Clinical Presentation of Atopic Dermatitis by Filaggrin Gene Mutation Status during the First 7 Years of Life in a Prospective Cohort Study

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.

Environmental risk factors and their role in the management of atopic dermatitis

“…Carson et al found a predilection for AD lesions on exposed body areas in children with filaggrin variants, suggesting that barrier defects may predispose to insult from environmental factors, e.g. pollution and climate [97,109]. Taken together, it appears that multiple outdoor and indoor pollutants may trigger and/or exacerbate childhood AD.…”

Skin Barrier Dysfunction and the Atopic March

“…In particular, eczema on the hands and cheeks in infancy and early childhood has been coupled to FLG mutations [8]. Older children more often experience flexural eczema, whereas in adults the eczema is confined mostly to the face, neck and hands although it can be more widespread and take a chronic course.…”

Current and future biomarkers in allergic asthma

“…References are described on the coloured side of the CD11b CD13 CD25 CD29 CD32 CD44 CD52 CD54 CD62L CD63 CD66e CD67 CD69 C5AR/CD88 CD108 CD125 CD193 CD244 CD294 FcεR1α Galectin-3 HLA-DR Siglec-8 CD11b CD14 CD35 CD62L CD63 CD64 CD66b CD88 CD274 CXCR2 TRL2 TLR4 CD44 CD54 CD63 CD69 CD193/CCR3 CD203c CD294/CRTH2 FcεR1α CD63 CD117 CD203c CXCR3 FcεR1α CD11a CD11b CD14 CD16 CD18 CD23 CD54 CD58 CD63 CD64 CD83 CD86 CD163 CD206 HLA- manifestation in childhood. This mutation can be used to define specific endotypes of atopic dermatitis characterized by an early onset of the disease and a more severe course (9). Clinically defined phenotypes include nonatopic wheezers, viral-induced asthma or multitrigger wheezers that may differentially respond to treatment or may even undergo spontaneous remission and therefore require personalized therapy (10).…”