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Contact Dermatitis. 2019 Jun;80(6):354-358. doi: 10.1111/cod.13268. Epub 2019 Apr 10.

Filaggrin gene loss-of-function mutations constitute a factor in patients with multiple contact allergies.

Author information

1
Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University, Halifax, Canada.
2
Division of Dermatology and Experimental Medicine, Department of Medicine, McGill University, Montreal, Canada.
3
Division of Dermatology, Department of Medicine, University of Ottawa, Ottawa, Canada.
4
Division of Dermatology, Department of Medicine, Queen's University, Kingston, Canada.
5
Research Methods Unit, Department of Medicine, Dalhousie University, Halifax, Canada.
6
Division of Molecular Medicine, School of Life Sciences, Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK.

Abstract

BACKGROUND:

Polysensitivity is defined as three or more positive patch test reactions. The role of filaggrin gene (FLG) loss-of-function mutations in patients with polysensitivity has not been studied when barrier bypass and possible preceding barrier damage have been excluded.

OBJECTIVES:

To determine whether FLG loss of function mutations play a role in patients with multiple contact sensitivities when barrier bypass is excluded.

METHODS:

One hundred and sixty-nine patients with three or more, non-cross-reacting, positive patch test reactions were prospectively enrolled in this study. Exclusion criteria were a history of hand dermatitis, nickel and metal implants, and stasis dermatitis. Subjects were patch tested with the North American extended patch test series, and with other relevant haptens. DNA was obtained and sequenced for the following FLG loss-of-function mutations: R501X, 2282del4, R2447X, and S3247X.

RESULTS:

One hundred and sixty-five patients were genotyped for the four FLG mutations. There was a significant association between R501X mutation and polysensitivity. For the other three tested mutations, there were no significant associations with polysensitivity. When all mutations were combined, there was a significant association between loss-of-function FLG mutations and polysensitivity in patients with a history of atopic dermatitis.

CONCLUSION:

When skin barrier bypass is excluded, there is a significant association between polysensitivity and FLG loss-of-function mutations.

KEYWORDS:

contact dermatitis; filaggrin; loss-of-function mutations; polysensitivity, skin barrier

PMID:
30868611
DOI:
10.1111/cod.13268

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