Pathogenesis and Treatment of Acne and Rosacea

Christos C. Zouboulis Andreas D. Katsambas Albert M. Kligman Editors

Pathogenesis and Treatment of Acne and Rosacea

ISBN 978-3-540-69374-1 ISBN 978-3-540-69375-8 (eBook) DOI 10.1007/978-3-540-69375-8 Springer Heidelberg New York Dordrecht London

Library of Congress Control Number: 2014939846

© Springer-Verlag Berlin Heidelberg 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher's location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

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Editors Christos C. Zouboulis Departments of Dermatology, Venereology, Allergology, and ImmunologyDessau Medical Center Dessau Germany

Andreas D. Katsambas Department of Dermatology Andreas Syngros Hospital University of Athens AthensGreece

Albert M. Kligman† Department of Dermatology University of Pennsylvania Philadelphia, PA USA

www.springer.com

In memoriam Dr. Albert Montgomery Kligman, 17.03.1916–09.02.2010.

Dedicated to Gundula, Konstantin and Viktor-Alexander for their enormous love and patience

vii

The History of this Book

It was a warm day in late July 2002 during the 50th Annual Montagna Symposium on the Biology of Skin when two of us met for the fi rst time. We knew each other longer; the younger part has admired the more experienced part for his pioneer work and great contribution to science, and the latter part was well informed on the scientifi c work of the younger, but they have simply never met before in person. There, in Snowmass, up on the mountains of Colorado, an invitation to lunch was followed by a long exchange of ideas and scientifi c arguments in the fi elds of sebaceous gland, acne, and rosacea that lasted for a few hours. Since then, the two discussants met once a year for lunch during the annual meeting of the Society of Investigative Dermatology and stayed for hours discussing, what else, the developments but also histories on the research of sebaceous gland, acne, and rosacea. They renewed their appointment for the next annual meeting with “a lot of new aspects to elucidate” in between. They even agreed for a common cruise at the islands of Greece in order to have plenty of time for scientifi c discussions under the inspiration of the plain sun and the magic of white and blue. Unfortunately, this journey never took place.

Pref ace

Christos C. Zouboulis

viii

During one of these annual discussions, the experienced part introduced the idea of a book on, what else, the sebaceous gland, acne, and rosacea and motivated the younger part to overtake the task. The latter felt the load too heavy to be carried on his shoulders, especially with all these giants, Albert M. Kligman, Gerd Plewig, and William J. Cunliffe, having overtaken this responsibility before him. But the most experienced insisted: “This volume will be a classic…This will be a great classic, and I am proud to be a part of it…It’s an enormous labor of love for you, but it will do you a great honor when it is fi nished.” So the younger part decided to start the long way, especially with the contribution of a third, politically experienced acneolo-gist, who joined the group and declared: “I have an invitation for a new acne book, would you like us to write it together?” Alea iacta est.

Since then, a few more years have passed; the three editors were accompanied by approximately 100 additional authors from all around the world, hundreds of pages have been written, rewritten, and actualized, and the time for this fi rst edition became mature. It is a great pity that the brain behind the book is not anymore among us to feel proud for the result of the common effort. Dr. Albert Montgomery Kligman died 93-year-old on February 9, 2010, in Philadelphia. He was prophetic regarding the long way to go; the rest two of us can only hope that he will also be prophetic in his prediction that “This volume will be a classic!”

We want to thank all our coauthors for their enormous work and group spirit. We are grateful to Spinger Verlag, especially Mrs. Ellen Blasig, Mrs. Ioanna Panos, and Mr. Sverre Klemp, for their continuous support. We also

Andreas D. Katsambas

Preface

ix

thank Dr. Clio Dessinioti for her tireless contribution. And all three of us are indebted to our families for their patience and love.

Dessau/Berlin, Athens and Philadelphia, 2008–2013

Dessau/Berlin, Germany Christos C. Zouboulis, Athens, Greece Andreas D. Katsambas, Philadelphia, PA, USA Albert M. Kligman†

Albert M. Kligman

Preface

xi

Contents

Part I The Pilosebaceous Unit

1 The Sebaceous Gland Through the Centuries: A Diffi cult Path to Independence . . . . . . . . . . . . . . . . . . . . . . . . 3Carlo Gelmetti

2 Embryology of the Pilosebaceous Unit. . . . . . . . . . . . . . . . . . . . 9Vladimir A. Botchkarev and Michael Y. Fessing

3 Molecular Aspects of Sebaceous Differentiation. . . . . . . . . . . . 19Christos C. Zouboulis, Georgios Nikolakis, and Clio Dessinioti

4 Anatomy of the Sebaceous Gland . . . . . . . . . . . . . . . . . . . . . . . . 27Fragkiski Tsatsou and Christos C. Zouboulis

5 Sebum and Sebaceous Lipids . . . . . . . . . . . . . . . . . . . . . . . . . . . 33Apostolos Pappas

6 Experimental Models of the Sebaceous Gland . . . . . . . . . . . . . 43Christos C. Zouboulis and Clio Dessinioti

Part II Acne Vulgaris: Epidemiology

7 Acne Epidemiology and Socioeconomic Aspects. . . . . . . . . . . . 53Christos C. Zouboulis, Clio Dessinioti,and Christina Antoniou

Part III Pathogenesis of Acne: Classical Aspects

8 Acne Pathogenesis: What We Have Learned Over the Years. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61Clio Dessinioti

9 The Role of Hyperkeratinization . . . . . . . . . . . . . . . . . . . . . . . . 71Ichiro Kurokawa

10 The Role of the Sebaceous Gland . . . . . . . . . . . . . . . . . . . . . . . . 77Christos C. Zouboulis and Evgenia Makrantonaki

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11 The Role of Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91Mark D. Farrar and Richard A. Bojar

12 Infl ammation in Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97Guy F. Webster

Part IV Pathogenesis of Acne: Modern Aspects

13 A New Concept of Acne Pathogenesis . . . . . . . . . . . . . . . . . . . . 105Christos C. Zouboulis and Clio Dessinioti

14 Acne and Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109Bodo C. Melnik

15 Acne and Androgens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131WenChieh Chen and Christos C. Zouboulis

16 Acne and Infl ammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135Christos C. Zouboulis and Clio Dessinioti

17 Acne and Neuropeptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143Ruta Ganceviciene

18 Acne and Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151Hirohiko Akamatsu, Setsuko Nishijima, and Yoshiki Miyachi

19 The Acne Biofi lm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155Kris Honraet, Bart Rossel, and Tom Coenye

20 The Evidence Supporting a Link Between Acne and Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161F. William Danby

21 Acne and Smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167Dimitrios Rigopoulos and Chrysovalantis Korfi tis

22 Antimicrobial Peptides in Acne . . . . . . . . . . . . . . . . . . . . . . . . . 171István Nagy and Lajos Kemény

23 Acne and Antimicrobial Lipids. . . . . . . . . . . . . . . . . . . . . . . . . . 179Christos C. Zouboulis

24 Natural and Artifi cial Suntanning . . . . . . . . . . . . . . . . . . . . . . . 185Anja Thielitz and Harald P.M. Gollnick

25 Acne and Environmental Pollution (Chloracne) . . . . . . . . . . . . 189Qiang Ju and Lonqing Xia

26 Myths and Beliefs of Acne Pathogenesis: Diet, Smoking, Hygiene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195Batya B. Davidovici and Ronni Wolf

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Part V Acne: Clinical Aspects

27 Understanding Acne as a Chronic Disease . . . . . . . . . . . . . . . . 209Christos C. Zouboulis and Harald P.M. Gollnick

28 Clinical Aspects of Acne Vulgaris. . . . . . . . . . . . . . . . . . . . . . . . 213Andreas D. Katsambas, William J. Cunliffe, and Christos C. Zouboulis

29 Clinical Aspects of Acne Fulminans . . . . . . . . . . . . . . . . . . . . . . 223Andreas D. Katsambas, Clio Dessinioti, and William J. Cunliffe

30 Childhood Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227Maria Isabel Herane

31 Congenital Adrenal Hyperplasia and Acne in the Male Patients . . . . . . . . . . . . . . . . . . . . . . . . . . 235Clio Dessinioti and Andreas D. Katsambas

32 Adult Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243Anne W. Lucky, Clio Dessinioti, and Andreas D. Katsambas

33 Drug-Induced Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251Jana Stojanova Kazandjieva and Nikolai Konstantinov Tsankov

34 Body-Builder Acne. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259Christiane Bayerl

35 Acne Cosmetica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265Zoe Diana Draelos

36 Acne in Persons with Dark Skin . . . . . . . . . . . . . . . . . . . . . . . . . 271Shyam Verma

Part VI Prognostic Factors of Acne

37 Acne and Heredity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279Brigitte Dréno

38 Acne Neonatorum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283Andreas D. Katsambas and Clio Dessinioti

39 Serum Androgens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291WenChieh Chen and Christos C. Zouboulis

40 Body Mass Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295Clio Dessinioti and Christos C. Zouboulis

41 Sebum Secretion, Skin Type, and pH. . . . . . . . . . . . . . . . . . . . . 299Sang-Woong Youn

42 Lipids in Serum and Sebum . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305Emanuela Camera and Mauro Picardo

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Part VII Clinical Evaluation of Acne

