title: Filaggrin loss-of-function mutation R501X and 2282del4 carrier status is associated with fissured skin on the hands: results from a cross-sectional population study.
abstract: BACKGROUND
  Filaggrin metabolites act as osmolytes and are important for skin hydration. Carriers of filaggrin loss-of-function mutations have a higher prevalence of atopic dermatitis and dry skin. There is also evidence to suggest that filaggrin mutations increase the risk of hand eczema in atopic individuals. In our clinic, we have observed a distinct phenotype of hand eczema in patients with filaggrin mutation carrier status, characterized by fissured dermatitis on the dorsal aspect of the hands and with only sparse involvement of the palms including fine scaling.
  
  
  OBJECTIVE
  To investigate whether filaggrin loss-of-function mutations are associated with skin fissures on the hands and/or fingers in the general population.
  
  
  METHODS
  Participants in a population-based study were questioned about skin symptoms, genotyped for filaggrin mutation, patch tested for nickel allergy and skin prick tested.
  
  
  RESULTS
  In an adjusted logistic regression analysis, filaggrin mutation status was significantly associated with fissured skin on the hands and/or fingers in adults (odds ratio 1·93, 95% confidence interval 1·05-3·55) and showed a nearly significant negative interaction with atopic dermatitis (P=0·055), suggesting that the effect was predominantly in subjects without atopic dermatitis.
  
  
  CONCLUSIONS
  Filaggrin loss-of-function mutations seem not only to increase the risk of atopic dermatitis and dry skin but also the risk of fissures on the hands and/or fingers in subjects without atopic dermatitis. Prophylactic emollient therapy should be particularly encouraged in filaggrin loss-of-function mutation carriers.
authors.affiliation: National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark. jacpth01@geh.regionh.dk
authors.forename: J P
authors.initials: JP
authors.lastname: Thyssen
authors.forename: K
authors.initials: K
authors.lastname: Ross-Hansen
authors.forename: J D
authors.initials: JD
authors.lastname: Johansen
authors.forename: C
authors.initials: C
authors.lastname: Zachariae
authors.forename: B C
authors.initials: BC
authors.lastname: Carlsen
authors.forename: A
authors.initials: A
authors.lastname: Linneberg
authors.forename: H
authors.initials: H
authors.lastname: Bisgaard
authors.forename: C G
authors.initials: CG
authors.lastname: Carson
authors.forename: N H
authors.initials: NH
authors.lastname: Nielsen
authors.forename: M
authors.initials: M
authors.lastname: Meldgaard
authors.forename: P B
authors.initials: PB
authors.lastname: Szecsi
authors.forename: S
authors.initials: S
authors.lastname: Stender
authors.forename: T
authors.initials: T
authors.lastname: Menné
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D005838:Genotype; D006229:Hand Dermatoses / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012882:Skin Tests; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins