygiene on respiratory illness is more limited. The magnitude of the overall impact of current available studies has been estimated to be an approximate 23% reduction in the incidence rate of respiratory infections. Thus, current data implies that hand hygiene has its largest impact on gastrointestinal versus respiratory illness. A recent metaanalysis by Aiello et al. [28], using hand hygiene intervention studies, indicated that overall hand hygiene reduces the incidences of gastrointestinal illness by 31% (95% CI = 19– 42%) and, to a lesser extent, respiratory illness by 21% (95% CI = 5–34%). There are many more studies that examined the impact of alcohol-based hand sanitizers on subsequent infection rates. The conclusion by Meadows and LeSaux [29] was that the data were of poor quality and that more rigorous intervention studies were needed. The current studies have demonstrated a reduction in the incidence of gastrointestinal illness from 0 to 59%. The magnitude for respiratory illness and infection and/or symptom reduction ranged from −6% to 26%. Thus, like the hand washing studies, the use of alcohol-based hand sanitizers appears to have a more robust effect on gastrointestinal infections.

Hospital epidemiology noscomial studies To date, several reviews have examined the database of studies evaluating the evidence of a causal link between hand hygiene and the reduced risk of hospital acquired infections. A recent comprehensive review by Backman et al. [30] evaluated 1120 articles on the subject and concluded that “there is a lack of rigorous evidence linking specific hand hygiene interventions with the prevention of health care acquired infections.” The conclusion from the Backman review was somewhat different from that of Larson’s review [31] but was similar to Silvestri et al.’s review [32] concerning the link between hand hygiene interventions and the risk of healthcare acquired infections. However, it is important to note that all three reviews focused on the lack of quality in studies published to date. It is speculated that the nature of the interventions utilized and the diverse factors affecting the acquisition of healthcare-associated infections that complicate the ability to demonstrate an effect of hand hygiene alone.

Safety of handwashes and hand sanitizers

healthcare workers [33]. It is most often attributed to irritation which occurs from repeated contact with detergents and is believed to be exacerbated by the wearing of gloves. A further concern has to do with contact allergies to antibacterial actives and perfumes that are incorporated within the products themselves. Although there are some reports of allergies to these chemistries the accounts of these are limited within the literature [34].

Safety concerns specific to alcohol-based hand sanitizers In terms of the alcohol-based hand sanitizers, there are occupational safety concerns with the chronic use of alcohol. First is the removal of the lipid barrier of the hands, leading to irritation and an increase in bacterial colonization. Second, the flammability of these alcohol-based formulations has caused some to question whether it is good practice to have them in various locations where the potential for ignition exists. Third are the reports in the literature of intentional ingestion of the alcohol-based products by those individuals with alcoholism and the accidental ingestion by children [35]. Lastly, a safety issue that has called alcoholbased systems into question is the misuse of these products for the prevention of infections. For example, use of alcohol-based hand sanitizers for prevention of infections by norovirus or C. difficile is not prudent because it is well established that alcohol has limited efficacy against these pathogens [36,37].

Microbial resistance to antimicrobial agents The major question concerning antimicrobial-containing hand washes and their use in consumer products has to do with the potential for the development of pathogen resistance [38]. The resistance issue has been divided into two questions: 1 Will the use of these agents in broad scale consumer use result in the loss of their effectiveness? 2 Will the use of these agents lead to cross-resistance to antibiotics? The majority of the work has been done with triclosan, which has been utilized as an antibacterial agent in several consumer products for 30 years. Triclosan is broad-spectrum antibacterial and antifungal agent. It is more potent against Gram-positive (e.g. S. aureus) than Gram-negative bacteria. Triclosan is utilized for therapeutic baths of MRSA-infected patients [39] and in the control of MRSA carriage and skin infections [40]. Unlike orally ingested antibiotics, triclosan elicits bactericidal actions against a variety of bacterial targets reducing the potential for resistance development.

Irritation associated with handwashes and hand sanitizers

Laboratory observations

A safety concern for both hand washes and hand sanitizers is the occurrence of dermatitis observed in up to 25% of

Chronic sublethal exposure of laboratory strains of E. coli to triclosan selected clones with reduced susceptibility [41].




Although these clones were less susceptible, they were still inhibited by in-use triclosan concentrations. Further studies demonstrated that these observations were limited only to laboratory strains of E. coli and in some cases the effects observed with triclosan could be reproduced with a variety of non-antimicrobial materials such as mustard, chili, and garlic [42,43]. Lambert [44] evaluated 256 clinical isolates of P. aeruginosa and S. aureus over a 10-year period. There was no difference in triclosan sensitivity between antibiotic sensitive and resistant strains. The authors concluded that there was a negative correlation between antibiotics and biocides. Suller and Russell [45] used clinical isolates of S. aureus (MSSA and MRSA) to demonstrate no correlation between MRSA and decreased triclosan susceptibility. Furthermore, continuous exposure of a triclosan-sensitive S. aureus strain to subinhibitory triclosan concentrations for 1 month did not decrease susceptibility either to triclosan or to other antibiotics.

Antibacterial exposure results from long-term studies Studies examining exposure to triclosan for 6 months of mixed microbial communities derived from natural environments [46] resulted in no change in triclosan or antibiotic sensitivities. Cole et al. [47] studied 60 homes, 30 of which used antibacterial products and 30 did not. A total of 1238 bacteria were evaluated, with more target bacteria being recovered from biocide users versus non-users. No methicillin, oxacillin, or vancomycin resistant S. aureus were isolated associated with the use of biocides. In fact, the incidence of resistance to antibacterials was higher in non-user households. Aiello et al. [48] conducted a large (224 households), 12-month study addressing the impact of antibacterial products in homes. Logistic regression analysis demonstrated that the use of biocide products did not result in significant increases in antimicrobial drug resistance nor did it impact susceptibility to triclosan. Thus, following a comprehensive review of the scientific literature, it is concluded that there is no evidence to support that use of triclosan in consumer products will reduce effectiveness nor contribute to the societal burden of antibiotic resistance. In fact, several accounts in the literature document the utility of triclosan in the reduction of antibioticresistant microorganisms including MRSA.

Formulations of hand sanitizers and hand washes Hand sanitizers can be categorized into three main classes: 1 Alcohol-based = ≥62% alcohol; 2 Alcohol-based supplemented = ≥62% alcohol plus antimicrobial agent;


3 Non-alcohol-based = the majority of the product is water plus surfactant and antimicrobial agent. In terms of product forms, they span from liquids to gels and foams. Most base efficacy on the fact that they are leaveon products. With the exception of the alcohol-based products that only deliver an immediate benefit and provide no residual activity, hand sanitizers provide both immediate plus a residual antimicrobial benefit. The antimicrobial hand washes are primarily water-based formulations that are composed of mixtures of surfactants, antimicrobial actives perfumes, and, in some cases, emollients. In many cases, these emollients and skin feel agents are added to improve the consumer experience with the hope of improving the overall compliance. In the USA, antimicrobial actives that can be incorporated within these products are regulated under the TFM. The ingredients are classified into three categories: 1 Category 1. Ingredients determined to be safe and effective; 2 Category 2. Ingredients determined to be neither safe nor effective; 3 Category 3. Ingredients for which there is insufficient evidence; however, the FDA is not objecting to marketing or sale of these products. Only active ingredients in categories 1 and 3 are allowed to be lawfully marketed in products within the USA. The formulating of non-alcohol-based hand sanitizers as well as antimicrobial hand washes must take into consideration the bioavailability of the antimicrobial active. For example, some of the surfactants within the formulation may complex or otherwise inactivate the formulation. Recent data with triclosan-containing formulations have demonstrated a difference in efficacy among various triclosan-containing hand washes [49] with varying formulations.

Future directions It is imperative for our future understanding of this area that improved epidemiologic studies be conducted with a variety of hand hygiene products to better demonstrate the role of hand hygiene for the prevention of infections both in the hospital as well as in the community setting. Additionally, complete hand hygiene strategies must be developed including product efficacy, skin feel, compliance, as well as education. Furthermore, hand hygiene must be examined to assure consumers that both residual as well as immediate germ removal is accomplished. Technologies need to be developed that address consumer as well as healthcare workers’ behavior and occupational needs. These technologies must be easy to use and provide the skin conditioning needs for consumers and be effective against a variety of pathogenic bacteria and viruses.

14. Liquid hand cleansers and sanitizers

References 1 Baker GR, Norton PG, Flintoft V, Blais R, Brown A, Cox J, et al. (2004) The Canadian Adverse Events Study: the incidence of adverse events among hospital patients in Canada. CMAJ 170, 1678–86. 2 Klevens RM, Edwards JR, Richards CL Jr, Horan TC, Gaynes RP, Pollock DA, et al. (2007) Estimating health care-associated infections and deaths in US hospitals, 2002. Public Health Rep 122, 160–6. 3 Hendley JO, Gwaltney JM Jr. (1988) Mechanisms of transmission of rhinovirus infections. Epidemiol Rev 10, 242–58. 4 Cogen AL, Nizet V, Gallo RL. (2008) Skin microbiota: a source of disease or defence? Br J Dermatol 158, 442–55. 5 McBride ME, Montes LF, Fahlberg WJ, Knox JM. (1975) Microbial flora of nurses’ hands. III. The relationship between staphylococcal skin populations and persistence of carriage. Int J Dermatol 14, 129–35. 6 Aiello AE, Cimiotti J, Della-Latta P, Larson EL. (2003) A comparison of the bacteria found on the hands of ‘homemakers’ and neonatal intensive care unit nurses. J Hosp Infect 54, 310–5. 7 Pancholi P, Healy M, Bittner T, Webb R, Wu F, Aiello A, et al. (2005) Molecular characterization of hand flora and environmental isolates in a community setting. J Clin Microbiol 43, 5202–7. 8 Gwaltney JM Jr, Moskalski PG, Hendley JO. (1978) Hand-tohand transmission of rhinovirus colds. Ann Intern Med 88, 463–7. 9 Hendley JO, Wenzel RP, Gwaltney JM Jr. (1973) Transmission of rhinovirus colds by self inoculation. N Engl J Med 288, 1361–4. 10 Larson EL. (1995) APIC guidelines for handwashing and hand antisepsis in health care settings, 1992, 1993, and 1994. APIC Guidelines Committee. Am J Infect Control 23, 251–69. 11 Centers for Disease Control and Prevention. (2002) Guideline for hand hygiene in health-care settings: recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. MMWR 51, 1–44. 12 US Department Of Health And Human Services. (2005) Public Health Service. Food Code.∼dms/ fc05-toc.html 13 Green LR, Selman CA, Radke V, Ripley D, Mack JC, Reimann DW, et al. (2006) Food worker hand washing practices: an observation study. J Food Prot 69, 2417–23. 14 Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. (2002) Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/ Infectious Diseases Society of America. MMWR Recomm Rep 51, 1–45. 15 van der Vegt D, Voss A. (2008) Hand hygiene after toilet visits. 18th European Congress of Clinical Microbiology and Infectious Disease April. [Abstract P1103]. 16 Duggan JM, Hensley S, Khuder S, Papadimos TJ, Jacobs L. (2008) Inverse correlation between level of professional education and rate of handwashing compliance in a teaching hospital. Infect Control Hosp Epidemiol 29, 534–8.

17 Larson EL, Gomez-Duarte C, Lee LV, Della-Latta P, Kain DJ, Keswick BH. (2003) Microbial flora of hands of homemakers. Am J Infect Control 31, 72–9. 18 Gunathilake HM, Sirimanna GM, Schürer NY. (2007) The pH of commercially available rinse-off products in Sri Lanka and their effect on skin pH. Ceylon Med J 52, 125–9. 19 Zukowski C, Boyer A, Andrews S, Trowbridge M, Grender J, Widmeyer V, et al. (2007) Immediate and persistent antibacterial and antiviral efficacy of a novel hand sanitizer. Presented at 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; Chicago, IL, September 17–20, 2007. 20 de Almeida e Borges LF, Silva BL, Gontijo Filho PP. (2007) Hand washing: changes in the skin flora. Am J Infect Control 35, 417–20. 21 Charbonneau DL, Ponte JM, Kochanowski BA. (2000) A method of assessing the efficacy of hand sanitizers: use of real soil encountered in the food service industry. J Food Prot 63, 495–501. 22 Hansen TB, Knøchel S. (2003) Image analysis method for evaluation of specific and non-specific hand contamination. J Appl Microbiol 94, 483–94. 23 Sattar SA, Ansari SA. (2002) The fingerpad protocol to assess hygienic hand antiseptics against viruses. J Virol Methods 103, 171–81. 24 Mbithi JN, Springthorpe VS, Boulet JR, Sattar SA. (1992) Survival of hepatitis A virus on human hands and its transfer on contact with animate and inanimate surfaces. J Clin Microbiol 30, 757–63. 25 Gibbs BM, Stuttard LW. (1967) Evaluation of skin germicides. J Appl Bacteriol 30, 66–77. 26 Kampf G, Ostermeyer C, Heeg P, Paulson D. (2006) Evaluation of two methods of determining the efficacies of two alcoholbased hand rubs for surgical hand antisepsis. Appl Environ Microbiol 72, 3856–61. 27 Bloomfield SF, Aiello AE, Cookson B, O’Boyle C, Larson EL. (2007) The effectiveness of hand hygiene procedures in reducing the risks of infections in home and community settings including handwashing and alcohol-based hand sanitizers. Am J Infect Control 35 (Suppl 1), S27–64. 28 Aiello AE, Coulborn RM, Perez V, Larson EL. (2008) Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis. Am J Public Health 98, 1372–81. 29 Meadows E, Le Saux N. (2004) A systematic review of the effectiveness of antimicrobial rinse-free hand sanitizers for prevention of illness-related absenteeism in elementary school children. BMC Public Health 4, 50. 30 Backman C, Zoutman DE, Marck PB. (2008) An integrative review of the current evidence on the relationship between hand hygiene interventions and the incidence of health careassociated infections. Am J Infect Control 36, 333–48. 31 Larson E. (2005) State-of-the science-2004: time for a “No Excuses/No Tolerance” (NET) strategy. Am J Infect Control 33, 548–57. 32 Silvestri L, Petros AJ, Sarginson RE, de la Cal MA, Murray AE, van Saene HK. (2005) Handwashing in the intensive care unit: a big measure with modest effects. J Hosp Infect 59, 172–9. 33 Larson E, Friedman C, Cohran J, Treston-Aurand J, Green S. (1997) Prevalence and correlates of skin damage on the hands of nurses. Heart Lung 26, 404–12.




34 Heydorn S, Menné T, Johansen JD. (2003) Fragrance allergy and hand eczema: a review. Contact Dermatitis 48, 59–66. 35 Emadi A, Coberly L. (2007) Intoxication of a hospitalized patient with an isopropanol-based hand sanitizer. N Engl J Med 356, 530–1. 36 Macinga DR, Sattar SA, Jaykus LA, Arbogast JW. (2008) Improved inactivation of nonenveloped enteric viruses and their surrogates by a novel alcohol-based hand sanitizer. Appl Environ Microbiol 74, 5047–52. 37 King S. (2004) Provision of alcohol hand rub at the hospital bedside: a case study. J Hosp Infect 56 (Suppl. 2), S10–2. 38 Aiello AE, Larson E. (2003) Antibacterial cleaning and hygiene products as an emerging risk factor for antibiotic resistance in the community. Lancet Infect Dis 3, 501–6. 39 Zafar AB, Butler RC, Reese DJ, Gaydos LA, Mennonna PA. (1995) Use of 0.3% triclosan (Bacti-Stat) to eradicate an outbreak of methicillin-resistant Staphylococcus aureus in a neonatal nursery. Am J Infect Control 23, 200–8. 40 Rashid A, Solomon LK, Lewis HG, Khan K. (2006) Outbreak of epidemic methicillin-resistant Staphylococcus aureus in a regional burns unit: management and implications. Burns 32, 452–7. 41 Levy CW, Roujeinikova A, Sedelnikova S, Baker PJ, Stuitje AR, Slabas AR, et al. (1999) Molecular basis of triclosan activity. Nature 398, 383–4. 42 Rickard AH, Lindsay S, Lockwood GB, Gilbert P. (2004) Induction of the mar operon by miscellaneous groceries. J Appl Microbiol 97, 1063–8.


43 McBain AJ, Ledder RG, Sreenivasan P, Gilbert P. (2004) Selection for high-level resistance by chronic triclosan exposure is not universal. J Antimicrob Chemother 53, 772–7. 44 Lambert RJ. (2004) Comparative analysis of antibiotic and antimicrobial biocide susceptibility data in clinical isolates of methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa between 1989 and 2000. J Appl Microbiol 97, 699–711. 45 Suller MT, Russell AD. (2000) Triclosan and antibiotic resistance in Staphylococcus aureus. J Antimicrob Chemother 46, 11–8. 46 McBain AJ, Bartolo RG, Catrenich CE, Charbonneau D, Ledder RG, Price BB, et al. (2003) Exposure of sink drain microcosms to triclosan: population dynamics and antimicrobial susceptibility. Appl Environ Microbiol 69, 5433–42. 47 Cole EC, Addison RM, Rubino JR, Leese KE, Dulaney PD, Newell MS, et al. (2003) Investigation of antibiotic and antibacterial agent cross-resistance in target bacteria from homes of antibacterial product users and nonusers. J Appl Microbiol 95, 664–76. 48 Aiello AE, Marshall B, Levy SB, Della-Latta P, Lin SX, Larson E. (2005) Antibacterial cleaning products and drug resistance. Emerg Infect Dis 11, 1565–70. 49 Fuls J, Fischler G. (2004) Antimicrobial efficacy of activated triclosan in surfactant-based formulation versus Pseudomonas putida. Am J Infect Control 32, E22.

Chapter 15: Shampoos for normal scalp hygiene and dandruff James R. Schwartz, Marcela Valenzuela, and Sanjeev Midha Procter & Gamble Beauty Science, Cincinnati, OH, USA

BAS I C CONCEPTS • Frequent scalp cleansing is important to prevent formation of unhealthy scalp. • Three classes of shampoos can be delineated: (1) cosmetic shampoos and two types of therapeutic products, (2) standard, and (3) cosmetically optimized therapeutics. • Both therapeutic scalp care shampoos are effective for normal scalp to prevent unhealthy conditions and for dandruff/seborrheic dermatitis scalp to treat the condition and subsequently prevent its reoccurrence. • All therapeutic shampoos are not equally efficacious, even though they may contain the same active. • Cosmetically optimized therapeutic shampoos are desirable as they increase compliance long term because of having no esthetic trade-offs and their affordability. • All shampoos, including cosmetics, must be mild to the skin while being effective cleansers to minimize irritation that could initiate scalp problems.

Introduction The scalp is a unique environment of the skin combining a high level of sebaceous lipid production with a physical covering of hair. The hair physically protects the scalp from UV light but also can inhibit the cleansing efficiency of the scalp surface by shampoos. These conditions allow for the colonization of commensal Malassezia yeasts which can, under the right conditions, cause inflammation and hyperproliferation [1] leading to symptoms [2] of flakes and itch (Figure 15.1). Lipases are secreted by the yeast into the surrounding medium to cause liberation of fatty acids from the triglycerides of the sebaceous lipids. Malassezia selectively consume long chain saturated fatty acids to live, the unsaturated fatty acids left behind can then be the initiators of inflammation. Cutaneous inflammation results in hyperproliferation in the epidermis leading to immature stratum corneum cells with incompletely degraded adhesive function resulting in removal as visible clumps. The resultant condition is called dandruff or seborrheic dermatitis (D/SD), depending on the severity of flaking and the presence of outward manifestations of inflammation. The presence of the condition places special requirements on effective scalp cleansing and it has been observed that

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

scalp issues such as D/SD occur more frequently when cleansing frequency decreases [3]. Because the sebaceous lipids are one of the key factors required for formation of D/SD, infrequent removal leads to the build up of the proinflammatory by-products of Malassezia metabolism.

Product and formulation technology overview Three categories of shampoos can be delineated (Figure 15.2). Cosmetic shampoos are primarily designed to cleanse the hair, but of course the scalp skin is cleansed simultaneously. Modern versions of these shampoos also condition the hair by depositing certain ingredients on the hair to improve cosmetic benefits such as ease of combing, shine maintenance, and other attributes important to all consumers. Therapeutic scalp care shampoos (often termed “antidandruff”) contain active ingredients to control the D/SD conditions, most often by reducing the Malassezia population on the scalp. Standard therapeutic products tend to focus on the drug active without full consideration of product esthetics. Cosmetically optimized therapeutic products also contain a drug active to achieve therapeutic benefits, but without the common esthetic trade-offs of therapeutic products. Recommendations involving therapeutic products must take into consideration that patients also have basic hair care needs and that if the product has significant negative esthetic trade-offs, compliance will be very poor thereby limiting therapeutic efficacy.







Figure 15.1 (a) Image of normal scalp skin. (b) Dandruff scalp image showing adherent white flakes. (c) Seborrheic dermatitis with more evidence of sebum yellowing on flakes and underlying erythema.

Cosmetic shampoos

Cosmetically-optimized therapeutics

Therapeutic shampoos

Mild for everyday usage Hair conditioning Pleasant product esthetics Cost effective Anti-dandruff efficacy

Figure 15.2 Representation of the shampoo segments, differentiating cosmetic from therapeutic shampoos and their key attributes. The category of cosmetically optimized therapeutics achieves therapeutic benefits without diminishing esthetic attributes.

The primary component of all shampoos is surfactants which help to remove sebaceous lipids, keratin debris, particulates from the air, and residues from styling products (Table 15.1). These materials are responsible for the lathering action of a product; the volume of lather is important in the user’s perception of cleaning activity. Most of the surfactants tend to be negatively charged (anionic), although some contain both positive and negative charges in the same molecule (amphoteric), and some are uncharged (nonionic); these latter types are considered co-surfactants and function to optimize the lather quality and amount and cleaning ability of the primary anionic surfactant. The surfactant system is optimized to achieve two opposing objectives – cleaning while minimizing irritation of the skin. All surfactants have the potential to irritate the skin to various degrees. The goal of the formulator is to achieve


effective cleaning and lathering while minimizing the irritation potential of the product by using the right surfactants. The addition of co-surfactants can synergistically decrease irritation potential without harming cleaning. Some antidandruff actives also can minimize the irritation potential of surfactants (see below); this is especially important for treatment of the D/SD condition which can be exacerbated by an irritating surfactant system. In addition to surfactants for cleaning, shampoos contain a wide range of other materials to care for the hair and scalp, deliver cosmetic benefits, enhance the usage experience, and to maintain the physical integrity of the product itself (e.g. preservatives, viscosity adjusters, pH control). Hair conditioning agents result in shiny, manageable hair and include such materials as silicones, cationic (positively charged) polymers that show enhanced deposition on the hair fiber to reduce static electricity, humectants to maintain hydration, and materials that penetrate the hair shaft to maintain a healthy-looking appearance. The cationic polymers mentioned as conditioning aids are also a critical component of the delivery system of many shampoos. While shampoos are first and foremost designed to clean, the achievement of additional hair and scalp benefits requires selected materials to be left behind after rinsing to deliver these benefits. The combination of oppositely charged surfactants and polymers results in an electrostatic association complex called coacervate which forms upon product use and rinsing. The coacervate is an aqueous gel that aids in the delivery of hair and scalp benefit agents to their respective surfaces. The manipulation of surfactant and polymer types affects deposition efficiency, and together with the type and level of hair benefit agent(s), affects how much conditioning is delivered to the hair. This is the basis for a wide offering of shampoo versions, to meet the diverse hair and scalp needs of users to deliver cosmetic benefits and a pleasant in-use experience, especially in terms of how much hair conditioning is needed and desired. Standard therapeutic shampoos

15. Shampoos

Table 15.1 Summary of common formulation components of various shampoo types. Function(s)

Material class(es)


Hair conditioning agents

Primary surfactants



Shine, manageability Detangling, Antistatic Hydration


Benefit delivery


Sodium lauryl sulfate, ammonium lauryl sulfate, sodium laureth sulfate, ammonium laureth sulfate Cocamidopropyl betaine, Cocamide MEA

Presence in Cosmetic shampoo

Cosmetically optimized therapeutic

Standard therapeutic shampoo









Dimethicone, dimethiconol, amodimethicone Polyquaternium-10, cationic guar derivatives Glycerin, urea





Panthenol and derivatives



Cationic Polymers

Polyquaternium-10, cationic guar derivatives




Isothiazalinone derivatives, parabens







Yes Some

Yes Some

Yes Some



Cationic polymers Humectants

Hair health Deposition aids

Common examples

Fragrance Thickeners


Salts Particles

Sodium chloride Glycol distearate

Antidandruff components

Scalp care


Pyrithione zinc (PTZ), selenium sulfide, ketoconazole (Table 15.2) Zinc carbonate


tend to be deficient in hair conditioning benefits. They also do not tend to have a range of versions to meet the esthetic needs of the user. Together these two factors limit compliance with standard therapeutic products. Therapeutic scalp care shampoos additionally contain active materials for resolving D/SD and preventing its reoccurrence. Because the commensal scalp fungus Malassezia clearly has a role in the etiology of the condition [1], the primary function of most scalp care active materials is antifungal; the most common are referred to in Table 15.2, grouped by their intrinsic anti-Malassezia potency. Many of the materials are accepted by global regulatory agencies, while some are used in more limited geographic applications. The most commonly used scalp active is pyrithione zinc (PTZ), a material developed as part of a program to identify biocides based on the naturally occurring antibiotic aspergillic acid [4]. Screening of over 1000 prospective antidandruff


materials in the late 1950s led to the selection of PTZ; novel formulation work then led to commercialization of shampoos with PTZ in the early 1960s [5]. Since that time, the efficacy, ease of formulation, cost, and compatibility with esthetic shampoos has resulted in very broad use and acceptance of PTZ and technical developments which continue to improve its therapeutic benefit (see below). Other effective actives such as ketoconazole and selenium sulfide are used fairly broadly, but tend to be more limited to the standard therapeutic class of shampoos either because of cost, regulatory, or esthetic limitations. Such products are generally used when especially difficult cases of D/SD occur. If such products are needed, subsequently switching to cosmetically optimized therapeutic shampoos should be advised for prophylactic usage. Materials such as climbazole and octopirox have been used regionally, but have been limited by the lack of acceptance by the US Food and Drug




Table 15.2 Overview of scalp care active materials. Common actives

Primary mechanism

Typical amount used



Physical characteristics


Most potent antifungal activity Pyrithione zinc (PTZ)



White powder


Wide. Positive impact on esthetics and hair care benefits




White powder


Limited. Is expensive and requires regulatory approval

Selenium sulfide



Red powder


Limited. Color and odor affect esthetics

Moderately potent antifungal activity Climbazole



White powder


Limited. Not accepted globally by regulatory bodies




White powder


Limited. Not accepted globally by regulatory bodies


Yellow powder


Limited. Color and odor affect esthetics

Sulfur Least potent antifungal activity Salicylic acid

Keratolytic agent


White powder


Limited. Low antifungal potency

Coal tar

Regulator of keratinization


Black viscous liquid


Limited. Color and odor affect esthetics

Administration (FDA). Although the FDA does accept the safety and efficacy of salicylic acid, coal tar, and sulfur, either low potency or poor esthetics have limited their broad utilization.

Table 15.3 Formulation factors affecting the realization of full efficacy. 1 Retention of active material on scalp after rinsing 2 Physical bioavailability: spatial coverage of active on scalp surface 3 Chemical bioavailability: prevalence of active species of active

Unique attributes of scalp care products The complexity of the shampoo delivery vehicle described above in combination with the unique attributes of the active material accounts for varying levels of efficacy obtained when using similar actives at identical levels. The case is well-illustrated for shampoos based on PTZ, in which the physical form of the material as well as the shampoo composition affect resultant activity [1] by three parameters (Table 15.3). Regardless of the type of active material used in shampoos, activity is derived from how much material is retained on the scalp surface after rinsing. This is a complex formulation technology task because cleaning is occurring simultaneously. The efficiency of the coacervate technology delivery system directly impacts how much of a material such as PTZ is retained on the scalp after rinsing. This efficiency of this deposition can vary dramatically between commercial prod-


ucts and will directly affect efficacy [6]. The achievement of effective active delivery is a complex balancing of parameters to maximize delivery while not compromising the esthetic properties of the product. While the amount of material remaining on the scalp surface is critically important, the physical distribution and bioavailability of the material is just as important. For a particulate material such as PTZ, there is substantial technology in the optimization of the particle morphology (shape and size) to improve physical distribution on the scalp surface. There are two types of PTZ in use today. Standard PTZ has a submicron size and a nondescript morphologic shape. Optimized PTZ is used by one manufacturer where the morphology is platelet (Figure 15.3) and the particle size has been optimized to 2.5 μm. Both of these parameters are designed to maximize the efficiency of scalp surface cover-

15. Shampoos age to achieve uniform benefits throughout the microenvironment of the scalp. This is important as the effective zone around a PTZ particle (Figure 15.4a) is limited by the molecular solubility of PTZ in the surrounding medium of sebaceous oils. By use of platelet morphology particles, the

tive zo fec n

PTZ particle



Figure 15.3 Electron micrograph of a unique form of pyrithione zinc (PTZ), optimized for size and morphology to maximize the efficiency of surface coverage.

spatial coverage is more efficient than use of a three-dimensionally symmetric particle. Particle size of the platelet is also important to achieve uniformity of coverage. Ideally, smaller particles are better, but they suffer from a trade-off that they are more difficult to retain through the rinsing step. Thus, practically, it has been observed [1] that an optimum particle size is 2.5 μm, which represents the average size of the optimized PTZ material. Together, these attributes constitute physical bioavailability. The third factor affecting delivered efficacy is optimization of chemical bioavailability [7]. Chemically, PTZ is considered a coordination complex between inorganic zinc ion (Zn) and the pyrithione (PT) organic moiety. In such a material, the bonds are weak and an equilibrium exists between the intact species and the separate components (Figure 15.4b). Neither of the separated components (Zn and PT) are effective antifungals; thus, to the extent this dissociation occurs, PTZ chemical bioavailability and resultant efficacy is reduced. By adding a common ion to the system (in the form of zinc carbonate), the equilibrium is shifted (exploiting LeChatelier’s principle) to the intact and more effective PTZ; this unique potentiated PTZ formula thus maximizes bioavailability of the deposited material. Another important aspect in product selection is that the cleaning activity of the shampoo not result in irritation of

(a) Standard PTZ formula O


Active species


Potentiated PTZ formula

Zn O






Zn O


Plus zinc carbonate O S


O +






(b) Figure 15.4 (a) Conceptual representation of the zone of inhibition of fungal growth surrounding PTZ particles and the importance of spatial distribution of particles to achieve uniformity of coverage. (b) PTZ can dissociate into component pyrithione (PT) and zinc (Zn) which reduces the presence of the intact bioactive species. The addition of zinc carbonate alters this equilibrium to maintain PTZ in its bioactive intact form.




Table 15.4 Summary of advantages and disadvantages of using scalp care shampoos.

Table 15.5 Summary of usage habits to maximize the therapeutic benefit.

Advantages Convenient form for treatment and prevention of dandruff/seborrheic dermatitis For cosmetically optimized therapeutics, compliance is increased • Affordability • No esthetic trade-offs For PTZ-based products, over 50 years of safe utilization For PTZ-based products, no tachyphylactic responses

1 Use the therapeutic shampoo for every shampooing to prevent a relapse 2 Use a therapeutic product that is cosmetically optimized and affordable 3 Shampoo as frequently as possible 4 Lather exposure time is not important but repeating the entire process can be beneficial 5 Product should be utilized all year 6 If a rinse-off conditioner is needed, use one that contains antidandruff active

Disadvantages For straight therapeutic products, compliance is reduced • Can be very expensive • Can have substantial esthetic trade-offs

the scalp. For those with D/DS this would interfere with the natural cutaneous repair processes that occur upon Malassezia population reduction. In addition to appropriate selection of the surfactant system as described above, some antifungal actives such as PTZ have been shown to reduce the irritation potential of the surfactants [8].

Advantages and disadvantages The use of therapeutic shampoos for effective treatment of D/SD as well maintenance of normal scalp hygiene is very convenient because the patient will be utilizing this product in the shower already (Table 15.4). By choice of a cosmetically optimized therapeutic product, the user suffers no esthetic trade-offs (compared to cosmetic shampoos) that would limit compliance. This class also tends to be more affordable than standard therapeutic products, which also increases long-term (prophylactic) usage. No diminution of benefit (e.g. tachyphylaxis) occurs upon long-term use of PTZ-based products; this is based on both designed clinical studies [9] as well as anecdotal evidence associated with over 50 years of usage history. The only disadvantage of using such scalp care products occurs when a strict therapeutic product is chosen. The expense and esthetic negatives that normally accompany such products limit patient compliance leading to frequent frustrating condition reoccurrence; these products should be limited to the most recalcitrant of cases.

Effective use of products D/SD is a chronic condition characterized by frequent reoccurrence, resulting in frustration on the part of the patient (Table 15.5) [10]. Initial treatment of the condition appears


to be managed fairly effectively by either independent use of therapeutic antifungal shampoos or by combination with topical corticosteroid usage. However, preventative treatment is required for long-term management of the condition. Because Malassezia easily recolonize, using a cosmetically optimized therapeutic product for each shampoo experience is the optimum method for preventing reoccurrence. If cosmetic shampoo usage is interspersed with therapeutic products, efficacy is decreased [11]; not only does the cosmetic shampoo not deliver active to the scalp, it washes off any deposited material from the prior exposure to the active-containing shampoo. The desire to switch between a cosmetic shampoo and therapeutic product is either the real or perceived esthetic trade-offs in use of a therapeutic product. It has been shown [12] that therapeutic products do not provide all of the desired esthetic benefits and that this will drive patients to choose cosmetically optimized therapeutic shampoos for treating scalp conditions. Even with cosmetically optimized therapeutic products, there is often a perception that these products are not equivalent to cosmetic shampoos. While this may have been true in the past, modern technologies can deliver efficacious therapeutic and cosmetic benefits without the traditional trade-offs of standard therapeutic treatments. A wide range of D/SD shampoo treatments are available [13], with widely ranging costs. By recommending a therapeutic product that has been cosmetically optimized and one that is affordable for ongoing usage, the patient is best advised to use this product as their normal product to prevent reoccurrence. Even by selection of an effective therapeutic product, how it is used can make a difference to the magnitude of benefit achieved. The length of time the lather is exposed to the scalp is generally not important as it is the material that is retained on the scalp after rinsing that provides the benefit. Using coacervate-based deposition technologies, it is the rinsing that triggers the deposition. Repeating the lathering and rinsing process twice will more thoroughly remove the sebaceous lipid and allow more active to be deposited.

15. Shampoos D/SD symptoms occur year-round and should be treated all year. There is a misperception that it is a seasonal condition, primarily occurring in cold, dry seasons. This has been shown not to be true [11]. Winter months with less humid air combined with the tendency to wear darker clothing make the patient more able to detect the flaking symptoms under these conditions, but they occur all of the time. Higher frequency of shampooing may occur in summer months resulting in a slight decrease in severity of symptoms. Another critical usage factor involves whether a rinse-off conditioner is used after the shampoo [11]. Rinse-off conditioners that do not contain antidandruff actives remove a portion of the deposited active from the prior therapeutic shampoo exposure thereby reducing efficacy. If the patient desires use of a rinse-off conditioner, one containing antidandruff active should be recommended so that loss of retained active does not occur once the entire hair care regimen is practiced.

Benefits of use of scalp care shampoos Resolution of D/SD is the primary motivation for initiation of use of therapeutic shampoos. The choice of shampoo should be motivated by, in order: efficacy, cosmetic hair benefits, and cost. Assessing the relative efficacy of a product usually involves double-blind placebo-controlled drug studies using medical experts to grade the severity of flaking and erythema. A review of the comparative efficacy of products [3] supports that the most effective products are those that contain an effective antifungal, the most potent of which are PTZ, selenium sulfide, and ketoconazole. Further rank-ordering within this group is somewhat difficult because of conflicting studies and the part that the specific formulation then plays. However, it is clear that cosmetically optimized therapeutics can be as effective as standard therapeutics; the marketing strategy used to position these products is not necessarily a good predictor of the true technical efficacy. The use of certain scalp care shampoos also demonstrate the ability to deliver anti-irritancy effects [14]. There appears to be a wide range in activities depending on the specific active used. PTZ, and especially the potentiated PTZ formula, appears to be most effective at reducing irritation. Irritation and inflammation are early steps in the etiology of D/SD as well as many other scalp conditions. Thus, use of the zincbased therapeutic products may well have general scalp health benefits beyond D/SD mitigation [15]. The scalp health benefits associated with use of antidandruff shampoos may extend to hair benefits as well. A number of studies have demonstrated (e.g. Berger et al. [16]) that use of these products can reduce the rate at which hair is lost. The mechanism for this benefit is not known, but may be speculated to originate in the reduction of inflam-

mation referred to above as follicular inflammation may impede regrowth of lost hairs. A further benefit of the scalp inflammation being reduced by these products is less itch and subsequent scratching which reduces hair damage and improves the quality and appearance of hair.

Conclusions Normal scalp hygiene requires frequent and effective cleaning of the scalp. Cosmetic shampoos do this effectively while providing conditioning benefits for the hair. For many individuals, this frequent cleaning is sufficient to prevent adverse scalp effects. However, many still experience the symptoms of D/SD. For this group, therapeutic products are required that contain antidandruff actives that control the scalp Malassezia population. A subset of this class is cosmetically optimized therapeutics in which the product delivers the therapeutic benfits without loss of the typical cosmetic shampoo esthetics. This leads to much higher compliance, leading to effective long-term care of the chronic condition. Other factors relevant for selecting the most useful product are that the active and shampoo composition be optimized to maximize the physical and chemical bioavailability of the active; this is especially true for PTZ-based treatments. Once the best shampoo is chosen, effective habits are required to realize the full benefit: frequent use without switching to cosmetic shampoos, use all year around, and the use of a rinse-off conditioner that also contains antidandruff active.

References 1 Schwartz J. (2007) Treatment of seborrheic dermatitis of the scalp. J Cosmet Dermatol 6, 18–22. 2 Elewski B. (2005) Clinical diagnosis of common scalp disorders. J Investig Dermatol Symp Proc 10, 190–3. 3 Schwartz J, Cardin C, Dawson T Jr. (2005) Dandruff and seborrheic dermatitis. In: Barran R, Maibach H, eds. Textbook of Cosmetic Dermatology, 3rd edn: New York: Taylor & Francis, pp. 259–72. 4 Shaw E, Bernstein J, Losee K, Lott W. (1950) Analogs of aspergillic acid. IV. Substituted 2-bromopyridine-N-oxides and their conversion to cyclic thiohydroxamic acids. J Am Chem Soc 72, 4362–4. 5 Snyder F. (1969) Development of a therapeutic shampoo. Cutis 5, 835–8. 6 Bailey P, Arrowsmith C, Darling K, Dexter J, Eklund J, Lane A, et al. (2003) A double-blind randomized vehicle-controlled clinical trial investigating the effect of ZnPTO dose on the scalp vs. antidandruff efficacy and antimicotic activity. Int J Cosmet Sci 25, 183–8. 7 Schwartz J. (2005) Product pharmacology and medical actives in achieving therapeutic benefits. J Investig Dermatol Symp Proc 10, 198–200. 8 Warren R, Schwartz J, Sanders L, Juneja P. (2003) Attenuation of surfactant-induced interleukin 1α expression by zinc pyrithione. Exog Dermatol 2, 23–7.




9 Schwartz J, Rocchetta H, Asawanonda P, Luo F, Thomas J. (2009) Does tachyphylaxis occur in long-term management of scalp seborrheic dermatitis with pyrithione zinc-based treatments? Int J Dermatol 48, 79–85. 10 Chen S, Yeung J, Chren M. (2002) Scalpdex: a quality-of-life instrument for scalp dermatitis. Arch Dermatol 138, 803–7. 11 Schwartz J. (2004) A practical guide for the treatment of dandruff and seborrheic dermatitis. J Am Acad Dermatol 50, P71. 12 Draelos Z, Kenneally D, Hodges L, Billhimer W, Copas M, Margraf C. (2005) A comparison of hair quality and cosmetic acceptance following the use of two anti-dandruff shampoos. J Investig Dermatol Symp Proc 10, 201–4.


13 Schwartz R, Janusz C, Janniger C. (2006) Seborrheic dermatitis: an overview. Am Fam Physician 74, 125–30. 14 Margraf C, Schwartz J, Kerr K. (2005) Potentiated antidandruff/ seborrheic dermatitis formula based on pyrithione zinc delivers irritation mitigation benefits. J Am Acad Dermatol 52, P56. 15 Schwartz J, Marsh R, Draelos Z. (2005) Zinc and skin health: overview of physiology and pharmacology. Dermatol Surg 31, 837–47. 16 Berger R, Fu J, Smiles K, Turner C, Schnell B, Werchowski K, et al. (2003) The effects of minoxidil, 1% pyrithione zinc and a combination of both on hair density: a randomized controlled trial. Br J Dermatol 149, 354–62.

Part 2: Moisturizers Chapter 16: Facial moisturizers Yohini Appa Johnson & Johnson, New Brunswick, NJ, USA

BAS I C CONCEPTS • Facial moisturizers can be used to improve skin texture, treat dry skin, and provide sun protection. • Occlusives, humectants, emollients, and sunscreens are important ingredient categories in facial moisturizers. • The efficacy of a facial moisturizer can be measured via transepidermal water loss and corneometry. • Facial moisturizers can be an important adjunct in the treatment of facial dermatoses, such as atopic dermatitis and eczema.

Introduction The face is the most conspicuous representation of age and health. While the eyes are considered the windows to the soul, the face is its billboard. No other body part demonstrates personal past history as convincingly as the face. Wrinkles form on the face well before the rest of the body and serve as an indicator of age and lifestyle. The relative color and luminosity of the facial skin represents overall health and emotional state. Facial skin can be dull to vibrant representing poor to excellent physical health. The face mirrors acute changes in well-being. For example, persons experiencing cardiac distress appear “ashen” while anger or embarrassment may be expressed as a reddened face. Thus, the face represents the current physical state of the individual. Moisturizers can enhance the appearance of the face and are thus important cosmeceuticals. The face is rarely covered and constantly subjected to the elements. It is one of the most light-exposed areas of skin on the body, the other areas being the shoulders, upper chest, and forearms; as a result it receives high amounts of UV radiation. The incidence of cutaneous melanoma as measured by relative tumor density is highest on the face in subjects over the age of 50 years, a statistic that is interpreted as directly correlating to the amount of long-term UV exposure [1]. This means that facial photoprotection is of great importance, thus the incorporation of efficacious UVA and UVB protection in daily facial moisturizers is worthwhile.

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

Facial skin is physiologically unique. It possesses numerous sweat glands and a relatively thin dermis. It is densely populated with sebaceous glands, possessing 400–900 glands per square centimeter [2]. The face is a major point of contact for sensory input, the facial skin possesses high innervation and is therefore more sensitive than skin elsewhere on the body [3]. The skin covering the face also has to allow for the subtleties of facial expressions and phonoation. Of all the areas on the body, the skin on the face has the highest level of hydration. When the ratio of transepidermal water loss (TEWL) to skin surface hydration was calculated in order to determine the most consistently hydrated area of the body, the forehead and cheek showed the lowest ratios (Figure 16.1).

Dry facial skin Dry skin is a term used to describe the condition that arises when the normal functioning of the skin is compromised. More specifically, it is a manifestation of the consequences that arise from a loss of water from the outermost layer of the dermis: the stratus corneum (SC). The SC is formed when keratinocytes, cuboidal cells in the lower half of the epidermis, migrate from the basal layer to the most superficial layer, producing large amounts of the water-insoluble protein keratin along the way. The keratinization and migration process results in flattened, keratin-filled keratinocytes, referred to as corneocytes, which create an overlapping barrier with a “brick and mortar” appearance that is nearly waterproof. The gaps between the corneocytes, or “bricks,” are filled with intercellular lipids, or “mortar” that is produced by keratohyaline granules. The SC layer is also



Moisturizers Forehead 257 0.055 Cheek 345 0.04

H2O TEWL/H2O ratio

Back of hand 97 0.12 Upper leg 106 0.1

Top of foot 72 0.14 Figure 16.1 Skin surface hydration and transepidermal water loss (TEWL) and SciCon ratio.

referred to as the “dead layer” because by this point the cells have stopped synthesizing proteins and are unresponsive to cellular signaling. Cells in the SC are eventually sloughed off and replaced by more cells coming up through the epidermis, thereby maintaining a continuous barrier. It normally takes 26–42 days for the epidermis to cycle completely [4]. The process of skin cell differentiation and maturation is a delicate balance that is easily disrupted. If the water content of the SC drops below 20% for an extended period of time, the enzymes involved in desquamation will be unable to function and the process of orderly epidermis cycling will be compromised. This especially apparent in dry facial skin. There are many functions that the epidermal barrier performs: 1 Maintains a 20–35% water content; 2 Limits TEWL; 3 Preserve water homeostasis in the epidermis; 4 Sustains optimal lipid synthesis; and 5 Allows for orderly desquamation of SC cells.


A shift away from equilibrium in one of these five functions can result in a compromise of the barrier and the basic consequence is what we refer to as “dry skin.” More specifically, when TEWL is increased to the point that the water content in the SC is reduced to below 10%, the clinical signs of xerosis will appear [5]. The orderly desquamation of the SC is a complex process which if disturbed can lead to a self-renewing cycle of dry skin. The corneocytes that make up the SC are highly interconnected and able to withstand a large amount of mechanical stress. When new cells are formed, enzymatic digestion of the proteins anchoring the old cells is required for removal. The level of humidity in the SC is a critical factor modulating the activity of these desquamatory enzymes, specifically stratum corneum chymotryptic enzyme (SCCE). When this process breaks down, desquamation becomes irregular and dead SC cells slough off in large clumps; representing the “flaking” seen in so many dry facial skin conditions [6]. The sebum-rich skin of the face can appear moisturized but possess a low water content. Sensory symptoms can include but are not limited to: dryness, discomfort, pain, itching, stinging, or tingling sensations. Tactile signs are rough, uneven, and sand-like feeling skin. Visible signs, which can be macroscopic or microscopic, are redness, dull surface, dry white patches, flaky appearance, and cracks and fissures. There are many causes for these signs and symptoms. In all, the presence of dry skin represents disorder in the complex system that continually renews the facial skin.

Facial moisturization The physiologic goal of facial moisturization is to restore the elasticity and flexibility of the SC, thereby restoring its barrier function. Additionally, the reintroduction of humidity to the SC allows for proper functioning of desquamation enzymes and restores the natural skin renewal cycle. Kligman and Leyden [7] defined a moisturizer as “a topically applied substance or product that overcomes the signs and symptoms of dry skin.” The esthetic goal of moisturization is achieving soft, supple, glowing, healthy looking skin, as subjectively evaluated by the end-user. Regular use of facial moisturizers mitigate and prevent signs of aging, especially when formulated with broad-spectrum sun protection for daytime use. Because the face is one of the most sensitive areas of the body, a facial moisturizer must meet esthetic goals in addition to fulfilling a broad set of performance attributes. Consumers expect a facial moisturizer to reduce dryness, improve dull appearance, smooth and soften the skin, and increase suppleness [8]. Furthermore, these expectations

16. Facial moisturizers

Table 16.1 Function of common moisturizer ingredients. This listing represents the common ingredients found in a moisturizer formulation identifying the role of each of the substances in the ingredient disclosure. Humectant













Glyceryl stearate


PEG 100 stearate


Potassium cetyl phosphate


Behenyl alcohol


Caprylyl methicone


Hydrogenated palm glycerides





Caprylyl glycol



Cetearyl glucoside


Cetearyl alcohol








must be achieved by a moisturizer with a minimal presence and pleasant sensory qualities. A properly formulated moisturizer can supplement the function of the endogenous epidermal lipids and restore the epidermal barrier function. This allows the skin to continue its natural process of renewal and desquamation at a normal rate. The substances utilized by all moisturizers to achieve this desired effect fall into a handful of basic categories (Table 16.1). Humectants, such as glycerin, attract and hold moisture, facilitating hydration. Emollients, typically lipids or oils, enhance the flexibility and smoothness of the skin and provide a secondary soothing effect to the skin and mucous membranes. Occlusives create a hydrophobic barrier to reduce water loss from the skin. Emulsifiers work to bring together immiscible substances; they are a critical element in the oil and water mixtures employed in moisturizer formulas. Preservatives prevent the premature breakdown of components and inhibit microbiologic growth. Fragrances not only add to the esthetic value but can also mask the odor of formulation ingredients. These components make up the basic formulation of any moisturizer, and the choices available to achieve the preferred outcome are vast. The formulation of an acceptable and effective moisturizer for the face, one that will enable

the natural processes of skin desquamation to occur and maintain healthy barrier function while meeting high esthetic standards, is as much an art as it is a science.

Facial moisturizer formulation Facial moisturizers are typically oil-in-water emulsions. The water improves skin feel and offers an acceptable, universally tolerated base for the active ingredients. The water or oil solubility of components is inconsequential because both are present. Emulsions allow for a wide range of properties, such as slow to fast absorption rates depending on the final viscosity of the formulation. The fine-tuning of these properties is important for achieving the high esthetic expectations of a facial moisturizer. For example, a daily-use formula with high emollient content may feel heavy in a cream but be acceptable in liquid form. Conversely, overnight creams with antiaging additives may be thick in order to remain on the face during sleep and to slow the absorption of active components. Therefore, by utilizing a range of water to oil ratios, and varying humectant and emollient mixtures, the desired effects can be formulated within the acceptable esthetic parameters for a facial moisturizer.




Moisturizer ingredients and function Humectants The overall hydration level of the SC affects its mechanical properties. If the water level in the SC drops below 10%, its flexibility can be compromised and it becomes susceptible to damage from mechanical stress [9]. Humectants are key substances to maintain skin hydration. Natural humectants, such as hyaluronic acid, are found in the dermis, but external humectants can be externally applied in moisturizers. Humectants draw water from the viable epidermis and dermis, but can draw water from the environment if the ambient humidity is over 80%. Humectants are water-soluble organic compounds that can sequester large numbers of water molecules. Glycerin, sorbitol, urea, and sodium lactate are all examples of externally applied humectants. Glycerin, also referred to as glycerol, is one of the most widely utilized compounds in cosmetic formulations because of its effects on multiple targets and its universal applications. Its chemical structure brings together the stability of three carbon atoms with three water-seeking oxygen atoms in an anisotropic molecule that is perfectly designed for use in skin and hair moisturizers. Glycerin also allows for the construction of different product physical forms that cover the spectrum from sticks to microemulsions to free-flowing creams that maintain stability over time. The degree of purity to which glycerin can be manufactured not only ensures consistency and facilitates microbiologic stability, but also guarantees the minimization of allergic reactions by contaminants. The pure form of glycerin has been tested on thousands of patients and millions more have used it with extremely few reports of ill effects. Glycerin is generally classified as a humectant; however, this characteristic is not the sole reason for its ability to achieve skin moisturization, in fact, it performs a number of different functions that are not directly related to its water-holding properties. Glycerin can restore the suppleness of skin without increasing its water content, a trait that is exploited by its use in the cryopreservation of skin, tissue, and red blood cells, where water would freeze and damage them. Glycerin enhances the cohesiveness of the intercellular lipids when delivered from high glycerin therapeutic formulations, thereby retaining their presence and function. Furthermore, glycerin has been identified as a contributor to the process of desquamation, a critical component of the dermal renewal cycle, through its ability to enhance desmosome digestion. In addition to its direct, humectant effects on skin moisturization, endogenously produced glycerin has exhibited effects at the molecular level in knockout mouse model studies, confirming its role in maintaining SC hydration and barrier maintenance. A recent study showed that glycerin content was three times lower, SC hydration was reduced,


and barrier function was impaired in mice deficient in the water/glycerin transporter protein, aquaporin-3 (AQP3) despite normal SC structure, protein–lipid composition and ion–osmolyte content. Glycerin, but not other small poly glycols, restored normal SC moisturization and TEWL values when applied to the AQP3-deficient mice, confirming that glycerin was physiologically necessary in the modulation of SC hydration and barrier maintenance [10]. Glycerin remains the gold standard for moisturization. The fact that it acts on so many different parameters with a nearly non-existent side-effect profile makes it a prime candidate for facial moisturizer formulations. It is also an excellent example of how moisturizer components, especially those used on the face, should be considered for their ability to enhance and protect the skin. Glycerin raises the bar for moisturizers in that it is capable of enhancing, or even rescuing, the intrinsic processes that are in place to maintain the orderly maturation of keratinocytes and the barrier function of the skin.

