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Human atopic dermatitis: a disease at the frontier between allergy and autoimmunity
Author(s) -
Bieber T.
Publication year - 2004
Publication title -
veterinary dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.744
H-Index - 60
eISSN - 1365-3164
pISSN - 0959-4493
DOI - 10.1111/j.1365-3164.2004.00410_1-1.x
Subject(s) - atopic dermatitis , immunology , immunoglobulin e , allergy , candidate gene , disease , medicine , single nucleotide polymorphism , genome wide association study , autoimmunity , genetics , biology , gene , genotype , antibody , pathology
Atopic dermatitis (AD) is a chronic inflammatory skin disease that develops on a complex genetic background, the so‐called atopic diathesis. Genetic epidemiological studies based on linkage analysis with full genome scan strategies, as well as association and case‐controlled studies, have unravelled several chromosomal loci with putative candidate genes. These loci were revealed to be distinct from those newly identified for allergic asthma. Some of these genes localized on chromosomes 3, 17 and 20 are shared with psoriasis, another chronic inflammatory skin disease. These observations suggest, at least, the role of putative genes involved in the down‐regulation of inflammation in the skin. Single nucleotide polymorphisms have been identified in several genes for which the functional significance remains to be determined. In most (70–80%), but not all patients, AD is characterized by the presence of elevated total serum IgE levels. However, a subgroup of atopic patients (20–30%) exhibit normal IgE levels. Mechanisms contributing to the extrinsic/IgE‐mediated and the intrinsic/non‐IgE‐mediated forms have been the focus of intensive research in recent years. These forms have been particularly studied in the context of AD, which has lead to new nomenclature recently approved by the World Allergy Organization. Moreover, we now have increasing evidence for the putative role of an autoimmune phenomenon in the complex pathophysiology of atopic dermatitis. Mainly adult patients exhibit specific IgE directed against self‐proteins of epidermal origin. A new picture emerges in which the natural history of AD seems to be divided into three phases. First, an initial intrinsic phase, eczema, occurs in early infancy. This is then followed in 60–80% of cases by a sensitization to food and/or environmental allergens with the development of the extrinsic phase, true AD. In this form, it is speculated that antigen‐presenting cells expressing the high‐affinity receptor for IgE (FcεRI) play a major role in the control of inflammation. Consequently, these AD patients will have benefit from prevention measures. Finally, most probably due to molecular mimicry, an IgE sensitization to self‐proteins is observed in 60–80% of AD patients. Whether these specific IgE antibodies have a pathophysiological role or are only to be considered as an epiphenomenon remains to be clarified. In summary, due to rapid advancements in the research field of atopic diseases, it now becomes possible for the first time to delineate a new disease classification of allergic and nonallergic subtypes of atopic diseases, thereby bringing hope to the clinician for a more specific treatment approach for each subgroup of these patients.