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HLA B5801

Approximately 1 in 1000 patients who are prescribed allopurinol for gout develop the allopurinol hypersensitivity syndrome, which includes Stevens- Johnson Syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS). These syndromes can be severe and have a mortality rate approaching 25%.

The presence of the HLA-B*5801 allele is strongly associated with allopurinol hypersensitivity syndrome.This allele is most prevalent in people of Han Chinese, Korean, and Thai descent. The risk of allopurinol hypersensitivity syndrome is highest in the initial months after starting allopurinol therapy and might be dose dependent. Additional risk factors include renal impairment and concurrent thiazide use.

The 2012 American College of Rheumatology (ACR) Guidelines for Management of Gout recommended that high risk populations be tested for HLA-B*5801 allele prior to initiation allopurinol therapy. This recommendation included patients of Korean descent with stage 3 chronic kidney disease or higher and patients of Han Chinese or Thai extraction irrespective of their renal function. Koreans have an HLA–B*5801 allele frequency of 12% and Han Chinese or Thai have an HLA–B*5801 allele frequency of 6 to 8%.

Patients testing positive for HLA-B*5801 should be prescribed an alternative to allopurinol, such as febuxostat or probenecid. Testing for HLA-B*5801 in high-risk populations is probably more cost-effective than automatic substitution of allopurinol with febuxostat, which is more expensive and might have increased cardiovascular risks.

The absence of HLA-B*5801 does not completely eliminate the risk of allopurinol hypersensitivity syndrome in patients taking allopurinol because, as mentioned above, other factors contribute to development of allopurinol hypersensitivity syndrome.

The American College of Rheumatology did not recommend allele testing of low risk populations, such as white, African American or Hispanic patients. Whites and Hispanics have an HLA–B*5801 allele frequency of less than 1% and African Americans 3.8%.

The preferred method for HLA–B*5801 allele testing is polymerase chain reaction (PCR). Only 10% of those tested have indeterminate results, requiring the more expensive technique of HLA–B*5801 gene sequencing.

References

Khanna D, et al. American College of Rheumatology guidelines for management of gout. Part 1. Arthritis Care Res. 2012;64, (10): 1431–1446.

Quach C and Galen BT. HLA-B*5801 testing to prevent allopurinol hypersensitivity syndrome: A teachable moment. JAMA published on line August 6, 2018, E1-E2.

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