Background/Purpose:

Allopurinol is the first line urate lowering drug used for treatment of gout. Its most feared side effect includes development of hypersensitivity drug reactions which may range from mild maculopapular eruption to life threatening severe cutaneous adverse reactions (SCARs) including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). HLA-B*58:01 is strongly associated with the development of allopurinol-associated SCAR’s in the Han Chinese, Thai and Korean populations. Interestingly, the association between HLA-B*58:01 and SCARs is not as strong in Japanese, European and Australian populations. This suggests that this HLA association with allopurinol-induced SCARs varies with ethnicity. Studies in the United States have suggested that Asians and Blacks have substantially increased risk of allopurinol-associated SJS/TEN as compared to Whites and Hispanics which correlates with the allele frequency (7.4%, 4%, 1% and 1%, respectively).

This study was conducted to evaluate the frequency of the HLA-B*58:01 allele and its possible relationship of allopurinol-associated SCAR’s in a predominately Black or African American population with advanced chronic kidney disease (CKD) undergoing evaluation for renal transplantation. Given that CKD is a risk factor for development of gout, this population of patients is at high risk for development of gout and thus for exposure to allopurinol.

Methods:

All patients with advanced CKD undergoing evaluation for renal transplantation from 5/1/2012 to 8/2/2017 who were genotyped as part of the transplant evaluation within the inclusion period were included in the study and assessment was made of the presence or absence of the HLA-B58:01 allele. The entire cohort was assessed for the presence of a documented allergy to allopurinol.

Results:

From 5/1/2012 to 8/2/2017, 2080 patients were assessed for renal transplantation and genotyped. Of these, 1355 (65%) were Black or African American, 587 (28%) were White, 42 (2%) were Asian. 92 patients were HLA-B*58:01 positive, 77 were HLA-B*58:02 positive and 42 were HLA-B58 positive, but the specific allele was not clear. Of the patients who were HLA-B*58:01 positive, 82 (89%) were Black or African American, 6 (6.5%) were White, 2 (2.2%) were Asian and 2 (2.2%) were another race. The prevalence of HLA-B*58:01 was 6% in this African American or Black population. Only one patient had allopurinol listed as a drug allergy with the reported reaction of DRESS. This patient was HLA-B*58:01 positive and was African American.

Conclusion:

In this cohort of predominately African American patients undergoing evaluation for renal transplant, there was a higher frequency of the HLA-B*58:01 allele in the African American or Black population, however overall incidence of allopurinol-associated SCARs was uncommon. This suggests that despite the increased frequency of the HLA-B*58:01 allele in this population and its noted association with allopurinol-associated SCARs in other ethnicities, genetic testing for the HLA-B*58:01 allele prior to initiation of allopurinol therapy for gout is not warranted in the African American or Black population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hla-b5801-genotype-and-the-risk-of-allopurinol-associated-severe-cutaneous-adverse-reactions-in-a-predominately-black-or-african-american-population-with-advanced-chronic-kidney-disease/