A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs

Pharmacogenetics and Genomics
C LonjouRegiSCAR study group

Abstract

Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are rare but life-threatening cutaneous adverse reactions to drugs, especially to allopurinol, carbamazepine, lamotrigine, phenobarbital, phenytoine, sulfamethoxazole, oxicam and nevirapine. Recently, a strong association between carbamazepine and allopurinol induced SJS or TEN has been described with respectively, HLA-B*1502 and HLA-B*5801 in a Han Chinese population from Taiwan and other Asian countries. The objective is to further investigate the relationship between SJS/TEN and HLA-B in a large number of patients in a European population. HLA-B genotyping was performed on 150 patients included in a European study (RegiSCAR) of SJS and TEN. We focused on patients related to 'high-risk' drugs including: 31 cases related to allopurinol, 28 to sulfamethoxazole, 19 to lamotrigine and 14 to oxicam. Sixty-one percent of 31 allopurinol-induced SJS/TEN patients carried the HLA-B*5801 allele and the figure was 55% for 27 patients of European ancestry [odds ratio=80 (34-187)], (P<10(-6)) as previously observed in Han Chinese. For other drugs, two rare alleles showed a weaker association with SJS/TEN in a limited number of patients: B*38 for sulfameth...Continue Reading

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