SAT0438\u2005TO SCREEN OR “WAIT AND SEE” – CAN HLA GENE TESTING PREVENT ALLOPURINOL RELATED SEVERE CUTANEOUS ADVERSE REACTION? AND WHO ARE AT RISK?

Abstract

Background Allopurinol is one of the most common causes of drug-induced severe cutaneous adverse reaction (SCAR). HLA-B*58:01 gene positivity is shown to be the strongest risk factor. However, local data on HLA-B*58:01 test and allopurinol-related SCAR is scanty. Moreover, there is no consensus on routine checking of HLA-B*58:01 before starting allopurinol in Hong Kong and this test is performed according to physicians’ clinical judgement. Objectives This study review the use of HLA-B*58:01 in daily practice, included the clinical characteristics and its implications in patients who developed allopurinol allergy in a tertiary internal medicine and rheumatology referral center. Methods This is a retrospective study of patients who had HLA-B*58:01 checked in Queen Elizabeth Hospital from January 2008 to December 2017. Patients’ demographic data, clinical characteristics, laboratory findings, gene profile, drug allergy records were retrieved from Clinical Data Analysis and Reporting System and outcomes were reviewed. Results Within 10 years, 432 patients had HLA-B*58:01 checked - 23% (N=99) were positive (Figure 1). Among patients who were HLA-B*58:01 positive, 86% had clinical and/or crystal proven gout and 68% were male (M:F=67:32). Gene testing was performed as screening in 58% (57/99) and after skin reaction in 42% (42/99). Alternative urate lowering therapy was considered for patients who screened positive for HLA-B*58:01 and none developed SCAR (Febuxostat 16 patients, probenecid 3 patients). For those who reported skin reaction after allopurinol, 50% had minor rash while 50% (each 21 patients) developed SCAR. In SCAR-group, 52% was male, 76% were chronic kidney disease (CKD) ≥stage 3 and/or age ≥60years, with mean age 71.2+/-14.2 and mean estimated glomerular filtration rate 57.1+/-30.7 mL/min/1.73m2 (Figure 2 and table 1). The mean time interval to SCAR was 44.8+/-52.1 days and the mean starting dose of allopurinol was 154.6+/-90.7 mg/day. SCAR was associated with substantial morbidity and mortality: 71% (15/21) required steroid and/or intravenous gammaglobulin in addition to supportive care and 17% (4/21) died in the same admission due to sepsis including pneumonia. For patients who were tested negative for HLA-B*58:01, although 12% reported skin reaction, these were self-limiting and all recovered after allopurinol was stopped. Renal impairment was less pronounced in this group, yet 38% were CKD ≥stage 3. Conclusion In our cohort, HLA-B*58:01 can identify most of the high risk patients who prompt to develop SCAR. Thus in routine practice, clinicians should consider screening HLA-B*58:01, especially in patients with CKD ≥stage 3 or age ≥60year, before starting allopurinol, and consider alternatives if positive, to prevent allopurinol-related SCAR. References [1] Richette P, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29-42. [2] Wang YH, et al. The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label. Clin Pharmacol Ther. 2018. [3] Khanna D, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-46. [4] 4. Stamp LK, Barclay ML. How to prevent allopurinol hypersensitivity reactions? Rheumatology (Oxford). 2018;57(suppl_1):i35-i41. Acknowledgement We would like to thank Mr. Kwok MF for his support in acquisition of data. Disclosure of Interests None declared