Deep palmar phenotyping in atopic eczema: patterns associated with filaggrin variants, disease severity and barrier function in a South Asian population

Loss-of-function (LoF) variants in filaggrin (FLG) are associated with hyperlinear palms (HLP). It is not clear what defines HLP and predictive studies typically show a high negative predictive value. Irrespective of filaggrin status, patterns of palmar linearity in subjects with atopic eczema associate with disease severity and barrier function. Specific palm patterns can predict filaggrin LoF status, although the heterogeneity of palmar phenotype in the presence/absence of FLG variants points towards altered filaggrin protein expression from another mechanism in some patients. Background Hyperlinear palms are described as a feature of loss-of-function (LoF) variants in filaggrin (FLG). Objectives To explore the phenotype of participants (age < 31 years) with atopic eczema of Bangladeshi ancestry from East London and investigate which factors best associate with LoF FLG variants. Methods A cross-sectional study with participants recruited between May 2018 and December 2020. Patterns of palmar linearity were categorized and modelled with the Eczema Area and Severity Index (EASI), transepidermal water loss (TEWL), skin hydration (SH) and LoF FLG variants. Results There were 506 complete cases available. Five palm patterns were noted. The 'prominent diamond' pattern associated best with EASI [marginal effects (ME) 2.53, 95% confidence interval (CI) 1.74-3.67], SH (ME 0.85, 95% CI 0.78-0.96) and TEWL (ME 1.32, 95% CI 1.11-1.62). Using five palm patterns had some ability to discriminate LoF FLG variants [area under the receiver operator characteristic (AUROC) 76.32%, 95% CI 71.91-80.73], improving to 77.99% (73.70-82.28) with the addition of SH. In subgroup analysis with only fine perpendicular/prominent diamond patterns the AUROC was 89.11% (95% CI 84.02-94.19). Conclusions This was a single-centre study design with humans classifying clinical patterns. The stability of temperature and humidity was not guaranteed across TEWL and SH measurements despite using a climate-controlled room. Palm patterns associate with EASI and TEWL. The fine perpendicular/prominent diamond patterns are markers to detect the absence/presence of LoF FLG variants, respectively.

Automated summary

This study explored the phenotype of participants with atopic eczema of Bangladeshi ancestry from East London and investigated the factors associated with LoF FLG variants. The results showed that palm patterns were associated with EASI and TEWL, and the fine perpendicular/prominent diamond patterns could be used as markers for detecting the presence/absence of LoF FLG variants.