1. HLA-B*58:01 remained the strongest predictor of allopurinol-induced severe cutaneous adverse reactions, but more than one-third of affected patients did not carry the allele.
2. HLA-A*34:02 was identified as a second independent genetic risk factor, showing a strong association even after statistical correction.
3. A gene-dose effect was observed for HLA-B*58:01, with homozygous carriage conferring markedly increased risk.
4. HLA-B*58:01 screening alone may miss a substantial proportion of at-risk patients, particularly in genetically diverse U.S. populations.
5. Broader HLA testing may improve risk stratification, especially for patients who require allopurinol and are from populations with varied allele frequencies.

Source: JAMA Dermatology