Recent genetic findings demonstrate an important role for the epidermal protein filaggrin in the aetiology of atopic diseases, including asthma as well as eczema. Filaggrin is critical to the conversion of keratinocytes to the protein/lipid squames that compose the stratum comeum, the outermost barrier layer of the skin. In 2006, icthyosis vulgaris, a disease characterised by dry, scaly skin, was found to be a semi-dominant Mendelian condition due to mutations at two sites (RSOIX and 2282del4) in the filaggrin gene. An exceptionally strong association has also been shown between these two mutations and the most common distinct form of eczema, atopic dermatitis, in 12 independent European populations, with odds ratios varying between 2.8 and 13.4. No negative studies have been reported in Europe, although these two mutations are not associated with AD in three non-European cohorts. Furthermore, FLG null mutations have since been identified in European and non-European cohorts with AD. Asthma on a background of AD is related to FLG null status, but not in the absence of AD. A primary defect in skin barrier function therefore appears to underlie atopic dermatitis and asthma. Immunological changes in atopic disease are probably secondary to enhanced antigen penetration through a deficient epidermal barrier.
|Number of pages||3|
|Journal||Journal of the Royal College of Physicians of Edinburgh|
|Publication status||Published - 17 Mar 2008|