HLA-B*58:01 and Risk of Allopurinol-Induced Severe Cutaneous Adverse Reactions in the US

Is the association between HLA-B*58:01 and allopurinol-induced severe cutaneous adverse reactions (SCARs) generalizable to admixed populations in the US, or are additional HLA associations involved?In this genetic association study of 16 patients with adjudicated allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms from a heterogenous US-based population, an association with the established risk allele HLA-B*58:01 was demonstrated, and HLA-A*34:02 was identified as an additional independent risk factor.These finding suggest that, although HLA-B*58:01 was found to be associated with allopurinol-induced SCARs, the allele was absent in more than one-third of the US patient cohort and is therefore an incomplete indicator of risk.

Corresponding Author: Elizabeth J. Phillips, MD, Center for Drug Safety and Immunology, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Ave S, Nashville, TN 37232 (elizabeth.j.phillips@vumc.org).

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