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Figure 1. Article selection process. [dagger] Some records were included in more than one category.
(Figure omitted. See article PDF.)
Allopurinol, a xanthine oxidase inhibitor, is the most prescribed agent for long-term prevention of recurrent gout and hyperuricemia. Other indications for allopurinol therapy include urate nephropathy and tumor lysis prophylaxis [1]. Nevertheless, the use of allopurinol is associated with various immune-mediated cutaneous adverse drug reactions (cADRs), which range from simple skin rash to rare severe cutaneous drug reactions (SCARs) such as drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DRESS/DIHS encompasses severe skin eruption with multiple systemic manifestations, including fever, eosinophilia and internal organ involvement [2]. SJS and TEN are characterized by painful blistering lesions, severe skin detachment and systemic symptoms such as respiratory symptoms, fever and headaches. They are considered as 'two forms of the same disease' [3], with TEN associated with a larger body surface involvement (typically >30%) [4]. Mortality rates as high as 5-10% and 30-40% have been reported for SJS and TEN, respectively [4]. A multinational case-control study [5] reported that allopurinol is the drug associated the most with SJS/TEN. The incidence of these cADRs varies between populations, being most frequent in Asian populations and much rarer in Caucasians. Other allopurinol-induced cADRs include maculopapular eruption (MPE) and erythema multiform major (EMM) [6].
In the last decades, studies have attempted to identify a genetic predisposition to these allopurinol-induced cADRs. Hung et al . [7] were the first to describe a strong association between HLA genomic markers and the risk of developing SJS/TEN in Han Chinese patients. Since then, a growing number of studies confirmed this association in other populations with variable results among ethnic groups. Genome-wide association studies (GWAS) have also been performed to identify new genetic markers for allopurinol-induced SCARs [4,8]. Given this wealth of information, we performed a systematic review to summarize the existing evidence regarding the pharmacogenomics of allopurinol-induced drug hypersensitivity.
Methods
Information sources & search & study selection
A systematic search was performed using the PubMed interface by two of the authors (S Jarjour and M Barrette). The search terms used were 'allopurinol' AND ('genotype' OR 'genetics') including all subcategories. Not enabling the Medical Subject Headings...