HLA-B*58:01is a risk factor for allopurinol-induced DRESS and Stevens–Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

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Abstract

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.

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