title: Clinical presentation of atopic dermatitis by filaggrin gene mutation status during the first 7 years of life in a prospective cohort study.
abstract: BACKGROUND
  Filaggrin null mutations result in impaired skin barrier functions, increase the risk of early onset atopic dermatitis and lead to a more severe and chronic disease. We aimed to characterize the clinical presentation and course of atopic dermatitis associated with filaggrin mutations within the first 7 years of life.
  
  
  METHODS
  The COPSAC cohort is a prospective, clinical birth cohort study of 411 children born to mothers with a history of asthma followed during their first 7 years of life with scheduled visits every 6 months, as well as visits for acute exacerbations of dermatitis. Atopic dermatitis was defined in accordance with international guidelines and described at every visit using 35 predefined localizations and 10 different characteristics.
  
  
  RESULTS
  A total of 170 (43%) of 397 Caucasian children developed atopic dermatitis. The R501X and/or 2282del4 filaggrin null mutations were present in 26 (15%) of children with atopic dermatitis and were primarily associated with predilection to exposed skin areas (especially the cheeks and back of the hands) and an up-regulation of both acute and chronic dermatitis. Furthermore, we found the filaggrin mutations to be associated with a higher number of unscheduled visits (3.6 vs. 2.7; p=0.04) and more severe (moderate-severe SCORAD 44% vs. 31%; p=0.14), and widespread dermatitis (10% vs. 6% of the body area, p<0.001) with an earlier age at onset (246 vs. 473 days, p<0.0001) compared to wild-type.
  
  
  CONCLUSIONS
  In children, filaggrin mutations seem to define a specific endotype of atopic dermatitis primarily characterized by predilection to exposed areas of the body, in particular hands and cheeks, and an up-regulation in both acute and chronic morphological markers. Secondary, this endotype is characterized by an early onset of dermatitis and a more severe course, with more generalized dermatitis resulting in more frequent medical consultations.
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood; COPSAC, Health Sciences, University of Copenhagen, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark.
authors.forename: Charlotte Giwercman
authors.initials: CG
authors.lastname: Carson
authors.forename: Morten Arendt
authors.initials: MA
authors.lastname: Rasmussen
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Thyssen
authors.forename: Torkil
authors.initials: T
authors.lastname: Menné
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003876:Dermatitis, Atopic / Q000453:epidemiology* / Q000235:genetics*; D000091344:Filaggrin Proteins; D005838:Genotype; D006801:Humans; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D044465:White People / Q000235:genetics
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins