When is HLA-B 5801 testing indicated before initiating allopurinol (xanthine oxidase inhibitor) therapy?

HLA-B*5801 Testing Before Initiating Allopurinol

HLA-B*5801 testing is strongly indicated before initiating allopurinol in patients of Southeast Asian descent (Han Chinese, Korean, Thai) and African American patients due to their higher prevalence of this allele and increased risk of severe cutaneous adverse reactions. 1

Patient Populations Requiring Testing

High-Risk Groups (Testing Recommended):

• Southeast Asian descent patients:
  • Han Chinese (7.4% prevalence of HLA-B*5801)
  • Korean (12.2% prevalence)
  • Thai populations
• African American patients (3.8% prevalence)

Low-Risk Groups (Testing Not Recommended):

• White/Caucasian patients (0.7% prevalence)
• Hispanic patients (0.7% prevalence)
• Other ethnic backgrounds not specified above

Rationale for Testing

The HLA-B*5801 allele is strongly associated with allopurinol hypersensitivity syndrome (AHS) and severe cutaneous adverse reactions (SCAR) including:

• Stevens-Johnson syndrome (SJS)
• Toxic epidermal necrolysis (TEN)
• Drug reaction with eosinophilia and systemic symptoms (DRESS)

These reactions carry significant morbidity and mortality risks. Testing in high-risk populations is cost-effective with incremental cost-effectiveness ratios <$109,000 per quality-adjusted life year 1.

Clinical Decision Algorithm

1. Determine patient ethnicity/race

   • If Southeast Asian descent or African American → Order HLA-B*5801 testing
   • If other ethnicity/race → Proceed without testing

2. If HLA-B*5801 testing ordered:

   • Positive result → Avoid allopurinol; use alternative therapy (e.g., febuxostat)
   • Negative result → Safe to initiate allopurinol

3. When initiating allopurinol (in HLA-B*5801 negative patients):

   • Start at low doses (≤100 mg daily)
   • Use even lower doses in patients with chronic kidney disease
   • Gradually titrate to achieve target serum urate levels

Important Considerations and Pitfalls

• Subpopulation variations exist: Not all Asian subpopulations carry the same risk. For example, Hmong populations in Minnesota show significantly lower HLA-B*5801 prevalence (2.1%) compared to Han Chinese (19.6%) 2.

• Underutilization of testing: Studies show that HLA-B*5801 testing is underutilized even in areas with large East Asian populations, leading to preventable cases of severe reactions 3.

• Alternative treatment options: For HLA-B*5801 positive patients, febuxostat has been shown to be an effective and safe alternative 4.

• Cost considerations: While cost may be a barrier to implementation in some settings 5, the high mortality and morbidity associated with allopurinol-induced SCAR justifies testing in high-risk populations.

• Avoid generalizing across Asian subpopulations: Significant genetic differences exist between Asian subgroups, requiring careful consideration of specific ancestry rather than broad racial categorization 2.

By following these guidelines for HLA-B*5801 testing before initiating allopurinol, clinicians can significantly reduce the risk of potentially life-threatening adverse reactions while ensuring appropriate treatment for patients with gout.