Philippe HumbertFerial FanianHoward I. MaibachPierre AgacheEditors

Agache’sMeasuring theSkinNon-invasive Investigations,Physiology, Normal ConstantsSecond Edition

Agache’s Measuring the Skin

Philippe Humbert • Ferial FanianHoward I. Maibach • Pierre AgacheEditors

Agache’s Measuring theSkin

Non-invasive Investigations,Physiology, Normal Constants

Second Edition

With 644 Figures and 157 Tables

Editors

Philippe HumbertDepartment of DermatologyUniversity Hospital of BesançonBesançon, France

Ferial FanianCenter for Study and Research onthe IntegumentsDepartment of DermatologyUniversity Hospital of BesançonBesançon, France

Howard I. MaibachDepartment of DermatologySchool of MedicineUniversity of CaliforniaSan Francisco, CA, USA

Pierre Agache (deceased)Department of DermatologyUniversity Hospital of BesançonBesançon, France

The original French edition Physiologie de la peau et explorations fonctionnellescutanées was published by Editions Médicales Internationales, Paris, 2000

ISBN 978-3-319-32381-7 ISBN 978-3-319-32383-1 (eBook)ISBN 978-3-319-32382-4 (print and electronic bundle)DOI 10.1007/978-3-319-32383-1

Library of Congress Control Number: 2016958724

1st edition: # Springer-Verlag Berlin Heidelberg 2004# Springer International Publishing Switzerland 2017This work is subject to copyright. All rights are reserved by the Publisher, whether the whole orpart of the material is concerned, specifically the rights of translation, reprinting, reuse ofillustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,and transmission or information storage and retrieval, electronic adaptation, computer software, orby similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in thispublication does not imply, even in the absence of a specific statement, that such names are exemptfrom the relevant protective laws and regulations and therefore free for general use.The publisher, the authors and the editors are safe to assume that the advice and information in thisbook are believed to be true and accurate at the date of publication. Neither the publisher nor theauthors or the editors give a warranty, express or implied, with respect to the material containedherein or for any errors or omissions that may have been made.

Printed on acid-free paper

This Springer imprint is published by Springer NatureThe registered company is Springer International Publishing AGThe registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

“This textbook is dedicated to the memory of its creator, Professor

Pierre Agache, whose fingerprints are visible in every page”.

Foreword

We live in a world of rapidly increasing information. The journalists andacademicians often speak about this in a negative sense – utilizing the word“overload.”

Many readers understand the overload phenomena and its impact on theirdaily life and work. Few of us can master the rapidly increasing data of theInformation Age.

The Googles of the universe have aided us greatly in dealing with infor-mation overload.

It is divided into the pre- and post-computer age and has been expeditedgreatly by electronic searching and indexing. The Google world is attemptingto ameliorate unmet need-indexing and electronic availability of the world’sbook collections.

In spite of all of these electronic advances and aids, we remain indebted tothe rare scholar – in this case the late Pierre Agache – for his seminalcontributions in the previous edition of this book.

Professor Agache was a dedicated, thoughtful, and disciplined scholar –making the previous edition one of the most valuable reference textbooks foranybody working in the dermatologic space, including the skin, hair, nails, andtheir other organ involvements.

This edition builds upon the work of Pierre’s work.We have in this edition – the current edition – a technology that Pierre did

not have available.The Springer organization has arranged so that this book will be updated –

almost on a daily basis –when needed. The reader is now able to get updates inboth electronic and print-on-demand versions.

We greatly appreciate the creativity and assistance of Dr. S. Klemp formaking this available. We also thank the Springer team for their skilledassistance in their editorial process.

Your editors appreciate corrections and suggestions and can be readilyreached by email and telephone.

Howard I. Maibach

vii

Preface

Measuring the Skin: A New Look in Dermatology

Measuring the skin succeeds now to looking at the skin or inspecting the skin.Many clinicians limited their diagnosis in dermatology on the only descrip-

tion of skin signs and skin lesions. The fundamental functions of the skin werenot considered except through the aspect of the skin. For example, loss ofbarrier function was deducted of the dryness pattern of the skin. The develop-ment of cosmetology with new active ingredients which are enable to modifythe skin physiology by targeting cell and their nucleus functions, has led thebiometrologists to create the new instrumental devices to accurately assess theimperceptible modifications of the skin.

Since the skin is an organ which can be easily analyzed by looking,touching and smelling to evaluate some of its patterns such as roughness/smoothness, dryness/moisture, Stiffness/sagging, elasticity, extensibility,resistance, radiance/dullness, temperature and etc., it is now appreciated tobe able to assess quantitative measurements, to visualize through the skin andinthe skin different structures such as dermis, vessels, appendages, etc.

The real development of methods to measure the skin took place during the1970s. Indeed, in the last fifty years, the knowledge on the skin physiology andanatomy has been significantly developed in such a manner we are not able toimagine correctly the problems existed many years ago.

Up to these last years, histology remained the gold standard for morpho-logical investigation of the skin, although biopsy may alter the originalmorphology. Advances in ultra-sound and optics provide nowadays a truein vivo analysis of the skin with precise and accurate signification, leading tothe non-invasive optical biopsies. These progresses have many clinical appli-cations in different fields of the medicine such as cancer diagnosis.

Thus a new semiology was born, requiring to be familiar with new patternsand signs. Healthy images at different anatomic sites as well as pathologicaldata regularly appear in the field of biometrology, and need to be known byyoung researchers and dermatologists.

The data and images given by new technologies could be now available forthe practitioners and physiologists which were reserved only to engineers andresearchers in the past,. These methods give the possibility of repetitivehistometric measurements of the same skin site.

ix

Inflammatory diseases, blistering dermatosis and skin tumors are easilyexplored using new sophisticated methods, and the treatment effects can beevaluated. Since biometrology permits to follow the effects of such activeprinciples, it is necessary to enter in the field of cutaneous pharmacology.

Another domain which interests the pharmacists, cosmeticians, doctors,researchers and also the people is skin aging. Indeed, skin appearance ischanging with age, not only in terms of wrinkles and loss of elasticity, butalso in terms of its moisture and radiance. Biometrological assessment allowsto determine the mechanisms between intrinsic and extrinsic factors which areinvolved in skin aging process. The quality of the barrier function of the skin isassessed by numerous methods more and more sophisticated, allowing to haveknowledges on the skin hydration in different levels. Further, new technolo-gies such as RAMAN method helps to determine the qualitative and quanti-tative constitution of the skin; The non-invasive imaging technologiessignificantly improve the diagnosis and also clinical management of skinconditions while giving the dermatologist and closely related specialists, thenew ways for assessing and exploring the skin in its unknown and invisibleparts.

The aim of this new edition of Measuring the skin is to provide the doctor,the researcher, the cosmetician and all person who is involved in assessing theskin, with the tools and their usefulness to characterize the skin. In none ofother field of medicine does such a book exist. Indeed, due to it superficiallocation and simple approach the skin is the target of every measure, everydevice, and all of its function have been explored. When written for the firsttime by Prof. Pierre Agache and myself in 2004, we didn’t imagine at that timethat a new edition will bring so many new information, and disclose so newfields of investigation.

This book has vocation to be the professional basic book of each of you,who wants to know how to characterize such skin property, and wants to knowmore on new skin physiology developments. In memory of my mentor, I amproud to follow him in this skin specialty he contributed to create and todevelop.

Philippe Humbert

x Preface

Acknowledgments

We would never have been able to finish this work without the help of ourcolleagues.

The authors would like to express their deepest gratitude to the personslisted below for their valuable help and support:

– Adeline Jeudy, Thomas Lihoreau, Sophie Mac-Mary, Jean-marieSainthillier, Alexandre Guichard and Ahmed Elkhyat for their help toupdate the table of contents and the new authors according to the recentpublications.

– Dr. Makan Rahshenas for his great help to carry out the correspondancewith authors

– Isabelle Bruey for her assistance in bibliography– Agnès Fontaine and Brigitte Boissenin for their precious help to organise

the work meetings.– Elisabeth Homassel for her valuable help in english translation of some

chapters.– Dr. Hui Xiaoying and Tita F. Reyes and other colleagues of Pr. Maibach in

San Francisco who helped us a lot in updating process.– Deep thanks to the Springer team who followed the redaction process

patiently and efficiently.– In memory of Pr. Xuemin Wang, Vice-Chairman of Shanghai Skin Disease

Hospital, who has written two wonderful chapters on microbiology of theskin in this edition. Unfortunately he expired on February 2016 withouthaving the opportunity to see the outcome.

– Special thanks to Mr. Emmanuel Leclerc, editorial director and Mrs. SylvieCortes, Edition Department assistant at « Lavoisier » editing house in Pariswho dedicated the all legal autorisations to Springer for the upcomingedition of this textbook.

– Finally a no-name appreciation to all secretaries, colleagues, collaboratorsand medical and university staffs who helped the authors/co-authors duringthis long project.

Phillippe HumbertFerial Fanian

Howard I. Maibach

xi

Introduction

Ferial Fanian

Readers of the previous edition of this book have relied on it to aid them inmeasuring all parameters of the skin through the appreciable work of PierreAgache and Philippe Humbert. After the heart-rending death of Pierre Agachein 2003, the first edition was published on 2004 by Springer which was amodified complete translation of the french version edited by him andpublished in 2000 by Lavoisier (Physiologie de la peau et explorationsfonctionnelles cutanées).

Unfortunately the second version was delayed according to several admin-istrative reasons till I have been asked on 2011 to start this big project.Although it was a noticeable major job, it was my great honnor to work withthe well known authors and also the two great editors, Howard Maibach andPhilippe Humbert who always made me the fruitful suggestions and were myenthusiastic supporter through out this long project.

I would like to appreciate all of the respected authors and editors and also allof my friends and colleagues which are named in acknowledgment.

I would like to express my special thanks to Doctor Aude Agache, theesteemed daughter of Professor Agache who did kindly help the team to carryout all administrative steps successfully.

At the end, I would like to dedicate this work to my mother and father,Saeideh Bashirazami and Mohamadali Fanian, which are my first and perma-nent encouraging teachers to study more and more, to my dear Professors,Yahya Dowlati and Alireza Firooz who gave me the scientific view andmotivated me always to go on even in the hard moments, and finally to myhusband, Massoud Salari, who was always at my side cheering me up andsupporting me through the happy and unhappy moments and also my son,Sepanta Salari, who understood patiently my busy time during this hard project.

Procedure

The table of the contents was modified in order to add the most updatedtechnologies in skin physiology, biometrologie, biophysics, imaging andclinical scoring. The authors have been selected according to the most recentpublished articles in each field.

xiii

Comparing to the first edition with 84 chapters and 784 pages, this newedition contain 160 chapters and 1652 pages which can cover the most of theresearchers’ needs in this domain.

Fortunately, this volume has been selected to become part of the Springer-Reference portfolio, which now comprises over 400 major reference worksand almost 500,000 entries/chapters online. This means it will not only be astatic printed book, but it will have a “living” update version online which isvery important for this book because of its gadget like nature.

Contents

In the first section, we have considered an anatomic approach for the chaptertitles : you will start with the surface of the skin and then you will go deeper byleafing the pages. Then you would discover the different measuring techniquesaccording to the functional approach : Mechanical, Photoprotection and sen-sory function of the skin. Furtherly, you will find the standard scoring scales(which will be more completed for the next edition) and the book finishes withskin maps.

We have kept most of the precious chapters of Pierre Agache whosescientific value still remain intact even after 10 years.

All of the reader’s precious comments are welcome.On behalf of the editors, I would like to invite all of the researchers who are

interested to introduce the new methods in the global domain of “Measuringthe Skin”, to contact the editors.

xiv Introduction

Contents

Volume 1

1 The Human Skin: An Overview . . . . . . . . . . . . . . . . . . . . . . . 1Pierre Agache, Thomas Lihoreau, Sophie Mac-Mary,Ferial Fanian, and Philippe Humbert

2 Measurements of the Human Skin: Why and How? . . . . . . . 5Pierre Agache

3 Chronobiology of the Skin: Cutaneous Clocks andBiorhythms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15Annette Mehling and Corinne Reymermier

4 The Skin Surface Ecosystem: A Presentation . . . . . . . . . . . . 23Thomas Lihoreau and Pierre Agache

5 Skin Color and Pigmentation . . . . . . . . . . . . . . . . . . . . . . . . . 35L. Duteil, K. Roussel, and P. Bahadoran

6 The Measurement of Skin Color . . . . . . . . . . . . . . . . . . . . . . . 49Behrooz Kasraee

7 Discrimination Between Cutaneous Pigmentation andErythema: Comparison of the Skin ColorimetersDermacatch and Mexameter . . . . . . . . . . . . . . . . . . . . . . . . . . 55Mathurin Baquié and Behrooz Kasraee

8 The Architectural Behavior of the Skin . . . . . . . . . . . . . . . . . 67J. C. Guimberteau, J. P. Delage, and E. Sawaya

9 Optical Properties of Skin Surface . . . . . . . . . . . . . . . . . . . . . 85Gladimir V. G. Baranoski and Tenn F. Chen

10 Microbiology of Skin Surface . . . . . . . . . . . . . . . . . . . . . . . . . 99Xuemin Wang, Chao Yuan, and Philippe Humbert

11 Evaluation of Skin Surface Flora . . . . . . . . . . . . . . . . . . . . . . 107Xuemin Wang, Chao Yuan, and Philippe Humbert

12 Measurement of Skin Surface Acidity . . . . . . . . . . . . . . . . . . 113Razvigor Darlenski and Joachim W. Fluhr

xv

13 Sebaceous Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121Alireza Firooz, Hamed Zartab, and Ali Rajabi-Estarabadi

14 Measurement of Skin Surface Sebum . . . . . . . . . . . . . . . . . . 133Alireza Firooz, Ali Rajabi-Estarabadi, and Hamed Zartab

15 Measurement of Skin Surface Hydration . . . . . . . . . . . . . . . . 143Peter Clarys and André O. Barel

16 Infant Skin Hydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149Marty O. Visscher

17 Measurement of Skin Radiance . . . . . . . . . . . . . . . . . . . . . . . 161Adeline Jeudy, Vanessa Ecarnot, and Philippe Humbert

18 Analysis of Skin Relief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177Jean-Marie Sainthillier, Sophie Mac-Mary, andPhilippe Humbert

19 Influence of the Sebum and the Hydrolipidic Layer in SkinWettability and Friction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191Ahmed Elkhyat, Ferial Fanian, Ahlam Abdou,Hajar Amarouch, and Philippe Humbert

20 Skin Friction Coefficient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203George Man and Mao-Qiang Man

21 Dermoscopy: Basic Knowledge of an InnovativeImaging Tool . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211Alexander Witkowski, Giovanni Pellacani,Salvador Gonzalez, and Caterina Longo

22 Digital Photography in Aesthetic Dermatology . . . . . . . . . . . 229Jean Marie Sainthillier, Sophie Mac-Mary, andPhilippe Humbert

23 Stratum Corneum Histopathology . . . . . . . . . . . . . . . . . . . . . 245Marek Haftek

24 Molecular Organization of the Skin Barrier . . . . . . . . . . . . . 255Lars Norlén

25 Stratum Corneum Desquamation . . . . . . . . . . . . . . . . . . . . . . 267Gérald E. Piérard, Trinh Hermanns-Lê, and ClaudinePiérard-Franchimont

26 Near-Infrared Densitometry for Improved Standardizationof Tape Stripping and In Situ Determination of the TotalStratum Corneum Thickness . . . . . . . . . . . . . . . . . . . . . . . . . 273Steffi Hansen

27 Infrared Densitometry for In Vitro Tape Stripping:Quantification of Porcine Corneocytes . . . . . . . . . . . . . . . . . . 281Victoria Klang, Magdalena Hoppel, and Claudia Valenta

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28 Standardized Tape Stripping: A Practical andReproducible Protocol to Reduce Uniformly the StratumCorneum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289Heinrich Dickel, Alexandros Goulioumis, Thilo Gambichler,Joachim W. Fluhr, Jeanette Kamphowe, Peter Altmeyer, andOliver Kuss

29 Physical Methods to Measure Stratum Corneum WaterContent In Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299Jean-claude Bernengo and Jean de Rigal

30 Stratum Corneum Dynamic Hydration Test . . . . . . . . . . . . . 341Katsuko Kikuchi and Hachiro Tagami

31 Optothermal Measurement of Water Distribution WithinStratum Corneum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355Perry Xiao

32 Cyanoacrylate Skin Surface Stripping for Visualizing theStratum Corneum Structures and Dynamics . . . . . . . . . . . . . 363Gérald E. Piérard and Claudine Piérard-Franchimont

33 Cyanoacrylate Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369Jakob Mutanu Jungersted

34 Stratum Corneum Biomechanics (Mechanics andFriction): Influence of Lipids and Moisturizers . . . . . . . . . . . 373Gustavo S. Luengo, Anne Potter, Marion Ghibaudo,Nawel Baghdadli, Ramona Enea, and Zhenhhua Song

35 Effects of Sebum on Drug Transport Across the HumanStratum Corneum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389Jui-Chen Tsai, Cheng-Che Eric Lan, and Hamm-Ming Sheu

36 Epidermal Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397Patricia Rousselle, Edgar Gentilhomme, and Yves Neveux

37 Markers of Epidermal Proliferation and Differentiation . . . 407Patricia Rousselle, Edgar Gentilhomme, and Yves Neveux

38 In Vivo Confocal Microscopy in Clinical Dermatology . . . . . 417Caterina Longo, Giovanni Pellacani, and Salvador Gonzalez

39 Ex Vivo Confocal Microscopy in Clinical Dermatology . . . . 429Julia Welzel, Raphaela Kästle, and Elke Sattler

40 A Pharmaceutical Approach of Transcutaneous OxygenTherapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435D. Salmon, S. Boutefnouchet, E. Gilbert, L. Roussel, andFabrice Pirot

41 Dermis Connective Tissue Histopathology . . . . . . . . . . . . . . . 443Pierre Agache

Contents xvii

42 Evaluation of the Cutis by High-ResolutionSonography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447Stephan El Gammal, Claudia El Gammal, Peter Altmeyer, andMichael Vogt

43 Ex Vivo High-Frequency Ultrasound Imaging of theSkin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465Paola Pasquali

44 In Vivo Magnetic Resonance Imaging of the Skin . . . . . . . . . 477Rachid Kechidi and Sébastien Aubry

45 Quantification of the Inhomogeneous Distribution ofTopically Applied Substances on the Human Skin byOptical Spectroscopy: Definition of a Factor ofInhomogeneity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487Hans-Jürgen Weigmann, Sabine Schanzer, Martina C. Meinke,Fanny Knorr, and Jürgen Lademann

46 Optical Coherence Tomography Imaging of the Skin . . . . . . 493Alia Arif Hussain, Lotte Themstrup, Mette Mogensen, andGregor B. E. Jemec

47 Skin Wound Healing Assessment . . . . . . . . . . . . . . . . . . . . . . 503Sylvie Meaume and Philippe Humbert

48 Skin Blood Flow: Histophysiology . . . . . . . . . . . . . . . . . . . . . 513Pierre Agache

49 Photoplethysmography in the Evaluation of SkinConditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521Pierre Agache

50 Skin Microcirculation: Choosing the AppropriateMethod . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529Pierre Agache

51 Lymphatic Microcirculation of the Skin . . . . . . . . . . . . . . . . 535Pascale Quatresooz

52 Assessment of Cutaneous Microvascular FunctionUsing Laser Doppler Flowmetry and AcetylcholineIontophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539Peter D. Drummond

53 Skin Capillaroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549Philippe Humbert, Jean-Marie Sainthillier, Sophie Mac-Mary,Thomas Lihoreau, Ferial Fanian, Adeline Jeudy, and Li Li

54 Assessing Cutaneous Sensory Function and VasomotorResponses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563Parisa Gazerani, Thomas A. Nielsen, and Lars Arendt-Nielsen

xviii Contents

55 Studying the Oscillatory Components of Human SkinMicrocirculation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 569Henrique Silva, Hugo Ferreira, and Luís Monteiro Rodrigues

56 Epicutaneous 133-Xenon Clearance . . . . . . . . . . . . . . . . . . . . 583Pierre Agache

57 Carbon Dioxide Transcutaneous Pressure . . . . . . . . . . . . . . . 587Pierre Agache

58 Transcutaneous Oxygen Pressure . . . . . . . . . . . . . . . . . . . . . . 591Pierre Agache

59 Skin Blood Flow in Systemic Sclerosis . . . . . . . . . . . . . . . . . . 599Alessandra Della Rossa, Chiara Baldini, Massimiliano Cazzato,Marta Mosca, and Stefano Bombardieri

60 Evaluation of Port-Wine Stains and Its Treatment . . . . . . . . 609Yuanhong Li

61 Rating Port-Wine Stains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615Pierre Agache, Yasser Afifi, and Philippe Humbert

62 Sweat Gland Histophysiology . . . . . . . . . . . . . . . . . . . . . . . . . 617Claudine Piérard-Franchimont, Gérald E. Piérard, andTrinh Hermanns-Lê

63 Sweat Gland Methods of Assessment . . . . . . . . . . . . . . . . . . . 623Claudine Piérard-Franchimont and Gérald E. Piérard

64 The Neurophysiology and Assessment of Human SkinWetness Perception . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 629Davide Filingeri, Simon Hodder, and George Havenith

65 Gravimetry in Sweating Assessment in PrimaryHyperhidrosis and Healthy Individuals . . . . . . . . . . . . . . . . . 657Tomasz J. Stefaniak

66 Subcutaneous Tissue Histophysiology . . . . . . . . . . . . . . . . . . 661Helene M. Langevin and Pierre Agache

67 Subcutis Metrology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669Pierre Agache and Stéphane Diridollou

68 Ultrasound of the Subcutaneous Tissue . . . . . . . . . . . . . . . . . 683Ximena Wortsman

69 Cellulite: Definition and Evaluation . . . . . . . . . . . . . . . . . . . . 695Doris Hexsel and Mariana Soirefmann

70 Practical Surface Anthropometry . . . . . . . . . . . . . . . . . . . . . . 703Shahram F. Mevaloo

71 Hair Histophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 711Francisco M. Camacho

Contents xix

72 Healthy Hair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 739Philippe Assouly

73 The Hair Growth Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743Bruno A. Bernard

74 Scalp Sebaceous Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . 749Yahya Dowlati, Alireza Firooz, and Hamed Zartab

75 Clinical Assessment of the Scalp and Hair . . . . . . . . . . . . . . . 757Won-Soo Lee

76 Scalp Sebaceous Function Assessment . . . . . . . . . . . . . . . . . . 761Yahya Dowlati, Alireza Firooz, and Ali Rajabi-Estarabadi

77 Photographic Techniques and Quantification ofHair Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 767Van Neste Dominique

78 Scalp Confocal Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . 787Marina Agozzino and Marco Ardigò

79 Trichoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795Lidia Rudnicka

80 Hair Trichogram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 801Alexandre Guichard and Ferial Fanian

Volume 2

81 Phototrichogram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813Pascal Reygagne

82 Hair Evaluation Method: Pull Test and Wash Test . . . . . . . . 827Marcella Guarrera and Alfredo Rebora

83 Hair Polarized Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . 831Adriana Rakowska

84 Hair-Hair Contact Dynamics and Interactions Studiedwith Atomic Force Microscopy . . . . . . . . . . . . . . . . . . . . . . . . 835Gustavo S. Luengo, Hiroyasu Mizuno, and Mark W. Rutland

85 Nail Anatomy and Physiology . . . . . . . . . . . . . . . . . . . . . . . . . 847Robert Baran

86 Nail Metrology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 853Robert Baran

87 Nail Growth Evaluation and Factors AffectingNail Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 867Shari R. Lipner and Richard K. Scher

88 The pH of the Human Nail Plate . . . . . . . . . . . . . . . . . . . . . . 883S. Murdan, G. Milcovich, and G. S. Goriparthi

xx Contents

89 High-Frequency Ultrasound of the Nail . . . . . . . . . . . . . . . . . 891Charles B. Kromann, Ximena Wortsman, andGregor B. E. Jemec

90 Fibroblast Evaluation: Extracellular Matrix Synthesis . . . . 897Céline Viennet and Patrice Muret

91 Mechanical Properties of Fibroblasts . . . . . . . . . . . . . . . . . . . 903Carol Courderot-Masuyer

92 Gene Expression and Genetic Evaluation of the Skin . . . . . . 911Philippe Benech

93 Biometrology Guidelines for the In Vivo Assessment ofSkin Surface pH in Nonclinical Settings . . . . . . . . . . . . . . . . . 925Aleksandr B. Stefaniak and Johan L. Du Plessis

94 Biometrology Guidelines for the In Vivo Assessment ofTransepidermal Water Loss and Skin Hydration inNonclinical Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 933Johan L. Du Plessis and Aleksandr B. Stefaniak

95 Skin Mechanical Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . 945Pierre Agache and Daniel Varchon

96 Mechanical Behaviour Assessment of the Skin . . . . . . . . . . . 963Pierre Agache and Daniel Varchon

97 The Durometer Measurement of the Skin: Hardware andMeasuring Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 985Salvatore Panduri, Valentina Dini, and Marco Romanelli

98 Skin Viscoelasticity by Acoustic Velocity and Dispersion:Effects of Tension in Stratum Corneum . . . . . . . . . . . . . . . . . 993Eduardo Ruvolo, Christina Lee, and Nikiforos Kollias

99 Skin Tensile Strength in Scleroderma . . . . . . . . . . . . . . . . . . 1011Gérald E. Piérard, Trinh Hermanns-Lê, and ClaudinePiérard-Franchimont

100 Model-Based Interpretation of Skin Microstructural andMechanical Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . 1019Jessica W. Y. Jor, Matthew D. Parker, Martyn P. Nash,Andrew J. Taberner, and Poul M. F. Nielsen

101 Skin Photoprotection Function . . . . . . . . . . . . . . . . . . . . . . . . 1039Dominique Leroy

102 Radical Production by Infrared Irradiation inHuman Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1051Maxim E. Darvin, Martina C. Meinke, and Jürgen Lademann

103 Phototoxicity, Photoirritation, and Photoallergy Detectionand Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1061Jean-Claude Beani

Contents xxi

104 Photobiological Assessment of Sunscreens . . . . . . . . . . . . . . . 1071D. Moyal

105 Skin Barrier Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1079Fabrice Pirot and Françoise Falson

106 In vivo Skin Absorption and Skin Pharmacology . . . . . . . . . 1091Youssef Lboutounne and Patrice Muret

107 Biological and Pharmacological Tests for the Explorationof Skin Barrier Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1115Pierre Treffel and Bernard Gabard

108 Transepidermal Water Loss . . . . . . . . . . . . . . . . . . . . . . . . . . 1119Bernard Gabard and Pierre Treffel

109 Suction Blisters and Microdialysis . . . . . . . . . . . . . . . . . . . . . 1131Sophie Mac-Mary and Patrice Muret

110 Measuring Silica Nanoparticles in the Skin . . . . . . . . . . . . . . 1141Shohreh Nafisi, Monika Schäfer-Korting, andHoward I. Maibach

111 Predicting Hydration’s Effects on Topical Delivery . . . . . . . . 1165Farhaan Hafeez and Howard I. Maibach

112 Multiphoton Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177Karsten König

113 Storage Conditions of the Skin Affect Tissue Structure andIn Vitro Percutaneous Penetration . . . . . . . . . . . . . . . . . . . . . 1191Jesper B. Nielsen and Luis Bagatolli

114 Epidermal Barrier Treatments Based on Vernix Caseosa . . . 1197Marty O. Visscher

115 Assessing the Effects of Fiber-Based Materials onthe Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1209Jackson Leong, Kathryn L. Hatch, and Howard I. Maibach

116 Human Epidermal Barrier May Be QuantitativelyDescribed by Compartmental Analysis of WaterDynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1227Luís Monteiro Rodrigues and Catarina Rosado

117 Skin Reactivity and Proneness to Irritation . . . . . . . . . . . . . . 1241Pierre Agache

118 Cutaneous Testing: Detection and Assessment ofAllergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1253Martine Vigan

119 Thermal Exchanges in Man . . . . . . . . . . . . . . . . . . . . . . . . . . 1265Jacques Bittel and Victor Candas

xxii Contents

120 Thermophysiological Parameters in Man . . . . . . . . . . . . . . . 1271Victor Candas

121 Functional Assessment of Thermoregulation in Man . . . . . . 1277Victor Candas and Jacques Bittel

122 Distribution of Skin Thermal Sensitivity . . . . . . . . . . . . . . . . 1285Nicola Gerrett, Yacine Ouzzahra, and George Havenith

123 Skin Thermal Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1303Francis J. Ring

124 Validity, Reliability, and Reproducibility of SkinTemperature in Healthy Subjects Using InfraredThermography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1311Ismael Fernández-Cuevas, Joao Carlos Marins,Javier Arnáiz Lastras, Pedro Gómez Carmona, andManuel Sillero Quintana

125 Potential Errors in Mean Skin Temperature CalculationDue to Thermistor Placement as Determined by InfraredThermography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1319David D. Pascoe

126 Skin Sensory Structural Component and Function . . . . . . . . 1329Laurent Misery

127 Skin Sensorial Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1333Loïc Rambaud and Laurence Kocher

128 Sensory Function of the Skin . . . . . . . . . . . . . . . . . . . . . . . . . 1337Laurent Misery

129 Quantitative Neurosensory Exploration of the Skin . . . . . . . 1341Loïc Rambaud

130 Thermal Sensory Analyzer and Skin . . . . . . . . . . . . . . . . . . . 1345Iqbaljit Singh and Howard I. Maibach

131 Itch Metrology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1355Emilie Brenaut and Laurent Misery

132 Morphometry in Clinical Dermatology . . . or MeasuringWithout a Device . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1361Pierre Agache

133 Assessment of Erythema and Pallor . . . . . . . . . . . . . . . . . . . . 1367Pierre Agache

134 Cosmetic Facial Skin Type . . . . . . . . . . . . . . . . . . . . . . . . . . . 1379Sang Woong Youn

135 Cellulite: Classification and Scoring . . . . . . . . . . . . . . . . . . . . 1385Doris Hexsel, Camile L. Hexsel, andFernanda Naspolini Bastos

Contents xxiii

136 Clinical Scoring of Atopic Dermatitis . . . . . . . . . . . . . . . . . . . 1391Golara Honari

137 Psoriasis Scoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1401Yasser Afifi and Philippe Humbert

138 Acne Vulgaris Scoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1405Devinder Mohan Thappa and M. Malathi

139 Photography in Acne: Skin Metrics . . . . . . . . . . . . . . . . . . . . 1425Audris Chiang, Farhaan Hafeez, and Howard I. Maibach

140 Classification and Scoring of Androgenetic Alopecia(Male and Female Pattern) . . . . . . . . . . . . . . . . . . . . . . . . . . . 1437Alireza Firooz, Ali Rajabi-Estarabadi, Hamed Zartab, HournazHassanzadeh, and Yahya Dowlati

141 Hirsutism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1443Ferial Fanian

142 Skin Scoring for Mycosis Fungoides and SézarySyndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1449Julia J. Scarisbrick

143 Impact of Excess Body Weight on Skin Hydration andBiomechanics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1461Liliana Tavares, Lídia Palma, Osvaldo Santos,MªAngélica Roberto, Mª Julia Bujan, and LuísMonteiro Rodrigues

144 Development and Diagnostic Accuracy and Reliability ofa Teledermatology Tool for Occupational SkinSurveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1471Markus F. C. Steiner

145 Sodium Lauryl Sulfate-Induced Irritation in the HumanFace: Regional and Age-Related Differences . . . . . . . . . . . . . 1481Slaheddine Marrakchi and Howard I. Maibach

146 Friction Foot Blisters: The Effect of Hydration on the Riskof Blister Creation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1487Farina Hashmi

147 Use of “Connectivity Map” (Cmap) to Identify Novel,Safe, Effective Antiaging Ingredients for Topical Use . . . . . . 1495Johanna M. Gillbro, Eve Merinville, Mia Nilsson,Eva Hagforsen, Garrett Moran, Tamara Al-Bader, andAlain Mavon

148 Measuring Skin Cell Stiffness . . . . . . . . . . . . . . . . . . . . . . . . . 1511Christian Schulze and Soeren Jaspers

xxiv Contents

149 Electron Paramagnetic Resonance Spectroscopy toEvaluate the Radical Scavenging Activity of the Skin . . . . . . 1523Martina C. Meinke, Anna-Christina Lauer, Annette Friedrich,Sophia Arndt, Stefan F. Haag, and Jürgen Lademann

150 Mechanical Properties of Three Different Types ofSkin Graft . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1535J. Pauchot, Alexandre Guichard, Thomas Lihoreau,Ahmed Elkhyat, Sophie Mac-Mary, and Philippe Humbert

151 Dynamic Infrared Thermography of InfantileHemangiomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1551Marty O. Visscher, Denise M. Adams, and Shona A. Burkes

152 Body Surface Area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1565Pierre Agache and Ferial Fanian

153 Blaschko Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1567Pierre Agache

154 Dermatomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1569Pierre Agache

155 Langer’s Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1573Pierre Agache

156 Main Skin Biological Constants . . . . . . . . . . . . . . . . . . . . . . . 1579Pierre Agache

157 Main Skin Physical Constants . . . . . . . . . . . . . . . . . . . . . . . . 1607Pierre Agache

158 Physical, Biological and General Constants of the Skin . . . . 1623Pierre Agache

159 Pressure Units of the Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1627Pierre Agache

160 Correspondence Between International SystemUnits (MKSA) and CGS Units . . . . . . . . . . . . . . . . . . . . . . . . 1629Pierre Agache

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1631

Contents xxv

About the Editors

Philippe HumbertDepartment of DermatologyUniversity Hospital of BesançonBesançon, France

Professor Humbert has been elevated to the grade of Professor of University in1993, at the age of 34 years. Specialist in Dermatology as well in internalMedicine, Allergology and clinical Immunology, and skin oncology, heperformed a Ph.D. in cutaneous Pharmacology.

During his position of head of the Department of Dermatology in theUniversity Hospital of Besançon from 1993 to 2015, he developed a clinicaldepartment with all the specialties of Dermatology, i.e., Allergology, Surgery,Laser, Internal Medicine, Oncology, pediatric Dermatology, Photobiology,Biometrology.

During the same period, he created the Laboratory of Cutaneous Biology inwhich news skin models are developed as well as cell cultures (keratinocytes,fibroblasts, melanocytes. . .) which are used as pharmacological models.

On a clinical point of view, he created the CERT (Center for Investigationand Research on the Skin) in which, with a team of engineers, doctors,pharmacists, technicians, he performss clinical studies for evaluation of cos-metics or drugs.

In this field of biometrology, he was elected as President of the ISBS(International Society for Bioengineering and Imaging of the Skin) from2005 to 2010 (he organized indeed the International Meeting of ISBS inBesançon in 2009), as well as President of the International Society ofCutaneous Pharmacology. He was President of ESCAD in 2011.

His bibliography includes more than 350 publications and five books.

xxvii

Professor Philippe Humbert received the Award of the French Society ofDermatology, of the French Society of Dermatological Research, as well theFrench Society of Cosmetology.

Known for his humanism and generosity, Professor Philippe Humbertwelcomes many students or professors coming from abroad, and he wasproud to contribute to teach six famous Chinese Professors. He collaborateswith many universities over the world. Believing in the creativity of hisstudents, he helped them to assess three innovative start ups in the domain ofskin biometrology (SkinexigenceR), skin biology (BioexigenceR), and skinpharmacology ( ProviskinR).

Student of Pr Agache, his Editor position is the way to honor his mentor,and to contribute to his artwork.

Ferial FanianCenter for Study and Research onthe IntegumentsDepartment of DermatologyUniversity Hospital of BesançonBesançon, France

Ferial Fanian is a French-Persian dermatologist working in Research Centre ofDepartment of Dermatology of Besançon, France (CERT). She has a remark-able experience on laser applications in dermatology while she was alwaysworking as a researcher in biometrology of the skin.

She is also familiar with optical Biopsy methods particularly with in vivoConfocal Microscopy and that is why she is the board member of ICNI group(Non-Invasive Cutaneous Imaging thematique Group) at French Society ofDermatology. She was working on melanocytes activity and morphologythrough her PhD thesis. She has also obtained two academic fellowship in« Laser and Cosmetic Dermatology » and also « Innovative Chronic WoundHealing » in 2012 and 2013 in France.

Actually, she is the reviewer or invited author for several English andFrench scientific journals in the field of dermatyology, aesthetic medicineand biometrology such as JEADV, Archives of Dermatology, Journal ofCosmetic Dermatology, Case Reports in Dermatological Medicine, MedicalStaff Dermatologie, Réalités Thérapeutiques en Dermato-Vénérologie.

xxviii About the Editors

Research InterestsAdvances and Emerging Techniques in DermatologyAnti-AgingCosmetic DermatologyInvasive and Non-Invasive Methods in DermatologyInvestigative Dermatology

Howard I. MaibachDepartment of DermatologySchool of MedicineUniversity of CaliforniaSan Francisco, CA, USA

Present Title: Professor

EDUCATION DEGREE

Tulane University, New Orleans, LA A.B.

Tulane University, New Orleans, LA M.D.

USPHS, Hospital of the University of Pennsylvania Resident/Fellow

HONORARY DEGREES DEGREE YEAR

L’Universite de Paris-Sud, France Ph.D. 1985

Université Claude Bernard Lyon 1, France Ph.D. 2008

University of Southern Denmark M.D. 2010

Dr. Howard Maibach joined the University of California Faculty in 1961 asAssistant Professor, and is currently Professor of Dermatology.

Dr. Maibach, an expert in contact and occupational dermatitis, sees patientsat the Environmental Dermatoses Clinic, which is part of the DermatologyClinic at UCSF. His most active fields of research are dermatopharmacology,dermatotoxicology, and environmental dermatoses. He has been doing humansubject research for 45 years.

He has been on the editorial board of more than 30 scientific journals. Hisbibliography includes more than 2790 publications and 100 books.

He is member of 19 professional societies, including the American Academyof Dermatology (AAD), San Francisco Dermatological Society (SFDS), NorthAmerican Contact Dermatitis Group (NACDG), American Contact DermatitisSociety (ACDS), International Contact Dermatitis Research Group (ICDRG),Society of Toxicology (SOT), European Environmental and Contact DermatitisResearch Group (EECDRG), and the Internal Commission on OccupationalHealth. He is a consultant to government, academia, and industry worldwide.

About the Editors xxix

Dr. Howard Maibach was honored as the 2013 recipient of The MasterDermatologist Award by The American Academy of Dermatology’s 71stAnnual Conference held in Miami, Florida. This prestigious award recognizesan Academy member’s significant contributions to the field of dermatologyand to the American Academy of Dermatology.

In March 2015, The International League of Dermatological Societies(ILDS) awarded Dr. Maibach their 2014 ILDS Certificate of Appreciation inrecognition of his outstanding contribution to dermatology, both nationallyand internationally, through his work, research, publications, and teaching inthe USA and over 60 countries.

xxx About the Editors

Contributors

Ahlam Abdou Department of Dermatology, Ibn Sina Hospital, RabatUniversity Hospital, Rabat, Morocco

Denise M. Adams Hemangioma and Vascular Malformation Center, Cincin-nati Children’s Hospital Medical Center, Cincinnati, OH, USA

Department of Pediatrics, College ofMedicine, Cincinnati Children’s HospitalMedical Center, Cincinnati, OH, USA

Yasser Afifi Private Clinic, Rabat, Moroccoe-mail: yaafifi@yahoo.fr

Pierre Agache Department of Dermatology, University Hospital ofBesançon, Besançon, Francee-mail: aude.agache@free.fr; ferial.fanian@chu-besancon.fr; ferial.fanian@cert-besancon.com

Marina Agozzino San Gallicano Dermatological Institute, Rome, Italye-mail: ardigo@ifo.it

Tamara Al-Bader Oriflame Skin Research Institute, Stockholm, Sweden

Oriflame R&D Ltd, Bray, Co Wicklow, Ireland

Department of Medical Sciences, Dermatology and Venereology, UppsalaUniversity, Uppsala, Sweden

Peter Altmeyer Department of Dermatology and Allergology, Ruhr Univer-sity Bochum, Bochum, Germany

Hajar Amarouch Department of Dermatology, Ibn Sina Hospital, RabatUniversity Hospital, Rabat, Morocco

Marco Ardigò San Gallicano Dermatological Institute, Rome, Italye-mail: ardigo@ifo.it

Lars Arendt-Nielsen Department of Health Science and Technology,Faculty of Medicine, Center for Sensory-Motor Interaction (SMI), AalborgUniversity, Aalborg, Denmark

Pierre Agache: deceased.xxxi

Javier Arnáiz Lastras Faculty of Sciences for Physical Activity and Sport(INEF), Universidad Politécnica de Madrid, Madrid, Spain

Sophia Arndt Department of Dermatology, Venereology and Allergology,Center of Experimental and Applied Cutaneous Physiology, Charité -Universitätsmedizin Berlin, Berlin, Germany

Philippe Assouly Centre Sabouraud, Saint-Louis Hospital, Paris, Francee-mail: philippe.assouly@orange.fr

Sébastien Aubry University Hospital of Besançon, Besançon, France

Department of Radiology, I4S Laboratory, INSERM EA4268, University ofFranche-Comte, Besançon, Francee-mail: radio.aubry@free.fr

Luis Bagatolli Membrane Biophysics and Biophotonics group/MEMPHYSCenter for Biomembrane Physics, Department of Biochemistry and MolecularBiology, University of Southern Denmark, Odense, Denmark

Nawel Baghdadli L’Oréal Research and Innovation, Aulnay-Sous- Bois,France

P. Bahadoran Department of Dermatology, Nice CHU Hôpital Pasteur, NiceCedex 3, Francee-mail: Philippe.BAHADORAN@unice.fr

Chiara Baldini Dipartimento di malattie muscolo-scheletriche e cutanee,U.O. Reumatologia, Pisa, Italye-mail: c.baldini@med.unipi.it

Mathurin Baquié Scientis Pharma SA, Geneva, Switzerland

Robert Baran Nail Disease Center, Cannes, Francee-mail: baran.r@wanadoo.fr

Gladimir V. G. Baranoski Natural Phenomena Simulation Group, Univer-sity of Waterloo, Waterloo, ON, Canadae-mail: gvgbaran@cs.uwaterloo.ca

André O. Barel Faculty of Physical Education and Physiotherapy, VrijeUniversiteit Brussel, Brussel, Belgiume-mail: anbarel@vub.ac.be

Fernanda Naspolini Bastos Universidade Luterana do Brasil, Canoas,Brazil

Jean-Claude Beani Clinique Universitaire de Dermato-Vénéréologie,Photobiologie et Allergologie, Pôle Pluridisciplinaire de Médecine, CHU deGrenoble, Grenoble, Francee-mail: jeanclaudebeani@gmail.com; jcbeani@chu-grenoble.fr

Philippe Benech Faculté de Médecine Secteur Nord, UMR 7259 (NICN)CNRS – Aix-Marseille Université, Marseille, Francee-mail: philippe.benech@univ-amu.fr

xxxii Contributors

Bruno A. Bernard L’Oréal Research and Innovation, Clichy, Francee-mail: bbernard@rd.loreal.com

Jean-claude Bernengo Non Invasive Technologies, Paris, Francee-mail: bernjc@free.fr

Jacques Bittel Cepa, CNRS, Strasbourg Cedex, France

Stefano Bombardieri Dipartimento di malattie muscolo-scheletriche ecutanee, U.O. Reumatologia, Pisa, Italye-mail: s.bombardieri@int.med.unipi.it

S. Boutefnouchet Unité de Préparation et de Contrôles des Médicaments,Service Pharmaceutique – Groupement Hospitalier Edouard Herriot-HospicesCivils de Lyon, Lyon cedex 03, France

Emilie Brenaut Department of Dermatology, University Hospital of Brest,Brest, France

Mª Julia Bujan Faculty of Medicine and Health Science, Universidad deAlcalá de Henares, Campus Universitario, Ctra. Barcelona, Madrid, Spain

Shona A. Burkes Skin Sciences Program, Division of Plastic Surgery,Department of Surgery, Cincinnati Children’s Hospital Medical Center,College of Medicine, University of Cincinnati, Cincinnati, OH, USA

James L. Winkle, College of Pharmacy, University of Cincinnati, Cincinnati,OH, USA

FranciscoM. Camacho School ofMedicine, Medical-Surgical DermatologyDepartment, Hospital Universitario Virgen Macarena, University of Seville,Seville, Spaine-mail: fmcamacho@us.es; camachodp@medynet.com

Victor Candas Ex Research Director at CNRS, Strasbourg Cedex 2, Francee-mail: v.candas@orange.fr

Massimiliano Cazzato Dipartimento di malattie muscolo-scheletriche ecutanee, U.O. Reumatologia, Pisa, Italye-mail: m_cazzato@virgilio.it

Tenn F. Chen Natural Phenomena Simulation Group, University of Water-loo, Waterloo, ON, Canadae-mail: t4chen@cs.uwaterloo.ca

Audris Chiang UC Irvine School of Medicine, Berkeley, CA, USA

Department of Dermatology, University of California, San Francisco, CA,USAe-mail: audrisc@uci.edu

