Study IDs Additional Risk Allele in Allopurinol-Induced Cutaneous Reactions in US Patients
Key Takeaways
HLA-A*34:02 was independently associated with allopurinol-induced SCARs in a US cohort, a new analysis found.
The allele remained a strong risk factor but was absent in more than one-third of patients.
A recently published genetic association study has identified HLA-A34:02 as an independent allele significantly associated with severe cutaneous adverse reactions (SCARs) to allopurinol in a US-based cohort.
Researchers from Vanderbilt University Medical Centerstudied compared data from 16 patients diagnosed with allopurinol-induced SCARs between 2015 and 2024 to 160 matched allopurinol-tolerant controls and a larger biobank population of 94,489 individuals with imputed HLA data. Patients and controls were matched on age, sex, and self-reported race, and HLA class I and II alleles were analyzed using conditional logistic regression.
According to the data, two HLA class I alleles showed associations with increased SCAR risk after Bonferroni correction (HLA-B58:01(OR = 28.0; 95% CI, 8.6 to 100.6) and HLA-A34:02 (OR = 20.6; 95% CI, 3.3 to 131.1). The absence of HLA-B*58:01 in over one-third of affected individuals showed a need for additional markers of risk, the researchers noted.
“These findings suggest that although HLA-B58:01 was found to be associated with allopurinol-induced SCARs, generalizing findings from previous studies, the allele was absent in more than one-third of the patient cohort and is therefore an incomplete indicator of risk,” the authors wrote. “Importantly, in the US allopurinol-induced SCAR cohort, HLA-A34:02 was found to be a second independent genetic risk factor for allopurinol-induced SCARs. These findings underscore the need to conduct population-based studies that both reproduce known and uncover novel HLA associations to reduce harm through contributions to screening, risk stratification, and diagnosis.”
Source: Campbell C, et al. JAMA Dermatology. 2025. doi:10.1001/jamadermatol.2025.4240