title: Individuals who are homozygous for the 2282del4 and R501X filaggrin null mutations do not always develop dermatitis and complete long-term remission is possible.
abstract: BACKGROUND
  About 8-10% of the general population in Europe carry a null mutation in the filaggrin gene which is associated with early onset of atopic dermatitis as well as persistence into adulthood. No studies have investigated whether individuals with the homozygous filaggrin null genotype always develop dermatitis.
  
  
  OBJECTIVE
  The aim of this study was to describe the natural history of individuals with no filaggrin expression.
  
  
  METHODS
  Three study populations were included: (i) a random sample of 3335 subjects aged 18-69 years from the general population in Copenhagen who underwent general health examination; (ii) a total of 499 patients seen in our dermatitis clinic since 2009 and who were filaggrin genotyped as a part of the routine diagnostic work up; and (iii) a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma. Filaggrin genotyping was performed for the 2282del4 and R501X mutations.
  
  
  RESULTS
  Filaggrin homozygous/compound heterozygous individuals accounted for 0.3% of adults, 3% of dermatitis patients and 0.7% of children. Respectively, one of nine adults and one of three children never experienced dermatitis until now. All hospital patients had atopic dermatitis with onset during (early) childhood. Year-long complete remission was observed in half of patients.
  
  
  CONCLUSIONS
  The natural history of individuals with the filaggrin null genotype is fairly good in the sense that they may not develop dermatitis at all, and if they do, they may experience complete remission.
authors.affiliation: National Allergy Research Centre, Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Denmark. jacpth01@geh.regionh.dk
authors.forename: J P
authors.initials: JP
authors.lastname: Thyssen
authors.forename: B C
authors.initials: BC
authors.lastname: Carlsen
authors.forename: H
authors.initials: H
authors.lastname: Bisgaard
authors.forename: C
authors.initials: C
authors.lastname: Giwercman
authors.forename: J D
authors.initials: JD
authors.lastname: Johansen
authors.forename: A
authors.initials: A
authors.lastname: Linneberg
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; D003718:Denmark; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D012074:Remission Induction; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins