HLA‐B*58:01 is a risk factor for allopurinol‐induced DRESS and Stevens–Johnson syndrome/toxic epidermal necrolysis in a Portuguese population. (30th August 2013)

• Record Type: Journal Article
• Authors: Gonçalo, M.; Coutinho, I.; Teixeira, V.; Gameiro, A.R.; Brites, M.M.; Nunes, R.; Martinho, A.
• Is Part Of: British journal of dermatology. Volume 169:Number 3(2013:Sep.)
• Page Start: 660
• Page End: 665
• Publication Date: 2013-08-30
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.12389
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: HLA‐B *58:01 is associated with allopurinol‐induced severe cutaneous adverse drug reactions (sCADR) particularly in Han Chinese, but the risk in European populations has seldom been studied. Objective: To study the association of HLA‐B *58:01 with allopurinol‐induced sCADR in a Portuguese population. Methods: We studied 25 patients (11 male/14 female, mean age 67·4 years) with sCARD from allopurinol: 19 DRESS (drug reaction eosinophilia and systemic symptoms) and six Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). HLA was genotyped by reverse sequence‐specific oligonucleotide–polymerase chain reaction and results compared statistically with a control group of 23 allopurinol‐tolerant individuals and the control population. Results: HLA‐B *58:01 was present in 16 patients with sCADR (64%) [12 DRESS (63%), four SJS/TEN (67%)], one allopurinol‐tolerant individual (4%) and 63 normal controls (1·96%), with a statistically significant difference between sCADR and the two control groups. When compared with the normal population, HLA‐B *58:01 was associated with a higher risk of sCADR, both DRESS [odds ratio (OR) 85·36, 95% confidence interval (CI) 32·52–224·04] and SJS/TEN (OR 99·59, 95% CI 17·91–553·72). There was no statistically different risk between these two types of CADR. Conclusions: Portuguese patients with sCADR from allopurinol, both DRESS and SJS/TEN, have a high frequency of HLA‐B *58:01, with an OR similar to European patients with SJS/TEN. This study also extends this association to DRESS in Europeans. The recommendation to genotype systematically before therapy is controversial, particularly when HLA‐B*58:01 prevalence in the normal population is low, as in Europe. However it could be an option for patients with other risks factors. Abstract : What's already known about this topic? Allopurinol‐induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS in Han Chinese occur almost exclusively in HLA‐B*58:01 ‐positve individuals. A less strong association with HLA‐B*58:01 and allopurinol‐induced SJS/TEN is observed in Europeans. What does this study add? In a European population, HLA‐B*58:01 is also associated with DRESS, with a similar strength as for SJS/TEN. With a low prevalence of HLA‐B*58:01 in Europeans and a less strong association, systematic genotyping before allopurinol therapy remains controversial.