Funding sources The Foundation Institute GAK (Hilversum, the Netherlands) funded this study. We appreciate the support of the SKINBAD COST Action BM0903. Filaggrin research in the McLean laboratory is supported by grants from the Wellcome Trust (references 090066/B/09/Z and 092530/Z/10/Z), the Medical Research Council (reference G0700314), the British Skin Foundation and the National Eczema Society.
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CUTANEOUS ALLERGY
Impact of atopic dermatitis and loss-of-function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis
Article first published online: 30 JAN 2013
DOI: 10.1111/bjd.12083
© 2012 The Authors. BJD © 2012 British Association of Dermatologists
Additional Information
How to Cite
Visser, M.J., Landeck, L., Campbell, L.E., McLean, W.H.I., Weidinger, S., Calkoen, F., John, S.M. and Kezic, S. (2013), Impact of atopic dermatitis and loss-of-function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis. British Journal of Dermatology, 168: 326–332. doi: 10.1111/bjd.12083
Conflicts of interest None declared.
M.J.V. and L.L. contributed equally to this manuscript.
Publication History
- Issue published online: 30 JAN 2013
- Article first published online: 30 JAN 2013
- Accepted manuscript online: 5 OCT 2012 10:44AM EST
- Accepted for publication 29 September 2012
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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.