Occlusives Humectants are only partially effective in moisturizing the skin. In order to maintain epidermal water content and preserve the barrier function of the SC, occlusive agents are employed in a role meant to complement the water-attracting nature of humectants. Occlusive agents inhibit evaporative water loss by forming a hydrophobic barrier over the SC and its interstitial areas. Occlusion is successful in the treatment of dry skin because the movement of water from the lower dermis to the outer dermis is a guaranteed source of physiologically available water. Moreover, these occlusive agents have an emollient effect, as is the case with behenyl alcohol. Petrolatum and lanolin are two historically popular occlusives that are slowly being replaced by more sophisticated alternatives. Petrolatum is a highly effective occlusive, but it suffers from an unfavorable esthetic. Lanolin is not recommended for use in facial formulations because of its odor and potential allergenicity [11]. Newly constructed silicone derivatives have been employed in moisturizers for their occlusive properties, and they further enhance the esthetic quality of the formulation by imparting a “dry” touch. This technologic advancement is also an example of how the esthetic parameter of a facial moisturizer can have a major effect on compliance and willingness to apply.

Emollients Emollients are agents, usually lipids and oils, designed to soften and smooth the skin. Lipids are non-polar molecules and as such they repel polarized water molecules, thereby limiting the passage of water to the environment. The most prevalent lipids in the SC, especially within the extracellular membranes, are ceramides. They comprise about 40% of the lipid content of the SC, the remainder of which is 25%

16. Facial moisturizers cholesterol, 10–15% free fatty acids, and smaller quantities of triglycerides, stearyl esters, and cholesterol sulfate. These lipids are synthesized throughout the epidermis, packaged in lamellar granules, and eventually differentiate into multilamellar sheets that form the ceramide-rich SC water barrier [12]. The purpose of an emollient is to replace the absent natural skin lipids in the space between the corneocytes in the SC. Additional benefits include the smoothing of roughened skin thereby changing the skin’s appearance, and providing occlusion to attenuate TEWL and enhance moisturization. Of the three components of skin moisturizers listed in the CTFA Cosmetic Ingredients Directory, emollients outnumber occlusives 2 to 1 and the humectants 10 to 1. This is an indication not only of the number of available compounds that can perform this function, but also the variety of lipids that can be utilized [13].

A key immediate event that leads to chronic photoaging is the production of proteases in response to UV irradiation at doses well below those that cause skin reddening. Matrix metalloproteinases (MMPs), for example, are zinc-dependent endopeptidases expressed in many different cell types and are critical for normal biologic processes. They may also be involved in desquamation processes, and overexpression would lead to early sloughing and increase in TEWL. With a proper sunscreen regimen, production of MMPs is minimized and their participation in chronic photoaging can be avoided. The addition of sunscreens to facial moisturizers also contributes to the prevention of reactive oxygen species (ROS) production, Langerhans cell depletion, and sensitivity to UV radiation, as is observed in polymorphous light eruption.

Facial moisturizer testing Fragrance Fragrance is a component of facial moisturizers that is often dismissed as an unnecessary potential irritant, but this idea is becoming increasingly antiquated as the science supporting its proper use and evaluation is improved. Vigorous protocols have been developed that comprehensively and conclusively assess the tolerance of formulations on human subjects. Fragrances are screened separately first and then together in both normal and sensitive populations, and utilized at the minimum concentration required to mask the smell of certain components, if necessary. Fragrance improves the overall esthetic qualities of the moisturizer, which is an important component of any moisturizer formulation, especially one that is applied to the face.

Preservatives Preservatives are also subject to the same rigorous testing protocols as fragrances. The preservative must be strong enough to completely inhibit bacterial growth, but must not be sensitizing or irritating. Preservatives are an important component in facial moisturizers to prevent the lipids in the formulation from becoming rancid. All facial moisturizers have some type of preservative, because there is really no such thing as a preservative-free formulation.

Photoprotection and facial moisturizers Sunscreens could be considered to be the most globally effective ingredient added to a facial moisturizer. Because the incidence and mortality rates of skin cancer have been steadily rising in the USA, the use of sunscreen as a daily protectant has become more important to consumers. There are both immediate and long-term benefits from photoprotection. The immediate benefit is the prevention of a painful sunburn while long photoprotection results in reduced photodamage manifesting as wrinkling, inflammation, and dryness.

The formulation of a moisturizer centers on the primary goal of delivering the perception of moisture to the skin. This includes not only adding moisture to the skin, but also the improvement of the barrier function and reinstating natural skin reparative processes. The testing of the efficacy of a moisturizer is based on barrier function assessment. There are many ways to assess the barrier function of the skin based on SC integrity. Measurement of the TEWL is one method. A damaged SC allows water to evaporate resulting in high TEWL readings. These measurements are taken with an evaporimeter, which measures the amount of water vapor leaving the skin. The amount of water in the skin can also be measured via skin conductance. This technique, known as corneometry, measures the amount of low level electricity conducted by the skin. Because water is the conductor of electricity in the skin, the amount of current conducted is directly related to the water content. Thus, the efficacy of a moisturizer can be measured by its effect on water vapor loss and skin conductance. Another method for evaluating skin dryness is D-squames. D-squames are circular, adhesive discs placed on the skin surface with firm pressure and then pulled away. The removed skin is observed and parameters such as the amount of skin removed, size of flakes, and coloration can be recorded. Differences between dry skin and normal moisturized skin are clearly evident upon examination of the disc, and further characterization can be carried out to differentiate levels of dryness and qualitative differences in desquamation. The barrier function of the skin can be assessed following application of an irritant to the skin surface. The introduction of an irritant can cause erythema and scaling in the compromised SC. A frequent irritant used for the assessment of barrier function is sodium lauryl sulfate (SLS). The amount of erythema and TEWL is measured following




scrubbing of the skin with SLS. Skin with a better barrier following use of an efficacious moisturizer will experience less damage than skin that possesses a compromised barrier. Finally, after testing the efficacy of the formulation in a controlled, laboratory setting, its efficacy must be evaluated on a group of consumers. Consumer testing is usually carried out in a blind study involving 200–300 subjects, from geographically disparate locales in order to normalize any differences in skin types or backgrounds. This testing will introduce parameters that are evaluated subjectively by the population of subjects such as skin feel, perception of texture, ease of application, and scent, among other things, that define its esthetic qualities. The functional qualities of the moisturizer, such as “immediate comfort” and “longlasting effect” will also be evaluated by the consumer group and incorporated into the overall assessment.

Use of facial moisturizers in common inflammatory dermatoses The face presents a set of unique challenges regarding the treatment of skin disorders. What may be acceptable for treatment regimens elsewhere on the body, such as a strong occlusive such as petrolatum or a humectant such as urea, will be esthetically challenging to the user and stand in the way of compliance. While it is easy to think of esthetics as secondary to efficacy of treatment, it should be considered of primary importance where the face is concerned. This concept cannot be overstressed because the sensitivity of the facial skin to the sensory and olfactory qualities of moisturizers is much higher than the rest of the body. It is generally believed that facial atopic dermatitis and various other facial skin diseases are associated with disturbances of skin barrier function as evidenced by an increase in TEWL, a decrease in water-binding properties, and a reduction in skin surface lipids. When chronic, inflammatory skin diseases manifest on the face, there is the challenge of reducing the lesion as quickly as possible to prevent it from worsening and further compromising the integrity of the skin involved. Because of the high sensitivity of the facial skin, what may start as a small lesion can quickly be exacerbated through physical intervention and quickly worsened. These problems can be addressed through the continual use of appropriate moisturizers, which have been shown to improve skin hydration, reduce susceptibility to irritation, and restore the integrity of the SC. Some moisturizers also supply the compromised SC with lipids that further accelerate barrier recovery. Moisturizers can serve as an important first-line therapeutic option for patients with atopic dermatitis and other chronic skin diseases [14]. Historically, moisturizers have been shown to have a steroid-sparing effect in patients with atopic dermatitis and eczema. Many of the elements in moisturizers, from lipids


to emollients, have been shown to significantly improve the condition of the skin when used by patients with various dermatoses [15]. Glycerin has been implicated in the molecular mechanism controlling keratinocyte maturation, an important aspect of normal desquamation and barrier maintenance. Furthermore, its role in maintenance of hydration for the proper functioning of proteases, especially filaggrin, is critical to the successful treatment of eczemas [16,17]. Recently, a comprehensive clinical study provided evidence that moisturizers not only enhance the efficacy of topical corticosteroids in patients with atopic dermatitis, but may also prevent the recurrence of disease [15]. In general, the maintenance of the SC along with rapid repair of disruptions to the barrier that would otherwise become larger and increase inflammation and discomfort as well seem to be central tenets in the approach to treating potential dermatoses on the face with moisturization. Therefore, facial moisturizers may represent a valuable first-line treatment option for many dermatologic diseases and confer a number of important therapeutic benefits that go beyond the surface of the facial skin and have a critical role in the molecular mechanisms that maintain healthy skin.

Conclusions Facial moisturizers fulfill an important need by providing skin comfort and alleviating dryness. Efficacious formulations contain ingredients that work directly to bring moisture to the skin, but also indirectly, as is the case with glycerin, induce the transport and retention of water molecules at the subcellular level. The goal of facial moisturizers is to enhance, or restart, the processes intrinsic to the skin’s natural ability to maintain its barrier function through the multiple pathways utilizing proteases, lipids, cell differentiation and, eventually, desquamation, all while maintaining an esthetically pleasant presence.

References 1 Elwood JM, Gallagher RP. (1998) Body site distribution of cutaneous malignant melanoma in relationship to patterns of sun exposure. Int J Cancer 78, 276–80. 2 Montagna W. (1959) Advances in Biology of Skin. Oxford, New York: Symposium Publications Division, Pergamon Press. 3 Montagna W, Kligman AM, Carlisle KS. (1992) Atlas of Normal Human Skin. New York: Springer-Verlag. 4 Baumann L. (2002) Cosmetic Dermatology: Principles and Practice. New York: McGraw-Hill. 5 Draelos ZK. (2000) Atlas of Cosmetic Dermatology. New York: Churchill Livingstone. 6 Watkinson A, Harding C, Moore A, Coan P. (2001) Water modulation of stratum corneum chymotryptic enzyme activity and desquamation. Arch Dermatol Res 293, 470–6. 7 Kligman AM, Leyden JJ. (1982) Safety and Efficacy of Topical Drugs and Cosmetics. New York: Grune & Stratton.

16. Facial moisturizers 8 Barton S. (2002) Formualtion of skin moisturization. In: Leyden JJ, Rawlings AV, eds. Skin Moisturization. New York: Marcel Dekker, pp. 547–84. 9 Rawlings AV, Canestrari DA, Dobkowski B. (2004) Moisturizer technology versus clinical performance. Dermatol Ther 17 (Suppl 1), 49–56. 10 Hara M, Verkman AS. (2003) Glycerin replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Proc Natl Acad Sci U S A 100, 7360–5. 11 Draelos ZK. (1995) Cosmetics in Dermatology, 2nd edn. New York: Churchill Livingstone. 12 Downing S, Stewart ME. (2000) Epidermal composition. In: Loden M, Maibach HI, eds. Dry Skin and Moisturizers: Chemistry and Function. Boca Raton: CRC Press, 2000: pp. 13–26. 13 Draelos ZK, Thaman LA. (2006) Cosmetic Formulation of Skin Care Products. New York: Taylor & Francis. 14 Lebwohl M. (1995) Atlas of the Skin and Systemic Disease. New York: Churchill Livingstone. 15 Ghali FE. (2005) Improved clinical outcomes with moisturization in dermatologic disease. Cutis 76 (Suppl), 13–8. 16 Hanifin JM. (2008) Filaggrin mutations and allergic contact sensitization. J Invest Dermatol 128, 1362–4. 17 Presland RB, Coulombe PA, Eckert RL, et al. (2004) Barrier function in transgenic mice overexpressing K16, involucrin, and filaggrin in the suprabasal epidermis. J Invest Dermatol 123, 603–6.

Further reading Bikowski J. (2001) The use of therapeutic moisturizers in various dermatologic disorders. Cutis 68 (Suppl), 3–11. Burgess CM. (2005) Cosmetic Dermatology. Berlin: Springer. Crowther JM, Sieg A, Blenkiron P, et al. (2008) Measuring the effects of topical moisturizers on changes in stratum corneum thickness, water gradients and hydration in vivo. Br J Dermatol 159, 567–77. Del Rosso JQ. (2005) The role of the vehicle in combination acne therapy. Cutis 76 (Suppl), 15–8.

Fisher GJ, Datta SC, Talwar HS, et al. (1996) Molecular basis of suninduced premature skin ageing and retinoid antagonism. Nature 379, 335–9. Fisher GJ, Varani J, Voorhees JJ. (2008) Looking older: fibroblast collapse and therapeutic implications. Arch Dermatol 144, 666–72. Fisher GJ, Voorhees JJ. (1996) Molecular mechanisms of retinoid actions in skin. FASEB J 10, 1002–13. Fisher GJ, Wang ZQ, Datta SC, et al. (1997) Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med 337, 1419–28. Fluhr J. (2005) Bioengineering of the Skin: Water and Stratum Corneum, 2nd edn. Boca Raton: CRC Press. Friedmann PS. (1986) The skin as a permeability barrier. In: Thody AJ, Friedmann PS, eds. Scientific Basis of Dermatology. Edinburgh, London: Churchill Livingstone, pp. 26–35. Held E, Jorgensen LL. (1999) The combined use of moisturizers and occlusive gloves: an experimental study. Am J Contact Dermatol 10, 146–52. Jungermann E, Norman O, Sonntag V. (1991) Glycerin: A Key Cosmetic Ingredient. Vol. 11, Cosmetic Science and Technology Series. New York: Marcel Dekker. Kafi R, Kwak HS, Schumacher WE, et al. (2007) Improvement of naturally aged skin with vitamin A (retinol). Arch Dermatol 143, 606–12. Loden M, Maibach HI. (1999) Dry Skin and Moisturizers: Chemistry and Function. Boca Raton: CRC Press. Orth DS. (1993) Handbook of Cosmetic Microbiology. New York: Marcel Dekker. Page-McCaw A, Ewald AJ, Werb Z. (2007) Matrix metalloproteinases and the regulation of tissue remodeling. Nat Rev Mol Cell Biol 8, 221–33. Rattan SI. (2006) Theories of biological aging: genes, proteins, and free radicals. Free Radic Res 40, 1230–8. Streicher JJ, Culverhouse WC Jr, Dulberg MS, et al. (2004) Modeling the anatomical distribution of sunlights. Photochem Photobiol 79, 40–7. Verdier-Sevrain S, Bonte F. (2007) Skin hydration: a review on its molecular mechanisms. J Cosmet Dermatol 6, 75–82.


Chapter 17: Hand and foot moisturizers Teresa M. Weber1, Andrea M. Schoelermann2, Ute Breitenbach2, Ulrich Scherdin2, and Alexandra Kowcz1 1 2

Beiersdorf Inc, Wilton, CT, USA Beiersdorf AG, Hamburg, Germany

BAS I C CONCE P T S • Xerosis of the hands and feet is common, caused by a paucity of sebaceous glands. • Moisturization of the hands and feet can prevent eczematous disease and aid in disease eradication. • Effective moisturizers provide occlusive lipophilic substances that act as protectants and barrier replenishers, as well as hydrophilic agents that function as humectants to bind and hold water. • Recent recognition of the role of aquaporins, special moisture regulating channels, in skin cells has provided the opportunity for a new moisturization technology, focusing on substances that stimulate and operate through aquaporins.

Introduction The hands and feet are prone to dryness and impaired barrier function because of their unique functional roles, predisposing the skin to heightened irritant sensitivity and the development of dermatoses. Protective and regenerative moisturizing skin care is the foundation for averting and treating dry skin associated skin diseases and disorders. Effective moisturizers provide occlusive lipophilic substances that act as protectants and barrier replenishers, as well as hydrophilic agents that function as humectants to bind and hold water. The importance of urea as a physiologic humectant and natural moisturizing factor is discussed. Application of moisturizers containing urea is shown to increase its concentration and exert ultrastuctural changes in the stratum corneum, hydrate severely compromised skin, and support and enhance barrier function. In addition, the role of aquaporins and the underlying mechanisms of moisture homeostasis of the skin are discussed vis-à-vis new opportunities to create better actives and product formulations which can help regulate moisturization from within the skin.

Moisturization needs of the hand and foot Skin of the hands and feet is different from other body sites. In particular, skin on the palms and soles is thicker, and has

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


a high density of eccrine sweat glands; however, it lacks apocrine glands. These sites are highly innervated and involved in most of the daily activities of life. Repetitive use of the hands and feet accompanied by pressure and friction can promote the formation of areas of thickened keratinized skin or calluses, which can crack and fissure. Site-specific requirements for hygienic care and diseases common to these sites have been described [1]. In addition, the hands and feet have special skincare needs for efficacious moisturization as well as unique requirements for formulations that are compatible with their special sensory and functional roles and needs. Hand skin is particularly susceptible to xerosis and dermatitis. Constant use of the hands, frequent washing, and environmental, chemical, and irritant exposure can provoke these problems. Further, because the hands are especially prone to injury and exposed to irritants and pathogens, specific protectant skincare formulations can be highly beneficial to prevent irritation or occupational dermatoses such as hand eczema [2]. While the feet may be less likely to suffer from deleterious occupational exposures, environmental factors can have an impact on the moisture status of the foot skin. Cold, dry weather in winter, bare feet in summer, and the confinement of shoes can compromise the hydration state. Occlusive shoes and socks can also trap moisture and render the foot susceptible to microbial infections, especially from fungus, damaging the barrier function and dehydrating the skin. In addition, certain metabolic diseases can impact circulation and innervation of the extremities, which in turn affects skin hydration. In particular, reduced circulation and eccrine sweat gland activity in diabetics cause severe xerosis which can spiral into other severe foot problems.

17. Hand and foot moisturizers Protective and regenerative moisturizing skin care is the foundation for treating all dry skin associated skin diseases and disorders. While the underlying cause of dry skin in any specific skin disorder needs to be addressed, frequently the symptomatic control of severe xerosis by appropriate moisturizers may reduce the need for more potent treatments, such as prolonged use of topical steroids and immune modulators, which can have detrimental side effects. Moisturizing creams containing urea have been reported to improve the physical and chemical nature of the skin surface, with the manifest benefits of smoothing, softening, and making dry skin more pliable [2]. Traditional moisturizing emulsions have utilized non-physiologic emollients, humectants, and skin protectants to rehydrate the skin and reduce moisture loss. The identification and understanding of the structure and function of the stratum corneum barrier lipids and the role of water binding physiologic substances collectively referred to as natural moisturizing factors (NMF) led to the development of formulations enriched in these actives. Recent recognition of the role of aquaporins, special moisture regulating channels, in skin cells has provided the opportunity for a new moisturization technology, focusing on substances that stimulate and operate through aquaporins.

Moisturizing formulations and technologies For thousands of years oils, animal and vegetable fats, waxes and butters have been used to moisturize the skin. Recognized for their emollient or skin smoothing and softening properties, these substances were used to help restore dry skin to a more normal moisture balance. The first significant advancement from these simple moisturizers occurred over a hundred years ago when emulsifiers were developed to create the first stable water-in-oil emulsion [3]. A simple emulsion can be defined as a heterogeneous system that contains very small droplets of an immiscible (or slightly miscible) liquid dispersed in another type of liquid. These emulsions consist of a hydrophilic (water loving) and a lipophilic (oil loving) portion, either of which can make up the external or internal phases of the emulsion system. The external phase generally comprises the majority of the emulsion while the smaller internal phase consists of the dispersed droplets. Most commonly used moisturizer formulations are either oil-in-water (O/W) emulsion systems, where aqueous components predominate, or water-in-oil (W/O), where the majority of ingredients are nonaqueous. Emulsifiers are necessary components of emulsion systems as water-soluble and oil-soluble ingredients are not miscible. Emulsifiers are surface active agents that reduce the inter-

facial tension between the two incompatible phases to create stable emulsion systems. The properties of the chosen emulsifiers determine the final emulsion type. Major progress in recent decades has enabled the formulation of increasingly complex emulsions (e.g. water-in-oil-inwater emulsions, multilamellar emulsions), which combine and stabilize many incompatible ingredients for moisturizing products with unique delivery characteristics that are both highly effective and esthetically pleasing [4,5]. However, it is beyond the scope of this chapter to discuss the multitude of emulsion technologies which have been developed since the advent of the simple W/O system [6]. Occlusive materials and humectants are two major classes of moisturizing ingredients in many current moisturizers (Table 17.1). Occlusive materials coat the stratum corneum to inhibit transepidermal water loss (TEWL). Additionally, cholesterol, ceramides, and some essential and non-essential free fatty acids present in oils can help to replenish the natural lamellar barrier lipids that surround the squames in the stratum corneum, fortifying the barrier function of the skin. Some common examples of occlusive materials are petrolatum, olive oil, mineral oil, soybean oil, lanolin, beeswax, and jojoba oil. Petrolatum, lanolin, and mineral oil are considered occlusive materials, yet they also serve as emollients on the skin [7,8]. Humectants are materials that are capable of absorbing high amounts of water from the atmosphere and from the epidermis, drawing water into the stratum corneum for a smoother skin feel and look. Examples of well-known humectants include glycerin (or glycerol), sorbitol, urea, sodium hyaluronate, and propylene glycol. Glycerin is a widely used humectant with strong water binding capacity and holding ability, making it ideal for dry skin moisturizing formulations. Because of its importance in moisturizing products, it has been extensively reviewed elsewhere [9,10]. A number of commercially available hand and foot moisturizers incorporate combinations of both humectants and occlusive materials to deliver the optimal skin benefits (Table 17.2).

Natural moisturizing factors The NMF are a collection of hygroscopic substances in the skin that act synergistically to confer effective water binding properties. The NMF has been reported to be composed of approximately 40% amino acids, 12% pyrrolidone carboxylic acid, 12% lactates, 7% urea, 18% minerals, and other sugars, organic acids, citrates, and peptides [11]. These substances, derived from eccrine sweat, extracellular components, largely from breakdown products of the insoluble protein filaggrin, have an important role in maintaining




Table 17.1 Key classes of commonly used moisturizing ingredients. Key classes

Moisturizing ingredients

Function in skin


Petrolatum Waxes Lanolin Mineral oil Cholesterol Ceramides Triglycerides and free fatty acids Sunflower oil Soybean oil Jojoba oil Olive oil Evening primrose oil Borage oil

Moisturization by occlusion of the stratum corneum and/or replenishment of lamellar barrier lipids


Glycerin/glycerol Sorbitol Sodium hyaluronate Propylene glycol Amino acids* Lactate* Pyrrolidone carboxylic acid* Urea* Salts*

Draws water from the formulation base, atmosphere, and from the underlying epidermis to increase skin hydration *Natural moisturizing factors – absorb large amount of water even in relatively low humidities. Provide aqueous environment for key enzymatic functions in the skin

Table 17.2 Examples of commercially available hand and foot creams. Key ingredients

Functions and claims Hand cream

Foot cream


Glycolic acid, mineral oil, petrolatum

Exfoliation and moisturization by “occlusives” to both smooth and soften skin

Exfoliation and moisturization by “occlusives” to both smooth and soften skin


Glycerin, shea butter, almond oil, olive oil

Moisturization of hands and softening of cuticles

Moisturizes, soothes, and protects dry, cracked, and callused heels


Caprylic/capric triglycerides, glycerin, sunflower oil, olive oil, almond oil

Moisturization of hands, nails, and cuticles

Soothes and heals severely dry, cracked heels


Beeswax, sweet almond oil

Moisturizes and softens dry skin

Prevents and heals cracked heels, calluses, corns, blisters


Lanolin, allantoin, glycerin, sunscreens: avobenzone, octinoxate

Moisturizes skin and helps treat the signs of aging


Glycerin, petrolatum, dimethicone, mineral oil

Helps form a protective moisture barrier; heals and protects dry hands with 24-hour moisturization


Urea, sodium lactate, glycerin

Gently exfoliates and moisturizes; relieves dry skin associated with hand eczema

Intensively moisturizes, smoothes and heals dry, cracked feet


Prescription urea (25%, 30%, 40%, or 50%), mineral oil, petrolatum

Healing and debriding of hyperkeratotic skin and nails

Healing and debriding of hyperkeratotic skin and nails


17. Hand and foot moisturizers moisture in the non-viable layers of the epidermis. Because of the moisture gradient that exists from the well-hydrated dermis to the relatively moisture-deprived stratum corneum, the cutaneous moisturization state is a function of the occlusive barrier lipids in the stratum corneum and the humectant properties of the NMF [12]. Both are critical to retain moisture and resist TEWL and the dehydrating effects of the environment. Therefore, qualitative or quantitative changes in either the barrier lipids or the NMF components can alter skin hydration. Urea is a major constituent of the water-soluble fraction of the stratum corneum [13]. Because of the high water binding capacity of urea, the water content in the skin depends on its concentration. In dry skin and in keratinization disorders, a deficit of urea is often found in the stratum corneum, confirming its importance in skin moisture balance. The concentration of urea has been reported to be reduced by approximately 50% in clinically dry skin compared to healthy skin [14,15]. The stratum corneum of unaffected psoriatic skin reveals no deficit in urea content, but levels in psoriatic lesions are reduced by 40% [16]. However, in patients with atopic dermatitis there is a deficit of about 70% in unaffected skin and about 85% in involved skin [17]. Urea has been demonstrated to be an effective moisturizer for a range of dry skin conditions [18] and especially xerosis of the elderly [19,20]. Lodén has recently compiled a summary of clinical data on the treatment of diseased skin with urea-containing formulations [21]. Besides improvements in skin hydration, urea may be enhancing the levels of linoleic acid and ceramides [22], providing an additional skin benefit. Urea is very soluble in water, but practically insoluble in lipids and lipid solvents. By its hydrogen-bond breaking effect, urea may expose water binding sites on keratin allowing the transport of water molecules into the stratum

corneum, thereby leading to a plasticizing effect [23]. In addition, urea has proteolytic and keratolytic effects in concentrations above 10% [21]. These activities are exploited in prescription formulations of 12–50%, which are often employed for debriding purposes in keratinization disorders. Lactic acid and salts of lactic acid, other efficacious components of the NMF, have also been used to treat dry skin conditions [11]. Like urea, the principal moisturizing effect is brought about by their humectancy. However, additional benefits of barrier support and restoration may be attributed to these NMF as an increase in ceramide synthesis in keratinocytes treated with lactic acid has been reported [24].

Ultrastructural effects Differential changes in skin hydration state and ultrastructure after the application of various moisturizing products can be observed using scanning electron microscopy (SEM) of frozen sections from skin biopsies [25]. Figure 17.1 depicts the epidermis of skin treated with a commercial lotion with 10% urea, sodium lactate, and glycerin (right), or treated with a vehicle lotion without urea, sodium lactate, and glycerin (left). From the SEM images it could be concluded that the product penetrated the entire stratum corneum, resulting in a more compact stratum corneum layer, with a 20–40% reduction in corneocyte thickness. When compared with an untreated control (not shown), the vehicle treatment did not have an influence on the stratum corneum thickness. The compaction of the stratum corneum by the urea product suggests an improved barrier function which has been confirmed in other clinical studies demonstrating a reduction in TEWL [22].


(b) Figure 17.1 Freeze–fracture scanning electron micrographs of the stratum corneum of skin treated with a vehicle lotion (a) or the vehicle lotion containing 10% urea and sodium lactate (b).




Clinical demonstrations of product efficacy of sodium lactate and urea formulations Hand care Several clinical studies were conducted to evaluate the ability of a fragrance-free, O/W emulsion containing 5% urea and 2.5% sodium lactate to fortify the skin of healthy subjects, and to moisturize, protect, and treat others with compromised hand skin.

Improvements in urea content Thirty-one volunteers with healthy skin were enrolled in this study. Subjects refrained from the use of topical treatments for a period of 1 week and then applied the test product twice daily for 2 weeks. Urea content of the skin, moisturization state, and skin roughness were assessed at baseline, after 2 weeks of treatment, and 3 days after the last application. A significant increase (p < 0.05) in the urea content of the skin compared with untreated skin was observed (Figure 17.2) as well as significant improvements in skin hydration levels and roughness (data not shown). Franz cell porcine skin penetration studies confirmed the

Stratum corneum urea levels (% of baseline)

1600 Untreated Urea cream






3 days regression Length of treatment


2 weeks

*Significant difference relative to untreated, p < 0.05 Figure 17.2 Stratum corneum urea content before application, after 2 weeks of daily use, and 3 days after discontinuing application of an oil-in-water emulsion containing 5% urea and 2.5% sodium lactate.

Table 17.3 Mean clinical grading scores at baseline and after 4 weeks of daily use of a 5% urea and sodium lactate oil-in-water emulsion. Cracking/fissuring

Dryness/scaling Eczema severity





Week 4




* Significant difference relative to baseline, p ≤ 0.05.


penetration and distribution of urea throughout the skin compartments 24 hours after application of a 5% urea body cream formulation: 54% stratum corneum, 7% in the viable epidermis, 22% in the dermis, and 17% in the receptor phase.

Improvement in eczema and xerosis In a second 4-week controlled usage study, 23 subjects with hand eczema and 14 subjects with hand dermatitis/xerosis were enrolled. The subjects applied the test cream at least twice per day (morning and evening), and as often as needed. Clinical evaluations were made at baseline, and after 2 and 4 weeks of hand cream use for cracking/fissuring and dryness/scaling (0–8 scale), and erythema, edema, burning, stinging, and itching (0–3 scale). Subjects with eczema were also evaluated using an Investigator’s Global Assessment for Eczema (0–5 scale). Digital photographs were taken at each of the clinical visits. Significant improvements (p < 0.05) in clinical grading scores at week 4 relative to baseline were observed for dryness/scaling and cracking/fissuring, and the Investigators Global Assessment for Eczema (Table 17.3). Average irritation scores were also significantly reduced and negligible by week 4 for itching, stinging, and burning (data not shown). Digital photographs captured the dry, compromised hand skin condition at the baseline visit, and demonstrated improvements that reflected the clinical assessments. Figure 17.3 shows the typical improvements observed in subjects at week 4 (right), compared with baseline (left). In conclusion, appropriate hand care can both treat and prevent common dermatoses such as hand eczema.

Foot care Patients with diabetes mellitus can exhibit a number of cutaneous manifestations as a result of changes in metabolic status and/or circulatory and neural degeneration [26]. Management of dry skin in these individuals is important to preserve barrier integrity which can help prevent bacterial and fungal infections. In particular, the heel skin can be very dry and scaly, prone to forming cracks and fissures which can lead to wounds that have difficulty healing. A 6-week controlled usage study of a cream containing 10% urea, 5% sodium lactate, and glycerin as a daily treatment for the feet was conducted in 31 type I and II diabetic patients. This patient population was chosen because of their highly compromised foot skin condition. The subjects’ heels were evaluated for roughness, scaling and cracking, and subjective irritation was also documented. Color photographs of the heels, taken before and after 6 weeks of treatment, documented the marked improvement in heel skin condition (Figure 17.4). In addition, significant reduction of roughness, scaling, and cracking was observed. In spite of the severely compromised skin condition at baseline, only one patient reported a mild irritation on the application site

17. Hand and foot moisturizers

Figure 17.3 Improvement in hand eczema (top) and xerosis (bottom) after 4 weeks of daily usage (right) of a hand cream containing 5% urea and sodium lactate.

which did not interfere with his completing the study according to the protocol. A second multicenter study of 604 patients with dry or severely dry, chapped feet and generalized xerosis (258, 42.7%), diabetes (179, 29.6%) or atopic dermatitis (113, 18.7%) was conducted in Germany and Austria. The patients applied a foot cream containing 10% urea, 5% sodium lactate, and glycerin at least twice daily for 2 weeks. While 319 patients used specific foot treatment products to care for their feet at the baseline visit, only 20 used other topical products in addition to the foot cream during the study period. The foot skin was clinically graded for xerosis, scaling, and cracking at baseline and after 2 weeks of treatment on a 5-point scale (none, slight, moderate, severe, or very severe). Table 17.4 documents the improvement in skin condition after 2 weeks of foot cream usage, showing significant and marked decreases in the percentage of patients with severe or very severe symptoms, and overall noticeable improvements in 95% of the patients. In this large patient population, the investigating dermatologists judged the tolerability to be very good or good in 96.7% of the patients, recommending continued product use.

These data and many other published studies [18–22] support the therapeutic value and excellent safety profile of urea when administered topically to treat various dry skin conditions.

The future: Next-generation moisturizers Water homeostasis of the epidermis is important for the appearance and physical properties of skin, as well as for the water balance of the body. Skin moisture balance depends on multiple factors including external humidity, uptake of water into the epidermis, skin barrier quality, and endogenous water binding substances. Biosynthesis and degradation of skin components is also influenced by water balance, impacting the moisturization state of the epidermal layers. In recent times, aquaporins (AQP), important hydrationregulating elements in the lower epidermis, have been described [27]. The first indications of the critical importance of AQP in regulating tissue hydration came from investigations of




Figure 17.4 Improvement in diabetic foot skin after 6 weeks of daily usage of a foot cream containing 10% urea and 5% sodium lactate. Pretreatment photos (left) of two different subjects (top and bottom) and their corresponding week 6 photos (right).

Table 17.4 Clinical grading scores before and after 2 weeks of treatment. Percentage of patients with none or slight and severe or very severe symptoms (100% = 604 patients). None or slight (%)

Severe or very severe (%)


Baseline Week 2

5 69

67 6


Baseline Week 2

22 79

44 6


Baseline Week 2

26 66

32 8

resulted in dry, compromised skin, showed a significant decrease in the number of AQP3 pores (p = 0.04). The pores were quantified by analysis of Western blots, and a 43% reduction in the dry skin samples was observed. Further, in other skin conditions associated with skin dryness, a reduction in AQP3 has also been observed. Specifically, an age-related decline in AQP3 levels, as well as decreases associated with chronic sun exposure were reported [31]. Water and the moisturizing substances glycerol and urea have been found to be transported through the AQP in skin, providing moisture from within to the epidermis [32]. Expanding knowledge on the activity and regulation of AQP3 has led to the pursuit of a new class of actives that can modulate the expression of these water channels.

Enhanced glycerol derivatives other organ systems, in particular the kidney [28]. Since their initial discovery, AQP genes have been cloned and, to date, 13 different genes (AQP1–13) have been identified [29]. The first proof for their relevance in skin came from Ma et al. [30] who produced knockout mice lacking AQP3, which exhibited a reduced stratum corneum hydration. Studies confirmed the importance of these findings in dry human skin. Subjects whose epidermal barriers were damaged by a week-long tenside-based treatment that


In vitro studies on human keratinocytes demonstrated a significant increase in AQP3 levels by a specific enhanced glycerol derivative (EGD), designed and synthesized to confer specific structural and osmotic properties. Figure 17.5 depicts the enhanced AQP3 levels of EGD treated human keratinocytes after 48 hours of incubation. Additional in vitro studies measuring AQP3 mRNA levels in human keratinocytes confirmed these findings. In contrast to glycerol treatment, EGD increased mRNA expres-

17. Hand and foot moisturizers

Figure 17.5 Immunohistochemical localization of the AQP3 protein in keratinocyte monolayers stained with a rabbit antihuman AQP3 antibody. Background control (left), untreated control (center), treatment with 3% enhanced glycerol derivative for 48 hours (right).


Change in mean TEWL relative to baseline (%)


Conclusions *






Vehicle + glycerol

Vehicle + glycerol+ EGD

*Significantly different, p < 0.05. Figure 17.6 In vivo study of 23 volunteers with dry skin. Transepidermal water loss (TEWL) measurement after the following treatments: vehicle; vehicle with 6.5% glycerol; and vehicle with 6.5% glycerol and 5% enhanced glycerol derivative (EGD).

sion relative to the control. Further, to assess the efficacy of this new active, in vivo placebo-controlled studies were conducted. Figure 17.6 demonstrates the results of a study of 23 subjects, whose epidermal barriers were damaged by a tenside-based treatment, resulting in dry, compromised skin. The restoration of the epidermal barrier was assessed weekly by measuring TEWL on treated skin sites. The applied topical test lotions included a vehicle preparation, vehicle plus 6.5% glycerol, and the vehicle with 6.5% glycerol and 5% EGD. After damaging the skin’s barrier for 1 week, vehicle treatment was ineffective at restoring the barrier to baseline levels, exhibiting greater moisture loss levels in the skin. Treatment with the glycerol-containing vehicle showed a reduction of the TEWL compared with the vehicle. However, a superior and significant barrier restoration and fortification is observed with the glycerol–EGD containing formulation compared with both vehicle and vehicle with glycerol.

Moisturizing substances have been used for thousands of years to improve the condition of compromised skin. The advent of stable emulsions and subsequent advancements in emulsion technologies provided improved elegance and efficacy for moisturizing products. More than 100 years of process refinements, discovery of new ingredients, and the growing understanding of the NMF and biologic mechanisms that regulate the skin’s moisture balance have contributed toward products with greatly enhanced stability, esthetics, and efficacy. In contrast to ingredients that exert their effects solely from the surface of the skin, the recent discovery and understanding of the function of AQP and new appreciation of the underlying mechanisms of moisture homeostasis of the skin provides new opportunities to create even better actives and product formulations which can help regulate moisturization from within the skin.

References 1 Draelos ZD. (2006) Cutaneous formulation issues. In: Draelos Z, Thamen L, eds. Cosmetic Formulation of Skin Care Products. New York: Taylor & Francis, pp. 3–34. 2 Zhai H, Maibach HI. (1998) Moisturizers in preventing irritant contact dermatitis: an overview. Contact Dermatitis 38, 241–4. 3 Lifschütz I. (1906) Verfahren zur Herstellung stark wasseraufnahmefähiger Salbengrundlagen. Patent DE 167849. 4 Fluhr JW, Darlenski R, Surber C. (2008) Glycerol and the skin: holistic approach to its origin and functions. Br J Dermatol 159, 23–34. 5 Epstein H. (2006) Skin care products. In: Paye M, Barel A, Maibach H, eds. Handbook of Cosmetic Science and Technology, 2nd edn. Boca Raton: CRC Press, pp. 427–39. 6 Schneider G, Gohla S, Kaden W, et al. (1993) Skin cosmetics. In: Uhlmann’s Encyclopedia of Industrial Chemistry. Weinheim: VCH Verlagsgesellschaft, pp. 219–43. 7 Rajka G. (1995) Atopic dermatitis. In: Baran R, Maibach H, eds. Cosmetic Dermatology. London: Martin Dunitz, pp. 253–8.




8 Draelos ZD. (2005) Dry skin. In: Draelos ZD, ed. Cosmeceuticals. Philadelphia: Elsevier Saunders, pp. 167–8. 9 Zocchi G. (2006) Skin feel agents. In: Paye M, Barrel A, Maibach H, eds. Handbook of Cosmetic Science and Technology, 2nd edn. Boca Raton: CRC Press, pp. 247–64. 10 Sagiv A, Dikstein S, Ingber A. (2001) The efficiency of humectants as skin moisturizers in the presence of oil. Skin Res Technol 7, 32–8. 11 Harding CR, Rawlings AV. (2006) Effects of natural moisturizing factor and lactic acid isomers on skin function. In: Maibach HI, Lodén M, eds. Dry Skin and Moisturizers: Chemistry and Function, 2nd edn. Boca Raton: CRC Press LLC, pp. 187–209. 12 Rawlings AV, Harding CR. (2004) Moisturization and skin barrier function. Dermatol Ther 17, 43–8. 13 Swanbeck G. (1992) Urea in the treatment of dry skin. Acta Derm Venereol 177, 7–8. 14 Mueller KH, Pflugshaupt C. (1979) Urea in dermatology I. Zbl Haut 142, 157–68. 15 Mueller KH, Pflugshaupt C. (1982) Urea in dermatology II. Zbl Haut 167, 85–90. 16 Proksch E. (1994) Harnstoff in der Dermatologie. Dtsch Med Wochenschr 119, 1126–30. 17 Wellner K, Wohlrab W. (1993) Quantitative evaluation of urea in stratum corneum of human skin. Arch Dermatol Res 285, 239–40. 18 Schölermann A, Filbry A, Rippke F. (2002) 10% urea: an effective moisturizer in various dry skin conditions. Ann Dermatol Venereol 129, 1S422, P0259. 19 Schoelermann A, Banke-Bochita J, Bohnsack K, et al. (1998) Efficacy and safety of Eucerin® 10% urea lotion in the treatment of symptoms of aged skin. J Dermatolog Treat 9, 175–9. 20 Norman RA. (2003) Xerosis and pruritus in the elderly: recognition and management. Dermatol Ther 16, 254–9. 21 Lodén M. (2006) Clinical evidence for the use of urea. In: Lodén M, Maibach HI, eds. Dry Skin and Moisturizers. Chemistry






26 27 28





and Function, 2nd edn. Boca Raton: Taylor & Francis, pp. 211–25. Pigatto PD, Bigardi AS, Cannistraci C, Picardo M. (1996) 10% urea cream (Eucerin) for atopic dermatitis: a clinical and laboratory evaluation. J Dermatolog Treat 7, 171–6. McCallion R, Wan Po AL. (1993) Dry and photo-aged skin: manifestations and management. J Clin Pharm Ther 18, 15–32. Rawlings AV, Davies A, Carlomusto M, et al. (1995) Effect of lactic acid isomers on keratinocyte ceramide systhesis, stratum corneum lipid levels and stratum corneum barrier function. Arch Dermatol Res 288, 383–90. Richter T, Peuckert C, Sattler M, et al. (2004) Dead but highly dynamic: the stratum corneum is divided into three hydration zones. Skin Pharmacol Physiol 17, 246–57. Nikkels-Tassoudji N, Henry F, Letawe C, et al. (1996) Mechanical properties of the diabetic waxy skin. Dermatology 192, 19–22. Hara-Chikuma M, Verkman AS. (2008) Roles of aquaporin-3 in the epidermis. J Invest Dermatol 128, 2145–51. Agre P. (2006) Aquaporin water channels: from atomic structure to clinical medicine. Nanomedicine: Nanotechnology, Biology and Medicine 2, 266–7. Verkman AS. (2008) Mammalian aquaporins: diverse physiological roles and potential clinical significance. J Exp Med 10, 1–18. Ma T, Hara M, Sougrat R, et al. (2002) Impaired stratum corneum hydration in mice lacking epidermal water channel aquaporin-3. J Biol Chem 27, 17147–53. Dumas M, Sadick NS, Noblesse E, et al. (2007) Hydrating skin by stimulating biosynthesis of aquaporins. J Drugs Dermatol 6 (Suppl), 20–4. Hara M, Verkman AS. (2003) Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Proc Natl Acad Sci U S A 100, 7360–5.

Chapter 18: Sunless tanning products Angelike Galdi, Peter Foltis, and Christian Oresajo L’Oréal Research, Clark, NJ, USA

BAS I C CONCEPTS • Tanned skin is considered attractive among fair-skinned individuals. • Self-tanning preparations containing dihydroxyacetone (DHA) induce a temporary safe staining of the skin simulating sun-induced tanning. • Self-tanners are formulated into sprays, lotions, creams, gels, mousses, and cosmetic wipes. • The tanning effect of DHA begins in the deeper part of the stratum corneum before expanding over the entire stratum corneum and stratum granulosum resulting in the production of brown melanoidins. • DHA products do not confer photoprotection unless sunscreen filters are added to the formulation.

Introduction Social norms for tanning in the USA have dramatically changed in recent times. The presence of a tanned body at one time conveyed the social status of an outdoor laborer. Now, having a tan, especially during the winter months, indicates affluence. More information has become available regarding the deleterious effects of UV exposure. [1–3]. The public is beginning to understand the dangers, thereby modifying their lifestyle choices towards safer practices. However, the change has been slow because sun exposure behavior is in part influenced by psychologic and societal factors [4–6]. Selftanning preparations are becoming an increasingly important option for those desiring the tanned look but not exposing themselves to undue harm.

Sunless tanning products Definition Self-tanning products, or sunless tanners, are preparations that when applied topically impart a temporary coloration to the skin mimicking skin color of naturally sun-tanned skin. Depending on the formulation and the active ingredients, the onset of color formation can be anything from immediate to several hours and can last up to 1 week. Self-tanning formulations were introduced in the 1960s. Consumers’ acceptability soon waned because of unattrac-

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

tive results such as orange hands, streaking, and poor coloration. Because of these drawbacks, consumers today still associate sunless tanning with these undesirable results. However, improved formulations have appeared on the market. Refinements in the dihydroxyacetone (DHA) manufacturing process has aided in the creation of formulations that produce a more natural-looking color and better longevity.

Active ingredients The most widely used and most efficacious active ingredient in self-tanners is DHA. It is the only ingredient that is currently recognized as a self-tanning agent by the US Food and Drug Administration (FDA) [7]. DHA-based sunless tanners have been recommended by the Skin Cancer Foundation, the American Academy of Dermatology Association, and the American Medical Association [8–10]. DHA is a triose and is the simplest of all ketoses (Figure 18.1).

Mechanism of action of DHA Ketones and aldehydes react with primary amines to form Schiff bases [11]. This is similar to the Maillard reaction, also known as non-enzymatic browning, and involves, more specifically, the reaction between carbohydrates and primary amines [12]. DHA is able to penetrate into the epidermis because of its size. Pyruvic acid is formed from DHA and either can react with sterically unhindered terminal amino groups in the amino acids of epidermal proteins. The epsilon amino group of lysine and the guanido group of arginine are particularly susceptible to nucleophilic attack by the reactive carbonyl oxygen. Epidermal proteins contain high concentrations of both of these amino acids. Based on photoacoustic depth profilometry, the tanning effect of DHA begins in the deeper




Figure 18.1 Chemical structure of dihydroxyacetone (DHA).

part of the stratum corneum layer (15–22 μm) before expanding over the entire stratum corneum and stratum granulosum [13,14]. Subsequent steps of the reaction mechanism are not fully understood. The resultant products are brown in color and are collectively referred to as melanoidins.

Alternate actives As previously stated, US federal regulations recognize only DHA as a sunless tanning agent [7]. Alternative technologies exist, however, with the capability to impart an artificial tan to the skin. Reducing sugars other than DHA can act as Maillard reaction intermediates and therefore have the potential for use as sunless tanning agents [15]. Reducing sugars, in basic solution, form some aldehyde or ketone. This allows the sugar to act as a reducing agent in the Maillard reaction of non-enzymatic browning. Reducing sugars include glucose, fructose, glyceraldehyde, lactose, arabinose, and maltose. Unfortunately, a large amount of heat energy is required to trigger the glycation reaction between glucose, the most commonly known reducing sugar, and free amines. Such properties render many reducing sugars useless for sunless tanning products. An exception is the keto-tetrose, erythulose. Although this reducing sugar produces a more gradual tan than DHA, it has been utilized as a self-tanning enhancer for years. As corporations continue to aggressively pursue new sunless tanning technologies, reducing sugars may provide the next generation of self-tanning actives.

Formulation challenges The content of DHA in self-tanning products depends on the desired browning intensity on the skin and is normally used in the range 4–8%. Depending on the type of formulation and skin type, a tan appears on the skin about 2–3 hours after use. During product storage, the pH of a DHAcontaining formulation will drift over time to about 3–4. At this pH, DHA is particularly stable. In order to ensure end product stability, certain key factors must be considered.

However, investigations have since shown that the storage stability of DHA could be increased when formulations are kept at a pH of 3–4 and buffering at a higher pH enhances the degradation of DHA [16]. The pH of a formulation may be adjusted to approximately 3–4 by using a small amount of citric acid or using acetate buffers as they do not affect DHA stability [17].

Processing and storage of DHA Storage and heating of DHA above 40 °C should be avoided as it causes rapid degradation. During manufacturing processes that require heating (as in the case of emulsions), DHA should not be added until the formulation has been cooled down to below 40 °C. Additionally, finished products containing DHA should be sold in opaque, or other UV-protective packaging, as well as resealable packaging, to limit exposure to air.

Nitrogen-containing compounds Amines and other nitrogen-containing compounds should be avoided in DHA-containing formulations. This includes collagen, urea derivatives, amino acids, and proteins. The reactivity of DHA towards these compounds can lead to its degradation, therefore resulting in the loss in efficacy and acceptability of resulting color. However, some commercial formulations combine DHA with nitrogen-containing containing compounds (e.g. amino acids). This combination provides a perceptual advantage to customers as provides within tanning 1 hour as a result of the accelerated reaction between DHA and amino acids. This tan is not substantive, however, and most of it is easily washed off [17].

Sunscreens A tan achieved with DHA alone does not offer sun protection comparable to that of sunscreens. However, it is possible to combine DHA with sunscreens to achieve a product with sun protection. Inorganic sunscreens such as titanium dioxide, zinc oxide, and nitrogen-containing sunscreens should be avoided as they induce rapid degradation of DHA. As a final stability check, periodic determination of DHA dosage is recommended to ensure end product and longterm stability and efficacy. A simple high performance liquid chromatography (HPLC) method exists using an amine column with acetonitrile/water (75 : 25) as a mobile phase. Detection is at 270 nm.

Delivery vehicles Creams and lotions

pH and buffers The pH of DHA-containing formulation drops during storage. The resulting pH lies in the range of 3–4. In the past, buffering was recommended to keep the pH at a level of 4–6.


Self-tanning creams and lotions tend to be the most widely used of all of the self-tanning vehicles. Our studies have confirmed that although conventional, creams and lotions are preferred by consumers because of their ease of use and

18. Sunless tanning products reduced likelihood of having streaky color results. This is most likely because of the extended play time (e.g. rub-in time) offered by cream and lotion vehicles. In selecting the appropriate ingredients for formulation, the use of non-ionic emulsifiers is recommended over ionic emulsifiers because of improved stability of the DHA [16]. Additionally, xanthan gum and polyquaternium-10 may be used for thickening emulsions. Emollients have an important role in many self-tanning formulations as they impart hydration to the skin, play time during application, and a smooth and silky after feel. Types of emollients include oils, waxes, fatty alcohols, silicone materials, and certain esters. Emulsions with DHA are particularly susceptible to microbial attack. Parabens, phenoxyethanol, and mixtures thereof are recommended [16].

Gels and gelees Thickening formulations containing DHA, particularly to produce a clear gel, is relatively difficult because many of the conventional thickeners are not compatible with DHA. Studies have found that hydroxyethylcellulose, methylcellulose, and silica are good choices, whereas carbomers, PVM/MA decadiene crosspolymer, and magnesium aluminum silicate are not acceptable as they cause rapid degradation of DHA [16]. Silicones such as dimethicone and cyclomethicones have increased in popularity over recent years, particularly for producing water-in-silicone emulsions (typically classified as gelees). Gelees are similar in appearance to gels; however, they tend to offer improved play time and skin feel over gels as they contain high levels of the silicone emollients.

Regulatory considerations The US FDA considers sunless tanning actives as color additives as they impart color to the skin. According to 21CFR70, color additives are defined as: “A dye, pigment, or other substance…that, when added or applied to a food, drug or cosmetic or to the human body or any part thereof, is capable (alone or through reaction with another substance) of imparting a color thereto” [18]. The actives permitted in the sunless tanning products in the USA are limited to those approved for use as such. The following color additives appear in the Code of Federal Regulations in Tables 18.1 and 18.2. Labeling requirements are also specified under current FDA guidelines. All sunless tanning products that do not contain sun protection factor (SPF) protection must be labeled with the following warning statement (US Code of Federal Regulations): “Warning – This product does not contain a sunscreen and does not protect against sunburn. Repeated exposure of unprotected skin while tanning may

Table 18.1 Color additives exempt from certification per 21CFR73 2003 (US Code of Federal Regulations). Aluminum powder

Copper powder

Luminescent zinc



Manganese violet


Disodium EDTA copper


Bismuth citrate

Ferric ammonium ferrocyanide

Potassium sodium copper

Ferric ferrocyanide







Titanium dioxide

Iron oxides


Lead acetate

Zinc oxide

Bismuth oxychloride Bronze powder Caramel Carmine Chromium oxide greens Chlorophyllin

Table 18.2 Color additives per 21CFR73 2003 (US Code of Federal Regulations). Citrus Red No. 2

D&C Red No. 17

D&C Yellow No. 10

D&C Blue No. 4

D&C Red No. 21

D&C Yellow No. 11

D&C Blue No. 6

D&C Red No. 22

Ext. D&C Violet No. 2

D&C Blue No. 9

D&C Red No. 27

Ext. D&C Yellow No. 7

D&C Brown No. 1

D&C Red No. 28

FD&C Blue No. 1

D&C Green No. 5

D&C Red No. 30

FD&C Blue No. 2

D&C Green No. 6

D&C Red No. 31

FD&C Red No. 3

D&C Green No. 8

D&C Red No. 33

FD&C Red No. 4

D&C Orange No. 4

D&C Red No. 34

FD&C Red No. 40

D&C Orange No. 5

D&C Red No. 36

FD&C Yellow No. 5

D&C Orange No. 10

D&C Red No. 39

FD&C Yellow No. 6

D&C Orange No. 11

D&C Violet No. 2

Orange B

D&C Red No. 6

D&C Yellow No. 7


D&C Red No. 7

D&C Yellow No. 8

increase the risk of skin aging, skin cancer and other harmful effects to the skin even if you do not burn” [18].

Product attributes Coloration The onset of coloration starts at approximately 2–3 hours and will continue to darken for 24–72 hours after a single application, depending on formulation and skin type.