43 The Leeds Acne Grading Technique . . . . . . . . . . . . . . . . . . . . . 317Alison M. Layton

44 Evaluation of Clinical Severity by Acne Grading and Lesion Counting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325Jerry K. Tan

45 Modern Technology for Imaging and Evaluation of Acne Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331Georgios N. Stamatas and Nikiforos Kollias

Part VIII Hormones and Acne

46 Acne and Congenital Adrenal Hyperplasia . . . . . . . . . . . . . . . . 343Catherine Dacou-Voutetakis

47 The Acne Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349Wen Chieh Chen, Chao-Chun Yang, and Christos C. Zouboulis

48 Vitamins and the Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355Apostolos Pappas, Clio Dessinioti, and Aikaterini I. Liakou

49 Urinary Hormone Analysis in Acne . . . . . . . . . . . . . . . . . . . . . . 363Markus G. Mohaupt and Bernhard Dick

50 Laboratory Evaluations in Acne. . . . . . . . . . . . . . . . . . . . . . . . . 369Clio Dessinioti and Christos C. Zouboulis

Part IX Treatment of Acne

51 Evidenced-Based Treatment of Acne . . . . . . . . . . . . . . . . . . . . . 379Christos C. Zouboulis and Aikaterini I. Liakou

52 The Diffi cult Acne Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383Andreas D. Katsambas and Clio Dessinioti

53 Improving Compliance with Acne Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389Andreas D. Katsambas

54 Keratolytic Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397Ali Alikhan and Howard I. Maibach

55 Topical Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415Brigitte Dréno

56 Benzoyl Peroxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419Joachim W. Fluhr

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57 Topical Retinoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425Anja Thielitz and Harald P.M. Gollnick

58 Azelaic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435Mauro Picardo and Monica Ottaviani

59 Emerging Acne Treatments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441Anthony V. Rawlings

60 Oral Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449Falk R. Ochsendorf

61 The Antibiotic Resistance in Acne . . . . . . . . . . . . . . . . . . . . . . . 459Cristina Oprica

62 Prescribing Oral Isotretinoin: The European Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465Alison M. Layton

63 Oral Isotretinoin: The US Approach . . . . . . . . . . . . . . . . . . . . . 471Jonathan Wilkin

64 Hormonal Therapy for Acne. . . . . . . . . . . . . . . . . . . . . . . . . . . . 477Clio Dessinioti and Christos C. Zouboulis

65 Less Common Treatments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483Ana Kaminsky

66 Risk Factors of Acne Relapse . . . . . . . . . . . . . . . . . . . . . . . . . . . 491Brigitte Dréno

67 Acne Maintenance Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497Lee T. Zane

68 Cosmetics and Cleansers in Acne . . . . . . . . . . . . . . . . . . . . . . . . 503Zoe Diana Draelos

69 Chemical Peeling in Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511Yoshiki Miyachi, Clio Dessinioti, and Andreas D. Katsambas

70 Lasers and Phototherapy in Acne . . . . . . . . . . . . . . . . . . . . . . . 519Leihong Flora Xiang and Harald P.M. Gollnick

71 Treatment of Acne Scarring . . . . . . . . . . . . . . . . . . . . . . . . . . . . 527Greg J. Goodman

72 Concepts of Future Acne Treatment . . . . . . . . . . . . . . . . . . . . . 537Clio Dessinioti and Christos C. Zouboulis

Part X Impact of Acne on Quality of Life

73 Acne and Quality of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545Uwe Gieler, Volker Niemeier, and Jörg Kupfer

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74 Instruments of Measurement of Quality of Life in Acne . . . . . 551Mohammad Khurshid Azam Basra and Andrew Y. Finlay

Part XI Acne in Systemic Disease

75 The SAHA Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563Christos C. Zouboulis and Clio Dessinioti

76 The Polycystic Ovary Syndrome and Acne . . . . . . . . . . . . . . . . 569Joseph L. Pace

77 The SAPHO Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 579Ignazio Olivieri, Vincenzo Giasi, Salvatore D′ Angelo, Carlo Palazzi, and Angela Padula

78 The PAPA Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 585Mosaad Megahed, Melanie Wosnitza, and Claudia N. Renn

79 Acne in Transplantation Patients . . . . . . . . . . . . . . . . . . . . . . . . 591Emmanuel Mahé

Part XII Pathogenesis of Rosacea

80 Rosacea: The State of the Art . . . . . . . . . . . . . . . . . . . . . . . . . . . 605Albert M. Kligman and Christos C. Zouboulis