Peter Clarys Faculty of Physical Education and Physiotherapy, VrijeUniversiteit Brussel, Brussel, Belgiume-mail: pclarys@vub.ac.be

Contributors xxxiii

Carol Courderot-Masuyer Bioexigence, Besançon, Francee-mail: bioexigence@wanadoo.fr

Razvigor Darlenski Department of Dermatology and Venereology, TokudaHospital Sofia, Sofia, Bulgariae-mail: darlenski@gmail.com

Maxim E. Darvin Department of Dermatology, Venereology andAllergology, Center of Experimental and Applied Cutaneous Physiology,Charité – Universitätsmedizin Berlin, Berlin, Germanye-mail: maxim.darvin@charite.de

J. P. Delage U688 Physiopathologie mitochondriale, Université VictorSegalen-Bordeaux 2, Bordeaux Cedex, France

Alessandra Della Rossa Dipartimento di malattie muscolo-scheletriche ecutanee, U.O. Reumatologia, Pisa, Italye-mail: a.dellarossa@ao-pisa.toscana.it

Heinrich Dickel Department of Dermatology and Allergology, Ruhr Univer-sity Bochum, Bochum, Germanye-mail: h.dickel@klinikum-bochum.de

Valentina Dini Department of Dermatology, University of Pisa, Pisa, Italy

Stéphane Diridollou L’Oreal Research and Innovation, Chevilly, Larue,Francee-mail: sdiridollou@rd.loreal.com

Van Neste Dominique Skinterface Tournai and Brussels’ Hair Clinic, Tour-nai, Belgiume-mail: info@skinterface.be

Yahya Dowlati Center for Research and Training in Skin Diseases andLeprosy, Tehran University of Medical Sciences, Tehran, Irane-mail: dowlatiy@yahoo.com

Peter D. Drummond School of Psychology and Exercise Science, MurdochUniversity, Perth, WA, Australiae-mail: p.drummond@murdoch.edu.au

L. Duteil CPCAD (Centre de Pharmacologie Clinique Appliquée à laDermatologie), Hôpital L’ARCHET 2, Nice Cedex 3, Francee-mail: philippe.BAHADORAN@unice.fr

Vanessa Ecarnot CERT, Department of Dermatology, CHRU Besançon,Besançon, France

Claudia El Gammal Dermatology,Medical Care Center, Diakonie KlinikumJung-Stilling, Siegen, Germany

Stephan El Gammal Dermatological Clinic, Diakonie Klinikum Bethesda,Freudenberg, Germanye-mail: stephan@ElGammal.de

xxxiv Contributors

Ahmed Elkhyat Center for Research and Studies on the Integument (CERT),Department of Dermatology, Clinical Investigation Center (CIC BT506),Besançon University Hospital, INSERM UMR1098, FED4234 IBCT,University of Franche-Comté, Besançon, Francee-mail: aelkhyat@chu-besancon.fr

Ramona Enea L’Oréal Research and Innovation, Aulnay-Sous- Bois, France

Françoise Falson ISPB-Faculté de Pharmacie, University of Lyon, Lyon,Francee-mail: francoise.rieg-falson@univ-lyon1.fr

Ferial Fanian Center for Study and Research on the Integuments,Department of Dermatology, University Hospital of Besançon, Besançon,Francee-mail: ferial.fanian@chu-besancon.fr; ferial.fanian@cert-besancon.com;fanian@gmail.com

Ismael Fernández-Cuevas Faculty of Sciences for Physical Activity andSport (INEF), Universidad Politécnica de Madrid, Madrid, Spaine-mail: ismael.fernandez@upm.es

Hugo Ferreira Faculty of Sciences, Institute of Biophysics and BiomedicalEngineering, Universidade de Lisboa, Lisboa, Portugal

Davide Filingeri Environmental Ergonomics Research Centre, Loughbor-ough Design School, Loughborough University, Loughborough, UKe-mail: davidefilingeri@hotmail.it

Alireza Firooz Center for Research and Training in Skin Diseases andLeprosy, Tehran University of Medical Sciences, Tehran, Irane-mail: firozali@sina.tums.ac.ir

Joachim W. Fluhr Department of Dermatology, Charité – Universi-tätsmedizin Berlin, Berlin, Germanye-mail: Joachim.Fluhr@charite.de

Annette Friedrich Department of Dermatology, Venereology andAllergology, Center of Experimental and Applied Cutaneous Physiology,Charité - Universitätsmedizin Berlin, Berlin, Germany

Bernard Gabard Lörrach, Germanye-mail: b.gabard@iderma.ch

Thilo Gambichler Department of Dermatology and Allergology, RuhrUniversity Bochum, Bochum, Germany

Parisa Gazerani Department of Health Science and Technology, Faculty ofMedicine, Center for Sensory-Motor Interaction (SMI), Aalborg University,Aalborg, Denmarke-mail: gazerani@hst.aau.dk

Contributors xxxv

Edgar Gentilhomme French Army Health Research Department, La tronche,Francee-mail: edgargentilhomme@crssa.net

Nicola Gerrett Institute of Sport and Exercise Science, University ofWorcester, Worcester, UKe-mail: n.gerrett@worc.ac.uk

Marion Ghibaudo L’Oréal Research and Innovation, Aulnay-Sous- Bois,France

E. Gilbert EA 4169 “Aspects Fondamentaux, Cliniques et Thérapeutiques dela Fonction Barrière Cutanée”, Laboratoire de Pharmacie GaléniqueIndustrielle – Faculté de Pharmacie., Université Claude Bernard Lyon 1,Lyon cedex 08, France

Johanna M. Gillbro Oriflame Skin Research Institute, Stockholm, Sweden

Oriflame R&D Ltd, Bray, Co Wicklow, Ireland

Department of Medical Sciences, Dermatology and Venereology, UppsalaUniversity, Uppsala, Swedene-mail: johanna.gillbro@oriflame.com

Pedro Gómez Carmona Faculty of Sciences for Physical Activity and Sport(INEF), Universidad Politécnica de Madrid, Madrid, Spain

Salvador Gonzalez Dermatology Service, Memorial Sloan-Kettering CancerCenter, New York, NY, USA

Medicine Department, Alcalá University, Madrid, Spain

G. S. Goriparthi Department of Pharmaceutics, UCL School of Pharmacy,London, UK

Alexandros Goulioumis Department of Anesthesiology, Intensive Care andPain Therapy, The Knappschaftskrankenhaus Dortmund, Dortmund, Germany

Marcella Guarrera Department of Health Sciences-Section of Dermatology,University of Genoa, Genoa, Italye-mail: guarrera@unige.it

Alexandre Guichard Center for Research and Studies on the Integument(CERT), Department of Dermatology, Clinical Investigation Center (CICINSERM 1431), Besançon University Hospital; INSERM UMR1098,FED4234 IBCT, University of Franche-Comté, Besançon, Francee-mail: guichard.alexandre@gmail.com

J. C. Guimberteau Institut Aquitain de la Main, Bordeaux-Pessac, Francee-mail: adf.guimberteau@wanadoo.fr

Stefan F. Haag Department of Dermatology, Venereology and Allergology,Center of Experimental and Applied Cutaneous Physiology, Charité -Universitätsmedizin Berlin, Berlin, Germany

Farhaan Hafeez Department of Dermatology, University of California, SanFrancisco, San Francisco, CA, USAe-mail: farhaanhafeez@gmail.com; farhaan.hafeez@yale.edu

xxxvi Contributors

Marek Haftek Laboratoire de Recherche Dermatologique, EA 4169, Facultéde Médecine et de Pharmacie, Université Claude Bernard Lyon 1, Lyon, Francee-mail: marek.haftek@univ-lyon1.fr

Eva Hagforsen Oriflame Skin Research Institute, Stockholm, Sweden

Oriflame R&D Ltd, Bray, Co Wicklow, Ireland

Department of Medical Sciences, Dermatology and Venereology, UppsalaUniversity, Uppsala, Sweden

Steffi Hansen Department Drug Delivery, Helmholtz Institute for Pharma-ceutical Research Saarland (HIPS), Helmholtz Center for Infection Research,Saarbruecken, Germanye-mail: steffihansen@web.de

Farina Hashmi School of Health Sciences Research, University of Salford,Manchester, UKe-mail: F.Hashmi@salford.ac.uk

Hournaz Hassanzadeh Center for Research and Training in Skin Diseasesand Leprosy, Tehran University of Medical Sciences, Tehran, Irane-mail: hasanzadeh.hoornaz92@gmail.com

Kathryn L. Hatch Department of Agricultural and Biosystems Engineering,University of Arizona, Tucson, AZ, USAe-mail: khatch@ag.arizona.edu

George Havenith Environmental Ergonomic Research Centre, Loughbor-ough Design School, Loughborough University, Loughborough, UKe-mail: G.Havenith@lboro.ac.uk

Trinh Hermanns-Lê Laboratory of Skin Bioengineering and Imaging(LABIC), Liège University, Liège, Belgium

Service de Dermatopathologie, CHU du Sart Tilman, Liège, Belgium

Department of Dermatopathology, Unilab Lg, University Hospital of Liège,Liège, Belgiume-mail: Trinh.hermanns@chu.ulg.ac.be; Trinh.le@ulg.ac.be

Camile L. Hexsel Brazilian Center for Studies in Dermatology, Porto Alegre,Brazil

Doris Hexsel Brazilian Center for Studies in Dermatology, Department ofDermatology, Pontificia Universidade Catolica do Rio Grande do Sul(PUC-RS), Porto Alegre, RS, Brazile-mail: doris@hexsel.com.br

Simon Hodder Environmental Ergonomics Research Centre, LoughboroughDesign School, Loughborough University, Loughborough, UKe-mail: S.Hodder@lboro.ac.uk

Golara Honari Department of Dermatology, Stanford School of Medicine,Redwood City, USAe-mail: Honari@stanford.edu

Contributors xxxvii

Magdalena Hoppel Department of Pharmaceutical Technology andBiopharmaceutics, Faculty of Life Sciences, University of Vienna, Vienna,Austriae-mail: magdalena.hoppel@univie.ac.at

Philippe Humbert Department of Dermatology, University Hospital ofBesançon, Besançon, Francee-mail: philippe.humbert@univ-fcomte.fr

Alia Arif Hussain Department of Dermatology, Roskilde Hospital, Univer-sity of Copenhagen, Roskilde, Denmarke-mail: alia.arif.hussain@gmail.com

Soeren Jaspers Research and Development, Beiersdorf AG, Hamburg,Germanye-mail: Soeren.Jaspers@beiersdorf.com

Gregor B. E. Jemec Department of Dermatology, Roskilde Hospital,University of Copenhagen, Roskilde, Denmarke-mail: gbj@regionsjaelland.dk

Adeline Jeudy Research and Studies Center on the Integument (CERT);Clinical Investigation Center (CIC BT506), Department of Dermatology,Besançon University Hospital, Besançon, Francee-mail: ajeudy@chu-besancon.fr

Jessica W. Y. Jor Auckland Bioengineering Institute, University of Auck-land, Auckland, New Zealande-mail: j.jor@auckland.ac.nz

Jakob Mutanu Jungersted Department of Dermatology, University ofCopenhagen, Copenhagen, NV, Denmarke-mail: jungersted@gmail.com

Raphaela Kästle Department of Dermatology and Allergology, GeneralHospital Augsburg, Augsburg, Germany

Karsten König Department of Biophotonics and Laser Technology, SaarlandUniversity, Saarbruecken, Germany

JenLab GmbH, Jena, Germanye-mail: k.koenig@blt.uni-saarland.de

Jeanette Kamphowe Department of Dermatology and Allergology, RuhrUniversity Bochum, Bochum, Germany

Behrooz Kasraee Scientis Pharma SA, Geneva, Switzerlande-mail: behroozkasraee@yahoo.com

Rachid Kechidi University Hospital of Besançon, Besançon, Francee-mail: r.kechidi@live.fr

Katsuko Kikuchi Department of Dermatology, Tohoku University GraduateSchool of Medicine, Sendai, Japane-mail: kkikuchi@med.tohoku.ac.jp

xxxviii Contributors

Victoria Klang Department of Pharmaceutical Technology andBiopharmaceutics, Faculty of Life Sciences, University of Vienna, Vienna,Austriae-mail: victoria.klang@univie.ac.at

Fanny Knorr Department of Dermatology, Venereology and Allergology,Center of Experimental and Applied Cutaneous Physiology, Charité -Universitätsmedizin Berlin, Berlin, Germanye-mail: fanny.knorr@charite.de

Laurence Kocher Service d’Explorations Fonctionnelles Neurologiques,Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, Francee-mail: laurence.kocher@chu-lyon.fr

Nikiforos Kollias Johnson & Johnson Consumer and Personal ProductsWorldwide, Skillman, NJ, USA

Charles B. Kromann Department of Dermatology, Roskilde, ZealandUniversity Hospital, University of Copenhagen, Copenhagen, Denmarke-mail: charles.kromann@gmail.com

Oliver Kuss Institute for Biometry and Epidemiology, German DiabetesCenter, Leibniz Institute for Diabetes Research at Heinrich Heine UniversityDüsseldorf, Düsseldorf, Germany

Jürgen Lademann Department of Dermatology, Venereology andAllergology, Center of Experimental and Applied Cutaneous Physiology,Charité – Universitätsmedizin Berlin, Berlin, Germanye-mail: juergen.lademann@charite.de

Cheng-Che Eric Lan Department of Dermatology, Kaohsiung MedicalUniversity, Kaohsiung, Taiwan

Helene M. Langevin Department of Neurological Sciences, University ofVermont, College of Medicine, Burlington, VT, USAe-mail: helene.langevin@med.uvm.edu

Anna-Christina Lauer Department of Dermatology, Venereology andAllergology, Center of Experimental and Applied Cutaneous Physiology,Charité - Universitätsmedizin Berlin, Berlin, Germany

Youssef Lboutounne CIC-BT CHU, Besançon, Francee-mail: youssef-lboutounne@hotmail.fr

Won-Soo Lee Department of Dermatology, Institute of Hair and CosmeticMedicine, Yonsei University Wonju College of Medicine, Wonju, Gangwon-Do, Republic of Koreae-mail: leewonsoo@yonsei.ac.kr

Christina Lee Johnson & Johnson Consumer and Personal Products World-wide, Skillman, NJ, USAe-mail: CLee56@its.jnj.com

Jackson Leong Dermatology Department, University of California, SanFrancisco, San Francisco, CA, USAe-mail: jacksonleong@gmail.com

Contributors xxxix

Dominique Leroy Dermatologist, Department of Dermatology, UniversityHospital centre, Caen, Francee-mail: dominique.leroy10@wanadoo.fr

Li Li Department of Dermatology, West China Hospital, Sichuan University,Chengdu, China

Yuanhong Li Department of Dermatology, No.1 Hospital of China MedicalUniversity, Shenyang, People’s Republic of Chinae-mail: liyuanhong@vip.sina.com

Thomas Lihoreau Center for Research and Studies on the Integument(CERT), Department of Dermatology, Clinical Investigation Center (CICINSERM 1431), Besançon University Hospital; INSERM UMR1098,FED4234 IBCT, University of Franche-Comté, Besançon, Francee-mail: tlihoreau@chu-besancon.fr

Shari R. Lipner Department of Dermatology, Weill Cornell Medical Col-lege, New York, NY, USAe-mail: shl9032@med.cornell.edu