Because DHA forms covalent bonds with epidermal proteins, the tan will not sweat off or wash away with soap or water. The color gradually fades over 3–10 days, in conjunction with stratum corneum exfoliation. Any product or process that increases the rate of cell turnover or removes portions of the stratum corneum will decrease the longevity of the color. Thus, preparations containing alpha- and betahydroxyacids and retinoids, as well as microdermabrasion creams and the process of shaving, decrease the longevity of coloration from self-tanning products.

Evaluation Various spectrophotometric methods can be used to evaluate the coloration parameters of self-tanners such as onset of color and longevity of color. The most popular is the L*a*b* standard from Commission Internationale d’Eclairage (CIE). The three coordinates of CIELAB represent the lightness of the color (L* = 0 yields black and L* = 100 indicates diffuse white), its position between red/magenta and green (a*, negative values indicate green while positive values indicate magenta), and its position between yellow and blue (b*, negative values indicate blue and positive values indicate yellow). The total color difference between any two colors in L*a*b* can be approximated by treating each color as a point in a three-dimensional space (with three components: L*, a*, b*) and taking the Euclidean distance between them (ΔE). ΔE is calculated as the square root of the sum of the squares of ΔL*, Δa* and Δb* [19]. It is generally recognized that 1.5 ΔE units is the minimal difference detectable to the eye. Comparisons to baseline readings can yield onset of tanning (usually readings at 30 minutes, 60 minutes, etc.) and longevity of tanning (readings at 48 hours, 72 hours, etc.).

Moisturization The recent trend in cosmetic products is to be multifunctional. Moisturizing formulations are increasing in popularity in keeping with this trend. Formulations with 8–24 hour hydration claims are not uncommon. Current self-tanners are formulated into sprays, lotions, creams, gels, mousses, and cosmetic wipes. In general, there are no obstacles to obtaining satisfactory levels of hydration, although there are some compromises that may have to be made. Alcohol is often incorporated to achieve quick-drying formulations. The trade off is sacrificing some level of hydration. This can be offset with humectants such as glycerin or sodium hyaluronate.

Trends in sunless tanning Daily use moisturizers/glow Face and body moisturizers with low levels of DHA have grown in popularity over the past 5 years. Although not new


to the market, the concept of using a daily moisturizer that imparts gradual color was particularly well-received by the faint in heart who were afraid of making mistakes and/or turning orange with the use of traditional sunless tanners. Typically formulated with 1–3% DHA, glow moisturizers are easy to apply and, depending on the formulation and user’s skin tone, may impart a darker shade to the skin after 1–3 applications.

No-rub mists No-rub sunless tanning mists have been sought out as the less expensive alternatives to the airbrushing trend. These multiangle applicator systems allow for simple, even, and often hands-free application. The formulation base systems are typically hydroalcoholic or aqueous solutions, therefore allowing for quick-drying properties.

Sunless tanning products with UV protection The tan imparted by sunless tanners is not adequate to protect against UVB and UVA damage. Sunless tanners must therefore carry the required FDA warning statement [19]. Sunless tanning products that do contain sunscreen are growing in popularity because of their multifunctional properties.

Conclusions With an increasing awareness of the harmful acute and chronic effects of UV damage, sunless tanning use remains a popular alternative to tan seekers. Modern day formulations are efficacious, well-tolerated, easy-to-use, and provide natural looking results. A probable increase in patient compliance of safe sun practices can therefore be anticipated.

References 1 Jemal A, Siegel R, Ward E, et al. (2006) Cancer statistics, 2006. CA Cancer J Clin 56, 106–30. 2 American Cancer Society. (2006) Cancer Facts and Figures 2006: American Cancer Society. 3 Elwood JM (1993). Recent developments in melanoma epidemiology, 1993. Melanoma Res 3, 149–56. 4 Garvin T, Wilson K. (1999) The use of storytelling for understanding women’s desires to tan: lessons from the field. Professional Geographer Vol. 51, 2, 297–306. 5 co*kkinides V, Weinstock M, Glanz K, Albano J, Ward E, Thun M. (2006) Trends in sunburns, sun protection practices, and attitudes toward sun exposure protection and tanning among US adolescents, 1998–2004. Pediatrics 118, 853–64. 6 co*kkinides V, Weinstock MA, O’Connell MC, Thun MJ. (2002) Use of indoor tanning sunlamps by US youth, ages 11–18 years, and by their parents or guardian caregivers: prevalence and correlates. Pediatrics 109, 1124–30. 7 United States Code of Federal Regulations 21CFR 73.2150, 2002.

18. Sunless tanning products 8 9 10 11 Morrison RT, Boyd RN. (1973) Organic Chemistry. Boston, MA: Allyn and Bacon. 12 Lloyd RV, Fong AJ, Sayre RM. (2001) In Vivo formation of Maillard reaction free radicals in mouse skin. J Invest Dermatol 117, 740–2. 13 Puccetti G, Tranchant JF, Leblanc RM. (1999) The stability and penetration of epidermal applications visualized by photoacoustic depth profilometry. Sixth Conference International Society of Skin Imaging, Skin Research and Technology, Berlin, Germany.

14 Puccetti G, Leblanc R. (2000) A sunscreen-tanning compromise: 3D visualization of the actions of titanium dioxide particles and dihydroxyacetone on human epiderm. Photochem Photobiol 71, 426–30. 15 Shaath N. (2005) Sunscreens Regulation and Commercial Development. Boca Raton, FL: Taylor & Francis Group. 16 Chaudhuri R. Dihydroxyacetone: Chemistry and Applications in Self-Tanning Products. White Paper; 7. 17 Kurz T. (1994) Formulating effective self-tanners with DHA. Cosmet Toiletries 109, 55–60. 18 United States Code of Federal Regulations. 21CFR740.19, 2003. 19 Minolta. (1993) Precise Color Communication, Color Control from Feeling to Instrumentation. Minolta Camera Co. Ltd.


Chapter 19: Sunscreens Dominique Moyal,1 Angelike Galdi2, and Christian Oresajo2 1 2

L’Oréal Recherche, Asnières, France L’Oréal Research, Clark, NJ, USA

BAS I C CONCE P T S • Sunscreens provide photoprotection from UV radiation (UVR). • Photoprotection is required for both UVB and UVA radiation. • Organic and inorganic filters are used in sunscreens. • Sunscreen filters must be carefully combined to achieve esthetically pleasing products with photostability and broad spectrum photoprotection.


Regulatory status of sunscreens

Human exposure to UVR from sunlight can cause many adverse effects. They involve both UVB (290–320 nm) and UVA (320–400 nm). UVB radiation is mainly responsible for the most severe damage: acute damage such as sunburn, and long-term damage including cancer. It has a direct impact on cell DNA and proteins [1]. Unlike UVB, UVA radiation is not directly absorbed by biologic targets [2] but can still dramatically impair cell and tissue functions: • UVA penetrates deeper into the skin than UVB. It particularly affects connective tissue where it produces detrimental reactive oxygen species (ROS). ROS cause damage to DNA, cells, vessels, and tissues [3–8]. • UVA is a potent inducer of immunosuppression [9,10] and there is serious concern about its contribution in the development of malignant melanoma and squamous tumors [11,12]. • Photosensitivity reactions and photodermatoses are primarily mediated by UVA [13]. As a result, a major concern has been raised that most available sunscreen products are incapable of preventing the harmful effects of UVA. It is important to note that under any meteorologic condition, the UVA irradiance is at least 17 times higher than the UVB irradiance. For all these reasons, it is evident that sunscreens must contain both UVA and UVB filters to cover the entire range of harmful radiation.

With increased knowledge about UV-induced skin damage and particularly the effects of UVA, public education programs have been developed with an emphasis on the proper use of sunscreen products. Many new UV filters have been made available in the last decade with improved efficacy and safety. The availability of new filters has been slow in some countries for regulatory reasons. An example is the USA where certain UVA and UVB filters, which are marketed elsewhere, are not approved for use. The availability of efficient sunscreen products depends not only on the regulatory status of the UV filters but also on the ability to inform the consumer about product efficacy with appropriate labels based on sun protection factor (SPF) and UVA protection levels. Sunscreen products can be classified in two main categories according to their purpose: 1 Primary sunscreens. Products whose main purpose is the protection of the skin from the effects of the sun, such as beach sunscreens and products used for outdoor activities. 2 Secondary sunscreens. Products that have a primary use other than skin protection, such as daily moisturizing creams, antiwrinkle/antiaging creams, and whitening skin products. In these products, sun protection is necessary to optimize the claimed effect. For this category of products, sun protection is an additional claim but not the main purpose.

Sunscreen classification

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


Sunscreen products can also be classified in terms of regulatory status. Sunscreen products are ordinary cosmetic products in Europe, EU and non-EU countries (e.g. Russia), most African and Middle-Eastern countries, India, Latin America,

19. Sunscreens and Japan. They can be classified “special” cosmetic products as in China (special cosmetics), Korea and Ethiopia (functional cosmetics), South Africa (under SABS standard), Australia (under standards) [14], and Taïwan (medicated cosmetics). They are over-the-counter (OTC) drugs in the USA [15] (all sunscreens and products with SPF). In Canada, they can be either OTC drugs or natural health products (NHP), in this case the sunscreen contains only “natural” active ingredients: titanium dioxide, zinc oxide.

Approved UV filters In Europe, the UV filters are listed in Annex VII of the Cosmetics Directive. There are 27 UV filters on this list. In the USA, there are 16 filters included in the sunscreen monograph (Table 19.1). There are two main regulatory methods to market OTC products: monograph or a New Drug Application (NDA). An NDA is necessary to obtain the approval of a formula containing a new UV filter, or a new concentration for an approved active, or a new mixture of approved actives. A Time and Extent Application (TEA) is a new procedure for an active ingredient already approved abroad. It allows the FDA to accept commercial data obtained on external markets in place of use of an authorized drug on the US market; however, toxicologic data requirements for a TEA are very similar to those for an NDA. Seven UV filters are currently eligible for evaluation through a TEA procedure (not yet finalized):

Table 19.1 Sunscreen approved in the USA. Sunscreen approved in USA

Maximum concentration (%)

p-Aminobenzoic acid (PABA) Avobenzone Cinoxate

15 3 3



Ensulizole (phenylbenzimidazole sulfonic acid) hom*osalate

4 15

1 Isoamyl p-methoxycinnamate (amiloxate) 10% max. 2 Methyl benzylidene camphor (enzacamene) 4% max. 3 Octyl triazone 5% max. 4 Methylene bis-benzotriazolyl tetramethylbutylphenol (Tinosorb® M, Ciba, Basel, Switzerland). 5 Bis-ethylhexyloxyphenol methoxyphenol triazine (Tinosorb® S, Ciba, Basel, Switzerland). 6 Diethylhexyl butamido triazone 3% max 7 Terephthalylidene dicamphor sulfonic acid (Ecamsule, Mexoryl® SX). In Australia, 26 UV filters are accepted by Therapeutic Goods Administration (TGA) and in Japan 31 UV filters are allowed. When comparison is made between the common UV filters approved in Europe and USA, only 11 filters are common, but p-aminobenzoic acid (PABA) will most likely be deleted in Europe and terephtalilydene dicamphor sulfonic acid (TDSA) is only available in USA under NDA for four formulas. Because of the importance of being well protected against UVA radiation, there are many new UVA filters or broad UVB/UVA filters, which have been developed and authorized in Europe, Australia, and Japan. It is obvious that the number of these filters is limited in the USA (Table 19.2). In addition, there are some limitations in the use of avobenzone in the USA. Combinations with some other UV filters, such as titanium dioxide and enzulizole, are not permitted and the maximum use level according to the sunscreen monograph is limited to 3%.

Development of sunscreens A proper sunscreen product must fulfill the following critical requirements: • Provide efficient protection against UVB and UVA radiation; • Be stable to heat and to UVR (photostable);

Table 19.2 Regulatory approval status for the main UVB/UVA and UVA filters.

Meradimate (menthyl anthranilate)


Octinoxate (octyl methoxycinnamate) Octisalate (octyl salicylate)


Benzophenone Oxybenzone BMDM (avobenzone)

EU, Japan, Aus, Can, USA EU, Japan, Aus, Can, USA


TDSA (Mexoryl SX)

EU, Japan, Aus, Can, USA (NDA)

DTS (Mexoryl XL)

EU, Japan, Aus, Can



Octyl dimethyl PABA


DPDT (Neo-Heliopan AP)




DHHB (Uvinul A+)

EU, Japan



MBBT (Tinosorb M)

EU, Japan, Aus

Titanium dioxide


BEMT (Tinosorb S)

EU, Japan, Aus

Trolamine salicylate


Titanium dioxide

EU, Japan, Aus, Can, USA

Zinc oxide


Zinc oxide

Japan, Aus, Can, USA




• Be user-friendly to encourage frequent application and provide reliable protection; and • Be cost-effective. In order to protect against both UVB and UVA, the sunscreen product must contain a combination of active ingredients within a complex vehicle matrix. Active ingredients can be either organic or inorganic UV filters. According to their chemical nature and their physical properties, they can act by absorption, reflection, or diffusion of UVR.

Zinc oxide has better absorption in the long UVA than titanium dioxide, but it is not very efficient. Because of possible photocatalytic activity, inorganic particles are frequently coated with dimethicone or silica for maintenance of their efficacy. When nanosized titanium dioxide (<100 nm) is combined with organic UV filters, it allows high SPF products to be formulated with a lower dependence on organic UV filters. In combination with organic UV filters, nanosized titanium dioxide has more a synergistic rather than only an additive effect.

Organic UV filters

Steps toward more efficient sunscreens

How do organic filters work?

As far as UVB protection is concerned, a large choice of filters has been available for a number of years. They are photostable except for the most common, ethylhexyl methoxy cinnamate (EHMC). The choice of UVA filters depends on the countries and is limited in the USA, as already explained. Inorganic pigments offer poor protection against UVA when used alone. Benzophenones are photostable but they are primarily UVB filters with some absorption in the short UVA range (peak at 328 nm). Butyl methoxy dibenzoyl methane (BMDM or avobenzone) has a high potency in the UVA1 range peaking at 358 nm; however, it undergoes significant degradation under UV exposure and this leads to a decrease in its protective UVA efficacy. Research on the photochemistry of filters has led to the identification of some potent photostabilizers (e.g. octocrylene) of avobenzone and the development of new UVA filters that have a photostable structure. Recently, in 2005, diethylamino hydroxybezoyl hexyl benzoate (DHHB) was approved in Europe and Japan. This UVA1 filter has UV-spectral properties similar to BMDM but DHHB is photostable. In order to provide full protection in the entire UVA range, it is necessary to have efficient absorption in the short UVA range. TDSA or Mexoryl SX™ (Chimex, Le Thillay, France), with a peak at 345 nm at the boundary between short and long UVA wavelengths, was first approved in Europe in 1993. This was followed by the approval of the broad UVB/ UVA filter drometrizole trisiloxane (DTS or Mexoryl XL) with two peaks (303 and 344 nm) in 1998. Since 2000, other short UVA (disodium phenyl dibenzimidazole tetrasulfonate [DPDT] or Neo-Heliopan AP®, Symrise, Holzminden, Germany, peak at 334 nm) and broadband UVB/UVA filters (MBBT, Tinosorb M and BEMT, Tinosorb S) have been approved in Europe. All these filters are photostable. UV filters are either hydrophilic or lipophilic. When combined a synergetic effect can be observed. This property is used to obtain higher efficacy against UVB and UVA radiation. Combinations of highly efficient and photostable filters provide an optimally balanced protection against both UVA and UVB [17]. Studies [18–20] have shown that the protection against UV induced skin damage provided by sunscreen

Organic filters are active ingredients that absorb UVR energy to a various extent within a specific range of wavelength depending on their chemical structure [16]. The molecular structure responsible for absorbing UV energy is called a chromophore. The chromophore consists of electrons engaged into multiple bond sequences between atoms, generally conjugated double bonds. An absorbed UV photon contains enough energy to cause electron transfer to a higher energy orbit in the molecule [16]. The filter that was in a low-energy state (ground state) transforms to a higher excited energy state. From an excited state, different processes can occur: • The filter molecule can simply deactivate from its excited state and resume its ground state while releasing the absorbed energy as unnoticeable heat. • Structural transformation or degradation may occur and the filter losses its absorption capacity. The filter is then said to be photo-unstable. • The excited molecule can interact with its surroundings, other ingredients of the formula, ambient oxygen, and thus lead to the production of undesirable reactive species. The filter is said to be photoreactive. The control of filter behavior under UV exposure is a critical point that needs to be investigated when new sunscreen products are developed.

Inorganic UV filters Pigment grade powders of metal oxides such as titanium dioxide or zinc oxide have been used for many years in combination with organic filters to enhance protection level in the longer UVA range. Unlike organic filters, they work by reflecting and diffusing UVR. However, as a result of the large particle sizes, these powders also diffuse light from the visible range of the sun spectrum and they tend to leave a white appearance on the skin. To overcome this drawback, which affects cosmetic acceptance, micronized powders of both titanium dioxide and zinc oxide have been made available. However, micronization leads to changes in the protective properties of titanium dioxide: the smaller particles shift the protection range from the longer UVA toward the UVB.


19. Sunscreens products with same SPF but different UVA protection factor is markedly different, emphasizing the importance of high UVA protection in preventing cell damage. Only wellbalanced, photostable sunscreens with absorption over the entire UV spectrum of sun radiation have been able to maintain intact essential biologic functions.

Formulation types Emulsions are the most popular of sunscreen vehicles. They offer versatility of texture (cream, lotion, milk) while exhibiting good performance. Emulsions can be placed into two main categories, oil-in-water (O/W) and water-in-oil (W/O). The W/O emulsions are intrinsically very water-resistant and will consistently yield higher SPF for the same concentration of sunscreen actives when compared with O/W emulsions. However, O/W emulsions are, by far, more widely used in sunscreens. This may be explained by the lower inherent cost for an O/W vehicle (where water is the outer phase) versus a W/O (where oil, a more expensive ingredient, is the outer phase). Aerosol spray vehicles have grown in popularity over the past few years. The multiposition spray nozzles allow for quick and easy application. Attention needs to be taken, however, that enough product is applied to ensure adequate protection. Oil, gel, stick, and mousse vehicles have decreased in popularity among formulators and consumers for several reasons. They are typically oil or wax-based, which makes then rather expensive and less efficacious. Additionally, they tend to be oily and greasy which result in lower usage and compliance.

Evaluation of the efficacy of sunscreen products Evaluation methods must take into account the photo-instability of products in order to avoid an overestimation of protection. In vivo SPF and in vivo UVAPF (Persistent Pigment Darkening) test methods take photodegradation into account. Appropriate UV doses are used to induce erythema on human skin for SPF determination or pigmentation for UVAPF determination. When in vitro methods are used they should also take into account this phenomenon to provide relevant evaluation [21].

Evaluation of the sun protection factor The international test method for SPF determination was first introduced in 2003. This method was published jointly by the Japanese Cosmetic Industry Association (JCIA), the European Cosmetic Industry Association (Colipa), and the Cosmetic Industry Association from South Africa (CTFA SA). In 2006, a revised version of this method was published with the support of the Cosmetic Toiletries and Fragrance Association (CTFA) from the USA [22]. In 1999, the US Food

and Drug Agency (FDA) published a final monograph [15]. FDA received comments and in August 2007 published a proposal of amendments [23]. This proposal includes a new SPF cap at 50+ and some amendments on technical points made in the 1999 monograph on sunscreen products. The Australian standards on SPF testing published in 1998 are similar to the other methods [14]. The International Standard Organization (ISO) TC217 WG7 working group is currently dealing with the standardization of a SPF method. The future ISO standard will be based on the international SPF test method including some improvements and it is expected to be published at the end of 2009.

Determination of UVA protection level The EU issued a recommendation on September 22, 2006 [24] to use a persistent pigment darkening (PPD) method similar to the JCIA method [25] or any in vitro method able to provide equivalent results. In addition, the critical wavelength [26] must be at least 370 nm. The EU Commission also recommends that the method used should take into account photodegradation. The first country that published an official in vivo method to assess UVA protection level was Japan. The JCIA adopted the PPD method as the official method for assessment of the UVA efficacy of sunscreen products in January 1996 [25]. Korea and China also adopted this method in 2001 and 2007, respectively. The PPD method was officially recommended by European Commission in September 2006 [24] and was recently proposed by FDA in the 2007 Sunscreen Monograph Amendment [23]. The method has been described with some minor differences by different countries or authorities. Finally, UVA method is currently in progress for standardization through the ISO. Since the PPD response requires doses greater than 10 J/ cm−2 (approximately 40 minutes of midday summer sunlight), the photostability of sunscreens is also challenged during the test procedure. To illustrate this point, avobenzone (BMDM, Parsol®1789) was tested [27] at concentrations of 1.0, 3.0, and 5.0% individually and in combination with 10% of octocrylene, a UVB filter, known to stabilize BMDM. The results of UVA-PF of avobenzone alone ranged from 2.2 with 1% BMDM to 4.6 with 5% BMDM. In combination with 10% octocrylene the results ranged from 4.6 with 1% BMDM to 10.6 with 5% BMDM. It is evident that UVA protection efficacy of avobenzone is significantly increased when it is combined with octocrylene, compared with the same concentration of BMDM alone. This can be explained by the fact that the PPD UVA doses affect the photostability of BMDM. It has been verified under real sun exposure conditions that when a photo-unstable product applied at 1 mg/cm2 is exposed to a UVA dose of about 30 J/ cm2 (about 2.5 hours) there is a dramatic decrease of the UVA absorption properties of avobenzone leading to a decrease of the UVA protection efficacy [28].




Critical wavelength method An in vitro approach to measure UVA protection using a thin film technique was proposed by Diffey et al. [26]. The UVB and UVA absorbance of the product is measured on a film of product applied on a substrate which can be quartz or polymethyl methacrylate (PMMA). The method yields a measure of the “breadth” of UVA protection using a test method called “critical wavelength” [26]. In this test proposal, the absorbance of the thin film of the sunscreen is summed (starting at 290 nm) sequentially across the UV wavelengths until the sum reaches 90% of the total absorbance of the sunscreen in the UV region (290–400 nm). The wavelength at which the summed absorbance reaches 90% of total absorbance is defined as the “critical wavelength” and is considered to be a measure of the breadth of sunscreen protection. The critical wavelength λc is defined according to equation (19.1):



lg [1 T (λ )] dλ = 0.9 ⋅



lg [1 T (λ )] dλ

(equation 19.1)

Because this is a relative measurement, the “absolute” absorbance of the sunscreen is not necessary, eliminating the operator dependence of the test method. Critics of the methods based on absorbance criteria point to the fact that it is not a true measurement of UVA protective potency of the test product. The critical wavelength determination (λc) addresses the broadness of the protection rather than the specific protection in the UVA. Products with widely different in vivo protection indices (i.e. UVAPF PPD) can have identical critical wavelengths [29]. Combining both the in vivo PPD method for measuring the level of UVA protection efficacy and the critical wavelength method to measure the broadness of UVA absorbance has been proposed for UVA protection assessment of sunscreen products by the European Commission [24]. Other studies have shown that the higher the UVA protection level as assessed by the PPD method the better the protection against damage induced by UVA radiation [18–20]. On the other hand, critical wavelength higher than 370 nm is not a sufficient, reliable criterion to ensure that a product can provide efficient protection against UVA damage.

Conclusions It is important that a minimal proportionality between UVA and UVB protection be ensured in order to avoid high UVB protection with low UVA protection. A UVAPF : SPF ratio of at least one-third as defined by the European Commission [24] should be universally adopted for harmonization of consumer protection. In order to reach balanced protection, combination of UV filters is necessary. The criteria of choice are the following: UV filters with different maximum absorb-


ance peaks (UVB, short UVA, and long UVA) to cover the entire UV spectrum, appropriate filters in different phases of sunscreen emulsion (lipophilic and hydrophilic), and ensuring the photostability of the UV filters. A high level of efficacy and protection against UVB and UVA radiation can be achieved by using available new filters.

References 1 Urbach F. (2001) The negative effect of solar radiation: a clinical overview. In: Giacomoni PU, ed. Sun Protection in Man, ESP Comprehensive Series in Photosciences. Vol. 3. Amsterdam: Elsevier Sciences, pp. 41–67. 2 Peak MJ, Peak JG. (1986) Molecular photobiology of UVA. In: Urbach F, Gange RW, eds. The Biological Effects of UVA Radiation. New York: Praeger Publishers, pp. 42–52. 3 Lavker RM, Kaidbey K. (1997) The spectral dependence for UVA-induced cumulative damage in human Skin. J Invest Dermatol 108, 17–21. 4 Lavker R, Gerberick G, Veres D, Irwin C, Kaidbey K. (1995) Cumulative effects from repeated exposures to suberythemal doses of UVB and UVA in human skin. J Am Acad Dermatol 32, 53–62. 5 Lowe NJ, Meyers DP, Wieder JM, Luftman D, Bourget T, Lehman MD, et al. (1995) Low doses of repetitive ultraviolet A induce morphologic changes in human skin. J Invest Dermatol 105, 739–43. 6 Séité S, Moyal D, Richard S, de Rigal J, Lévêque JL, Hourseau C, et al. (1997) Effects of repeated suberythemal doses of UVA in human skin. Eur J Dermatol 7, 204–9. 7 Séité S, Moyal D, Richard S, de Rigal J, Lévêque JL, Hourseau C, et al. (1998) Mexoryl SX: a broadspectrum absorption UVA filter protects human skin from the effects of repeated suberythemal doses of UVA. J Photochem Photobiol B Biol 44, 69–76. 8 Moyal D, Fourtanier A. (2004) Acute and chronic effects of UV on skin. In: Rigel DS, Weiss RA, Lim HW, Dover JS, eds. Photoaging. New York: Marcel Dekker, pp. 15–32. 9 Moyal D, Fourtanier A. (2002). Effects of UVA radiation on an established immune response in humans and sunscreen efficacy. Exp Dermatol 11 (Suppl 1), 28–32. 10 Kuchel J, Barnetson R, Halliday G. (2002) Ultraviolet A augments solar-simulated ultraviolet radiation-induced local suppression of recall responses in humans. J Invest Dermatol 118, 1032–7. 11 Garland CF, Garland FC, Gorham EC. (2003) Epidemiologic evidence for different roles of ultraviolet A and B radiation in melanoma mortality rates. Ann Epidemiol (AEP) 13395–404. 12 Agar NS, Halliday GM, Barnetson RS, et al. (2004) The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis. Proc Natl Acad Sci U S A 101, 4954–9. 13 Moyal D, Binet O. (1997) Polymorphous light eruption (PLE): its reproduction and prevention by sunscreens. In: Lowe NJ, Shaat N, Pathak M, eds. Sunscreens: Development and Evaluation and Regulatory Aspects, 2nd edn. New York: Marcel Dekker, pp. 611–7. 14 Australian/New Zealand standard AS/NZS 2604 (1998) Sunscreen Products: Evaluation and Classification. Standards Australia and New Zealand.

19. Sunscreens 15 Department of Health and Human Services, Food and Drug Administration (USA). (1999) Sunscreen drug products for over-the-counter human use. Fed Register 43, 24666–93. 16 Kimbrough DR. (1997) The photochemistry of sunscreens. J Chem Ed 74, 51–3. 17 Marrot L, Belaidi J, Lejeune F, Meunier J, Asselineau D, Bernerd F. (2004) Photostability of sunscreen products influences the efficiency of protection with regard to UV-induced genotoxic or photoaging-related endpoints. Br J Dermatol 151, 1234–44. 18 Fourtanier A, Bernerd F, Bouillon C, Marrot L, Moyal D, Seité S. (2006) Protection of skin biological targets by different types of sunscreens. Photodermatol Photoimmunol Photomed 22, 22–32. 19 Moyal D, Fourtanier A. (2001) Broad spectrum sunscreens provide better protection from the suppression of the elicitation phase of delayed-type hypersensitivity response in humans. J Invest Dermatol 117, 1186–92. 20 Damian DL, Halliday GM, Barnetson RSC. (1997) Broad spectrum sunscreens provide greater protection against ultravioletradiation-induced suppression of contact hypersensitivity to a recall antigen in humans. J Invest Dermatol 109, 146–51. 21 Colipa. (2007) Method for the in vitro determination of UVA protection provided by sunscreen products. Guidelines. 22 Colipa, JCIA, CTFA SA, CTFA. (2006) International Sun Protection Factor (SPF) Test Method.

23 Department of Health and Human Services. Food and Drug Administration. (2007) CFR Parts 347 to 352. Sunscreen drug products for OTC human use: proposed amendment of final monograph; proposed rule. 24 European Commission Recommendation on the efficacy of sunscreen products and the claims made relating thereto. OJL 265/39, (26.9.2006). 25 Japan Cosmetic Industry Association (JCIA). (1995) Japan Cosmetic Industry Association measurement standard for UVA protection efficacy. November 15. 26 Diffey BL, Tanner PR, Matts PJ, Nash JF. (2000) In vitro assessment of the broadspectrum ultraviolet protection of sunscreen products. J Am Acad Dermatol 43, 1024–35. 27 Moyal D, Chardon A, Kollias N. (2000) UVA protection efficacy of sunscreens can be determined by the persistent pigment darkening (PPD) method. Part 2. Photodermatol Photoimmunol Photomed 16, 250–5. 28 Moyal D, Refrégier JL, Chardon A. (2002) In vivo measurement of the photostability of sunscreen products using diffuse reflectance spectroscopy. Photodermatol Photoimmunol Photomed 18, 14–22. 29 Forestier S. (1999) Pitfalls in the in vitro determination of critical wavelength using absorbance curves. SÖFW J 125, 8–9.


Part 3: Personal Care Products Chapter 20: Antiperspirants and deodorants Eric S. Abrutyn TPC2 Advisors Ltd. Inc. Boquete, Chiriqui, Republic of Panama

BAS I C CONCE P T S • Antiperspirants are US Food and Drug Administration (FDA) regulated drugs to be used in the underarm axilla vault only. • Antiperspirants are primarily complexes of aluminum (e.g. Aluminum Chlorohydrate) and aluminum zirconium (e.g. Aluminum Tetrachlorohydrex-GLY). • Deodorants, not to be confused with antiperspirants, are cosmetics and do not typically contain any aluminum-type salt complexes. • Antiperspirants are associated with few dermatologic issues; slightly irritating under certain conditions, but not scientifically associated with breast cancer or Alzheimer disease.

Introduction This chapter deals with the technologies for wetness and odor protection of the human axilla, how they are applied, and potential adverse effects of use of these products on a regular basis. Antiperspirants and deodorants have been used for centuries,1 evolving from simple fragrances that masked offensive odors to today’s complex ingredients based on aluminum and zirconium chemistries that act to slow or diminish sweat production. Odors (scents) and sweating have a biologic significance. Body scents are primeval and most likely evolved genetically to attract the opposite sex. Sweating is regulated by the sympathetic nervous system and is an important body temperature regulator, especially in warm weather climates or during heavy exercise, and functions to remove waste and toxic by-products of the body. The axilla area of the body represents a small contribution to sweating to control body temperature and removal of biologic by-products, so the controlling of sweat from this area has less health risks than other portions of the body. There is little scientific evidence that supports the use of antiper-


Over 5500 years ago, every major civilization has left a record of its efforts to mask body odors. The early Egyptians recommend following a scented bath with an underarm application of perfumed oils (special citrus and cinnamon preparations).

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


spirants, based on aluminum or aluminum–zirconium chemistry causes appreciable lasting adverse effects other than possible temporary and reversible irritation.

Physiology Sweat glands and how they work Sweat by itself is odorless and only establishes a characteristic odor when exposed to moisture (humidity) in the presence of bacterial flora on the skin surface, breaking down the sweat’s composition and resulting in unpleasant odors. The use of antimicrobial agents is a good defense in preventing odor development from bacteria and yeast present on the skin. Another defense is the reduction of excretion from the eccrine gland to minimize the appearance of uncomfortable or unsightly wetness production. According to Gray’s Anatomy [1], most people have several million sweat glands distributed over their bodies, to include the underarm axilla and thus providing plenty of opportunity for underarm odors to develop. Skin has two types of sweat glands: eccrine glands and apocrine glands (Figures 20.1 and 20.2). Eccrine glands open directly on to the surface of the skin and exude sweat in the underarm, subsequently contributing to odor formation. These glands are located in the middle layer of the skin called the dermis, which is also made up of nerve endings, hair follicles, and blood vessels. Sweat is produced in a long coil embedded within the dermis where the long part is a duct that connects the gland to the opening (pore) on the skin’s surface. When body temperature rises, the autonomic nervous system stimulates these

20. Antiperspirants and deodorants

Eccrine sweat

Apocrine sweat

H2O, Na+, K+, Cl– Urea, lactic acid, ammonia Traces of amino acids and proteins

H2O anorganic substances S-containing organic substances, lipids Steroids, pheromones

No odor

Bacterial growth

Unpleasant odor

Deodorants Less odor or not noticed

Antiperspirants Less sweat

Perfume Antibacterials (preservatives) Smell ‘catchers’

Aluminium derivatives Water-soluble salts AlC13 or Al2Cl6 first on market Al(OH)6Cl3 • H2O AlZr(OH)Cl • H2O

Figure 20.1 Underarm sweat gland mechanism.

Stratum corneum Pigment layer Stratum germinativum: - Stratum spinosum - Stratum basale

Sweat pore Hair shaft

Dermal papilla Epidermis Sensory nerve ending for touch

Sebaceous gland Arrector pili muscle

Hair follicle Dermis Papilla of hair Sweat gland Pacinian corpuscle Subcutis (Hypodermis)

Blood and lymph vessels



Nerve fiber

Figure 20.2 Cross-section of skin and sweat glands.



Personal Care Products Iso-valeric acid

3-methyl 4-hexanoic acid



Acidic odor

S.epidermiis (smell of sweat acidic odor)

Sterilizing pathogens

Suppressing microorganism enyzmes

Axillary odor

Brevibacterium (smell of axillary odor)

Volatile steroids odor

Propionibacterium sp. (smell of steroid odor)


Bacillus spp. Corynebacterium spp. (smell of spoiled socks-like odor) Sweat (sebaceous lipid)

Eccrine gland

Apocrine gland

Figure 20.3 Sweat metabolism cycle.

glands to secrete fluid on to the surface of skin, where it then cools the body as it evaporates. The composition of the eccrine gland secretion is about 55–60% fluid, mostly water with various salts (Primarily: sodium chloride, potassium chloride) and various electrolytic components (ammonia, calcium, copper, lactic acid, potassium, and phosphorus). The warmth and limited air flow is conducive to allowing for rapid decomposition of organic matter made up of primarily low molecular weight volatile fatty acids (Figure 20.3). These fatty acids and the steroidal compounds produce the recognizable body odors. The apocrine glands are triggered by emotions. These glands are dormant until puberty, at which time they start to secrete. Apocrine glands secrete a fatty substance. When under emotional stress, the wall of the tubule glands contract to push the fatty exudates to the surface of skin where bacterial flora begin breaking it down. In a regulatory monograph [2] the FDA, through the Food Drug and Cosmetic Act, defines antiperspirants as an overthe-counter (OTC) drug when applied topically to reduce production of underarm sweat (perspiration). They are considered drugs because they can affect the function of the body by reducing the amount of sweat that reaches the skin surface. In the USA, OTC drugs are subjected to monograph rules, which define standards and requirements, premarket approval process, acceptable actives, and allowable formulation percentages of actives. Other countries’ regulations vary in content and scope. Some countries consider antiperspirants as cosmetics and not affecting the biologic physiology


of the body; as such they are not held to the same strict standards as in the USA. As an example, Canada has recently (2008) ruled that antiperspirants will longer be considered a drug; use of them now only needing to comply with cosmetic regulations.

Wetness and odor control and testing The consumer typically confuses what antiperspirants and deodorants do, mostly caused by a misunderstanding of marketing claims and product positioning. For the most part, antiperspirants are based on aluminum-based cationic salt chloride complexes (as well as complexes with zirconium acid salts) and are referred to as “actives” on back label of consumer antiperspirant products. There are numerous types of antiperspirant actives listed in the FDA monograph as well as in the US Pharmacopia (USP) [3]. Antiperspirant actives are responsible for blocking sweat expulsion through the formation of temporary plugs within the sweat duct, thus stopping or slowing down the flow of sweat to the surface of the eccrine gland. A theory to wetness control that has been accepted over the years is that the hydrated aluminum or aluminum–zirconium cationic salt chloride is transported to the eccrine gland, interacting with the protein contained within the gland. In this basic protein environment, the antiperspirant active is reduced, producing a gelatinous proteinaceous plug. By plugging the gland, sweat is prohibited from transporting to the surface, causing osmotic pressure. Eventually, this plug is pushed out of the eccrine gland and the gland is

20. Antiperspirants and deodorants allowed to operate again in a normal fashion. This can take 14–21 days for all the eccrine gland, to begin firing; known as a wash-out period. Without going into detail, one can describe how antiperspirants are tested for their Wetness Inhibiting Performance (“WIP”™)2 effectiveness. The FDA prescribes a methodology for testing the effectiveness of an antiperspirant by having participants tested in a controlled environment – 30–40% relative humidity at approximately 100 °C. Sweat is continuously collected during 20-minute intervals and reported as the production or percentage change in production over the average of two 20-minute collection periods. To be accepted as a participant one must exceed production of 100 mg collected sweat per 20-minute period and should not exceed more than 600 mg difference between the highest and lowest sweat production within the test population. The results of testing need to meet a minimum of 20% sweat reduction in 50% of the test population in order to be considered an antiperspirant. Deodorants cover odor through a variety of mechanisms, which include the neutralization or counteracting of odoriferous axilla odor through the retardation of the odor development, or the reduction in perception of odor through masking of the odor. Masking is basically accomplished via use of fragrances and other volatile components. Neutralization is the chemical reaction to modify low molecular weight fatty acids that are excreted from the apocrine gland. One type of neutralization agent is antimicrobials that disrupt cell barrier viability causing the bacterial microbes to perish (triclosan is one popular example). Deodorants are designed to minimize underarm axilla odor, not to reduce or eliminate perspiration. So, deodorants are best for those people who do not have a problem with sweating yet want to feel fresh and odor free. It is important to note that deodorants have no antiperspirant physiologic activity, but antiperspirants can function both as antiperspirants and deodorants; thus, consumers needing odor and wetness control will require the use of antiperspirants to achieve their needs.

Chemistry and formulation of antiperspirants It is important to have some understanding of the chemistry of antiperspirants to gain a better appreciation of their physiologic action in the axilla mantle. Antiperspirants are divided into two categories of functional aluminum-based and zirconium-based actives (typically: aluminum chlorohydrate, aluminum zirconium tetrachlorohydrex-GLY, alumi-

2 Trademarked 2008 and property of Eric Abrutyn, TPC2 Advisors Ltd., Inc., Republic of Panama Corporation.

num zirconium trichlorohydrex-GLY, or aluminum chloride) plus an inactive formula matrix for consumer acceptable aesthetics. The basic building block of antiperspirant actives is based on aluminum chemistry in which elemental aluminum is reduced in an acidic medium to produce what is traditionally known as aluminum chlorohydrate (ACH) with an atomic ratio of 2 : 1 aluminum to chloride. These inorganic cationic polymer salts are classified as octahedral complexes of a basic aluminum hydroxide, stabilized with an anionic chloride to maintain their water solubility. Within the monograph boundaries [2], the atomic ratio of aluminum to chloride can range from 2 : 1 to 1 : 1 within three different segmentations (aluminum chlorohydrate, aluminum sesquichlorohydrate, and aluminum dichlorohydrate). Antiperspirant actives can also be complexed with hydrated acidic zirconium cationic salts of chloride to make what is traditionally known as aluminum zirconium chlorohydrate (ZAG or AZG). Like ACHs, AZGs can have various ratios of atomic aluminum to zirconium of 2 : 1 to 10 : 1 and atomic total metals to chloride of 0.9 : 1 to 2.0 : 1. These AZG complexes can be buffered with glycine (an amino acid) to stabilize the complex and mitigate the acidic harshness which could result when applied to underarm axilla. There is a growing interest in aluminum-free odor and wetness controlling products. One product that has emerged is based on a natural stone “crystal.” “Crystal” products are made from a mineral known as potassium alum, also known as potassium aluminum sulfate and contain aluminum. Unlike aluminum salts used in antiperspirants, alum does not prohibit sweating; it only helps control the growth of bacteria that can cause an underarm odor.

Delivery systems The formulation matrix delivery system is the key to effectiveness of antiperspirant active performance and acceptable consumer application. The most common delivery systems are roll-ons (either aqueous or cyclosiloxane suspensions), aerosol (hydrocarbon propellant suspensions), extrudable clear gels (water-in-cyclosiloxane emulsions), extrudable opaque soft solids (anhydrous cyclosiloxane suspension pastes), or sticks (anhydrous cyclomethicone suspension solids) (Figure 20.4). Within each form there are typical inactive ingredients that support a stable formula with consumer-acceptable esthetics so as not to interfere with the WIP™ delivery of the antiperspirant active. Although this chapter does not focus on details of formulation development, this subject can be researched in more detail in the literature [4,5]. In general, aqueous-based hydrous formulas (mostly based on roll-on and clear gel delivery systems) will have some type of emulsifier or stabilizing agent. In the case of aqueous roll-ons, they tend to



Personal Care Products



Soft solid



16% Cyclics

40-50% Cyclics

60% Cyclics

45-75% Cyclics

8-15% Silicones

1% Dimethicone copolyol

20-25% AP salts (no water)

25% AP salts

20-25% AP salts

8-15% AP salts

50% AP salts in water

15-25% Waxes

11% Organic emulsifier

2-4% Bentone 0-10% Other

0-10% Others 15% Propylene glycol

2% Bentone 75-85% Propellant

4% Organic thickener

17% Water Figure 20.4 Antiperspirant formula matrix delivery systems.

be Polyethylene Glycol (PEG) or Polypropylene Glycol (PPG) ethoxylated alcohols (INCI e.g.: PEG-2, PEG-20) and for clear gel emulsions they are based on PEG and PPG alkoxylated functional siloxanes (INCI e.g.: PEG/PPG-18/18 Dimethicone Copolymer). Anhydrous-based formulas (typically: solid sticks, some types of roll-ons, extrudable creams) include cyclosiloxane (preferably Cyclopentasiloxane) for transient solvent delivery of the active and its eventual evaporation to leave no residue on the skin, solidification agent (INCI e.g.: Stearyl Alcohol, Hydrogenated Castor Oil, and miscellaneous fatty acid ester wax), and dispersing agent (INCI e.g.: PPG-14 Butyl Ether). Most antiperspirant formulas include other ingredients for cosmetic purposes, such as fragrance, antioxidants (BHT – Butylated Hydroxytoluene), chelating agents (Disodium EDTA – Disodium Edetate), soft feel powders (Talc, Corn Starch, and Corn Starch Modified), and emollients and/or moisturizers (petrolatum, mineral oil, fatty acid esters, non-volatile hydrocarbons). These ingredients have been used in the industry for well over 25 years with accepted safety profiles; reviewed by Cosmetic Ingredient Review ( and other governmental or medical agencies.

Dermatologic concerns Each manufacturer of antiperspirants keeps a thorough record of adverse affects as reported by the consumer. For the most part, there is a low incident of adverse affects when the product is use as prescribed. Issues tend to revolve around skin irritation and sensitization. These adverse affects are reversible with cessation of use. Irritation can be brought


about for a number of reasons, but most often by application on broken skin (e.g. from shaving) or sensitivity to the fragrance or one of the metallic components of the antiperspirant active. Switching brands or fragrances types is one remedy to alleviate adverse affects. In some cases a person is so sensitive to an antiperspirant active that he or she can no longer use a product containing an aluminum-based antiperspirant. Health concerns regarding antiperspirants have been discussed in the literature over the last 40–50 years and mostly relate to breast cancer or Alzheimer disease. According to the Alzheimer’s Association (, the linkage of aluminum and Alzheimer disease is most likely linked to a single study in the 1960s where an abnormally high concentration of aluminum was observed in the brains of some Alzheimer patients. However, “After several decades of research,” reports the Alzheimer’s Association, “scientists have been unable to replicate the original 1960s study.” In fact, there is still no scientific correlation on the cause and effect relationship for contracting Alzheimer disease. The research community is generally convinced that aluminum is not a key risk factor in developing Alzheimer disease. Public health bodies sharing this conviction include the World Health Organization, the US National Institutes of Health, the US Environmental Protection Agency, and Health Canada. According to the National Cancer Institute (NCI) and the American Cancer Society, rumors connecting antiperspirant use and breast cancer are largely unsubstantiated by scientific research. The rumors suggest that antiperspirants prevent a person from sweating out toxins and that this helps the spread of cancer-causing toxins via the lymph

20. Antiperspirants and deodorants nodes. The NCI discusses two studies that address the breast cancer rumor. A 2002 study of over 800 patients at the Fred Hutchinson Cancer Research Institute found no link between breast cancer and the use of antiperspirant and/or deodorant [6]; and a study of 437 cancer patients, published in 2003 in the European Journal of Cancer Prevention, found no correlation between earlier diagnosis of breast cancer and antiperspirant and/or deodorant use [7]. The NCI’s analysis of the second study was that it “Does not demonstrate a conclusive link between these underarm hygiene habits and breast cancer. Additional research is needed to investigate this relationship and other factors that may be involved.” Through the evaluation of these and other independent studies, it can be concluded that there is no existing scientific or medical evidence linking the use of underarm products to the development of breast cancer. The FDA (Food & Drug Administration), the Mayo Clinic, the American Cancer Society, and the Personal Care Products Council (formerly Cosmetic, Toiletry, and Fragrance Association) have come to a similar conclusion. Sweating is necessary to control body temperature, especially during times of exercise and warm or hot surroundings. In a small portion of the population the sympathetic nervous system can go awry, affecting the complex biologic mechanism of perspiration, resulting in either excessive perspiration (hyperhidrosis) or little or no perspiration (anhidrosis). Currently, there are no known cures for hyperhidrosis but there are a number of treatment options: injectable treatment such as botulinum toxin type A (Botox), topical agents such as prescribed antiperspirants, oral medications, and surgery. Based on information from the International Hyperhidrosis Society, over 87% of people with hyperhidrosis say that OTC antiperspirants do not provide sufficient relief. Thus, it is important for the medical community to understand the other options available to treat excessive sweating. Botox, a drug that has been approved for use as an injectable treatment in the axilla area, works to interrupt the chemical messages (anticholinergic) released by nerve endings to signal the start of sweat production. It is important to understand how to administer Botox in a manner that will not cause medical issues, thus only a trained practitioner should administer treatment. Unfortunately, Botox is not a permanent solution, and patients require repeat injections every 6–8 months to maintain benefits. There are other options for treating excessive sweating, but none have been demonstrated to be either safe or effective for use by consumers. Most systemic medications, in particular anticholinergics, reduce sweating but the dose required to control sweating can cause significant adverse effects (e.g. dizziness), thus limiting the medications’ effectiveness. Iontophoresis is a simple and well-tolerated method for the treatment of hyperhidrosis without long-term adverse effects; however, long-term maintenance treatment is

required to keep patient’s symptom free. Psychotherapy has been beneficial in a small number of cases.

Strengths and weakness of antiperspirants Based on all the information known about antiperspirants one would surmise there are few weaknesses regarding the use of them. Basically, they serve the purpose of reducing the discomfort and potential observation of underarm wetness, and can lead to reduced underarm offensive odors. Except in the case of hyperhidrosis, antiperspirants serve to provide cosmetic esthetics and social acceptance. It is important to note that, even if used twice a day, antiperspirants do not completely stop axilla sweating, but provide a significant reduction in the amount of sweating produced in the axilla. With almost 70 years of use for antiperspirant actives, there is almost no association with adverse affects when properly used in the underarm area. So, the risk–benefit is minimal and is balanced by the ability to maintain a more comfortable and socially appealing state.

Conclusions Because they are regulated in the USA and other countries as drugs, it is foreseen that introduction of new antiperspirant actives will be restricted. To introduce new antiperspirant actives, one would have to go through an extensive New Drug Application process, requiring costly studies on safety and effectiveness. Aside from the introduction of new antiperspirant drugs, dermatologists need to continue monitoring the introduction of unregulated new ingredients that would be included in existing or new formula matrices.

References 1 Gray’s Anatomy: The Anatomical Basis of Clinical Practice, 39th edn. (2004) CV Mosby. 2 USA Department of Health and Human Services: Food and Drug Administration. (2003) Antiperspirant Drug Products for Over-the-Counter Human Use, Final Rule. 68 CFR, Part 110. antiperspirant_FR_20030609.pdf 3 USP 27/NF 22 (2004) United States Pharmacopeial Convention, Rockville, MD, pp. 83–91; 93–106. 4 Abrutyn E. (1998) Antiperspirant and Deodorants: Fundamental Understanding. IFSCC Monograph Series No. 6. Weymouth, Dorset, UK: Micelle Press. 5 Abrutyn E. (2000) Antiperspirant and deodorants. In: Reiger MM, ed. Harry’s Cosmetology, 8th edn. New York: Chemical Publishing Company, Inc., 6; 94/20/1578.pdf (Vol. 94, No. 20, Pg 1578, October 16, 2002). 7 McGrath KG. (2003) An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving. Eur J Cancer Prev 12, 479–85.


Chapter 21: Blade shaving Keith Ertel1 and Gillian McFeat2 1 2

Procter & Gamble Co, Cincinnati, OH, USA Gillette, Reading Innovation Centre, Reading, UK

BAS I C CONCE P T S • Hair removal practices have their roots in antiquity. While modern global attitudes towards hair removal vary, consumers around the world use blade shaving as a method to effect hair removal. • Modern blades and razors are the product of extensive research and technologically advanced manufacturing procedures; these combine to provide the user with an optimum shaving experience. • Effective shaving involves three steps: preparation, including skin cleansing and hair hydrating; hair removal, including the use of an appropriate shaving preparation; and post-shave skin care, including moisturizer application.

Introduction Like many personal care practices, the roots of shaving lie in the prehistoric past. Hair removal for our cave dwelling ancestors was probably more about function than esthetics; hair could provide an additional handle for an adversary to grab during battle, it collected dirt and food, and provided a home to insects and parasites. Flint blades possibly dating as far back as 30 000 BC are some of the earliest examples of shaving implements. Archaeologic evidence shows that materials such as horn, clamshell, or shark teeth were used to remove hair by scraping. Pulling or singeing the hair, while somewhat more painful, were also methods used to effect hair removal. Attitudes towards hair became more varied in ancient times. The Egyptian aristocracy shaved not only their faces, but also their bodies. The Ancient Greeks viewed a beard as a sign of virility but Alexander the Great, who is said to have been obsessed with shaving, popularized the practice among Greek males. Greek women also shaved; a body free from hair was viewed as the ideal of beauty in Greek society. Shaving was viewed as a sign of degeneracy in early Roman society, but an influx of clean-shaven foreigners gradually changed this attitude. For affluent Romans shaving was performed by a skilled servant or at a barbershop, which was popularized in Ancient Rome as a place of grooming and socializing. Shaving implements at this time were generally made from metals such as copper, gold, or iron. The barbershop took on an expanded role in the Middle Ages. In these shops barbers provided grooming services and

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


routinely performed other duties such as bloodletting and minor surgical and dental procedures. Shaving injuries were common and the striped pole that is today associated with barbershops has its origin in these times, its red and white stripes symbolizing blood and the bandages that were used to cover the wound, respectively. The Industrial Revolution heralded a number of advancements in shaving technology. The straight razor was first introduced in Sheffield, England and became popular worldwide as a tool for facial shaving. While an improvement over earlier shaving implements, the straight razor dulled easily, required regular sharpening or stropping, and a high skill level, and shaving injuries were still a problem, which earned it the nickname of “cutthroat razor.” Many credit Jean Jacques Perret with inventing the safety razor in 1762. His device, which he apparently did not patent, consisted of a guard that enclosed all but a small portion of the blade. Variations on the design followed from other inventors, many using comb-like structures to limit blade contact with the skin. The Kampfe brothers filed a patent in 1880 for a razor, marketed as the Star Safety Razor that used a “hoe” design in which the handle was mounted perpendicular to the blade housing. The blade, essentially a shortened straight razor, was held in place by metal clips. While generally successful, the blade in the Star Safety Razor still required stropping before each use. In 1904, King C. Gillette introduced the real breakthrough that brought shaving to the masses. Unlike its predecessors, the Gillette Safety Razor used an inexpensive, disposable blade that was replaced by the user when it became dull. The new razor quickly gained popularity because of a variety of promotional efforts, including a “loss leader” marketing model pioneered by Gillette. Shaving was not only promoted to males. The practice of shaving among females was prompted by the May 1915

21. Blade shaving issue of Harper’s Bazaar magazine that featured a picture of a female model wearing a sleeveless evening gown and sporting hairless axillae. The Wilkinson Sword Company built on the idea by running a series of advertisem*nts targeting women in the 1920s to promote the idea that underarm hair was not only unhygienic, but was also unfeminine. Sales of razor blades doubled over the next few years. Razor developments during the next several decades were primarily limited to improvements in single blade technology, including the switch from carbon steel to stainless steel blade material in the 1960s pioneered by Wilkinson Sword. This prevented corrosion, thus increasing blade life. The next major change occurred in the 1971 with the introduction of the Trac II, the first multiblade razor. Innovation has continued along this track and today consumers can choose from a variety of razor models having multiple blades contained in a disposable cartridge, with specialized designs available to meet the shaving needs of both sexes. The relatively simple appearance of these devices belies their sophistication; they are the product of years of development and technically advanced manufacturing processes. Of course, not all shaving is done with a blade. Electric razors remove hair without drawing a blade across the skin. There are two basic types of electric razors, both relying on a scissor action to cut hairs using either an oscillatory or circular motion. When the razor is pressed against skin the hairs are forced up into holes in the foil and held in place while the blade moves against the foil to cut the trapped hairs. Colonel Jacob Schick patented the first electric razor in 1928. Electric razors were for many decades confined to use on dry skin, but some modern battery-powered razors are designed for use in wet environments, including the shower.

