Background Allopurinol allergy (drug eruption, severe cutaneous adverse reactions [SCAR] and drug induced hypersensitivity syndrome [DiHS]) develops during the first 2–12 weeks after initiation. SCAR risk factors include Chinese ethnicity, HLA-B*5801 positivity and chronic kidney disease. HLA-B*5801 testing to prevent SCAR has not been shown to be cost-effective in Singapore.
Objectives To retrospectively study whether a structured monitoring program (SMP) can lead to early diagnosis of allopurinol allergy and prevent development of SCAR/DiHS.
Methods SMP patients (cases) managed by rheumatologists were compared with controls managed by non-rheumatologists during the study period 1 Jan 2015 to 30 Jun 2016. Cases upon initiation of allopurinol had baseline full blood count (FBC), serum creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) measured. If drug eruptions/abnormal laboratory tests developed during monitoring, allopurinol was stopped. The electronic dispensing system and computerized medical records were used for collection of patient demographics, indication for allopurinol use, initiation dose, monitoring intervals, laboratory results and clinical features of drug allergy. This was compared with the control group without an SMP. Chi square tests were used to compare differences in proportions and Mann-Whitney U test for differences in medians. P value ≤0.05 was considered statistically significant.
Results There were 61 cases and 30 controls with comparable age (p=0.81), ethnicity (>80% Chinese) (p=0.63) and estimated glomerular filtration rate, eGFR (p=0.72). There were significantly more cases with tophaceous gout (41% vs 10%, p=0.003), while more controls tumour lysis syndrome prophylaxis (30% vs 0%, p<0.001). Median (interquartile range, IQR) starting dose of 50 (50) mg was lower among cases versus controls of 100 (200) mg (p<0.001); all cases had baseline and follow-up laboratory tests compared to controls (p<0.001). Cases were followed up at a median (IQR) of 2 (1.1) weeks after initiation then 5 (2.0) weeks after the first visit, whereas controls were reviewed 8 (8.9) weeks after initiation, then 11 (4.6) weeks after the first visit. Two patients in the SMP group with normal eGFR developed maculopapular eruption (MPE), 1 elevated ALT/AST, and 1 both MPE and elevated ALT/AST within the first 14 days of initiation. One control with lymphoma and baseline eGFR 31 ml/min/1.73m2 developed DiHS (fever, MPE, elevated ALT/AST less than twice upper limit of normal) 43 days after initiation for tumour lysis prophylaxis. This occurred while on 2-weekly monitoring of FBC, ALT, AST. There were no cases of SCAR in both groups.
Conclusions SMP facilitates early diagnosis of allopurinol allergy/DiHS which occurred during the first 2–6 weeks after initiation. Whether early cessation of allopurinol prevents development of SCAR, and reduces the need for HLA-B*5801 testing will require a larger prospective study.
Wang CW, Dao RL, Chung WH. Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions. Curr Opin Allergy Clin Immunol 2016;16:339–45.
Dong D, Tan-Koi WC, Teng GG, Finkelstein E, Sung C. Cost-effectiveness analysis of genotyping for HLA-B*5801 and an enhanced safety program in gout patients starting allopurinol in Singapore. Pharmacogenomics 2015;16:1781–93.
Disclosure of Interest None declared