Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.

Total infusion time: 324 min Volume of each solution administered: solution A,21.25 mL;solution B, 42.25 mL; and solution C, 516.67 mL. Solutions were prepared in the cytotoxicity unit of the pharmacy department. The tubing of each bag is primed with the antineoplastic drug in the pharmacy and connected to a running saline line in close proximity to the patient, thus enabling delivery of small volumes during the initial steps of the desensitization protocol. The protocol was adapted from Castells et al [4]. Irinotecan is always diluted in 500 mL in our hospital, instead of 250 mL, as per the original protocol, and the infusion rate is adapted to that change. No diluent is removed when a solution is prepared owing to our local safety requirements: the amounts added are 0.