Authors (including presenting author) :
CHAN PSJ (1), Ng SN (1), LEUNG MH (1)
Affiliation :
(1) Deparement of Medicine, Queen Elizabeth Hospital, Hong Kong
Introduction :
Allopurinol is one of the most common causes of drug-induced severe cutaneous adverse reaction (SCAR) and HLA-B*58:01 gene positivity is shown to be the strongest risk factor. Till now, 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 audit aims to review (1) the use of HLA-B*58:01 and (2) its clinical implication in a regional hospital in Hong Kong.
Methodology :
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.
Result & Outcome :
Results Within 10 years, 432 patients had HLA-B*58:01 checked - 23% (N=99) were positive. 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. 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. 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. Conclusions 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 induced SCAR.
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