Caterina Longo Dermatology and Skin cancer Unit, Arcispedale SantaMaria Nuova-IRCCS, Reggio Emilia, Italye-mail: longo.caterina@gmail.com

Gustavo S. Luengo L’Oréal Research and Innovation, Aulnay-Sous- Bois,Francee-mail: gluengo@rd.loreal.com

Sophie Mac-Mary Skinexigence SAS, Bioparc, Besançon, Francee-mail: smac@skinexigence.com

Howard I. Maibach Department of Dermatology, School of Medicine, Uni-versity of California, San Francisco, CA, USAe-mail: maibachh@derm.ucsf.edu

M. Malathi Department of Dermatology, Jawaharlal Institute of Post Grad-uate Medical Education and Research, Gorimedu, Puducherry, Indiae-mail: mmalathi.dr@live.com

George Man Department of Dermatology, Dermatology Service, VeteransAffairs Medical Center San Francisco, University of California San Francisco,School of Medicine, San Francisco, CA, USAe-mail: georgeisman@gmail.com

Mao-Qiang Man Department of Dermatology, Dermatology Service, Vet-erans Affairs Medical Center San Francisco, University of California SanFrancisco, School of Medicine, San Francisco, CA, USAe-mail: mqman@hotmail.com

Joao Carlos Marins Human Performance Laboratory – LAPEH,Universidade Federal de Viçosa (Brazil), Minas Gerais Código, Viçosa, Brazil

Slaheddine Marrakchi Department of Dermatology, Hedi CHAKER Hos-pital, Sfax, Tunisiae-mail: slaheddine.marrakchi@tunet.tn

xl Contributors

Alain Mavon Oriflame Skin Research Institute, Stockholm, Sweden

Oriflame R&D Ltd, Bray, Co Wicklow, Ireland

Department of Medical Sciences, Dermatology and Venereology, UppsalaUniversity, Uppsala, Sweden

Sylvie Meaume Department of Geriatrics, Wound Care Unit, RothschildHospital, Paris, Francee-mail: sylvie.meaume@rth.aphp.fr

Annette Mehling BASF Personal Care and Nutrition GmbH, Düsseldorf,Germanye-mail: annette.mehling@basf.com

Martina C. Meinke Department of Dermatology, Venereology andAllergology, Center of Experimental and Applied Cutaneous Physiology,Charité – Universitätsmedizin Berlin, Berlin, Germanye-mail: martina.meinke@charite.de

Eve Merinville Oriflame Skin Research Institute, Stockholm, Sweden

Oriflame R&D Ltd, Bray, Co Wicklow, Ireland

Department of Medical Sciences, Dermatology and Venereology, UppsalaUniversity, Uppsala, Sweden

Shahram F. Mevaloo Health Studies Group, Center for Strategic Research,I.R.I Ministry of Sport and Youth, Tehran, Irane-mail: sfaradjzadeh@yahoo.com

G. Milcovich Department of Pharmaceutics, UCL School of Pharmacy,London, UK

Laurent Misery Department of Dermatology, University Hospital of Brest,Brest, Francee-mail: laurent.misery@chu-brest.fr

Hiroyasu Mizuno L’OREAL, KSP Research and Innovation center, Kawa-saki, Japan

Mette Mogensen Department of Dermatology and Venereology, BispebjergHospital, University of Copenhagen, Copenhagen, Denmarke-mail: mogensen.mette@gmail.com

Garrett Moran Oriflame Skin Research Institute, Stockholm, Sweden

Oriflame R&D Ltd, Bray, Co Wicklow, Ireland

Department of Medical Sciences, Dermatology and Venereology, UppsalaUniversity, Uppsala, Sweden

MartaMosca Dipartimento di malattie muscolo-scheletriche e cutanee, U.O.Reumatologia, Pisa, Italye-mail: marta.mosca@med.unipi.it

D. Moyal La Roche-Posay Laboratoire Dermatologique, Asnieres Sur Seine,Francee-mail: dominique.moyal@loreal.com

Contributors xli

S. Murdan Department of Pharmaceutics, UCL School of Pharmacy,London, UKe-mail: s.murdan@ucl.ac.uk

Patrice Muret Engineering and Cutaneous Biology Laboratory, UMR 1098,University of Franche-Comte, Besançon, France

Clinical Pharmacology Department, University Hospital, Besançon, Francee-mail: patrice.muret@univ-fcomte.fr; p1muret@chu-besancon.fr

Shohreh Nafisi Department of Chemistry, Central Tehran Branch, IAU,Tehran, Iran

Department of Dermatology, University of California, San Francisco, CA,USAe-mail: drshnafisi@gmail.com

Martyn P. Nash Auckland Bioengineering Institute, University of Auckland,Auckland, New Zealand

Department of Engineering Science, University of Auckland, Auckland,New Zealand

Yves Neveux Livernon, Francee-mail: yves.neveux@free.fr

Poul M. F. Nielsen Auckland Bioengineering Institute, University of Auck-land, Auckland, New Zealand

Department of Engineering Science, University of Auckland, Auckland,New Zealand

Jesper B. Nielsen Department of Public Health, University of SouthernDenmark, Odense, Denmarke-mail: jbnielsen@health.sdu.dk

Thomas A. Nielsen Department of Health Science and Technology, Facultyof Medicine, Center for Sensory-Motor Interaction (SMI), Aalborg University,Aalborg, Denmark

Mia Nilsson Oriflame Skin Research Institute, Stockholm, Sweden

Oriflame R&D Ltd, Bray, Co Wicklow, Ireland

Department of Medical Sciences, Dermatology and Venereology, UppsalaUniversity, Uppsala, Sweden

Lars Norlén Department of Cell and Molecular Biology (CMB), KarolinskaInstitutet, and Dermatology Clinic, Karolinska University Hospital, Stock-holm, Swedene-mail: lars.norlen@ki.se

Yacine Ouzzahra Institute for Health and Behaviour, University of Luxem-bourg, Walferdange, Luxembourge-mail: Yacine.Ouzzahra@uni.lu

Lídia Palma CBIOS – Research Center for Health Science and Technolo-gies, Universidade Lusófona, Lisbon, Portugal

xlii Contributors

Salvatore Panduri Department of Dermatology, University of Pisa, Pisa,Italy

Matthew D. Parker Auckland Bioengineering Institute, University of Auck-land, Auckland, New Zealand

David D. Pascoe School of Kinesiology, Auburn University, Aubur, Al, USAe-mail: Pascodd@auburn.edu

Paola Pasquali Dermatology Department, Pius Hospital de Valls, Valls,Spaine-mail: pasqualipaola@gmail.com

J. Pauchot Orthopedic Surgery, Traumatology, Plastic Aesthetic, Recon-structive Surgery, and Hand Surgery Department, EA 4268, IFR 133 INSERMI4S, Besançon University Hospital, Besançon, Francee-mail: julien.pauchot@gmail.com

Giovanni Pellacani Dermatology Unit, University of Modena and ReggioEmilia, Modena, Italy

Gérald E. Piérard Laboratory of Skin Bioengineering and Imaging(LABIC), Liège University, Liège, Belgium

Service de Dermatopathologie, CHU du Sart Tilman, Liège, Belgiume-mail: Gerald.pierard@ulg.ac.be

Claudine Piérard-Franchimont Laboratory of Skin Bioengineering andImaging (LABIC), Department of Clinical Sciences, Liège University,Liège, Belgiume-mail: Claudine.franchimont@ulg.ac.be

Fabrice Pirot EA 4169 “Aspects Fondamentaux, Cliniques etThérapeutiques de la Fonction Barrière Cutanée”, Laboratoire de PharmacieGalénique Industrielle – Faculté de Pharmacie., Université Claude BernardLyon 1, Lyon cedex 08, France

Unité de Préparation et de Contrôles des Médicaments, ServicePharmaceutique – Groupement Hospitalier Edouard Herriot-Hospices Civilsde Lyon, Lyon cedex 03, Francee-mail: fabrice.pirot@univ-lyon1.fr

Johan L. Du Plessis Occupational Hygiene and Health Research Initiative,North-West University, Potchefstroom, South Africae-mail: Johan.DuPlessis@nwu.ac.za

Anne Potter L’Oréal Research and Innovation, Aulnay-Sous- Bois, France

Pascale Quatresooz Laboratory of Skin Bioengineering and Imaging,Department of Dermatopathology, University Hospital of Liège, Liège,Belgium

Department Histology, University of Liège, Liège, Belgiume-mail: Pascale.quatresooz@chu.ulg.ac.be

Contributors xliii

Ali Rajabi-Estarabadi Center for Research and Training in Skin Diseasesand Leprosy, Tehran University of Medical Sciences, Tehran, Irane-mail: dralirajabi@yahoo.com

Adriana Rakowska Department of Dermatology, Medical University ofWarsaw, Warsaw, Polande-mail: adriana.rakowska@gmail.com

Loïc Rambaud French Institute for Public Health Surveillance, Saint Mau-rice, Francee-mail: l.rambaud@invs.sante.fr; l-rambaud@wanadoo.fr

Alfredo Rebora Department of Health Sciences-Section of Dermatology,University of Genoa, Genoa, Italy

Pascal Reygagne Centre de Santé Sabouraud, Hôpital Saint Louis, Paris,Francee-mail: p.reygagne@centresabouraud.fr

Corinne Reymermier BASF Beauty Care Solutions France S.A.S, Lyon,Francee-mail: corinne.reymermier@basf.com

Jean de Rigal L’Oréal Recherche, Chevilly Larue, Francee-mail: jderigal@rd.loreal.com; jderigal@bbox.fr

Francis J. Ring Medical Imaging Research Unit, University of South Wales,Pontypridd, UKe-mail: efring@glam.ac.uk

MªAngélica Roberto Plastic Surgery Service, Rua José António Serrano,Lisboa, Lisbon, Portugal

Luís Monteiro Rodrigues CBIOS – Research Center for Health Science andTechnologies, Universidade Lusófona, Lisbon, Portugal

Department of Pharmacological Sciences, Universidade de Lisboa – School ofPharmacy, Lisbon, Portugale-mail: monteiro.rodrigues@ulusofona.pt; monteirorodrigues@sapo.pt

Marco Romanelli Department of Dermatology, University of Pisa, Pisa,Italye-mail: m.romanelli@med.unipi.it

Catarina Rosado Universidade Lusófona (CBIOS – Research Center forHealth Science and Technologies), Lisbon, Portugal

K. Roussel CPCAD (Centre de Pharmacologie Clinique Appliquée à laDermatologie), Hôpital L’ARCHET 2, Nice Cedex 3, France

L. Roussel EA 4169 “Aspects Fondamentaux, Cliniques et Thérapeutiquesde la Fonction Barrière Cutanée”, Laboratoire de Pharmacie GaléniqueIndustrielle – Faculté de Pharmacie., Université Claude Bernard Lyon 1,Lyon cedex 08, France

xliv Contributors

Patricia Rousselle Tissue Biology and Therapeutic Engineering Unit, Insti-tute of Protein Biology and Chemistry, UMR 5305 – CNRS, University ofLyon, Lyon, Francee-mail: patricia.rousselle@ibcp.fr

Lidia Rudnicka Department of Dermatology, Medical University ofWarsaw, Warsaw, Polande-mail: lidia.rudnicka@dermatolodzy.com.pl

MarkW. Rutland KTH, Royal Institute of Technology, Stockholm, Swedene-mail: mark@kth.se

Eduardo Ruvolo Johnson & Johnson Consumer and Personal ProductsWorldwide, Skillman, NJ, USAe-mail: eruvolojr@gmail.com

Jean-Marie Sainthillier Skinexigence, Besançon, Francee-mail: jmsainthillier@skinexigence.com

D. Salmon EA 4169 “Aspects Fondamentaux, Cliniques et Thérapeutiquesde la Fonction Barrière Cutanée”, Laboratoire de Pharmacie GaléniqueIndustrielle – Faculté de Pharmacie., Université Claude Bernard Lyon 1,Lyon cedex 08, France

Unité de Préparation et de Contrôles des Médicaments, ServicePharmaceutique – Groupement Hospitalier Edouard Herriot-Hospices Civilsde Lyon, Lyon cedex 03, Francee-mail: damien.salmon01@chu-lyon.fr

Osvaldo Santos Faculty of Medicine, Public Health Preventive MedicineInstitute and Environmental Health Institute, Universidade de Lisboa, Lisbon,Portugal

Elke Sattler Department of Dermatology, Ludwig Maximilian UniversityMunich, Munich, Germany

E. Sawaya Institut Aquitain de la Main, Bordeaux-Pessac, France

Julia J. Scarisbrick Department of Dermatology, Queen Elizabeth MedicalCentre, University Hospitals Birmingham NHS Foundation Trust, QueenElizabeth Hospital, Birmingham, UKe-mail: juliascarisbrick@doctors.net.uk

Monika Schäfer-Korting Institute of Pharmacy, Pharmacology and Toxicol-ogy, FreieUniversität Berlin, Berlin, Germany

Sabine Schanzer Department of Dermatology, Venereology andAllergology, Center of Experimental and Applied Cutaneous Physiology,Charité - Universitätsmedizin Berlin, Berlin, Germanye-mail: sabine.schanzer@charite.de

Richard K. Scher Department of Dermatology, Weill Cornell MedicalCollege, New York, NY, USAe-mail: scherri@med.cornell.edu

Contributors xlv

Christian Schulze Research and Development, Beiersdorf AG, Hamburg,Germanye-mail: Christian.Schulze@beiersdorf.com

Hamm-Ming Sheu Department of Dermatology, National Cheng Kung Uni-versity College of Medicine and Hospital, Tainan, Taiwane-mail: hmsheu@mail.ncku.edu.tw

Manuel Sillero Quintana Faculty of Sciences for Physical Activity andSport (INEF), Universidad Politécnica de Madrid, Madrid, Spain

Henrique Silva CBIOS – Research Center for Biosciences and Health Tech-nologies, Universidade Lusófona, Lisboa, Portugal

Department of Pharmacological Sciences, Universidade de Lisboa – School ofPharmacy, Lisbon, Portugal

Iqbaljit Singh Department of Dermatology, UCSF, Fremont, CA, USAe-mail: gill1606@gmail.com

Mariana Soirefmann Dermatology Department, Pontificia UniversidadeCatolica do Rio Grande do Sul (PUC-RS), Porto Alegre, Brazil

Zhenhhua Song L’Oréal Research and Innovation, Aulnay-Sous- Bois,France

Aleksandr B. Stefaniak Centers for Disease Control and Prevention,National Institute for Occupational Safety and Health, Morgantown,WV, USAe-mail: AStefaniak@cdc.gov

Tomasz J. Stefaniak Department of General, Endocrine and TransplantSurgery, Medical University of Gdansk, Gdansk, Polande-mail: wujstef@gumed.edu.pl

Markus F. C. Steiner GO Health Services, NHS Grampian, Aberdeen, UKe-mail: m.steiner@abdn.ac.uk; m.steiner@nhs.net

Andrew J. Taberner Auckland Bioengineering Institute, University ofAuckland, Auckland, New Zealand

Department of Engineering Science, University of Auckland, Auckland,New Zealand

Hachiro Tagami Department of Dermatology, Tohoku University GraduateSchool of Medicine, Sendai, Japane-mail: hachitagami@ybb.ne.jp

Liliana Tavares CBIOS – Research Center for Health Science and Technol-ogies, Universidade Lusófona, Lisbon, Portugal

Devinder Mohan Thappa Department of Dermatology and STD, TheJawaharlal Institute of Postgraduate Medical Education and Research,Pondicherry, Puducherry, Indiae-mail: dmthappa@gmail.com

xlvi Contributors

Lotte Themstrup Department of Dermatology, Roskilde Hospital, Univer-sity of Copenhagen, Roskilde, Denmarke-mail: lotte.themstrup@gmail.com

Pierre Treffel Pharmaceutical laboratory, Codexial Dermatologie,Vandœuvre-lès-Nancy, Francee-mail: Pierre.treffel@codexial-dermatologie.com

Jui-Chen Tsai Institute of Clinical Pharmacy and Pharmaceutical Sciences,National Cheng Kung University, College of Medicine, Tainan, Taiwan

Claudia Valenta Department of Pharmaceutical Technology andBiopharmaceutics, Faculty of Life Sciences, University of Vienna, Vienna,Austriae-mail: claudia.valenta@univie.ac.at

Daniel Varchon Laboratoire deMécanique Appliquée R. Chaléat, Universityof Franche-Comté, Besançon, Francee-mail: daniel.varchon@univ-fcomte.fr

Céline Viennet Engineering and Cutaneous Biology Laboratory, UMR 1098,University of Franche-Comte, Besançon, Francee-mail: celine.viennet@univ-fcomte.fr

Martine Vigan Department of Dermatology, University Hospital ofBesancon, Besançon, Francee-mail: martine.vigan@gmail.com

Marty O. Visscher Skin Sciences Program, Division of Plastic Surgery,Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

Department of Surgery, College of Medicine, University of Cincinnati,Cincinnati, OH, USAe-mail: marty.visscher@gmail.com

Michael Vogt Institute for High Frequency Techniques of the Ruhr-University, Bochum, Germany

Xuemin Wang Shanghai, China

Hans-Jürgen Weigmann Department of Dermatology, Venereology andAllergology, Center of Experimental and Applied Cutaneous Physiology,Charité - Universitätsmedizin Berlin, Berlin, Germanye-mail: hweinet@alice-dsl.net

Julia Welzel Department of Dermatology and Allergology, General HospitalAugsburg, Augsburg, Germanye-mail: julia.welzel@klinikum-augsburg.de

Xuemin Wang: deceased.

Contributors xlvii

AlexanderWitkowski Dermatology Unit, University of Modena and ReggioEmilia, Modena, Italy

Ximena Wortsman Department of Radiology and Department of Dermatol-ogy, Institute for Diagnostic Imaging and Research of the Skin and SoftTissues, Clinica Servet, Faculty of Medicine, University of Chile, Santiago,Chilee-mail: xworts@yahoo.com

Perry Xiao School of Engineering, London South Bank University, London,UKe-mail: xiaop@lsbu.ac.uk

Sang Woong Youn Department of Dermatology, Seoul National UniversityBundang Hospital, Seongnam, Gyeonggi-do, South Koreae-mail: swyoun@snu.ac.kr

Chao Yuan Department of Skin and Cosmetic Research, Shanghai SkinDisease Hospital, Shanghai, Chinae-mail: dermayuan@163.com

Hamed Zartab Center for Research and Training in Skin Diseases andLeprosy, Tehran University of Medical Sciences, Tehran, Iran

Tissue Engineering andWound Healing Lab, Department of Surgery, Divisionof Plastic Surgery, Brigham andWomen’s Hospital –HarvardMedical School,Boston, USAe-mail: hzartabmd@yahoo.com; hzartab@partners.org; hzartabmd@gmail.com

xlviii Contributors

The Human Skin: An Overview 1Pierre Agache, Thomas Lihoreau, Sophie Mac-Mary,Ferial Fanian, and Philippe Humbert

Contents

1 A Few Figures About the Skin . . . . . . . . . . . . . . . . . 2

2 Skin Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.1 Annexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.2 Variations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

3 Skin Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33.1 Specific . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33.2 Exerted in Cooperation with Other Organs . . . . . . 3

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Pierre Agache: deceased.

P. Agache • P. HumbertDepartment of Dermatology, University Hospital ofBesançon, Besançon, Francee-mail: aude.agache@free.fr; ferial.fanian@chu-besancon.fr;ferial.fanian@cert-besancon.com;philippe.humbert@univ-fcomte.fr

T. Lihoreau (*)Center for Research and Studies on the Integument(CERT), Department of Dermatology, ClinicalInvestigation Center (CIC INSERM 1431), BesançonUniversity Hospital; INSERM UMR1098, FED4234IBCT, University of Franche-Comté, Besançon, Francee-mail: tlihoreau@chu-besancon.fr

S. Mac-MarySkinexigence SAS, Bioparc, Besançon, Francee-mail: smac@skinexigence.com

F. FanianCenter for Study and Research on the Integuments,Department of Dermatology, University Hospital ofBesançon, Besançon, Francee-mail: ferial.fanian@chu-besancon.fr;ferial.fanian@cert-besancon.com; fanian@gmail.com

# Springer International Publishing Switzerland 2017P. Humbert et al. (eds.), Agache’s Measuring the Skin,DOI 10.1007/978-3-319-32383-1_1

1

KeywordsHuman skin • Body temperature control •Chemical barrier • Elasticity • Hydration •Immune function • Mechanical protection •Microcirculation • Self-maintenance and self-repair • Sensory function • Sexual function •Skin appendages • Topographical variations

1 A Few Figures About the Skin

Area: 1.8 m2

Average thickness: 1.2 mmAverage volume: 3.5 dm3 = 0.035 m3

Weight with blood: 4.7 kgWeight without blood: 4.2 kgRatio area/thickness = 150,000

The skin participates in many physiological andpathological events and processes of the humanorganism, owing to its large area of contact withthe internal milieu, but also to its volume and vari-ety of tissues. The cutaneous expression of internaldiseases is frequent, varied, and often specific.

2 Skin Structure

The general structure of the skin is a stratified tissuewhose four layers are, from the top to the bottom,the stratum corneum (8–20 μm thick, could go up to1.5 mm on palms and soles), the viable epidermis(30–80 μm), the dermis (1–2 mm), and the hypo-dermis or subcutis (0.1 to several cm) (Fig. 1). Eachof these layers has its own physiology, functions,and evolution along life.

2.1 Annexes

The skin is a heterogeneous organ (dead tissue,epithelium, connective tissue, muscles, etc.), andfurthermore it harbors four types of independentmini-organs, also called skin appendages:

– The nails, growing at a speed of 3 mm/monthon hands and 1–1.5 mm/month on feet, with

this speed decreasing with age (Scher andDaniel 2007)

– The pilosebaceous follicles and hair: between90,000 and 130,000 on the scalp, with a termi-nal hair diameter of 40–120 μm, depending ofthe phototype; 60–100 hair fall per day, andthey grow at a speed of 0.35–0.44 mm/day,(1 cm/month, 12 cm/year) (Blume-Peytavi2008; Guichard et al. 2013)

– The eccrine sweat glands (three millions)– The apocrine sweat glands (armpit, perineum)

2.2 Variations

Topographical variations in its structure andfunctions are considerable: the scalp, the skin ofthe face, the dorsal skin of the hands and feet, the

Fig. 1 A vertical section of the plantar skin. dr reticulardermis. ds superficial dermis. e viable epidermis,h hypodermis and adipose tissue, sc stratum corneum.Stars coiled part of sweat glands (both secretory segmentand lower duct). Arrows sweat ducts. Note the large skinthickness (1.8 mm, in other sites it would be close to1 mm), the absence of pilosebaceous follicles, the largethickness of the stratum corneum, and the great number ofsweat glands. In vivo dimensions were about 15 % larger.Bar = 200 μm (From Degos and Civatte 1977)

2 P. Agache et al.

palms and soles, the armpits, and the perineumhave their own anatomy, functions, and reactivity(Tagami 2008; Sandby-Møller et al. 2003; Wallerand Maibach 2006).

To briefly give some examples, in usual tem-perature and hygrometric atmosphere conditions(20–22 �C, 40–60 %), skin sebum excretion couldvary from 0 (arms, legs, etc.) to more than 200 μg/cm2 (greasy subjects forehead), and hydrationindex could go from 10 (dry skin on the legs) to100 (well-hydrated skin on the forehead, withoutunity).

Aging (intrinsic or extrinsic) is obviouslymodifying skin structure (Lévêque and Agache1993):

– Hydration presents maximum values between20 and 40 and then regresses.

– Elasticity is the mechanical property that betterreflects skin aging: it decreases and becomesoriented with age, is sun exposure dependent,and more important on women, and its valuesdecrease from head to feet.

– Skin microrelief, roughness, and wrinkles arenot involving on the whole body in the samemanner, again depending on topology (gravity,expressions, etc.) or environmental factors(sun, tobacco, etc.), along life (Guinotet al. 2006);

– Microcirculation: capillary density, structuredat the beginning even if variable in density indifferent body areas (mean of 60–70/mm2),could worse until a disorganized (orientation),heterogeneous (size, shape of the capillaries)network, characterized by a density of 30/mm2

or less.

The skin characteristics are also function of sexand ethnicity of the subject; it could even bedependent on the side of the face (Mac-Maryet al. 2010) or environmental factors (season,weather, etc.) (Fanian et al. 2013).

Due to these important variations, parame-ters previously cited appear in publications incomparison before and after a treatment, ratherthan compared to “normal” or “pathologic”values.

3 Skin Functions

3.1 Specific

– Self-maintenance and self-repair (but there isno repair of appendages)

– Mechanical protection: resistance to frontaland tangential shocks, attenuation of externalpressures, body external shape maintenancethrough reversible deformations, adhesion ofthe palms and soles to objects in the hand andon the ground

– Chemical barrier: limitation of foreign sub-stances penetration, prevention of water andendogenous fluid loss

– Protection against ultraviolet rays– Protection against environmental pathogenic

microorganisms– Social and psychological function through the

physical aspect and mimic

3.2 Exerted in Cooperationwith Other Organs

– Sensory function: tactile senses, perceptionof temperature and pain and even of light(popliteal region) (Campbell andMurphy 1998)

– Body temperature control: especially regula-tion of heat gains and losses

– Immune function: the skin is the first line ofinformation and defense in the process ofimmunity, especially “delayed immunity”

– Ossification: synthesis of provitamin D (vita-min D is responsible for the intestinal absorp-tion of calcium)

– Sexual function: conversion of testosteroneinto more active dihydrotestosterone

References

Blume-Peytavi U. Hair Growth and disorders: with85 tables. Springer: Berlin; 2008.

Campbell SS, Murphy PJ. Extraocular circadianphototransduction in humans. Science.1998;279:396–9.

1 The Human Skin: An Overview 3

Degos R, Civatte J, editors. Dermatologie. Paris: Flamma-rion; 1977.

Fanian F, Mac-Mary S, Jeudy A, Lihoreau T, Messikh R,Ortonne J, Sainthillier JM, Elkhyat A, Guichard A,Hejazi K, Humbert P. Efficacy of micronutrient supple-mentation on skin ageing effects and seasonal variation.Clin Interv Aging. 2013;8:1–11.

Guichard A, Humbert P. Développement et déploiementd’une expertise trichologique au sein du service deDermatologie du CHRUdeBesançon. Thèse d’exerciceen pharmacie, Université de Franche-Comté, 2013.

Guinot C, Latreille J, Mauger E, Ambroisine L,Gardinier S, Zahouani H, Gue´henneux S, TschachlerE. Reference ranges of skin micro-relief according toage in French Caucasian and Japanese women. SkinRes Technol. 2006;12:268–78.

Lévêque JL, Agache P. Aging skin, properties and func-tional changes. Dekker: New york; 1993.

Mac-Mary S, Sainthillier JM, Jeudy A, Sladen S,Williams C, Bell M, Humbert P. Assessment of cumu-lative exposure to UVA through the study of asymmet-rical facial skin aging. Clin Interv Aging.2010;5:277–84.

Sandby-Møller J, Poulsen T, Wulf HC. Epidermal thick-ness at different body sites: relationship to age, gen-der, pigmentation, blood content, skin type andsmoking habits. Acta Derm Venereol. 2003;83:410–3.

Scher RK, Daniel CR. Onychologie. Diagnostic,traitement, chirurgie. 3rd ed. Paris: Elsevier; 2007.

Tagami H. Location-related differences in structure andfunction of the stratum corneum with special emphasison those of the facial skin. Int J Cosmet Sci.2008;30:413–34.

Waller J, Maibach H. Thickness of aging skin. CosmetToiletries. 121(11). Nov 2006; 295–299.

4 P. Agache et al.

Measurements of the Human Skin:Why and How? 2Pierre Agache

Contents

1 The Relevance of Measurements . . . . . . . . . . . . . 6

2 Types of Measurements . . . . . . . . . . . . . . . . . . . . . . . 72.1 Nominal Scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72.2 Ordinal Scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72.3 Interval Scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

3 Selecting the Suitable Unit . . . . . . . . . . . . . . . . . . . . 9

4 Data Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

5 Precision of Measures . . . . . . . . . . . . . . . . . . . . . . . . . 105.1 Calculation of the Maximum Experimental

Error in Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . 105.2 Variation in a Gaussian Distribution . . . . . . . . . . . . 105.3 Variation in an Atypical Distribution . . . . . . . . . . . 10

6 Comparative Measurements . . . . . . . . . . . . . . . . . . 106.1 Comparison of an Isolated Value (x) to a

Gaussian Series of More than 30 Numbers . . . . . 106.2 Comparisons of Two Series

of Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116.3 Simultaneous Comparison of Several Sets

of Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

7 Minimizing the Numberof Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

7.1 Sequential Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127.2 Taguchi Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

8 Good Measuring Practice . . . . . . . . . . . . . . . . . . . . . 12

9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

This chapter was originally published under the ISBN978-3-540-01771-4 with the following book titleMeasuring the Skin. The content has not been changed.

Pierre Agache: deceased.

P. Agache (*)Department of Dermatology, University Hospital ofBesançon, Besançon, Francee-mail: aude.agache@free.fr; ferial.fanian@chu-besancon.fr;ferial.fanian@cert-besancon.com

# Springer International Publishing Switzerland 2017P. Humbert et al. (eds.), Agache’s Measuring the Skin,DOI 10.1007/978-3-319-32383-1_2

5

KeywordsGaussian distribution • Good measuring prac-tice • Interval scales • Comparative measure-ments • MKSA system • Nominal scale •Nongaussian series •Ordinal scale • Parametricevaluation • Sequential analysis • Standarddeviation • Taguchi designs

In experimental sciences, measuring phenomena isa key point, since it is through the quantitativeevaluation of an effect related to a given cause thatthe law of phenomena can be founded. (Bernard1984)

1 The Relevanceof Measurements

Metrology is the science of measurement, of eval-uation of its requirements, limitations, and inter-pretations. The primary reason for usingmetrology in cutaneous noninvasive investiga-tions is its role as a major source of progress, notonly because impressions are replaced by objec-tive facts and qualitative descriptions by quantita-tive assessments, but also because new situationsare unveiled. Even the simplest phenomenonbecomes complex when measured; one startsfrom one fact and then discovers its possible com-ponents and variations, which induces newhypotheses and opens a pathway for new knowl-edge. Physics in the past could only progressthrough the development of measurementmethods. The remarkable advances in humanphysiology during the nineteenth century, whichpreceded modern medicine and allowed it to pro-gress, came about because of a double process ofdiscovery and quantification. Skin metrology pro-vides many examples. The measurement ofsebum secretion with a view to correcting theremoval of lipid from the surface quickly showedthat the measured phenomenon was not the oneexpected, but rather the partial emptying of afollicular reservoir, the existence of which hadpreviously been ignored. The measurement ofepidermal turnover in psoriasis provided a leapforward in understanding the disease.

