SG10 Ichthyosis vulgaris in a South Asian population with atopic eczema: prevalence, clinical phenotypes and filaggrin variants
Authors: Jonathan Chan, Xiang Li Tan, Bjorn Thomas, Aaron Hughes, Rebecca McCarthy, Soha Tawfik, Sasha Dhoat, Ravinder Atkar, Jaheda Begum, Syedia Rahman, Samiha Rahman, Rehana Ahmed, Rubina Begum, Habiba Khanam, David Kelsell, Edel O’Toole
Journal: British Journal of Dermatology (2024)

Abstract Ichthyosis vulgaris (IV) affects up to 1 in 250 people, presenting with a spectrum of severity. Loss-of-function filaggrin variants cause IV and are implicated in atopic eczema (AE). Variants have not been widely investigated in people of South Asian ancestry. We aimed to investigate its prevalence, phenotype and link to loss-of-function (LoF) variants in a Bangladeshi cohort. British Bangladeshi patients with AE and aged 0–30 years were recruited between May 2018 and December 2020. Targeted gene sequencing was undertaken using DNA from saliva. Univariable and multivariable logistic regression models were used to estimate odds ratios of the LoF variant for each pattern. Statistical analysis performed with R v4.3.1 (R Foundation, Vienna, Austria). In total, 568 patients had suitable data for analysis: 318 were male (56%), the mean age was 10.2 years, the mean Patient-Oriented Eczema Measure was 12.6, and the mean Eczema Area and Severity Index (EASI) was 7.2. Overall, 175 (31%) had ichthyosis. Four patterns were identified: (i) smooth, (ii) hyperlinear, (iii) diamond scales and (iv) hyperkeratotic. Hyperlinear may represent a precursor form of IV, but for the current analyses types (iii) and (iv) were classed as IV. When compared with the smooth pattern, odds ratios (ORs) demonstrated significant association between LoF variants and diamond scale [OR 2.42, 95% confidence interval (CI) 1.43–4.14, P = 0.001)] and hyperkeratotic patterns (OR 2.37, 95% CI 1.27–4.48, P = 0.007). Significant differences were seen between leg patterns in EASI (P &amp;lt; 0.001), corneometry (P &amp;lt; 0.001; Kruskal–Wallis test) and palmar pattern (P &amp;lt; 0.001; χ2-test). Prominent diamond palmar pattern had the strongest association with IV (OR 5.49, 95% CI 2.61–11.9, P &amp;lt; 0.001). The 10 most common variants in patients with both IV and AE, vs. AE only are seen in the Table. In summary, IV is common (31%) in Bangladeshi patients with AE, four patterns exist, and severe phenotypes show strong links to LoF variants. Future work should explore the specific variants in IV, the effect of climate on masking subtle phenotypes, and examination of healthy controls to distinguish subtle patterns as normal variants or IV.90 patients (out of 175, 51%) with AE and IV with LoF variants123 patients (out of 393, 31%) with AE only with LoF variantsFilaggrin variantNumber with variantFilaggrin variantNumber with variantc.7031C&amp;gt;gG, S2344*18c.7031C&amp;gt;gG, S2344*17c.2282_2285del, S761Cfs*3615c.2282_2285del, S761Cfs*3614c.3191G&amp;gt;A, W1064*10c.2976_2977del, R992Sfs*317c.2767_2768insT, S923Ffs*27c.2767_2768insT, S923Ffs*25c.3418C&amp;gt;T, R1140*7c.3191G&amp;gt;A, W1064*5c.2476C&amp;gt;T, R826*6c.3424del, Q1142Kfs*445c.2976_2977del, R992Sfs*315c.7339C&amp;gt;T, R2447*5c.3424del, Q1142Kfs*444c.1501C&amp;gt;T, R501*4c.2185C&amp;gt;T, Q729*2c.2185C&amp;gt;T, Q729*4c.6986_6987del, R2329Tfs*372c.2476C&amp;gt;T, R826*421 other variants36 other variants