Genetic Risks and Severe Cutaneous Reactions to Allopurinol Save
A matched cohort study shows that HLA-B*58:01 and HLA-A*34:02 are strongly associated with allopurinol-induced severe cutaneous adverse reactions (SCARs), these alleles were absent in more than one-third of those affected, suggesting these are strong but incomplete indicators of SCAR risk.
HLA-B*58:01 (especially in blacks and asians) has been shown to be associated with allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in many populations globally. but does this apply to the USA, where there is a greater ancestral mix?
In this genetic association study they examine 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.
Sixteen patients with specialist-adjudicated allopurinol-induced SJS/TEN or DRESS (collectively allopurinol-induced severe cutaneous adverse reactions [SCARs]) (diagnosed between 2015 and 2024) were matched 1:10 with 160 allopurinol-tolerant individuals.
Two HLA class I alleles were found to be independently associated with increased risk of allopurinol-induced SCAR:
- HLA-B*58:01 (OR, 28.0 [95% CI, 8.6-100.6])
- HLA-A*34:02 (OR, 20.6 [95% CI, 3.3-131.1])
HLA-B*58:01 was absent in more than one-third of the patient cohort, as was HLA-A*34:02.
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