81 The Vascular Concept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611Sabine Fimmel, Heinz Kutzner, and Christos C. Zouboulis

82 Rosacea and Neuropeptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . 621Maeve A. McAleer and Frank C. Powell

83 Rosacea and Demodex folliculorum . . . . . . . . . . . . . . . . . . . . . . 627Noreen Lacey and Frank C. Powell

84 The Role of Adenosine Triphosphate in the Pathogenesis of Rosacea: An Explanation for the Mode of Action of Tetracyclines for the Treatment of Rosacea . . . . . . . . . . . . . . . . . . . . . . . . . . . 641Albert M. Kligman

Part XIII Classifi cation and Clinical Types of Rosacea and Differential Diagnoses

85 Standard Grading System for Rosacea . . . . . . . . . . . . . . . . . . . 647Gregor B.E. Jemec

86 Classical Clinical Presentations of Rosacea. . . . . . . . . . . . . . . . 653Uwe Wollina

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87 Rhinophyma: A Variation of Rosacea? . . . . . . . . . . . . . . . . . . . 661Uwe Wollina and Shyam B. Verma

88 Ocular Rosacea. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665Dietrich Trebing

89 Childhood Rosacea. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669Clio Dessinioti

90 Differential Diagnosis of Rosacea . . . . . . . . . . . . . . . . . . . . . . . . 673M. Badawy Abdel-Naser

Part XIV Management of Rosacea

91 A Treatment Strategy for Rosacea . . . . . . . . . . . . . . . . . . . . . . . 683Mark V. Dahl

92 Topical Treatment of Rosacea. . . . . . . . . . . . . . . . . . . . . . . . . . . 693Uwe Wollina

93 Systemic Treatment of Rosacea . . . . . . . . . . . . . . . . . . . . . . . . . 699Clio Dessinioti and Christina Antoniou

94 Laser and Light Therapy of Rosacea . . . . . . . . . . . . . . . . . . . . . 707Dae Hun Suh

95 Nonclassical Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 713Uwe Wollina

96 Cosmetics in Rosacea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 719Zoe Diana Draelos

97 Treatment of Rhinophyma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 729Uwe Wollina and Shyam B. Verma

98 The Future of Rosacea Treatment . . . . . . . . . . . . . . . . . . . . . . . 733Frank C. Powell and Maeve A. McAleer

Part XV Rosacea and Quality of Life

99 Impact of Rosacea on Quality of Life. . . . . . . . . . . . . . . . . . . . . 743Mohammad Khurshid Azam Basra and Andrew Y. Finlay

Erratum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E1

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 749

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Contributors

M. Badawy Abdel-Naser Departments of Dermatology and Venereology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Hirohiko Akamatsu Department of Applied Cell and Regenerative Medicine , Fujita Health University School of Medicine , Toyoake , Aichi , Japan

Ali Alikhan Department of Dermatology , University of California, San Francisco , San Francisco , CA , USA

Christina Antoniou Department of Dermatology , Andreas Syngros Hospital, National and Capodistrian University of Athens , Athens , Greece

Mohammad Khurshid Azam Basra Department of Dermatology and Wound Healing , Cardiff University School of Medicine , Heath Park , Cardiff , UK

Christiane Bayerl Department of Dermatology and Allergology Wiesbaden , HSK, Wilhelm Freseniusklinik , Wiesbaden , Germany

Richard A. Bojar Leeds Skin Centre for Applied Research Ltd. , Wetherby , UK

Vladimir A. Botchkarev Centre for Skin Sciences , School of Life Sciences, University of Bradford , Bradford , UK

Emanuela Camera Laboratory of Cutaneous Physiopathology , San Gallicano Dermatological Institute (IRCCS) , Rome , Italy

WenChieh Chen Department of Dermatology and Allergy , Technische Universitaet Muenchen , Munich , Germany

Tom Coenye Laboratory for Pharmaceutical Microbiology , Ghent University , Ghent , Belgium

William J. Cunliffe Department of Dermatology , Skin Research Centre, University of Leeds , Leeds , UK

Salvatore D’Angelo Rheumatology Department of Lucania , San Carlo Hospital of Potenza , Potenza , Italy

Madonna delle Grazie Hospital of Matera , Matera , Italy

xx

Catherine Dacou-Voutetakis Pediatric Endocrinology, First Department of Pediatrics , “Aghia Sophia” Children’s Hospital, Athens University, Medical School , Athens , Greece

Mark V. Dahl Department of Dermatology , Mayo Clinic, College of Medicine , Scottsdale , AZ , USA

F. William Danby Department of Dermatology , Dartmouth Medical School , Hanover , NH , USA

Batya B. Davidovici Dermatology Unit , Kaplan Medical Center , Rechovot , Israel

Clio Dessinioti Department of Dermatology , Andreas Syngros Hospital, National and Capodistrian University of Athens , Athens , Greece

Bernhard Dick Department of Nephrology and Hypertension , University of Bern , Berne , Switzerland

Brigitte Dréno Department of Dermatology , Hotel Dieu Hospital University , Nantes , France

Zoe Diana Draelos Dermatology Consulting Services , High Point , NC , USA

Emmanuel Mahé Dermatology Department , Victor Dupouy Hospital , Argenteuil , France

Mark D. Farrar Epithelial Sciences, School of Translational Medicine, Salford Royal NHS Foundation Trust , University of Manchester , Manchester , UK

Michael Y. Fessing Centre for Skin Sciences , School of Life Sciences, University of Bradford , Bradford , UK

Sabine Fimmel Departments of Dermatology, Venereology, Allergology and Immunology , Dessau Medical Center , Dessau , Germany

Andrew Y. Finlay Department of Dermatology and Wound Healing , Cardiff University School of Medicine , Heath Park , Cardiff , UK

Joachim W. Fluhr Department of Dermatology and Allergology , Charité Universitätsmedizin , Berlin , Germany

Ruta Ganceviciene Centre of Dermatovenereology, Vilnius University Hospital, Santariskiu Klinikos , Vilnius , Lithuania

Carlo Gelmetti Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche , Università degli Studi di Milano and Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico , Milan , Italy

Vincenzo Giasi Rheumatology Department of Lucania , San Carlo Hospital of Potenza , Potenza , Italy

Madonna delle Grazie Hospital of Matera , Matera , Italy

Uwe Gieler Psychodermatology, Clinic for Psychosomatic Medicine and Psychotherapy , Justus Liebig University of Giessen , Giessen , Germany

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Harald P. M. Gollnick Department of Dermatology and Venereology , Otto von Guericke University , Magdeburg , Germany

Greg J. Goodman Department of Community Medicine , Skin and Cancer Foundation of Victoria and Monash University , Toorak , VIC , Australia

Maria Isabel Herane Department of Dermatology , University of Santiago der Chile , Santiago , Chile

Kris Honraet Oystershell NV , Drongen , Belgium

Gregor B. E. Jemec Department of Dermatology, Health Sciences Faculty , University of Copenhagen, Roskilde Hospital , Roskilde , Denmark

Qiang Ju Department of Dermatology , Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China

Ana Kaminsky Catedra de Dermatologia, Facultad de Medicina , Universidad de Buenos Aires , Buenos Aires , Argentina

Andreas D. Katsambas Department of Dermatology , National and Capodistrian University of Athens, Andreas Syngros Hospital , Athens , Greece

Jana Stojanova Kazandjieva Department of Dermatology , Medical University , Sofi a , Bulgaria

Lajos Kemény Department of Dermatology and Allergology , University of Szeged , Szeged , Hungary

Dermatological Research Group of the Hungarian Academy of Sciences , University of Szeged , Szeged , Hungary

Albert M. Kligman†

Nikiforos Kollias Johnson and Johnson Consumer Companies Inc. , Skillman , NJ , USA

Chrysovalantis Korfi tis Department of Dermatology , Veterans Administration Hospital , Athens , Greece

Jörg Kupfer Institute of Medical Psychology, University of Giessen , Giessen , Germany

Ichiro Kurokawa Department of Dermatology , Meiwa Hospital , Nishinomiya , Hyogo , Japan

Heinz Kutzner Dermatopathology Practice , Friedrichshafen, Germany

Noreen Lacey Clinical Research Centre, Catherine McAuley Centre, University College Dublin , Dublin , Ireland

Alison M. Layton Department of Dermatology , Harrogate and District Foundation Trust , Harrogate , UK

Aikaterini I. Liakou Departments of Dermatology, Venereology, Allergology and Immunology , Dessau Medical Center , Dessau , Germany

Contributors

xxii

Anne W. Lucky Division of Pediatric Dermatology , Cincinnati Children’s Hospital , Cincinnati, OH , USA

Emmanuel Mahé Dermatology Department , Victor Dupouy Hospital , Argenteuil , France

Howard I. Maibach Department of Dermatology , University of California, San Francisco , San Francisco , CA , USA

Evgenia Makrantonaki Departments of Dermatology, Venereology, Allergology and Immunology , Dessau Medical Center , Dessau , Germany

