Allopurinol hypersensitivity syndrome (AHS) is a severe adverse drug reaction
Allopurinol hypersensitivity syndrome includes Stevens–Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms. It affects about 1 in 1000 patients prescribed allopurinol, and reported mortality is between 20% and 25%.1 Patients typically present with an exanthem (e.g., morbilliform eruption, erythema multiforme or exfoliative dermatitis), renal impairment, liver injury and eosinophilia. The syndrome may occur within weeks to months of drug exposure, but most cases occur within 8–9 weeks.2
Guidelines recommend screening for the HLA-B*58:01 allele in high-risk populations before starting allopurinol
Risk of AHS is nearly 100-fold higher in carriers of the HLA-B*58:01 allele than in noncarriers.3 Populations with high allele frequency include people of Han Chinese (6%–8%), Korean (12%) and Thai (6%–8%) descent.3 Testing for the allele is widely available in Canada. In the absence of other risk factors, the risk of AHS is low in people with a negative test result for the HLA-B*58:01 allele.4
Chronic kidney disease and cardiovascular disease are clinical risk factors for AHS
Population-based studies have shown an 11-fold increased risk of hospital admission for AHS in patients with chronic kidney disease and cardiovascular disease treated with high doses of allopurinol (> 100 mg/d).5
Starting low-dose allopurinol and titrating slowly might mitigate the risk of AHS
Although the relation between maintenance dose and AHS risk is controversial, allopurinol should be started at a low dose (≤ 100 mg/d) and lower (≤ 50 mg/d) in patients with stage 4 chronic kidney disease or higher.1,2
Treatment includes stopping allopurinol and supportive care
Systemic steroids and immunomodulatory therapies may be useful. Specific treatment depends on whether the patient has Stevens–Johnson syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms. Patients who develop AHS should not be re-exposed to allopurinol; however, alternate urate-lowering therapies (e.g., febuxostat) can be considered.1
Footnotes
Competing interests: Bourne Auguste received speaking honoraria from Baxter Healthcare and Amgen, outside of the submitted work. Jonathan Zipursky received payments from private law firms for medico–legal opinions regarding the safety and effectiveness of drugs, outside of the submitted work. No other competing interests were declared.
This article has been peer reviewed.
References
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