P083 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, 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 (LoF) filaggrin variants cause IV and are implicated in atopic eczema (AE). These have been widely investigated in White European populations but not in South Asian patients. Studies suggest that 2.5–37% patients with AE have IV. We aimed to investigate its prevalence, phenotype and link to LoF variants in Bangladeshi patients. British Bangladeshi patients with AE aged 0–30 years were recruited from secondary care between May 2018 and December 2020. Targeted gene sequencing was undertaken using DNA from saliva. Univariable and multivariable logistic regression models estimated odds ratios of LoF variants 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, mean Patient-Oriented Eczema Measure was 12.6, and mean Eczema Area and Severity Index was 7.2. Overall, 175 (31%) had ichthyosis. Four patterns were identified: (i) smooth (clear), (ii) hyperlinear, (iii) diamond scales and (iv) hyperkeratotic. Hyperlinear may represent a subtle or precursor form of IV, but for current analyses types three and four were classed as IV. Patients with hyperkeratosis had the lowest mean vitamin D (21.3 nmol L−1) and corneometry (22.4 AU). When compared with smooth pattern, odds ratios (ORs) demonstrated significant association between LoF variants and diamond scale (OR 2.42, 95% confidence interval 1.43–4.14; P = 0.001) and hyperkeratosis (OR 2.37, 95% confidence interval 1.27–4.48; P = 0.007). The top 10 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 further explore specific LoF 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.TableTop 10 filaggrin LoF variants seen in patients with AE and IV, and AE only90/175 patients (51%) with AE and IV with LoF variants.123/393 patients (31%) with AE only with LoF variantsLoF filaggrin variantPatients with LoF variantLoF filaggrin variantPatients with LoF variantc.7031C&amp;gt;G, S2344*18c.7031C&amp;gt;G, 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