Maeve A. McAleer The Charles Center for Dermatology , St. Vincent’s University Hospital, University of Dublin, Dublin , Ireland

Mosaad Megahed Faculty of Medicine, Department of Dermatology and Allergy , University Hospital of the RWTH Aachen , Aachen, Germany

Bodo C. Melnik Department of Dermatology, Environmental Medicine and Health Theory , University of Osnabrück , Osnabrück , Germany

Yoshiki Miyachi Department of Dermatology , Graduate School of Medicine, Kyoto University , Sakyo-ku , Kyoto , Japan

Markus G. Mohaupt Division of Hypertension, Department of Nephrology and Hypertension , University of Bern , Berne , Switzerland

István Nagy Institute for Plant Genomics, Human Biotechnology and Bioenergy, Bay Zoltán Foundation for Applied Research , Szeged , Hungary

Volker Niemeier Institute of Medical Psychology, University of Giessen , Giessen , Germany

Georgios Nikolakis Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center , Dessau , Germany

Setsuko Nishijima Nishijima Skin Clinic , Neyagawa , Osaka , Japan

Falk R. Ochsendorf Department of Dermatology and Venereology , J.W. Goethe University , Frankfurt , Germany

Ignazio Olivieri Rheumatology Department of Lucania , San Carlo Hospital of Potenza , Potenza , Italy

Madonna delle Grazie Hospital of Matera , Matera , Italy

Cristina Oprica Division of Dermatology and Venereology, Department of Medicine , Karolinska Institutet, Karolinska University Hospital – Huddinge , Stockholm , Sweden

Monica Ottaviani Laboratory of Cutaneous Physiopathology , San Gallicano Dermatological Institute , Rome , Italy

Joseph L. Pace Dermatology Practice , Valetta , Malta

Contributors

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Angela Padula Rheumatology Department of Lucania , San Carlo Hospital of Potenza , Potenza , Italy

Madonna delle Grazie Hospital of Matera , Matera , Italy

Carlo Palazzi Rheumatology Division of “Villa Pini” Clinic , Chieti , Italy

Apostolos Pappas Skin Biology TRC , Johnson and Johnson Consumer Companies Worldwide , Skillman , NJ , USA

Mauro Picardo Laboratory of Cutaneous Physiopathology , San Gallicano Dermatological Institute (IRCCS) , Rome , Italy

Frank C. Powell The Charles Center for Dermatology, St. Vincent’s University Hospital, University of Dublin , Dublin , Ireland

Anthony V. Rawlings AVR Consulting Ltd , Northwich , Cheshire , UK

Claudia N. Renn Faculty of Medicine, Department of Dermatology and Allergy , University Hospital of the RWTH Aachen University , Aachen , Germany

Dimitrios Rigopoulos Department of Dermatology , Attikon Hospital, National and Capodistrian University of Athens , Athens , Greece

Bart Rossel Oystershell NV , Drongen , Belgium

Georgios N. Stamatas Johnson and Johnson Consumer France SAS , Issy-les-Moulineaux , France

Dae Hun Suh Department of Dermatology , Seoul National University College of Medicine , Seoul , South Korea

Jerry K. Tan Windsor Clinical Research Inc. , Windsor , ON , Canada

Anja Thielitz Dermatologisches Zentrum/iDerm , Berufsgenossenschaftliches Unfallkrankenhaus Hamburg , Hamburg , Germany

Dietrich Trebing Departments of Dermatology, Venereology, Allergology and Immunology , Dessau Medical Center , Dessau , Germany

Nikolai Konstantinov Tsankov Department of Dermatology , Medical University , Sofi a , Bulgaria

Fragkiski Tsatsou Department of Dermatology, Venereology, Allergology and Immunology , Dessau Medical Center , Dessau , Germany

Shyam B. Verma Nirvana Skin Clinic , Vadodara , India

Guy F. Webster Department of Dermatology , Jefferson Medical College , Philadelphia , PA , USA

Jonathan Wilkin Columbus , OH , USA

Ronni Wolf Dermatology Unit , Kaplan Medical Center , Rechovot , Israel

Contributors

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Uwe Wollina Department of Dermatology and Allergology , Hospital Dresden-Friedrichstadt , Dresden , Germany

Melanie Wosnitza Faculty of Medicine, Department of Dermatology and Allergy , University Hospital of the RWTH Aachen , Aachen , Germany

Lonqing Xia Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College , Nanjing , China

Leihong Flora Xiang Department of Dermatology , Huashan Hospital, Fudan University , Shanghai , China

Chao-Chun Yang Department of Dermatology , National Cheng Kung University College of Medicine and Hospital , Tainan , Taiwan