Biological phenomena are changeable and dif-ficult to quantify. At first glance, observation mayprevail over measurement, but the notion ofdimension is required to investigate a structureand the magnitude of change. The pathologistmust decide whether, in the visualized skin sec-tion, the tissue components are modified indimension and number by a pathological process.Furthermore, normal characteristics varydepending on the anatomical site, which has notyet been quantified; consequently, the pathologistremains unable to reach a conclusion unless majorchanges are seen. When the noninvasive anatom-ical or functional investigations are quantitative,they provide a measure with low subjectivity. Theclinician evaluating a new medication would liketo rapidly and accurately assess treatment effi-cacy; this goal can be reached only by quantifica-tion of clinical symptoms. Accordingly, it isnecessary to know whether the measure is accu-rate (degree of precision and variability) and if ittruly reflects the targeted phenomenon.

Numerical results of blood sample examina-tions is standard practice. It is likely to be thesame for most clinical symptoms in the years tocome. This is possible today in the detection andsubstantiation of subtle changes (e.g., aging(Escoffier et al. 1989; Larnier et al. 1994)) or theeffect of a therapy on a chronic disease such asscleroderma (Humbert et al. 1993). The last decadeof progress in molecular genetics has emphasizedthe considerable benefit that the collection of dataprovided by everyday medical practice might gen-erate, and in years to come practitioners will cer-tainly be involved in collecting and processing thisdata. Such information requires classification, sub-stantiation, and treatment using statistical parame-ters. A few nondermatological specialties alsoutilize skin measurements, e.g., in physiology(endocrinology, body temperature regulation,immunology, etc.), where the skin is an effectororgan readily examined noninvasively because ofits accessibility. It is also the case for cosmetologyresearch, where innocuousness and efficacycriteria may become visually unattainable becauseof their subtlety, and require instrumental measure-ments for assessment.

6 P. Agache

2 Types of Measurements

Before choosing an appropriate evaluationmethod, it is necessary to look at the nature ofthe data. If they relate to individuals or categories,hence with no possibility of converting them intonumbers, the evaluation mandates a nominalscale. If the data can be translated into numbers,but on a scale where intervals are unknown oruneven, they can only be ranked. Finally, if thevariation is measured on a continuous scale witheven intervals, then the traditional evaluation isused: the so-called parametric evaluation (Siegel1956).

2.1 Nominal Scale

This is the only means of measuring categories,facts or states, named by a word or an expression,and not put into numbers, for example, aggrava-tion, desquamation, over 60-year-old subjects,etc. The nominal scale uses a number or the per-centage of a total. If the measured category is partof a series, it can be replaced by a number foreasier presentation, but without ranking.

A percentage should be presented with itsuncertainty margins, thus its standard deviation(SD). The latter is calculated by the formulaSD = [p(1 � p)/n]1/2, where p is the percentage(from 0 to 1) and n the total number of data. Theconfidence interval for an occurrence by chance ofless than 5 % is that between two standard devia-tions on each side of p. Tables of 5 % confidenceintervals can be found in statistics textbooks. Aclose evaluation can be obtained using an abacus(Fig. 1).

2.2 Ordinal Scale

The ordinal scale provides only a ranking. Thistype of scale should be selected for two reasons:either the data are part of a discontinuous series,thus one cannot apply a number to them, or theycome from a continuous series, but on an unknownscale on which it is not known if the distances

between the measured objects are equal or propor-tional: only the rank is identified. For instance,nonexistent, slight, good, and very good improve-ments can be rated 0, 1, 2, 3, knowing that 3 doesnot mean that the improvement was 3 times betterthan 1. To describe series of this type, the adequateparameters are the median and the extreme values.Graduated scales should be avoided (especiallywhen the series is made up of averages) becausethey may be mistakenly used for parametric mea-surements instead of being more accurately appliedto ranking measurements. This type of classifica-tion is particularly indicated in psychosensorialevaluations in which the phenomenon understudy varies discontinuously, or continuously butwith unknown intervals.

2.3 Interval Scale

Interval scales are most commonly used in eval-uation for numbers in a continuous series. Unitsmay be changed if the scale is the same (e.g.,temperature in the same series can be convertedfrom Celsius into Fahrenheit degrees and viceversa). If the data have a gaussian (or normal)distribution, they can be described by the meanand its standard error (i.e., the standard deviationof the mean); otherwise the adequate parametersare the median and the extreme values. If it ispreviously known that the studied parameter hasa gaussian distribution, one can surmise that themeans of samples equal to or greater than 30 arealso normally distributed. In a comparative eval-uation, it is often possible that each subject is itsown reference; this avoids the interindividualsource of variation (important in biology) andmakes it possible to use statistical tests formatched pairs.

2.3.1 Opposition MethodThe opposition method, also called the zeromethod, is used to obtain a higher degree of pre-cision than a direct measurement. The rationale isto measure only the difference between theunknown quantity and another very close andalready precisely known value. The measure of

2 Measurements of the Human Skin: Why and How? 7

the difference can be more precise because it dealswith a much smaller quantity. Consequently itsprecision, related to the initial value to be mea-sured, becomes more accurate. For instance, toweigh sebum laid on a glass slide, the slide isplaced on one pan of a pair of scales and a stan-dard mass of a similar weight known with greatprecision (e.g., a glass slide without sebum) isplaced on the other. Then a weight is added onthe lighter side to make up the difference and thisdifference is then measured. The InternationalBureau of Weights and Measures has scalesdesigned for this type of differential weighing.

2.3.2 Psychosensorial EvaluationsFor the psychosensorial evaluations in which thestudied phenomenon is believed to vary in a con-tinuous and uniform way (equal intervals), anongraduated linear scale is used for each mea-surement. Generally this measurement consists ofa 10-cm-long horizontal line, with zero on the leftend and ten on the right; the measurement isindicated by a small vertical stroke. Graduatedscales are less suitable because they tend to distortthe scoring by favoring values close to the gradu-ations, with the operator influenced by the valueindicated. However, operators should be well

1010000

20

30

40

50

50

40

30

20

1010

20

30

40

50

60

70

80

90% in sample

Samplesize

60

70

70

60

60

9080

90

50004000300020001500

1000800700600500

400

300

200

150

120

100

90

80

70

60

50

40

30

Fig. 1 Confidence intervalof a percentage when theprobability of a greater orlower number occurring bychance only is limited to5 %. As shown, if thesample size is 120, the 5 %confidence interval of 30 %is 22–39 %. If the samplesize is 40, the 5 %confidence interval of 30 %is 18–47 %

8 P. Agache

aware of the scale extremes (zero and ten), whichsets the limits of the measure; consequently itsvariability is lessened. Another way to decreasevariability is to replace the absolute measurementby a comparative measurement: the objects to becompared are placed next to each other so that theyare perceived almost simultaneously; the nearerthey are in time and space, the more accurate themeasurement is. Operator training is also important.

3 Selecting the Suitable Unit

The units can be either arbitrary (e.g., millimeterson the linear scales used for psychosensorialmeasures), or arbitrarily linked to internationalphysical units (e.g., skin blood flow measured involts by the Doppler), or absolute (e.g., skinblood flow measured by the epicutaneous xenonclearance in milliliters per minute per 100 g softtissue). Physical units are always better thanarbitrary units, and absolute units are preferredto those of other associated physical phenomena(e.g., measuring stratum corneum water deple-tion in milliliters per square centimeter per hour,as compared to decreased electrical impedance).Creating dermatological or biological unitsshould be avoided when it is possible to useinternationally approved units so that skin struc-ture and properties remain within the physics ofall other materials for easier comparison and theopportunity to use the laws of physics and chem-istry for interpretation, thus considerably in-creasing the benefit of the measurements, alsonecessary for scientific progress.

We recommend measurements in units of theSystème International d’Unités (SI), also calledthe MKSA system, the four fundamental units ofwhich are the meter (m), the kilogram (kg), thesecond (s) and the ampere (A). Skin area iscommonlymeasured in square centimeters, its thick-ness in millimeters, etc. For the derived units, theconversion between the centimeter-gram-second(CGS) system, MKSA, or other systems is oftena source of error. See conversion tables in▶Chap. 160, “Correspondence Between Interna-tional System Units (MKSA) and CGS Units.”

4 Data Presentation

Facedwith a variation or a distribution, the first stepto prepare is a graphic representation: a curve or ahistogram. The eye appreciates at once a series offeatures necessary for the interpretation and theprocessing of the information, for example, thegaussian or nongaussian characteristic of a distribu-tion, the linear or nonlinear character of a relation,and the absolute level of a measure.Misunderstand-ings often stem from skipping this step.

When studying a histogram, the first question is“Does it fit a well-known distribution?” becausethe processing and interpretation of the data is theneasier. A gaussian distribution, bell-shaped andsymmetrical, means that data are independent ofeach other and that the distribution most probablyresults only from their summation. A distributionwith two peaks may correspond to twointerpenetrated gaussian curves. To rapidly checkif a distribution is gaussian, the use of gaussometricgraph paper (or gaussologarithmic if the abscissa isin logarithms) is suitable: it provides a quick cal-culation of the adjustment to this type of distribu-tion. An asymmetrical histogram may indicate abinomial distribution. A substantial asymmetrysuggests a Poisson distribution (a particular caseof binomial distribution). An asymmetrical distri-bution can sometimes be transformed into a gauss-ian one by using the logarithm of the data.

Showing a variation through a mathematicalfunction (of time or any other parameter) indicatesmajor progress in data interpretation, if the vari-able has an anatomical or functional meaning.This makes it possible to use the function inother situations, sometimes to generalize its use,with further progress in knowledge. However, apurely descriptive mathematical model (i.e., whenvariables are devoid of biological meaning) is ofminimal interest. The linear function speaks foritself and is one of the most profitable functionsthrough the calculation of the slope and interceptswith the axes. It can be deduced from an exponen-tial function by taking the logarithm of the data,and from any other function by replacing x on thex-axis with a power of x (e.g., for y = a + b/x, 1/xis put on the x-axis).

2 Measurements of the Human Skin: Why and How? 9

5 Precision of Measures

In a common parametric measurement, thehighest level of accuracy is desirable, even ifultimately the decimals are rounded for conve-nience. Only the significant figures must be men-tioned. Sampling uncertainty should always bementioned, together with the observed variation.

5.1 Calculation of the MaximumExperimental Errorin Measurements

To predict the maximum possible error in a mea-sure of combined quantities from the separatemeasure of each quantity, the standard rules are:

– The absolute error Δy on a sum y = u + v isthe sum of the errors on each componentΔy = Δu + Δv.

– The absolute errorΔy on a difference y = u �v is the sum of the errors on each componentΔy = Δu + Δv.

– The absolute error Δy on a product y = uvcorresponds to the formula Δy = uΔv + vΔu.The relative error Δy/y = Δu/u + Δv/v.

– The absolute error Δy on a quotient y = u/vcorresponds to the formula Δy = (uΔv +vΔu)/v2. The relative error Δy/y = Δu/u + Δv/v.

Note that these errors (Δu, Δv, etc.) are exper-imental errors on crude data and have no relationto statistical errors which are dealt with in thefollowing paragraphs.

5.2 Variation in a GaussianDistribution

In a gaussian distribution, the mean (m) must bepresented with its uncertainty limits (i.e., either stan-dard deviation and number of data, or standard errorof the mean). The standard deviation (SD) must bementioned with the number of observations(n) because the confidence interval it indicates

(95 % confidence interval ranges between two stan-dard deviations on each side of m) differs with thenumber of measurements. The standard error couldeither be mentioned (SD divided by the square rootof the number of observations), as in the error bars ofa graph of means. If the data are logarithmic, themean must be geometrical (nth root of the product ofn data). In the case of a percentage, both the SD andthe number of data should be mentioned.

5.3 Variation in an AtypicalDistribution

If the histogram does not show a gaussian distri-bution, it should be described using the medianinstead of the mean, i.e., the value under andabove which 50 % of the observations are found.The variability around this value is indicated inthe quartiles, which are the values under which25 %, 50 %, and 75 % of the observations aremade. One can also mention the centiles(or percentiles), the 80th centile being the valueunder which 80 % of the data are found.

The constant search for precision must not besterilizing. An isolatedmean, a separate percentage,a graph with no mention of variation are only indi-cators, but are always preferable to the text alone.

6 Comparative Measurements

One purpose of a measurement is to compare theobtained value to others, to ascertain whether theobserved difference is true, or rather to calculatethe probability that it might originate from chancealone. The methods chosen vary according to thetype of measurement.

6.1 Comparison of an IsolatedValue (x) to a Gaussian Seriesof More than 30 Numbers

Its distance to the mean of the series determinesthe probability for the value x to belong to thisreference population by chance alone. For a

10 P. Agache

distance of 1 SD, the probability is 15.9 %, fortwo SDs 2.3 %, and for three SDs 0.13 %. Theexact probability is the total area (=1) under theGauss curve minus the part of that area beyond xon the x-axis. It can be found in gaussian curvetables, where it has to be divided by 2 since thevalue of x is located on one side of the mean(one-tailed test).

6.2 Comparisons of Two Seriesof Measurements

6.2.1 Gaussian Series or Series Largerthan 30

Use the test of comparison of variances (statisticsmanuals: F tables), followed by the usual para-metric tests of comparison of means.

Series with Variances (s2) Not SignificantlyDifferent– Independent samples na and nb are �30; use

the formula:

� ¼ ma �mbð Þ= sa2=na þ sb

2=nb� �0, 5

with degree of freedom dfð Þ ¼ na þ nb � 2

– Independent samples na and nb are <30; usethe formula:

t ¼ ma �mbffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi1

naþ 1

nb

� �s2a na � 1ð Þ þ s2b nb � 1ð Þ

na þ nb � 2

s

with df ¼ na þ nb � 2

– Matched samples: the calculation ismade on thepaired differences (n pairs): use the formula:

t or�ð Þ ¼ m:n0:5=s, where

df ¼ n� 1 and

m ¼ the mean of differences:

The parameter (distance to the mean, calculated instandard deviation) is the same for the three situ-

ations, but it is called � or t depending on the sizeof each sample (30 or <30, respectively).

Serieswith SignificantlyDifferent Variances (s2)The same formulas are used but the number ofdegrees of freedom used to refer to the probabilitytable must bemodified according to the formula ofWelch’s G test,

1

ddl¼ 1

na � 1

s2anas2

� �þ 1

nb � 1

s2bnbs2

� �

the global variance s2, calculated by the equation:s2 = s2a/na + s2b/nb

The threshold value of parameter t depends onthe risk α and the one-tailed or two-tailed charac-ter of the hypothesis to be checked.

6.2.2 Nongaussian SeriesNonparametric tests should be used, for example:

– Comparison of two nominal-type series: χ2 test– Comparison of two independent ordinal-type

series: Mann and Whitney test– Comparison of twomatched ordinal-type series:

Wilcoxon’s matched pairs signed-ranks tests– Comparison of two independent interval-type

series: randomization test for two independentsamples (Siegel 1956)

– Comparison of twomatched interval-type series:randomization test for matched pairs (Siegel1956) (the most powerful nonparametric test)

6.3 Simultaneous Comparisonof Several Setsof Measurements

• Gaussian series: one-way variance analysis(ANOVA)

• Nongaussian series:– Nominal type series: #χ2 test– Independent ordinal- or interval-type series:

Kruskal-Wallis variance analysis (Siegel1956)

– Matched ordinal- or interval-type series:Friedman’s variance analysis (Siegel 1956)

2 Measurements of the Human Skin: Why and How? 11

7 Minimizing the Numberof Measurements

7.1 Sequential Analysis

When observing the sequential chance occurrenceof two types of events in order to know if one typeis more probable than the other, intuitively onefeels the most probable is the one that happensmore often. Indeed, when the difference in occur-rences increases, at one point it becomes statisti-cally significant at the 5 % probability level(or any level chosen in advance). On a graphshowing the sequence of events, each one markedby an oblique dash in a specific direction (e.g.,upward for one series, downward for the other), abroken line is obtained, the global direction ofwhich leans toward the direction of the mostprobable event. The limits the line would crosswhen the difference is significant can then bedrawn on each side of the central line. As soonas this happens, the experiment can be stopped(Fig. 2) (Whitehead 1997).

These limits can be computed using mathe-matic formulas which can be found in the bookof Armitage et al. signalled at the end of thischapter.

7.2 Taguchi Designs

Taguchi designs are the most widely used exper-imental plans aimed at reaching the desired resultwith a minimum of experiments Taguchi and Wu(1980). For example, for the study of the effect ofthree parameters, each having two possibilities, itis possible to carry out four experiments insteadof eight corresponding to the possible combina-tions. Among the categories of plans, the maintypes are:

– Designs with two parameters, each having twomodes (L4 designs)

– Designs with three to five parameters, eachhaving two modes (L8 designs)

– Designs for parameters with three modes(L9 designs)

– Designs allowing the combination of oneparameter with two modes with parameterswith three modes (L18 designs)

– Crossed designs, i.e., combining controlledparameters (as in the above designs) withso-called external parameters that are notunder control.

8 Good Measuring Practice

Any measurement, especially in biology, has adegree of uncertainty, due to the nature of themeasured phenomenon, as well as the measuringdevice and the operator. The reliability of a mea-surement can only be obtained if these last twofactors are under control.

Equipment on the market must comply withtechnical standards. However, with time, perfor-mance may weaken, due to climatic, magnetic orother factors; we recommend placing the equip-ment on a test bench at regular intervals (forinstance every year) in order to check the accuracyof its technical performance. For example, when a

x xx x

x xxx x x

xxx x x x x

xx x x x

x xx

Compound B

Compound A

Fig. 2 Sequential trial. In the first patient, compound Awas more effective than compound B, thus the first verticalbox above the black one was checked. In the secondpatient, compound B was more effective thancompound A, thus the next horizontal box was checked.In this example, the exit lies between the two wings of thegrid, indicating no significant difference in effectivenessbetween the two compounds. Significance would be indi-cated by an exit at the exterior side of the wings

12 P. Agache

device uses several pressures, are the displayedpressures correct? Does a cast meant to last sev-eral years lose its shape with time? It may be wiseto check the device completely every year bymeasuring the equivalent skin standard. Forexample, the reliability of an ultrasound imagingdevice is checked by measuring the thickness ofthe layers of a stratified material. These methodsare rarely used but should become common prac-tice. Indeed, it is difficult to find standard mate-rials that are reliable over prolonged periods.Manufacturers should assist users on this matter.

Most errors are caused by the operator and notthe equipment. They tend to occur if the operatordoes not systematically ask: Have I read thor-oughly and understood the instruction manual?Have I followed the recommendations? It is notpossible to be a good operator instantly; patience,a critical mind, and experience are necessary.

The second question is related to the conditionsin which the measurement is taken. Environmentalconditions: temperature and relative humidity ofthe room must always be noted. Other conditionsare specific to the type of measurement (e.g., forthermography). Physiological conditions relatedto the subject should be respected: minimum of15 min acclimation to the room temperature, rest,relaxation (made easier when the test is noninva-sive), thermal comfort, absence of sweating. Athird question arises when subjects are their owncontrols: is the test site appropriate? Symmetry isno guarantee (Treffel et al. 1994), neither is prox-imity (Panisset et al. 1992). The random permuta-tion of control and active sites obviates thisproblem. Finally a mandatory procedure is toalways write down the date and hour, the environ-mental conditions, and an identification mark ofthe tested subjects, including the control subjects.Good practice in metrology implies that a manualor computerized logbook be kept with each device.

A rational catalog of possible errors sources is(Serup 1994):

1. Study design (strategic error)2. The measuring device (technical error)3. The use of the device (performance error)4. Measuring conditions (inadequate laboratory

facilities)

5. Selection and preconditioning of test subject(subject-related error)

6. Data acquisition, storing, and handling (dataerror)

7. Reporting and publication policies (explana-tory mistake)

Even when these rules are observed, it is usefulto know the results obtained by others. It oftenhappens that the values given by a device in alaboratory group are not exactly the same as thosegiven by similar equipment in another group.When new equipment is implemented, the oper-ating team should check the reliability of theirmeasurements on the same subjects, and knowthe variation coefficient (standard deviation/mean) of the measured parameters in a sample ofat least 30 people. This is also essential in order toforecast the number of subjects (belonging to thetested sample) that will have to be recruited incomparative studies using this method.

For two independent samples, this number isgiven by the formula:

N � 2 � α þ � β� �

s=Δ 2

where � α is the accepted limit probability forconsidering as true a difference Δ that does notexist (risk α): usually one takes � α = 1.96 for a�5 % risk of error. And � β is the risk of ignoringa real difference Δ (risk β): usually the chosenfigure is: � β = 1.28 for a �10 % risk of error.

If the samples are matched (i.e., if subjects aretheir own controls) the formula is:

N � � α þ � β� �

s=Δ 2

Misinterpretation is forgivable. Mistakes are oftenmade because of ignorance of what is actuallymeasured. Upon obtaining results, the operatormust ask the following two questions:

1. Beyond the object that is officially measured,what is the real phenomenon, e.g., the so-calledsebum excretion rate? Possible answers are:– The follicular reservoir excretion rate– The sebaceous gland secretion rate

2 Measurements of the Human Skin: Why and How? 13

– The absorbing paper absorption rate– The stratum disjunctum absorption rate

or what is the measuring method rationale,e.g., skin thickness measurement by ultra-sound. The possible answer is the time for theultrasound to go forward and backwarddivided by its assumed constant speed.

2. What is the measurement unit and why? Forexample, the cutaneous blood flow is mea-sured in volts by the Doppler because anabsolute calibration of the device has notbeen possible. A bias in the measurementtechnique may also alter the interpretation. Itcan be caused by subject and/or operator sub-jectivity or biased sample selection. The for-mer problem is circumvented by using asingle- or double-blind protocol, the latter byrandomization of the sample or the sites so asto cancel unknown physiological variation(always use an algorithm-generated list ofrandom numbers).

9 Conclusion

The following procedure should be followed bythe operator:

1. Ascertain the reliability and accuracy of theequipment.

2. Meticulously follow all the manufacturer’sinstructions for using the equipment.

3. Set up the laboratory so that the material andphysiological conditions of a precise measure-ment are routinely ensured.

4. Systematically record the above-mentionedelements on a specific logbook.

5. Determine the variance of the equipment’smeasures, preferably before the method isused routinely.

Acknowledgments The author thanks Mrs. MarietteMercier, Professor of Statistics at the Faculty of Medicineand Pharmacy of Besançon (France), who kindly revisedthis chapter and provided the information aboutWelch’s test.

References

Bernard C, editor. Introduction à l’étude de la médecineexpérimentale. Paris: Flammarion; 1984. p. 185. Paris,1865.

Escoffier C, De Rigal J, Rochefort A, Vasselet R, LévêqueJ-L, Agache P. Age-related mechanical properties ofhuman skin: an in vivo study. J Invest Dermatol.1989;93:353–7.

Humbert P, Dupond JL, Agache P, et al. Treatment ofscleroderma with oral 1,25-dihydrovitamin D3: evalu-ation of skin improvement using non-invasive tech-niques. Acta Derm Venereol. 1993;73:449–51.

Larnier C, Ortonne JP, Venot A, Faivre B, Beani JC,Thomas P, Brown TC, Sendagorta E. Evaluation ofcutaneous photodamage using a photographic scale.Br J Dermatol. 1994;130:167–73.

Panisset F, Treffel P, Faivre B, Brunet-Lecomte P, Agache P.Transepidermal water loss related to volar forearm sitesin humans. Acta Derm Venereol. 1992;72:4–5.

Serup J. Bioengineering and the skin: from standard errorto standard operating procedure. Acta Derm VenereolSuppl. 1994;185:5–8.

Siegel S, editor. Nonparametric statistics for the behavioralsciences. London: McGraw-Hill; 1956.

Taguchi G, Wu Y, editors. Introduction to off line qualitycontrol. Nagoya: Central Japan Quality Control Asso-ciation; 1980.

Treffel P, Panisset F, Faivre B, Agache P. Hydratation,transepidermal water loss, pH and skin surface parame-ters: correlations and variations between dominant andnon-dominant forearms. Br J Dermatol. 1994;130:325–8.

Whitehead J. The design and analysis of sequential clinicaltrials. 2nd ed. Chichester: Wiley; 1997.

Suggested Reading

Altman DG, editor. Practical statistics for medical research.London: Chapman & Hill; 1993.

Armitage P, Berry G, editors. Statistical methods in medi-cal research. 2nd ed. Oxford: Blackwell Scientific Pub-lications; 1987.

Bailar JC, Mosteller F, editors. Medical uses of statistics.Waltham: NEJM Books; 1986 (This is a general statis-tical handbook devoted to biologists and physicians,and written in simple language that would be under-stood even by readers who had no education inbiostatistics).

Beyer WH, editor. Handbook of tables for probability andstatistics. 2nd ed. Boca Raton: CRC Press; 1968.

Box GEP, Hunter WG, Hunter JS, editors. Statistics forexperimenters. New York: Wiley; 1978.

Salsburg DS, editor. The use of restricted significance testsin clinical trials. Berlin/Heidelberg/New York:Springer; 1992.

14 P. Agache

Chronobiology of the Skin: CutaneousClocks and Biorhythms 3Annette Mehling and Corinne Reymermier

Contents

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2 Functional Chronobiological Rhythmsof the Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

3 Cutaneous Clocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

KeywordsBiorhythms • Chronobiology • Circadian •Clocks • Skin

1 Introduction

Cognizance of time and its influence on the recur-ring behavioral patterns of plants and animalsdates back many centuries (reviewed by Reinbergand Smolensky 1983; Moser et al. 2006; Halberget al. 2001). The study of the rhythmic time-basedrelationships found in biological systems has beencoined chronobiology – the science of investigat-ing and objectively quantifying phenomena andmechanisms of the biological time structure,including the rhythmic manifestations of life(American Association for Medical Chronobiol-ogy and Chronotherapeutics, www.aamcc.net/glossary.htm). Chronobiological rhythms have aprofound influence on organisms by providing thetemporal structure for biological processes. To“tell time,” most living organisms use timekeep-ing mechanisms known as “biological clocks.”These “clocks” coordinate our physiological andbehavioral functions, thereby optimizing theadaptations to and interactions with our environ-ment. In the last decades, hundreds of differentclocks/cycles have been identified sparkingrenewed interest in chronobiology. In addition,the awareness of the implications of chronobio-logical effects has increased, and it is now

A. Mehling (*)BASF Personal Care and Nutrition GmbH, D€usseldorf,Germanye-mail: annette.mehling@basf.com

C. ReymermierBASF Beauty Care Solutions France S.A.S, Lyon, Francee-mail: corinne.reymermier@basf.com

# Springer International Publishing Switzerland 2017P. Humbert et al. (eds.), Agache’s Measuring the Skin,DOI 10.1007/978-3-319-32383-1_3

15

recognized that these have true mechanistic andtherapeutic implications (e.g., chronotherapy;reviewed by Kaur et al. 2013; Librodoet al. 2012). A short description of typical chro-nobiological rhythms is depicted in Fig. 1.

While the underlying science of biologicaloscillators is intricate and complex and thereforenot entirely understood, our master clocks aremost likely set according to the world’s mostreliable timekeeper: the sun. The circadianrhythm, the daily cycle, is probably the mostpronounced and therefore the best researched.Light is assumed to be the most important zeitge-ber, the external stimuli which entrain the rhythmsand govern the synchronization of the circadianrhythm. Circadian timekeeping systems in mam-mals are organized into a complex hierarchicalnetwork of oscillators with the suprachiasmaticnucleus (SCN) of the hypothalamus acting as theprincipal pacemaker. The SCN receives light sig-nals from specialized cells in the retina, the retinalganglion cells, which entrain the SCN to light-dark cycles via glutaminergic innervation and/orphotoreceptive systems based on melanopsin.This in turn triggers circadian rhythms, e.g., via

the release of the hormone melatonin or adreno-corticotropic hormone (ACTH; Bersonet al. 2002; Hastings et al. 2003; Luboshitzky2000), which influences the peripheral clocksubiquitously found in human cells. Although theexact functions are not yet well elucidated, it isreasonable to assume that the peripheral clocks arethen responsible for the physiological fine-tuningleading to optimized responses to environmentaland internal occurrences and processes. Biologi-cal periodicities can also be governed by otherenvironmental cues, e.g., by the lunar cycle, butalso by daily social rhythms, e.g., work. Interest-ingly, if left undisturbed, the “free-running” circa-dian rhythm in humans is approximately 25 h(possibly reflecting lunar influences as secondarysynchronizers as this time period corresponds tothe orbit time of the moon and with it, the tidalpeaks that occur every 12 h and 25 min). Oneaspect that should not be forgotten is that life itselfis a biological rhythm. Malfunctions of the bio-logical clocks can lead to various disorders,including hypertension, sleep, psychosomatic dis-orders, and a number of chronobiological rhythmsmost likely out of phase in the elderly population

Endogenous clockse.g. clock genes

Diurnal/Nocturnal:Day or night rhythms

Circadian:Approx. 24 h rhythms

Circalunar:Approx. 30 days

Circaannual/seasonal:Approx. 1 year rhythms

Lifespan dependent rhythms:Birth, childhood, puberty,

adolescence,adulthood, aging(meno-/andropause), senescence,

death

So

cial clocks

e.g. work schedules, social activitiesE

nvi

ron

men

tal a

nd

so

lar

clo

cks

e.g.

sun

light

, sea

sons

and/

or te

mpe

ratu

re

Fig. 1 Schematicrepresentation of typicalchronobiological rhythmsand the clocksinfluencing them

16 A. Mehling and C. Reymermier