Skin Barrier Function

Skin Barrier Function

Current Problems in Dermatology Vol. 49 Series Editors Peter Itin Basel Gregor B.E. Jemec Roskilde

Skin Barrier Function Volume Editor Tove Agner Copenhagen 26 figures, 6 in color, and 14 tables, 2016 Basel Freiburg Paris London New York Chennai New Delhi Bangkok Beijing Shanghai Tokyo Kuala Lumpur Singapore Sydney

Current Problems in Dermatology Prof. Tove Agner Bispebjerg University Hospital Department of Dermatology Copenhagen (Denmark) Library of Congress Cataloging-in-Publication Data Names: Agner, Tove, editor. Title: Skin barrier function / volume editor, Tove Agner. Other titles: Current problems in dermatology ; v. 49. 1421-5721 Description: Basel ; New York : Karger, 2016. Series: Current problems in dermatology, ISSN 1421-5721 ; vol. 49 Includes bibliographical references and indexes. Identifiers: LCCN 2015047342 ISBN 9783318055856 (hard cover : alk. paper) ISBN 9783318055863 (electronic version) Subjects: MESH: Skin Physiological Phenomena Epidermis--physiology Classification: LCC QM481 NLM WR 102 DDC 612.7/9--dc23 LC record available at http://lccn.loc.gov/2015047342 Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents and Index Medicus. 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 2016 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) www.karger.com Printed in Germany on acid-free and non-aging paper (ISO 9706) by Kraft Druck, Ettlingen ISSN 1421 5721 e-issn 1662 2944 ISBN 978 3 318 05585 6 e-isbn 978 3 318 05586 3

Contents VII Preface Agner, T. (Copenhagen) Section I: Basic Parameters 1 Filaggrin and Skin Barrier Function Kezic, S. (Amsterdam); Jakasa, I. (Zagreb) 8 Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients van Smeden, J.; Bouwstra, J.A. (Leiden) 27 Importance of Tight Junctions in Relation to Skin Barrier Function Brandner, J.M. (Hamburg) 38 Antimicrobial Peptides, Infections and the Skin Barrier Clausen, M.-L.; Agner, T. (Copenhagen) 47 Biological Variation in Skin Barrier Function: From A (Atopic Dermatitis) to X (Xerosis) Danby, S.G. (Sheffield) Section II: External Factors Influencing Skin Barrier 61 Methods for the Assessment of Barrier Function Antonov, D.; Schliemann, S.; Elsner, P. (Jena) 71 In vivo Raman Confocal Spectroscopy in the Investigation of the Skin Barrier Darlenski, R. (Sofia); Fluhr, J.W. (Berlin) 80 Irritants and Skin Barrier Function Angelova-Fischer, I. (Lübeck) 90 Skin Barrier Function and Allergens Engebretsen, K.A.; Thyssen, J.P. (Hellerup) 103 Penetration through the Skin Barrier Nielsen, J.B. (Odense); Benfeldt, E. (Roskilde); Holmgaard, R. (Copenhagen) Section III: Optimizing Skin Barrier Function 112 Treatments Improving Skin Barrier Function Lodén, M. (Solna) V

Section IV: Clinical Aspects of Skin Barrier Function 123 Standards for the Protection of Skin Barrier Function Giménez-Arnau, A. (Barcelona) 135 The Role of the Skin Barrier in Occupational Skin Diseases Kasemsarn, P. (Carlton, Vic.; Bangkok); Bosco, J.; Nixon, R.L. (Carlton, Vic.) 144 Wet Work and Barrier Function Fartasch, M. (Bochum) 152 Saving the Barrier by Prevention Weisshaar, E. (Heidelberg) 159 Author Index 160 Subject Index VI Contents

Preface The skin barrier is important to human life. Physically, it protects us from external threats such as infectious agents, chemicals, systemic toxicity and allergens; internally, the skin helps to maintain homeostasis and to protect from enhanced loss of water from the body. Both of these are lifesaving qualities. Another aspect is the esthetic appearance of the skin, which should not be underestimated. Since ancient times, a well-hydrated skin texture has been treasured, with tradition featuring bathing in milk as the ultimate luxury to secure soft and moisturized skin. Since in the last decade filaggrin mutations were discovered as a major risk factor for atopic dermatitis, an inflammatory skin disease with a particularly impaired barrier function, research in skin barrier function has escalated. The skin barrier is located in the stratum corneum, made up of flattened, anucleated cells and a highly organized lipid matrix. The filaggrin protein helps to maintain an organized barrier, and loss-offunction mutations in the filaggrin gene are a major determinant of filaggrin expression in the skin. Natural moisturizing factor, an amorphous substance highly important for hydration of the stratum corneum, is a degradation product of filaggrin. An extremely interesting finding is the interplay between the immune system and barrier function; it has been documented that impaired barrier function leads to up-regulation of certain interleukins, which again influence the amount of natural moisturizing factor. Other very important players in the maintenance of an intact barrier are lipids, in particular long-chained ceramides. Tight junctions are important for maintaining the structure of the stratum corneum, and antimicrobial peptides help to fight infectious agents. Clarification of up- and down-regulation, and interaction between all the factors involved, will be an important future research subject. The permeability of the skin barrier is of outmost importance for the penetration of toxic chemicals, but also for pharmacological treatment. Precise and reproducible experimental models exist, but are difficult to transfer to human real-life exposures due to great heterogeneity between individuals. The skin barrier function is hampered in many (most?) skin diseases, with atopic dermatitis and ichthyosis being the most obvious ones. The clinical look of these diseases is characterized by dry, scaly and fissured skin, and experimentally by increased transepidermal water loss and a decreased amount of natural moisturizing factor. VII

Environmental as well as inherited factors may affect the barrier function negatively, and irritant contact dermatitis is an example of this. Wetwork exposure is a particularly significant factor, and recent research within this area focuses on its influence on an interplay between work-related and domestic exposures. Although the last decade has seen significant progress in the understanding of the skin barrier function, this has yet to be reflected in the treatment of xerosis and other barrier defects. Additionally, there is a lack of evidence and standardized recommendations with regard to protecting and restoring skin barrier function. However, a real breakthrough has taken place in the understanding of barrier function, an important and necessary step in the direction of improved treatment. Tove Agner, Copenhagen VIII Agner