Severe Cutaneous Reactions Requiring Hospitalization in Allopurinol Initiators: A Population‐Based Cohort Study

Abstract

Background Rare but potentially life-threatening cutaneous adverse reactions have been associated with allopurinol, but population-based data on incidence and mortality of such reactions is scarce. Methods We conducted a propensity score-matched cohort study to evaluate incidence rate (IR) and in-hospital mortality of hospitalization for severe cutaneous adverse reactions (SCARs) in allopurinol initiators compared to non-allopurinol users, using data from five large Medicaid programs. The primary outcome was identified by the principal discharge diagnosis code 695.1. Cox proportional hazards model evaluated the relative risk of SCARs associated with use of allopurinol and determined the relative risk of SCARs associated with allopurinol dose. Results During a follow-up period of 65,625 person-years for allopurinol initiators, 45 were hospitalized with SCARs. The crude IR was 0.69 (95% CI 0.50–0.92) per 1,000 person-years. All 45 cases occurred within 365 days and 41 (91.1%) within 180 days after initiating treatment with allopurinol. Twelve (26.7%) patients died during the hospitalization. The crude IR in non-allopurinol users was 0.04 (95% CI 0.02–0.08) per 1,000 person-years. The risk of SCARs was increased in allopurinol initiators vs. non-users (HR 9.67, 95% CI 4.55–20.57). Among allopurinol initiators, the HR for the high- (>300mg/day) vs. low-dose allopurinol was 1.30 (95% CI 0.31–5.36) after adjusting for age, comorbidities and recent diuretic use. Conclusions Among allopurinol initiators, SCARs were found to be rare but often fatal and occurred mostly in the first 180 days of treatment. The risk of SCARs was ten times as high in allopurinol initiators compared to allopurinol non-users.

Severe Cutaneous Adverse Drug Reactions Associated with Allopurinol: An Analysis of Spontaneous Reporting System in Southern Italy

“…Compared to all ADRs associated with allopurinol, serious cutaneous ADRs more commonly presented unfavorable outcomes (46%). In line with our results, Kim et al [48] showed that although the incidence of hospitalization due to the occurrence of SCARs is < 1/1000 person-year, the in-hospital mortality is around 27%. Further studies confirmed that SCARs frequently led to patients' hospitalization and unfavorable outcomes [49][50][51][52] and that these ADRs were often acute emergencies [53].…”

Adherence and Outcomes with Urate-Lowering Therapy: A Site-Randomized Trial

“…Recognizing that allopurinol dose escalation is associated with an increased risk of severe cutaneous reactions, we examined the frequency of this complication. In line with reported frequencies 39,40 , we observed two related events, one with usual care and one with the intervention. Both cases occurred with "low dose" allopurinol (100 mg/day) more than one year after allopurinol initiation, outside the risk window typically attributed to hypersensitivity 41 .…”

Reply to “Restricting maintenance allopurinol dose according to kidney function in patients with gout is inappropriate!” by Stamp et al.

“…Thirdly, we agree with Stamp et al that allopurinol hypersensitivity syndrome (AHS) is a rare but very serious adverse drug reaction, with a high mortality rate . The EuroSCAR study revealed that allopurinol was the drug most commonly associated with Stevens‐Johnson syndrome and toxic epidermal necrolysis .…”