Sang-Woong Youn Department of Dermatology , Bundang Hospital, Seoul National University College of Medicine , Seongnam , South Korea

Lee T. Zane Anacor Pharmaceuticals, Inc., Palo Alto , CA , USA

Christos C. Zouboulis Departments of Dermatology, Venereology, Allergology and Immunology , Dessau Medical Center , Dessau , Germany

Contributors

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Introduction

Diseases of facial skin have been mentioned repeatedly in medical history, starting with Greek physicians in antiquity. Hippocrates of Kos and Aristotle in Athens used the term “ίονθοι” (ionthoi, pl.) to describe lesions located on the face as a well-recognised disease appearing during the time when “the fi rst beard grows”, most likely corresponding to what we call acne today. Roman physicians and/or scholars such as Plinius used the term “vari” or “vari seu ionthi” referring to similar skin lesions located in the face, with peaks of oozing and pain. For management honey, soaps, mineral waters and baths, often containing sulphur, were applied in the ancient Roman Empire for cleaning and drying out the skin, as mentioned by Celsus (fi rst century ad ) in his “De Medicina”, a major source of Greco-Roman medicine. Sulphur-containing ointments were still used for the same purpose in Europe during the last centuries, together with laxatives and various diets.

The word “Acne” is obviously derived from the Greek “Ακμή” (acme) and entered the medical literature to indicate a high point, the peak of develop-ment or maturation (of a general condition or disease), as has been used by Galenos from Pergamon (129–201 ad ), though unrelated to skin. During the following centuries, however, this expression came into use also to express the same for an individual, i.e. the fl ourishing period of puberty. It seems that the term took its present signifi cance after having been misspelled in “Ακνή” by the Byzantine physician and medical scholar Aetius Amidanus (502–575 ad ) in writing one of his numerous books (Polybiblia) transferring and com-menting the wisdom of Hippocrates and Galenos . Interestingly, acne is still called “acme” in contemporary Greek medical nomenclature, while the term maintains its original meaning in spoken Greek.

The history of rosacea is less known, although the condition may have been early mentioned by Theocritos in the third century bc , and the fl ushing condition of the face (nose) was later brought in relation to lying and shame. As a medical term “gutta rosacea” was documented by J. Plenck (1735–1807), who separated this entity from “vari” or “ionthi” in classifying cutane-ous diseases, whereas R. Willan (1757–1812) with Th. Bateman (1778–1821) linked rosacea to acne; they listed “acne rosacea” in their nomenclature sys-tem based on clinical morphology, although they recognised the differences.

It seems that C.H. Fuchs , in expressing his disagreement, coined the term “acne vulgaris” (“Die Krankhaften Veränderungen der Haut”, Göttingen, 1840), indicating a disease of facial skin affecting young individuals and

xxvi

leaving pitted scars, aiming to clearly separate the condition from “acne rosacea”. The specifi c denominations of distinctive clinical phenotypes and variants of acne commonly used today, such as comedonic/papulopustular, conglobate, nodulocystic, acne tarda, androgenica, venenata, etc., were compiled by various authors over the last century.

Why such a comprehensive book on acne and rosacea? In our modern societies skin diseases are most common and due to their

visibility and identifi cation with the suffering individual have reached great attention by the medical community and the public. Acne in particular, with all its variants, is a leading diagnosis in the dermatologist’s offi ce and has become a hot issue in recent years. In European populations over 70–80 % of all males will experience acne in some point of their lifetime. In the USA acne has been reported to affect an estimated number of over 25 (17–45) mil-lion Americans, while spending on topical anti-acne preparations and oral anti acne drugs amounted billions of dollars in recent years.

The presence of acne on the face is visible to all while appearing in early life during a critical phase of individual self-recognition. In addition, some mystery of acne derives from its unclear aetiopathology and its incidence in young boys and girls, obviously in relation with the synthesis of hormones and their precursors in menarche and adrenarche, an imagined relation to sexual activities, and its interaction with the psychological status of the patient during adolescence. Needless to say, there are a series of misconcep-tions referring to the signifi cance of the disease for life quality, but indisput-ably, most of the young patients with acne clearly suffer, some of them having the feeling of being inferior and stigmatised. They all look for understanding and treatment.

Over the past decades thorough laboratory investigations on the piloseba-ceous unit have been performed and a series of possible acnegenic mecha-nisms were elucidated in experimental and clinical models. As a result, both the causes and pathogenesis of acne have become increasingly expanding, complicated issues in part, and diffi cult to overlook. The numerous reasons for developing acne may overlap or even clearly differ from one individual to another. Especially the mechanisms of persisting comedogenesis, the genera-tion of pro- and anti-infl ammatory lipids, the consecutive receptor processing and the intriguing pathways leading to transformation of comedonal, non- infl ammatory, into infl ammatory skin lesions, including the governance of their particular clinical morphology and course, are not fully clarifi ed, being still under ongoing investigation.

