P102 Severe atopic eczema is associated with reduced acne vulgaris in Bangladeshi children and young adults: a retrospective analysis from a cross-sectional study

Abstract Atopic eczema (AE) is the most common inflammatory dermatosis, affecting up to 20% of children. Loss of function (LoF) mutations in FLG are the most strongly implicated genetic risk factor for eczema. To understand the effect of FLG on the pathobiology of AE, we knocked down FLG in primary keratinocytes using short hairpin RNA and performed phosphoproteomic analysis, which showed downregulation of the AKT signalling pathway, confirmed using Western blotting to phospho-AKT and immunostaining of biopsies from patients with AE. Given that AKT signalling is increased in acne vulgaris, we hypothesized that loss of FLG may protect patients with AE from acne. The Tower Hamlets Eczema Assessment (THEA) study is a cross-sectional study that aims to phenotype and genotype 1000 Bangladeshi children and young adults with AE. So far, 620 participants have undergone genotyping, 37% of whom have LoF mutations in FLG. We selected patients from this cohort who were older than 12 years of age. In total, 204 patients (99 FLG wild type, 86 heterozygotes, 19 compound heterozygotes) were included. We identified a diagnosis of acne or previous prescription of topical acne therapies or tetracycline antibiotics from the patients’ general practice e-health records. We stratified the patients by genotype, Eczema Area and Severity Index (EASI) score, Patient Oriented Eczema Measure (POEM) score, transepidermal water loss (TEWL) and palmar hyperlinearity groups. The χ2-test was used to determine differences between groups. A lower proportion of patients with AE with FLG mutations had acne (27% wild type vs. 19% FLG mutations), which was more pronounced, but not statistically significant, in the compound heterozygote group (16%). We saw a nonsignificant reduction in acne in patients who had the top 25% of TEWL measurements, those with the most severe form of hyperlinearity and those with higher POEM scores. Patients with severe AE, measured as an EASI score > 21, had a more reduced incidence of acne than those with lower EASI scores (9% vs. 26%; P = 0.04). Overall, this suggests that patients with more severe AE are protected from developing acne. There was insufficient evidence to establish if this was mediated by a reduction in filaggrin (FLG) and AKT signalling. This may be because the groups were too small to determine this. Given that all patients with severe AE have reduced FLG expression regardless of genotype, it is possible that this is mediated through FLG–AKT signalling.