allopurinol hypersensitivity syndrome

allopurinol hypersensitivity syndrome (AHS)?

• • AHS is a rare (0.1%–0.4% of patients) complication of allopurinol use with high morbidity and mortality (25% in some studies).
• • AHS typically occurs 2 to 4 weeks after initiating therapy.
• • Clinical manifestations include severe skin rash (e.g., Stevens–Johnson syndrome, toxic epidermal necrolysis), fever, eosinophilia, hepatic necrosis, leukocytosis, and renal failure.
• • Treatment of AHS includes high-dose steroids and hemodialysis (to remove oxipurinol).

Which patients are most at risk of developing AHS?

• • Risk factors for developing AHS include: female sex, history of rash on allopurinol (5%–10% of patients, avoid in this setting), renal insufficiency, concomitant diuretic therapy, and elderly.
• • HLA-B∗5801 in patients of Korean descent with CKD stage 3 or worse, and in ethnic Han Chinese and Thai patients.

Pearl: starting dose of allopurinol is associated with AHS. Start at 100 mg daily if GFR >30 mL/minute (50 mg daily for GFR ≤30 mL/minute) and titrate every 2 to 4 weeks by 100-mg increments (50 mg for GFR <30 mL/minute). Start low and go slow.

Pearl: ask patients about ethnic background regardless of the country of origin. Check HLA-B∗5801 prior to starting allopurinol in those of Korean descent with CKD stage 3 or worse, and in all ethnic Han Chinese and Thai patients. Avoid allopurinol if HLA-B∗5801 is present in these patients.