Diagnostic Tests

What Physicians Need to Know

Allopurinol Hypersensitivity Assay HLA-B*58:01 Genotyping

 

Am Fam Physician. 2019 Nov 1;100(9):530-531.

The allopurinol hypersensitivity assay, or HLA-B*58:01 test, is a blood test to detect the presence of a human leukocyte antigen B (HLA-B) genetic variant that increases the risk of life-threatening, severe cutaneous adverse reactions in patients taking allopurinol. Although the HLA-B*58:01 test has not been approved by the U.S. Food and Drug Administration, the American College of Rheumatology and the Clinical Pharmacogenetics Implementation Consortium recommend it for select populations before initiation of allopurinol therapy.1,2

Accuracy

A systematic review including 7,534 patients found that the HLA-B*58:01 test is 78% sensitive and 96% specific, with a negative predictive value of 99% for the development of severe cutaneous adverse reactions associated with allopurinol treatment. Most patients in the study were Asian. No studies from America, India, or Africa were identified.3 Depending on the technology used, it may take up to three weeks to receive test results.4 The absence of the HLA-B*58:01 allele does not eliminate the risk of severe cutaneous adverse reactions because additional factors such as renal impairment and concurrent thiazide use have also been shown to increase risk.1

Benefit

In patients with the HLA-B*58:01 allele, the odds ratio for the development of a severe cutaneous adverse reaction is 74 (95% CI, 27 to 204) in Asians and 101 (95% CI, 45 to 229) in non-Asians.5,6 These reactions occur at a baseline rate of 0.69 per 1,000 person-years among allopurinol users in the United States. Patients hospitalized with severe cutaneous adverse reactions in the United States have a mortality rate of 27%.5

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TestIndicationPopulation, age range, and frequencyCost*

HLA-B*58:01 genotyping

Individuals being considered for long-term gout prophylaxis with allopurinol

Highest yield in Korean adults with stage 3 or higher chronic kidney disease and in all adults of Han Chinese or Thai descent

$170

Test once per lifetime


HLA-B = human leukocyte antigen B.

*—Payment rate according to the 2019 Centers for Medicare and Medicaid Services clinical laboratory fee schedule.10

TestIndicationPopulation, age range, and frequencyCost*

HLA-B*58:01 genotyping

Individuals being considered for long-term gout prophylaxis with allopurinol

Highest yield in Korean adults with stage 3 or higher chronic kidney disease and in all adults of Han Chinese or Thai descent

$170

Test once per lifetime


HLA-B = human leukocyte antigen B.

*—Payment rate according to the 2019 Centers for Medicare and Medicaid Services clinical laboratory fee schedule.10

In a prospective study, 2,910 Taiwanese patients with recurrent gout underwent

Address correspondence to Carl Bryce, MD, at carlbryce13@gmail.com. Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431–1446....

2. Saito Y, Stamp LK, Caudle KE, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update. Clin Pharmacol Ther. 2016;99(1):36–37.

3. Yu KH, Yu CY, Fang YF. Diagnostic utility of HLA-B*5801 screening in severe allopurinol hypersensitivity syndrome: an updated systematic review and meta-analysis. Int J Rheum Dis. 2017;20(9):1057–1071.

4. Nguyen DV, Vida C, Chu HC, et al. Validation of a rapid, robust, inexpensive screening method for detecting the HLA-B*58:01 allele in the prevention of allopurinol-induced severe cutaneous adverse reactions. Allergy Asthma Immunol Res. 2017;9(1):79–84.

5. Kim SC, Newcomb C, Margolis D, et al. Severe cutaneous reactions requiring hospitalization in allopurinol initiators: a population-based cohort study. Arthritis Care Res (Hoboken). 2013;65(4):578–584.

6. Cheng CY, Su SC, Chen CH, et al. HLA associations and clinical implications in T-cell mediated drug hypersensitivity reactions: an updated review. J Immunol Res. 2014;2014:565320.

7. Ko TM, Tsai CY, Chen SY, et al. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ. 2015;351:h4848.

8. White WB, Saag KG, Becker MA, et al.; CARES Investigators. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med. 2018;378(13):1200–1210.

9. Jutkowitz E, Dubreuil M, Lu N, et al. The cost-effectiveness of HLA-B*5801 screening to guide initial urate-lowering therapy for gout in the United States. Semin Arthritis Rheum. 2017;46(5):594–600.

10. Centers for Medicare and Medicaid Services. Clinical laboratory fee schedule. Accessed September 23, 2019. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/index.html.

This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

 

 

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