Are blood tests required before initiating allopurinol therapy, including HLA-B*5801 (Human Leukocyte Antigen B*5801) genetic testing and renal function assessment?

Blood Tests Required Before Initiating Allopurinol

Yes, blood tests are required before starting allopurinol—specifically renal function assessment is mandatory for all patients, and HLA-B*5801 genetic testing is strongly recommended for high-risk populations including Southeast Asian descent (Han Chinese, Korean, Thai) and African American patients. 1

Renal Function Assessment (Required for All Patients)

• Baseline renal function testing is essential because impaired kidney function is a major risk factor for allopurinol hypersensitivity syndrome and directly determines safe starting doses 2, 1
• The American College of Rheumatology explicitly recommends against using fixed-dose allopurinol without checking baseline renal function, as this approach fails to achieve target serum uric acid in more than half of patients and increases hypersensitivity risk 1
• Patients with stage 4 or worse CKD should start at 50 mg daily due to greatly prolonged oxipurinol half-life in severe renal impairment 1
• Patients with normal or mildly impaired renal function should start at no more than 100 mg daily to minimize hypersensitivity risk in the first few months of therapy 1
• The combination of renal impairment and HLA-B5801 positivity dramatically compounds risk—patients with homozygous HLA-B5801 and severe renal impairment have an odds ratio of 1269.45 for cutaneous adverse reactions 3

HLA-B*5801 Genetic Testing (Population-Specific)

High-Risk Populations Requiring Testing

• Southeast Asian patients (Han Chinese, Korean, Thai) should undergo HLA-B*5801 testing before allopurinol initiation due to allele frequencies of 6-15% and hazard ratios in the hundreds for severe cutaneous adverse reactions 1, 4
• African American patients should also be tested, with an allele prevalence of 3.8% and a 3-fold increased risk compared to white patients 1, 4
• The 2012 American College of Rheumatology guidelines specifically recommended testing for Korean patients with CKD stage 3 or worse, and all Han Chinese or Thai patients regardless of renal function 2, 4

Clinical Significance of Testing

• The HLA-B*5801 allele confers an odds ratio of 80-580 for allopurinol hypersensitivity syndrome, which carries a 20-25% mortality rate 2, 5, 1
• HLA-B*5801 is the strongest risk factor for allopurinol-induced severe cutaneous adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS 4, 3
• A prospective study demonstrated zero cases of severe cutaneous adverse reactions when HLA-B5801 screening was implemented, compared to 18% in unscreened HLA-B5801-positive patients 6
• In Chinese CKD patients, pre-treatment HLA-B*5801 screening reduced the incidence of severe cutaneous adverse reactions from 2.14% to 0% 7

Action Based on Test Results

• If HLA-B*5801 is positive, prescribe an alternative urate-lowering therapy such as febuxostat rather than allopurinol 1, 4
• HLA-B*5801-negative patients can proceed with allopurinol at appropriate renal-adjusted doses 6, 7
• A tolerance induction protocol over 28 days may be considered for HLA-B*5801-positive patients if alternatives are unavailable, though this requires specialized protocols 6

Cost-Effectiveness

• HLA-B*5801 testing is cost-effective in Asian and African American populations with incremental cost-effectiveness ratios <$109,000 per quality-adjusted life year 5, 1
• Targeted screening in Chinese CKD patients was associated with lower healthcare costs ($92,430 vs $281,226) compared to no screening 7

Important Caveats

• The negative predictive value for HLA-B*5801 is not 100%, meaning a negative test does not completely eliminate risk of hypersensitivity reactions 5
• Europeans and Hispanics have much lower HLA-B*5801 prevalence (0.7-2%), making universal screening less cost-effective in these populations, though testing may still be considered in the presence of CKD stage 3 or worse 4
• Recent therapy initiation itself is a risk factor independent of genetic status, emphasizing the importance of low-dose initiation and gradual titration regardless of testing 2
• Patient education about early signs of hypersensitivity (rash, fever, eosinophilia) requiring immediate medical attention is essential even when testing is performed 4