ALLOPURINOL STARTING DOSE AS A RISK FACTOR FOR ALLOPURINOL HYPERSENSITIVITY SYNDROME IN PATIENTS WITH GOUT

Background: Allopurinol hypersensitivity syndrome (AHS) is a rare but potentially fatal adverse reaction. Dosing guidelines based on creatinine clearance (CrCL) were proposed on recognition that allopurinol ≥300mg/d may be associated with AHS particularly in those with renal impairment. However, the relationship between starting dose of allopurinol and AHS remains controversial. Objectives: To determine the relationship between starting dose of allopurinol and the development of AHS. Methods: A retrospective case-controlled study of patients with gout who developed AHS was undertaken. AHS cases were identified from 1/1/1998 to 31/9/2010 by ICD code search. For each case, three controls receiving allopurinol who did not develop AHS were identified. Controls were matched for known AHS risk factors; gender, diuretic use, age ± 10 years, and eGFR. Results: Fifty-four cases were identified. For 49 cases three well matched controls could be identified and in five cases only two controls could be identified (total 157 controls). Of the cases 55.6% were male, mean age was 64.8 years (24-87), 48.1% were receiving a diuretic and mean eGFR was 50.2ml/min (6-112ml/min). There was good matching between cases and controls. Patients with AHS commenced allopurinol at a significantly higher dose compared to controls (mean dose ± SEM 183.5±10.8mg/d vs. 111.9±6.5 mg/d; p<0.001). Approximately 19% of both cases and controls were commenced on the CrCL-based allopurinol dose. Cases were more likely to be commenced on a higher then CrCL-based dose compared to controls (OR=16.7 (95%CI 5.7-47.6; p<0.001)) and controls were more likely to be commenced on a lower than CrCL-based dose compared to cases (OR=6.9 (95%CI 2.9- 16.5; p<0.001)). The starting dose of allopurinol (corrected for CrCL) was a significant independent risk factor for AHS (Figure 1). Fig. 1. The percentage of patients developing AHS for each quintile of allopurinol dose/CrCL and the odds ratio for eacht quintile (*p<0.05). Conclusions: This is the largest reported case series of AHS. Starting dose is an important risk factor for AHS and there is a clear starting dose-risk relationship. However, AHS may occur at CrCL-based doses, and vigilance is important for all patients starting allopurinol. Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 180Session: Bone and crystal diseases (Poster Presentations )