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Back for a new edition, Zoe Draelos' outstanding resource to cosmetic dermatology again provides a highly-illustrated, clinical guide to the full range of cosmetic skin treatments.

Bringing together experts from research, industry, surgery and practice, it is structured in four distinct parts for easy navigation by the busy clinician:

Basic Concepts - giving an overview of the physiology pertinent to cosmetic dermatology and the delivery systems by which treatments can take effect;
Hygiene Products - evaluating cleansing and moisturising products;
Adornment - looking at aesthetic techniques such as cosmetics, nail protheses and hair treatment;
Antiaging - ie, injectables, resurfacing and skin contouring techniques, and the rapidly growing area of Cosmeceuticals.

With over 300 high-quality images and key summary boxes throughout, this new edition incorporates the newest procedural innovations in this rapidly developing field. Perfect for all dermatologists, especially those specialising in cosmetic dermatology and whether hospital-based or in private practice, it provides the complete cosmetic regimen for your patients and will be an indispensable tool to consult over and over again.

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2016
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Second edition
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Wiley Blackwell
언어:
english
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560
ISBN 10:
1118655567
ISBN 13:
9781118655566
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1

The cosmetic gaze : body modification and the construction of beauty

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Cosmeceuticals and active cosmetics

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second edition

Cosmetic
Dermatology
Products and Procedures
edited by Zoe Draelos

Cosmetic Dermatology
Products and Procedures

Cosmetic
Dermatology
Products and Procedures
Edited by

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

Second Edition

This edition first published 2016
© 2016 by John Wiley & Sons, Ltd
© 2010 by Blackwell Publishing, Ltd
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 www.wiley.com/wiley-blackwell
The right of the author to be identified as the author of this work has been asserted in accordance with the UK 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
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Act 1988, without the prior permission of the publisher.
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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. It is sold on the understanding that the publisher is not
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The contents of this work are intended to further general scien; tific research, understanding, and discussion only and are not
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damages arising herefrom.
Library of Congress Cataloging-in-Publication Data
Cosmetic dermatology (Draelos)
Cosmetic dermatology : products and procedures / edited by Zoe Diana Draelos.—Second edition.
   p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-118-65558-0 (cloth)
I. Draelos, Zoe Kececioglu, editor. II. Title.
[DNLM: 1. Cosmetics. 2. Dermatologic Agents. 3. Cosmetic Techniques. 4. Dermatologic Surgical Procedures.
5. Skin Care—methods. QV 60]
RL87
646.7′2—dc23
2015030110
A catalogue record for this book is available from the British Library.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic
books.
Cover images: background © Getty Images/Ian Hooton/SPL; middle © Getty Images/Renee Keith
Set in 9.5/12pt Minion Pro by Aptara Inc., New Delhi, India
1

2016

Contents

Contributors, viii
Foreword, xii
Preface, xiii

Part I: Basic Concepts, 1
Section 1: Skin Physiology Pertinent to Cosmetic
Dermatology, 3
1 Epidermal Barrier, 3

Sreekumar Pillai, Megan Manco, and Christian Oresajo

2 Photoaging, 13

Kira Minkis, Jillian Havey Swary, and Murad Alam

3 Pigmentation and Skin of Color, 23

Jasmine C. Hollinger, Chesahna Kindred, and Rebat M.
Halder

4 Sensitive Skin and the Somatosensory System, 33

Francis McGlone and David Reilly

5 Novel, Compelling, Non-invasive Techniques for

Evaluating Cosmetic Products, 42
Thomas J. Stephens, Christian Oresajo, Lily I. Jiang, and
Robert Goodman

6 Contact Dermatitis and Topical Agents, 52

David E. Cohen, Alexandra Price, and Sarika
Ramachandran

Section 2: Delivery of Cosmetic Skin Actives, 65
7 Percutaneous Delivery of Cosmetic Actives to

the Skin, 65
Sreekumar Pillai, Surabhi Singh, and Christian Oresajo

8 Creams and Ointments, 75

10 Personal Cleansers: Body Washes, 96

Keith Ertel and Heather Focht

11 Facial Cleansers and Cleansing Cloths, 103

Thomas Barlage, Susan Griffiths-Brophy, and Erik J.
Hasenoehrl

12 Hand Cleansers and Sanitizers, 110

Duane Charbonneau

13 Shampoos for Normal Scalp Hygiene and Dandruff, 124

James R. Schwartz, Eric S. Johnson, and Thomas L.
Dawson, Jr.

Section 2: Moisturizers, 132
14 Facial Moisturizers, 132

Yohini Appa

15 Hand and Foot Moisturizers, 139

Teresa M. Weber, Andrea M. Schoelermann, Ute
Breitenbach, Ulrich Scherdin, and Alexandra Kowcz

16 Sunless Tanning Products, 148

Angelike Galdi, Peter Foltis, and Christian Oresajo

17 Sunscreens, 153

Dominique Moyal, Angelike Galdi, and Christian Oresajo

Section 3: Personal Care Products, 160
18 Antiperspirants and Deodorants, 160

Eric S. Abrutyn

19 Blade Shaving, 166

Kevin Cowley, Kristina Vanoosthuyze, Gillian McFeat,
and Keith Ertel

Part III: Adornment, 175

Irwin Palefsky

Section 1: Colored Facial Cosmetics, 175

Part II: Hygiene Products, 81
Section 1: Cleansers, 83
9 Bar Cleansers, 83

Anthony W. Johnson, K.P. Ananthapadmanabhan, Stacy
Hawkins, and Greg Nole

20 Facial Foundation, 177

Sylvie Guichard and Véronique Roulier

21 Camouflage Techniques, 186

Anne Bouloc

22 Lips and Lipsticks, 193

Catherine Heusèle, Hervé Cantin, and Frédéric Bonté

v

vi

Contents

23 Eye Cosmetics, 199

Sarah A. Vickery, Robyn Kolas, and Fatima Dicko

Section 2: Nail Cosmetics, 207
24 Nail Physiology and Grooming, 207

Anna Hare and Phoebe Rich

25 Colored Nail Cosmetics and Hardeners, 217

Paul H. Bryson and Sunil J. Sirdesai

26 Cosmetic Prostheses as Artificial Nail Enhancements, 226

Douglas Schoon

Section 3: Hair Cosmetics, 234
27 Hair Physiology and Grooming, 234

Maria Hordinsky, Ana Paula Avancini Caramori, and Jeff
C. Donovan

28 Hair Dyes, 239

Rene C. Rust and Harald Schlatter

29 Permanent Hair Waving, 251

Annette Schwan-Jonczyk, Gerhard Sendelbach, Andreas
Flohr, and Rene C. Rust

30 Hair Straightening, 262

Harold Bryant, Felicia Dixon, Angela Ellington, and
Crystal Porter

31 Hair Styling: Technology and Formulations, 270

Thomas Krause and Rene C. Rust

39 The Contribution of Dietary Nutrients and Supplements

to Skin Health, 357
Helen Knaggs, Steve Wood, Doug Burke, Jan Lephart, and
Jin Namkoong

Section 2: Injectable Anti-aging Techniques, 364
40 Botulinum Toxins, 364

J. Daniel Jensen, Scott R. Freeman, and Joel L. Cohen

41 Hyaluronic Acid Fillers, 375

Mark S. Nestor, Emily L. Kollmann, and Nicole Swenson

42 Calcium Hydroxylapatite for Soft Tissue

Augmentation, 380
Stephen Mandy

43 Autologous Skin Fillers, 385

Amer H. Nassar, Andrew S. Dorizas, and Neil S. Sadick

44 Polylactic Acid Fillers, 390

Kenneth R. Beer and Jacob Beer

Section 3: Resurfacing Techniques, 395
45 Superficial Chemical Peels, 395

M. Amanda Jacobs and Randall Roenigk

46 Medium Depth Chemical Peels, 402

Gary D. Monheit and Virginia A. Koubek

47 CO2 Laser Resurfacing: Confluent and Fractionated, 412

Mitchel P. Goldman and Ana Marie Liolios

48 Nonablative Lasers, 429

Part IV: Anti-aging, 281

Adam S. Nabatian and David J. Goldberg

49 Dermabrasion, 437

Section 1: Cosmeceuticals, 283
32 Botanicals, 283

Carl R. Thornfeldt

33 Antioxidants and Anti-inflammatories, 295

Bryan B. Fuller

34 Peptides and Proteins, 308

Karl Lintner

35 Cellular Growth Factors, 318

Rahul C. Mehta and Richard E. Fitzpatrick

36 Topical Cosmeceutical Retinoids, 325

Olivier Sorg, Gürkan Kaya, and Jean H. Saurat

37 Topical Vitamins, 336

Donald L. Bissett, John E. Oblong, and Laura J. Goodman

38 Clinical Uses of Hydroxyacids, 346

Barbara A. Green, Eugene J. Van Scott, and Ruey J. Yu

Christopher B. Harmon and Daniel P. Skinner

Section 4: Skin Modulation Techniques, 445
50 Laser-assisted Hair Removal, 445

Keyvan Nouri, Voraphol Vejjabhinanta, Nidhi Avashia,
and Jinda Rojanamatin

51 Radiofrequency Devices, 451

Vic Narurkar

52 LED Photomodulation for Reversal of Photoaging and

Reduction of Inflammation, 456
David McDaniel, Robert Weiss, Roy Geronemus, Corinne
Granger, and Leila Kanoun-Copy

Section 5: Skin Contouring Techniques, 463
53 Liposuction: Manual, Mechanical, and Laser

Assisted, 463
Anne Goldsberry, Emily Tierney, and C. William Hanke

Contents

54 Liposuction of the Neck, 476

58 Rosacea Regimens, 509

55 Hand Recontouring with Calcium Hydroxylapatite, 485

59 Eczema Regimens, 517

Kimberly J. Butterwick
Kenneth L. Edelson

Section 6: Implementation of Cosmetic Dermatology
into Therapeutics, 492
56 Anti-aging Regimens, 492

Karen E. Burke

57 Over-the-counter Acne Treatments, 501

Emmy M. Graber and Diane Thiboutot

Joseph Bikowski
Zoe D. Draelos

60 Psoriasis Regimens, 522

Laura F. Sandoval, Karen E. Huang, and Steven
R. Feldman

Index, 529

vii

Contributors

Eric S. Abrutyn

Kimberly J. Butterwick

Murad Alam

Hervé Cantin

K.P. Ananthapadmanabhan

Ana Paula Avancini Caramori

TPC2 Advisors Inc., Boquete, Chiriqui, Republic of Panama

Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Unilever HPC R&D, Trumbull, CT, USA

Yohini Appa

Johnson & Johnson, New Brunswick, NJ, USA

Cosmetic Laser Dermatology, San Diego, CA, USA

LVMH Recherche, Saint Jean de Braye, France

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

Duane Charbonneau

Procter and Gamble Company, Health Sciences Institute, Mason, OH, USA

Nidhi Avashia

Boston University School of Medicine, Boston, MA, USA

Thomas Barlage

Procter & Gamble Company, Sharon Woods Technical Center,
Cincinnati, OH, USA

Jacob Beer

Department of Dermatology, University of Pennsylvania, PA, USA

Kenneth R. Beer

General, Surgical and Esthetic Dermatology, West Palm Beach, FL, USA

David E. Cohen

The Ronald O. Perelman Department of Dermatology, New York University
School of Medicine, New York, NY, USA

Joel L. Cohen

AboutSkin Dermatology and DermSurgery, Englewood, and Department of
Dermatology, University of Colorado at Denver, Aurora, CO, USA

Kevin Cowley

Gillette Innovation Centre, Reading, UK

Thomas L. Dawson, Jr.

Joseph Bikowski

Bikowski Skin Care Center, Sewickley, PA, USA

Agency for Science, Technology and Research (A*STAR), Institute for
Medical Biology, Singapore

Donald L. Bissett

Fatima Dicko

Procter & Gamble Beauty Science, The Procter & Gamble Co., Sharon Woods
Innovation Center, Cincinnati, OH, USA

Procter & Gamble Cosmetics, Hunt Valley, MD, USA

Frédéric Bonté

L'Oréal Institute for Ethnic Hair and Skin Research, Chicago, IL, USA

Felicia Dixon

LVMH Recherche, Saint Jean de Braye, France

Anne Bouloc

Jeff C. Donovan

Division of Dermatology, University of Toronto, Toronto, Canada

Vichy Laboratoires, Cosmétique Active International, Asnières, France

Ute Breitenbach

Andrew S. Dorizas

Sadick Dermatology, New York, NY, USA

Beiersdorf AG, Hamburg, Germany

Harold Bryant

Kenneth L. Edelson

Icahn School of Medicine at Mount Sinai and Private Practice, New York, NY, USA

L'Oréal Institute for Ethnic Hair and Skin Research, Chicago, IL, USA

Paul H. Bryson

OPI Products Inc., Los Angeles, CA, USA

Doug Burke

Nu Skin and Pharmanex Global Research and Development, Provo, UT, USA

Karen E. Burke

The Mount Sinai Medical Center, New York, NY, USA

viii

Angela Ellington

L'Oréal Institute for Ethnic Hair and Skin Research, Chicago, IL, USA

Keith Ertel

Procter & Gamble Co., Cincinnati, OH, USA

Steven R. Feldman

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

Contributors

Richard E. Fitzpatrick (deceased)

C. William Hanke

Andreas Flohr

Anna Hare

Heather Focht

Christopher B. Harmon

Peter Foltis

Erik J. Hasenoehrl

Scott R. Freeman

Jillian Havey Swary

Bryan B. Fuller

Stacy Hawkins

Angelike Galdi

Catherine Heusèle

Roy Geronemus

Jasmine C. Hollinger

Department of Dermatology, UCSD School of Medicine, San Diego, CA, USA

Wella/Procter & Gamble Service GmbH, Darmstadt, Germany

Procter & Gamble Co, Cincinnati, OH, USA

L'Oréal Research, Clark, NJ, USA

Sunrise Dermatology, Mobile, AL, USA

DermaMedics LLC, Oklahoma City, OK, USA

L'Oréal Research and Innovation, Clark, NJ, USA

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

David J. Goldberg

Mount Sinai School of Medicine, New York, NY, and Skin Laser and Surgery
Specialists of New York and New Jersey, USA

Mitchel P. Goldman

Cosmetic Laser Dermatology and Volunteer Clinical Professor of Dermatology at the
University of California, San Diego, CA, USA

Anne Goldsberry

Laser and Skin Surgery Center of Indiana, Carmel, IN, USA

Laura J. Goodman

Procter & Gamble Beauty Science, The Procter & Gamble Co., Sharon Woods
Innovation Center, Cincinnati, OH, USA

Robert Goodman

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

Emmy M. Graber

Boston University School of Medicine, Boston, MA, USA

Corinne Granger

Director of Instrumental Cosmetics, L'Oreal Research, Asnieres, France

Laser and Skin Surgery Center of Indiana, Carmel, IN, USA

Emory School of Medicine, Atlanta, GA, USA

Surgical Dermatology Group, Birmingham, AL, USA

Procter & Gamble Company, Ivorydale Technical Center, Cincinnati, OH, USA

Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Unilever HPC R&D, Trumbull, CT, USA

LVMH Recherche, Saint Jean de Braye, France

Howard University College of Medicine, Washington, DC, USA

Maria Hordinsky

Department of Dermatology, University of Minnesota, Minneapolis, MN, USA

Karen E. Huang

Center for Dermatology Research, Wake Forest University School of Medicine;
Winston-Salem, NC, USA

M. Amanda Jacobs

Division of Dermatology, Geisinger Health Systems, Danville, PA, USA

J. Daniel Jensen

Scripps Clinic, Bighorn Mohs Surgery and Dermatology Center, La Jolla, CA, USA

Lily I. Jiang

Thomas J. Stephens & Associates Inc., Texas Research Center, Richardson,
TX, USA

Anthony W. Johnson

Unilever HPC R&D, Trumbull, CT, USA

Eric S. Johnson

Procter & Gamble Beauty Science, Cincinnati, OH, USA

Leila Kanoun-Copy

L'Oréal Research, Chevilly Larue, France

Barbara A. Green

NeoStrata Company, Inc., Princeton, NJ, USA

Gürkan Kaya

Department of Dermatology, Geneva University Hospital, Geneva, Switzerland

Susan Griffiths-Brophy

Procter & Gamble Company, Sharon Woods Technical Center, Cincinnati,
OH, USA

Chesahna Kindred

Sylvie Guichard

Helen Knaggs

L'Oréal Research, Chevilly-Larue, France

Rebat M. Halder

Howard University College of Medicine, Washington, DC, USA

Howard University College of Medicine, Washington, DC, USA

Nu Skin and Pharmanex Global Research and Development, Provo, UT, USA

Robyn Kolas

Procter & Gamble Cosmetics, Hunt Valley, MD, USA

ix

x

Contributors

Emily L. Kollmann

Amer H. Nassar

Virginia A. Koubek

Mark S. Nestor

Center for Clinical and Cosmetic Research, Aventura, FL, USA

Total Skin and Beauty Dermatology Center, PC, and Departments of Dermatology
and Ophthalmology, University of Alabama, Birmingham, AL, USA

Alexandra Kowcz

Beiersdorf Inc, Wilton, CT, USA

Thomas Krause

Wella/Procter & Gamble Service GmbH, Darmstadt, Germany

Jan Lephart

Sadick Dermatology, New York, NY, USA

Center for Clinical and Cosmetic Research, Aventura, FL, USA

Greg Nole

Unilever HPC R&D, Trumbull, CT, USA

Keyvan Nouri

University of Miami Miller School of Medicine, Miami, FL, USA

John E. Oblong

Nu Skin and Pharmanex Global Research and Development, Provo, UT, USA

Procter & Gamble Beauty Science, The Procter & Gamble Co., Sharon Woods
Innovation Center, Cincinnati, OH, USA

Karl Lintner

Christian Oresajo

KAL'IDEES SAS, Paris, France

Ana Marie Liolios

Private Practice, Fairway, Kansas, MO, USA

Megan Manco

L'Oréal Recherche, Clark, NJ, USA

Stephen Mandy

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

David McDaniel

McDaniel Institute of Anti Aging Research, Virginia Beach, VA, Eastern Virginia
Medical School, Norfolk VA and Old Dominion University Norfolk VA, USA

Gillian McFeat

Gillette Innovation Centre, Reading, UK

Francis McGlone

School of Natural Sciences and Psychology, Liverpool John Moores University,
Liverpool, UK

L'Oréal Research, Clark, NJ, USA

Irwin Palefsky

Cosmetech Laboratories, Inc., Fairfield, NJ, USA

Sreekumar Pillai

L'Oréal Research, Clark, NJ, USA

Crystal Porter

L'Oréal Institute for Ethnic Hair and Skin Research, Chicago, IL, USA

Alexandra Price

The Ronald O. Perelman Department of Dermatology, New York University School of
Medicine, New York, NY, USA

Sarika Ramachandran

The Ronald O. Perelman Department of Dermatology, New York University School of
Medicine, New York, NY, USA

David Reilly

Unilever Research, Colworth Science Park, Sharnbrook, Bedford, UK

Rahul C. Mehta

Phoebe Rich

SkinMedica, Inc, An Allergan Company, Carlsbad, CA, USA

Oregon Health and Science University, Portland, OR, USA

Kira Minkis

Randall Roenigk

Department of Dermatology, Weill Cornell Medical College, New York, NY, USA

Department of Dermatology, Mayo Clinic, Rochester, MN, USA

Gary D. Monheit

Jinda Rojanamatin

Total Skin and Beauty Dermatology Center, PC, and Departments of Dermatology
and Ophthalmology, University of Alabama, Birmingham, AL, USA

Institute of Dermatology, Bangkok, Thailand

Dominique Moyal

L'Oréal Research, Chevilly-Larue, France

Véronique Roulier

La Roche-Posay Laboratoire Dermatologique, Asnières sur Seine, France

Adam S. Nabatian

Rene C. Rust

GSK/Stiefel, Brentford, Middlesex, UK

Albert Einstein College of Medicine, Bronx, NY, USA

Jin Namkoong

Neil S. Sadick

Nu Skin and Pharmanex Global Research and Development, Provo, UT, USA

Sadick Dermatology, New York, NY and Department of Dermatology, Weill Medical
College of Cornell University, New York, NY, USA

Vic Narurkar

Laura F. Sandoval

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

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

Contributors

Jean H. Saurat

Nicole Swenson

Ulrich Scherdin

Diane Thiboutot

Harald Schlatter

Carl R. Thornfeldt

Andrea M. Schoelermann

Emily Tierney

Swiss Centre for Applied Human Toxicology, University of Geneva, Geneva, Switzerland

Beiersdorf AG, Hamburg, Germany

Procter & Gamble German Innovation Centre, Schwalbach am Taunus, Germany

Beiersdorf AG, Hamburg, Germany

Douglas Schoon

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

Annette Schwan-Jonczyk
Private Practice, Darmstadt, Germany

James R. Schwartz

Procter & Gamble Beauty Science, Cincinnati, OH, USA

Gerhard Sendelbach
Darmstadt, Germany

Surabhi Singh

L'Oréal Research, Clark, NJ, USA

Sunil J. Sirdesai

OPI Products Inc., Los Angeles, CA, USA

Daniel P. Skinner

Surgical Dermatology Group, Birmingham, AL, USA

Olivier Sorg

Swiss Centre for Applied Human Toxicology, University of Geneva, Geneva, Switzerland

Thomas J. Stephens

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

Center for Clinical and Cosmetic Research, Aventura, FL, USA

Private Practice, Boston, MA, USA

Episciences, Inc., Boise, ID, USA

Department of Dermatology, Tufts University School of Medicine, Boston,
MA, USA

Eugene J. Van Scott

Private Practice, Abington, PA, USA

Kristina Vanoosthuyze

Gillette Innovation Centre, Reading, UK

Voraphol Vejjabhinanta

Institute of Dermatology, Bangkok, Thailand

Sarah A. Vickery

Procter & Gamble Cosmetics, Hunt Valley, MD, USA

Teresa M. Weber

Beiersdorf Inc, Wilton, CT, USA

Robert Weiss

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

Steve Wood

Nu Skin and Pharmanex Global Research and Development, Provo, UT, USA

Ruey J. Yu

Private Practice, Chalfont, PA, USA

xi

Foreword

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 has 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.
Dr. 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 Anti-aging,
which includes cosmeceuticals, injectable anti-aging 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

Addendum
Who better to author and edit a textbook on cosmeceuticals
than Zoe Draelos. She is the recognized leader in the field, having done most of the premier studies and written many of the
definitive articles on the topic over the last decades.
In her first edition, Dr. Draelos set the standard for comprehensive texts on the subject of cosmeceuticals. With this second edition, she has raised the bar even further, producing a
near encyclopedic, comprehensive tome on the subject. It is a

xii

t­ reasure trove of information on the subject, without which anyone interested in the topic would be sorely lacking.
Use it as a reference text, dip into chapters or sections from
time to time, or if you really want to know this subject, read it
from cover to cover.
Enjoy and treasure this work.
Jeffrey S. Dover
Boston, April 2015

Preface

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, non‐foaming, 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, anti‐inflammatories, 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
addressed 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 nonablative. Other rejuvenative devices
affecting 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

xiii

xiv

Preface

the topic, discuss unique attributes, advantages and disadvantages, and indications.
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 knowledge base. This is no longer the case. Cosmetic dermatology has become a field unto itself.
Zoe D. Draelos
Durham, NC

Part I

Basic Concepts

Sec tion 1:

Skin Physiology Pertinent to Cosmetic Dermatology

Chapter 1

Epidermal Barrier
Sreekumar Pillai, Megan Manco, and Christian Oresajo
L’Oréal Research, Clark, NJ, USA

Basic Concepts
• The outermost structure of the epidermis is the stratum corneum (SC) and it forms the epidermal permeability barrier which prevents
the loss of water and electrolytes.
• Understanding the structure and function of the stratum corneum and the epidermal barrier is vital because it is the key to healthy skin.
• Novel delivery systems play 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.
• Cosmetic companies will exploit this new knowledge in developing more efficacious products for strengthening the epidermal barrier
and to enhance the functional and aesthetic 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,
dermis and the hypodermis. Epidermis is the outermost
structure and it is a multi‐layered epithelial tissue divided into
several layers. The outermost structure of the epidermis is the
stratum corneum (SC) and it forms the epidermal permeability
barrier which prevents the loss of water and electrolytes. Other
protective/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 stratum corneum 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, that are arranged
in several stratified layers – the basal cell layer, the spinous cell
layer and the granular cell layer whose differentiation eventu-

ally produces the stratum corneum (SC). Unlike other layers, SC
is made of anucleated cells called corneocytes that are derived
from keratinocytes. 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. SC is a structurally heterogeneous
tissue composed of non‐nucleated, flat, protein‐enriched
corneocytes and lipid‐enriched 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 stratum corneum 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 play important roles in the protective barrier of the skin. A
list of the different structural as well as functional components
of the stratum corneum 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 contains 70% water as do most tissues, yet the
SC contains 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

Cosmetic Dermatology: Products and Procedures, Second Edition. Edited by Zoe Diana Draelos.
© 2016 John Wiley & Sons, Ltd. Published 2016 by John Wiley & Sons, Ltd.

3

4

BASIC CONCEPTS  Skin Physiology Pertinent to Cosmetic Dermatology

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.

leaving a proteinaceous core containing keratins, other structural proteins, free amino acids and amino acid derivatives,
and melanin particles that 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
cornified cell envelope, formed from cross‐linked cytoskeletal
proteins [3].

Proteins of the cornified envelope
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

Table 1.1 Structural and functional components of the stratum corneum
Components

Function

Location

Stratum corneum (SC)

Protection

Topmost layer of epidermis

Cornified envelope (CE)

Resiliency of SC

Outer surface of the SC

Cornified envelope
Precursor proteins

Structural proteins that are cross‐linked to
form CE

Outer surface of the SC

Lamellar granules (LG)

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 bilayers

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

Natural Moisturizing Factor (NMF)

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

1. Epidermal Barrier

protease inhibitors. The cross‐linking is promoted by the
enzyme transglutaminase that 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.
Lamellar granules and inter‐corneocyte lipids
Lamellar granules or bodies (LG or LB) are specialized
lipid carrying 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 stratum corneum, 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 sulphate, respectively. These
enzymes include: lipases, phospholipases, sphingomyelinases,
glucosyl ceramidases, and sterol sulphatases [8,9]. The lipids
fuse together in the stratum corneum 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 [4,21].
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 SC to release the omega hydroxyl
ceramide that gets cross‐ linked to the amino groups of the
cornified envelope proteins. 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 [5,21]. 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.
Desmosomes and corneodesmosomes
Desmosomes are specialized cell structures that provide cell‐
to‐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

5

stabilizes desmosomes. Corneodesmosomes are remnants
of the desmosomal structures that provide the attachment
sites between corneocytes and cohesiveness for the corneocytes in the stratum corneum. Corneodesmosomes have
to be degraded by specialized proteases and glycosidases,
mainly serine proteases, for the skin to shed in a process called
desquamation [6].
Keratohyalin granules
Keratohyalin granules are irregularly shaped granules present
in the granular cells of the epidermis, thus providing these
cells the 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 stratum corneum.
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 [7,8].

Functions of epidermal barrier
Water evaporation barrier (epidermal
permeability barrier)
Perhaps the most studied and the most important function
of SC is the formation of the epidermal permeability barrier
[1,7,8]. SC limits the transcutaneous movement of water and
electrolytes, a function that is essential for terrestrial survival.
Lipids, particularly ceramides, cholesterol, and free fatty
acids, together form lamellar membranes in the extracellular
spaces of the SC that 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 [9,11,12].
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.

6

BASIC CONCEPTS  Skin Physiology Pertinent to Cosmetic Dermatology

Table 1.2 Barrier functions of the epidermis

Table 1.3 Antimicrobial components of epidermis and stratum corneum

Function

Localization/components involved

Component

Class of compound

Localization

Water and electrolyte
permeability barrier

SC/corneocyte proteins and
extracellular lipids

Free fatty acids

Mechanical barrier

SC/corneocytes, cornified envelope

Microbial barrier/immune
function

SC/lipid components/viable epidermis

Hydration/moisturization

SC/NMF

Protection from
environmental toxins/drugs

SC/corneocytes, cornified envelope

Lipid

Stratum corneum

Glucosyl ceramides Lipid

Stratum corneum

Ceramides

Lipid

Stratum corneum

Sphingosine

Lipid

Stratum corneum

Defensins

Peptides

Epidermis

Cathelicidin

Peptides

Epidermis

Psoriasin

Protein

Epidermis

Nucleic acid

Epidermis

Desquamation

SC/epidermis/proteases and
glycosidases

RNAse 7
Low pH

Protons

Stratum corneum

UV barrier

SC/melanins of SC/epidermis

Protein signaling molecules

Epidermis

Oxidative stress barrier

SC, epidermis/antioxidants

“Toll‐like”
receptors
Proteases

Proteins

Stratum corneum
and epidermis

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 stratum
corneum. One such protein, trichohyalin is a multi‐functional
cross‐bridging protein that forms intra and inter protein cross‐
links between cell envelope structure and cytoplasmic keratin filament network [13]. Special enzymes called transglutaminases,
some present exclusively in the epidermis (transglutaminase
3), catalyzes this cross‐linking reaction. In addition, adjacent
corneocytes are linked by corneodesmosomes, and many of
the lipids of the stratum corneum 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.
Microflora that normally inhabit human skin can contribute
to the barrier defenses by competing for nutrients and niches
that more pathogenic organisms require, by expressing
antimicrobial molecules that kill or inhibit the growth of
pathogenic microbes and by modulating the inflammatory
response [32]. Desquamation that 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. 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. They contain common secondary structures that vary from α helical to β sheets,
and their unifying characteristic is the ability to kill microbes
or inhibit them from growing. Pathways that generate and
regulate the antimicrobial barrier of the skin are closely tied
to pathways that modulate the permeability barrier function.
Expression of endogenous AMPs coincides with the presence of a number of epidermal structural components that
may become part of the permeability barrier. For instance,
murine cathelin‐related antimicrobial peptide CRAMP and
mBD‐3 are essential for permeability barrier homeostasis. In
addition, acute and chronic skin barrier disruption lead to
increased expression of murin β‐defensins (mBDs)‐1, ‐3, and
‐14 and this increase in expression is diminished when the
barrier is artificially restored [32].
NMF and skin hydration/moisturization
Natural moisturizing factor (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 corneocyte. Many of the components of the NMF
are derived from the hydrolysis of filaggrin, a histidine‐ and
glutamine‐ rich basic protein of the keratohyalin granule. SC
hydration level controls the protease that hydrolyze filaggrin
and histidase that converts histidine to urocanic acid. As NMF
is water soluble and can easily be washed away from 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,
SC also acts to provide hydration and moisturization to skin.
NMF components absorb and hold water allowing the outermost layers of the stratum corneum to stay hydrated despite
exposure to the harsh external environment. Glycerol, a major
component of the NMF, is an important humectant present
in skin that contributes skin hydration. Glycerol is produced

1. Epidermal Barrier

Table 1.4 Approximate composition of skin Natural Moisturizing Factor
Components

% levels

Amino acids and their salts (over a dozen)

30–40

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

7–12

Urea

5–7

Glycerol

4–5

Glucosamine, creatinine, ammonia, uric acid
Cations (sodium, calcium, potassium)
Anions (phosphates, chlorides)

1–2
10–11
6–7

Lactate

10–12

Citrate, formate

0.5–1.0

locally within 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
[14]. Other humectants in the NMF include urea, sodium and
potassium lactates and PCA [7].
Protection from environmental toxins and topical
drugs penetration
The SC also has the important task of preventing toxic
substances and topically applied drugs from penetrating the
skin. SC acts as a protective wrap due to 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. 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 [6].
In addition, SC also contains protease inhibitors that keep
these proteases in check and the balance of protease – protease
inhibitors play a regulatory role in the control of the desquamatory process. The desquamatory process is also highly regulated
by the epidermal barrier function.

7

The SC contains three families of proteases (serine, cysteine,
and aspartate proteases), including the epidermal‐specific 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
play specific roles in the desquamatory process at different layers of the epidermis.
Melanin and UV barrier
Although melanin is not typically considered a functional
component of 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 melanin, depending on the composition and the
color. The darker eumelanin is most protective to UV than the
lighter, high sulphur 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 ultraviolet radiation is very damaging to proteins, lipids and nucleic acids and cause oxidative damage to these
macromolecules. The SC absorbs some ultraviolet 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 (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 UV‐damaged cells
play a critical role in the decreased photocarcinogenesis seen
in individuals with darker skin [15]. In addition to melanin,
trans‐urocanic acid (tUCA), a product of histidine deamination
produced in the stratum corneum, also acts as an endogenous
sunscreen and protects skin from UV damage.
Oxidative stress barrier
The stratum corneum has been recognized as the main cutaneous
oxidation target of UV and other atmospheric oxidants such
as pollutants and cigarette smoke. Depletion of atmospheric
“ozone layer” allows most energetic UV wavelength of sun radiation, i.e. UVC and short UVB to reach earth level. This high
energy UV radiation penetrates deep into papillary dermis.
UVA radiation in addition to damaging 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 [16]. In addition to its effects on SC, UV also initiates and activates a complex cascade of biochemical reactions

8

BASIC CONCEPTS  Skin Physiology Pertinent to Cosmetic Dermatology

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 [17]. 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 [18]. Skin
naturally uses antioxidants to protect itself from photodamage.
UV depletes antioxidants from outer stratum corneum. A
gradient in the antioxidant levels (alpha‐tocopherol, Vitamin
C, glutathione and urate) with the lowest concentrations in
the outer layers and a steep increase in the deeper layers of the
stratum corneum protects the SC from the oxidative stress [19].
Depletion of antioxidant protection leads to UV induced barrier abnormalities. Topical application of antioxidants would
support these physiological mechanisms and restore a healthy
skin barrier [20,21].

Regulation of barrier homeostasis
Epidermal barrier is constantly challenged by environmental
and physiological factors. Since 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.
Continuous renewal process is balanced by desquamation that
removes individual corneocytes in a controlled manner by degradation of desmosomal constituent proteins by the stratum
corneum proteases. The protease activities are under the control
of protease inhibitors that are co‐localized 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 sulphate also regulate desquamation by controlling the activities of the SC proteases [22].
Corneocyte maturation
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. 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 that 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 / ligands for
the nuclear hormone receptors (example: PPAR – peroxisome

proliferation activator receptor and vitamin D receptor) that
influence keratinocyte terminal differentiation are endogenous
lipids synthesized by the 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
free fatty acids (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, as explained in the previous section, many of the hormonal regulators of corneocyte
maturation are lipids or lipid intermediates synthesized by the
epidermis. Stratum corenum lipid synthesis and lipid content
are also altered with various skin conditions such as inflammation and winter xerosis [23,24].
Environmental and physiological factors
Barrier homeostasis is under control of environmental factors such as humidity variations. High humidity (increased
SC hydration) downregulates barrier competence (as assessed
by barrier recovery after disruption) whereas low humidity
enhances barrier homeostasis. Physiological factors can also
have influence on barrier function. High stress (chronic as well
as acute) increases corticosteroid levels and causes disruption
of barrier homeostasis. During periods of psychological stress
the cutaneous homeostatic permeability barrier is disturbed, as
is the integrity and protective function of the stratum corneum.
Many skin diseases, including atopic dermatitis and psoriasis
are precipitated or exacerbated by psychological stress [34]. Circadian rhythmicity also applies to skin variables related to skin
barrier function. Significant circadian rhythmicity has been
observed in transepidermal water loss, skin surface pH, and
skin temperature. These observations suggest skin permeability
is higher in the evening than in the morning [35]. 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/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

1. Epidermal Barrier

ligands are endogenous lipids control barrier homeostasis. These
liporeceptors include peroxisome proliferator activator receptor
(PPAR alpha, beta and gamma) and Liver X receptor (LXR). The
activators for these receptors are endogenous lipids and lipid
intermediates or metabolites such as certain free fatty acids, 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.
pH and calcium
Outermost stratum corneum pH is maintained in the acidic
range, typically in the range of 4.5–5.0 by a variety of different
mechanisms. This acidity is maintained by formation of free
fatty acids 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, plays a major role in
maintaining the acid pH of the stratum corneum. Maintenance
of an acidic pH in the stratum corneum is important for the
integrity/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 stratum
corneum such as the thiol proteases and cathepsins are more active
in the acidic pH, whereas the SCCE and SCTE present in the lower
stratum corneum are more active at the neutral pH. Under conditions 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 intra‐epidermal
calcium gradient, with peak concentrations of calcium in the
granular layer and decreasing all the way up to the stratum corneum
[10]. 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 lamellar bodies, 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 co‐ordinated. For
example, epidermal permeability barrier, antimicrobial barrier,

9

mechanical protective barrier and UV barrier are all co‐localized
in the stratum corneum. A disruption of one function can lead
to multiple barrier disruptions, and therefore, multiple barrier
functions are coordinately regulated. Disruption of permeability
barrier leads to activation of cytokine cascade (increased levels
of primary cytokines, interleukin‐1 and tumor necrosis factor‐
alpha) which in turn activates the synthesis of antimicrobial
peptides of the stratum corneum. 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 that release the free amino acids
that form the NMF (histidine, glutamine arginine and their
biproducts) and trans‐urocanic acid (deamination of histidine)
that serves as UV barrier.

Methods for studying barrier structure
and function
Physical methods
Stratum corneum integrity/desquamation can be measured
using tape stripping methods. Under dry skin conditions, when
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
SC using cyanoacrylate glue. These physical methods provide a
clue to the binding forces that hold the 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 or 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 epidermal
barrier (TEWL) after barrier disruption using physical methods
(e.g.: tape strips) or chemical methods (organic solvent washing) provide valuable information on the epidermal barrier
properties [26].
Skin hydration can be measured using Corneometer®.
The measurement is based on capacitance of a dielectric
medium. Any change in the dielectric constant due to skin

10

BASIC CONCEPTS  Skin Physiology Pertinent to Cosmetic Dermatology

surface hydration variation alters the capacitance of a precision measuring capacitor. The measurement can detect even
slightest changes in the hydration level. Another important
recent development in skin capacitance methodology is using
SkinChip®. Skin capacitance imaging of skin surface can be
obtained using SkinChip. This method provides information
regarding skin microrelief, level of stratum corneum 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 the Magnetic Resonance Imaging (MRI) can provide useful information on internal structures of SC/epidermis and
its improvements with treatment. MRI has been successfully
used to evaluate skin hydration and water behavior in aging
skin [29].
Biological methods
Ultrastructural details of SC and the intercellular spaces of the SC
can be visualized using transmission electron microscopy (TEM)
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 bilayers within the SC can be visualized by EM after fixation
using ruthenium tetroxide. The existence of corneodesmosomes
in the SC, and their importance in desquamation can be measured
by Scanning electron microscopy (SEM) 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 detergent
solution. The suspension so obtained can be analyzed by microscopy, biochemical or immunological techniques.
Punch or shaved biopsy techniques can be combined with immunohistochemistry using specific SC/epidermis specific antibodies to quantify the SC quality. Specific antibodies for keratinocyte
differentiation specific proteins, desmosomal proteins or specific
proteases can provide answers relating to skin barrier properties.

Relevance of skin barrier to cosmetic
product development
Topical products that influence barrier functions
The human skin is constantly exposed to hostile environment.
These include 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 [7,8]. 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. Moisturizers affect the SC
architecture and barrier homeostatsis, that is, topically applied
ingredients are not as inert to the skin as one might expect. A
number of different mechanisms behind the barrier‐influencing
effects of moisturizers have been suggested, such as simple
deposition of lipid material outside the skin. Ingredients in
the moisturizers may also change the lamellar organization
and the packing of the lipid matrix and thereby change skin
permeability [33]. 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 either or 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
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/
nonessential free fatty acids (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 [20,21].
Topically applied substances may penetrate deeper into the
skin and interfere with the production of barrier lipids and

1. Epidermal Barrier

the maturation of corneocytes. Creams may influence the desquamatory proteases and change the thickness of the SC. The
increased understanding of the interactions between topically
applied substances and epidermal biochemistry will enhance
the possibilities to tailor skin care products for various SC
abnormalities [33].
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 skin
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 due to its increased penetration
into deeper layers of the skin.

Summary and future trends
Major advances have been made in the last several decades in
understanding the complexity and functions of the stratum
corneum. Extensive research by several groups has elucidated
the metabolically active role of the SC and have characterized the
major components and their importance in providing protection
for the organism 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 in 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 into barrier homeostasis
mechanisms.
Novel delivery systems play an increasingly important role
in the development of effective skin care products. Delivery

11

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 Elias PM. (1996) Stratum corneum architecture, metabolic activity
and interactivity with subjacent cell layers. Exp Dermatol 5, 191–201.
5 Uchida Y, Holleran WM. (2008) Omega‐O‐acylceramide, a lipid
essential for mammalian survival. J Dermatol Sci 51,77–87.
6 Harding CR, Watkinson A, Rawlings AV, Scott IR. (2000) Dry skin,
moisturization and corneodesmolysis. Int J Cosmet Sci 22, 21–52.
7 Schaefer H, Redelmeier TE, eds. (1996) Skin Barrier. Principles of
Percutaneous Absorption. Basel: Karger.
8 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.
9 Elias PM (2005). Stratum corneum defensive functions: an integrated view. J Invest Dermatol 125, 183–200.
10 Menon GK, Grayson S, Elias PM. (1985) Ionic calcium reservoirs in
mammalian epidermis: Ultrastructural localization by ion‐capture
cytochemistry. J Invest Dermatol 84, 508–512.
11 Elias PM, Menon GK. (1991) Structural and lipid biochemical
correlates of the epidermal permeability barrier. Adv Lipid Res 24,
1–26.
12 Elias PM, Feingold KR. (1992) Lipids and the epidermal water
barrier: metabolism, regulation, and pathophysiology. Semin Dermatol 11, 176–82.
13 Steinert PM, Parry DA, Marekov LN. (2003) Trichohyalin mechanically
strengthens the hair follicle: multiple cross‐bridging roles in the inner
root shealth. J Biol Chem 278, 41409–19.
14 Choi EH, Man M‐Q, Wang F, Zhang X, Brown BE, Feingold KR,
Elias PM. (2005) Is endogenous glycerol a determinant of stratum
corneum hydration in humans. J Invest Dermatol 125, 288–93.
15 Yamaguchi Y, Takahashi K, Zmudzka BZ, Kornhauser A, Miller
SA, Tadokoro T, Berens W, Beer JZ, Hearing VJ. (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.
16 Sander CS, Chang H, Salzmann S, Muller CSL, Ekanayake‐Mudiyanselage S, Elsner P, Thiele JJ. (2002) Photoaging is associated with
protein oxidation in human skin in vivo 118, 618–25.
17 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, 213–16.

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BASIC CONCEPTS  Skin Physiology Pertinent to Cosmetic Dermatology

18 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 inflammation‐induced matrix degradation. Int J Cosmet Sci 27, 17–34.
19 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.
20 Pinnell SR. (2003) Cutaneous photodamage, oxidative stress, and
topical antioxidant protection. J Am Acad Dermatol 48, 1–19.
21 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.
22 Madison KC. (2003) Barrier function of the skin: “La Raison d'Etre”
of the epidermis. J Invest Dermatol 121, 231–41.
23 Chatenay F, Corcuff P, Saint‐Leger D, Leveque JL. (1990) Alterations
in the composition of human stratum corneum lipids induced by
inflammation. Photoderamtol Photoimmunol Photomed 7, 119–22.
24 Saint‐Leger D, Francois AM, Leveque JL, Stoudemayer TJ, Kligman
AM, Grove G. (1989) Stratum corneum lipids in skin xerosis. Dermatologica 178, 151–5.
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 Research 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, Leveque JL. (1993) Characterization of skin in vivo by high resolution magnetic resonance imaging: water behavior and age‐related
effects. J Invest Dermatol 100, 705–709.
30 Corcuff P, Fiat F, Minondo AM. (2001) Ultrastructure of human
stratum corneum. 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.
32 Gallo R, Borkowsk, A. (2011) The coordinated response of the
physical and antimicrobial peptide barriers of the skin. J Invest Dermatol 131, 285–7.
33 Loden M. (2012) Effect of moisturizers on epidermal barrier
function. Clin Dermatol 30, 286–96.
34 Slominski A. (2007) A nervous breakdown in the skin: stress and
the epidermal barrier. J Clin Invest 11, 3166–9.
35 Yosipovitch G, Xiong G, Haus E, Sackett‐Lundeen L, Ashkenzai I, Maibach H. (1998) Time‐dependent variations of the skin barrier function
in humans: transepidermal water loss, stratum corneum hydration,
skin surface pH, and skin temperature. J Invest Dermatol 1, 20–23.