Hair biology basics Much of the hair targeted for removal by shaving or other means is terminal hair (i.e. hair that is generally longer, thicker, and more darkly pigmented than vellus hair). In prepubescent males and females this hair is found primarily on the head and eyebrow regions, but with the onset of puberty terminal hair begins to appear on areas of the body with androgen-sensitive skin, including the face, axillae, and pubic region. Further, vellus hairs on some parts of the body, such as the beard area, may convert to terminal hairs under hormonal influence.

The pilosebaceous unit A pilosebaceous unit comprises the hair follicle, the hair shaft, the sebaceous gland, and the arrector pili muscle. The hair follicle is the unit responsible for hair production. Hair growth is cyclical, and depending on the stage of hair growth, the follicle extends to a depth as shallow as the upper dermis

to as deep as the subcutaneous tissue during the active growth phase. The hair shaft is the product of matrix cells in the hair bulb, a structure located at the base of the follicle. The hair shaft is made up primarily of keratins and binding material with a small amount of water. A terminal hair shaft comprises three concentric layers. Outermost is the cuticle, a layer of cells that on the external hair are flattened and overlapping. The cuticle serves a protective function for external hair, regulates the water content of the hair fiber, and is responsible for much of the shine that is associated with healthy hair. The cortex lies inside the cuticle and is composed of longitudinal keratin strands and melanin. This layer represents the majority of the hair shaft and is responsible for many of its structural qualities (e.g. elasticity and curl). The medulla is the inner most layer found in some terminal hair-shafts, made up of large loosely connected cells which contain keratin. Large intracellular and intercellular air spaces in the medulla to some extent determine the sheen and colour tones of the hair. Each hair follicle is associated with a sebaceous gland. This gland lies in the dermis and produces sebum, a lipophilic material composed of wax monoesters, triglycerides, free fatty acids, and squalene. Sebum empties into the follicle lumen and provides a natural conditioner for the forming and already extruded hair. The arrector pili is a microscopic band of smooth muscle tissue that connects the follicle to the dermis. In certain body sites, when stimulated the arrector pili contracts and causes the external hair to stand more erect, resulting in the appearance of goose bumps.

Hair growth cycle Hair growth is not a continuous process but occurs over a cycle that is conveniently divided into three stages; at any given time hairs on a given body site are at various points in this cycle. The dermal papilla orchestrates the hair growth cycle. Anagen is the phase of hair follicle regrowth and hair generation. During this stage the hair follicle grows downward into the dermis and epidermal cells that surround the dermal papilla undergo rapid division. As new cells form they push the older cells upward. The number of hairs in anagen varies according to body site. At any given time approximately 80% of scalp hairs are in anagen. This is lower for beard and moustache hairs (around 70%) and only 20–30% for the legs and axillae. The length of the anagen phase also varies; on the scalp anagen typically lasts from 3 to 6 years, in the beard area this is closer to 1 year and in the moustache area anagen lasts from 4 to 14 weeks. Anagen is typically 16 weeks for the legs and axillae. The time in anagen determines the length of the hair produced [1]. Anagen is followed by catagen, a transitional phase in the hair growth cycle that sets the stage for production of a new follicle. In catagen the existing follicle goes through



Personal Care Products

controlled involution, with apoptosis of the majority of follicular keratinocytes and some follicular melanocytes. The bulb and suprabulbar regions are lost and the follicle moves upward, being no deeper than the upper dermis at phase end. The dermal papilla becomes more compact and moves upward to rest beneath the hair follicle bulge. On the scalp catagen lasts 14–21 days. Telogen is a phase of follicular quiescence that follows catagen. The final cells synthesized during the previous cycle are dumped at the end of the hair shaft to form a “club” that holds the now non-living hair in place. These hairs are lost by physical action (e.g. combing) or are pushed out by the new hair that grows during the next anagen phase. The percentage of follicles in telogen also varies by body site (e.g. 5–15% of scalp follicles are normally in telogen whereas 30% of follicles on the beard area are normally in telogen and 70–80% of leg and axillae hairs). Telogen typically lasts for 2–3 months, although this is slightly longer for leg hairs [1].


Properties of hair – impact on shaving The beard area of an adult male contains between 6000 and 25 000 hair fibers and beard growth rate has been reported in the literature to be 0.27 mm per 24 hours, although this can vary between individuals [2]. There are two types of hair fibers found in the beard area. Fine, non-pigmented vellus hairs are distributed amongst the coarser terminal hairs. While the literature abounds in publications on the properties of scalp hair, studies of beard hair are relatively scarce. Tolgyesi et al. [3] published the findings of a comparative study of beard and scalp terminal hair with respect to morphologic, physical, and chemical characteristics. Scalp fibers were reported to have half the number of cuticle layers compared to beard hairs from the same subject (10–13 in facial hair, 5–7 in scalp hair). Scalp fibers also had smaller cross-sectional areas (approximately half the area) and were less variable in shape than beard hairs, which exhibited asymmetrical, oblong, and trilobal shapes. These differences can be seen in Figure 21.1. Thozur et al. [4] further showed considerable variations in beard hair follicle shape and diameter within and between individuals. A number of factors contribute to this variation including anatomical location, ethnicity, age, and environmental factors. The structural properties of the hair impact shaving. The force required to cut a hair increases with increasing fiber cross-sectional area [5]. Thus, it requires more force to cut a larger fiber. Indeed, it requires almost three times the force to cut a beard hair than a scalp or leg hair. One important property of hair is that the force required to cut it can be greatly reduced by hydrating the hair. Hydration causes the hair to become significantly softer and much easier to cut so that it offers less resistance to the blade and minimizes any discomfort.


(b) Figure 21.1 Optical micrographs of hair cross-sections taken from the beard (a) and scalp (b) area of the same subject. Beard fibers have a greater cross sectional area and more cuticle layers.

The human hair follicle and the surrounding skin are richly innervated. In particular, the terminal hairs of the human skin are supplied with several types of nerve endings most of which are sensory in nature. It is hypothesized that discomfort associated with shaving (during shaving or postshave) is a result of localized skin displacement and/or the rotation and extension of the beard fiber in its follicle. The current neurologic literature clearly demonstrates that such local cutaneous distortions bring about the release of various chemical communicators (e.g. histamine, prostaglandins, bradykinins) that heighten the sensitivity of the response of pain-mediating nerve endings for a period of time [6]. The contribution to shaving comfort and irritation remains to be elucidated. Shaving can also cause irritation by physical damage. There is evidence to suggest that shaving irritation involves the removal of irregular elevations of the skin by the razor blade, particularly around follicular openings [7,8]. The topography of the skin is highly variable and combined with the presence of hairs this creates a very irregular terrain over which an incredibly sharp blade traverses (Figure 21.2). This can result in irritation, generally characterized in this context by the presence of attributes such as nicks or cuts, redness, razor burn, sting, or dryness. In order to achieve a close and comfortable shave with minimal irritation it is essential to use a good quality, sharp blade and

21. Blade shaving

Shaving angle




Cap Guard

Figure 21.3 Cross-section of a double-edge razor showing exposure geometry.

Figure 21.2 A scanning electron micrograph of a replica of an area of cheek on a male face. The topography of the skin is highly variable and combined with the presence of hairs this creates a very irregular terrain over which an incredibly sharp blade traverses.

adopt a shave care regimen designed to remove as much hair as possible while inflicting minimal damage to the underlying skin.

Shaving and the razor explored Since the invention of the safety razor, consumer product industries have invested a considerable amount of time, money, and expertise in improving the design of the razor and blade in order to provide a closer, more comfortable, and safer shave. To date, few reports have been available in the literature detailing the shaving process and the mechanisms involved. The following section aims to provide an overview of the razor and the complex mechanisms by which the blade cuts the beard hair and interacts with the underlying skin.

Evolution of the system razor With a system razor, only the cartridge containing the blades is replaced, unlike a disposable razor which is thrown away in its entirety when blunt. In the first double edge razor systems, the consumer had to position and tension a single blade within the handle. As a result, there was variability and inconsistency in how the blade interacted with the skin. In contrast, the advanced shaving systems of today are precisely assembled during manufacture. Figure 21.3 shows a cross-section of a double edge razor with the key parameters of the cartridge geometry indicated. The shaving angle is the angle between the center plane of the blade and a plane tangent to the guard. The blade exposure is the amount by which the tip of the blade projects beyond the plane tangent to the cap and guard. Altering any

of these parameters has both good and bad effects. For example, an increase in blade exposure brings the blades into closer contact with the underlying skin and hair, increasing the closeness of a shave at the expense of more nicks and cuts and discomfort. A reduction in the shaving angle improves comfort but reduces cutting efficiency. Consequently, all aspects of the double edge blade system were compromises and the user was able to adjust the razor to suit their individual preferences [9]. Modern systems have reduced the need to compromise and achieved the previously unattainable: improving closeness, safety, and comfort simultaneously. The improvement in closeness is attributed to, and exploits the mobility of the hairs within the follicle. Observation of the movement of hairs during shaving has shown that they are not cut through immediately upon contact with the blade; rather, they are carried along by the embedded blade tip, and effectively extended out of the follicle. This extension is primarily brought about by the distortion of the soft tissue between the hair root and the skin surface layers. Because of the viscoelastic nature of the tissue, once severed the hair rapidly retracts back into the follicle. If a second blade follows closely behind the first, it can engage the hair in the elevated state, cutting it further down the hair shaft, before it has time to fully withdraw into the follicle [9]. By having multiple blades, this process can be exploited to give a measurable improvement in closeness. It is therefore possible to use a lower blade exposure to achieve closeness while minimizing skin contact and thus the potential for nicks, cuts, and discomfort. Simply adding more blades to razors is not a new idea (the first US patent for a 5-blade razor was filed in 1929, US1920711) and from the above it is clear that on its own this will not deliver a great shave. In addition to precisely controlling the razor geometry, it is essential that the underlying skin is carefully managed to ensure a safe and comfortable shave. Adding more blades improves closeness by virtue of hair extension and probability of cutting, but can also create drag and discomfort. The pressure exerted on the skin by the additional blades can cause the skin to bulge between



Personal Care Products

the inter blade span. By spacing the blades closer together, both the drag and skin bulge are reduced and a more uniform stress is placed on the skin leading to a safer, more comfortable shave (Figure 21.4). Manipulating these parameters can greatly alter the characteristics of a shave; consequently cartridge geometry and blade spacing are carefully controlled and set during manufacturing using specifications determined through extensive research. This ensures that the consumer receives a targeted and consistent shave with the optimum blade– skin contact.

Cutting edge technology A further critical component of the shaving process, and central to a great shave, is the razor blade edge. The narrower the blade edge the more easily it can cut through a hair, leading to a closer and more comfortable shave. However, if the blade is too narrow it can collapse under the

cutting force. Thus, the industry strives to produce the thinnest blade edge possible while retaining blade edge strength. This is typically achieved by treating a stainless steel substrate with thin film coatings such as diamond-like carbon to enhance edge strength or platinum-chromium to enhance corrosion resistance. The blades are further coated in a telomer like material to create a low friction cutting surface. This greatly reduces the force required to cut hair, minimizing hair “pulling,” providing additional comfort. Additional key components of a modern razor are shown in Figure 21.5. First introduced in 1985, lubricating strips are now found on most disposable and permanent system cartridges. The strips distribute water-soluble lubricant following each shaving stroke, resulting in a significant reduction in drag of the cartridge over the skin and allowing additional strokes to be taken comfortably even after most of the shaving preparation has been shaved off. The strips also allow the skin to release freely from the tension created


(b) Figure 21.4 Multiple blade razors and skin management. Spacing 5 blades closer together (b), creates a shaving surface that helps spread shaving force for a safer, more comfortable shave.

Lubricating strip: Low friction, releases skin tension, lubricates for next stroke

Fin guard: Tensions skin ahead of blades

Pivot: Rotation point of cartridge, ensure cartridge follows contours

Trimmer blade: Precision trimming

Blade springs: Allows blades to react to load

Blades: Extend and cut hair Interact with skin Figure 21.5 The key components of a razor and their functions.


21. Blade shaving

Cutting force relative to dry hair (%)

Dry hair

Figure 21.6 Effect of hydration time on force required to cut (beard) hair. The most significant reduction occurs over the first 2 minutes.

by the skin guard. The guard is typically comprised of soft, flexible microfins or rigid plastic which precede the blades. These microfins gently stretch the skin, causing beard hairs to spring upward so they can be cut more efficiently. Additional features include pivoting heads that allow the cartridge to follow the contours of the face and trimmer blades allow the shaver to get exact positioning of the blade for a closer, more precise shave. The recent introduction of oscillating wet shaving systems increases razor glide for improved comfort. Such advances in blade edge and razor technology, coupled with an understanding of the needs of the consumer, have significantly enhanced the quality, closeness, safety, and comfort of the shave. This is most evident when combined with a shave care regimen designed to maximize hair removal and minimize skin damage.

The shaving process Drawing a sharpened implement across the skin’s surface has the potential to cause damage and dry shaving can result in the immediate appearance of uplifting skin cells and perturbation of stratum corneum barrier function, with an increase in dryness observed several days subsequent to the initial damage [10]. Body site will likely influence the response to this insult because the number of stratum corneum cell layers varies over the body surface, averaging 10 layers on the cheek or neck and 18 layers on the leg [11]. The potential for damage is compounded by non-uniform skin surface topography and the presence of hair (Figure 21.2), which when dry is relatively tough. A dry hair has about the same tensile strength as a copper wire of equivalent diameter. A few simple steps can help prepare the skin and hair for an optimum shaving experience. First, the skin should be thoroughly cleansed. Cleansing removes surface soils that

100 90

Significant reduction in cutting force after 2 min hydration

80 70 60 50 40 0



6 8 10 Hydration time (min)




can interfere with the shaving process and also helps hydrate the hair. The latter is especially important and shaving during or after showering or bathing is ideal but short of this, the area to be shaved should be washed with a cleanser and warm water. In some situations applying a warm, wet towel or cloth to the skin for a few minutes before shaving may also help. Hair is mostly keratin, and keratin has a high affinity for water. Hydrating softens the hair to make it more pliable and easier to cut; the force required to cut a hair decreases dramatically as hydration increases (Figure 21.6). Short-term hydration will also improve the skin’s elasticity [12], making it better able to deform and recover as the blade is drawn over its surface. However, more is not necessarily better; prolonged soaking can macerate skin and cause the surface to become uneven, making effective hair removal more difficult and increasing the risk of damaging the skin. Excessive soaking can also deplete the stratum corneum of substances such as natural moisturizing factor (NMF) that help it hold on to water [13], which can exacerbate any dryness induced by the shaving process. A preparation such as a shaving gel or cream can also improve the shaving experience. A preparation serves several functions. The physical act of applying preparation to the skin can remove oils and dead skin cells from the surface and aid in the release of trapped hairs, with the potential to improve the efficiency of the cutting process. Shaving preparation formulas typically contain a high percentage of water, which provides an additional hydration source for the hair and skin. Finally, shaving preparations are usually based on surfactants and contain other ingredients such as oils or polymers. For reasons already noted hydrating hair and skin is important for the shaving process, but hydration increases the coefficient of friction for an object sliding across the skin’s surface [14]. The surfactants, oils, and polymers in shave gels can reduce friction to improve razor glide, provide a cushion between the blade and skin, and improve cutting efficiency.



Personal Care Products

Table 21.1 Summary of some differences between males and females related to hair characteristics and blade shaving behaviors and attitudes. Male


Onset of shaving behavior

Most males begin shaving between the ages of 14 and 15

Most females begin shaving between the ages of 11 and 13

Body areas shaved

Most male shaving occurs on the face and neck areas. The average male shaves an area of ∼300 cm2

Female shaving is focused on the leg and underarm areas. The average female shaves an area of ∼2700 cm2

Relative hair density

Higher hair density. On average the male face has 500 hair follicles per cm2 [7]

Lower hair density. On average the leg and axillae have 60–65 hair follicles per cm2 [7]

Hair growth pattern

Hair on the face tends to grow in multiple directions

Hair on the legs tends to grow in the same direction, but hair in the underarm area grows in multiple directions

Location where shaving occurs

Males tend to shave at the bathroom sink

Females tend to shave in the shower or bath

Attitudes towards shaving

Males tend to view shaving as a skill

Females tend to view shaving as a chore

Equipment and technique are also important for an optimum shaving experience. The razor should be in good condition with a sharp blade. A dull blade will not cut the hair cleanly and will pull the hair, increasing discomfort and the likelihood of nicks and cuts. Shaving in the direction of hair growth with a light pressure is recommended to reduce pulling, at least for the first few strokes. These preliminary strokes can be followed up with strokes against the grain if additional hair removal is needed. On the face, feeling the beard with the hand can help identify hair growing patterns and guide stroke direction. Skin on some areas of the body, such as the underarms, has a naturally uneven or very pliable surface. Pulling the skin taut on these areas during shaving can improve the efficiency of the hair removal process and reduce nicking or cutting. In all cases the razor should be rinsed often to keep the blade surface clean. Some situations may require extra care during the shaving process. For example, pseudofolliculitis barbae (PFB) is a condition that affects individuals with very tightly curled hair, such as those who are of African descent. In PFB hairs may grow parallel to, rather than out from, the skin’s surface and in some cases the tip of the hair curves back and grows into the surface of the skin, causing inflammation. Individuals prone to developing PFB should thoroughly hydrate the hair before shaving, liberally use a shaving preparation and if blade shaving, shave daily with a sharp razor. Following the shave, skin should be thoroughly rinsed with water to remove all traces of shaving preparation, because these products are generally surfactant-based and leaving surfactant in contact with the skin can induce or exacerbate irritation. Rinsing with cool water can have a soothing effect on the skin. Applying a moisturizer can also have a soothing effect and will hydrate the skin to help


prevent dryness. Moisturizers can also speed the barrier repair process and thus help to mitigate any stratum corneum damage that might result from shaving. These steps apply generally to blade shaving needs for both sexes. However, there are differences between males and females in terms of hair characteristics and blade shaving behaviors and attitudes. As a result, razors for females are often designed to accommodate body specific needs. Some of these differences are summarized in Table 21.1.

References 1 Richards R, Meharg, G. (1991) Cosmetic and Medical Electrolysis and Temporary Hair Removal: A Practice Manual and Reference Guide. Medric Ltd, Toronto. 2 Saitoh M, Uzuka M, Sakamoto M. (1969) Rates of hair growth. Adv Biol Skin 9, 183–201. 3 Tolgyesi E, Coble DW, Fang FS, Kairinen EO. (1983) A comparative study of beard and scalp hair. J Soc Cosmet Chem 34, 361–82. 4 Thozhur SM, Crocombe AD, Smith AP, Cowley K, Mullier M. (2007) Cutting characteristics of beard hair. J Mater Sci 42, 8725–37. 5 Deem D, Rieger MM. (1976) Observations on the cutting of beard hair. J Soc Cosmet Chem 27, 579–92. 6 Michael-Titus A, Revest P, Shortland P, Britton R. (2007) The Nervous System: Basic Science and Clinical Conditions. Elsevier Health Sciences, UK. 7 Bhaktaviziam C, Mescon H, Matoltsy AG. (1963) Shaving. I. Study of skin and shavings. Arch Dermatol 88, 874–9. 8 Hollander J, Casselman EJ. (1937) Factors involved in satisfactory shaving. JAMA 109, 95. 9 Terry J. (1991) Materials and design in Gillette razors. Mater Des 12, 277–81. 10 Marti VPJ, Lee RS, Moore AE, Paterson SE, Watkinson A, Rawlings AV. (2003) Effect of shaving on axillary stratum corneum. Int J Cosmet Sci 25, 193–8.

21. Blade shaving 11 Ya-Xian Z, Suetake T, Tagami H. (1999) Number of cell layers of the stratum corneum in normal skin: relationship to the anatomical location on the body, age, sex and physical parameters. Arch Dermatol Res 291, 555–9. 12 Auriol F, Vaillant L, Machet L, Diridollou S, Lorette G. (1993) Effects of short-term hydration on skin extensibility. Acta Derm Venereol [Stockh] 73, 344–7.

13 Visscher MO, Tolia GT, Wickett RR, Hoath SB. (2003) Effect of soaking and natural moisturizing factor on stratum corneum water-handling properties. J Cosmet Sci 54, 289–300. 14 Highley DR, Coomey M, DenBeste M, Wolfram LJ. (1977) Frictional properties of skin. J Invest Dermatol 69, 303–5.


Section III Adornment

Part 1: Colored Facial Cosmetics Chapter 22: Facial foundation Sylvie Guichard and Véronique Roulier L’Oréal Recherche, Chevilly-Larue, France

BAS I C CONCEPTS • Facial foundation places a pigment over the skin surface to camouflage underlying defects in color and contour. • Facial foundations must be developed to match all ethnicities and facial needs. • New optic technologies have allowed modern facial foundations to create a flawless facial appearance more effectively. • Facial foundations impact skin health because they are worn daily for an extended period.


Complexion makeup – an ancient practice

Complexion makeup is anything but a trifling subject. The practice is deeply rooted in human history. It has evolved along with civilizations, fashions, scientific knowledge, and technologies to meet the various expectations depending on mood, nature, culture, and skin color. A prime stage to beautifying the face, complexion makeup creates the “canvas” on which coloring materials are placed. Women consider it as a tool to even skin color, modify skin color, or contribute to smoothing out the skin surface. To fulfill these different objectives, substances extracted from nature took on various forms over time until formulation experts developed a complex category of cosmetics including emulsions, poured compacts, and both compact and loose powders. These developments have improved the field of skin care providing radiance, wear, and sensory effects. It remains a challenge to adequately satisfy the varying makeup requirements of women from different ethnic origins, who do not apply products in the same way and do not share the same diverse canons of beauty. It is therefore necessary to gain a thorough understanding of the world’s skin colors. Finally, as a product intended to be in intimate contact with the skin, facial foundations must meet the most strenuous demands of quality and safety. This has motivated evaluation teams to develop methods for assessing product performance.

Modifying one’s self-appearance by adding color and ornament to the skin of the face and body skin is hardly a recent trend [1–3]. From Paleolithic times, man has decorated himself with body paint and tattoos for various ritual activities. In the Niaux Cavern (Ariège, France), the cave of Cougnac (Lot, France), and the Magdalenian Galleries of le Mas d’Azil (Ariège), the past ages have left evidence of these practices. Along with the flint tools in the Magdalenian Galleries at le Mas d’Azil ochre nodules were found that look like “sticks of makeup” as well as grinding instruments, jars, spatulas, and needle-like “rods” 8–11 cm long, tapered at one end and spatula-shaped on the other end, suitable for applying body paint. From the earliest of ancient civilizations, there are cosmetic recipes containing a variety of ingredients which are often closer to magic than to rational chemistry, aimed particularly at modifying the complexion. Usually used exclusively by high dignitaries, cosmetics were intended to whiten the complexion.

Ancient Mesopotamia (2500


The queen and the princes of Ur used cosmetics consisting of a mixture of mineral pigments based on Talak (from which the word “talc” is derived). Nowadays such cosmetics are still commonly used in some parts of the Middle East.

Ancient Egypt (3rd millennium Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


The priests used plaster to cover their faces. It was also desirable for women to exhibit very white skin without blemishes, as these were indications of a privileged life of leisure.



Colored Facial Cosmetics

The complexion was whitened with mixtures of plaster, calcium carbonate, tin oxide, ground pearls, and lead carbonate (ceruse) mixed with animal grease, waxes, and natural resins. Evidence of the complexity of the ancient recipes has been determined by chemical analyses carried out jointly by the Centre National de la Recherche Scientifique, L’Oréal’s Recherche department, the Research Laboratory of the Museums of France, and the European Synchrotron Radiation Facility on the content of cosmetic flasks found in archeologic excavations [4]. The earliest cosmetic formulary is attributed to Cleopatra – “Cleopatrae gyneciarum libri.”

have made them disappear from the market, but it was not until 1915 that the use of ceruse was officially prohibited. In 1873, Ludwig Leichner, a singer at the Berlin Opera, sought a way to preserve his skin tone by creating his own foundation base from natural pigments. In 1883, Alexandre Napoléon Bourjois devised the first dry or pastel foundation. Bourjois was about to launch his first dry blush, Pastel Joue. With the birth of the cosmetics industry, products were widely distributed. Modern manufacturing techniques with production on an industrial scale coupled with the beginning of mass consumer use started at the beginning of the 20th century.

Ancient Greece In Ancient Greece, the white, matte complexion symbolizing purity was obtained through generous application of plaster, chalk, kaolin (gypsos), and ceruse (psimythion), but Plato was already denouncing the harmfulness of these cosmetics.

Ancient Rome Ancient Rome raised the use of makeup to the level of an art form. In addition to cosmetics that enhance the beauty of face and body, cosmetics were applied to improve appearance and hide flaws, notably those caused by the aging process. Women of the upper classes “coated” their face with complex mixtures with recipes reported in Ovid’s Cosmetics or in Pliny the Elder’s Natural History. For instance, hulled barley, powdered stag antlers, narcissus bulbs, spelt, gum, and honey were the components of a mixture to make the face shiny. Dried crocodile excrement, ceruse, vegetal extracts, as well as lanolin or suint (also known as oesype) were used to whiten the complexion. Recently, an analysis was made of an ointment can, christened Londinium, discovered in London when excavating a temple dated at the middle of the 2nd century AD. It contained glucose-based polymers, starch, and tin oxide. The white appearance of the cream reflects a certain level of technological refinement [5].

From the Middle Ages to the 19th century In Europe, from the Middle Ages up to the middle of the 20th century, good breeding and good manners were associated with a white complexion. In the Middle Ages, makeup was based on water, roses, and flour, which did not prevent ceruse from making a strong comeback in the Renaissance. It was then subsequently mixed with arsenic and mercury sublimates to give the complexion a fine silver hue. Toxic effects of these cosmetics, however, was beginning to worry the authorities. In 1779, following the onset of a number of serious cases, the manufacture of “foundation bases” was placed under the control of the Société Royale de Médicine, which had just been set up in 1778. The toxic components were then removed. This measure seems to


20th century: the industrial era and diversification In the 20th century, fashionable powders for the complexion became more sophisticated [6,7]. Market choice extended with the launch of new brands such as Gemey, Caron, and Elizabeth Arden. The 1930s saw the development of trademarks such as Helena Rubinstein and Max Factor created by professional movie and Hollywood makeup artists. The products were suited to the requirements of the movie studios. Extremely opaque, tinted with gaudy colors, they were compact and difficult to apply. After the success of Max Factor’s Pancake and Panstick cosmetics, use of the word “makeup” became widespread. Initiated by Chanel in 1936, the fashion in Europe and the USA began to switch from white to a tanned complexion. Even though women were more inclined to wear cosmetics, makeup was still not part of everyday life. Pancake makeup, a mixture of stearate, lanolin, and dry powders, was not easy to apply. Technical advances gradually made products more practical. The box of loose powder was equipped with a sieve in 1937 (Caron). In 1940, Lancôme launched Discoteint, a creamy version of its compact. Coty micronized its powder (Air Spun) in 1948. Yet, it was not until the 1950s that a real boom occurred in the number of products on the market. Compact makeup was made available in creamy form; foundation became a fluid cream (Gemey, Teint Clair Fluide, 1954). It was the start of a great diversification of formulations: fluids, dry or creamy compacts, sticks, and powders. Makeup became multifaceted, with more sophisticated effects, including moisturizing, protection from damaging environmental factors, and other skincare properties in addition to providing color. Since then, complexion makeup has followed the continuous changes in regulations and advances in biologic knowledge, especially in the area of skin physiology. Over the last decades, it has benefitted from technologic progress in the field of raw materials, as well as from enhanced understanding and gains in optics and physical chemistry. Finally, makeup was enriched with the diversity of cultures from all over the world prompted by globalization. The

22. Facial foundation beginning of the 21st century opens a new era of visual effects, sensory factors, and multiculturalism.

Formulation diversity Women expect foundations to effect a veritable transformation that hides surface imperfections, blemishs, discolorations, and wrinkles, while enhancing a dull complexion and making shiny skin more satiny. Whereas making up the eyes and the lips is generally done playfully, the complexion receives more attention. It is in this area that women display their greatest expertise and are the most demanding. Women have high expectations for their foundation including: • Guaranteed evenness and concealment of flaws; • Hiding of wrinkles and pores; • Good adherence to the skin; • Matting of lustrous skin; • Excellent wear all day long; • Unaltered color over time; • Pleasant, easy application; and • Appropriate for sensitive skin.

Variety of formulations In order to satisfy diverse demands, a large number of products types and forms have been developed (Figure 22.1): • Fluid foundations; • Compact, easy-to-carry foundations with adjustable effects; and • Powders to be used alone or in combination with a fluid foundation.

Fluid foundations: emulsions Fluid foundations include both oil-in-water (O/W) and water-in-oil (W/O) emulsions. Until the 1990s, most foun-

dations were O/W emulsions. Generally intended for mixed to oily skin, they are characterized by: • Very rapid drying, which can complicate even application; • Poor coverage; • Reduced wear; • Appropriate for mixed to oily skin with their external aqueous continuous phase, which makes them feel fresh on the skin. In the 1990s, the first W/O formulations revolutionized the foundation market. The external oil continuous phase gives textures with longer drying times more suitable for perfect product application. The progressive coating of pigments has improved their dispersion in the oil phase and helped to stabilize the emulsion. Throughout the years, the oil phase has been diversified mainly as a result of introducing silicone oils, first in conventional then in volatile forms. Silicone oils have dramatically changed the cosmetic attributes of facial foundation. Foundation no longer has to be spread evenly over the face. Its slickness makes it slide on the skin evenly with a single stroke without caking. The use of volatile oils, siliconated or carbonated, gave rise to the design of long-lasting foundations. As the volatile phase evaporates, the tinted film concentrates on the skin. Adhering during drying on the skin surface, the tinted film withstands friction and does not stain clothes. Thus, the “non-transfer” facial foundation was born. In the 21st century, combining volatile oils with different volatilities will lead to novel cosmetic attributes; the oily phase gradually evaporates accompanying finger strokes during application. Today, 90% of the foundations on the market are water/silicone/oil emulsions. Over the past few years, the chemistry of the emulsifying agents have also expanded as new functionalized emulsifiers become available. Either endowed with moisturizing effects or able to enhance optical properties, they contribute to the comfort and the performance of facial foundations.

Compact foundations

Figure 22.1 Diversity of textures: from fluid emulsion to paste dispersion.

Compact foundations are made up of waxes and oils in which powders and pigment phases are dispersed under heat, but compact foundations can be greasy, heavy, and streaky. The more recent use of esters and siliconated oils has made it possible to lighten the texture and improve application qualities. Volatile oils also help the facial foundation film remain unaltered for a longer time and provide long-lasting coverage. Compact foundations display the advantage of being adjustable with a sponge, which is ideal for concealing localized defects. Packaging the foundation in compact cases makes it practical for touching up during the day. Waterpacts are a special compact type that contain water. They consist of W/O or O/W emulsions rich in waxes that



Colored Facial Cosmetics

are poured into the compact under heat. The water content makes it necessary to use waterproof packaging. These solid emulsions are difficult to manufacture and preserve, but they have the huge advantage of making the compact fresh as well as practical in use. Compacts can also be packaged as sticks for more precise and localized strokes, such as around the eyes.

Powders Compact powders are distinct from loose powders as they represent the “portable to go” version of loose powders. They are composed of fillers and pigments. A binder containing 10% oils and grease ensures the compact powder particle cohesion, while also providing comfort and ease of application. To make a high-quality powder a suitable milling procedure must be used in order to disperse the pigments finely and evenly throughout the powder phase.

Figure 22.2 The four iron oxides used in foundations.

Loose powders A loose powder is characterized by weak particle cohesion. It does not contain binder or may contain just enough to provide a degree of cohesion that controls the final product volatility. Loose powders are generally applied with a puff, but manufacturers are developing tricks for easy application by using more finely tuned application brushes. Unlike with a puff, the powder does not scatter.

are formulated to provide fuller coverage than powder foundations. They give a very matte appearance that will not wear off in hot, humid conditions such as in the Asiatic climate. The main drawback of all powders is a certain discomfort relative to foundation, mainly because of the absence of any moisturizing effect (Table 22.1).

Compact powders There are different kinds of compact powders: • Finishing powders provide sheer coverage and are used for touch-up during the day. They are usually applied with a sponge over a foundation to mask facial shine. The fillers used in these powders tend to be organic, because they are more transparent. They also have the advantage of absorbing sebum while still leaving a natural look. The formulation challenge is to find a good balance between texture quality and the ease in placing the proper amount of powder on the applicator. • Powder foundations are compact or loose powders whose covering power is equivalent to that of a foundation (i.e. better than a finishing powder). They can be used instead of foundation, for instance by women who dislike fluid textures. The loose powder version known as mineral makeup is currently enjoying considerable success. • Two-way cakes, which are available in compact form, can be used either wet or dry. This kind of powder is popular with Japanese women. Using it dry gives the same kind of makeup as a powder foundation, while using it wet gives more even coverage. This dual usage requires the vast majority of the fillers to be hydrophobic. Treated fillers, coated with silicone oils that cannot be wetted, are mostly used. In this way, the compact remains unaltered after contact with water and does not cake. These two-way cakes


Color creation At the core of foundation formulations there is a combination of colored powders that must be: • As finely dispersed as possible with optimal stability; and • Able to create a natural-looking tinted film once smeared over the skin. To achieve this end, the formulator has available various colorants that comply with the different cosmetics legislations (positive lists) and are thus certified to be harmless, chemically pure, and microbiologically clean. These are inorganic pigments such as metallic oxides – yellow, red, and black iron oxides – to which colored and uncolored pearls can be added to give a lustrous effect. To brighten foundations (especially the darkest ones) blue pigment can be substituted for black. For improved pigment dispersion and formula stability, the process of pigment coating has gradually become the standard. In water/silicone emulsions, a silicone coating is most frequently used. Coating with an amino acid aims at developing products for sensitive skin.

Pigments and coverage The amount of titanium oxide pigment in the product is an indication of its ability to cover skin flaws (i.e. the level of coverage provided). A foundation is characterized by theoretical coverage on a scale from 7 (natural effect) to 50

22. Facial foundation

Table 22.1 Products categories overview. Skin type target

Formulations characteristics

Name of category

Main objectives

All types of skin but adapted to Asian routine

Uncolored formulations To be applied under foundation

Foundation base

Application: Lasting effect – spreadability Moisturizing effect – matt finish

All types of skin

Weakly colored

Tinted creams

Strong skincare attributes

All types of skin

Weakly colored but pearly

Bronzers Highlighters

Healthy “glow” effect, suntan color

All types of skin

Greens, purples, blues, apricot

Complexion correctors

Correction of discoloration (red spots by green tints) Complexion freshener (apricot – blue)

All types of skin

Low to full coverage

Fluid foundations

Wear – matt finish Antiaging – radiance

Normal to oily skin

Low to full coverage

Compacted powders, such as two-way cakes (adapted to Asian routine)

Matt finish – complexion evenness

Normal to dry skin

Medium to full coverage

Compact foundation

Evenness – adjustability of the result. Comfort – mobility

Normal to oily skin

Weak to medium coverage

Waterpacts (poured emulsions)

Same properties as compacts, plus freshness and hydrosoluble actives

Eye contour

Medium to full coverage


Hides dark circles under the eyes

All types of skin

Transparent to opaque (mineral makeup)

Loose powders

Matt finish and adhesion – evenness

(corrective makeup). However, this ignores the optical properties of the product, which may also be able to mask skin defects through a soft focus effect [8]. It also does not take into account the influence of texture, which will determine how transparent or opaque the colored deposit is according to the ability of the product to spread evenly as a thin layer over the skin.

• Different varieties of silica, sometimes porous forms; • Polymers such as nylon and polymethylmethacrylate (PMMA); and • Mica platelets that can also be coated. Not only are these powders essential to the basic properties of a product, but they also contribute to its optical properties. Transparent or opaque, lustrous, matte, or soft focus, they help to achieve the desired finish on the skin.

Importance of fillers Fillers are all the non-pigment powders introduced in the product to provide: • Covering power; • The ability to absorb sebum and sweat so as to make the skin velvety and fix the color to the skin; • Fineness and smoothness, which enhances cosmetic qualities of the textures; and • Spreadability, which makes application easier. Both form and chemical nature govern the final qualities of fillers (Figures 22.3a–c). Talc is an example of a spreadable, lamellar powder that is widely used for its extreme softness and absorbing power. Kaolin, starches, and calcium carbonate used to be widely employed but they have now been superseded by:

Facial foundation application Most women usually apply their facial foundation first when applying cosmetics. They may choose to modify their complexion color or make it more glowing and even without changing the color. Whatever effect is desired, makeup is used to recreate an ideal of color and finish peculiar to each individual according to ethnic and cultural practices. It must also be adapted to suit the woman’s routine: application of a single product, use over a base or under a powder, stroked on by finger or by sponge. There is a great diversity in the use of complexion makeup. The formulator must address several issues. Being familiar



Colored Facial Cosmetics




Figure 22.3 Shape variety of fillers (a–c).

with the various skin color characteristics is a primary requisite for recreating the shades that closely match the ethnic origin of the user. For any given product, this is a necessary prerequisite for creating a range of shades that will likely satisfy the women throughout the world, whether Caucasian, Hispanic, African, or Asian. A large study carried out on a widely representative panel demonstrated significant differences in the colorimetric characteristics of skin color of six ethnic groups living in nine different countries [9,10]. The recorded measurements enabled the definition of a wide color space showing the various color spectra typical of each ethnic group’s skin color mesh and overlap (Figure 22.4). Further studies showed that the variety of makeup routines reflected the ethnic origin and cultural heritage which determines whether a woman feels positive toward her natural skin color. For many women, skin color is a major factor in their cultural identity. Complexion makeup is the easiest way to achieve even skin color by erasing surface color variations or correcting color unevenness. Some women wish to appear more deeply “tanned” than their natural color. This behavior is commonly found in Caucasian and Hispanic women. Japanese women, however, desire their makeup to give them a lighter complexion (Figure 22.5) [10]. The formulator works within this defined scope to develop shades matching natural skin colors. To meet women’s expectations, it is necessary to analyze how women selfperceive their complexion. By identifying skin colors within a definite color range and precisely identifying the makeup habits of women over the world, it is now possible to formulate a variety of shades that match up with the wishes of all women.

undergo a battery of tests to confirm its safety and performance. There are several steps in this process.

Design stage The formulator must ensure high quality ingredients are used by defining specifications and analytical controls and carrying out screening for the non-toxicity of the ingredients with in vitro tests on reconstructed skin models. Each raw material used must be cleared for safety and have a proper toxicologic dossier.

Formulation stage It is necessary to: • Evaluate stability by subjecting products to thermal cycles to accelerate aging. • Confirm the level of microbiologic preservation of the formulas using challenge tests. The selected method of preservation and the nature of the preservatives depend on the technology involved (powder emulsion, anhydrous compact). The risk of microbiologic contamination increases with the water content. It also depends on the packaging; a pump bottle provides better protection than a jar. • Check it is harmless through using alternate methods: in vitro testing and including tests run on reconstructed skin model, e.g. (EpiSkin®, L’Oréal Episkin SNC, Lyon, France); clinical tests (simple patch test [SPT] and repeated patch test [RPT]); and, finally, user tests under dermatologic controls, carried out on the product’s targeted skin types, particularly on sensitive skins and using wide ranging, representative panels. Use testing under ophthalmologic controls is carried out systematically on products intended to mask under-eye rings.

Performance stage

Emphasis on quality, safety and confirmed performance Complexion makeup creates an intimate relationship between the skin and a complex formulation that is left on for hours. Before being marketed, every product has to


The performance of the product must be studied to ensure that it complies with consumer wishes and to obtain an unbiased opinion on advertising claims and consumer complaints. Sensorial analysis tests provide qualitative and quantitative assessments of a product’s features by a trained panel of experts, as well as by untutored panels performing the tests under the formula’s normal user conditions.

22. Facial foundation



Reflectance 0.8 0.7 0.6 Figure 22.4 (a) The color of the forehead was measured using a spectroradiometer inside a Chromasphere™. (b) The volunteer placed her face into the Chromasphere. A standardized camera was used to acquire pictures of the face. (c) A spectroradiometer measured the reflectance of forehead in the visible field 400–700 nm every 4 nm. The recorded spectrum was expressed in the CIE 1976 standard colorimetric space L*C*h D65/10 ° where each color is described through three coordinates that reflect perception by human eye. h, Hue angle (angular coordinate); C*, chroma (radius coordinate); L*, lightness (z axis).

0.5 0.4 0.3 0.2 0.1 Wavelength (nm) 0 350





Additionally, a complexion product can be tested with the conventional methods used for skincare cosmetics: • Measurement of moisturizing effects using SkinChip® (L’Oréal, Chevilly-Larue, France) or Corneometer® (Courage & Khazaka, Köln, Germany); • Effects on skin firmness with using the Dermal Torque Meter® (Dia-Stron Ltd, Andover, UK); • Image analysis on skin imprints or, even better, projection of light fringes involving no contact with skin (i.e. skin in real conditions with makeup as applied) to assess antiwrinkle performance.









Also specific tests: • Color appraisal using the Chromasphère® (L’Oréal, Chevilly-Larue, France): the difference in the color of the skin before and after applying makeup quantifies the improvement in color evenness and change in color effect. Moreover, it makes it possible to monitor both. As a result, the manufacturer can claim that its makeup effects last a given number of hours. • Evaluation of the matt finish with a suitable device (Samba® [Bossa Nova Technologies, Venice, CA, USA]).




Colored Facial Cosmetics



Group 5 Group 6 Group 3

Group 4


Group 2 50 Group 1 40



20 20







Figure 22.5 The worldwide skin color space depicted in (h, L*) and split in six groups of skin tones that reflect the color diversity.

Conclusions and prospects Beauty is diverse. Textures, tones, matte or lustrous results, play time, and sensoriality must all come together to give a woman a simple means to recreate her ideal complexion. Complexion makeup products today benefit from knowledge of physical chemistry, resulting in better understanding of the relationships between chemical composition, texture, and application behavior. Facial foundations benefit from technologic advances in optics, which has generated formulations that are sheer, glowing, matte, able to provide soft focus concealment of flaws, while simultaneously giving shades that mirror the natural hues of the skin. Complexion makeup products have been expanded to deliver multisensory effects and address ethnic diversity issues. From simple emulsions applied by finger, facial foundations have evolved into mousses, creamy compacts, and soft powders that can be applied by brush or sponge, and layered. Facial foundations contribute to beauty of the face respecting the women’s own skin, but also addressing their


culture and ethic diversity [11,12]. New forms, new optical effects, and new application methods will permit users to attain their ideal complexion irrespective of origin or own canons of beauty.

References 1 Claude C. (2006) Histoire du maquillage du teint: une vision croisée des cultures, des modes et des évolutions technologiques. Thèse pour l’obtention du Diplôme d’Etat de Docteur en Pharmacie Faculté Paris V. 2 Gröning K. (1997) La Peinture du Corps. Arthaud Editions. 3 Gründ F. (2003) Le Corps et le Sacré. Editions du Chêne Hachette Livre. 4 Walter P, Martinetto P, Tsoucaris G, Breniaux P, Lefebvre MA, Richard G, et al. (1999) Making make-up in ancient Egypte. Nature 397, 483–4. 5 Evershed RP, Berstan R, Grew F, Copley MS, Charmant AJH, Barham E, et al. (2004) Formulation of a Roman cosmetic. Nature 432, 35–6. 6 Chanine N, Deprund MC, De La Forest F, et al. (1996) 100 Ans de Beauté. Atlas Editions. 7 Pawin H, Verschoore M. (2001) Maquillage du Teint du Visage. Paris: Encyclopédie Médicale Chirurgicale, Cosmétologie

22. Facial foundation Dermatologie Esthétique Editions Scientifiques et Médicales Elsevier. 8 Takayoshi I, Miyoji O. (2002) Appealing the technical function of the optical characteristic foundation from the view point of marketing. Fragrance J 30, 59–63. 9 Caisey L, Grangeat F, Lemasson A , Talabot J, Voirin A. (2004) Skin color and make-up strategies of women from different ethnic groups. Int J Cosmet Sci 28, 427–37. 10 Baras D, Caisey L. Skin, lips and lashes of different skins of color: typology and make-up strategies. In AP Kelly and SC Taylor,

Dermatology for Skin of Color. McGraw-Hill, Berkshire, UK, pp. 541–9. 11 Mulhern R, Fieldman G, Hussey T, Lévêque JL, Pineau P. (2003) Do cosmetics enhance female Caucasian facial attractiveness? Int J Cosmet Sci 25, 199–205. 12 Korichi R, Pelle-de-Queral D, Gazano G, Aubert A. (2008) Why women use make-up: implication of psychological traits in make-up functions. J Cosmet Sci 59, 127–37.


Chapter 23: Camouflage techniques Anne Bouloc Cosmetique Active International, Asnières, France

BAS I C CONCE P T S • Camouflage makeup is used to cover facial defects of contour and color. • Camouflage makeup must be artistically applied to achieve an optimal result. • Camouflage techniques can improve quality of life. • Camouflage therapists can train patients in the proper application techniques for cosmetics.

Introduction Camouflage techniques can be helpful in patients who do not achieve complete or immediately attractive results from dermatologic therapy. Because appearance is one of the pivotal factors influencing social interactions, facial blemishes and disfigurements are a psychosocial burden in affected patients leading to low self-esteem and poor body image. Camouflage makeup can normalize the appearance of skin and improve quality of life. Training in camouflage techniques is essential because the application is different from regular foundations. This chapter discusses the use of camouflage cosmetics.

Definitions Camouflage cosmetics were introduced more than 50 years ago to improve the appearance of World War II pilots who had sustained burns. The products provided an opaque cover over the damaged skin areas. Modern high quality camouflage products provide a excellent coverage, but with a more natural appearance (Figure 23.1). There are several brands of camouflage makeup on the market. They aim to conceal skin discoloration and scars and to impart a natural, normal appearance. Camouflage products differ from makeup products purchased over the counter. They contain up to 25% more pigment, as well as fillers endowed with optical properties. Camouflage makeups are waterproof and designed to cover and mask a problem, but must be mixed to match the patient’s skin tone. The goals of camouflage cosmetics are to provide [1]:

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


1 Color: Camouflage makeup must match all skin tones as it should blend into the color of the area on the face it is intended to cover evenly. 2 Opacity: Camouflage makeup must conceal all types of skin discoloration, yielding as natural and normal an appearance as possible. 3 Waterproof: Camouflage makeup must be rain and sweatresistant, remaining unaltered with athletics (e.g. swimming). 4 Holding power: Camouflage makeup must adhere to skin without sliding off. 5 Longer wear: Camouflage makeup must provide the assurance of long wear with easy reapplication, if necessary. 6 Ease of application: Camouflage makeup must be easy to apply. Too many steps and color applications may create patient confusion. There are several different types of camouflage cosmetics: 1 Full concealment: A method referring to complete coverage of the damaged skin and extending beyond the boundaries of the injured area. High coverage foundation creams or cover creams should be used for full concealment. 2 Pigment blending: A method that involves selection of a cover cream that matches the color of patient’s foundation. 3 Subtle coverage: A light application of foundation cream that conceals only moderately. Contouring is used to minimize areas of hypertrophy or atrophy present in facial scars, using highlighting or shading to create the illusion of smoothness.

Camouflage makeup application procedures It is important to remember that camouflage makeup is most effective when applied over skin with color abnormalities or

23. Camouflage techniques High level of coverage High coverage potential Difficult to apply No natural result Heaviness



IDEAL CORRECTIVE MAKE-UP High coverage potential Easy to apply Natural result

Less coverage potential Good playtime Comfortable texture

10 Low level of coverage Figure 23.1 Ideal corrective makeup: a compromise between coverage and cosmetic qualities. After Sylvie Guichard, L’Oreal Recherche.

Low cosmetic qualities

discoloration. The size of the defect is immaterial, because it is as easy to cover a large blemish as a smaller one. However, the camouflage of texture abnormalities is more challenging. Rough scars are more difficult to conceal than smooth scars because unevenness is exaggerated after camouflaging [2]. This section of the chapter presents the steps necessary to complete a camouflage makeup application procedure for a given patient. First, patients should be asked about prior experience in attempting to camouflage their lesions with or without medical makeup. If they have no experience, the necessary steps should be discussed in detail. Second, the patient’s skin should be cleansed with a product selected according to patient’s skin type. For an optimal camouflage result, the skin should be well exfoliated and moisturized. If using a camouflage product without sun protection factor (SPF) protection, a sunscreen-containing moisturizer should be selected otherwise a bland moisturizer can be used. Third, the camouflage product must be selected to match the patient’s skin. The camouflage therapist should identify the underlying tones that contribute to skin color: haemoglobin produces red, keratin produces yellow, and melanin produces brown [3]. Thinner skin possesses more red tones while thicker skin appears more yellow. For this reason, it is almost impossible to mimic natural skin color with only one shade. Fourth, the camouflage therapist must understand color. There are three color coordinates: hue, value, and intensity. 1 Hue is the coordinate for the pure spectrum colors commonly referred to as “color name” – red, orange, yellow, blue, green, violet – which appear in the hue circle or rainbow. Each different hue is a different reflected wavelength of light. White light splitting up through a prism has seven hues: red, orange, yellow, green, blue, indigo, and violet. 2 Value is defined as the relative lightness or darkness of a color. Adding white to a hue produces a high value color,

Excellent cosmetic qualities

often called a tint. Adding black to a hue produces a low value color, often called a shade. 3 Intensity, also called chroma or saturation, refers to the brightness of a color. A color is at full intensity when not mixed with black or white – a pure hue. The intensity of a color can be altered, making it duller or more neutral by adding gray to the color. Matching a color from one manufacturer to another one is a very difficult procedure because of the variety of shades that can be produced by combining various colors and the tints of the color that can be made by varying the amount of white. Judgment of color should always be made on the skin and never in the container because what seems to be the same shade may appear quite different on the skin. The use of neutralizers in camouflaging is somewhat controversial. Some experts think it is possible to neutralize undesirable skin discoloration [2]. For example, green undertoner neutralizes a red complexion and lavender undertoner negates a yellow complexion. Other authors think that makeup undertoners do nothing but create a third color [4]. They consider that when two colors are mixed, the result is a third color. Mixing opposite colors on the color wheel (e.g. green and red or yellow and purple) will result in an unattractive gray–brownish color that must be concealed with a color that matches the skin, which adds an extra step and thickness to the makeup. For contouring, several products have to be applied. Hypertrophic scars appear lighter than surrounding skin, and have to be camouflaged applying a darker product than to surrounding skin. Atrophic scars, however, appear darker than surrounding skin, and have to be corrected using lighter product. Once the shades have been selected, the camouflage therapist should apply them to the back of the hand as a painter uses a palette to warm and soften the product (Figure 23.2a,b). The warm skin makes the product more malleable so it will apply more easily. Camouflage products are best



Colored Facial Cosmetics







Figure 23.2 Camouflage makeup technique. (a) Remove a small amount of the corrective makeup. (b) Warm the product on the back of the hand. (c) Apply over the imperfection to be covered. (d) Blend in round the edges. (e) Generously apply the powder. (f) Remove any surplus with a brush.

applied with a sponge in a patting motion but can also be applied with the fingertips (Figure 23.2c). The patting motion applies the product to the surface of the skin and does not clog pores, which allows the skin to retain its natural characteristics. Distinct borders are eliminated by blending the edges (Figure 23.2d). A camouflage product often is not used over the entire face like a regular facial foundation, but the surrounding skin must be matched as closely as possible. Patients have to be reminded that skin color on the hands does not really correspond to skin color of the face. The application is generally followed up with an application of powder which sets and waterproofs the camouflage product (Figure 23.2e,f). The setting powder used should be translucent so that the camouflage product does not change color. For patients with very dry skin, it is not necessary to use a powder as the oils are quickly absorbed into the skin. Many patients may prefer using only one shade even when the color match is not perfect. Men may not wish to mix colors. It might be of interest to show the patient the


coverage with one shade and the coverage using more than one shade while demonstrating that color blending is relatively easy and worthwhile. For men, common skin flaws must be reproduced in order to prevent a “mask-like” appearance [5]. Beard stubble can be recreated by using different sponges and a brown or black pigment that mimics surface irregularities. Other colored powdered blushes can be used on the cheeks to simulate the natural glow of youth and around the eyes and mouth to attract the attention on other parts of the face [6]. Pictures should be taken before and after the application to document the cosmetic results. Finally, the cosmetics must be removed each evening prior to bed. Removing camouflage makeup is more difficult than regular makeup. Alcohol or acetone-based removers are too irritating for sensitive skin, thus it is better to use watersoluble cream-type makeup remover. The remover is applied generously to emulsify the makeup followed by wiping with cotton pads. The face is then rinsed with tepid water and patted dry [7].

23. Camouflage techniques

Other camouflage therapies A few other options than camouflage makeup therapies have been suggested. Dihydroxyacetone, the main ingredient in self-tanning creams, has been proposed for camouflaging in patients with vitiligo [8]. It may be a cheap, safe, and effective alternative especially for the hands and the feet as cover creams are waterproof but not rubproof. Medical tatooing under local anesthesia has also been tried to create the appearance of hair in hairless areas [9]. The pigment used is made of ferrous oxide, glycerol, and alcohol. A test on a small area should be performed to evaluate the outcome. The needle should be introduced into the dermis similarly to the natural hair pattern of the patient.

Medical indications for camouflage makeup There are various medical indications for camouflage makeup. The lesion requiring camouflage can be permanent or temporary. The best results are obtained with macules, but papules, nodules, or scars can also be camouflaged. Macular lesions for camouflaging include pigmentary disorders such as vitiligo (Figure 23.3), chloasma (Figure 23.4), lentigenes, postinflammatory hypopigmentation or hyperpigmentation (Figure 23.5); hypervascular disorders such as telangiectasia (Figure 23.6) and angioma (Figure 23.7); and tattoos. Papulonodular lesions for camouflaging include discoid lupus, acne, dermatosis papulosa nigra, and facial scars. After a graft for oncologic surgery, or for other postsurgical scars, there may be variation in pigmentation and/or relief and corrective cosmetics may be of interest. Depending on

Figure 23.3 Perioribital hyperpigmentation: (a) before and (b) after camouflage.

the skin’s ability to heal, camouflage therapy can be applied 7–10 days after most surgical procedures. However, the premature use of makeup following epidermal damage may cause a secondary infection or tattooing effect. There may be transient injuries or lesions of the skin that can be camouflaged with makeup. An injury may produce hematoma and oedema that should be concealed for occupational reason or social event. Corrective makeup can also be used after medical procedures such as laser resurfacing, peels, and microdermabrasion to camouflage erythema. After filler injections, redness may also appear. Laser hair removal will induce temporary redness, but following some lasers the skin may become purpuric. Camouflage makeup optimizes the patient’s postprocedure appearance. Indeed, if the patient knows he or she will be red, he or she will require an appointment at the end of the day or of the week. With corrective makeup, patients are able to go back straight to work. Similarly, after filler or botulinum toxin injections, hematomas may appear which can be camouflaged with corrective makeup.

Beginning a camouflage clinic It is important to offer patients camouflaging makeup knowledge [6]. In general, the dermatologist will delegate this activity to a staff member. Many physicians find that a camouflage therapist can bring an added value to the practice by enhancing patient recovery. The room for teaching camouflaging techniques should contain a table with a mirror and fluorescent bulbs to provide adequate light. A chair should be placed in the room tall enough to allow the camouflage therapist to stand. Several camouflage products should be available in various shades to match the different skin colors.








Figure 23.4 Vitiligo: (a) (i & ii) before and (b) (i & ii) after camouflage.



Figure 23.5 Melasma: (a) before and (b) after camouflage.

23. Camouflage techniques

Figure 23.6 Vascular malformation: (a) (i & ii) before and (b) (i & ii) after camouflage.





The camouflage therapist In the USA, camouflage therapists are state-licensed and medically trained skincare professionals, with both clinical knowledge and therapeutic skill [5]. They do not treat patients but educate them by providing information on the best way to go about applying camouflage makeup. In other countries of the world such a degree does not exist. Camouflage therapists should obtain appropriate training

and education. They should be trained to select and apply cosmetics beyond the application of standard cosmetics. Their training should include the study of facial anatomy, highlighting and contouring techniques, and prosthetic makeup techniques similar to those used in the stage and motion picture industry. The camouflage therapist should be a good communicator to teach patients how to apply various products, which the patient can easily reproduce without assistance. Camouflage therapists should be genuinely interested in the patient’s



Colored Facial Cosmetics


(b) Figure 23.7 Telangiectasia: (a) before and (b) after camouflage.

well-being. Therefore, they should be mature enough to work with people who have a severely damaged appearance. The camouflage therapist must record the patient’s history and identify needs based on the patient’s perception of the problems. Because of the clinical knowledge and personal qualities required, a trained nurse would be an ideal camouflage therapist [7,10]. The camouflage therapist can design a cosmetic treatment plan. During the interview four issues should be addressed [5]: 1 The ability of the patient to follow simple instructions. 2 The patient’s social activities and job environment. 3 The patient’s prior makeup experience. 4 The financial status of the patient.

Camouflage makeup and quality of life Psychosocial aspects of skin disease has important implications for optimal management of patients. The presence of abnormal visible skin lesions may result in significant psychologic impairment. Health-related quality of life (QOL) is a measurement method to describe physical, social, and


psychologic well-being and to assess the burden of disease on daily living. Several general measures have been developed [11]. Surprisingly, women who used facial foundation reported a poorer QOL than those who did not. This was interpreted to mean that more severely impacted patients are more likely to hide the disorder using camouflage cosmetics, albeit inadequately. Yet, wearing makeup may improve appearance and looking better translates into feeling better. Those who feel better show signs of higher self-esteem. Many studies have been performed in order to demonstrate the effects of corrective makeup on patients’ QOL [12–14] and remove misconceptions that the use of cosmetics can be tedious and difficult for ordinary people. A wide range of facial blemishes and disfigurements such as pigmentary disorders, vascular disorders, scars, acne, rosacea, lupus, lichen sclerosus, and keratosis pilaris have been included in these studies. QOL questionnaires were completed before the first application and after applying corrective makeup. Results show that corrective cosmetics are well-tolerated and patients report high satisfaction rates. There is an immediate improvement in skin appearance and no significant adverse effects. Corrective cosmetics rapidly improve QOL, which persists with continued use. There was

23. Camouflage techniques no difference in QOL according to the type of facial disfigurement or the size of the affected area. Not only were patients improved with pigmentary or vascular disorders, but also with scars. Camouflage therapy can help patients cope with skin disorders that affect appearance. The cosmetics can be used long-term without difficulty. Camouflage therapy is of great help to patients who cannot be medically improved.

Conclusions Camouflage techniques help affected patients cope with the psychologic implications of facial blemishes or disfigurements. Covering visible signs of the disease minimizes stigmatization. Today’s high quality camouflage products provide excellent good coverage with a natural appearance. Many physicians find that a camouflage therapist can bring an added value to the practice by enhancing patient recovery.

References 1 Westmore MG. (2001) Camouflage and make-up preparations. Dermatol Clin 19, 406–12. 2 Draelos ZK. (1993) Cosmetic camouflaging techniques. Cutis 52, 362–4.

3 LeRoy L. (2000) Camouflage therapy. Dermatol Nurs 12, 415–6. 4 Westmore MG. (1991) Make-up as an adjunct and aid to the practice of dermatology. Dermatol Clin 9, 81–8. 5 Rayner VL. (1995) Camouflage therapy. Dermatol Clin 13, 467–72. 6 Deshayes P. (2008) Le maquillage médical pour une meilleure qualité de vie des patients. Ann Dermatol Venereol 135, S208–10. 7 Rayner VL. (2000) Cosmetic rehabilitation. Dermatol Nurs 12, 267–71. 8 Rajatanavin N, Suwanachote S, Kulkllakarn S. (2008) Dihydroxyacetone: a safe camouflaging option in vitiligo. Int J Dermatol 47, 402–6. 9 Tsur H, Kapkan HY. (1993) Camouflaging hairless areas on the male face by artistic tattoo. Dermatol Nurs 5, 118–20. 10 McConochie L, Pearson E. (2006) Development of a nurse-led skin camouflage clinic. Nurs Stand 20, 74–8. 11 Balkrishnan R, McMichael AJ, Hu JY, et al. (2006) Correlates of health-related quality of life in women with severe facial blemishes. Int J Dermatol 45, 111–5. 12 Boehncke WH, Ochsendorf F, Paeslack I, Kaufmann R, Zollner TM. (2002) Decorative cosmetics improve the quality of life in patients with disfiguring diseases. Eur J Dermatol 12, 577–80. 13 Holme SA, Beattie PE, Fleming CJ. (2002) Cosmetic camouflage advice improves quality of life. Br J Dermatol 147, 946–9. 14 Balkrishnan R, McMichael AJ, Hu JY, et al. (2005) Corrective cosmetics are effective for women with facial pigmentary disorders. Cutis 75, 181–7.


Chapter 24: Lips and lipsticks Catherine Heusèle, Hervé Cantin, and Frédéric Bonté LVMH Recherche, Saint Jean de Braye, France

BAS I C CONCE P T S • The lips possess a complex anatomy consisting of mucosa and skin. • Lipsticks are designed to enhance the appearance of the lips. • Lipstick is an anhydrous paste of oils and waxes in which pigments are dispensed along with other coloring agents.

Introduction Lip makeup is an essential element in seduction and women frequently use lipsticks to make their faces more attractive. The lips are muscular membranous folds surrounding the anterior part of the mouth. This tissue is both mucosa and skin and has a complex anatomy. Labial tissue has a dense population of sensory receptors, is very sensitive to environmental stress, can present pigmentation defects, and is modified during aging. Lipstick formulations are most widely used to enhance the beauty of lips and to add a touch of glamour to women’s makeup. The lipstick that we know today is a makeup product composed of anhydrous pastes such as oils and waxes in which are dispersed pigments and other coloring agents designed to accentuate the complexion of the lips. This chapter draws together our knowledge of the biology of this special tissue, and gives detailed information on the formulation elements of lipsticks.

Lip anatomy The lips are muscular membranous folds surrounding the anterior part of the mouth. The area of contact between the two lips is called the stomium and forms the labial aperture. The external surfaces of the lips are covered by skin, with its hair follicles, sebaceous glands, and sweat glands; the inner surface is covered by the labial mucosa, a non-stratified, non-keratinized epithelium bearing salivary glands. The transitional zone between these two epithelia is the red vermilion border of the lips (Figure 24.1). It has neither hair follicles nor salivary glands, but sebaceous glands are present in about 50% of adults [1]. The red area

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


is also keratinized, with rete ridges more marked than in the neighboring cutaneous zone. Several studies have identified an intermediate area between the vermilion zone and the mucosa that does not contain a cutaneous annex; it is covered by a stratified epithelium that lacks a stratum granulosum but does have a thick parakeratin surface layer. This intermediate zone increases with age [2–4]. The deeper region of this soft tissue forming the lips is made up of a layer of striated muscle, the orbicularis orbis muscle, and loose connective tissue. The muscle makes a hooked curve towards the exterior at the edge of the vermilion area which gives the lips their shape. Immediately above the transition between the skin and the vermilion zone is the Cupidon arch, a mucocutaneous ridge, also called a white roll, or the white skin roll. Its physical appearance and lighter color seem to be essentially caused by the configuration of the underlying muscle [5]. This region is rich in fine, unpigmented, “vellous” hairs that may influence the appearance of this zone. The lips have great tactile sensitivity. Labial tissue has a dense population of sensory receptors, including Meissner corpuscles, Merkel cells, and free nerve endings. The sensitivity of the lips is somewhere between that of the tongue and the fingertips [6].

Labial epidermis The epidermis of the vermilion region is twice as thick (180 μm) as the adjacent skin [4,7,8]. It still has the markers of cutaneous epidermis differentiation, even though it has fewer keratinized layers than the skin [9]. Barrett et al. [4] found that the distribution of cytokeratins (CK) differed from that of the intermediate zone, with a loss of the skin cytokeratins CK1 and CK10 and the presence of the mucosal cytokeratins CK4, CK13, and CK19. CK5 and CK14 were still present in the basal layer and occasionally in the suprabasal layer. CK8, CK18, and CK20 were found only in Merkel cells. Involucrin was present in all the zones, but its

24. Lips and lipsticks MUCOSA Lamina propria Salivary glands VERMILION BORDER


Orbicularis orbis muscle Blood vessels Follicles




Figure 24.1 Lip histology.

restricted distribution in the stratum granulosum of the skin extended to the stratum spinosum and the parabasal keratinocytes of the lip zone and the mucosa. Loricrin, profilaggrin, and filaggrin were found in the stratum granulosum of the orthokeratinized zones but not after the junction between the vermilion zone and the intermediate zone. The corneocytes in the mucosa are flat, smooth cells. In contrast, most of the corneocytes on the surface of the vermilion border are seen to have microvilli on all their internal surfaces when examined under the high power microscope [10]. These projections are rarely seen on the corneocytes of the adjacent skin [11]. The cell turnover of the epidermis of the vermilion border seems to be more rapid than that of the adjacent skin cells. The vermilion border also appears to lose water three times as fast as the cheeks and to have only one-third the conductance. Thus, the lips function as a barrier but their capacity to retain water is much poorer than that of facial skin [1]. Hikima et al. [11] showed that the surface of the lips, like the surface of the skin, has cathepsin D-like activity and chymotrypsin-like activity. These enzymes are involved in the hydrolysis of corneodesmosomes, and hence in the release of corneocytes from the skin surface. Like the skin, the vermilion border epithelium contains melanocytes and there is melanin in the cytoplasm of basal cells [4]. However, as the melanin pigmentation is light and associated with reduced keratinization, the color of the hemoglobin is seen more clearly. There are also Langerhans cells in this zone [8]. Cruchley et al. [12] used immunodetection of CD1a to show that there were more Langerhans cells per unit area of the lips than in abdominal skin.

Sallette et al. [13] recently showed that there is more neuropeptide-type neurotransmitter in the epidermis of the lips than in the eyelids, which seems to indicate that the lips are better innervated.

Lip dermis and lamina propria The epithelium of the vermilion border lies on a layer of connective tissue, which ensures the continuity of the cutaneous dermis and the lamina propria. This tissue is composed of collagen fibers and a network of elastic fibers. There is a thin layer of fatty tissue between the muscle and the dermis in the cutaneous part of the lips with many attachments between the muscle and the skin [14]. The deep part of the lamina propria of the mucosa lies above the hypodermis of the subcutaneous zone. The invagin*tions at the junction between the epithelium and the connective tissue of the vermilion border are higher than those of the skin [15]. These papillae contain blood capillaries. The capillary loops in the vermilion border are higher than those of the skin, which accentuates the red color of the lips because of the hemoglobin in them [16]. The lymph drainage of the red border is not uniform; it flows towards the cutaneous system on the external side of the lips and towards the mucosal system on the inner side [17].

Lip topology The description of lip topology first interested legal medicine because each individual has a different organization, much like fingerprints. The study of lip prints is called cheiloscopy. The development of kiss-proof lipsticks led legal medicine to develop protocols for revealing latent prints at a crime scene [18]. Lip prints can be classified in several ways and their distributions in populations have been quantified [19–22].

Sensitivity of lips to the environment As the lips have little cornified tissue or melanin they are very sensitive to chemical, physical, or microbial damage. Their prolonged exposure to sunlight, particularly for fairskinned people, may lead to the appearance of actinic cheilitis and even spinocellular carcinoma [23]. Pogoda and Preston-Martin [24] suggested that frequent applications of sunscreen can have a positive protective effect. Smoking has also been found to be a major risk factor for lip cancers.

Aging of the lips The esthetic consequences of aging of the superficial lip tissues (sagging, distension, and ptosis) are aggravated by changes in the shape of the bone and dental infrastructure and the aging of the underlying muscles and adipose tissue. The orientation of the labial aperture changes with a drooping of the lateral commissures: from a concave curve in newborns and children to a horizontal line in adults, and then to an inverted curve in the elderly. In profile, the lips,



Colored Facial Cosmetics

particularly the lower lip, recede with age. The upper lip becomes lower and enlarged [3,22]. Tissues become less extensible and elastic because of repeated mechanical stresses and the weakening of the orbicularis orbis muscle with age [3,25]. The vermilion border becomes larger, longer, and thicker at the corners of the mouth [2]. While wrinkles develop in the skin around the lips with age, the outline of the lips themselves becomes sunken [22]. The depth and organization of the lips varies greatly from one person to another and some young people have deep furrows. Both the spatial resolution and the tactile sensitivity of the lips decrease with age [3,6,25,26]. There may also be histologic signs of solar elastosis. The superficial microcirculatory network (both papillary and mucosal) may become smaller and less dense (reticular and mucosal), together with an apparent thinning of the lips in older people who have lost their teeth [15]. Cosmetic surgery can be used to “refresh” and to fill the tissue to rejuvenate the lips. This might involve reducing the upper lip or recovering the shape of a young lip by a series of interventions to reinforce the shape and projection of the lips and restructure the Cupid’s bow, better define the lip outline, and lift the corners of the mouth. This surgery is accompanied by a rejuvenation of the perioral region, including removal of peribuccal wrinkles, peeling, laser resurfacing, and dermabrasion [27–30].

Lip plumpness and cheilitis Cheilitis can be caused by a cold or dry environment, repeated pressure on the lips – as it can develop in players of wind instruments – or by defective dental work. It can also occur in people taking oral retinoids, or from a lack of dietary vitamin B12 (riboflavin), B6 (pyridoxine), nicotinic acid, folic acid, or iron [31]. Hikima et al. [11] reported that the corneocytes at the edges of dried out lips become flattened and their surface area increased. This suggests that the turnover of these cells is slowed in dried out lips. The degree of visible dryness is also correlated with a reduction in cathepsin D, one of the enzymes involved in desquamation, but the chymotrypsinlike activity remains unchanged. The upper lip seems to dry out less than the lower lip as it is less exposed. While the hydration measured by the capacitance does not seem to change with age, the loss of water via the lips decreases [25]. Clinically assessed drying out increases with age [22].

Defects of lip pigmentation Pigmentation defects, particularly ephelides and lentigos, may also occur. The lips of some populations, like those from Thailand, may become dark because of the accumulation of melanin in the basal layer of the epidermis without any increase in the number of melanocytes [32]. This disorder may be congenital, caused by smoking, or an allergic reac-


tion to a topical compound. Smoking can also increase pigmentation of the buccal mucosa in darker-skinned people (Africans, Asians, Indians) [33].

Lipsticks Lipstick, a symbol of feminine beauty and sensuality and a method of attracting attention, has a very long history. The red color and bloom (lively, plump) of the lips was first accentuated in the ancient world. Today, a woman uses lipstick to highlight her individuality, character, and seductive capacity and to underline her smile [34]. It is everything but an empty gesture; it reflects the image that the woman has of herself and what she wants to project in society. In the 18th century, people distinguished between the red coloring used for the lips and the rouge used for the cheeks. Many rather toxic substances have been used in the past. The red coloring material used can be of animal, vegetable, or mineral origin. It could be obtained from the cochineal beetle imported from Mexico, the purple dye extracted from molluscs, red sandalwood from Brazil, or the orcanette root. The minerals most frequently used were lead oxide (minium), mercuric sulfate (cinnabar), and antimony. The popularity of lipstick exploded in the 20th century with the use of lip makeup based on a colored paste made from grapes and sold in little jars. These were deep colors. The mouth became much fuller with the arrival and spread of talking movies in the 1930s. The first “indelible” or “kissproof” lipstick was the lipstick Rouge Baiser sold by the French chemist Paul Baudecroux in 1927. Red, pouting lips became all the rage in the 1950s, while in the 1990s lip gloss or brilliant was produced as a paste rather than a stick.

Lipstick formulation The lipstick that we know today is a makeup product composed of anhydrous pastes in which are dispersed pigments and other coloring agents designed to accentuate the complexion of the lips. It is formed into a stick by pouring the hot material into a mould. A classic lipstick formula is: • Wax (about 15%) which is solid at room temperature. It provides hardness and creaminess when applied; • Waxy paste (20%) helps lubricate the lipstick after application; • Oil (30%) for dispersing the pigments; • Texturing agents (about 10%) to improve the texture; • Coloring agents, pigments, and/or pearls (20%) to give color; • Preserving agents and antioxidants (1%) to stabilize the formulation; • Perfume (1%); • Active ingredients including UV filters to improve longterm benefit.

24. Lips and lipsticks

Table 24.1 Waxes. Origin







Composed of fatty acids and alcohols Thickener


Relatively solid, give a lustrous appearance


Carnuba wax

Harder than bees wax Very slightly acid, but brittle Often used mixed with bees wax Very hard wax

From the leaves of the carnuba palm (Brazil)

Relatively hard, and give a lustrous appearance

From the candelilla plant

Matte appearance

Non-stick Non-polar White, fairly transparent and odorless

Paraffin is obtained from oil refining

More malleable

Candelilla wax Mineral

Paraffin Ozokerite

Table 24.2 Waxy pastes. Origin







Adherence Brilliance Extremely hydrophobic

Synthesis from ethylene

Very viscous transparent, viscous liquid


Methyl hydrogenated rosinate

Waxes The wax may be of vegetable, animal, or synthetic origin. They are solid at room temperature and must be melted for use. They create a crystalline network within the formulation that gives the lipstick its shape. The wax is chosen to give the stick a suitable hardness so that it does not break during application. They also give the lipstick a rather matte appearance (Table 24.1). Lipsticks are currently made using specific fractions of wax that provide specific fusion points. These refined fractions are whiter and more odorless than the original waxes, which were a complex mixture of natural lipids.

Table 24.3 Oils. Name




Di isostearylmalate

Emollient Not oxidized Colorless Odorless


Colorless liquid

Trimethylolpropane Triisostearate

Emollient Comfort


Colorless, viscous liquid

Polyglyceryl-2 Triisostearate

Emollient Comfort Dispersant


Transparent pale yellow liquid

Waxy pastes They are called pastes because they are semi-solid forms of wax at room temperature (Table 24.2). They contribute to the cosmetic function of the lipstick by helping to keep the color on the lips. They can do this because they are sticky and because their fusion point is close to the temperature of the lips, thus enabling the stick to melt during application.

Oils These hydrophobic liquids are solvents for the coloring agents that allow them to diffuse so as to develop their color. The oils provide comfort, lubrication during application, and contribute greatly to the cosmetic effect. They may also

provide brilliance and subtlety (Table 24.3). Castor oil has been used for many years but is now less often utilized. It has excellent pigment-dispersing properties because of its polarity; its main inconvenience is its unpleasant taste and odor (caused by oxidation). It is gradually being replaced by stable, odorless, fatty acid esters.

Texturing agents These components can be very different; they provide moisturizing, brightness, and subtlety. For example, polyamide



Colored Facial Cosmetics

Active ingredients

Table 24.4 Pigments and coloring agents. Component


Titanium (IV) oxide – mica


Ferrous oxide (II)


Ferric oxide (III)


DC Red 33


DC Red 27


DC Red 21


DC Red 7


DC Red 6


DC Red 28


DC Red 30


powders bring softness, silica beads provide subtlety and a matte finish, titanium dioxide flakes give a soft-focus effect, while bismuth oxychloride gives a satin, shimmering effect.

Pigments Pigments are synthetic substances or of mineral origin. They are fine powders when dry and are used because they are very opaque and have great coloring properties (Table 24.4). The solid powders are suspended and dispersed in oil. The covering property of a lipstick depends on its pigment content; these pigments can hide the underlying lip color. International regulations strictly limit the use of pigments. Only a restricted number can be used on the face because of the risk of ingestion. The pearly and metallic effects are obtained with composite materials, often multilayered. These are interference pigments because they create long wavelength interference patterns in natural light. Holographic effects may be obtained by liquid crystals (cholesterol derivatives) or multilayer plastic slabs (terephthalates).

Antioxidants and preserving agents The most frequently used antioxidants are the β-carotenes (provitamins A), ascorbic acid, and tocopherol, which are all powerful, natural antioxidants. The preserving agents are used to control bacterial proliferation. There are few preserving agents (phenoxyethanol mainly) in anhydrous products such as lipsticks.

Perfume Perfume provides the desired smell to the lipstick. It is generally used as an oil-based concentrate that is miscible with the other oils in the formulation.


These are used to provide their specific properties to the finished product and often permit claims of antiaging or moisturizing. They must be included at the considered concentration to be effective. Vitamin A, as β-carotene, vitamin E (tocopherol), and vitamin C are classically used in lipstick. Sunscreen can be used to protect the lips against UV rays for an antiaging quality.

Lip glosses and brilliances A lip brilliance is a makeup product that generally has low covering qualities but reflects light and gives the lips a shiny appearance. A brilliant lipstick has a gloss effect. So, by extension, the term lip gloss includes lip brilliants. Lip glosses nourish the lips and give them a light, wonderfully supple appearance and a long-lasting sparkle. Their crystalline effect is brought about by their ultra-brilliant, transparent base. They may be used over a lipstick to give a new sparkle to the lipstick color, or simply provide the lips with a very pure, superfine color. Its formulation differs from that of lipstick only in the quantity and nature of the components classically used in lipsticks. Lip glosses are frequently sold in small flasks and are applied with a special applicator. They are not applied directly to the lips, so they do not need to have a solid structure like a lipstick. The wax content is lower and the content of waxy paste higher.

Conclusions Lipsticks and lip glosses are essential to a women’s makeup, and have a key role in the affirmation of her personality and well-being. These skin surface products – thanks to their simple formula that contains a limited number of constituents – are usually well accepted and adverse reactions are very rare. Pink, purple, even blue, the colors follow the fashion trends, and, most of the time, they are coordinated with clothes and nail polishes. The shapes and textures that women appreciate remain quite classic. Indeed, if raw materials are constantly evolving, cosmetic regulations worldwide lay down some new restrictions to the manufacturers of the beauty sector. Nevertheless, these regulatory evolutions still allow the creation of ever more innovative and qualitative products.

References 1 Kobayashi H, Tagami H. (2005) Functional properties of the surface of the vermilion border of the lips are distinct from those of the facial skin. Br J Dermatol 150, 563–7. 2 Binnie WH, Lehner T. (1970) Histology of the muco-cutaneous junction at the corner of the human mouth. Arch Oral Biol 15, 777–86.

24. Lips and lipsticks 3 Fogel ML, Stranc MF. (1984) Lip function: a study of normal lip parameters. Br J Plast Surg 37, 542–9. 4 Barrett AW, Morgan M, Nwaeze G, et al. (2005) The differentiation profile of the epithelium of the human lip. Arch Oral Biol 50, 431–8. 5 Mulliken JM, Pensler JM, Kozakewich HPW. (1993) The anatomy of vermilion bow in normal and cleft lip. Plast Reconstr Surg 92, 395–404. 6 Stevens JC, Choo KK. (1996) Spatial acuity of the body surface over the life span. Somatosens Mot Res 13, 153–66. 7 Lafranchi HE, de Rey BM. (1978) Comparative morphometric analysis of vermilion border epithelium and lip epidermis. Acta Anat 101, 187–91. 8 Heilman E. (1987) Histology of the mucocutaneous junctions and the oral cavity. Clin Dermatol 5, 10–6. 9 Kuffer R. (1982) Pathologie de la muqueuse buccale et des lèvres. Encyclopédie Médicochirurgicale (Paris), Dermatologie, 12830 A10. 10 Muto H, Yoshioka I. (1980) Relation between superficial fine structure and function of lips. Acta Dermatol Kyoto Engl Ed 75, 11–20. 11 Hikima R, Igarashi S, Ikeda N, et al. (2004) Development of lip treatment on the basis of desquamation mechanism. IFSCC Magazine 7, 3–10. 12 Cruchley AT, Williams DM, Farthing PM, et al. (1994) Langerhans cell density in normal human oral mucosa and skin: relationship to age, smoking and alcohol consumption. J Oral Pathol Med 23, 55–9. 13 Sallette J, Al Sayed N, Laboureau J, Adem C, Soussaline F, Breton L. (2006) Neuropeptide Y may be involved in human lip keratinocytes modulation. J Invest Dermatol 126, suppl 3, s13. 14 Choquet P, Sick H, Constantinesco A. (1999) Ex vivo high resolution MR imaging of the human lip with a dedicated low field system. Eur J Dermatol 9, 452–4. 15 Wolfram-Gabel R, Sick H. (2000) Microvascularisation of lips in ageing edentulous subjects. Surg Radiol Anat 22, 283–7. 16 Iwai I, Yamash*ta T, Ochiai N, et al. (2003) Can daily-use lipstick make lips more fresh and healthy? A new lipstick containg αglucosyl hesperidin can remove the dull-color from lips. 22nd IFSCC Conference, pp. 162–77. 17 Ricbourg B. (2002) Vascularisation des lèvres. Ann Chir Plast Esthet 47, 346–56. 18 Ball J. (2002) The current status of lip prints and their use for identification. J Forensic Odontostomatol 20, 43–6.

19 Sivapathasundharam B, Prakash PA, Sivakumar G. (2001) Lip prints (cheiloscopy). Indian J Dent Res 12, 234–7. 20 Hirth L, Göttsche H, Goedde HW. (1975) Lips print: variability and genetics. Humangenetik 30, 47–62. 21 Hirth L, Goedde HW. (1977). Variability and formal genetics of labial grooves. Anthrop Anz 36, 51–7. 22 Lévêque JL, Goubanova E. (2004) Influence of age on the lips and perioral skin. Dermatology 208, 307–14. 23 Calvalcante ASR, Anbinder AL, Carvalho YR. (2008) Actinic cheilitis: clinical and histological features. J Oral Maxillofac Surg 66, 498–503. 24 Pogoda JM, Preston-Martin S. (1996) Solar radiation, lip protection, and lip cancer risk in Los Angeles County women (California, United States). Cancer Causes Control 7, 458–63. 25 Caisey L, Gubanova E, Camus C, Lapatina N, Smetnik V, Lévêque JL. (2008) Influence of age and hormone replacement therapy on the functional properties of the lips. Skin Res Technol 14, 220–5. 26 Wohlert AB. (1996) Tactile perception of spatial stimuli on the lip surface by young and older adults. J Speech Hearing Res 39, 1191–8. 27 Simon E, Stricker M, Duroure F. (2002) Le vieillissem*nt labial: composantes et principes thérapeutiques. [The lip ageing.] Ann Chir Plasti Esthét 47, 556–60. 28 Aiache AE. (1997) Rejuvenation of the perioral area. Dermatol Clin 15, 665–72. 29 Guerrissi JO. (2000) Surgical treatment of the senile upper lip. Plast Reconstr Surg 92, 938–40. 30 Ali MJ, Ende K, Maas CS. (2007) Perioral rejuvenation and lip augmentation. Facial Plast Surg Clin North Am 15, 491–500. 31 Zugerman C. (1986) The lips: anatomy and differential diagnosis. Cutis 38, 116–20. 32 Kunachak S, Kunachakr S, Kunachark S, Leelaudomlipi P, Wongwaisatawan S. (2001) An effective treatment of dark lip by frequency-doubled Q-switched Nd:YAG laser. Dermatol Surg 27, 37–40. 33 Sarswathi TR, Kumar SN, Kavitha KM. (2003) Oral melanin pigmentation in smoked and smokeless tobacco users in India: clinico-pathological study. Indian J Dent Res 14, 101–6. 34 Dong JK, Jin TH, Cho HW, et al. (1999) The esthetics of the smile: a review of some recent studies. Int J Prosthodont 12, 9–19.


Chapter 25: Eye cosmetics Sarah A. Vickery, Peter Wyatt, and John Gilley Procter & Gamble Cosmetics, Hunt Valley, MD, USA

BAS I C CONCE P T S • Mascara is intended to darken, thicken, and lengthen the lashes to make them more noticeable. Careful selection of mascara film materials and new applicator technologies are enhancing women’s abilities to accentuate these characteristics quickly and effectively. • Other eyelash products, beyond mascara, such as lash perms and lash tints are becoming more prevalent and are beginning to gain mainstream acceptance. These new products are changing the way women think about eyelash beauty. • Eyeshadow is color applied to the upper eyelids that is used to add depth and dimension to the eyes, thus drawing attention to the eye look or eye color. • Eyeliner is used to outline the eyelids, serving to define the eyes and to make the eye look more bold or to give the illusion of a different eye shape. • New eye cosmetic products are being introduced that feature enhanced long wear, new applicator surfaces, novel color effects, sustainable natural materials, improved application, and even lash growth.

Introduction This chapter gives a broad introduction to eye cosmetics. Mascara, eyeshadows, and eyeliners are presented along with the physiology of eyelashes and future trends.

Eye cosmetic history Cosmetics have been used to decorate the eyes for thousands of years. In Ancient Egypt materials such as charcoal and kohl were mixed with animal fat to create ointment for darkening the lashes and eyelids. They used eye cosmetics for the same reasons that we do now: in youth to attract by accentuating and drawing attention to the eyes, and in age to preserve beauty as it starts to fade [1,2]. Moving forward to more modern times, in the 18th and 19th centuries, men would condition their hair and mustaches with a touch-up product for graying hair called Mascaro. This was also used in stage makeup as both an eyelash and brow cosmetic. In the 19th century women darkened their lashes with lamp black, which they could collect simply by holding up a plate to catch the soot above a lamp or candle flame. They also used cake mascara (soap, wax, and pigment wetted with a moistened brush) to darken their lashes, or they could plump their lashes with petro-

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


leum jelly. Since then a wide variety of innovations have changed both the way we decorate eyes and the penetration of these products into daily use by the majority of women [3]. The first half of the 20th century saw a range of new product forms emerge including liner pencils, melted wax dripped onto lashes, eyelash curlers, eyebrow pencils, lash dye, cream mascara (toothpaste style tube with brush), false lashes, liquid drops, and even turpentine-based waterproof mascara. As the century progressed, more and more women were using eye cosmetics, driven in part by the makeup of the popular actresses in the Hollywood movies and also because of new distribution systems, such as Maybelline’s mail order mascara and availability at local stores. By the late 1930s, the majority of women applied cosmetics around their eyes [4]. In 1957, Helena Rubenstein launched the first modern day mascara – a tube of mascara cream with the applicator stored inside the tube. No longer was the mascara applicator separate from the mascara formulation. This efficient and more sanitary design took off quickly and, by the 1960s, became the standard form of mascara. Once this new product form was established, the applicator quickly changed from a simple grooved aluminum rod to the ubiquitous twisted wire brush applicator that is the predominant applicator today [3]. By the 1970s, waterproof mascaras were more appealing than the past turpentine-based versions because of the availability of purified petroleum-based volatile solvents [4]. Fibers were introduced into mascaras for a “lengthening” benefit. Eyeshadows were available in a broad range of

25. Eye cosmetics matte and sparkling colors, partly because of the growth of iridescent pigments in the 1960s. By the 1980s and into the 1990s, the rapidly improving performance of polymers resulted in more durable eye cosmetics that would glide on with ease and maintain their effect for hours [5].

Eyelash physiology Eyelashes are terminal hairs growing from follicles around the eye. Like all hair, the eyelash is a mixture of dead cells that have been keratinized, binding material, melanin granules, and small amounts of water. The outer surface is comprised of a series of overlapping, transparent scales called cuticle cells that protect the inside, called the cortex. The cortex contributes to the eyelash’s shape, mechanical properties, and color. Eyelashes vary by ethnicity and, as a result, can have an elliptical or circular cross-section with an average diameter of 60–120 μm, tapering to a fine, barely pigmented tip [6–8]. Figure 25.1 is a series of scanning electron micrographs that show the shape, cross-section, and surface morphology of an eyelash. While hair over the body is likely there for thermal insulation and proximity sensation, eyelashes protect the eye from debris and signal the eyelid to close reflexively when something is too close to the eye. Chemically, eyelashes are the same as scalp hair, and across ethnicities the chemistry of lashes is the same. Eyelashes have a substantially shorter, slower growth phase than scalp hair, hence their shorter length, and they typically last for 5–6 months before falling out. An active follicle, during the anagen (growth) cycle, will typically produce a lash at approximately 0.15 mm/day, half the growth rate of scalp hair. If a lash if plucked from the hair follicle, a new hair can begin growing in as little as 8–10 weeks [6–7,9].

Figure 25.1 Scanning electron microscope images of the eyelash. The eyelash tapers to a fine tip. The cross-section may be circular or elliptical (A), and the surface is composed of overlapping cuticle cells (B).

The direction that the eyelash protrudes from the eyelid is based on the follicle’s position in the skin. The curvature of the lash is derived from the shape of the follicle. As the lash forms inside the follicle, and the protein strands are bonded together, the lash shape that is formed corresponds to the shape of the follicle they are formed within. Eyelashes are arranged around the eye in a narrow band 1–2 mm wide. Lashes are longer (8–12 mm) and more numerous (90–200) on the upper eyelid, while lower eyelid lashes number 30– 100 and are typically 6–8 mm long [8]. There are a number of ailments to which the eyelashes are prone, the most common of which are listed in Table 25.1.

Mascara Over half of women who wear cosmetics wear mascara. In fact, mascara is a product that women tend to be passionate about. When asked which cosmetic they would choose if they could only choose one, over 50% of women would choose mascara. Mascara is intended to darken, thicken, and lengthen the lashes to make them more noticeable. Through careful selection of materials, mascara films can be produced to accentuate these characteristics. Mascara formulations can be roughly divided into two different types: water-resistant and waterproof.

Table 25.1 Common eyelash ailments. Ailment


Madarosis, or hypotrichosis

Thinning, or loss, of eyelid and eyebrow hairs. Can be caused by aging, physical trauma, burns, X-ray therapy, overuse of glued false lashes, and trichotillomania (impulse to pull out one’s hairs, including eyelashes)


A stye can be caused, among other things, from a bacterial infection of the eyelash follicle’s sebaceous glands, leading to an inflammation of skin tissue around the eyelash follicle


Lashes losing their pigmentation with age, caused by less melanin granules being present in the lashes. Gray lashes are pigmented, just with less pigment than those of a younger person. Completely unpigmented lashes are white


This is the abnormal growth of lashes directed towards the eyeball, causing irritation and possibly leading to infection



Colored Facial Cosmetics

Mascara composition Water-resistant mascaras typically deliver a combination of waxes, polymers, and pigments in a water-based emulsion to the lashes. The water helps contribute to the enhanced lash attributes by absorbing into the lash, bloating its diameter by as much as 30% and in many cases forcing the lashes to curl. The waxes are emulsified into the water creating a thick, creamy texture that glides onto the lashes in a thick film that resists fading, abrasion, and flaking throughout the day, but is still easily removed with warm water and soap. Polymers are often included to bind the mascara to itself as well as to the lashes. Advances in polymer technology over the last 20 years have led to very substantive films that last throughout the day, even though they are delivered to the lash in an aqueous medium. Consumers who desire the longest lasting mascara will select the anhydrous waterproof formulations which contain little to no water and deliver very durable, but difficult to remove films. Waterproof mascaras usually use hydrocarbon solvents and anhydrous raw materials. They provide a longwearing film on the lashes, which is very resistant to water, smudging, and smearing. Its anhydrous nature makes it more difficult to both apply and remove, and it may have more eye irritation potential. A list of common water-resistant and waterproof mascara ingredients and their functions can be found in Table 25.2.

Additional ingredients can be added to a formulation to enhance particular eyelash characteristics. A common method for producing lengthening mascara is to include fibers in the formulation so that, when applied, the fibers will extend beyond the natural ends of the eyelashes. Similarly, large, lightweight, hollow particles may be incorporated into the mascara film to create a thicker film for bolder lashes. Synthetic or natural polymers with novel properties can also be incorporated to induce a curling effect on the lashes. Other forms of mascara are available such as clear mascaras, waterproofing topcoats, pearlescent topcoats, and lash primers. This breadth of cosmetic options gives consumers many choices to groom and decorate their lashes.

Mascara applicator technology Consumers will typically judge a better mascara applicator as one that creates more clumps of lashes that are uniformly spaced apart [10]. However, different consumers apply their mascara for different end looks – some aspiring for only a few (spiky) clumps of lashes, others working towards wellseparated lashes. The twisted wire brush has been the mainstay mascara applicator for 50 years. As seen in Figure 25.2, it is simply a metal wire bent back upon itself into two parallel wires. Bristles, typically made of nylon, are inserted between the bent wire and it is twisted around to form a

Table 25.2 Water-resistant and waterproof mascara ingredients and function. Class

Material type



Water-resistant solvent

Carrier fluid

Water, propylene glycol

Deliver mascara ingredients to lashes in liquid vehicle

Waterproof solvent

Carrier fluid

Isododecane, cyclomethicone, petroleum distillates

Deliver mascara ingredients to lashes in liquid vehicle

Film former


Cellulosic polymers, acrylates co-polymer/xanthan or acacia gum

The main constituent of the mascara film and serves to bind the other ingredients together in the wet and dried film



Beeswax, carnauba wax/bentonite clay

Provides body and structure to the mascara film during application and wear

Surfactant or emulsifier

Anionic/non-ionic, etc.

Sodium laureth sulfate/TEA soap, polysorbates

In a formulation with two immiscible substances, an emulsifier stabilizes the two dissimilar parts of the formulation, preventing separation



Iron oxides, mica, ultramarines

Provides color to the mascara film

Care or attribute

Hair treatment/ lengthening, etc.

Panthenol, keratin/nylon or silk fiber

An ingredient included for a specific effect in the mascara film


Antimicrobial/pH adjuster/chelator

Parabens, potassium sorbate/citric acid/EDTA

Prevents contamination of harmful microorganisms such as bacteria, mold, and fungus


25. Eye cosmetics helical arrangement of bristles. The bristles are very effective at depositing mascara onto lashes, but the inconsistent spacing between bristles on the brush can lead to excessively large clumps of lashes, uneven lash separation, and the need for compensatory grooming of the lashes. The skill of the consumer plays a large part in achieving her desired look in a timely manner, and the twisted wire applicator has seen many adjustments over the years to make mascara application easier and quicker for consumers to achieve their desired lash appearance. Innovations include tapering the end of the applicator, curving the brush, hollow

bristles, changing the diameter or length of the applicator, and even cutting shapes out from the applicator’s profile to create channels within the collection of bristles. Despite the wide variety of twisted wire applicator innovations, the bristles all converge around a central shaft and the spacing between adjacent bristles is highly variable. This limits the consistency of both lash clump size and gaps between clumps of lashes. In the last 5 years, technology advancements have enabled a whole new category of molded mascara applicators to emerge. The precisely engineered surfaces of a molded applicator, shown in Figure 25.3, give control over the placement, number, and physical properties of bristles or other grooming surfaces. The result is consistent gaps between bristles, enabling the bristles to penetrate deeper into the lashes for increased mascara transfer and more efficient and regular separation of lashes. In addition, the varieties of colors, shapes, and textures that can be created are almost limitless and offer new opportunities to delight consumers. A few examples of these are shown in Figure 25.4.

Other eyelash treatments

Figure 25.2 Twisted wire brush mascara applicators.

The ability to change the appearance of eyelashes extends beyond mascara. False eyelashes may be applied as entire strips or as individual groups of lashes. They are adhered to the eyelid with a non-permanent adhesive. This allows easy application and removal at the end of the day. Lash tinting involves application of a semi-permanent dye for color that lasts about a month. This is a two part product, just like permanent coloring for scalp hair. An oxidative cream is mixed with an oxidizing agent and then applied

Figure 25.3 Molded mascara applicator with precisely engineered, parallel bristles.



Colored Facial Cosmetics

Figure 25.4 Various molded mascara applicator designs showing the wide range of possibilities that are possible with this emerging applicator type.

onto the lashes and left for 15–20 minutes. The dye forms while it is penetrating into the lashes. Lash perming is achieved by rolling the lashes of the top eyelid around a thin cotton tube. The lashes are then coated with a high pH gel that penetrates into the lashes and breaks disulfide bonds holding together keratin protein strands in the cortex. After about 15 minutes, a second neutralizing coat is applied to the lashes to neutralize the high pH and reform bonds between protein strands to hold the lash in its new shape after the cotton cylinder is removed. Eyelash extensions are synthetic fibers that are bonded to individual lashes, usually with a cyanoacrylate adhesive. Typically, 30–80 lashes per eyelid will have eyelash extensions applied, and they typically last 1–2 months. Eyelash transplants involve relocating scalp follicles to the eyelids. Small incisions are made in the top and bottom eyelids into which are placed the transplanted follicles. Manual curling and trimming is necessary because the scalp follicles will continue to grow hair for years in a relatively straight direction. Blepharopigmentation, or eyelid tattooing, involves application of pigmentation into skin at the edges of the eyelid to simulate either eyeliner or the appearance of lashes. This is permanent but can be reversed with laser surgery. Over the past 3 years, a number of products have launched with claims that suggest physiologic stimulation of lash growth for darker, thicker, longer, and curlier lashes. Most of these make use of prostoglandin analogs that are typically used for treating glaucoma, but are known to have the above (beneficial) side effects [11].


Eyeshadow Eyeshadow is color applied to the upper eyelids. It is used to add depth and dimension to the eyes, thus drawing attention to the eye look or eye color. The predominant form is powder, both pressed and loose, but eyeshadow is also available in other forms, such as creams, sticks, and liquids. Eyeshadows are very similar to blushes and pressed powder in terms of their key ingredients (Chapter 22). They are usually comprised of pigments and pearls, and fillers bound together with a volatile or non-volatile binder. They may also contain other powder particles such as boron nitride or polytetrafluoroethylene to improve slip and pay-off on application.

Eyeliners Eyeliner is used to outline the upper and lower eyelids. This serves to define the eyes against the backdrop of the face. Eyeliner can also be used to make the eye look more bold or to give the illusion of a different eye shape. They are typically available in liquid form and wood or mechanical pencils. Wood pencils excel at creating a softer, more natural look. Mechanical pencils tend to be a bit bolder, and the gel forms are good for gliding easily across the eyelid. Liquid liners can create a distinctively defined eye and provide longer wear but can be difficult to apply correctly. Most eye pencils are comprised of colorants dispersed in a waxy

25. Eye cosmetics matrix for ease of application and to help the color adhere to the skin. Liquid liners, although not as popular as the pencil form, contain colorants that are dispersed in volatile solvents so they can be applied with a brush or pen-like applicator.

Product application Eyeshadow application techniques vary according to the look you are trying to achieve but, generally, an appealing look can be achieved using three complementary shades in light, medium, and dark. The lightest shade highlights the area below the eyebrow, the medium shade is applied to the creased area, and the darkest shade is reserved for the area immediately above the upper eyelashes. Matte, silky shadows tend to blend nicely and are better for mature eye skin than iridescent or sparkly shades which can highlight fine lines or puffiness. Generally, eyeliner is applied to the outer two-thirds of the lower lid below the lashes and to the entire upper lid above the lashes in a thin line. An angled brush can be used to gently soften the look. Although dark liners draw a lot of attention to the eyes, softer shades of brown, especially in the daytime, can be used to avoid looking too harsh. Curling the lashes with an eyelash curler prior to mascara application will make the eyes seem more wide open and bright. Usually, mascara is applied generously to upper lashes and to a lesser extent to the lower lashes. Color choice of mascaras can change the look obtained. For instance, on light-haired individuals brown mascara can be used for a softer, more natural look. Black or brown–black is best for deeper skin tones or for a more dramatic look. Figure 25.5 shows the effect of applying eye cosmetics.

Safety and regulatory considerations for eye area cosmetics Most countries or regions regulate cosmetics to a varying degree of complexity, largely because of safety considerations. Because cosmetics touch and interact directly with the human body, the various regulations are in place to ensure that consumers are not exposed to materials that may be harmful. This stems from various safety incidents that have occurred with personal care products. For instance, consumers can have allergic reactions to lash dyes, which were becoming a popular product in the 1930s. In one case, an allergic reaction to a lash dye led to one consumer becoming blind [4]. Ultimately this was one of many cases in the USA that led to Food and Drug Administration (FDA) overseeing of cosmetics. In particular, it led to a positive list of colorants that could be used for eye area cosmetics [12]. In later years, other regulatory bodies, such as the European Commission, adopted similar restrictions to the FDA’s on colorants for use in the eye area [13]. Because of their intimate contact with the human body, all cosmetics should be adequately preserved from microbiologic insults. This is especially true for eye cosmetics where contact with a contaminated product could lead to an eye area infection and the possibility of more serious complications.

The future of eye cosmetics For a mature category such as eye cosmetics, it is surprising how much potential still exists for product innovation. New products are being introduced that feature enhanced long wear, new applicator surfaces, novel color effects,


(b) Figure 25.5 The impact of eye cosmetics on eye beauty. (a) Before. (b) After.



Colored Facial Cosmetics

Figure 25.6 Digital simulations of lashes aid cosmetic scientists in visualizing potential lash looks for product design.

sustainable natural materials, improved application, and even lash growth. The mascara application experience is being improved with automated applicators that use vibrating or rotating brushes to take away some of the skill necessary to achieve beautiful lashes. These applicators can be held up against the lashes while they work for the consumer by exposing more of the applicator surface to the lashes, encouraging more deposition of mascara and more grooming of the lashes. Products are coming onto the market that claim to actually stimulate and enhance lash growth. While there are regulatory considerations that make these products controversial, if approved for consumer use they may negate the need of some women to use mascara to achieve beautiful lashes. Scientists around the world are even starting to tap in to virtual modeling to peel back the individual factors of eye beauty, and to design looks not yet achievable with today’s products. Three-dimensional modeling and simulation are being exploited to mimic consumers’ real eyelashes, and then simulate how those lashes may be made more beautiful. For the first time we can explore both the true limits of eye beauty and the individual impacts of single lash variables (e.g. lash separation, thickness, lift, color, curl) on beauty. An optimized digital representation of a consumer’s lashes can be used to design a formula and applicator to deliver the right personalized lash look for them. Figure 25.6 shows several related simulations where only lash clumping is adjusted [14].


References 1 Kunzig R. (1999) Style of the Nile. Discover September, p. 80. 2 Ahuja A. (1999) Chemistry and eye make-up – science. Times September 22. 3 Geibel V. (1991) Mascara. Vogue August. 4 Riordan T. (2004) Inventing Beauty: a history of the innovations that have made us beautiful. New York: Broadway Books, pp. 1–31. 5 Balaji Narasimhan R. (2001) Pearl luster pigments. In: Paintindia Vol. 51, pp. 67–72. 6 Elder MJ. (1997) Anatomy and physiology of eyelash follicles: relevance to lash ablation procedures. Ophthal Plast Reconstr Surg 13, 21–5. 7 Na J, Kwon O, Kim B et al. (2006) Ethnic characteristics of eyelashes: a comparative analysis in Asian and Caucasian females. Br J Dermatol 155, 1170–6. 8 Liotet S, Riera M, Nguyen H. (1977) Les cils: Physiologie, structure, pathologie. Arch Opht 37, 697–708. 9 10 Sheffler RJ. (1998) The revolution in mascara evolution. Happi April, pp. 48–52. 11 Wolf R, Matz H, Zalish M, Pollack A, Orion E. (2003) Prostaglandin analogs for hair growth: great expectations. Dermatology 9, 7. 12 21C.F.R. Part 700, Subchapter G. 13 Directive 76/768/EC, OJ L 262, p. 169 of 27.9.1976. 14 Wyatt P, Vickery S, Sacha J. (2006) Poster given at SIGGRAPH 2006.

Part 2: Nail Cosmetics Chapter 26: Nail physiology and grooming Phoebe Rich1 and Heh Shin R. Kwak2 1 2

Oregon Dermatology and Research Center, Portland, OR, USA Knott Street Dermatology, Portland, OR, USA

BAS I C CONCEPTS • Knowledge of nail unit anatomy and physiology and an understanding of nail plate growth and physical properties are important prerequisites for understanding nail cosmetics. • Disruption and excessive manipulation of certain nail structures, such as the hyponychium and eponychium/cuticle, should be discouraged during nail cosmetic procedures and nail salon services. • In addition to beautifying natural nails, nail cosmetics are beneficial in camouflaging unsightly medical and infectious nail problems, especially during the lengthy treatment period. • Some nail cosmetics provide a protective coating for fragile, weak, and brittle nails. • Proper nail grooming is crucial for maintaining nail health. • Although most nail cosmetics are used safely, it is important to be aware of potential complications associated with nail cosmetic materials and application processes.

Introduction: Nail physiology Nail unit anatomy Understanding nail unit anatomy is an essential first step to comprehending the complexity of nail cosmetics use, including pathology induced by cosmetic materials and procedures. The nail unit is composed of the nail matrix, proximal and lateral nail folds, the hyponychium, and the nail bed (Figure 26.1). Table 26.1 lists common nail signs and definitions relevant to nail cosmetics.

