Abstract
BackgroundFilaggrin 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.MethodThe 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.ResultsA 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.ConclusionIn 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.
Highlights
10% of the general population carry at least one null mutation in the filaggrin gene (FLG) [1]
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, 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
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
Summary
10% of the general population carry at least one null mutation in the filaggrin gene (FLG) [1]. Heterozygous, and in particular homozygous or compound heterozygous carriers of FLG null variants, experience dry, scaly and fissured skin more often that non-mutation carriers [4,5] and recent in vivo measurements of the stratum corneum in patients with AD found lower levels of natural moisturizing factor among FLG deficient patients [6,7]. FLG mutations are major predisposing factors for atopic dermatitis (AD) [1,8,9,10,11] and are associated with early onset of AD, persistence of AD into adulthood and asthma and allergic sensitization [8,9,12,13,14]. 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
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