Understanding the genotype/phenotype associations will help us predict high risk of eczema and related disease. We present preliminary associations between loss-of-function (LoF) FLG variants and eczema phenotype in the THEA cohort. Data and samples were collected from Paediatric/Adult Dermatology in a large teaching hospital. Clinical patterns of palmar linearity were grouped – fine perpendicular lines (FP), thick perpendicular lines (TP), fine thenar cross-hash (FX), extensive palmar cross-hash (EX) and a prominent diamond (PD) group. EASI score, TEWL and skin hydration (SH) were measured. Presence/absence of disease at 53 body sites was collected. DNA from saliva was used for FLG sequencing. Multivariate logistic regression with Firth’s correction was used for the models. Bernoulli Mixture Models were used to create clusters for lesional disease distributions. A total of 349 participants were available for this analysis. 27.7% (n=97) had at least one LoF FLG variant. EASI (OR 1.04; 95% CI 1.01-1.05) and SH (OR 1.04; 95% CI 1.01-1.05) were associated with LoF variants. For palm patterns, 8.3% of FP, 43.9% of TP, 10.2% of FX, 33.7% of EX and 82.7% of PD individuals had at least one LoF variant in FLG. The same variants can be seen across all patterns. Palm pattern models suggest a 7.95 (95% CI 3.11-23.97), 4.93 (95% CI 1.97-14.61) and 54.61 (95% CI 15.74-237.17) fold increase in odds of having a LoF FLG variant in the TP, EX and PD groups respectively. Nine distribution clusters from our data were proposed. Three of the clustered groups were acral predominant and were the only patterns to be associated with LoF FLG variants and food allergy. Our findings show that LoF FLG variants are associated with eczema severity, skin hydration/epidermal moisture and specific lesional patterns. LoF variants do not account for all the plasticity in phenotype.

ESDR179 - Phenotype association with Filaggrin loss of function from the Tower Hamlets Eczema Assessment (THEA)

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING