Impact of atopic dermatitis and loss-of-function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis

Summary Background Atopic dermatitis (AD) and loss‐of‐function mutations in the filaggrin gene (FLG) are both associated with chronic irritant contact dermatitis (ICD). As FLG mutations also are a major risk factor for AD, it is not clear whether FLG mutations are an independent risk factor for ICD...

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Published in:	British journal of dermatology (1951) 2013-02, Vol.168 (2), p.326-332
Main Authors:	Visser, M.J., Landeck, L., Campbell, L.E., McLean, W.H.I., Weidinger, S., Calkoen, F., John, S.M., Kezic, S.
Format:	Article
Language:	eng
Subjects:	Adult Age of Onset Allergic diseases Biological and medical sciences Dermatitis, Atopic - genetics Dermatitis, Irritant - genetics Dermatitis, Occupational - genetics Dermatology Female Filaggrin Proteins Genetic Predisposition to Disease - genetics Genotype Humans Immunopathology Intermediate Filament Proteins - genetics Male Medical sciences Middle Aged Mutation - genetics Risk Factors Skin allergic diseases. Stinging insect allergies
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Summary:	Summary Background Atopic dermatitis (AD) and loss‐of‐function mutations in the filaggrin gene (FLG) are both associated with chronic irritant contact dermatitis (ICD). As FLG mutations also are a major risk factor for AD, it is not clear whether FLG mutations are an independent risk factor for ICD or whether the risk is mediated by AD. Objectives To investigate the relative contribution and interaction of FLG mutations and AD in German patients with occupational ICD and controls (vocational school apprentices). Methods A total of 634 patients and 393 controls were genotyped for R501X, 2282del4, R2447X and S3247X. Current or past flexural eczema was used as an indicator of AD. Results FLG mutations were found in 15·9% of the patients with ICD and 8·3% of the controls, with a crude odds ratio (OR) of 2·09 [95% confidence interval (CI) 1·33–3·28] for the combined genotype. The adjusted OR for FLG mutations, corrected for AD, was 1·62 (95% CI 1·01–2·58). Subjects with AD were at approximately three times higher risk of developing ICD than controls (OR 2·89; 95% CI 2·09–3·99). There was no evidence of an interaction between these two risk factors. Conclusions Our results indicate that both FLG mutations and AD increase the risk of ICD. Individuals with concurrent FLG mutations and AD are at the highest risk of developing ICD. What’s already known about this topic? •Filaggrin gene (FLG) loss‐of‐function mutations increase the risk of developing atopic dermatitis (AD). It has been reported that FLG mutations are associated with irritant contact dermatitis (ICD); however, it is unclear whether they are an independent risk factor or work through AD. What does this study add? •FLG mutations are associated with ICD even when adjusted for AD. • Individuals with concurrent FLG mutations [odds ratio (OR) 1·61] and AD (OR 2·89) are at the highest risk of developing ICD (combined OR 4·7). See also the Commentary by Thys sen
ISSN:	0007-0963 1365-2133