The major tissue component involved in the pathogenesis of acne is the sebaceous gland as a mastermind of hormone metabolism and, possibly, hormone synthesis in skin. Hyperseborrhea, hyperkeratinisation of the duct lumina with appearance of microcomedos and insuffi cient comedolysis, bacterial colonisation and infl ammatory tissue response leading to papules, pustules, nodules and cysts are major causes for generating the disease; however, a series of side pathways and the sequence of events involved remain to be elucidated. Hormonal disorders (systemic and/or peripheral hyperandrogenism), inappropriate skin care and hygienic conditions (oily bases and other acnegenic cosmetics), bacteria ( P. acnes, etc.), various

Introduction

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drugs (anticonvulsants, lithium, androgens, anabolic steroids with resting androgenic properties, corticosteroids), toxic agents (chlorinated polyphe-nols), halogens (iodine, chlorine, bromides, etc.), nutrition (fats, seafood, chocolate, nuts, milk products, westernised food with high carbohydrates and diverse relation of ω-unsaturated lipids) and stress (neuropeptides) may all have an infl uence in generating acne lesions, based on genetic predisposition that controls the frequency of infl ammatory lesions, and, possibly, their severity. The question arises as far as genuine infl ammatory mechanisms are contributory factors in acne, with PPAR and stimulated toll-like receptors being primarily involved in its pathogenesis.

Overall, acne may be regarded as a model of a complex cascade of events, controlled by hormones, leading to infl ammation.

Therapy of acne is a challenge in a considerable number of cases, also because disfi guring scars may result and become permanent, if the disease progresses. Individualised treatment is recommended. Therefore, a wide range of anti-acne preparations are of growing signifi cance for the prescrip-tion market, both topical remedies and systemic drugs including antikeratinising and antiseborrhoeic agents, antibacterials, antibiotics, reti-noids, hormones and hormone-like products and various others. Retinoids in particular have revolutionised the treatment of acne, and after its fi rst intro-duction into the market in 1982 isotretinoin has been a global frontrunner. It is still today the most successful drug in the treatment of severe acne, and its worldwide sales were a few years ago at the level of one billion dollars, growing by 5–10 % per year. However, although the anti-acne potency of isotretinoin is unsurpassed, its teratogenicity, among other side effects, is a serious risk that limits its oral use requiring continuing contraception. Recently, an assumed relation of isotretinoin to 5-serotonin metabolism sus-pected to cause depression and suicidal ideation is of additional concern.

Thus, the evolution of acne therapy is still ongoing, and, in addition to further improvement of conventional modalities, new potent anti-acne agents surface, also based on the concept that acne, may represent a genuine infl am-matory disorder per se . Together with new antibiotics and conventional reti-noids, rexinoids, 5α-reductase inhibitors, leukotriene antagonists and 5-lipoxygenase inhibitors are under current investigation. In addition, new therapeutic and managing options are being reported for the practicing der-matologist by using modern technical devices, such as light and UV thera-pies, photodynamic agents, various types of lasers, etc.

The three editors of this comprehensive book represent three generations of prominent dermatologists with profound and long-lasting experiences on acne and rosacea, covering all related clinical and investigational issues. They faced together the challenge to approach and cover the multifactorial issues in several small and specifi c chapters written by an international community of colleagues, all experts in their fi elds. Thus, different aspects and emerging views are presented in this book, summarising our accumulating knowledge. The editorship maintains a red line by having clustered and reviewed the manuscripts. This book has been designed as an indispensable work of refer-ence for all physicians dealing with acne or rosacea and for scientists having specifi c questions on any relevant issue, including the established theories on

Introduction

xxviii

the clinical entities covered, their treatment and pathogenesis, while also referring to new concepts and alternative views.

Acne and rosacea is a most interesting fi eld of expanding dermatological research on a series of intriguing scientifi c and clinical mechanisms leading to disfi guring skin lesions. Such a comprehensive textbook epitomises our updated knowledge and current understanding on acne and rosacea.

I sincerely hope that it will also stimulate the fantasy and catalyse the vigour of young dermatologists and researchers, in their attempt to present new evidence on this important section of dermatology, following their own visions.

At the end, the patients who suffer will harvest the real benefi t.

Introduction

PrefaceThe History of this Book

ContentsContributorsIntroduction