Chapter 2

Photoaging
Kira Minkis,1 Jillian Havey Swary,2 and Murad Alam2
1

Weill Cornell Medical College, New York, NY, USA
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

2

Basic 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. The skin is at the frontline of defense
of the human body against the harmful effects of UV exposure.
Chronic absorption of UV radiation leads to potential injuries
to the skin which includes 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. Photoaging describes clinical, histologic, and functional changes that are
characteristic of older, chronically sun‐exposed skin. Photoaging
culminates from a combination of predominantly chronic UV
radiation superimposed on intrinsic aging of the skin. 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. Loss of connective tissue, interstitial 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].
The significance of photoaging lies in both the cosmetic and
medical repercussions, i.e. in the demand for agents that can
prevent or reverse the cutaneous signs associated with photoaging
and its strong association with cutaneous malignancies.

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 sun‐exposed 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,
sun‐protected skin is characterized by dryness, fine wrinkles,
skin atrophy, homogeneous pigmentation, and seborrheic keratoses [6]. Extrinsically aged skin, on the contrary, is characterized
by roughness, dryness, fine as well as 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.

Cosmetic Dermatology: Products and Procedures, Second Edition. Edited by Zoe Diana Draelos.
© 2016 John Wiley & Sons, Ltd. Published 2016 by John Wiley & Sons, Ltd.

13

14

Basic Concepts Skin Physiology Pertinent to Cosmetic Dermatology

While the pathophysiology of photoaged and photo‐protected
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, 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.

UV-B

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 penetrates deeper into the skin, with
~50% of UVA penetrating into the skin in a fair‐skinned individual
(versus <10% of UVB photons). UVA therefore 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 absorbing chromophores and causes
cross-linking of adjacent DNA pyrimidines and other DNA-related

UV-A

Epidermis

Keratinocytes
AP-1
NF- B

ROS
Dermis

Fibroblasts

MMP and mtDN A

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. (Source: Berneburg et al., 2000
[30]. Reproduced with permission of John
Wiley & Sons.)

2. Photoaging

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].
Thus UVB induced photodamage is implicated as the predominant
cause of photoaging. The important role of UVA in photoaging,
however, stems from the fact that in distinction to UVB, UVA is
also transmitted through glass. This enables exposure indoors, near
windows, as well as while driving allowing for significant long‐term
exposure. Evidence for this includes dramatic unilateral dermatoheliosis as evident in some chronic occupational drivers [16].
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 [17-19]. 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 [20].
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 [17].
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
[21,22]. 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 [17] 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.

15

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 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, it is important to consider the structure and
function of collagen and its role in maintain the strength and
integrity of the skin.

Molecular mechanisms of photoaging

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 [23]. Dermal collagen has
a half‐life of greater than 1 year [23], 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) [24]. Therefore, in the absence of any
inhibiting factors, the TGF‐β/Smad signaling pathway results
in a net increase in procollagen production.

Mechanisms of intrinsic aging and extrinsic aging (photoaging)
have a significant amount of overlap ultimately culminating in
DNA damage as the underlying mechanism. During the last

How does UV irradiation stimulate photoaging?
UV irradiation stimulates photoaging through several molecular
mechanisms, discussed in detail below.

16

Basic Concepts Skin Physiology Pertinent to Cosmetic Dermatology

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 complex.
This, in turn, reduces TGF‐β target gene expression, such as
expression of type I procollagen [29].

TGFTGFSmad 2,3
Smad 7
T R I/II

*

Smad 2,3
Smad 4

*

Smad 2,3

Smad 4
AP-1

*

Smad 2,3

Smad 4

TGF- target gene

Collagen

Figure 2.2 The regulation of procollagen production: the TGF‐β/Smad sig-

naling pathway. AP‐1, activator protein 1; TβR, TGF‐β receptor; TGF‐β,
transforming growth factor β. (Source: Kang et al., 2001 [3]. Reproduced
with permission of Elsevier.)

Reactive oxygen species
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].
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 [25].
Generation of ROS occurs during normal chronologic aging as
well as in response to UV light exposure in photoaging [26].
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 marker of
UVA photodamage in human dermal fibroblasts is a 4977 base‐
pair deletion of mtDNA that is induced by UVA via ROS [27].
The role of ROS in photoaging is not limited to UVA induced
photodamage. UVB enhances the levels of NF‐κB responsive
proteins, such as, inducible nitric oxide synthase (iNOS) and
cyclooxygenase‐2 (COX‐2), and induces the production of
nitric oxide (NO). NO is a central player in the regulation of
skin cell apoptosis. Furthermore, upon reacting with ROS,
NO is transformed into cytotoxic peroxynitrite (ONOO‐)
which causes lipid peroxidation. Lipid peroxidants are, in
part, responsible for the wrinkle formation that is indicative of
photoaging [28].
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

UV‐induced matrix metalloproteinases stimulate
collagen degradation
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) [30]. 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 [31].
Fibroblasts regulate their own collagen synthesis
Fibroblasts have evolved to regulate their output of extracellular
matrix proteins (including collagen) based on internal
mechanical tension [32]. 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 [32].
This mechanical tension model is different in photoaged
human skin. Fibroblast–integrin attachments are lost, which prevents collagen fragments from binding to fibroblasts. Collagen–

2. Photoaging

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 [32]. Collagen is continually lost as this cycle
repeats itself.
Elastosis and cathepsins
One of the histologic hallmarks of photoaging is elastolysis and
an accumulation of abnormal elastin in the superficial dermis
known as elastosis. One of the most potent enzymes involved in
the degradation of elastin is cathepsin K [33]. This enzyme was
recently shown to be induced in young fibroblasts in response to
UVA irradiation which lead to digestion and clearance of extracellular elastin. This, induction was not seen in fibroblasts from
old donors [34]. Thus, cathepsin K appears to play a critical part
in clearing MMP‐digested elastin in the ECM, a function which
is lost with age and leads to the histologic (and corresponding
clinical effects) of elastosis [35]. Other studies have also demonstrated the downregulation of cathepsins B, D, and K and
upregulation of cathepsin G was seen in photoaged skin and
senescent fibroblasts in vitro [36].
UVA induces the aging‐associated progerin
Recent data has implicated a protein called progerin as a mechanism of UV induced aging. Patients with Hutchinson–Gilford
progeria syndrome (HGPS) have a mutation in LMNA, which
encodes an abnormal and truncated form of Lamin A, called