Filaggrin mutations may confer susceptibility to chronic hand eczema characterized by combined allergic and irritant contact dermatitis.

Abstract

The pathogenesis of chronic hand eczema (CHE) is multifactorial and involves both endogenous predisposition and environmental triggers. Filaggrin is a structural protein of the cornified envelope and important for the formation of the epidermal skin barrier. The aim of this investigation was to evaluate the role of mutations in the filaggrin gene (FLG) in the development of CHE. In total, 122 German patients with clearly defined CHE subtypes were screened for the FLG variants R501X and 2282del4 by polymerase chain reaction and restriction enzyme digest analysis. The prevalence of these variants in CHE patients was compared with that in 95 healthy individuals. Overall, allele frequency and the number of mutation carriers were similar in both the CHE and control groups. When classified according to clearly defined CHE subtypes, however, the nonfunctional FLG variants showed an association with CHE involving an aetiological combination of contact allergy and irritant factors [P = 0.04; P (exact test) = 0.06; P (difference in rates) = 0.09; 95% confidence interval (CI) 0-56.8)], or with excessive daily exposure to water and irritants [P = 0.003; P (difference in rates) < 0.001; 95% CI 29.3-67.9]. Heterozygosity for nonfunctional mutations in the FLG gene may contribute to the manifestation and maintenance of a particular CHE subtype that is characterized by the combination of allergic and irritant contact dermatitis.