In a 53-year-old Thai man with gout, hypertension, moderate chronic kidney disease, and elevated serum uric acid, what is the most appropriate next step in management?

HLA-B*5801 Testing Before Allopurinol Initiation

Order HLA-B*5801 allele testing before starting allopurinol in this Thai patient, as this is conditionally recommended by the American College of Rheumatology for all patients of Thai descent regardless of renal function. 1

Rationale for Testing in Thai Patients

The HLA-B5801 allele is strongly associated with allopurinol hypersensitivity syndrome (AHS), a potentially fatal reaction with a reported mortality rate of 20-25%. 1 Thai patients have a particularly high prevalence of this allele (6-8%) and demonstrate hazard ratios of several hundred for developing AHS when HLA-B5801 positive. 1

The 2020 ACR guidelines specifically recommend HLA-B*5801 testing for patients of Southeast Asian descent (including Han Chinese, Korean, and Thai) prior to allopurinol initiation. 1 This recommendation applies to Thai patients regardless of their renal function status. 1

Why Testing Takes Priority Over Immediate Treatment

• Testing is a one-time, relatively inexpensive PCR-based test that can prevent a life-threatening hypersensitivity reaction. 1
• The test results will guide whether allopurinol can be safely initiated or whether an alternative urate-lowering therapy (such as febuxostat) should be prescribed instead. 1
• If HLA-B*5801 positive, allopurinol should be avoided and an alternative agent selected. 1
• If HLA-B*5801 negative, allopurinol can be safely initiated with appropriate low-dose start and gradual titration. 1

Why Other Options Are Inappropriate

Probenecid is not appropriate because this patient has stage 3 CKD, and uricosuric agents are not recommended as first-line monotherapy when creatinine clearance is <50 mL/min. 1, 2

Beginning allopurinol immediately without testing would expose this high-risk Thai patient to potential AHS without appropriate risk stratification, which contradicts guideline recommendations. 1

Measuring antinuclear antibodies has no role in gout management or allopurinol initiation decisions. 1

Aspirin is not indicated for gout management and can actually worsen hyperuricemia at low doses. 1

Subsequent Management After Testing

Once HLA-B*5801 testing confirms the patient is negative:

• Start allopurinol at 50 mg daily (lower dose due to stage 3 CKD) rather than the standard 100 mg. 1, 3
• Titrate upward by 50-100 mg every 2-5 weeks to achieve serum urate target <6 mg/dL. 1, 4
• Doses can exceed 300 mg daily even with CKD as long as accompanied by adequate patient education and monitoring for drug toxicity (pruritis, rash, elevated liver enzymes). 1
• Provide flare prophylaxis with colchicine, NSAIDs, or low-dose corticosteroids for 3-6 months during initiation. 3, 5, 4

Critical Safety Monitoring

• Monitor for signs of hypersensitivity including rash, fever, eosinophilia, hepatitis, or worsening renal function throughout treatment. 3
• Check serum uric acid every 2-5 weeks during dose titration. 3, 5
• Continue monitoring renal function regularly as worsening kidney function can be a component of AHS. 3