Nail matrix The nail matrix is comprised of germinative epithelium from which the nail plate is derived (Figure 26.2). The majority of the matrix underlies the proximal nail fold. The distal portion of the nail matrix is the white lunula visible through the proximal nail plate on some digits. It is hypothesized that the white color of the lunula can be attributed to both incomplete nail plate keratinization and loose connective tissue in the underlying dermis. The proximal nail matrix generates the dorsal (superficial) nail plate, while the distal nail matrix generates the ventral (inferior) nail plate. This

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

concept is crucial to understanding nail pathology. Preserving and protecting the matrix during nail cosmetic processes is essential for proper nail plate formation. Significant damage to the nail matrix can result in permanent nail plate dystrophy. The nail plate is derived from the nail matrix and composed of closely packed, keratinized epithelial cells called onychocytes. Cells in the matrix become progressively flattened and broadened and lose their nuclei as they mature into the nail plate. The nail plate is curved in both the longitudinal and transverse planes, allowing for adhesion to the nail bed and ensheathment by in the proximal and lateral nail folds. Longitudinal ridging may be present on both the dorsal and ventral surface of the nail plate. Mildly increased longitudinal ridging on the dorsal nail plate is considered a normal part of aging. Ridging on the ventral surface of the nail plate is caused by the structure of the underlying nail bed and vertically oriented blood vessels. The composition and properties of the nail plate are further discussed below.

Nail folds The nail folds surround and protect the nail unit by sealing out environmental irritants and microorganisms through tight attachment of the cuticle to the nail plate. The cuticle is often cut or pushed back during cosmetic nail procedures which can allow moisture, irritants, bacteria, and yeasts under the nail fold, resulting in infection or inflammation of the nail fold, termed paronychia (Figure 26.3). Chronic



Nail Cosmetics

Table 26.1 Common nail signs associated with or helped by nail cosmetics. Nail sign




Separation of the nail plate from the nail bed

Vigorous cleaning of hyponychium exacerbates. Polish hides


Increased longitudinal ridging

Associated with aging, distal notching. Polish may help


Lamellar splitting of the free end of the nail plate


Inflammation of the nail fold

Dyschromia yellow

Staining of the surface of the nail plate yellow from the dye in nail polish

Green/black discoloration

Pseudomonas is a bacteria that generates a green–black pigment that discolors the nail plate

Nail bed changes as in psoriasis, onychomycosis

Nail matrix (nail root) Cuticle (stratum corneum of the nail fold) Lunula

Free edge of nail plate

Eponychium Cuticle


Nail bed

Nail plate Nail bed

Proximal nail fold

Hyponychium Hyponychium Distal groove

Lateral nail fold

Figure 26.1 Nail unit with lines indicating important structures.

Figure 26.2 Diagram of the nail unit.

paronychia may disrupt the underlying nail matrix and subsequently lead to nail plate dystrophy.


Figure 26.3 Paronychia.


The hyponychium is the cutaneous margin underlying the free edge of the nail plate. The nail bed ends at the hyponychium. It is contiguous with the volar aspect of the fingertip. The hyponychium has a similar function as the cuticle and acts as an adherent seal to protect the nail unit. The hyponychium should not be overmanipulated during nail grooming to avoid onycholysis, or separation of the nail plate from the nail bed. This space created between the nail plate and

26. Nail physiology and grooming bed retains moisture and establishes an environment for potential pathogens, such as yeast, bacteria, or fungi.

Nail bed The nail bed is thin, 2–5 cell layer thick epithelium that underlies the nail plate. It extends from the lunula to the hyponychium. The nail bed is composed of longitudinal, parallel rete ridges with a rich vascular supply which is responsible for the pink coloration of the bed, as well as longitudinal ridges on the ventral surface of the nail plate. In chronic onycholysis the nail plate is separated from the nail plate for an extended duration, the nail bed epithelium may become keratinized, form a granular layer, and lead to permanent onycholysis (Figure 26.4).

Several factors affect nail growth. Nail growth peaks at 10–14 years and declines after 20 years. Nail growth is proportional to finger length, with fastest growth of the third fingernail and slowest growth of the fifth fingernail. Nails grow slower at night and during the winter. Other factors causing slower nail plate growth include lactation, immobilization, paralysis, poor nutrition, yellow nail syndrome, antimitotic drugs, and acute infection. Faster nail growth has been noted during the summer and in the dominant hand. Pregnancy, psoriasis, and nail biting are other factors linked to faster nail growth. Table 26.2 summarizes factors influencing nail growth.

Physical properties of nails Nail composition

Other structures The distal phalanx lies immediately beneath the nail unit. The extensor tendon runs over the distal interphalangeal joint and attaches to the distal phalanx 12 mm proximal to the eponychium. Given that there is little space between the nail unit and distal phalanx, minor injury to the nail unit may extend to the periosteum and lead to infection.

Nail growth Normal nail growth has been cited to vary from less than 1.8 mm to more than 4.5 mm per month. Average fingernail growth is 0.1 mm per day, or 3 mm per month. This information is useful when determining the duration of nail pathology. For example, if splinter hemorrhages are located 6 mm from the proximal nail fold, it can be estimated that they occurred from injury approximately 2 months prior. Based on this growth rate, fingernails grow out completely in 6 months. Toenails grow at one-third to half of the rate of fingernails and take 12–18 months to grow out completely.

The nail plate is composed mainly of keratin, which is embedded in a matrix of non-keratin proteins. There is wide variation in reported percentage of inorganic elements found in the nail plate. Several elements, including sulfur, calcium, iron, aluminum, copper, silver, gold, titanium, phosphorus, zinc, and sodium, are constituents of the nail plate. Of these elements, sulfur has the greatest contribution to nail structure and comprises approximately 5% of the nail plate. Nail plate keratin is cross-linked by cysteine bonds, which contain sulfur. Some studies attribute brittle nails to decreased cysteine levels. There is a popular misconception that calcium content is responsible for nail hardness. This idea likely stems from knowledge that bone density is related to calcium intake. Calcium comprises less than 1% of the nail plate by weight. No evidence supports that decreased calcium is linked to brittle nails and that calcium supplementation increases nail strength. In fact, kwashiorkor, a nutritional deficiency caused by insufficient protein intake, is manifested by soft, thin nails and demonstrates increased nail plate calcium.


(b) Figure 26.4 (a & b) Onycholysis.



Nail Cosmetics

Table 26.2 Nail cosmetic products: ingredients and uses. Product


Application procedures

Benefits of use

Potential complications

Nail polish

Film former: nitrocellulose Thermoplastic resin: (toluene sulfonamide formaldehyde resin) Plasticizer: dibutyl pthalate Solvents and pigments

Polish is applied in several coats with a small brush and allowed to dry by evaporation

Provides an attractive glossy smooth decorative surface and camouflages nail defects Protects nail from dehydration and irritants

Yellow staining of nail plate. Potential for allergy to toluene sulfonamide formaldehyde resin and other ingredients

Nail hardener

May contain formaldehyde in a nail polish base, also may have fibers that reinforce the nail

Application similar to nail polish which is applied in several coats

Forms several layers of protection on the nail plate

Potential allergy to formaldehyde and possible brittleness

Acrylic nail extensions

Acrylic monomer, polymer, polymerized to form a hard shell attached to the nail plate or to a plastic tip glued to the nail

Monomer (liquid) and polymer (powder) mixed to form a paste and polymerized with a catalyst to a harden the product

Cover unsightly nail defects, may help manage onychotillomania and habit tic disorder

Possible allergy to acrylates, inflexibility of artificial nail may cause injury to nail unit

Cuticle remover

Contains potassium hydroxide or sodium hydroxide plus humectants

Applied to cuticle for 5–10 minutes to soften cuticle adhered to nail plate

Gently removes dead skin attached to the nail plate without mechanical trauma

Over removal of cuticle and result in the potential for paronychia and secondary bacteria and Candida infections. Can soften the nail plate

Nail polish remover

Acetone, butyl acetate, ethyl acetate, may also contain moisturizer such as lanolin or synthetic oils

Wiped across nail plate with cotton or tissue to remove nail polish

Removes polish smoothly without removing layers of nail plate

May dehydrate the nail plate and periungual tissue

Water content of the normal nail plate is reported to range between 10% and 30%. The most commonly accepted value is 18% water content in normal nails and 16% in brittle nails. However, a study aimed at confirming this demonstrated no statistically significant difference between normal and brittle nails [1]. In addition, this study showed lower water content than previously thought, with a mean water content of 11.90% in normal nails and 12.48% in brittle nails. Some limitations in this study were noted, including analysis of only the distal nail plate. In addition, the time between sample collection and analysis was variable, with an average of 24 hours, and a subanalysis demonstrated loss of water content varied significantly between those samples analyzed at 1 and 24 hours. Lipids, including squalene and cholesterol, are also constituents of the nail plate and comprise 5% of the nail plate by weight. These lipids are thought to diffuse from the nail bed to the nail plate.

Nail flexibility Most references to nail strength and hardness actually refer to nail flexibility. A flexible nail will bend and conform to


physical force, whereas a hard nail will break and become brittle. Nail flexibility is aided by plasticizers, which are liquids that make solids more flexible. Examples of nail plasticizers are water and lipids. Flexibility is decreased by solvents, such as nail polish removers, which remove both water and lipids, and detergents, which remove lipids. Nail brittleness is caused by loss of flexibility. Brittle nails are a common complaint and are found in 20% of the general population and more commonly in females (Figure 26.5). Brittleness encompasses several nail features including onychoschizia which is lamellar peeling of distal nail plate (Figure 26.6), splitting and notching sometimes associated with ridges, and fragility of the distal nail plate, lamellar splitting of the free end of the nail plate. Several attempts have been made to define brittleness with objective measurements, including Knoop hardness, which evaluates indentation at a fixed weight; modulus of elasticity, which describes the relationship between force/area and deformation produced; tensile strength; and a brittleness grading system. Although there are systemic and cutaneous conditions that may cause brittle nails, exogeneous causes are more

26. Nail physiology and grooming




Figure 26.5 (a–c) Brittle nails.


(b) Figure 26.6 Onychoschizia, distal lamallar peeling of the nail plate.



Nail Cosmetics




(d) Figure 26.7 (a) Manicure; (b–d) Pedicure.

common. These include mechanical trauma, exposure to solvents and extraction of plasticizers, and repeated hydration and drying of nails.

Nail grooming principles

Manicure and pedicures are the process of grooming the fingernails and toenails respectively at home or in a nail salon (Figure 26.7). The procedure involves soaking the nails to soften prior to trimming and shaping the nail plate. Excess cuticle is removed from the nail plate using a chemical cuticle remover and often a metal implement. The nails are then finished with a shiny, smooth coat of nail enamel, commonly called nail polish, sandwiched between a base coat and top coat, or the nails may be buffed to a soft luster. Other procedures such as acrylic gel or silk wrap enhancements may be added to the basic manicure. These nail extension procedures involve applying product to the natural nail or to a plastic tip glued to the nail. The material are applied and shaped before curing or polymerizing to form a hard surface.

Nail care

Nail trimming

Several principles of nail care should be observed during nail grooming to maintain normal nail structure.

Most nail experts advocate shaping nails with an emery board rather than clipping or cutting nails. Filing should be

Nail thickness Thickness of the nail plate is determined primarily by matrix length and rate of growth. Measurements of distal plate thickness demonstrate greatest thickness in the thumbnail, followed by the second, third, fourth, and fifth fingernails. Thickness also is influenced by sex, with males having an average nail plate thickness of 0.6 mm, compared to 0.5 mm in females.


26. Nail physiology and grooming carried out with the file exactly perpendicular to the nail surface to avoid inducing onycholysis. Proper filing of the free edge of nail plate reduces sharp edges that may catch and cause nail plate tearing. If nails must be clipped or cut, this should be performed after they have been hydrated which maximizes nail flexibility and prevents breakage during trimming. Nails should also be kept as short as possible. Long nails, especially those that are brittle, may act as a lever and create onycholysis.

Nail buffing and filing The dorsal nail plate surface is often filed to remove shine from the natural nail plate at nail salons prior to application of nail products or artificial nails. Care must be taken to avoid excessive filing, especially with electric drills. The nail plate is approximately 100 cell layers thick. If filing must be done, only 5% of the nail plate thickness, or approximately five cell layers, should be removed which is just enough to remove the shine of the dorsal nail plate in order to facilitate adherence of the product to the nail plate. Limited buffing to reduce nail ridging is acceptable, but excessive buffing thins the nail plate and should be avoided.

Figure 26.8 Psoriasis: salmon patch oil drop discoloration.

Care for brittle nails Brittle nails should be treated by avoiding nail trauma and increasing flexibility. Nails should be kept short. This prevents lifting of the nail plate, disruption of the hyponychium, and onycholysis. In addition, nails should be trimmed after they have been hydrated and are the most flexible. Moisturizing the nail plate increases flexibility and helps avoid brittle nails. Some experts recommend moisturizing up to four times daily. Avoiding solvents and frequent hydration and dessication of nails also helps maintain flexibility. There is controversy regarding avoidance of nail cosmetics in the management of brittle nails. Some believe that nail polish is protective and seals the moisture in the nail plate by preventing rapid evaporation. Nail polish also protects the nail plate from some environmental irritants. There is some concern that overuse of nail polish remover will dehydrate the nail and exacerbate brittleness. Biotin has also been advocated for brittle nails, but results are inconclusive. The recommended dose is 2.5–5 mg/day, which is 100–200 times the recommended daily allowance. Given that biotin has relatively few side effects, most experts recommend its use, in addition to the above grooming recommendations.

Adverse effects from nail grooming Nail cosmetics are safely used by millions of people worldwide. In addition to enhancing the appearance of normal nails, cosmetics are useful for improving the appearance of unsightly nail dystrophy caused by medical disease, such as psoriasis (Figure 26.8), onychomycosis (Figure 26.9), or trauma. Although nail cosmetics rarely cause problems, it is

Figure 26.9 Onychomycosis.

important to be aware of possible adverse effects related to procedures or to materials used in nail cosmetics (Figure 26.10).

Allergic reactions to nail cosmetic ingredients The most common allergen in nail polish is toluene sulfonamide formaldehyde resin with sensitization occurring in up to 3% of the population. Other potential allergens are cyanoacrylate nail glue, formaldehyde in nail hardeners, and ethylmethacrylate in sculptured nails. Allergic contact dermatitis from nail cosmetics is seen on periungual skin, as well as the eyelids, face, and neck, caused by touching these areas with freshly polished fingernails (Figure 26.11).

Irritant reactions Common nail products that cause irritant reactions include acetone or acetate nail polish removers and cuticle removers



Nail Cosmetics with sodium hydroxide. Reactions are manifested as an irritant dermatitis of the periungual skin and as brittle nails, including onychoschizia. Prolonged use of nail polish induce keratin granulations on the nail plate. This commonly is seen when fresh coats of nail enamel are applied on top of old enamel for several weeks. These granulations cause superficial friability of the nail plate (Figure 26.12).

Nail cosmetic procedures

Figure 26.10 Yellow staining from nail polish.

Several nail problems, including paronychia, onycholysis, and thinning of the nail plate, may be mechanically induced by cosmetic procedures. Paronychia, or inflammation of the proximal nail fold, is often caused by cutting or pushing back the cuticle, leading to separation of the proximal nail fold and the nail plate. Sharp manicure instruments used to clean under the nail plate may induce onycholysis and create an environment for secondary bacterial and


(b) Figure 26.11 Allergic contact dermatitis from nail cosmetics. (a) On the eyelid. (b) On periungal skin caused by acrylates.


(b) Figure 26.12 (a & b) Keratin granulations.


26. Nail physiology and grooming

Table 26.3 Information for patients for safe nail cosmetic use. After Rich [2]. • Be sure that the salon sterilizes instruments, preferably with an autoclave. Some salons offer instruments for clients to purchase • Stinging, burning, or itching following a nail salon treatment may be signs of an allergic reaction to a cosmetic ingredient. Remove the product and seek medical evaluation by a dermatologist • If using artificial nail extensions, keep them short. Long nails can cause mechanical damage to the nail bed. Remove extensions at the first sign of onycholysis and avoid enhancements until the nail is reattached • Do not allow nail technician to cut or clip cuticles. Cuticles serve an important function and should not be cut. They may be pushed back gently with a soft towel after soaking the nails or bathing


Figure 26.13 Infection caused by Pseudomonas.

1 Stern DK, et al. (2007) Water content and other aspects of brittle versus normal fingernails. J Am Acad Dermatol 57, 31–36. 2 Rich P. (2001) Nail cosmetics and camouflaging techniques. Dermatol Ther 14, 228–36.

Further reading fungal infection. Onycholysis may be exacerbated by long artificial nails because of increased mechanical leverage. Nail drills or excessive filing and buffing may lead to thinning of the nail plate and brittle nails. Breaks in the integrity of the nail unit allow access of microorganisms such as Candida and Pseudomonas (Figure 26.13) and result in exacerbation of paronychia and onycholysis. Some basic principles for safe use of nail cosmetics are outlined in Table 26.3.

Conclusions Nail cosmetics is a multibillion dollar industry which continues to grow. Thorough knowledge of nail anatomy and physiology is essential for the safe use and development of nail cosmetics.

Chang RM, Hare AQ, Rich P. (2007) Treating cosmetically induced nail problems. Dermatol Ther 20, 54–9. Baran R, Dawber RPR, de Berker DAR, Haneke E, Tosti A. (2001) Diseases of the Nails and their Management, 3rd edn. Malden, MA: Blackwell Science. DeGroot, AC, Weyland JW. (1994) Nail cosmetics. In: Unwanted Effects of Cosmetics and Drugs used in Dermatology, 3rd edn. New York, Oxford: Elsevier, 524–9. Draelos Z. (2000) Nail cosmetic issues. Dermatol Clin 18, 675–83. Iorizzo M, Piraccini B, Tosti, A. (2007) Nail cosmetics in nail disorders. J Cosmet Dermatol 6, 53–6. Paus R, Peker S, Sundberg JP. (2008) Biology of hair and nails. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology, 2nd edn. Elsevier, pp. 965–86. Rich P. (2008) Nail surgery. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology, 2nd edn. Elsevier, pp. 2259–68. Schoon DD. (2005) Nail Structure and Product Chemistry, 2nd edn. Thompson Corporation. Scher RK, Daniel CR. (2005) Nails: Diagnosis, Therapy, Surgery, 3rd edn. Elsevier.


Chapter 27: Colored nail cosmetics and hardeners Paul H. Bryson and Sunil J. Sirdesai OPI Products Inc, Los Angeles, CA, USA

BAS I C CONCE P T S • Nail lacquers contain resins that create a thin, resistant film over the nail plate. • Adding color to the nail plate surface is accomplished with a variety of nail lacquers including a basecoat, color coat, and topcoat. • Nail hardeners cross-link nail protein to increase strength, but overuse may contribute to brittle nails. • Nail lacquers are resistant to contamination and cannot spread nail infectious disease.


Application techniques

The use of colored nail polish and nail hardeners has increased among consumers with the rise of the manicure industry. With nail salons found in almost every strip mall, painting nails is a very popular service for the customers of the professional manicurist. The use of nail cosmetics is well rooted in history. Ancient Chinese aristocrats colored their nails red or black with polishes made with egg white, bees wax, and gelatin. The Ancient Egyptians used henna to dye the nails a reddish brown color (J. Spear, editor of Beauty Launchpad, Creative Age Publications, Van Nuys, CA, personal communication). In the 19th and early 20th centuries, “nail polish” was a colored oil or powder, which was used to rub and buff the nail, literally polishing and coloring the nail simultaneously. Modern nail polish was created in the 1920s, based on early nitrocellulose-based car paint technology [1]. The term “nail polish” is somewhat of a misnomer for modern products, because no actual polishing is involved in its application. The product is composed of dissolved resins and dries to a hard, glossy coat, so the technically correct name is “nail lacquer.” However, the terms “nail polish,” “nail enamel,” “nail varnish,” “nail paint,” and “nail lacquer” are used interchangeably. Several specialty products have developed from nail lacquer, including basecoats, topcoats, and hardeners. A newer technology involves pigmented UVcurable resins. This chapter discusses the current use of these modern formulations (Table 27.1).

These nail products are applied by painting the nail with a brush. In best manicuring practices, old nail lacquer is removed with a solvent followed by application of a basecoat, two coats of colored nail lacquer, and a topcoat allowing sufficient time for drying between coats. The basecoat increases the adhesion of the colored nail lacquer to the nail while the topcoat increases the chip-resistant characteristics of the colored nail lacquer. These products are applied on both natural and artificial nails. Nail hardener is only applied to natural nails, either as a basecoat or a stand alone product. UV-curing nail “lacquers” are hardened with a UV light after application; no evaporation is necessary. In all cases, best practice dictates that the products be kept off the skin. Failure to do so can result in eventual, irreversible sensitization and allergic contact dermatitis [2]. Proper nail cosmetic application dictates the maintenance of excellent hygiene in the nail salon. Unsanitary procedures may result in medical problems [3]. Nail technicians must use cleaned, disinfected, or disposable nail files and tools. Clipping or cutting the cuticles before applying nail lacquer can also lead to infection. Infections with staphylococcus [4] and herpetic whitlows [5] have been attributed to unsanitary manicures. Nail technicians should not perform services on diseased nails.

Lacquers, topcoats, and basecoats

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


Nail lacquers contain six primary ingredients: resins, solvents, plasticizers, colorants, thixotropic agents, and color stabilizers. By law, all ingredients must be disclosed on the

27. Colored nail cosmetics and hardeners

Figure 27.2 Painting a nail. Reproduced by permission of OPI Products, Inc.

Figure 27.1 Lacquered nails. Reproduced by permission of OPI Products, Inc.

Figure 27.3 Be careful with the cuticle. Reproduced by permission of OPI Products, Inc.

Table 27.1 Overview of product types. Product class

Nail lacquer



Nail hardener

UV curable

Coating created by

Solvent evaporation

Solvent evaporation

Solvent evaporation

Mainly solvent evaporation; some polymerization of formalin may occur


Resin type or mix


Biased toward adhesion

Biased towards glossiness, hardness

Balanced or biased towards adhesion

Balanced; resin formed by reacting directly on nail



Little or none

Little or none

Usually none



Easily dissolves in solvent

Easily dissolves in solvent

Easily dissolves in solvent

Easily dissolves in solvent

Soften by acetone soak, then peel


Attractive color; can be applied over natural nails or enhancements

Helps color coat last longer; protects natural nail from staining

Helps color coat last longer; some contain optical brighteners or UV protectants

Strengthens natural nail by cross-linking proteins; may be used as a basecoat

Attractive color; tough cured-in-place resin protects nail



Nail Cosmetics

Figure 27.5 Dermatitis on the finger. Reproduced by permission of Nails Magazine.

Figure 27.4 Infected nail. Reproduced by permission of Nails Magazine.

product packaging, usually by means of the International Nomenclature for Cosmetic Ingredients (INCI) names. Understanding the chemistry nomenclature is important for isolating the causes of allergic contact dermatitis. Each of these ingredients is discussed in detail.

Resins Resins hold the ingredients of the lacquer together while forming a strong film on the nail. Chemically, the resins are polymers – long-chain molecules – that are solid or gummy in their pure state. Two types of resins are used. Hard, glossy resins give the lacquered nail its desired appearance; these include nitrocellulose and the methacrylate polymers or co-polymers (usually labeled by their generic INCI name, “acrylates co-polymer”). Topcoat formulations have a higher percentage of these harder resins. Softer, more pliable resins, which enhance adhesion and flexibility, include tosylamide/ formaldehyde resin, polyvinyl butyral, and several polyester resins. Basecoats incorporate a higher proportion of pliable resins. Of all the resins, tosylamide/formaldehyde resin is the most commonly implicated in allergic reactions [6] affecting not only the fingers, but other parts of the body by transfer [7].

Solvents Solvents are the carriers of the lacquer. They must dissolve the resin, suspend the pigments, and evaporate leaving a smooth film. The drying speed must be controlled to prevent bubbling and skinning, thus faster drying is not necessarily better. Optimum drying speed requires a careful blend of solvents. Ethyl acetate, n-butyl acetate, and isopropyl alcohol are common solvents, other acetates and alcohols are also


occasionally employed. All solvents have a dehydrating and defatting action on the skin, but this usually occurs during the removal of the lacquer, not its application. Formerly, toluene was a commonly used solvent, but the industry trend is to move away from it in response to expressed health concerns. Research indicates that toluene exposure for a nail technician and consumer is far below safe exposure limits [8]; however, consumer perceptions are negative for toluene, necessitating its replacement. A related chemical, xylene, has already virtually vanished from the industry. Ketones such as acetone or methyl ethyl ketone are not amenable to suspension of pigments and are therefore used at low levels, if at all, in lacquers, although these substances will dissolve the resins effectively and therefore are useful as lacquer removers. A few water-based nail lacquers are now on the market. Because of their much slower drying time they are unlikely to replace solvent-based products in the foreseeable future. If they are ever perfected, they will completely take over the industry, because water is cheaper, non-flammable (which reduces shipping costs), and odorless.

Plasticizers Plasticizers keep the resins flexible and less likely to chip. Camphor and dibutyl phthalate (DBP) have long been used for this purpose; however, the EU maintains its 2004 ban of DBP, despite authoritative findings regarding its safety in nail lacquer [9]. Because many manufacturers sell globally, DBP has largely been replaced by other plasticizers, including triphenyl phosphate, trimethyl pentanyl diisobutyrate, acetyl tributyl citrate, ethyl tosylamide, and sucrose benzoate.

Colorants Colorants are selected from among various internationally accepted pigments. They are mostly used in the “lake” form,

27. Colored nail cosmetics and hardeners of the spectrum. It can usually be prevented by using a basecoat between the lacquer and the natural nail [10]. Topcoats can also cause apparent yellowing, but this is usually the product rather than the natural nail – as can be easily seen by removing the product [10].

Thixotropic agents Thixotropic agents provide flow control and keep the lacquer colorants dispersed. They are usually clay derivatives such as stearalkonium bentonite or stearalkonium hectorite. Most topcoats and basecoats are uncolored and do not require these additives. Silica is also sometimes used as a thickener.

Color stabilizers

Figure 27.6 Nail lacquer. Reproduced by permission of OPI Products, Inc.

meaning that the organic colorants have been adsorbed or co-precipitated into inorganic, insoluble substrates such as the silicates, oxides, or sulfates of various metals. A shimmer effect is created by minerals such as mica, powdered aluminum, or polymer flakes. Guanine from fish scales is falling out of favor but is still occasionally used. Following INCI convention, most colorant materials are labeled by their international “Color Index” (CI) numbers. This is a convenient way to identify colors, which have different national designations. Labeling colorants by their CI numbers is either legal or de facto accepted by most regulatory agencies around the world; even so, out of deference to local custom, colors are often declared binonially (e.g. CI 77891/Titanium Dioxide). However, because of space limitations, lacquer manufacturers may declare only the CI numbers on the bottle – often on a small peel-off sticker at the bottom of the bottle. This can pose a problem as few nail lacquer users are aware that, for example, “CI 60725” means the same as “D&C Violet #2” (USA) or “Murasaki 201” (Japan). Fortunately, the full designations of the colors are usually listed on the box (which has more space than the bottle) and/or the Material Safety Data Sheet (MSDS). If these are unavailable, a web search or a phone call to the manufacturer is usually sufficient to obtain this information. Another difficulty with international designations is that some closely related colorant chemicals and their lakes are lumped under one CI number. An example is the ubiquitous CI 15850, which covers D&C Red #6, D&C Red #7, and all the various lakes of both. Normally, the manufacturer can provide more specific information if needed. Colorants sometimes cause staining of the nail. Although uncommon, it is more often seen with colors at the red end

Color stabilizers, such as benzophenone-1 and etocrylene, are added to prevent color shifting of the lacquer on exposure to UV light. These substances are better known as sunscreens, but their use in nail lacquer is to protect the color. Some specialty topcoats have a high level of UV protectants, for application over colored nail lacquer to prevent fading during tanning booth use.

Minor ingredients Minor ingredients may include vitamins, minerals, vegetable oils, herbal extracts, or fibers such as nylon or silk. Some companies may include adhesion-enhancing agents in lacquers or basecoats, or other proprietary ingredients whose functions they elect not to disclose (Table 27.2).

Antifungal agents Antifungal agents may be added to nail lacquer for therapeutic purposes. However, as of this writing, there is only one prescription US Food and Drug Administration (FDA) approved antifungal nail lacquer, a topical solution of 8% ciclopirox (Penlac®, Sanofi-Aventis, Bridgewater, NJ, USA). According to FDA Consumer Magazine, “There are no approved nonprescription products to treat fungal nail infections … fungal infections of the nails respond poorly to topical therapy … the agency ruled that any OTC product labeled, represented or promoted as a topical antifungal to treat fungal infections of the nail is a new drug and must be approved by FDA before marketing” [11]. Furthermore, the FDA’s policy is to “prohibit claims that nonprescription topical antifungals effectively treat fungal infections of the scalp and fingernails” [12].

Preservatives Preservatives are not present in nail lacquer. Regulatory authorities inquired if microbial cross-contamination could occur when the same nail lacquer bottle and brush are used on multiple clients. In response, a series of experiments was performed to investigate microbe survival in nail lacquer. The results indicate that nail lacquers do not support micro-



Nail Cosmetics

Table 27.2 Common ingredients of nail lacquer and related products. Ingredient category and examples


Hard resins Nitrocellulose Acrylates co-polymer

Gloss Toughness

Soft resins Tosylamide/formaldehyde resin Polyvinyl butyral

Flexibility Adhesion

Solvents Ethyl acetate Butyl acetate Isopropyl alcohol Acetone (removers only)

Carrier for the resin and pigment Removing lacquer Soaking and removing UV-cured colors

Monomers and oligomers Polyurethane acrylate oligomer Hydroxypropyl methacrylate Various other acrylates and methacrylates

Hardens to hold color on nail Only in UV-curable colors, not standard lacquer

Photoinitiators Benzoyl isopropanol Hydroxycyclohexyl phenyl ketone

Initiates the light cure reaction Only in UV-curable colors, not standard lacquer

Colorants FDA/EU approved colorant Mica


Plasticizers Camphor Dibutyl phthalate (formerly)

Keeps resin flexible to prevent chipping

Thixotropic agents Stearalkonium hectorite Stearalkonium bentonite UV stabilizers Benzophenone-1 Etocrylene

Controls flow Suspends pigment until use

Prevents light-induced color fading

Hardeners Formalin Dimethyl urea

Hardens nail protein by cross-linking Only in hardener products

Hydrolyzed proteins Keratin Wheat, oats, etc.

Thought to bond with formalin and nail protein Usually used in hardeners

bial growth in the laboratory or salon (OPI Products Inc., and Nail Manufacturers Council, unpublished data) [13]. The solvents are sufficiently hostile to microbes that no preservative is required. This does not apply to water-based products, because water is required for microbial growth. Although solvent-based water-free lacquer is hostile to microbes, it would be a mistake to assume that it has any curative value for nail fungus or other infections.


Nail hardeners Modern nail hardeners are quite a contrast to an antique method of nail hardening which used fire. On the early American frontier, the combat sport called “rough and tumble” or “gouging” allowed fingernails to be used as weapons, and expert “gougers” hardened their nails by

27. Colored nail cosmetics and hardeners heating them over candles [14]. The heat of the candle flame caused cross-linking of the nail proteins. Modern nail hardeners contain a chemical cross-linking agent. Otherwise, their composition is similar to ordinary nail lacquer. As with lacquers, care must be taken to avoid skin contact during application to avoid allergic sensitization, particularly to the most common hardener, formalin (which is mistakenly equated with “formaldehyde” under current labeling rules.) Formalin cross-links proteins primarily by reacting with their nitrogen-containing side groups, forming methylene bridges [15]. Overuse causes too many cross-links, reducing the flexibility of the protein and causing brittleness, yellowing, and cracking of the nails. Manufacturers generally recommend avoiding overuse by cycling the products, alternating between the hardener and a non-hardening topcoat every week or two. Other hardeners include dimethyl urea (DMU), which is does not cross-link as aggressively as formalin. It is also less allergenic [16]. Glyoxal, a relative of formaldehyde, is larger and less able to penetrate the skin, also contributing to reduced allergenicity. Hydrolyzed proteins are common additives in hardeners and may chemically bond to the formalin. Many nail hardeners are simply clear lacquers with no cross-linking agents at all. These products rely on the

Figure 27.7 Brittle nail. Reproduced by permission of Nails Magazine.

strength of the resins to protect the nails. Until DMU or some other alternative proves itself, the most effective nail hardeners will likely continue to rely on formalin.

Formaldehyde issues Formalin, formaldehyde, and tosylamide/formaldehyde resin warrant some additional discussion. True formaldehyde is a highly reactive gas. Obviously, it cannot be a part of nail products in that form. It is therefore combined with water to make a product traditionally called “formalin.” Formalin contains water and a reaction product of water and formaldehyde, properly known as methylene glycol. Published literature [17] on the hydration of formaldehyde reveals a chemical equilibrium constant for this reaction, which confirms the near complete conversion of formaldehyde to methylene glycol. This chemical equilibrium constant yields the presence of 0.0782% free formaldehyde in formalin. A nail hardener that is 1.5% formalin, the typical upper limit, therefore contains less than 0.0012% or 12 parts per million of formaldehyde. This is not to dismiss “formaldehyde allergy”, which causes significant suffering to some patients, but it would be more accurately known as methylene glycol or formalin allergy (Figure 27.8). Unlike formaldehyde, methylene glycol is non-volatile; this explains why a California study showed that formaldehyde gas levels in nail salons were not above the normal background levels found in other settings such as offices [8]. This is significant because the only identified cancer risk associated with formaldehyde exposure results from inhalation in industrial settings [18], not cosmetic skin or nail exposure. Tosylamide/formaldehyde resin is also a cause for controversy solely because of the word “formaldehyde” in its name. It is an inert macromolecule, created by reacting tosylamide and formaldehyde. However, the formaldehyde is consumed in the reaction, and any leftover formaldehyde is hydrated to methylene glycol by the water molecules generated in the reaction. Hence the formaldehyde content of the resin is essentially nil. However, allergies nevertheless occur; it has been speculated that trace formaldehyde is




H Figure 27.8 Formaldehyde versus methylene glycol. Reproduced by permission of OPI Products, Inc.




Formaldehyde (gas)



Methylene glycol (liquid)




Nail Cosmetics CH3












Figure 27.9 Tosylamide formaldehyde resin. Reproduced by permission of OPI Products, Inc.



responsible but sensitization to tosylamide/formaldehyde resin can occur in the absence of formaldehyde sensitization [19,20], and tests indicate that side products of the synthesis reaction can be responsible for the resin allergies [21] (Figure 27.9). A final concern occasionally raised regarding formaldehyde is its absence. Because formaldehyde-releasing agents have a long history as preservatives in other forms of cosmetics, it is sometimes mistakenly assumed that formaldehyde was added to nail lacquer for preservative purposes. As a result, publicity regarding “formaldehyde-free” products has inspired fears of microbial cross-contamination via nail lacquer brushes. As noted above, experiments have shown that solvent-based nail lacquer is hostile to microbes and needs neither formaldehyde nor any other preservative.


Table 27.3 Common health effects of nail color ingredients. Ingredients

Health concerns


Possible allergies, particularly to tosylamide/formaldehyde resin


Dehydration and defatting of skin and nails Irritant dermatitis

UV-curable acrylates/methacrylates

Allergy after repeated exposure to uncured monomer or oligomer


Possible allergies Possible photosensitization


Occasional staining Occasional allergies


Possible allergies Camphor exposure is contraindicated for some patients with fibromyalgia

Thixotropic agents

None known

UV stabilizers

Possible allergies

Hardeners (cross-linkers)

Formalin sensitization and allergies are common Overuse may cause brittleness or splitting of nail Not recommended for nails that are already brittle

Hydrolyzed proteins

Possible allergies May trigger gluten sensitivity via transfer to mouth

UV-cured “lacquers” UV-cured nail enhancements are discussed elsewhere (Chapter 28); however, a relatively new class of UV-curing nail “lacquers” merits mention here. The same pigments are used as in standard nail lacquer but instead of a solvent/resin base, curable methacrylate or acrylate oligomers and monomers are used. A photoinitiator causes polymerization of the monomers on exposure to UV light, leaving a polymer/ pigment coat. Unlike the products to create nail enhancements, these curable colored products are not used to sculpt nails, but are designed to apply as a thin coat of color, resembling conventional lacquer. Allergic sensitization may result from repeated skin exposure to uncured or incompletely cured monomers; the fully cured coat is inert. Good manicuring technique can mitigate this risk, but once an allergy is established it is irreversible. Allergies to the photoinitiators and pigments are also possible. The low-power UVA lamps used to activate the photoinitiator are comparable to summer sunshine [10], so the 1–3 minute curing time poses no hazard to healthy skin (Table 27.3).


Nail lacquer removers In contrast to nail enhancements for nail elongation purposes, no polymerization takes place during the drying of nail lacquer; the resin is simply deposited on the nail as the

27. Colored nail cosmetics and hardeners

Figure 27.10 UV curing lamp. Reproduced by permission of OPI Products, Inc.

solvent evaporates. Therefore, removing nail lacquer is easy: it can be redissolved and wiped off with a solvent-soaked cloth pad, tissue, or cotton ball. Any solvent that dissolves the resin, and is safe for skin exposure, can be successfully used. Although UV-curable nail colors are polymerized, they are far less cross-linked than enhancements, and can be removed with a short acetone soak. Acetone, chemically known as dimethyl ketone or 2propanone, is the preferred solvent, because it is the least physiologically hazardous. Other removers are based on ethyl acetate or methyl ethyl ketone (MEK). Ethyl acetate has the advantage of not damaging acrylic nails, so it is used for removing lacquer from nail elongation enhancements. However, because of air quality regulations in California, ethyl acetate, MEK, and most other acetone alternatives are prohibited for nail lacquer removers, and other states and countries are considering similar actions. Acetone is exempt because its atmospheric breakdown produces less photochemical smog than almost any other solvent. One other “clean air” solvent, methyl acetate, is allowed in California, but has been avoided by most manufacturers because of toxicity concerns; those who use it add an embittering agent to deter accidental ingestion. Other hazardous solvents such as methanol and acetonitrile are seldom used, and are not California-compliant (Figure 27.11). All solvents can have significant drying and defatting effects on the skin, leading to irritation. This can be mitigated by using a lacquer remover with added moisturizers, or by using lotion afterwards. Drying and cracking of the nail can also result; oiling the nail is the most common way to counteract this. Some removers contain fragrances or botanical additives, which may pose allergy risks. Low-odor, non-volatile removers have been created based on methylated vegetable oils and/or various dibasic esters. As with water-based nail lacquer, however, the slow speed of nail polish removal with these products prevents them from finding general marketplace acceptance. These products are less damaging to the skin barrier.

Figure 27.11 Polish remover in action. Reproduced by permission of OPI Products, Inc.

Conclusions and future developments Arguably the largest potential for future improvement lies in cleaner application techniques, not new products. As more cases of manicure-transmitted infection are publicized, customers and governments will demand that nail technicians practice proper sanitation and disinfection. Most manufacturers are looking to develop “greener” products, whether in perception or reality. The trends away from toluene and DBP will surely continue, as will efforts to find a functional substitute for formalin. As for removers, most likely only acetone will survive the regulatory concerns. Water-based and UV-cured products have the potential to reduce solvent emissions, but still have unresolved disadvantages compared to traditional lacquers. Research continues in realm of nail polish as adding nail color is commonly practiced form of adornment.

References 1 Gorton A. (1993) History of nail care. Nails, February. Torrance, CA: Bobit Business Media. 2 Schultes SE. (Ed.) (2007) Miladay’s Standard Nail Technology, 5th edn. New York: Thomson Delmar Learning, pp. 129–32. 3 Baran R, Maibach HI. (2004) Textbook of Cosmetic Dermatology. New York: Taylor & Francis, p. 295. 4 Lee W. (2005) Bill targets nail salon outbreaks. Los Angeles Times, August 25, p. B-1. 5 Anon. (2002) Nightmare manicure: woman who says she got herpes from manicure is awarded $3.1 million, May 29. 6 Linden C, Berg M, Färm G, Wrangsjö K. (1993) Nail varnish allergy with far reaching consequences. Br J Dermatol 128, 57–62. 7 Frosh PJ, Menne T, Lepoittevin JP. (2006) Contact Dermatitis, 4th edn. Basel: Birkhäuser, p. 499.



Nail Cosmetics

8 McNary JE, Jackson EM. (2007) Inhalation exposure to formaldehyde and toluene in the same occupational and consumer setting. Inhalat Toxicol 19, 573–6. 9 Dibutyl phthalate – Summary risk assessment (2003, with 2004 addendum), European Commission Joint Research Centre, Institute for Health and Consumer Protection, European Chemicals Bureau, Italy. 10 Schoon DD. (2005) Nail Structure and Product Chemistry, 2nd edn. New York: Thomson Delmar Learning. 11 Kurtzweil P. (1995) Fingernails: Looking good while playing safe. FDA Consumer Magazine, December. 12 US Food And Drug Administration (1993) Answers, September 3. Available from: ANS00529.html; retrieved September 3, 2008. 13 Nail Manufacturers Council (NMC) data, publication forthcoming. 14 Fischer DH. (1989) Albion’s Seed: Four British Folkways in America. Oxford: Oxford University Press, p. 738. 15 Kiernan JA. (2000) Formaldehyde, formalin, paraformaldehyde and glutaraldehyde: What they are and what they do. Microscopy Today 00-1, 8. 16 Schoon DD. (2005) Formaldehyde vs. DMU; What’s the Difference? Vista, CA: Creative Nail Design. Available from: www.






21; retrieved August 25, 2008. Winkelman JGM, Voorwinde OK, Ottens M, Beenackers AACM, Janssen LPBM. (2002) Kinetics and chemical equilibrium of the hydration of formaldehyde. Chem Engineering Sci 57, 4067–76. International Agency for Research on Cancer (IARC) – Summaries & Evaluations (Group 2A) (1995) Formaldehyde. 62, 217. Available at: formal.html; retrieved July 4, 2009. Fuchs T, Gutgesell C. (1996) Is contact allergy to toluene sulphonamide-formaldehyde resin common? Br J Dermatol 135, 1013–14. Final Report on Hazard Classification of Common Skin Sensitisers (January 2005), National Industrial Chemicals Notification and Assessment Scheme, Australian Government, Department of Health and Ageing, p. 106. Hausen BM, Milbrodt M, Koenig WA. (1995) The allergens of nail polish. (I). Allergenic constituents of common nail polish and toluenesulfonamide-formaldehyde resin (TS-F-R), Contact Dermatitis 33(3), 157–64.

Chapter 28: Cosmetic prostheses as artificial nail enhancements Douglas Schoon Schoon Scientific and Regulatory Consulting, Dana Point, CA, USA

BAS I C CONCEPTS • Artificial nail enhancements are commonly used to address malformed fingernails. • The major forms of artificial nail enhancements include nail wraps, liquid and powder, or UV gels. • Methacrylate monomer liquid systems remain the most widely used type of artificial nail enhancement. • Proper application of artificial nail enhancements can avoid infection and sensitization.

Introduction The natural nail plate can not only be cosmetically elongated and enhanced to beautify the hands, but also to effectively address discolored, thin, and weak or malformed fingernails. When used properly, these cosmetic products and services provide great value and enhance self-esteem. Artificial nails not only add thickness and strength to the nail plate, they extend its length, typically 0.25–0.75 inches. A skilled nail technician can closely mimic the length and shape of the final product to create natural-looking artificial nails. Certain techniques utilizing custom blending of colored products allow the appearance of the nail bed to be extended beyond its natural boundary, which can dramatically lengthen the appearance of the fingers (Figure 28.1). A typical nail salon client wears artificial nail products to correct problems they are having with their own natural nails such as discoloration, splitting, breaking, unattractive or deformed nails (i.e. median canal dystrophy or splinter hemorrhages). There are several basic types from which to choose: nail wraps, liquid and powder, or UV gels. An overview of each type is given in Table 28.1.

Liquid and powder Liquid and powder systems (“acrylic nails”) were the original artificial nail enhancements. These systems were similar to certain dental products made from methacrylate monomers and polymers. Methacrylates are structurally different

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

from acrylates, have different safety profiles, and should not be confused with one another. The literature frequently confuses methacrylates with acrylates and/or incorrectly suggests they are a single category (i.e. [meth] acrylate). The first structure shown in Figure 28.2 has a branching methyl group (–CH3) attached to the double bond of ethyl methacrylate. The branching changes both the size (10% larger) and shape of the methacrylate molecule, which reduces the potential for skin penetration. This helps explain why methacrylate monomers are less likely to cause adverse skin reactions than hom*ologous acrylate monomers (i.e. ethyl acrylate and ethyl methacrylate). It is also one important reason why artificial nails containing acrylates are more likely to cause adverse skin reactions than those based solely on methacrylate monomers [1]. Methacrylate monomer liquid systems remain the most widely used type of artificial nail enhancement in the world. The “liquid” is actually a complex mixture of ethyl methacrylate (60–95%) and other di- or tri-functional methacrylate monomers (3–5%) that provide cross-linking and improved durability, inhibitors such as hydroquinone (HQ) or methyl ether hydroquinone (MEHQ) (100–200 p.p.m.), UV stabilizers, catalysts such as dimethyl tolyamine (0.75–1.25%), flexibilizing plasticizers and other additives. The “powder” component is made from poly methyl and/or ethyl methacrylate polymer beads (approximately 50–80 μm), coated with 1–2% benzoyl peroxide as the polymerization initiator, colorants, opacifiers such as titanium dioxide, and other additives. Liquid and powder systems are applied by dipping a brush into the monomer liquid, wiping off the excess on the inside lip of a low volume container (3–5 mL) called a dappen dish. The excess monomer is removed by wiping the brush on the edge of the dappen dish. The tip of the brush is drawn through the polymer powder, also in a dappen dish, and a small bead or slurry forms at the end of the brush. Three to



Nail Cosmetics

Table 28.1 The three main types of artificial nail enhancements. Type


Also known as


Nail wraps

Cyanoacrylate monomers

Fiberglass wraps, resin wraps, no-light gels, silk or paper wraps

Spray, drops, powder, or fabric treated with an tertiary aromatic amine

Liquid and powder

Methacrylate monomers and polymers

Acrylic, porcelain nails, solar nails

Polymer powder treated with benzoyl peroxide; monomer liquid contains tertiary aromatic amine

UV gels

Urethane acrylate or urethane methacrylate oligomers/monomer

Gel nails UV gels Soak-off gels

Low-power UVA lamp to activate the photoinitiator and tertiary aromatic amine catalyst

Figure 28.1 The use of custom-blended colored powders with methacrylate monomers to “illusion sculpt” and extend the apparent length of a short nail bed while also correcting a habitually splitting nail plate. (Courtesy Creative Nail Design, Inc., Vista, CA, USA.)

six beads are normally applied and smoothed into shape with the brush. Pink powders are applied over the nail bed and white powders are used to simulate the free edge of the nail plate. The slurry immediately begins to polymerize and hardens on the nail within 2–3 minutes. Over 95% of the polymerization occurs in the first 5–10 minutes, but complete polymerization can take 24–48 hours [2]. After hardening, the nail is then shaped either by hand filing or with


an electric file to achieve the desired length and shape. The finished nail can be buffed to a high shine or nail color applied. Length is added to the nail plate in one of two ways: 1 Adhering an ABS plastic nail tip to the nail plate with a cyanoacrylate adhesive, coating the tip with the liquid and powder slurry, and filing as described above. This technique is called “tip and overlay.” 2 A non-stick (Mylar© or Teflon© coated paper) form is adhered underneath the free edge of the natural nail and used as a support and guide to which the liquid and powder slurry is applied, then shaped and filed. This technique is called “nail sculpting.” Proper preparation of the natural nail’s surface is the key to ensuring good adhesion. Before the service begins, natural nails should be thoroughly scrubbed with a clean, disinfected, soft-bristled brush to remove contaminants from the service of the nail plate as well as underneath the free edge (Figure 28.3). This removes surface oil and debris that can block adhesion. The nail is then lightly filed with a low grit abrasive file (180–240 grit) to increase surface area for better adhesion. Nail surface dehydrators containing drying agents such as isopropyl alcohol are applied to remove surface moisture and residual oils. Adhesion promoting “primers” are then applied to increase surface compatibility between the natural nail and artificial nail product. These adhesion promoters contain proprietary mixtures of hydroxylated monomers or oligomers, carboxylic acids, etc. In the past, methacrylic acid was frequently used but has fallen out of favor because of its potential as a skin and eye corrosive [3].

UV gels Products that cure under low intensity UVA lights, typically 435–325 nm, to create artificial nails are called “UV gels.” UVB and UVC are not used to create UV gel nails [4]. Unlike liquid and powder systems, UV gels are not mixed with

28. Artificial nail enhancements O O


Ethyl methacrylate Figure 28.2 Chemical structure differences between methacrylates and acrylates.

Ethyl acrylate



Molecular weight 114 Daltons

Molecular weight 100 Daltons

of the uppermost layers of UV gel products. This layer can also be observed with certain types of liquid monomers: “odorless” products that utilize hydroxyethyl or hydroxypropyl methacrylate as the main reactive monomer. This residual sticky surface layer is called the “oxygen inhibition layer” [5]. UV gels can be clear, tinted, or heavily colored. The natural nail is cleaned, filed, dehydrated, and coated with adhesion promoters. The UV gel is then applied to the nail, shaped, and finished in the same fashion as two-part liquid and powder systems and produces very similar looking results. In most cases, the same equipment used to create other types of artificial nails is used (Table 28.2). A notable exception is UV gel curing achieved by placing the artificial nail under a UVA lamp for 2–3 minutes per applied layer. Because UVA does not efficiently penetrate more than a few millimeters into the UV gel, these products are applied and cured in several successive layers. UV gels are also applied over ABS nail tips or non-stick nail forms to lengthen the appearance of the natural nail.

Nail wraps

Figure 28.3 Equipment used to create liquid and powder artificial nails. 1, Nail scrub brush; 2, dappen dishes containing liquid and powder; 3, Mylar nail form; 4, abrasive files; 5, nail enhancement application brush; 6, ABS preformed nail tips; 7, plastic-backed cotton pad; 8, Nitrile gloves; 9, N-95 dust mask. (Courtesy Paul Rollins Photography, Inc. Laguna Niguel, CA, USA.)

another substance to initiate the curing process. Historically, UV gels have been blends of polymerization photoinitiators (1–4%), urethane acrylate oligomers, and durability improving, cross-linking monomers (approximately 75–95%), and catalysts such as dimethyl tolyamine (0.75–1.25%). Newer formulations using urethane methacrylate oligomers and monomers lower the potential for adverse skin reactions. Rate of cure is a hindrance for UV-curable artificial nails. Slow cure rates allow atmospheric oxygen to prevent curing

Methyl and ethyl cyanoacrylate monomer is used not only for adhering ABS nail tips to the natural nail, but also to create artificial nail coatings called “nail wraps.” This technique is not widely used, but accounts for at least 1% of the worldwide market [6]. The natural nail is precleaned, shaped, and filed as described above, but the cyano functional group provides tremendous adhesion to the natural nail plate, eliminating the need for adhesion-promoting primers (Figure 28.4). Nail enhancements relying on cyanoacrylate monomers do not contain other cross-linking monomers and therefore are inherently weaker than cross-linking artificial nail enhancement systems. To improve durability and usefulness, a woven fabric (silk, linen, or fiberglass) is impregnated with cyanoacrylate monomer and adhered to the nail plate. Even so, these types of coatings are not strong enough to be sculpted on a non-stick nail form and cannot be extended beyond the free edge of the natural nail plate, unless the



Nail Cosmetics

Table 28.2 Specialized equipment used to create artificial nail enhancements. Item



Natural or synthetic hair brush for application, spreading, and shaping of monomer and oligomers products on the nail plate

Dappen dish

Small containers that hold liquid artificial nail monomer, oligomers, or polymer powders during the application process

Manual files

Wooden or plastic core boards coated with abrasive particles (e.g. silicon nitride, aluminium oxide or diamond) used to shape, shortening, smooth, thin, or buff both natural and artificial nails

Electric files

Handheld, variable speed, rotary motors that securely hold barrel-shaped abrasive bits and are use for the same purposes as manual files


Small clippers sometimes used to remove old artificial nail product from the nail plate

Wood stick

A thin, pencil-shaped, plastic implement used to remove cuticle tissue from the nail plate


Block shape, high grit abrasive buffers use for shape refining (180–240 grit) or buffing to a high shine (>1000 grit)

UV lamp

Electrical device that holds either 4 or 9 W UVA producing bulbs and is used to cure UV gel nail products

Cotton pads

Disposable pads or balls used to remove old nail polish and/or dusts after filing

Scrub brush

Soft bristle, disinfectable brushes used to clean natural and artificial nails

Nail forms

Mylar© or Teflon© coated paper used as a support and guide to extending artificial nails beyond the natural nail’s free edge

Nail tips

Preformed ABS plastic tips adhered to the natural nail to support artificial nail products and create nail extensions beyond the nail’s free edge

Wrap fabric

Loosely woven silk, linen, or fibreglass strips adhered to the natural nail plate with cyanoacrylate monomer to create nail wraps


Used to transfer product from larger containers into dappen dishes or to apply nail wrap curing accelerators


Slightly curved blades use for trimming or cutting natural nails and wrap fabrics

Disinfectant container

Containers designed to hold EPA registered disinfectants needed to properly disinfectant tools and implements

Remover bowl

Container that holds solvents (e.g. acetone) for artificial nail removal

nail wrap is applied over an ABS nail tip, as previously described. Usually, cyanoacrylate monomers are very low viscosity, mobile liquids, but they are sometimes thickened with polymers (e.g. polymethyl methacrylate) and used without a reinforcing fabric. Such systems are referred to as “no-light gels.” Cyanoacrylate monomers are applied without the use of a brush, directly from the container’s nozzle and will cure


upon exposure to moisture in the nail plate, but the process can be greatly hastened by solvent mixtures containing a tertiary aromatic amine such as dimethyl tolylamine (0.5– 1%), which is either sprayed on, applied with an dropper, or impregnated into the woven fabric. After curing (5–10 seconds), the nail wrap coating can be shaped and buffed to a high shine or nail color applied. This technique is also used to mend cracks or tears in the nail plate, by using the

28. Artificial nail enhancements

Figure 28.4 Materials needed to apply nail wraps. 1, Abrasive file for nail preparation and final shaping; 2, scissors for cutting fabric; 3, block buffer for high-shining; 4, cyanoacrylates; 5, spray-on catalyst; 6, silk fabric; 7, pusher to gently remove skin from the nail plate. (Courtesy Paul Rollins Photography, Inc. Laguna Niguel, CA, USA.)

cyanoacrylate monomer to adhere a small piece of fabric over the broken or damaged area of the plate.

