O11 Associations between hyperlinearity of the sole and filaggrin variants in atopic eczema in a South Asian population: a cross-sectional study
Authors: Xiang Li Tan, Jonathan Chan, Bjorn Thomas, Stefan Van Duijvenboden, Sarah Hogan, Aaron Hughes, Soha Tawfik, Sasha Dhoat, Ravinder Atkar, Elizabeth Robinson, Syedia Rahman, Samiha Rahman, Rehana Ahmed, Rubina Begum, Habiba Khanam, Emma Bourne, Eva Wozniak, Charles Mein, David Kelsell, Edel O’Toole
Journal: British Journal of Dermatology (2024)

Abstract Loss-of-function (LoF) variants in the filaggrin gene (FLG) can lead to increased severity of atopic eczema. These variants have been reported in hyperlinear palms, ichthyosis vulgaris and keratosis pilaris (Smith FJD, Irvine AD, Terron-Kwiatkowski A et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006; 38: 337–42; Thomas BR, Tan XL, van Duijvenboden S et al. Deep palmar phenotyping in atopic eczema: patterns associated with filaggrin variants, disease severity and barrier function in a South Asian population. Br J Dermatol 2023; 188: 785–92). However, the association with hyperlinear sole in atopic eczema is unknown. We aimed to explore the sole phenotype of Bangladeshi children and young adults with atopic eczema and to determine whether any associations exist with LoF FLG variants, eczema severity or skin barrier function. British Bangladeshi participants under the age of 30 years were recruited to this single-centre cross-sectional study between May 2018 and December 2020. Logistic regression using unadjusted models and models adjusted for age and sex were carried out to assess associations between sole hyperlinearity and LoF FLG variant status. Eczema severity or skin barrier function were also assessed, using Eczema Area and Severity Index, transepidermal water loss and skin hydration. In total, 685 participants were included (mean age 10.6 years, SD 6.8). Five sole patterns were identified: (i) clear [wildtype (WT) n = 43, LoF FLG n = 17; mean age 13.0 years, SD 7.2], (ii) ­parallel lines (WT n = 133, FLG n = 34; mean age 11.8 years, SD 6.5), (iii) polygonal shapes in the medial instep (WT n = 148, FLG n = 56; mean age 12.1 years, SD 6.4), (iv) polygonal shapes over the whole foot (WT n = 82, FLG n = 93; mean age 8.5 years, SD 6.5) and (v) polygonal shapes over the ball of the foot (WT n = 12, FLG n = 30; mean age 5.4 years, SD 5.9), as well as ‘not applicable’ (WT n = 27; FLG n = 10). There were significant associations between LoF FLG with shapes over the whole foot and over the ball of foot in both unadjusted models [odds ratio (OR) 2.87, 97.5% confidence interval (CI) 1.54–5.53; and OR 6.32, 97.5% CI 2.70–15.7, respectively] and models adjusted for age and sex (OR 3.11, 95% CI 1.65–6.11; and OR 7.51, 95% CI 3.12–19.1). Clear pattern was least associated with LoF FLG variants in both unadjusted (OR 0.40, 95% CI 0.22–0.68) and adjusted models (OR 0.31, 95% CI 0.15–0.62). There were significant differences between sole patterns and Eczema Area and Severity Index (P = 0.008), transepidermal water loss (P &amp;lt; 0.001) and skin hydration (P = 0.002). Hyperlinearity sole patterns (shapes over the whole foot and over the ball of the foot) were associated with younger age (P &amp;lt; 0.001). This is the first large-scale study on hyperlinearity of the sole and FLG variants. We have identified five distinct sole patterns and shown that clear pattern and polygonal shapes over the ball of the foot are markers to detect the absence and presence of LoF FLG variants, respectively. Identifying patients with FLG variants clinically will allow early risk stratification without genetic testing and will also allow prog­nostication.