Atopic eczema: genetics or environment?

Brunello Wuthrich 1, Antonio Cozzio 2, Antonie Roll 2, Gabriela Senti 2, Thomas Kundig 2, Peter Schmid-Grendelmeier 2
1 - Spital Zollikerberg, Allergologie, klinische Immunologie und Dermatologie, Trichtenhauserstrasse 20, 8125 Zollikerberg, Switzerland; bs.wuethrich@bluewin.ch.
2 -
Ann Agric Environ Med
2007; 14 (2):
ICID: 778094
 
 
Atopic eczema (AE) is a multifactorial skin disease caused by a variety of factors such as genetic conditions, alterated skin structure, immunologic deviations and environmental factors, among others. There are two main subtypes of AE, i.e. the IgE-associated ("atopic eczema") and the non-IgE-associated type ("nonatopic eczema") with different prognosis concerning the development of respiratory diseases ("atopy march"). Recently, it was demonstrated that Filaggrin (= filament-aggregating protein, FL) is a major gene for atopic eczema. Filaggrin binds to and aggregates the keratin cytoskeleton in the epidermis. Homozygous FLG mutation leads to complete loss of filaggrin expression in skin. Half or more of children with moderate to severe AE carry FLG mutations. Moreover, filaggrin loss-of-function mutations predispose to phenotypes involved in the atopy march. The altered skin structure and a deficiency in antimicrobial peptides favour colonization with Staphylococcus aureus and yeasts (Malassezia sp.). Sensitization to the yeast occurs almost exclusively in AE patients. S. aureus enterotoxins with superantigenic activity stimulate activation of T cells and macrophages. So far, AE skin lesions are orchestrated by the local tissue expression of proinflammatory cytokines and chemokines with activation of T lymphocytes, dendritic cells, macrophages, keratinocytes, mast cells, and eosinophils which lead to the skin inflammatory responses. From the therapeutic point of view, besides emollients and local corticosteroids, topic immunomodulatory drugs (tacrolimus and pimecrolimus) have substantially improved the treatment of AE.
PMID 18247450 - click here to show this article in PubMed
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