Plewig and Kligman’s Acne and Rosacea Gerd Plewig • Bodo Melnik • WenChieh Chen Plewig and Kligman’s Acne and Rosacea Fourth Edition Gerd Plewig Bodo Melnik Department of Dermatology and Allergy Department of Dermatology Ludwig-Maximilian-University Munich Environmental Medicine and Health Theory Munich University of Osnabrück Germany Osnabrück Germany WenChieh Chen Department of Dermatology and Allergy Technical University of Munich Munich Germany ISBN 978-3-319-49273-5 ISBN 978-3-319-49274-2 (eBook) https://doi.org/10.1007/978-3-319-49274-2 © Springer Nature Switzerland AG 1975, 1993, 2000, 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms 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. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from 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 this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland In Memory of Albert Montgomery Kligman, M.D., Ph.D., Dr. hc. mult. Philadelphia 17 March 1916–Philadelphia 9 February 2010 Mentor—Teacher—Scientist—Physician—Friend (Portrait. Oil on canvas, painted in 1995 by John Boyd Martin, who is born in 1936 Located outside the laboratory named for Albert M. Kligman, Biochemical Research Building, Department of Dermatology, University of Pennsylvania, Philadelphia With kind permission, George Cotsarelis, M.D., Ph.D., Professor and Chairman) To our wives, Helga, Susanne, and Pei-Hsiu Preface to the Fourth Edition More than 50 years have elapsed since the first publication of this book, compiled and written with the brilliant ideas and energy of Albert Montgomery Kligman (1916–2010) from Philadelphia, one of the greatest experimental and clinical dermatologists of his time. Sadly enough, we miss him as an author of this new work but express our deepest gratitude to a life- long teacher, mentor, and friend. After the English editions (1975, 1993, 2000) and German editions (1978, 1994), time was ready for a new team of authors to continue this monograph. Colleagues the world over encour- aged us to bring the vast new information on these common diseases, acne and rosacea, and also demodicosis and acne-associated autoinflammatory diseases into a new volume of text and atlas. The growth of basic knowledge coupled with clinical experience since has been enormous. This has been a joyous enterprise for us. The ability to treat acne and rosacea effectively was accompanied by the vastly expanded understanding of their etiologies and pathogenesis, thanks to the remarkable input of eminent researchers and clinicians worldwide. Acne is not only an eminently treatable disease; even worst cases, for example, acne con- globata and acne fulminans, are actually curable. No case is so severe as to be beyond help with the array of diverse drugs now available. Treatment failure is mostly physician failure. Prevention of acne in highly susceptible children is well possible with topical agents pre- scribed at the incipient stage, thus preventing the dreaded sequel of scarring. We continue in the beliefs expressed in 1975 regarding our mission. This text and atlas is dedicated to dermatologists and other colleagues who must diagnose and treat these disfigur- ing, remarkably protean, common diseases. This is a reference work for investigators, including a selective review of the literature. The references we cite have been selected for their relevance to daily practice, for their educational worth, and for their readability and historical impact. This meant for a massive culling of thou- sands of articles piled up in past decades. We apologize to those authors whose contributions are not listed here. A quote from the first edition epitomizes our current attitude: “We have sought to create a portfolio of still-life pictures of gross and microscopic anatomy of acne and rosacea. This will be a photographic record of what these maladies look like, their usual and unusual features…” The views we present in respect to pathogenesis and treatment are in the first place our own and much less constructed from recommendations of other authorities. Thus, some of our pro- posals may not meet the stringent requirements of evidence-based medicine. Since this is a practice-orientated text, we have taken on the hazardous responsibility of expressing our per- sonal options and not the many alternatives which can be found in the literature. Consensus conferences and guidelines, based on national or international participation, are helpful but may not be applicable to regional or in loco demands. We do not wish to pretend that no quan- daries remain or that everything is simple and straightforward as our style might suggest. Over the past years, new concepts of pathogenesis, new variants, new syndromes of acne, and new therapies have emerged. To name but a few, these include autoinflammatory syn- dromes of acne associated with arthritis and pyoderma gangrenosum, hidradenitis suppurativa/­ vii viii Preface to the Fourth Edition acne inversa now redefined as dissecting terminal hair folliculitis, the role ofDemodex follicu- lorum mites in healthy people and diseased state, and the role of microbiota and biofilm. There is evidence to support our hypotheses concerning signal transduction pathways such as the role of FoxO1 and mTORC1 in acne, endoplasmic reticulum stress responses in rosacea, and the T cells and Th17 cells in dissecting terminal hair folliculitis, the impact of hyperglycemic food and milk, and the p53-associated sebocyte apoptosis caused by isotretinoin. Newly introduced drugs and topical remedies were discussed. Many acne-mimicking diseases are commonplace but can be confusing. Acne, syndromic constellations of acne, and rosacea not infrequently coexist in overlap mixtures, which may be present at the same time, with one slowly disappear- ing and the other emerging. Physicians must keep abreast with this fascinating new wealth of science. Our patients expect that we physicians have enough time for them, listening is as important as looking. Even today, our well-educated patients and their custodians sometimes hold a bag full of irrational folkloristic beliefs and myths, which need to be dispelled. It is well accepted that placebo effects are prominent in medicine and, of course, in acne and rosacea alike. This explains why some popular, unproven remedies seem to work. Even in properly controlled studies, it is astonishing how often the efficacy of the vehicle approaches that of the active drug. Important regular changes took place in the last decades. Acne conglobata and severe inflammatory acne seem to be on the wane, possibly as the result of so effective treatments such as isotretinoin, oral antibiotics, and new topical formulations. Rosacea seems to steadily increase. We speculate that also epidemiological changes reflect the environmental exposure and nutrition. Furthermore, migration across continents and countries with new in loco cir- cumstances of health care and living standards may have their impact on expression of these dermatoses. Fascinating are the enormous steps forward of surgical interventions with lasers, fillers, and peels, as they all revolutionized our treatment possibilities. Highly specialized colleagues have become masters in this field. The reader is referred to the most experienced authorities in this rapidly moving field. Munich, Germany Gerd Plewig Osnabrück, Germany Bodo Melnik Munich, Germany WenChieh Chen Acknowledgments It is with joy that we thank so many highly skilled professionals who generously helped to recreate this book. Our gratitude for their superb collaboration is acknowledged herewith. Our thanks are but a small recompense for their contributions. Mr. Peter Bilek (1936–2009), master of photography, Department of Dermatology, Ludwig-­ Maximilian-­University Munich. Mr. Winfried Neuse, retired photographer, photo designer, and enthusiastic artist with the camera, Department of Dermatology, Heinrich-Heine-University Düsseldorf. Privatdozent Dr. Thomas Jansen, Duesseldorf, contributed faithfully to the 1994 and 2000 editions. Professor Dr. Helmut H. Wolff and Mrs. Elfriede Januschke, medical technician, formerly in the Department of Dermatology, Ludwig-Maximilian-University Munich, contributed to the exquisite transmission electron microscopies. Professor Dr. med., Dr. h.c. mult. Thomas Ruzicka, former chairman of the Munich Department, generously provided unrestricted access to essential sections of the clinic