HLA‐B*58:01 allele is strongly associated with allopurinol‐induced severe cutaneous adverse reactions in a Thai population

Abstract

Background Allopurinol has been reported as the most frequent causes of SCARs (severe cutaneous adverse reactions) in Thailand. Recent publications have shown that HLAB*58:01 allele is a strong marker for allopurinol-induced SJS/TEN (Stevens-Johnson syndrome/toxic epidermal necrolysis). The aim of this study was to clarify the association of allopurinol-induced SCARs with the HLA-B*58:01 allele in Thai patients. Method To investigate this relationship, we performed PCR-SSOP (sequence specific oligonucleotide probe) on allopurinoltolerant controls (n=56) and patients affected by allopurinol-induced SCARs (n=14). Among of allopurinol-induced SCARs, including 3 patients with allopurinol-induced DRESS (drug reaction with eosinophilia and systemic symptoms), 9 patients with SJS/TEN and 2 patients with MPE (maculo-papular exanthema) were included. The presence of HLA-B*58:01 allele were genotyped by PCRSSOP method at Laboratory for Pharmacogenomics, Ramathibodi Hospital. Results Of the 14 patients with allopurinol-induced SCARs, 13 (92.8%) patients (3 DRESS, 9 SJS/TEN and one severe MPE) had HLA-B*58:01 while only 6 (10.71%) of the allopurinol-tolerant controls had this allele. The risk of allopurinol-induced SCARs was significantly higher in the patients with HLA-B*58:01 with an OR (odd ratios) of 108.33 (95% CI 11.96-980.82, p<10-6). When compared with normal population, HLA-B*58:01 was associated with a higher risk of SCARs, both DRESS (OR: 80, 95% CI 3.42-372.87) and SJS/TEN (OR: 217.26, 95%CI 12.41-925.35). Conclusion In this study we confirmedthat HLA-B*58:01 allele is strongly associated with allopurinol-induced SCARs in Thai population. Therefore, screening tests for HLAB*58:01 allele in patients who will be treated with allopurinol will be clinically helpful in preventing the risk of developing SCARs.