Pathogenesis and Management of Atopic Dermatitis

Pathogenesis and Management of Atopic Dermatitis

Current Problems in Dermatology Vol. 41 Series Editors Peter Itin Basel Gregor Jemec Roskilde

Pathogenesis and Management of Atopic Dermatitis Volume Editor Tetsuo Shiohara Tokyo 26 figures, 20 in color, and 9 tables, 2011 Basel Freiburg Paris London New York New Delhi Bangkok Beijing Tokyo Kuala Lumpur Singapore Sydney

Current Problems in Dermatology Tetsuo Shiohara Department of Dermatology Kyorin University School of Medicine 6-20-2 Shinkawa, Mitaka Tokyo 181-8611 Japan Library of Congress Cataloging-in-Publication Data Pathogenesis and management of atopic dermatitis / volume editor, Tetsuo Shiohara. p. ; cm. -- (Current problems in dermatology, ISSN 1421-5721; vol. 41) Includes bibliographical references and indexes. ISBN 978-3-8055-9686-2 (hard cover : alk. paper) -- ISBN 978-3-8055-9687-9 (electronic) 1. Atopic dermatitis. I. Shiohara, Tetsuo. II. Series: Current problems in dermatology ; v. 41. [DNLM: 1. Dermatitis, Atopic. W1 CU804L v.41 2011 / WR 160] RL243.P38 2011 616.5'1--dc22 2011003457 Bibliographic Indices. This publication is listed in bibliographic services, including MEDLINE/Pubmed. Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 2011 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) www.karger.com Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel ISSN 1421 5721 ISBN 978 3 8055 9686 2 e ISBN 978 3 8055 9687 9

Section Title Contents VII Preface Shiohara, T. (Tokyo) 1 Atopic Dermatitis and the Hygiene Hypothesis Revisited Flohr, C.; Yeo, L. (London) 35 Loss-of-Function Mutations within the Filaggrin Gene and Atopic Dermatitis Kawasaki, H.; Kubo, A.; Sasaki, T.; Amagai, M. (Tokyo) 47 FcεRI-Toll-Like Receptor Interaction in Atopic Dermatitis Novak, N.; Bieber, T. (Bonn) 54 The Antimicrobial Skin Barrier in Patients with Atopic Dermatitis Schittek, B. (Tübingen) 68 Defective Sweating Responses in Atopic Dermatitis Shiohara, T.; Doi, T.; Hayakawa, J. (Tokyo) 80 The Role of Cytokines/Chemokines in the Pathogenesis of Atopic Dermatitis Yamanaka, K.; Mizutani, H. (Tsu) 93 Contribution of Interleukin 18 to the Development of Infection-Associated Atopic Dermatitis Tsutsui, H. (Nishinomiya); Mizutani, H. (Tsu); Nakanishi, K. (Nishinomiya/Tokyo) 104 Innate Immunity in Atopic Dermatitis Mrabet-Dahbi, S.; Maurer, M. (Berlin) 112 The Role of Regulatory T Cells in Atopic Dermatitis Agrawal, R.; Wisniewski, J.A.; Woodfolk, J.A. (Charlottesville, Va.) 125 Increased Susceptibility to Cutaneous Viral Infections in Atopic Dermatitis: The Roles of Regulatory T Cells and Innate Immune Defects Shiohara, T.; Sato, Y.; Takahashi, R.; Kurata, M.; Mizukawa, Y. (Tokyo) 136 Biomarkers for Itch and Disease Severity in Atopic Dermatitis Lee, C.-H.; Yu, H.-S. (Kaohsiung) V

149 Practical Issues on Interpretation of Scoring Atopic Dermatitis: SCORAD Index, Objective SCORAD, Patient-Oriented SCORAD and Three-Item Severity Score Oranje, A.P. (Rotterdam) 156 Systemic Therapy of Atopic Dermatitis in Children and Adults Simon, D. (Bern) 165 Author Index 166 Subject Index VI Contents

Section Title Preface Atopic dermatitis (AD) is indeed a multifactorial genetic disease arising as a result of the complicated interaction of many genes with environmental factors. It has long been thought that a genetic predisposition to a defective skin barrier represents a primary event that can favor the increased penetration of allergens, thereby facilitating the occurrence of allergic inflammatory responses. A recent breakthrough in the understanding of AD pathogenesis has been made with the studies successfully linking loss-of-function mutations in the genes encoding the epidermal structure protein filaggrin with the subsequent risk of developing AD. Another area of AD research apparently points us to the importance of the increase in exposure to various environmental agents, particularly deprived of microbial stimuli, which is known as the hygiene hypothesis. Recent studies also suggest specific mechanisms whereby innate immune responses are functionally defective in AD. After a long period of neglect, sweating disturbance in AD has recently received increasing attention, because sweat is now recognized as the first element of the innate immune system. Nevertheless, the most common emergent theme has been the role of adaptive immunity in providing cytokines and chemokines that sustain the recruitment, retention and activation of allergen-specific T cells, dendritic cells, eosinophils, basophils and mast cells in the involved tissues. However, no single text concerning the entire spectrum has been available. The key message of this book is to address the questions raised by dermatologists, pediatricians, practicing physicians, basic immunologists, biologists, pharmacologists and students studying medicine on the pathogenesis, management and therapies of AD. To this end, virtually all chapters have been authored by original investigators who have contributed significantly to the establishment of current concepts. I would like to thank the distinguished authors who made tremendous efforts to make this book very useful, and I am also very thankful to the staff of Karger AG, in particular Ms. Tanja Sebuk. Tetsuo Shiohara, Tokyo VII