Clinical examination for hyperlinear palms to determine filaggrin genotype: A diagnostic test accuracy study

Bradshaw, Lucy E.; Haines, Rachel H.; Thomas, Kim S.; Chalmers, Joanne R.; Irvine, Alan D.; Williams, Hywel C.; Brown, Sara J.

Abstract

Background: Palmar hyperlinearity is a feature of ichthyosis vulgaris, the monogenic skin disorder caused by FLG loss-of-function mutations. Objective: To investigate how well the presence or absence of hyperlinear palms (HLP) detect FLG genotype in children. Methods: STARD criteria are used to report this diagnostic accuracy study. Phenotype and genotype data (four most prevalent FLG null mutations) were obtained from a total of 3656 children in three studies: the UK CLOTHES trial (children 1–5years with moderate–severe atopic eczema); UK BEEP trial (2year olds at high risk of developing atopic eczema); UK-Irish eczema case collection (0–16year olds with atopic eczema). All participants included in analyses of HLP as the index test and FLG genotype as the reference were of white European ancestry. Results: Thirty-two percent of participants (1159/3656) had FLG null mutation(s) and 37% (1347/3656) had HLP. In 13% (464/3656), HLP was recorded as ‘unsure’ or not recorded. The sensitivity and specificity of HLP for detecting FLG mutations in each of the studies was: 67% (95% CI 55–78%) and 75% (67–82%) in CLOTHES; 46% (36–55%) and 89% (86–91%) in BEEP; 72% (68–75%) and 60% (57–62%) in the UK-Irish case collection. Positive and negative likelihood ratios were: 2.73 (1.95–3.81) and 0.44 (0.31–0.62) in CLOTHES; 4.02 (2.99–5.40) and 0.61 (0.52–0.73) in BEEP; 1.79 (1.66–1.93) and 0.47 (0.42–0.53) in the UK-Irish collection. Discussion: Trained observers were able to define palmar hyperlinearity in the majority (3191/3656, 87%) of cases. The presence of HLP is not a reliable sign to detect FLG mutations, but the absence of HLP excludes FLG null genotype with a reasonable degree of certainty.

Citation

Bradshaw, L. E., Haines, R. H., Thomas, K. S., Chalmers, J. R., Irvine, A. D., Williams, H. C., & Brown, S. J. (2021). Clinical examination for hyperlinear palms to determine filaggrin genotype: A diagnostic test accuracy study. Clinical and Experimental Allergy, 51(11), 1421-1428. https://doi.org/10.1111/cea.14025

• Journal Article Type: Article
• Acceptance Date: Sep 22, 2021
• Online Publication Date: Oct 18, 2021
• Publication Date: Nov 1, 2021
• Deposit Date: Nov 8, 2021
• Publicly Available Date: Nov 8, 2021
• Journal: Clinical and Experimental Allergy
• Print ISSN: 0954-7894
• Electronic ISSN: 1365-2222
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 51
• Issue: 11
• Pages: 1421-1428
• DOI: https://doi.org/10.1111/cea.14025
• Keywords: Immunology; Immunology and Allergy
• Public URL: https://nottingham-repository.worktribe.com/output/6673827
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/cea.14025