Prevention of severe cutaneous adverse drug reactions: the emerging value of pharmacogenetic screening.

CMAJ © 2009 Canadian Medical Association or its licensors 1 A35-year-old man of Chinese ethnicity presented to the emergency department with fever, rash, mouth pain and visual impairment after two weeks of therapy with allopurinol. On examination, the patient had a generalized maculopapular rash, orolabial ulceration (Figure 1), keratoconjunctivitis with pseudomembrane formation (Figure 2) and urethritis. He was given intravenous immunoglobulin for five days and cyclosporin for 14 days, and the allopurinol was discontinued. A skin biopsy later showed dermo-epidermal separation and a dermal lymphocytic infiltrate, consistent with overlapping Stevens– Johnson syndrome and toxic epidermal necrolysis. The rash, oral mucositis and urethritis resolved completely after two weeks of therapy. After 18 months, the patient still had visual impairment and dry eye from corneal ulceration for which he was continuing to receive treatment with topical corticosteroids, cyclosporin, vitamin A and lubricants. Genotyping showed the presence of the human leukocyte antigen (HLA) allele-B*5801, which has been shown to have a strong association with allopurinol-induced hypersensitivity, especially among Han Chinese. