The correct answer is:

Test patient for the human leukocyte antigen (HLA)-B*58:01 allele.

Educational Objective:

Treat gout and hyperuricemia, recognizing the increased risk of allopurinol toxicity in some patients of Asian descent.

Key Point:

Before treating gout patients of Chinese, Thai, or Korean descent with allopurinol, test them for the human leukocyte antigen (HLA)-B*58:01 allele.

Explanation:

This patient has had multiple gout flares and has had uric acid kidney stones. His uric acid level is elevated, and he is a candidate for uric acid lowering therapy.

Initial therapy, after lifestyle intervention, for most patients, is treatment with a xanthine oxidase inhibitor.

The commonly available xanthine oxidase inhibitors are allopurinol and febuxostat.

Allopurinol is preferred, as febuxostat carries an FDA warning for increased all-cause mortality.

Uricosuric therapy, such as probenecid, is usually second line therapy for patients with inadequate urinary excretion of uric acid.

Uricosuric drugs are contraindicated in patients, such as this one, who have had uric acid kidney stones, since increased uric acid urinary levels could precipitate more stones.

Patients who possess the human leukocyte antigen (HLA)-B*58:01 allele should not be treated with allopurinol, as they have a several-hundred-fold increased risk of severe cutaneous or hypersensitivity reactions to allopurinol. That allele is much more common among patients of Chinese, Thai, and Korean descent than among Caucasians.

When allopurinol is started, the initial dose should be 100mg, as starting with a low dose helps to reduce the incidence of severe reactions.

Subsequently, the uric acid levels should be checked after two weeks, and the drug titrated until the uric acid levels are less than 6 mg/dL.

More than half of patients will require an allopurinol dose greater than 300 mg daily to achieve that goal, and allopurinol is approved for daily dosage up to 800 mg daily.

Treatment to target uric acid levels is important, since uric acid crystals precipitate from solution at a level of 6.8 mg/dL or higher. Particularly in tophaceous gout, lower levels will help to resolve crystalline deposits.

References

Seth R, Kydd AS, Buchbinder R, et al. Allopurinol for chronic gout. Cochrane Database Syst Rev 2014

White WB, Saag KG, Becker MA, et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med 2018; 378:1200

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 2012; 64:1431

Zhang W, Doherty M, Bardin T, et al. EULAR evidence-based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006; 65:1312

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