Artificial nail removal Improper removal of artificial nails can lead to nail damage; however, they can be safely removed if the proper procedures are followed. Acetone (dimethyl ketone) is the preferred remover for artificial nail products, but methyl ethyl ketone (MEK) is also used. The artificial nails are placed in a small bowl and immersed in solvent. Nail wraps are the easiest to remove because they are not cross-linked polymers and have lower solvent resistance. They usually require less than 10 minutes immersion for full removal. Liquid and powder products are cross-linked polymers and can take 30–40 minutes to remove. UV gels are also cross-linked and these urethane acrylate or methacrylate based artificial nails have inherently greater solvent resistance so removal can take 45–60 minutes. The removal process is greatly accelerated by prefiling to remove the bulk of the artificial nail. Improper removal can cause significant damage to the nail plate. Prying or picking off the artificial nails can lead to onycholysis [7]. A common myth is that artificial nail should be regularly removed to allow nails to “breathe”; in reality they should only be removed when there is a need. Frequent removal is not advised.

Rebalancing As the natural nail grows, the artificial nail advances leaving a small space of uncoated nail plate. Every 2–3 weeks the

Figure 28.5 Example of an adverse skin reaction caused by repeated contact to the skin. (Courtesy Paul Rollins Photography, Inc. Laguna Niguel, CA, USA.)

nail technician will file the artificial nail down to one-third its thickness, reapply fresh product, and reshape the artificial nail, thereby covering the area of new growth. This process is called “rebalancing” and is essential to maintaining the durability and appearance of the artificial nail. “Soak-off gels” are highly plasticized, which softens the coating, making it more susceptible to solvent removal. This type of artificial nail often has low durability and therefore must be frequently removed and replaced, which can lead to excessive nail damage.

Adverse reactions Both nail technicians and those wearing artificial nails can develop adverse skin reactions if steps are not taken to avoid prolonged and/or repeated skin contact with artificial nail products. For example, the product should be applied to the nail plate in such a manner that skin contact is avoided (i.e. a tiny free margin left between the eponychium and artificial nail). Typically, reactions are a result of many months of overexposure to eponychium, hyponychium, or lateral side walls (Figure 28.5). Reactions can appear as paronychia, itching of the nail bed and, in extreme cases, paresthesia and/or loss of the nail plate [8,9]. Onycholysis can be a result of allergic reactions, but the nail plate is resistant to penetration from external agents and this condition is more likely to be caused by overly heavy handed, aggressive filing techniques with coarse abrasives or overzealous manicuring of the hyponychium area [10]. Allergic contact dermatitis can affect the chin, cheeks, and eyelids as a result of touching the face with the hands [11]. Filings and dusts may contain small amounts of unreacted monomers and oligomers, because it can take



Nail Cosmetics

24–40 hours for the artificial nails to finish the curing process. Nail technicians should be instructed to wash their hands thoroughly before touching the face or eye area. They should be warned to avoid contact with the dusts and filings, especially the oxygen inhibition layer created on the surface of UV gels and odorless monomer liquid systems (see above), which can contain substantial amounts of unreacted ingredients. Gloves (nitrile) and/or plastic-backed cotton pads should be used to remove the oxygen inhibition layer as skin contact should be avoided. The UV bulbs in the curing lamps should be changed every 2–4 months (depending on usage) to ensure thorough cure and lessen the amount of unreacted ingredients, thereby lowering the potential for adverse skin reactions. For liquid and powder systems, it is common for technicians to use excessive amounts of liquid monomer, creating a wet consistency bead. Nail technicians should avoid applying beads of product with a wet mix ratio because this can lower the degree of curing and increase the risk of overexposure to unreacted ingredients. Nail technicians should be instructed to avoid all skin contact with uncured artificial nail products or dusts and not to touch them to client’s skin prior to curing.

Nail damage and infection Avoiding the use of heavy grit abrasives (<180 grit) or electric files directly on the nail plate will lessen the potential for damage and injury (e.g. onycholysis). Plate damage can occur when nail technicians aggressively file the natural nail, rather than use safer, smoother abrasive files (>180 grit). These gentler methods also increase the surface area for better adhesion, but without overly thinning or damaging the nail plate. Methyl methacrylate (MMA) monomer is sometimes used illegally in artificial nail monomer liquids because of its low cost when compared to better alternatives (e.g. ethyl methacrylate [EMA]). MMA has very poor adhesion to the natural nail plate so technicians who use these liquid monomers frequently abrade away the uppermost layers of the natural nail plate to achieve significantly more adhesion by allowing for deposition into the more porous layers underneath. However, this poor technique can compromise the nail plate’s strength and durability, so liquid monomer MMA containing products should be avoided [12]. The other artificial nail systems described in this chapter have improved adhesion and do not require technicians to heavily abrade the nail plate in order to achieve proper adhesion. Infections can occur underneath the artificial nail to produce green or yellow stains (Figure 28.6). Several types of bacteria and dermatophytes can cause such infections (Pseudomonas aeruginosa, Staphylococcus aureus, Trichophyton rubrum). To avoid this, state regulations require nail techni-


Figure 28.6 Example of an nail infection growing underneath an artificial nail. (Courtesy Paul Rollins Photography, Inc. Laguna Niguel, CA, USA.)

cians to properly clean and disinfect all implements in an Environmental Protection Agency (EPA) registered disinfectant to avoid transmission of pathogenic organisms, and to dispose of all single-use items. Clients should wash their hands, scrubbing under the nails with a clean and disinfected, soft-bristled brush before receiving any services.

Education Almost every US state requires specialized nail training and education, typically 300–750 hours depending on the state, to obtain a professional license and some states have continuing education requirements. The textbooks teach a surprisingly wide range of topics including anatomy and physiology of the skin and nails, product chemistry, an overview of common nail related diseases and disorders, contamination and infection control and universal precautions, safe working practices, as well as manicuring, pedicuring, and the artificial nail techniques described in this chapter [13–15]. Multilingual information sources for proper use and other safety information can be found from a wide range of sources, including the EPA [16] and Nail Manufacturers Council [17].

References 1 Baran R, Maibach HI. (2005) Cosmetics for abnormal and pathologic nails. Textbook of Cosmetic Dermatology, 3rd edn. Taylor & Francis, London/New York, pp. 304–5. 2 Schoon D. (1994) Differential scanning calorimeter determinations of residual monomer in ethyl methacrylate fingernail formulations and two addendums. Unpublished data submitted by the Nail Manufacturers Council to the Cosmetic Ingredient Review (CIR) Expert Panel. 3 Woolf A, Shaw J. (1998) Childhood injuries from artificial nails primer cosmetic products. Arch Pediatr Adolesc Med 152, 41–6.

28. Artificial nail enhancements 4 Newman M. (2001) Essential chemistry of artificial nails. The Complete Nail Technician. London: Thompson Learning, p. 41. 5 Schoon D. (2005) Liquid and powder product chemistry. Nail Structure and Product Chemistry, 2nd edn. New York: Thomson Delmar Learning, p. 138. 6 Kanerva S, Fellman J, Storrs F. (1966) Occupational allergic contact dermatitis caused by photo bonded sculptured nail and the review on (meth) acrylates in nail cosmetics. Am J Contact Derm 7, 1–9. 7 Schoon D. (2005) Trauma and damage. Nail Structure and Product Chemistry, 2nd edn. New York: Thomson Delmar Learning, p. 52. 8 Fisher A, Baran R. (1991) Adverse reactions to acrylate sculptured nails with particular reference to prolonged paresthesia. Am J Contact Derm 2, 38–42. 9 Fisher A. (1980) Permanent loss of fingernails from sensitization and reaction to acrylics in a preparation designed to make artificial nails. J Dermatol Surg Oncol 6, 70–6. 10 Baran R, Dawber R, deBerker D, Haneke E, Tosti A. (2001) Cosmetics: the care and adornment of the nail. Disease of the

11 12

13 14 15



Nails and their Management, 3rd edn. Oxford: Blackwell Science, p. 367. Fitzgerald D, Enolish J. (1994) Widespread contact dermatitis from sculptured nails. Contact Derm 30, 118. Nail Manufactures Council (NMC). (2001) Update for Nail Technicians: Methyl Methacrylate Monomer. Scottsdale, AZ: Professional Beauty Association, Jefford J, Swain A. (2002) The Encyclopedia of Nails. London: Thompson Learning. Frangie C, Schoon D, et al. (2007) Milady’s Standard Nail Technology, 5th edn. New York: Thomson Delmar Learning. Schoon D. (2005) Trauma and damage. Nail Structure and Product Chemistry, 2nd edn. New York: Thomson Delmar Learning. United States Environmental Protection Agency (2007) Protecting the Health of Nail Salon Workers, Office of Pollution Prevention and Toxics. EPA no. 774-F-07-001. Nail Manufacturers Council (NMC). A series of safety related brochures for nail technicians. Scottsdale, AZ: Professional Beauty Association.


Part 3: Hair Cosmetics Chapter 29: Hair physiology and grooming Maria Hordinsky,1 Ana Paula Avancini Caramori,2 and Jeff C. Donovan3 1

Department of Dermatology, University of Minnesota, Minneapolis, MN, USA Department of Dermatology, Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, Brazil 3 Division of Dermatology, University of Toronto, Toronto, Canada 2

BAS I C CONCE P T S • The hair follicle is a complex structure that produces an equally complex structure, the hair fiber. • Human hair keratins consist of at least 19 acidic and basic proteins which are expressed in various compartments of the hair follicle. • The science behind modern shampoos and conditioners has led to the development of rationally designed products for normal, dry, or damaged hair.

Definitions The use of hair cosmetics is ubiquitous among men and women of all ages. Virgin hair is the healthiest and strongest but basic grooming and cosmetic manipulation cause hair to lose its cuticular scale, elasticity, and strength. Brushing, combing, and shampooing inflict damage on the hair shaft, much of which can be reversed with the use of hair conditioners. In this chapter, the physiology of hair, grooming techniques including the science and use of shampoos and conditioners, are reviewed.

Physiology Hair follicle The hair follicle is a complex structure that demonstrates the ability to completely regenerate itself – hair grows, falls out and then regrows. Plucked hairs can regrow. Important cells for the development of hair follicles include stem cells in the bulge region and dermal papilla cells [1]. Hair follicle stem cells are described as being present just below the entrance of the sebaceous duct into the hair follicle. The hair follicle’s complexity is further appreciated when examining the organization of follicles in the scalp and the complexity of

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


its vascular complex and nerve innervation. Scalp hair follicles present in groups of one, two, three, or four follicular units (Figure 29.1). The hair follicle is defined histologically as consisting of several layers (Figure 29.2). It is the interaction of these layers that produces the hair fiber. The internal root sheath consists of a cuticle which interdigitates with the cuticle of the hair fiber, followed by Huxley’s layer, then Henle’s layer. Henle’s layer is the first to become keratinized, followed by the cuticle of the inner root sheath. The Huxley layer contains trichohyalin granules and serves as a substrate for citrulline-rich proteins in the hair follicle. The outer root sheath has specific keratin pairs, K5–K16, characteristic of basal keratinocytes and the K6–K16 pair characteristic of hyperproliferative keratinocytes, similar to what is seen in the epidermis. Keratin K19 has been located in the bulge region [2,3]. The complexity of the hair follicle is further demonstrated by the fact the follicle cycles from the actively growing phase (anagen), through a transition phase (catagen), and finally a loss phase (telogen). The signals associated with the transition from anagen, catagen to telogen are the subject of current research activities in this field.

Product of the hair follicle: the hair fiber The hair follicle generates a complex fiber which may be straight, curly, or somewhere in between. The main constituents of hair fibers are sulfur-rich proteins, lipids, water, melanin, and trace elements. The cross-section of a hair shaft has three major components, from the outside to the inside: the cuticle, the cortex and the medulla [4].

29. Hair physiology and grooming



Figure 29.1 (a) Horizontal section of a 4 mm scalp biopsy specimen demonstrating follicular units containing 1, 2, 3, or 5 anagen follicles. (b) Vertical section of a 4-mm scalp punch biopsy specimen from a normal, healthy Caucasian female in her early twenties.

Fibers can be characterized by color, shaft shape – straight, arched, or curly – as well as microscopic features. The cuticle can be defined by its shape – smooth, serrated, or damaged, and whether or not it is pigmented. The cortex can be described by its color and the medulla by its distribution in fibers. It can be absent, uniform, or randomly distributed. Lastly, fibers can be abnormal and present with structural hair abnormalities such as trichoschisis or trichorrhexis nodosa. Both of these structural abnormalities can commonly be seen in patients with hair fiber injury related to routine and daily cosmetic techniques including application of high heat, frequent perming as well as from weathering, the progressive degeneration from the root to the tip of the hair initially affecting the cuticle, then later the cortex [3]. The cuticle is also composed of keratin and consists of 6–8 layers of flattened overlapping cells resembling scales. The cuticle consists of two parts: endocuticle and exocuticle. The exocuticle lies closer to the external surface and comprises three parts: b-layer, a-layer, and epicuticle. The epicuticle is a hydrophobic lipid layer of 18-methyleicosanoic acid on the surface of the fiber, or the f-layer. The cuticle protects the underlying cortex and acts as a barrier and is considered to be responsible for the luster and the texture of hair. When damaged by frictional forces or chemicals and subsequent removal of the f-layer, the first hydrophobic defense, the hair fiber becomes much more fragile. The cortex is the major component of the hair shaft. It lies below the cuticle and contributes to the mechanical properties of the hair fiber, including strength and elasticity. The cortex consists of elongated shaped cortical cells rich in

keratin filaments as well as an amorphous matrix of sulfur proteins. Cysteine residues in adjacent keratin filaments form covalent disulfide bonds, which confer shape, stability, and resilience to the hair shaft. Other weaker bonds such as the van der Waals interactions, hydrogen bonds and coulombic interactions, known as salt links, have a minor role. These bonds can be easily broken just by wetting the hair. It is the presence of melanin in the cortex that gives hair color; otherwise, the fiber would not be pigmented [4]. The medulla appears as continuous, discontinuous, or absent under microscopic examination of human hair fibers. It is viewed as a framework of keratin supporting thin shells of amorphous material bonding air spaces of variable size [4]. Fibers with large medullas can be seen in samples obtained from porcupines or other animal species. Other than in gray hairs, human hairs show great variation in their medullas.

Human hair keratins Human hair keratins are complex and, until recently, research suggested that the hair keratin family consisted of 15 members, nine type I acidic and six type II basic keratins, which exhibited a particularly complex expression pattern in the hair-forming compartment of the follicle (Figure 29.2). However, recent genome analyses in two laboratories has led to the complete elucidation of human type I and II keratin gene domains as well as a completion of their complementary DNA sequences revealing an additional small hair keratin subcluster consisting of genes KRT40 and KRT39. The discovery of these novel genes brought the hair keratin family to a total of 17 members [3].



Hair Cosmetics
















CU mod






CU dp





CU dp

dp K40













Figure 29.2 Schematic presentation of the complex pattern of hair keratin expression in the human hair follicle. (Reprinted by permission from Macmillan Publishers Ltd, J Invest Dermatol 127, 1532–5, 2007.)


*Zone of keratinization*

Ku Hu Ho

Suprabasal Basal





K36 K33a K86 K33b K83 K37** K81


K38* (Ha8)


Start of mRNA/protein synthesis

K81 (Hb1) K83 (Hb3) K86 (Hb6)

K37** (Ha7)

K33a (Ha3-I) K33b (Hb3-II) K36 (Ha6) K31 (Ha1)

K85 (Hb5)


K35 (Hb5)

K82 (Hb2) K85 (Hb5)

K35 (Ha5) K32 (Ha2)



Type II




Type I

Ho Hu Ku

Basal Suprabasal

K39 (Ka35)

K39 (Ka35) K40 (Ka36)


Zones of mRNA/protein synthesis

K34 (Ha4)


K32+K40 Hair fiber










29. Hair physiology and grooming The human type II hair keratin subfamily consists of six individual members which are divided into two groups. Group A members hHb1, hHb3, and hHb6 are structurally related, while group C members hHb2, hHb4, and hHb5 are considered to be rather distinct. Both in situ hybridization and immunohistochemistry on anagen hair follicles have demonstrated that hHb5 and hHb2 are present in the early stages of hair differentiation in the matrix (hHb5) and cuticle (hHb5, hHb2), respectively. Cortical cells simultaneously express hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In contrast, hHb4, has been undetectable in hair follicle extracts and sections, but has been identified as the most significant member of this subfamily in cytoskeletal extracts of dorsal tongue [3].

Grooming Shampoos: formulations and diversity Cleaning hair is viewed as a complex task because of the area that needs to be treated. The shampoo product has to also do two things – maintain scalp hygiene and beautify hair. A well-designed conditioning shampoo can provide shine to fibers and improve manageability, whereas a shampoo with high detergent properties can remove the outer cuticle and leave hair frizzy and dull.

Formulations Shampoos contain molecules with both lipophilic and hydrophilic sites. The lipophilic sites bind to sebum and oilsoluble dirt and the hydrophilic sites bind to water, permitting removal of the sebum with water rinses. There are four basic categories of shampoo detergents: anionics, cationics, amphoterics, and non-ionics (Table 29.1). A typical shampoo will typically have two detergents. Anionic detergents have a negatively charged hydrophilic polar group and are quite good at removing sebum; however, they tend to leave hair

Table 29.1 Four categories of shampoo detergents. 1. Anionics Lauryl sulfate Laureth sulfates Sarcosines Sulfosuccinates 2. Cationics

rough, dull, and subject to static electricity. In contrast, ampotheric detergents contain both an anionic and a cationic group allowing them to work as cationic detergents at low pH and as anionic detergents at high pH. Ampotheric detergents are commonly found in baby shampoos and in shampoos designed for hair that is fine or chemically treated [5]. The number of shampoo formulations on the market can be overwhelming but when the chemistry behind those marketed for “normal hair” or “dry hair” is understood, recommending the best product becomes easier (Table 29.2). Shampoos for “normal” hair typically have lauryl sulfate as the main detergent and provide good cleaning of the scalp. These are best utilized by those who do not have chemically treated hair. Shampoos designed for “dry hair” primarily provide mild cleansing but also excellent conditioning. An addition to shampoo categories has been the introduction of conditioning shampoos which both clean and condition. The detergents in these types of shampoos tend to be amphoterics and anionics of the sulfosuccinate type. These work well for those with chemically damaged hair and those who prefer to shampoo frequently. For individuals with significant sebum production, oily hair shampoos containing lauryl sulfate or sulfosuccinate detergents can work well but can by drying to the hair fiber. Hydrolyzed animal protein or dimethicone are added to conditioning shampoos, also commonly called 2-in-1 shampoos. These chemicals create a thin film on the hair shaft to increase manageability and even shine. For individuals with tightly kinked hair, conditioning shampoos with both cleaning and conditioning characteristics that are a variant of the 2-in-1 shampoo can be beneficial. These shampoos can be formulated with wheatgerm oil, steartrimonium hydrolyzed animal protein, lanolin derivatives, or dimethicone and are designed for use either weekly or every 2 weeks.

Conditioners Conditioners can be liquids, creams, pastes, or gels that function like sebum, making hair manageable and glossy appearing. Conditioners reduce static electricity between fibers following combing or brushing by depositing charged ions on the hair shaft and neutralizing the electrical charge. Another benefit from conditioners is improved hair shine

Table 29.2 Categories of shampoos are available for the following hair types.

3. Amphoterics Betaines such as cocamidopropyl betaine Sultaines Imidazolinium derivatives

Normal hair

4. Non-ionics

Tightly kinked hair

Dry hair Oily hair



Hair Cosmetics

Table 29.3 Categories of hair conditioners. Category

Primary ingredient

Cationic detergent

Quaternary ammonium compounds




Hydrolyzed proteins


Dimethicone Cyclomethicone Amodimethicone

reduce static electricity and friction. Dimethicone is the most common form of silicone used.

Conclusions The hair follicle is recognized as being a complex structure consisting of at least 17 different keratins as well as lipids, water, melanin, and trace elements. The follicle produces an equally complicated structure, the hair fiber which may be straight, wavy, or curly. Hair is cited as a factor contributing to attractiveness and is frequently styled to convey cultural affiliations [4].

References which is related to hair shaft light reflection. Conditioners may also improve the quality of hair fibers by reapproximating the medulla and cortex in frayed fibers [5,6]. There are several hair conditioner product types including instant, deep, leave-in, and rinse. The instant conditioner aids with wet combing; the deep conditioner is applied for 20–30 minutes and works well for chemically damaged hair. A leave-in conditioner is typically applied to towel dried hair and facilitates combing. A rinse conditioner is one used following shampooing and also aids in disentangling hair fibers. There are at least four conditioner categories, summarized in Table 29.3. The quaternary conditioners are cationic detergents. The film-forming conditioners function by coating fibers with a thin polymer layer. Protein-containing conditioners contain small proteins with a molecular weight of 1000–10 000 Da. These penetrate the hair shaft and are thought to increase fiber strength temporarily. Silicone conditioners form a thin film on the hair shaft and, by doing so,


1 Cotsarelis G, Millar SE. (2001) Towards a molecular understanding of hair loss and its treatment. Trends Mol Biol 293–301. 2 Langbein L, Rogers MA, Praetzel-Wunder S, Böckler D, Schirmacher P, Schweizer J. (2007) Novel type I hair keratins K39 and K40 are the last to be expressed in differentiation of the hair: completion of the human hair keratin catalog. J Invest Dermatol 127, 1532–5. 3 Langbein L, Rogers MA, Winter H, Praetzel S, Schweizer J. (2001) The catalog of human hair keratins. II. Expression of the six type II members in the hair follicle and the combined catalong of human type I and type II keratins. J Biol Chem 34, 35123–32. 4 Gray J. (2008) Human hair. In: McMichael A, Hordinsky M, eds. Hair and Scalp Diseases. New York: Informa Healthcare, pp. 1–17. 5 Draelos ZD. (2008) Nonmedicated grooming products and beauty treatments. In: McMichael A, Hordinsky M, eds. Hair and Scalp Diseases. New York: Informa Healthcare, pp. 59–72. 6 McMullen R, Jachowicz J. (2003) Optical properties of hair: effect of treatments on luster as quantified by image analysis. J Cosmet Sci 54, 335–51.

Chapter 30: Hair dyes Frauke Neuser1 and Harald Schlatter2 1 2

Procter & Gamble Technical Centres Ltd, Egham, Surrey, UK Procter & Gamble German Innovation Centre, Darmstadt, Germany

BAS I C CONCEPTS • Hair dyes are a cosmetic product category that can be traced back thousands of years. Modern hair dyes have been developed since the late 19th century and are now available in a broad range of products delivering a variety of color results and usage conditions. • Hair dyes constitute a large product category – over 70% of women in the developed world color their hair at least once, and many do so regularly. Psychologic aspects of color transformation should not be underestimated; especially dyeing gray hair can contribute significantly to the confidence and self-perceived attractiveness of many people. • Within the category, permanent or oxidative hair dyes represent the largest market share with around 80% of all products. A combination of hydrogen peroxide and an alkalizing agent (typically ammonia) form the basis to lighten the natural hair color while at the same time depositing oxidatively coupled dyes inside the hair shaft. • Disadvantages of using particularly permanent hair dyes regularly include a high maintenance routine, and changes to the hair structure which require special care and attention. • Because of the complex chemistry of hair dyes, safety and regulatory criteria are important aspects of modern hair dyes. Special emphasis needs to be put on proper safety and use instructions to further minimize a potential allergy risk.

Introduction Modern hair dyes offer a broad range of products and a variety of color results. They constitute a large category – over 70% of women in the developed world color their hair at least once, and many do so regularly. The number one reason for dyeing hair is to cover gray hair and look younger. Within the category, permanent or oxidative hair dyes represent the largest market share with around 80% of all products. A combination of hydrogen peroxide and an alkalizing agent (typically ammonia) form the basis to lighten the natural hair color while at the same time depositing wash-resistant color complexes inside the hair shaft. Because of the complex chemistry of hair dyes, safety and regulatory criteria are important aspects of modern hair dyes. Special emphasis needs to be put on proper safety and use instructions to further minimize a potential allergy risk.

thousands of years humans have attempted to enhance or change their natural hair color, initially with the help of natural preparations such as kohl and henna [1], nowadays with modern products which offer anything from subtle results to dramatic changes. Hair dyes can be defined as products that alter the color appearance of hair temporarily or permanently, by removing some of the existing color and/or adding new color. They constitute a significant category in the cosmetics market – it is estimated that over 70% of women in the developed world have used hair color, and a large proportion of those do so regularly [2]. Consumers have the choice between home hair dye kits, and having their hair dyed professionally at a salon. While each woman may have a very individual reason for coloring her hair, covering gray can be considered a universal key motivator. Other desired performance aspects include enhancing the existing color, wanting a different color from the one given by nature, or achieving a more striking looking appearance.

Definitions Product subtypes Natural hair color manifests itself in a vast multitude of shades and tones – from the lightest blonde and warmest brunette to the most vibrant red and deepest black. Yet, for

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.

• Temporary hair dyes. • Semi-permanent hair dyes. • Permanent (oxidative) hair dyes. • Hair bleaching. A wide range of products for changing the color of hair is available to consumers. Today’s hair dyes can remove (lift)



Hair Cosmetics

Table 30.1 Overview of hair dye product types. Hair dye product types

Dye technology

Level of lastingness


Preformed FD&C and D&C dyes

Wash out (with one wash)


Preformed HC and disperse dyes

Wash out (with 6–8 washes)


Oxidative dyes, reduced peroxide concentration

Wash out (with up to 24 washes)


Oxidative dyes

Permanent (grows out)


Oxidative bleaching, no dye deposition

Permanent (grows out)

D&C, dyes to be used in drugs and cosmetics; FD&C, dyes allowed to be used in food, drugs and cosmetics; HC, dyes to be used in hair colorants.

Figure 30.1 Hair cross-section showing color penetration after semi-permanent dyeing.

natural hair color, add (deposit) new artificial color, or indeed do both at the same time. They offer a variety of results, from a subtle color refresher to a significant change in the natural hair color, based on very different dye technologies. The classification of hair dyes is based on the permanency of the induced color change (Table 30.1). It should be noted that home and salon hair dyes are based on the same technologies, while there are key differences in shade and application variety.

Nitro-dyes are the most important group of dyes used in semi-permanent colorants [5]. These uncharged (non-ionic) dyes are barely influenced by negative charges on the surface of the hair. As a result, and because of their relatively small size, they are able to penetrate into the hair cuticle. Washing hair opens the cuticle, allowing color to escape over time because of the solubility of the dyes in water. The products contain a mixture of preformed dyes and are usually on the hair for approximately 20–30 minutes. Color results are limited (no lightening, blend away first grays).

Temporary dyes

Demi-permanent and permanent dyes

Temporary dyes or color rinses are usually formulated with high molecular weight acid or dispersed dyes, which have little affinity for hair and are quite soluble in the dye base. The dye is complexed with a cationic polymer to decrease solubility and increase affinity for hair, and the complex dispersed in the dye base by surfactants. The complex coats the hair and excess can be rinsed off [3]. The binding forces between hair substrate and dyes are low so color is easily washed out after the first shampoo. Each product contains a mixture of generally two to five color ingredients to achieve the desired shade [4]. Typical product forms include shampoos and sprays. While color results are very limited (no lightening, no grey coverage), temporary dyes may be a good option to test colors or refresh dyed hair.

Demi-permanent and permanent hair dyes involve oxidative chemistry, requiring different product components to be mixed just before they are applied. Oxidative dyes are the most frequently used and commercially most relevant hair dyes. Within this category we differentiate two product groups: permanent and demi-permanent dyes. The primary distinctions between those two are the type and level of alkalizing agent and the concentration of peroxide, which result in different color results with regard to lastingness, gray coverage, and lightening performance. Demi-permanent colors typically use 2% hydrogen peroxide (concentration on head) and low levels of alkalizer (usually monoethanolamine, not ammonia), leading to a less efficient dye penetration (ring dye effect; Figure 30.2). They wash out in up to 24 shampoos. While they can be used to enhance and brighten natural color and blend or cover up grays up to 50%, they have little or no lightening potential. Permanent colorants use up to 6% peroxide (concentration on head) and contain ammonia as alkalizer to bring the pH of the final product to 9.0–10.5. This allows complete penetration across the cortex (Figure 30.3). They are the

Semi-permanent dyes Semi-permanent hair dyes use a combination of preformed (direct) dyes to obtain results that last up to 6–8 shampoos. The dyes are generally characterized by their low molecular weight, allowing them to diffuse into the outer cuticle layers without binding firmly to the hair protein (Figure 30.1).


30. Hair dyes reapplication is needed to prevent visible regrowth of the naturally darker hair.

Chemistry Natural hair pigmentation

Figure 30.2 Hair cross-section showing color penetration after demi-permanent dyeing.

Figure 30.3 Hair cross-section showing color penetration after permanent dyeing.

most versatile and long-lasting hair dyes and are also available in the widest spectrum of shades. Permanent dyes can lighten hair significantly, change color in subtle or dramatic ways, and provide 100% gray coverage, even on resistant grays. Reapplication is required every 4–6 weeks to avoid a noticeable regrowth at the root line.

Bleaches Hair bleaches are products that lighten hair without adding a new color. In addition to hydrogen peroxide and ammonia they contain persulfates to boost and accelerate the bleaching efficacy. Bleaching is the most efficient method of lightening natural and precolored hair. In the case of a partial bleaching, especially on very dark hair, the results can be an unwanted yellow to orange-colored shade. Bleaches can lift the natural hair color most significantly and are often used with special techniques to apply highlighting effects to hair. Just as with permanent dyes, regular

The natural coloration of hair is caused by the presence of melanin in the cortex of the hair shaft, which occurs in the form of minute pigment granules. All natural hair color shades are created by just two types of melanin: the more common brownish black eumelanin, and the less common reddish yellow pheomelanin. The final color of hair is determined by the amount of melanin it contains, by the size of the pigment granules, and by the ratio between the two melanin types [6]. Black hair contains eumelanin in high concentration, whereas we find less pigment overall – and higher ratios of pheomelanin – in blonde and red hair. Despite clear differences in molecular size and general properties, the two melanin types are biogenetically related and develop from a common metabolic pathway involving dopaquinone as a key intermediate [7]. The pigments are present as oval or spherical granules, generally in the range 0.2–0.8 μm in length, and constitute less than 3% of the total hair mass [4]. Production of the pigment particles is located in specialized cells, the melanocytes, deep within the hair follicle. Melanocytes are hidden in the dermal papilla of the hair bulb where they secrete tiny packages called melanosomes into the surrounding keratinocytes. Natural hair color changes are often observed over the years from birth to old age. Many fair-haired children gradually become darker and by middle age have brown hair. Graying hair affects all to a greater or lesser extent as part of the aging process. It seems to appear earlier in dark- than in light-haired people, and is less common in black people. Graying of the hair is usually a gradual process and irreversible. The reason for going gray is not the production of a new “gray” pigment, but the visual result of a mixture of dark and non-pigmented, colorless hair. Due to the dispersion of light, hair which no longer contains any melanin appears to be white. The precise causes of graying hair are still under discussion. Hereditary factors seem to be predominant, meaning that genes regulate the exhaustion of the pigmentary potential of each individual hair follicle leading to reduced melanogenic activity with age. Recent research specifically traced the loss of hair color to the gradual dying off of melanocyte stem cells. Not only do they become exhausted with age, they also progressively make errors, turning into fully committed pigment cells in the wrong place within the hair follicle, where they are ineffective for providing color to hair [8]. For products designed to change the natural color of hair it is important to consider that the melanin granules are


Hair Cosmetics


distributed throughout the cortex of the hair shaft, showing the greatest concentration towards the outer edge (Figure 30.4). As a general rule, the cuticle layer of hair carries no natural pigments and is therefore transparent. It is therefore imperative for any effective hair dye product to penetrate past the cuticle layer into the cortex of the hair fiber.

Permanent hair dyes There are two chemical processes that take place during the permanent dyeing process, both of which contribute to the final color. The first is the oxidation of the melanin pigments and previously deposited dyes that lightens the underlying color. The second is the oxidation of the dye precursors to form color giving chromophores [9].

Melanin bleaching Permanent hair dyes and hair bleach products have the capability to lighten the natural color of hair by removing some of the existing pigment. The melanin granules are partly dissolved and broken down. During a complete bleaching procedure the melanin granules are dissolved completely, leaving behind a tiny hole in the cortex of the hair. The process can be described as oxidative degradation of the melanins, leading to a variety of smaller degradation products. The reaction is diffusion-controlled and therefore time dependent [4]. It has been reported that pheomelanins is more resistant to photobleaching, and probably also chemical bleaching, than eumelanins [10].

Oxidative dye formation Permanent hair dyes are based on the oxidation by hydrogen peroxide of so-called dye precursors or primary intermediates which typically belong to the chemical groups of p-diamines and p-aminophenols, in the presence of various couplers (for examples see Figure 30.5). To start the process, the highly alkaline pH of the dye formulations swells the hair fiber and allows the small active molecules to penetrate into the cortex where the dye formation takes place in three

Figure 30.4 Longitudinal section of hair fiber showing melanin distribution across the cortex.














OH m-Aminophenol




Figure 30.5 Some typical oxidative dye precursors (top) and couplers (bottom).

30. Hair dyes NH





NH + H2N






Figure 30.6 The three main steps in oxidative dye formation (here with p-phenylenediamine and m-phenylenediamine).


Table 30.2 Variety in color results given by different couplers in the presence of p-diamines and p-aminophenols. Coupler

Color on hair with p-diamines

Color on hair with p-aminophenols


Bluish brown–black

Reddish brown





Greenish brown

Light brown


Warm brown/magenta



Warm brown

Warm brown

main steps. The first step of the dye formation process is the oxidation of the primary intermediates to highly active imines, which are capable of reacting with their unoxidized counterparts to form polynuclear brown or black colored complexes. In the presence of couplers or color modifiers the imines then react preferentially with the coupler molecules at the most nucleophilic carbon atom on the structure. In step 3 this coupled reaction product is oxidized to form wash-resistant indo dyes (for an overview of the dye formation process see Figure 30.6). Couplers do not themselves produce color but modify the color produced by the oxidation of the primary intermediates (Table 30.2). The final color is a function of the amounts and nature of the individual primary intermediates and couplers in the composition and consists of a variety of large color molecules. Their size makes them particularly resistant to removal by washing the hair, and means they undergo little fading [5].








Formulation All permanent hair dyes are generally marketed as two component kits. One component (tint) contains the dye precursors and an alkalizer (typically ammonia or monoethanolamine) in a surfactant base, and the other is a stabilized solution of hydrogen peroxide (developer). The two components are mixed immediately prior to use and then applied to the hair. With the developer component being a liquid, the tint is usually a cream or a liquid. Which one to use is mainly a matter of individual preference, the liquids might be easier to mix while the creams might be applied with less dripping. Table 30.3 summarizes common hair dye components and their functions, while also naming some specific examples as they would appear in the ingredients list of a marketed product.

Advantages and disadvantages If all goes well, coloring hair can be life-transforming but there are a couple of considerations when it comes to weighing advantages and disadvantages of this category.

Advantages The key strength of the hair dye category lies in its transformational potential. Changing one’s hair color can have a dramatic physical effect but, more importantly, it can also have an impact on a psychologic level. Patients may not only feel more attractive and younger looking, they also report increased confidence both in their private and work environments which should not be discounted or belittled [2].



Hair Cosmetics

Table 30.3 Overview of common hair dye ingredients. Component


Sample ingredients


Oxidant, bleaching

Hydrogen peroxide


Swell hair, bleaching

Ammonia, monoethanolamine (MEA), aminomethylpropanol (AMP)

Dye precursors

Impart color

p-Aminophenol, 1-naphtol, p-phenylenediamine, 4-amino-2-hydroxytoluene


Dye vehicle

Water, propylene glycol, ethanol, glycerin


Foaming, thickening

Sodium lauryl sulfate, ceteareth-25, cocoamide MEA, oleth-5



Disodium phosphate, citric acid

Fatty alcohols


Glyceryl stearate, cetearyl alcohol

Quaternary compounds


Polyquaternium, cetrimonium chloride

In our youth-obsessed society coloring gray hair can be seen as a simple yet powerful tool in the arsenal of “antiaging” procedures and products. Another advantage of modern hair dyes is the variety of technologies and benefits that it offers. Virtually everyone can find a product that suits them and their personal requirements, and the range of offered shades is ever-expanding.

as poor shine, poor feel, and reduced strength [11]. It should be noted that these problems mostly occur with frequent use and that they can be reduced with the right application techniques. We return to this in more detail in the section “Physiological changes to hair during coloring”.

Product application Disadvantages Most hair dyes (with the exception of pure bleaching products) have the potential to cause allergic reactions, even if only a small fraction of the population is affected (see section on ‘Safety and regulatory considerations’ for more detail). All oxidative hair dyes, including demi-permanent, permanent, and bleaching products, contain ingredients such as hydrogen peroxide and ammonia, which may cause irritation. It is imperative that usage instructions are followed carefully, and that all products are kept well out of the reach of children. It should also be mentioned that permanent hair dyes require a certain amount of upkeep and maintenance from the user. Visible root regrowth, especially if the natural color has been significantly changed, necessitates the regular reapplication of product. This is one of the main reasons why a large group of consumers who color their hair choose to do so themselves, at home, rather than visiting a professional hairdresser every single time they feel the need to recolor. Lastly, one drawback of hair dyes, again mainly relevant to oxidative products, lies in the fact that hydrogen peroxide at alkaline pH conditions can alter the hair structure, leading to undesirable sensorial attributes described by consumers


The most important step in hair dyeing is the right choice of product, including both the type of hair dye and the color shade. Individuals with no previous experience in dyeing their hair who want to blend away some first grays, or a subtle enhancement of their natural color, are perhaps best advised to choose a semi-permanent colorant. If the person has a higher percentage of gray (up to 30%) and wants to stay close to their natural hair color, a demi-permanent product could be the best solution. Covering larger percentages of gray and/or achieving significant changes in the natural hair color will require the application of a permanent hair dye product. Once the right type of hair dye has been identified, it is all about finding the right shade. The final color result is a combination of the existing hair color and the shade produced by the colorant – shade guides on the packaging are usually very helpful in exploring which result should be expected based on those two parameters. For home hair dyes a useful guideline is to stay within two shades of one’s natural color, and if in doubt chose a lighter over a darker shade. To be sure about the outcome of the coloring process, which will also be affected by the condition of the hair and

30. Hair dyes previous treatments, a strand test can be helpful. For this test a small strand of hair (0.25 inch) is cut from the darkest or grayest part of the head and covered with the product for the advised time. Checking after different time points allows finding the optimum processing time to accomplish the desired end result. Another check that should always be completed before coloring hair is a skin sensitivity test. The test should be carried out 48 hours prior to product use and involves applying a small amount of the product to the skin (typically recommended is the inside of the elbow). If a rash or redness, burning, or itching occurs the patient may be allergic to certain product ingredients and must not use the tested product. Lastly, it is very important, especially for first time colorers, to read the (admittedly often lengthy) product usage directions carefully. Oxidative colorants require the mixing of several components before application and each product might be slightly different in terms of how it should be mixed and used. It is therefore imperative for a successful coloring experience to follow the recommended procedure step by step.

to oxidative degradation products. The resulting physicochemical changes of the hair surface are irreversible and can lead to hair that feels coarse, is more difficult to comb, lacks shine, and is weakened [11,13]. Importantly, hair that has been treated and thus changed by oxidative treatments is more prone to physical and environmental stress and subsequent damage [14].

Recent formulation strategies to minimize fiber damage While the above described hair fiber changes can be mainly attributed to hydrogen peroxide itself, it is also well known that hydrogen peroxide at high pH is likely to form reactive radical species which have been shown to be an additional source of fiber damage. The reaction is catalyzed by the presence of redox metal ions such as copper and iron which are prevalent in tap water. It has been reported that the addition of metal chelating agents to oxidative colorants can reduce the surface damage caused in the presence of copper in tap water [15]. Key is to find a chelant that selectively binds to transition metal ions such as copper in the presence of high concentration of water hardness ions, especially calcium. N,N′-ethylenediamine disuccinic acid (EDDS) has been found to fulfill this requirement [15].

Impact of hair dyes on hair structure Caring for colored hair Oxidative coloring and bleaching have been shown to cause several changes to the hair structure, especially with frequent use (Figure 30.7). Alkaline peroxide partially removes the outer hydrophobic surface barrier of hair, called the f-layer, made of 18-methyl eicosanoic acid. This layer can be considered a natural protection or conditioning system of hair and its destruction leads to significant changes in how hair feels and behaves [12]. At the protein level, peroxide at alkaline pH conditions attacks certain amino acids which are part of the hair fiber structure, especially cystine, leading

Based on the described changes to the hair surface structure, it is important that consumers take the right steps to care for their hair after coloring. This will help in keeping the color vibrant for as long as possible, and in protecting the already weakened hair from further damage from daily wear and tear. The first step in treating colored hair correctly is to use the most appropriate application technique when recoloring. Covering visible regrowth only requires the hair dye to be used on the hair sections affected – the hair roots. This


(b) Figure 30.7 Change in surface hydrophobicity before (a) and after (b) bleaching.



Hair Cosmetics

will protect the bulk of the hair from unnecessary exposure and overprocessing. The basis for a suitable hair care routine after dyeing should be the use of a shampoo and conditioner specifically developed for colored hair. They contain ingredients that are tailored to the altered hydrophilic surface conditions of the hair and help to smoothen the cuticle surface, protecting it against mechanical damage. Secondly, sun exposure should be minimized because UV radiation not only contributes to hair damage but also has a direct impact on color fading. Lastly, it should be pointed out that water exposure is the biggest contributor to color fading (also called wash fading). It can therefore be beneficial not to wash freshly colored hair too frequently.

Safety and regulatory considerations As part of cosmetics, hair dyes are thoroughly safety regulated by global regulatory authorities such as the US Food and Drug Administration (FDA) or EU Cosmetic Directive, and their scientific advisory board, the Scientific Committee on Consumer Safety (SCCS, formerly SCCP, SCCNFP) [16,17]. Hair dyes are one of the most thoroughly studied cosmetics and consumer products and there is an overwhelming amount of safety data on hair dyes [18]. Despite the extensive safety testing and close safety regulation regimen, two safety concerns are typically associated with hair dyes: skin allergy and allegations regarding a slightly increased cancer risk.

Allergy Like other products such as certain foods or drugs, hair dyes can cause allergic reactions in a few individuals. Allergic reactions to hair dyes are well known but still relatively rare when compared to the daily global use of millions of hair colorants. The majority of allergic reactions to hair dyes are classified as delayed hypersensitivity or type IV reactions. Type IV reactions are normally localized to the area where the product is applied. Only in very rare exceptional cases more severe and spreading symptoms like facial oedema can occur. Type IV reactions are triggered by a different immuneresponse mechanism than the systemic type I allergies, which are more typically reactions to food or drugs and in severe cases may be life-threatening. Type IV reactions typically are not life-threatening. Key hair dye ingredients such as para-phenylenediamine (pPD), but also para-toluenediamine (pTD), are known skin sensitizers. pPD is part of the standard patch test series in certain countries; pTD is part of the hairdresser patch test series [19]. Used for many decades as key hair dyes, no superior technology emerged to date, despite intensive research efforts.


Among consumers and clients, allergy incidence against pPD has been more or less stable over the past years [20]. While a few authors have concluded that pPD allergy incidence among patch-tested individuals has slightly increased over the years [21], most authors conclude that pPD allergy incidence is stable or even slightly decreasing [22–24]. Nonetheless, hair dye allergy remains an issue for a small number of consumers and therefore following safety measures can help to minimize the allergy risk [25]: • Consumers should read and follow the usage instructions of hair colorants carefully. All concerned hair dyes carry clear allergy warning labels, making aware of the potential allergy risk. • For permanent and most semi-permanent hair colorants, consumers are advised to conduct a product tolerance test (also called skin sensitivity or consumer self test) with the shade of interest 48 hours before each hair coloring, by following the recommendations of each product. However, the absence of a reaction at the test site is no guarantee that a reaction will not occur during hair coloring. In case of a skin reaction at the test site, consumers should not color their hair and seek dermatologic advice. When consumers experience initial signs of an adverse reaction at the scalp during the hair coloring session, the hair dye should be rinsed off immediately. • Temporary black henna tattoos are an important contributor to pPD allergy in humans [26,27]. Consumers may develop an allergy to hair dyes over time as a result of other products than hair dyes. This emphasizes the importance of conducting a skin sensitivity test. • Professional hairdressers should follow key occupational safety measures, such as wearing protective gloves during preparation, application, and rinsing of hair colorants [28]. • In the case of consumers who are positively patch-tested against a specific hair dye ingredient, special caution should be applied to using a hair dye lacking the respective allergen. Some hair dyes are known to cross-react (e.g. pPD and pTD). Overall, it should be emphasized that vast majority of consumers can safely use hair colorants and that following the use instructions plus the above guidance can help to minimize the allergy risk for the small number of individuals who may be allergic to hair dyes.

Cancer Cancer concerns were raised early in the context of oxidative hair dyes, because of their chemical nature. Numerous epidemiologic studies into hair dye safety have been conducted, the vast majority concluding that there is no association of hair dye use and an increased cancer risk. Occasional, single epidemiologic studies reporting a slightly increased risk for certain cancer types have not been confirmed by multiple epidemiologic studies. Early 2008, leading cancer experts of the International Agency of Cancer Research

30. Hair dyes (IARC, a subsidiary of the WHO) reviewed all relevant studies and scientific papers published to date and concluded that there is no evidence that personal hair dye use is associated with any increased cancer risk [29]. The US Cosmetic Ingredient Review (CIR) panel came to the same conclusion.

Conclusions Modern hair dyes are an effective tool in altering the natural color of hair. Different product types offer a wide range of results, from subtly enhancing color to dramatic color changes and complete gray coverage. While the potentially huge beneficial effect on peoples’ perceived attractiveness is undisputed, a thorough understanding of the different available technologies and their benefits and drawbacks is essential to advise consumers on the most suitable products to use. The main future challenge in hair color lies in preventing or even reversing hair graying via stimulating melanocyte activity at the molecular or even genetic level. The recently reported modulation of hair follicle melanocyte behavior with corticotropin-releasing hormone peptides could be a first step into an exciting new world of changing hair color [30].

References 1 Zviak C. (1986) The Science of Hair Care. New York: Marcel Dekker. 2 Gray J. (2005) The World of Hair Colour. London: Thomson. 3 Brown K. (2000) Hair coloring products. In: Schlossman M, ed. The Chemistry and Manufacture of Cosmetics, Vol. II Formulating. Carol Stream, IL: Allured Publishing, pp. 397–454. 4 Robbins CR. (2002) Chemical and Physical Behavior of Human Hair. New York: Springer. 5 Corbett JF. (1998) Hair Colorants: Chemistry and Toxicology. Cosmetic Science Monographs. Weymouth, UK: Micelle Press. 6 Schwan-Jonczyk A. (1999) Hair Structure. Darmstadt, Germany: Wella AG. 7 Prota G, Ortonne JP (1993) Hair melanins and hair color: Ultrastructural and biochemical aspects. J Invest Dermatol 101, 82S–9S. 8 Nishimura EK, Granter SR, Fisher DE. (2005) Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307, 720–4. 9 Brown KC, Pohl S, Kezer AE, Cohen D. (1985) Oxidative dyeing of keratin fibers. J Soc Cosmet Chem 36, 31–7. 10 Wolfram LJ, Albrecht L. (1987) Chemical and photobleaching of brown and red hair. J Soc Cosmet Chem 38, 179–91. 11 Jachowicz J. (1987) Hair damage and attempts to its repair. J Soc Cosmet Chem 38, 236–86. 12 Lodge RA, Bhushan B. (2006) Wetting properties of human hair by means of dynamic contact angle measurement. J Appl Polym Sci 102, 5255–65.

13 Wortmann FJ, Schwan-Jonczyk A. (2006) Investigating hair properties relevant for hair “handle”. Part I: hair diameter, bending and frictional properties. Int J Cosmet Sci 28, 61–8. 14 Takada K, Nakamura A, Matsua N, Inoue A, Someya K, Shimogaki H. (2003) Influence of oxidative and/or reductive treatment on human hair (I): Analysis of hair damage after oxidative and/or reductive treatment. J Oleo Sci 52, 541–8. 15 Marsh JM, Flood J, Damaschko D, Ramji N. (2007) Hair coloring systems delivering color with reduced fiber damage. J Cosmet Sci 58, 495–503. 16 European Union Cosmetic Directive (76/768/EEC): http://ec. 17 SCCP/1005/06 Notes of guidance for testing of cosmetic ingredients for their safety evaluation, 6th revision, adopted by the SCCNFP during the plenary meeting of December 19, 2006. 18 Nohynek GJ, Fautz R, Benech-Kieffer F, Toutain H. (2004) Toxicity and human health risk of hair dyes. Food Chem Toxicol 4, 517–43. 19 Diepgen TL, Coenraads PJ, Wilkinson M, Basketter DA, Lepoittevin JP. (2005) Para-phenylendiamine (PPD) 1% pet. is an important allergen in the standard series. Contact Dermatitis 53, 185. 20 Gerberick GF, Ryan CA. (2005) Hair dyes and skin allergy. In: Tobin DJ, ed. Hair in Toxicology: An Important Biomonitor. London: CRC Press, pp. 212–28. 21 McFadden JP, White IR, Frosch PJ, Sosted H, Johansen JD, Menne T. (2007) Allergy to hair dye. Br Med J 334, 220. 22 Uter W, Lessmann H, Geier J, Schnuch A. (2003) Contact allergy to ingredients of hair cosmetics in female hairdressers and clients: an 8-year analysis of IVDK data. Contact Dermatitis 49, 236–40. 23 DeLeo VA. (2006) p-Phenylenediamine. Dermatitis 17, 53–5. 24 Wetter DA, Davis MDP, Yiannias JA, et al. (2005) Patch test results from the Mayo Clinic Contact Dermatitis Group, 1998– 2000. J Am Acad Dermatol 53, 416–21. 25 Schlatter H, Long T, Gray J. (2007) An overview of hair dye safety. J Cosmet Dermatol 6, 32–6. 26 Onder M. (2003) Temporary holiday “tattoos” may cause lifelong allergic contact dermatitis when henna is mixed with PPD. J Cosmet Dermatol 2, 126–30. 27 Nawaf AM, Joshi A, Nour-Eldin O. (2003) Acute allergic contact dermatitis due to para-phenylenediamine after temporary henna painting. J Dermatol 30, 797–800. 28 Dickel H, Kuss O, Schmidt A, Diepgen TL. (2002) Impact of preventive strategies on trend of occupational skin disease in hairdressers: population based register study. Br Med J 324, 1422–3. 29 Baan R, Straif K, Grosse Y, Secretan B, Ghissassi FE, Bouvard V, et al. (on behalf of International Agency for Research on Cancer, IARC). (2008) Carcinogenicity of some aromatic amines, organic dyes and related exposures. Lancet Oncol 9, 322–3. 30 Kauser S, Slominski A, Wei ET, Tobin DJ. (2006) Modulation of the human hair follicle pigmentary unit by corticotropinreleasing hormone and urocortin peptides. FASEB J 20, 882–95.


Chapter 31: Permanent hair waving Annette Schwan-Jonczyk and Gerhard Sendelbach Wella/Procter & Gamble Service GmbH, Darmstadt, Germany

BAS I C CONCE P T S • Permanent hair waving is a two-step chemical treatment modifying hair protein to achieve and retain a curly shape. • The chemical treatment involves a thioglycolate reduction reaction that plasticizes hair while being wound on a rod. The following oxidation step with hydrogen peroxide reforms the hair in a new curly shape. • Curl retention depends on hair thickness, rod diameter, and hair quality. • Undesirable hair damage can occur with the wrong choice of perm and neutralizer, too much heat, incorrect processing time, or improper perm solution amount.

