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      Atopic Dermatitis: Global Epidemiology and Risk Factors

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          Abstract

          Atopic dermatitis (AD) is a chronic inflammatory skin disease posing a significant burden on health-care resources and patients' quality of life. It is a complex disease with a wide spectrum of clinical presentations and combinations of symptoms. AD affects up to 20% of children and up to 3% of adults; recent data show that its prevalence is still increasing, especially in low-income countries. First manifestations of AD usually appear early in life and often precede other allergic diseases such as asthma or allergic rhinitis. Individuals affected by AD usually have genetically determined risk factors affecting the skin barrier function or the immune system. However, genetic mutations alone might not be enough to cause clinical manifestations of AD, and it is merely the interaction of a dysfunctional epidermal barrier in genetically predisposed individuals with harmful effects of environmental agents which leads to the development of the disease. AD has been described as an allergic skin disease, but today, the contribution of allergic reactions to the initiation of AD is challenged, and it is proposed that allergy is rather a consequence of AD in subjects with a concomitant underlying atopic constitution. Treatment at best achieves symptom control rather than cure; there is thus a strong need to identify alternatives for disease prevention.

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          Most cited references45

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          Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.

          Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.
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            From atopic dermatitis to asthma: the atopic march.

            To examine the mechanisms whereby allergen exposure through the epidermis could initiate systemic allergy and predispose individuals to the development of 1 or more atopic diseases via the so-called atopic march. PubMed databases from 1950 to the present were searched for relevant articles pertaining to epidemiologic and genetic evidence of the progression of the atopic march. Articles concerning pathophysiologic conditions that link atopic dermatitis, allergic rhinitis, and asthma were examined. The data suggest that a sequence of atopic manifestations occurs, typically atopic dermatitis in infancy followed by allergic rhinitis and/or asthma in later stages. Reduced filaggrin expression is implicated as a major predisposing factor for atopy in multiple lines of evidence, including genome-wide analysis and microarray investigations. Other gene products have an important role. Cross-sectional and longitudinal studies provide preliminary epidemiologic support for the sequential development of allergic diseases. The mechanisms by which allergen exposure through the epidermis can initiate systemic allergy and predispose individuals to atopic dermatitis, allergic rhinitis, and asthma have become clearer in recent years. Longitudinal studies of individuals carrying loss-of-function filaggrin gene mutations are needed to further define the risks associated with epidermal barrier dysfunction and potentially identify specific targets for barrier repair and prevention of atopic dermatitis and other atopic disease. The effects of preventive and treatment strategies have been inconsistent across studies, and further research is warranted before any definitive recommendations can be made. Copyright 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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              Reduced diversity in the early fecal microbiota of infants with atopic eczema.

              It might be that early intestinal colonization by bacteria in westernized infants fails to give rise to sufficient immune stimulation to support maturation of regulatory immune mechanisms. The purpose of the present study was to characterize the very early infantile microbiota by using a culture-independent approach and to relate the colonization pattern to development of atopic eczema in the first 18 months of life. Fecal samples were collected from 35 infants at 1 week of age. Twenty infants were healthy, and 15 infants were given diagnoses of atopic eczema at the age of 18 months. The fecal microbiota of the infants was compared by means of terminal restriction fragment length polymorphism (T-RFLP) and temporal temperature gradient gel electrophoresis (TTGE) analysis of amplified 16S rRNA genes. By means of T-RFLP analysis, the median number of peaks, Shannon-Wiener index, and Simpson index of diversity were significantly less for infants with atopic eczema than for infants remaining healthy in the whole group and for the Swedish infants when AluI was used for digestion. The same was found when TTGE patterns were compared. In addition, TTGE analysis showed significantly less bands and lower diversity indices for the British atopic infants compared with those of the control subjects. There is a reduced diversity in the early fecal microbiota of infants with atopic eczema during the first 18 months of life.
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                Author and article information

                Journal
                ANM
                Ann Nutr Metab
                10.1159/issn.0250-6807
                Annals of Nutrition and Metabolism
                S. Karger AG
                978-3-318-03032-7
                0250-6807
                1421-9697
                2015
                April 2015
                24 April 2015
                : 66
                : Suppl 1
                : 8-16
                Affiliations
                Nutrition and Health Department, Nestlé Research Center, Lausanne, Switzerland
                Author notes
                *Sophie Nutten, PhD, Nutrition and Health Department, Nestlé Research Center, PO Box 44, CH-1000 Lausanne 26 (Switzerland), E-Mail sophie.nutten@rdls.nestle.com
                Article
                370220 Ann Nutr Metab 2015;66(suppl 1):8-16
                10.1159/000370220
                25925336
                94b98671-2b09-4480-baff-baa986d0b1d7
                © 2015 S. Karger AG, Basel

                Copyright: 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. 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 changes 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. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication 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.

                History
                Page count
                Figures: 3, Tables: 2, References: 65, Pages: 9
                Categories
                Atopic Dermatitis

                Nutrition & Dietetics,Health & Social care,Public health
                Genetics,Atopic dermatitis,Immune dysregulation,Environment,Atopic march,Skin barrier defect

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