TOPLINE:

A small study tied specific human leukocyte antigen (HLA) class I alleles to a higher risk for allopurinol-induced severe cutaneous adverse reactions (SCARs) in the US. 

METHODOLOGY:

• Researchers analyzed 16 patients (mean age, 61.1 years; 56.3% women; 69% Black and 31% White individuals) with specialist-adjudicated allopurinol-induced SCARs. All but one patient had gout.
• Adult control individuals with allopurinol tolerance (n = 1122) from the Vanderbilt University Medical Center biobank were identified, and 160 matched control individuals were selected.
• HLA class I and II alleles were imputed from genotyping array data, and HLA typing was performed using Illumina MiSeq.
• Carriage of HLA class I and II alleles was compared between patients with allopurinol-induced SCARs and control individuals with allopurinol tolerance.

TAKEAWAY:

• The HLA class I allele HLA-B*58:01 was associated with an increased risk for allopurinol-induced SCARs (odds ratio [OR], 28.0; Bonferroni-corrected P < .001).
• HLA-B*58:01 was present in 62.5% of patients with allopurinol-induced SCARs compared with 5.6% of matched control individuals with allopurinol tolerance and 2.3% of the overall population (P < .001 for both).
• The HLA class I allele HLA-A*34:02 was found in 18.8% of patients with allopurinol-induced SCARs compared with 1.3% of the overall population (P = .001).
• Homozygosity vs heterozygosity in HLA-B*58:01 was linked to an increased risk for allopurinol-induced SCARs (OR, 55.3; 95% CI, 2.5-1208.6).

IN PRACTICE:

“The absence of HLA-B*58:01 in more than one third of the cohort and the identification of HLA-A*34:02 as an additional risk allele exemplify that population-based studies and multiallelic testing are needed to mitigate harm among those most vulnerable to these severe, life-threatening reactions,” the authors wrote.

SOURCE:

The study was led by Chelsea N. Campbell, MS, and Matthew S. Krantz, MD, Vanderbilt University Medical Center, Nashville, Tennessee. It was published online on October 29, 2025, in JAMA Dermatology.

LIMITATIONS:

The study’s sample size was small.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health; the American Academy of Allergy, Asthma & Immunology Foundation; and other sources. One author reported receiving personal fees from various sources outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.