Introduction Since ancient cultures curly hair represented femininity and beauty. Women with straight hair purchased expensive wigs or spent hours for hair ondulation with water and heat, which was temporary. A ground breaking invention occurred in 1906 when Carl Nessler offered irreversible hair shaping to clients by means of heat and borax. Improvements followed during the 20th century by creation of “cold waves,” using sulfite or thioglycolate as actives, which still are the most popular waving agents in home and salon perms.

Hair physiology Hairs are composed of cells packed in tight cell bundles that grow out from up to 3 mm skin depth. About 5 million hairs cover the human body and scalp classified as vellus hairs (5–10 μm in diameter) or terminal hairs (5–120 μm in diameter). The human head contains 100 000–150 000 fibers, which grow 1 cm per month through rapid cell division in the living, lowest part of their hair follicle, known as the hair bulb. The hair surface contains flattened cells, known as the cuticle, which forms an imbricated structure resembling shingles on a roof. The cuticle provides protection and support for the inner spindle-shaped “cortical cells,” which makeup 80% of the hair mass. During hair growth, the interdigitated cells are organized into a three-dimensional

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


network resembling a jigsaw puzzle. This construction contributes to cell cohesion and hair fiber strength (Figure 31.1). While all hair fibers contain a cuticle, only thicker hair fibers with a diameter greater than 75 μm contain a central line of hollow cells, known as the medulla (Figure 31.2). The medulla functions in animal hair to provide enhanced thermal insulation. The active growth period of scalp hair is known as the anagen phase and is limited to 3–6 years. Then the hair disconnects from the papilla, a period known as the catagen phase, and enters a 2-month resting phase, known as the telogen phase, and subsequently sheds. Hair shedding and renewal results in an average loss of up to 100–125 scalp hairs per day. With constant hair growth and no cutting, bulk hair may reach up to 1 m in length (for more hair growth details, the reader is referred to more detailed references [1,2]).

Permanent wave hair relevant properties Hair geometry Usually, scalp hair is visualized as a circular fiber but crosssections of individual hairs reveal variation in hair shape. The typical appearance of a person’s hair is determined by its special mixture of thick, thin, elliptical, kidney-shaped, and triangular cross-sectional shapes [3]. Unmanageable hair is often because of a high percentage of irregular hair shapes. Irregular hair geometry, small diameter, and large hair diameter all create permanent waving challenges. Hair thickness has a large influence on the shape and hold of permanent wave curls [4]. Naturally curly hair [5] can also be challenging as it is sometimes desirable to use a permanent for straightening purposes.

31. Permanent hair waving


4 3


2 2 1

1 (a)


Figure 31.1 (a) The fracture plane of a hair fiber clearly shows the composite of a fibrillar core with flattened cuticle cell coating (SEM ×1420). (b) Just emerging hair: 1, scalp surface; 2, cuticle pattern of hair fiber surface; 3, interior of the hair with cortical cells; 4, medullary cells; 5, cell membrane.

step in the curling process. Under certain climatic conditions, hair adsorbs atmospheric water up to 30% of its weight. Although feeling dry at ambient temperature, hair still contains 15% water. Excess water can be bound by capillary forces. The hair water content dictates its chemical reactivity because water widens the hydrogen-bond network of protein side chains and acts as the vehicle for all permanent waving ingredients. Proper water balance is important for a successful permanent waving. Moreover, water functions as the plasticizer for hair; permed hair loses curls more rapidly after washing or exposing it to humid conditions, which can be measured by a curl retention test [7]. In presence of water, hair displays its amphoteric character. A hair “isoionic point” exists where the positive and negative charges of hair proteins are at equilibrium. The natural “intrinsic point of neutrality” of hair is pH 6, slightly more acidic than water at pH 7. This is the point of greatest stability. This intrinsic point of neutrality must be restored after permanent waving to maintain the structural integrity of the hair. Closely related to hair fiber water hydrophilicity is its thermal behavior. Dry hair can withstand a temperature of 240 °C for a short time but wet hair suffers damage at 140 °C. Figure 31.2 The intact cuticle pattern of the hair fiber near the scalp (SEM ×800).

Hair and water interaction Although hair is not soluble in water, its interaction with water is of particular importance [2,6]. Hair surface is hydrophobic and water repellent. Permanent waving lotions contain surfactants for enhanced wetting, which is the first

Hair aging Hair fibers undergo aging when exposed to grooming trauma and the environment [2,6,8]. The hair emerges in a virgin state but suffers heat damage during blow-drying, physical trauma from daily brushing with constant stretching, and photodamage. Oxygen radicals further cause chemical oxidation of the hair surface. The final effect is chemical and mechanical wear of the hair. Hair proteins are cleaved, amino acids are converted,



Hair Cosmetics

cystine is oxidized to cysteic acid, and histidine is decomposed. As a consequence, stability and elasticity of hair ends decrease, flexibility is reduced, and hair fibers get more rigid and brittle, a process termed “weathering” of hair. Unsightly split ends occur and the hair feels dry (Figure 31.3). The structural differences between hair roots and hair ends require special attention in hair permanent waving because hair ends react faster and break more easily.

Hair chemical structure The protein content of a normal hair at ambient conditions is approximately 80 wt% [2,9]. Further components are approximately 5 wt% internal lipids; <1 wt% trace elements and metals; 14 wt% water. Of the 22 amino acid types found in hair, the most important is “L-cystine” (56-89-3), a sulfur-containing amino acid (Figure 31.5), which facilitates covalent cross-linking between two different protein chains. Up to the high amount of 9 mol% (750 μmol/g hair) [10] is typical for cornified tissues, such as hair, nail, hooves, horn, or cornea. Covalently cross-linked by this interproteinacous amino acid, hair demonstrates high mechanical strength and shear resistance, insolubility in water, but is prone to swelling.

Two types of proteins constitute the hair content: low and high sulfurous proteins. It is their typical arrangement that differentiates hair proteins from proteins in the rest of the body: • About 50% of the proteins are present in an unorganized, amorphous form, called matrix proteins, with frequent disulfide bridges. • The rest coil up to form a helical configuration in certain sections, constitute microfibrils, which are embedded in and anchored to the matrix proteins. Figure 31.4 shows the network of hair proteins, with the “disulfide bonds” marked in yellow, which gives hair properties similar to a fiber-reinforced plastic [11] or the elastic rubber of a tire. This special architecture is the source of hair’s elasticity. Perming agents cleave disulfide bonds in these matrix proteins, causing the plastification or softening that is necessary for shaping hair.

Figure 31.4 Coiled (alfa-helical) and amorphous molecules of hair proteins are cross-linked by disulfide bonds inside the cortical cells. Helical proteins are stabilized by hydrogen bonds.





H2N Figure 31.3 The worn cuticle-free split end of hair (SEM ×800).





Figure 31.5 Chemical formula of the amino acid “cystine”.

31. Permanent hair waving However, an excess of a reducing agent is necessary, as cross-linked sulfur proteins in the cuticle make the hair mantle hard to dissolve and penetrate. Additional support of the chemical network is provided by the acid and basic amino acids in hair protein. As these make up more than 40%, low energy bridges, salt linkages, and hydrogen bonds are formed, which are also cleaved and reformed in the perming process.

Chemophysical principles of hair waving Because of hair’s great elasticity and strong resilient forces, it quickly resumes its original straight shape. Therefore it has to be softened and subsequently rehardened chemically to maintain a conformation change. Especially with permanent waving, it is important to select a reversible reaction to allow repeated treatments without hair destruction. The sulfur bridges of the amino acid cystine, linking the proteins, are best suited [6,12,13]. The conditions for permanent waving to be well tolerated are: • Low temperature (20–50 °C), convection or contact heat; • Short process time (5–30 minutes); and • Mildness to the skin.

A permanent wave occurs with two solutions: 1 Solution 1: the perming lotion, which contains a reducing agent, a “thiol” compound, designed to split off about 20– 40% of hair cystine bonds. 2 Solution 2: a fixing lotion, which contains an oxidizing agent, usually hydrogen peroxide, designed to rebuild cystine bridges between proteins at new sites in the curled hair shape (Figure 31.6). It must be emphasized that permanent waving is a twostep procedure where the chemical reaction and physical effects run in parallel (Figures 31.7 and 31.8) [14–16]: reduction of disulfide-bonds, softening of hair, lateral swelling and length contraction, stress development and protein flow, then reoxidation of cystin bonds and deswelling, fixation of a new curly shape. Table 31.1 summarizes how hair reacts chemically and physically during each of the permanent waving steps. Usually only 85% of the cleaved disulfide is reformed during neutralization. Some hair cysteine oxidizes to give cysteic acid (Figure 31.6, formula 2), which renders hair more hydrophilic, incompletely cross-linked, and more vulnerable to subsequent treatments. Therefore, permed hair gradually loses its curl and relaxes to a straight hair conformation again (for additional details, the reader is referred to Robbins [2] and Wickett and Savaides [17]).

Step 0: Activation R-SH



Thioglycolic acid







Step 1: Reduction Hair–SS–Keratin

2 RS–

2 Hair–S–


Reduced hair




Dithio-diglycolic acid

Step 2: Oxidation 2 Hair–SH Reduced hair





Re-oxidized hair


2 H2O Water

peroxide Hair–SO3H Cysteic acid Figure 31.6 Chemical reaction formulas 0–2.



Hair Cosmetics




Figure 31.7 (a) Sulfur bridges between the proteins are closed. (b) Part of the sulfur bridges are being cleaved, proteins shift, take on the form. (c) Sulfur bridges are being rebuilt at a different site, neutralizer fixes the new shape.




Figure 31.8 (a) Shampooed hair is wound on curlers while still moist. Bending strain is applied to the protein chains. (b) Perm-wave lotion 1 is applied to the hair and cleaves part of the sulfur bridges by the reducing (thioglycolic acid) and the alkalizing agent. Hair is softened, proteins creep and adjust to the shape of the curler. (c) Neutralizing process: an acid neutralizer (peroxide) rebuilds the sulfur bridges at different sites and the new shape is permanent.

Perm products and types Permanent waving products contain an elaborate mixture of ingredients to make the reactions controllable and appropriate for different hair types, such as normal hair (N-type), sensitive hair (S-type), coarse/difficult hair (F-type), and colored/bleached hair (C- or G-type). Typical formulations for a one-component perm lotion and a fixing lotion are shown in Table 31.2. Each ingredient is listed by its International Nomenclature of Chemical Ingredients (INCI) name as is on the package; each ingredi-


ent has its own distinct role in making the solution active, pleasant to the hair, and odor free (for different formulations see [18,19]).

Role of permanent waving product ingredients This section reviews the individual ingredients important in achieving a successful permanent waving solution [20].

Reducing agents Reducing agents, most commonly ammonia or sodium salts of thioglycolic acid (TGA), have been used since the late 1950s to avoid skin and hair irritation while producing a

31. Permanent hair waving

Table 31.1 The usual steps of perming. Steps in practical perming

Hair reacts chemically/physically

1. Ask and consult the client concerning the desired hairstyle (curly head or gentle waves)

2. Assess the hair quality regarding the hair thickness, hair and scalp health, split ends

3. Shampoo the hair with a mild shampoo to remove fat and residual cosmetics

Water swells hair by 15% in diameter, about 2% in length and softens it at the same time

4. Apply a conditioning pre-product, aqueous or oily

Hair surface, root to tip differences in hair structure are equalized, lowers chemical reactivity of hair tips

5. Divide hair into sections with comb to get flat and small hair tresses

6. Take/use endpapers, wrap them around the weathered hair tips, wind the hair tightly on curlers, up to 60 on one head of hair

Paper helps to align tip end hair fiber, protects and delays instant reaction. Moistened hair is usually wound on a rigid rod. Bending hair around the curler produces a slight tension on hair

7. Take on gloves, protect clients face by cotton plugs

Protection for hands and face/neck skin against dripping solution

8. Apply the perming lotion (about 75 mL), avoid dripping

Fluid penetrates into the hair, starts chemically reducing it from outside in, softens hair

9. Apply heat by means of a hairdryer, heat processor or use ambient temperature

Heat accelerates: (a) penetration; (b) the reduction step; (c) moveability of hair proteins

10. Develop process time of perming lotion with heat for 5–20 minutes

Reductive cleavage of the hair cystine-network proceeds, hair swells up to 50%, contracts approx. 2% generates internal stress, which relaxes by creeping and flowing of the protein mass The hair substance is transferred from an elastic into a “plastic” state adopting the shape of the curler

11. Monitor curl development unwinding a test curler

Although wet, unwound test lock shows degree of wave/hair deformation (measurable by an electronic test curler), proteins cysteine side chains changed their position relative to each other

12. Rinse thoroughly off the perming lotion with water (up to 3 minutes)

Chemicals are diluted, removed from hair, reaction stops, but physical swelling and shrinking onto the curler peaks by osmotic forces

13. Apply a neutralizing liquid or foam. Process the neutralizer for up to 10 minutes followed by rinsing and unwinding the hair

Reoxidation of cysteine to cystine by hydrogen peroxide restores hair’s protein network again, fixing new cystine cross-links at different positions. Residual cysteine oxidizes to cysteic acid Deswelling and hardening occurs Unwinding the hair results in curl relaxation

14. Apply an acid conditioning product as an after treatment

Restores hairs neutrality, also neutralizes residual perm molecules. The deformation process is now complete

15. Dry and style the hair by means of a brush or setting curlers and a hairdryer

Curl relaxation starts in wet hair, brushing, combing diminishes curl retention. Best: air drying



Hair Cosmetics

Table 31.2 Ingredients in a typical perm solution 1 and neutralizer solution 2. Ingredient

Content % w/w


Ammonium thioglycolate 70%


Waving agent

Ammonium hydrogen carbonate



Ammonia 25%


Alkalizing agent

1,2 Propylene glycol



Styrene/PVP copolymer



Polyquaternium-6 [poly(dimethyl diallyl ammonium chloride)]


Conditioning agent




Coceth-10 (alkyl polyglycol ether)


Solubilizing agent

Water pH




Neutralizer Hydrogen peroxide 50%


Oxidizing/fixing agent

Ammonium hydrogen phosphate


Stabilizing agent

Phosphoric acid


Stabilizing agent



Complexing agent

Perfume, conditioning agent, surfactant, water pH

As in perm solution 2.5–3.5

lasting hair curl. Other alternatives are glycerol monothioglycolate (GMT), active at neutral pH. Cysteine [21] and cysteamine (2-mercaptoethylamine) are used for perming Asian hair. Thiolactic acid, with less reducing power, can be used as co-reducing agent. Many home permanent waves contain sulfite.

Alkalizing additives Alkalizing additives, such as ammonia or monoethanol amine, are included in the formulation to achieve the appropriate pH at which the reducing agent as well as the hair disulfide is activated, which is normally at pH 7–9.5 (Figure 31.6, step 0). Glycerol monothioglycolate, the active component of an “acid wave”, works at pH 7; however, TGA requires a pH of 8.5–9. Hair damage is often related to a higher product pH.

Buffer salts Buffer salts, such as ammonium (hydrogen) carbonate, affect the alkalinity. These ingredients buffer the working pH as hair, a natural ion exchanger, lowers the pH when it comes into contact with the perm solution.


Carriers Carriers (e.g. urea, ethanol, or 2-propanol) enhance penetration of actives into hair and thus the effectiveness of the perm product.

Surfactants Surfactants are included to ensure wettability of the originally hydrophobic hair surface. They also facilitate foaming of perm solutions or neutralizers to be applied without dripping. In permanent wave foams, the type and concentration of surfactants are especially critical for skin compatibility [13].

Conditioning polymers Conditioning polymers are included to allow an easy manageability of the new shape and mask the somewhat harsh handle of hair after perming.

Complexing agents Complexing agents in thioglycolate-based perm lotions prevent intensive red–violet coloring with iron contamina-

31. Permanent hair waving tion. In the neutralizer lotion, complexing agents avoid decomposition and boosting of hydrogen peroxide.

Opacifiers Opacifiers, such as styrene-vinyl-pyrrolidone-copolymers, and coloring agents (e.g. azulene) give a pleasant appearance to the product, but also serve as an identifying feature.

Thickeners Thickeners (e.g. cellulose derivatives or polyacrylate salts) are used to convert fluid preparations to gels, which prevent dripping off from the hair or enable a more intensive perm treatment of the hair root portion.

Solubilizing agents Oily fragrances afford a solubilizing agent for better miscibility.

Acidic and neutral permanent wave Acidic and neutral permanent wave preparations mostly contain glycerol monothioglycolate (GMTG) as reducing agent. It allows easy control of the processing behavior, leaves hair with a pleasant feel, and the danger of overwaving is slight. Often it is highly retained in hair, imparts an unpleasant smell, and causes sensitization of hairdressers’ hands even by touching hair that was processed weeks ago. Therefore, although it is not legally forbidden, esters must not be used according to the technical directives for dangerous substances in hair salons [22].

Thermal waves Thermal waves produce heat during the perming procedure. Hydrogen peroxide reacts with excess thioglycolic acid to release heat. Such warming is meant to generate a pleasant feeling on the client’s head and to render the addition of external heat unnecessary.

Neutralizers Neutralizer ingredients are in principle oxidizing agents, mostly hydrogen peroxide at concentrations of roughly 0.5– 3% and acid at pH 2–4.5. Advantages are: • Low solution concentrations; • Excellent environmental compatibility; and • Physiologic safety. Moreover, at acid pH hydrogen peroxide has no bleaching power for the natural hair color, but specifically reoxidizes hair cystein to cystin and truly neutralizes the alkaline hair. However, metal salts catalyze the explosion of hydrogen peroxide, which contains as stabilizer inorganic phosphates, phenacetin, or 4-acetaminophenol. As alternatives, bromate salts are used. The concentration is roughly 6–12 wt% at pH 6–8.5. Bromate-based neutralizers are preferentially used in Asia, because they do not lighten dark hair. Less widely used are sodium perborate and percarbamid.

Different product types The majority of commercial waving and neutralizing lotions are aqeuous solutions, but a few are designed as gels, creams, or aerosol permanent waves [17,18]. Preparations chiefly differ in: • Mixture of reducing agent; • Concentration of reducing agent; • pH value; • Form of application.

Alkaline perms Alkaline perms are alkalinized by ammonia to a pH 9–9.5. Because of their frequent association with skin inflammation, these products were largely replaced by mildly alkaline preparations at pH 7.5–9.

Sulfite perms Perming lotions containing ammonium sulfite are used in home waving. At neutral pH 7 and without thiols, they act best on healthy, undamaged hair. However, stable “Bunte” salts are formed during their chemical reaction with hair. This leads to poor fixation, rough feel, and hair damage on tinted or fine hair. An overview of product types is summarized in Lee et al. [23].

Regulatory aspects Formulation is limited by some legal regulations [20]. First, the cosmetic chemist selects the ingredients from a pool of chemicals, which are compatible with the cosmetic legislation in the countries where the product is introduced. The EC Cosmetics Directive, Annex III, Part 1 [24], restricts the pH of permanent wave preparations with thioglycolic acid, its salts, and esters to pH 7–9.5 for the acid and salts, pH 6–9.5 for esters. The maximum concentration calculated as thioglycolic acid is 8 wt% ready for use for retail and 11 wt% for professional use. A special warning label is required. In the USA, the Cosmetic Ingredient Review (CIR) expert panel considers 15.4 wt% maximum of thioglycolic acid as safe in permanent wave products. The CIR recommendations are respected by the manufacturers. In Japan, permanent wave products are classified as quasidrugs. Thioglycolic acid and its salts are permitted, as is cysteine, but restrictions on concentration and pH are given. Thioglycolic esters are not allowed. Hydrogen peroxide concentrations are limited to 12% in the EU [24].



Hair Cosmetics



Figure 31.9 Hair, properly wound, fixed on rollers, and wetted by the perming lotion (a) delivers perfect locks (b).

Perming practise – how to achieve a perfect curl The question of perming safety is not only a function of product composition, but also depends on the use conditions [6,25]. Therefore, each package of perms on the market contains a list of instructions for the hairdresser or consumer. Table 31.2 summarizes the recommended steps and how hair answers (i.e. reacts), chemically and physically. Any deviations from this course of action will be specified in the instructions for use. The correct execution of each step should produce the desired result, a curl lasting up to 3 months, a well-preserved hair structure, and an easy styling of the hair assembly (Figure 31.9). In salons, where hairdressers use long-lasting perms, an appropriate permanent wave must be selected to achieve the best result. The hair thickness and quality must be assessed to determine if the hair is healthy or damaged. If the hair feels rough, is of a lighter color, or possesses split ends, it may have a porous structure produced by previous weathering, bleaching, coloring, or perming. This increased porosity allows the perming lotion to react faster. Damaged hair requires bigger curlers, a reduced perm strength, and shortened processing time. Heat from a drying hood (45 °C) accelerates the chemical reaction, but should not be used in persons with sensitive scalp skin.


To ensure that the proper amount of curling has been achieved, a test curl should be performed. A test curl is loosely unwound from a curler after several minutes to determine the degree of curl achieved and whether to extend the processing time. After thoroughly rinsing off the perming lotion, complete hair neutralization is strongly advised as the second fundamental step in perming. Three to ten minutes are recommended to obtain a lasting perm, to reoxidize the hair, and to neutralize the alkalinity of the reducing step. Physically, hair only gains its strength and integrity with thorough neutralization. Application of an acidic conditioning lotion as an aftertreatment, removes residual peroxide, restores the hair internal pH to neutrality, helps to stabilize the hold of the curl, and makes it less prone to future damage.

Safety and adverse reactions to perm products Safety requirements from consumer expectations are adequately summarized by the corresponding text within the EU Cosmetics Directive: “A cosmetic product put on the market within the Community must not cause damage to human health when applied under normal or reasonably foreseeable conditions of use” [24].

31. Permanent hair waving Therefore, as permanent wave preparations contain reactive chemicals, these have to pass a complete toxicologic characterization. Essentially, the potential for: • Acute systemic toxicity; • Local compatibility and irritation; • Sensitizing potential, allergenicity; • Mutagenicity; • Tumorigenicity; • Teratogenicity; and • Percutaneous absorption. From past experience with the safety of waving products, and regularly updated statistics published by intoxication advisory centeres, manufacturers obey the rules. Statistics of adverse reactions from cosmetic products sold between 1976 and 2004 revealed only 1.1 undesired effects per 1 million packages sold [26]. This confirms cosmetic products are very safe (for more detailed information about toxicologic test methods and safety assessment processes see references [20,27,28]). Even though a perm product has been approved as safe by legal authorities, occasional hair or skin damage can occur from incorrect usage: • Consumers apply a home wave without reading/understanding instructions; or • New hairdressers in salons are untrained and less skilful. The first signs of a failure in perming are lack or excess of curliness. This is not only because of the wrong choice of product, excessive development time, and temperature, but may also result from incomplete rinsing of the active substances and shampoo components. Surfactant residues, residual reducing, and oxidizing agents in the hair encourage irreversible side reactions, such as incomplete reoxidation and cysteic acid formation. Moreover, the stylist or the client may try to “repair” the unexpected result by repetition of the permanent waving process. Multiple treatments, as well as the combination of perming and bleaching or coloring in the same session, lead to heavily damaged hair. Electron microscopy reveals residual softening, even complete peeling of hair surfaces (Figures 31.10 and 31.11). Instrumental methods can further detect the degree of damage. These include hair tensile testing, elasticity, curl hold, swelling behavior, and static charging [2,20]. Chemical damage of hair may also be assessed by analyzing dissolved hair proteins [29,30] and hair lipids [30]. Residual cysteine and cysteic acid are signs of weak hair structure [30]. Table 31.3 lists examples for hair and skin symptoms indicating mistakes during a perm treatment [25,31–34]). Although ammonium thioglycolate has been reported to have a low sensitization potential, occasionally sensitization, skin irritation, contact dermatitis [33,34], or seborrhea occur [32]. Itching, burning, and redness are normally con-

Figure 31.10 The curtain-like structure of a hair surface indicates heavy perming damage.

Figure 31.11 A bleach applied immediately after a perming treatment chips off the cuticle as a whole (SEM ×700).

fined to the neck and scalp margins after prolonged contact with perm solution [31]; however, high levels of alkalinity and heat [33,34] may also precipitate irritation. Scalp skin damage seldom occurs. Scalp skin, which contains keratin proteins like hair, is less reactive to reduction by thioglycolate. This contributes to a lower swelling response of the skin than hair (22% vs. 38%) and the lower cystine content and hydrophobic nature of skin vs. more cystine and hydrophilicity in hair [35]. The skin is more susceptible to surfactants, however, causing hairdresser’s hands to be affected by an allergy to perms. When the hands are softened by routinely shampooing of clients’ hair, monothioglycolate esters found in acid waves may be problematic [31].



Hair Cosmetics

Table 31.3 Symptoms of hair/skin damage by perm products. Symptom

How it happened

Hair loss (rarely)

Telogen hair effluvium Temporary contact allergic reaction

Hair breakage Near root

False hair quality diagnosis Perm choice too strong for fine or predamaged/ bleached hair Stress on root hair by tight winding or rubber band Winding against hair growth direction Hair growth with thinning diameters Winding on curlers with “ fish hooks” Incomplete neutralization Forgot pretreatment with equalizer Processing without wrap end paper protection Excess perm solution stored by hair tips

In hair length

Near tip ends

Hair modification (consumer complaints) Unwanted kinky curls

Limp hair/curls without springiness

Wet hair feels plastified, spongy, extensible

Dry hair feels rough, brittle, uncombable, “matting”, is dull, ready to break Highlighted natural color or tint

Perming power of product too high Curler thickness too thin Processing time with heat too long Loose winding, impaired protein creep False time and fluid saving as well as excess time, heat, fluid Overprocessed by extended application Loss of keratin elasticity Increased hydrophilicity Neutralization too short Intermediate rinsing too short Increased hair surface friction by shrunken cuticle cells Loss of hair lipids and proteins Dissolution of natural pigment/tint Excess perm conditions

Skin damage Redness

Too much heat (heat rollers, hood defect)


Skin swelling during extensive prewash

Irritant skin

Soaked cotton pads for face protection not removed

References 1 Jollès P, Zahn H, Höcker H, eds. (1997) Formation and Structure of Human Hair. Basel: Birkhäuser Verlag. 2 Robbins CR. (2002) Chemical and Physical Behaviour of Human Hair, 4th edn. Berlin, Heidelberg: Springer Verlag. 3 Schwan-Jonczyk A, Schmidt CU. (2007) Hair geometry changes during lifespan. Proceedings of the 15th International Hair Science Symposium, HAIRS 07, Banz. 4 Robbins CR. (1983) Load elongation of single hair fiber coils. J Soc Cosmet Chem 34, 227–39. 5 Wolfram L, Dika E, Maibach HI Hair anthropology, or Swift JA. The transverse dimensions of human head hair. (2007) In: Berardesca E, Leveque JL, Maibach HI, eds. Ethnic Skin and Hair. New York: Informa Healthcare. 6 Schwan-Jonczyk A, Arlt T, Maresch G, Schonert D. (2003) Curls, Curls, Curls. Darmstadt: Wella AG (inhouse publication).


7 Franbourg A, et al. (2005) Evaluation of product efficacy. In: Bouillon C, Wilkinson J, eds. The Science of Hair Care. Boca Raton, FL: CRC Press, pp. 351–76. 8 Swift JA. (1997) Fundamentals of Human Hair Science. Weymouth UK: Micelle Press. 9 Franbourg A, Leroy F. (2005) Hair structure and physicochemical properties. In: Bouillon C, Wilkinson J, eds. The Science of Hair Care. Boca Raton, FL: CRC Press, pp. 351–76. 10 Marshall RC. (1986) Nail, claw, hoof and horn keratin. In: Bereiter-Hahn J, Matoltsy AG, Richards KS, eds. Biology of the Integument II. Berlin: Springer Verlag, pp. 722–38. 11 Zahn H. (1977) Wool as a biological composite structure. Lenzinger Ber 42, 19–34. 12 Umprecht JG, Patel K, Bono KP. (1977) Effectiveness of reduction and oxidation in acid and alcaline permanent waving. J Soc Cosmet Chem 28, 717–32.

31. Permanent hair waving 13 Lang G, Schwan-Jonczyk A. (2004) Haarverformungsmittel (Hair waving preparations). In: Umbach W, ed. Kosmetik und Hygiene, 3rd edn. Weinheim: Wiley-VCH Verlag, pp. 264–78. 14 Schwan A, Zang R. (1993) Method and apparatus for the shaping treatment of hair wound on to rollers, including human hair. Wella AG EP 0321939B1. 15 Borish ET. (1997) Hair waving. In: Johnson D, ed. Hair and Hair Care, Cosmetic Science and Technology, Vol. 17. Marcel Dekker, pp. 167–90. 16 Garcia ML, Nadgorny EM, Wolfram LJ. (1990) Letter to the Editor: Physicochemical changes in hair during permanent waving. J Soc Cosmet Chem 41, 149–53. 17 Wickett R, Savaides A. (1993) Permanent waving of hair. In: Knowlton J, Pearce S, eds. Handbook of Cosmetic Science and Technology, 1st edn. Oxford: Elsevier Science, pp. 511–34. 18 Shipp JJ. (1996) Hair care products. In: Williams DF, Schmitt WH, eds. Chemistry and Technology of the Cosmetics and Toiletries Industry, 2nd edn. Chapman & Hall. 19 Dallal JA. (2000) Permanent waving, hair straightening and depilatories. In: Rieger MM, ed. Harry′s Cosmeticology, 8th edn. New York: Chemical Publishing, Chapter 32. 20 Clausen T, Schwan-Jonczyk A, Lang G, Clausen T, Liebscher KD, et al. (2006) Hair preparations. In: Ullmann′s Encyclopedia of Industrial Chemistry, 7th edn, Vol. A 12, Weinheim: Wiley, pp. 571. 21 Shansky A. (2008) Antichaotropic salts for stabilizing cysteine in perm solutions. In: Koslowsky AC, Allured J, eds. Hair Care: From Physiology to Formulation. Carol Stream, IL: Allured, pp. 341–6. 22 Technische Regeln für Gefahrstoffe, Friseurhandwerk TRGS530 (2007) GMBL, Bundesministerium für Arbeit und Soziales. 23 Lee AE, Bozza JB, Huff S, Mettric R. (1988) Permanent waves: an overview. Cosmet Toiletr 103, 37–56.

24 EU Council Directive of 27 July 1976 on the approximation of the laws of the Member States relating to cosmetic products (76/768/EEC). 25 Meisterburg M, Riehl U, et al. (2007) Friseurwissen (Hairdresser’s knowledge). Schmidt W, ed. Troisdorf, Germany: Bildungsverlag EINS. Available at 26 IKW information. (2008) Undesireable effects of cosmetics. Available at 27 Draelos ZD. (2000) Safety and performance. In: Rieger MM, ed. Harry’s Cosmeticology, 8th edn. New York: Chemical Publishing, Chapter 34. 28 Hourseau C, Cottin M, Baverel M, Meurice P, Riboulet-Delmas G. (2005) Hair product safety. In: Bouillon C, Wilkinson J, eds. The Science of Hair Care. Boca Raton, FL: CRC Press, pp. 351–76. 29 Han M, Chun J, Lee J, Chung C. (2008) Effects of perms on changes of protein and physicomorphological properties in human hair. J Soc Cosmet Chem 59, 203–15. 30 Hilterhaus-Bong S, Zahn H. (1989) Protein and lipid chemical aspects of permanent waving treatments. Int J Cosmet Sci 11, 164–74, 221–34. 31 Wilkinson JD, Shaw S. (2005) Adverse reactions to hair products. In: Boullion C, Wilkinson J, eds. The Science of Hair Care. Boca Raton, FL: CRC Press, p. 521. 32 Bergfeld WF. (1981) Side effects of hair products on the scalp and hair. In: Orfanos CE, Montagna W, Stüttgen G, eds. Hair Research. Berlin: Springer Verlag, pp. 507–12. 33 Ishihara M. (1981) Some skin problems due to hair preparations. In: Orfanos CE, Montagna W, Stüttgen G, eds. Hair Research. Berlin: Springer Verlag, pp. 536–42. 34 Orfanos CE, Sterry W, Leventer T. (1979) Hair and hair cosmetic treatments. In: Orfanos CE, ed. Hair and Hair Diseases. Stuttgart: G. Fischer Verlag, pp. 853–85. 35 Robbins CR, Fernee KM. (1983) Some observations on the swelling of human epidermal membrane. J Soc Cosmet Chem 34, 21–34.


Chapter 32: Hair straightening Harold Bryant, Felicia Dixon, Angela Ellington, and Crystal Porter L’Oréal Institute for Ethnic Hair and Skin Research, Chicago, IL, USA

BAS I C CONCE P T S • Hair is straightened to improve manageability and provide style versatility. • To straighten hair, an alteration of the cortex must occur. • To achieve temporary straightening – a lower energy process – hydrogen bonds and salt linkages are altered while permanent straightening is achieved through the modification of covalent bonds, which requires more energy. • Permanent hair straightening can be accomplished with ammonium thioglycolate, sulfites, and hydroxide.

Introduction The desire for straight hair was once attributed to a “universal” vision of beauty and social status associated with straight hair; however, recent information links this style preference to improved manageability and style versatility. In order to achieve the straight look, it is necessary to transform the natural hair configuration, which has been linked to the shape of the follicle. Bernard et al. [1,2] found that the asymmetric protein expression in curved follicles was associated with the formation of curly hair. At this time, it is not possible to straighten hair by changing the shape of the follicle. However, it is possible to straighten hair based on its chemical composition. For mature hair, the composition is generally the same and consists of roughly 90% protein with smaller quantities of water, lipids, and minerals but does not vary by degree of curl, despite differences that exist in the early stages of hair production. To understand how hair can be transformed, it is important to know the different components of hair. Hair is made-up of three macro structures including the cuticle, cortex, and medulla, the latter being of little significance. The major morphologic part of the hair is the cortex, which is made up of highly organized α-helical proteins packed in a cystine-rich matrix. To straighten hair, an alteration of the cortex must occur. There are three types of bonds in hair: hydrogen, electrostatic salt linkages, and covalent, each consecutively requiring more energy to break. Based on the bonds that can be affected, there are two categories of straightening: temporary and permanent. To achieve temporary straightening, a lower energy process is required involving alteration of

Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. ©2010 Blackwell Publishing.


hydrogen bonds and salt linkages while permanent straightening is achieved through the modification of covalent bonds, which requires more energy. Thermal appliances can be used to disrupt and rearrange the weaker hydrogen bonds and salt linkages required for temporary straightening. Depending on the approach, the results can last from a few days to several months. However, permanent straightening is obtained through a chemical process that alters the protein structure by cleaving and reforming covalent bonds, preventing the hair from returning to its natural curly state until it grows out from the scalp. The following are usually considered when choosing the type of hair straightening process or treatment: degree of curl, degree of desired straightness, point of service, convenience, environmental conditions, and the desired frequency of straightening. All of these are important; however, the degree of curl in hair may be the most influential because it impacts other desired attributes. It is often subjectively described and ranges from various degrees of wavy to tightly curled. These descriptors are relative and can be confusing because they often overlap. Thus, the L’Oréal Curl Classification was recently developed to quantitatively describe the degree of curl in hair (Figure 32.1) [3]. This classification used hair from around the world and identified eight distinct curl types, where the degree of curl increases directly with number. People with curl types I–IV often have concerns about hair frizz and volume while higher curl types are more concerned about manageability. Thermal techniques can be used to achieve straight hair for all curl types but, typically, curl types V and above are difficult to straighten permanently without the use of hydroxide-based systems. Hair straightening appliances and chemicals are centuries old; however, instrument designs and formulations have evolved to improve effectiveness while limiting the negative attributes. New materials are used for the heated surface of flat irons and product formulas have been modified and

32. Hair straightening









Figure 32.1 Hair classification types to differentiate the degree of curl in hair.

developed to protect hair and scalp and aid in the ease of application. In some markets, the combination of heat and chemicals is often used. This chapter briefly reviews the most common straightening practices, including a description of the procedures and perceived advantages and disadvantages.

Thermal processing The use of thermal appliances dates back to the Egyptian period and is still considered to be a necessity to most women in today’s world. In the Egyptian period, hot metal was used to straighten hair. A less aggressive method was popularized in the late 1800s with the invention of the blow-dryer; the handheld version for home use became available in the 1920s. This increased the ability for women with curl types I–IV to have a variety of temporary and permanent styles (hot waving). Because curl types V–VIII were inherently more resistant to reconfiguration, there was a specific need to straighten these hair types. This was achieved with the popularization of the hot comb combined with pressing oil, attributed to Madame C.J. Walker in the early 1900s. The hot comb, still in use today, is a metal comb heated to temperatures

reaching 450 °F. Whether utilizing a hot comb, professional tongs heated in a Marcel oven, or one of the electronic devices such as a blow-dryer, curling iron, or flat iron, the process involves using heat and mechanical stress. These common thermal appliances represent an alternative way for people with naturally curly hair to achieve manageability and straight hair styles. The combination of heat and mechanical stress, in the form of combing or brushing while blow-drying and smoothing with the other devices, straightens hair by rearranging hydrogen bonds. Once straightened, the new configuration of the hair is only temporary and will revert back to its natural state after exposure to moisture from any source such as environmental conditions and perspiration. Temperatures of thermal appliances typically range from 150–232 °C (302–450 °F). While thermal processing is considered temporary in terms of styling, it can have a permanent effect on hair. For example, the proteins in hair can start to denature at high temperatures. Protein denaturation is a process by which proteins are irreversibly altered by an external stimulus, and for hair can result in decreased fiber integrity. The denaturation temperature is 235–250 °C (455– 482 °F) and 155–160 °C (311–320 °F) for dry and wet hair, respectively [4–6]. The upper temperature limits for some of the appliances exceeds the denaturation temperature for



Hair Cosmetics

wet and dry hair so care must be taken to avoid repeated applications and overheating. Of all heat appliances currently available to straighten hair, the flat iron is rapidly becoming the most popular; therefore, it is the focus of technologic advancements. Important attributes of a good flat iron are the ability to provide even heat and maintain a consistent temperature. Recent improvements in temperature control promote thermal stability and coatings, including ceramic and titanium, provide durability and reduced friction. Reduced friction is critical to maintaining a smooth cuticle surface and reducing breakage during thermal processing. Other advances in materials include the incorporation of pure ceramic heating elements and minerals (tourmaline) that allow manufacturers to make claims about the positive effects of ions and far infrared radiation on the final state of the hair. The product offerings associated with the use of thermal appliances typically contain hydrocarbon-based ingredients (e.g. petrolatum and mineral oil) and polymers (e.g. silicone-derived, cationic, and non-ionic) to condition, protect, and accommodate styling preferences. Because blow-drying typically starts in the wet state when hair is vulnerable to damage, conditioning polymers (e.g. polyquaternium 10) that improve wet combing by reducing frictional forces are typically used. Prior to heat application, products that contain ingredients such as sugars and silicones can be applied. Sugars help to increase thermal integrity while silicones protect the hair by acting as a thermal barrier. Silicones also can function as lightweight films whereas hydrocarbons are often used when a heavier coating is desired for style preferences.

Reducing agents Reducing treatments are traditionally known to curl hair (hot and cold permanent waving); however, they can also be used to straighten hair. The chemistry involves a two-step process where the disulfide bonds in hair keratin are cleaved in the first (reducing) step followed by oxidization in the second step to form new disulfide bonds (Scheme 32.1). The difference between straightening and waving using reducing agents is the configuration of hair prior to oxidation and the form of the product during the reducing step. The reducing product for waving the hair is usually a liquid and the hair is curled using rollers before oxidizing. For straightening, the product is usually in the form of a thick cream so that the viscosity of the product can assist in holding hair fibers in a straightened configuration during manipulation. The most commonly used reducing agents in this process are ammonium thioglycolate (thiols) and sulfite.

Ammonium thioglycolate Thioglycolate straighteners come in several product strengths. Treatment procedures and strength should be based on the hair attributes according to product recommendations. For curl types V–VIII, these products usually leave the hair with residual curl so the result can be disappointing if a straight style is desired. In addition, the hair can feel dry as a result of the treatment; thus, products that contain glycerin are used to provide moisture. Thioglycolate straighteners can be used on hair that has been previously colored or permed; however, it is not recommended for bleached or relaxed hair.

Reduction step









CO + 2R


2 HS



R +






Oxidation step





CO +










NH Scheme 32.1


32. Hair straightening In addition to traditional thiol straighteners, a new technique is becoming popular that includes the incorporation of heat with thiol-based cream products. These treatments are used to permanently straighten and/or reduce volume in curl types I–V. They are commonly used on Asian and Brazilian hair and go by several names that are listed in Table 32.1. Even though there are several names, they all use similar processes to achieve hair characteristics that consumers describe as straight, soft, and shiny. The main point of differentiation between this new treatment and the traditional straightening method is the application of heat prior to the oxidation step for the Asian and Brazilian treatments. Details about the specific procedure can be found in the appendix. This straightening technique is not recommended for natural hair that is higher than curl type V, particularly hair from people of African descent because it is inherently more fragile than other hair [7]. After a period of time, the processes described above will need to be repeated to the new hair growth because of its natural configuration. The treatment should only be per-

Table 32.1 Common names for thiol-based straighteners that use heat. Culture that introduced the technique

Popular thiol-based treatments


Hair rebonding Thermal reconditioning and restructuring Ion retexturizing Bio ionic system Japanese hair restructuring Straightening and reconditioning Japanese straightening perm




Sulfites are an additional class of reducing agents that can be used for hot waving or straightening depending on the procedure. Even though sulfite straighteners have been around for decades, they are less common than hydroxide relaxers because they tend to result in less effective straightening of highly curled hair (types VI–VIII). However, they are believed to be less irritating to the scalp. The decrease in straightening efficacy may be related back to the reactivity of the disulfide bonds, which depends on the pH of the active solution. The maximum reactivity is reached at pH 4–6, but sulfites are not stable at such low pH conditions [8,9]. Because of this, commercial products generally range in pH from 6.5 to 7.5. At pH 7, only about 15% of the cystine residues can be reduced [10]. The first step of the reaction mechanism involves a reduction of the cystine via a nucleophilic reaction similar to thioglycolate, with the exception of the formation of Bunte salt (Scheme 32.2). To lock the hair into the desired conformation, a neutralizing solution is used which typically contains sodium carbonate or bicarbonate. The application procedure is similar to that of a thioglycolate straightener except no oxidant is used, resulting in poor or modest straightening.

According to legend, Garrett A. Morgan was the first person to stumble upon a chemical to permanently straighten hair in the early 1900s [11]. While experimenting with substances to reduce the heat of friction during sewing, he wiped his hands on a cloth that was made of curly pony fur. Later, he found that the fur had been straightened. Following trials on different types of hair, including his own, he started selling the G.A. Morgan Hair Refining Cream. To this day, the identity of this substance is a mystery, but the first known composition for chemically straightening hair was formulated in household kitchens in the 1930s. This contained a chemical mixture of potato starch, lard, egg, and sodium or potassium hydroxide. Because of its corrosive

Note: To be comprehensive, it is cautiously noted that products containing or that are altered with formaldehyde (formol) at higher than approved levels (0.2% as an antimicrobial) are sometimes used to straighten hair. However, formaldehyde is classified as a probable human carcinogen by the Environmental Protection Agency and should not be used to straighten hair.

Scheme 32.2


Hydroxide straighteners

Chocolate, strawberry, kelp, milk, sugar, passion, mint, gold, orchid, French, gumbo, etc. treatment (or brushing) Brazilian keratin treatments (may contain up to 2% formaldehyde)


formed on the new growth, referred to as a “touch-up,” to minimize overlapping of treatments which may result in overprocessed hair. It is recommended that the time between treatments is maximized, with a minimum of 6 weeks, depending on the rate of hair growth.





CO 2–

CH + SO3







Bunte salt







Hair Cosmetics

nature, it was advised to protect or base the scalp with petrolatum before treatment. The use of this concoction led to the development of relaxers. The first commercially available relaxer, based on sodium hydroxide (lye), was introduced in the 1950s by Johnson Products. Even though the relaxer formula included petrolatum, basing the scalp was still a requirement to minimize scalp irritation. The relaxer technology continued to improve in the early to mid 1960s with the invention of the no-base relaxer. This version incorporated higher percentages of petrolatum and mineral oil in the formula and decreased the amount of sodium hydroxide to make it less irritating, thus it claimed to eliminate the need to base the scalp. In the late 1970s, the first no-lye relaxer was marketed that significantly reduced the amount of irritation during treatment [12]. The technology uses a two-part system where a calcium hydroxide cream is mixed with a guanidine carbonate liquid activator to produce guanidine hydroxide. Several other relaxer versions were introduced over time that improved the product attributes, the cosmetic properties, and integrity of the hair. This was achieved through the addition of conditioning agents such as cationic polymers and by incorporating various alkali metal hydroxides in both product forms, mix or no-mix [13,14]. The most commonly used hydroxides are sodium, guanidine, lithium, and potassium (see Table 32.2 for definitions of key terms).

abstraction of the hydrogen beta to the disulfide (Scheme 32.3) [15]. This results in the formation of dehydroalanine, cysteinate ion, and sulfur. Dehydroalanine is a highly reactive intermediate that continues to react with cysteine and lysine moieties in hair to form lanthionine and lysinoalanine, respectively. It can also react with ammonia to form betaaminoalanine. The new thioether bonds (lanthionine) are stable in the presence of reducing agents, such as thioglyco-

Table 32.2 Vocabulary list of select terms related to straightening curly hair.

Chemistry of relaxing Amino acid analysis of relaxed hair hydrolysates indicates lanthionine is the primary product of the reaction. The formation of lanthionine can occur via two pathways. The first is through a binuclear nucleophilic substitution reaction [10]. The second is beta-elimination that is initiated by

CO β


Lye relaxer

Technology that commonly utilizes sodium hydroxide as the active ingredient

No-lye relaxer

Non-sodium hydroxide-based system that includes but is not limited to guanidine and lithium hydroxides. Some of these products require mixing prior to use; those that do not are sometimes referred to as no-lye no-mix

No-base relaxer

A relaxer that may not require basing the scalp with a petrolatum product prior to relaxer application


A lower concentration version of relaxer used to permanently reduce or loosen curl in hair


Thiol-based products used to permanently curl hair according to a sequential reduction– oxidation process













Cysteinate Ion




CH2 +



NH Lysinoalanine







Hydroxide technology used to permanently straighten curly hair. It is sometimes mistakenly referred to as a “perm”


CO α CH2













Scheme 32.3

32. Hair straightening late or sulfite, compared to cystine. This is evidenced by the decrease in solubility of hair protein and the inability to permanently curl relaxed hair. While lanthionization is popularly believed to be the cause of permanent straightening of curly hair, Wong et al. [16] believe that it is not the critical step in hair straightening. They propose that the permanent straightening depends on supercontraction of the fiber. They report that fiber supercontraction is what “locks” the fiber into the straight configuration and the formation of lanthionine is a by-product rather than a requirement.

Effect of relaxers on hair

quality, and relaxer efficiency. Users of lye technology reported a higher incidence of scalp irritation while no-lye users experienced more hair quality issues. The same study showed that consumers were more likely to take action for hair quality issues and more often seek advice from a stylist as opposed to consulting a dermatologist or physician. In a separate study, it was noted that those who frequently obtain services at a salon, more than 50% of them were unaware of the specific relaxer type being used [20]. All hydroxide-based relaxers follow the same chemistry and are designed to straighten hair but to varying degrees. Due to the high pH, relaxers cause swelling of the fiber, cuticle abrasion, loss of the hydrophobic lipid layer, an increase in porosity, a loss in tensile strength, and an increase in plasticity.1 All of these affects weaken the hair compared with its natural state. The swelling and deswelling of the hair during the process may in part, be responsible for loss in fiber strength as it can result in cracks proposed to be related to the change in osmotic pressure also associated with permanent waving [18]. In addition to cracks, cuticle swelling may cause cuticle erosion. Figure 32.2 shows the progression of the cuticle surface during the relaxer process. After the relaxer has been rinsed from the hair before neutralizing, the image shows the presence of cuticle scales that have been abstracted from the hair fiber but still remain on the hair. After neutralizing, the loose cuticle scales are removed. The images representing neutralized and conditioned fiber surfaces show that while relaxers erode cuticle layers from the hair, some amount of the protective layer is still present. In addition to the cuticle, the cortex, which is mainly responsible for the hair’s strength, is also affected during relaxing. The original protein linkages in hair are altered, and when this occurs the hair becomes more fragile. The decrease in break stress and increase in break extension indicates that the hair becomes weaker and is more prone to deformation after relaxing. Even though hair quality is compromised, the straightened configuration of hair increases combability as shown in Figure 32.3. This in turn helps to decrease breakage that is known to be associated with combing curly hair and mitigates further decreases in mechanical properties [21]. It is important to follow relaxer services with post-relaxer treatments such as conditioners to further enhance manageability and improve the quality of hair. A good conditioner should exhibit the following qualities: improved wet and dry combing, flyaway reduction, and surface protection of the hair. These qualities can be achieved by adding conditioning agents that will reduce the frictional force during combing. Key ingredients commonly used are conditioning agents

In 2006, Yang and Barbosa [19] performed a national study to obtain consumer perceptions of relaxers. From this study, consumer responses on the effects from relaxer use were grouped into three categories including scalp irritation, hair

1 Plasticity: a material property whereby it undergoes irreversible deformation when a high enough force is applied.

Application The relaxer process involves a chemical reaction in addition to mechanical manipulation, which involves the action of smoothing the hair into the desired configuration during application. This can be accomplished with the back of a comb, an application brush, or the fingers. However, the most recommended tool is a comb. Applicator brushes can increase the chance of scalp irritation and the use of fingers is not suggested because of the caustic nature of the relaxer ingredients. The initial relaxer is applied to the full length of the fiber. Subsequent treatments are only applied to new growth, which typically occurs within 6–8 weeks. The exact period of time should be determined based on the amount of new hair growth, which varies with the individual. For example, hair growth rates can range from approximately 4 mm/month to 18 mm/month [17]. Several key factors are used to determine the relaxer type, such as hair diameter, degree of curl, porosity, and type of prior chemical treatments. To help maintain the integrity of hair, it is important to follow the directions on the package carefully. Overprocessing and improper neutralization are problems that are commonly associated with relaxer misuse. Similar to thermal processing, repeat application on the same section of hair and treating the hair longer than the recommended time can result in overprocessing and may result in hair breakage. Determination of proper application time can be achieved by performing the recommended strand test. To insure proper removal of the relaxer, hair should be rinsed thoroughly followed by the application of a neutralizing shampoo, sometimes referred to as chelating or decalcifying. These shampoos are acidic with a pH typically ranging from 4.5 to 5.5. The neutralizing step is an important part of the relaxer process because it helps return the hair to a neutral pH. This is necessary because, at high pH, hair swells up to 70–80% during relaxing making the hair susceptible to damage [18].



Hair Cosmetics





Figure 32.2 Scanning electron micrograph images of hair fibers under different treatment conditions, (a) virgin; (b) after relaxer rinse only; (c) after neutralization; (d) after conditioning.

Combing force vs. distance


Combing force (g)

Curly Straightened




0 0


80 40 60 Combing distance (mm)

such as polyquaternium-6, behentrimonium chloride, and hexadimethrine chloride. In addition, ceramides and panthenol are linked to increasing the cuticle integrity and relative strength of hair [22]. Although sodium hydroxide (lye) and guanidine (no-lye) relaxers straighten the hair via the same chemical pathway, some important differences exist between the two technologies. It is well established through published and unpublished studies that the guanidine systems are milder to the




Figure 32.3 Combing profiles of curly and straightened hair.

scalp causing less incidence of irritation [23]. In addition, unpublished laboratory studies indicate that guanidine systems create more lanthionine (7.4% vs 5.2% lanthionine) in the same time than the sodium hydroxide systems. The majority of sodium hydroxide relaxer users visit the salon while home users tend to use the guanidine system. These differences should be considered by professionals, home users, and dermatologists involved in deciding which relaxer system is most appropriate for individual use.

32. Hair straightening

Conclusions Hair straightening treatments are popular and can be used to achieve individually desired styles. However, care must be taken to decrease the chances of overprocessing that may occur when processes and chemical treatments are performed improperly. The future of straightening processes and treatments is only limited by science and technology. History shows that even though there have been major scientific advancements, the technology to straighten hair either temporarily or permanently still involves the use of heat with mechanical stress or chemical products. Over time, incremental improvements in thermal appliances and formulations for chemical treatments will continue to occur. Despite the advances, it will remain important to understand the advantages and disadvantages and proper techniques of each method based on personal style preference, hair type, and quality to reduce adverse effects.

Appendix Thiol procedure with heat After the hair is washed and towel-dried, the reducing cream is applied to a small section of hair for the recommended time for a strand test. The minimum time that it takes to achieve the level of curl reduction in that section is noted and the section of hair is rinsed after that time. The hair is then saturated with the cream and gently smoothed into a straight configuration. The cream should be left on the hair for the minimum time that was noted during the strand test; however, the time should not exceed the recommended time. The hair is rinsed thoroughly with water then the hair is 80% dried. A protecting smoothener is applied to the hair and then a brush in conjunction with a blow-dryer or a flat iron is used to straighten the hair in small sections. The ha