Current Problems in Dermatology Editors: P. Itin, G.B.E. Jemec Vol. 49 Skin Barrier Function Editor T. Agner 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. Phys- terplay between the immune system and barrier ically, it protects us from external threats such as function; it has been documented that impaired infectious agents, chemicals, systemic toxicity barrier function leads to up-regulation of certain and allergens; internally, the skin helps to main- interleukins, which again influence the amount tain homeostasis and to protect from enhanced of natural moisturizing factor. Other very im- loss of water from the body. Both of these are life- portant players in the maintenance of an intact saving qualities. Another aspect is the esthetic ap- barrier are lipids, in particular long-chained cer- pearance of the skin, which should not be under- amides. Tight junctions are important for main- estimated. Since ancient times, a well-hydrated taining the structure of the stratum corneum, and skin texture has been treasured, with tradition antimicrobial peptides help to fight infectious featuring bathing in milk as the ultimate luxury to agents. Clarification of up- and down-regulation, secure soft and moisturized skin. and interaction between all the factors involved, Since in the last decade filaggrin mutations will be an important future research subject. were discovered as a major risk factor for atopic The permeability of the skin barrier is of out- dermatitis, an inflammatory skin disease with a most importance for the penetration of toxic particularly impaired barrier function, research chemicals, but also for pharmacological treat- in skin barrier function has escalated. The skin ment. Precise and reproducible experimental barrier is located in the stratum corneum, made models exist, but are difficult to transfer to hu- up of flattened, anucleated cells and a highly or- man real-life exposures due to great heterogene- ganized lipid matrix. The filaggrin protein helps ity between individuals. to maintain an organized barrier, and loss-of- The skin barrier function is hampered in many function mutations in the filaggrin gene are a ma- (most?) skin diseases, with atopic dermatitis and jor determinant of filaggrin expression in the ichthyosis being the most obvious ones. The clin- skin. Natural moisturizing factor, an amorphous ical look of these diseases is characterized by dry, substance highly important for hydration of the scaly and fissured skin, and experimentally by in- stratum corneum, is a degradation product of fil- creased transepidermal water loss and a decreased aggrin. An extremely interesting finding is the in- amount of natural moisturizing factor. VII Environmental as well as inherited factors may function, this has yet to be reflected in the treat- affect the barrier function negatively, and irritant ment of xerosis and other barrier defects. Addi- contact dermatitis is an example of this. Wet- tionally, there is a lack of evidence and standard- work exposure is a particularly significant factor, ized recommendations with regard to protecting and recent research within this area focuses on its and restoring skin barrier function. However, a influence on an interplay between work-related real breakthrough has taken place in the under- and domestic exposures. standing of barrier function, an important and Although the last decade has seen significant necessary step in the direction of improved treat- progress in the understanding of the skin barrier ment. Tove Agner , Copenhagen VIII Agner Section I: Basic Parameters Agner T (ed): Skin Barrier Function. Curr Probl Dermatol. Basel, Karger, 2016, vol 49, pp 1–7 (DOI: 10.1159/000441539) Filaggrin and Skin Barrier Function a b Sanja Kezic ؒ Ivone Jakasa a Coronel Institute of Occupational Health, Academic Medical Center, University of Amsterdam, Amsterdam , The Netherlands; b Laboratory for Analytical Chemistry, Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb , Croatia Abstract of potentially hazardous chemicals, which might cause The skin barrier function is greatly dependent on the adverse effects in the skin, such as contact dermatitis, or structure and composition of the uppermost layer of the systemic toxicity after their passage into blood. In an- epidermis, the stratum corneum (SC), which is made up other direction, a leaky epidermal barrier will lead to en- of flattened anucleated cells surrounded by highly orga- hanced loss of water from the skin. A recent study has nized and continuous lipid matrix. The interior of the shown that even subtle increase in epidermal water loss corneocytes consists mainly of keratin filaments aggre- in newborns increases the risk for AD. Although there gated by filaggrin (FLG) protein.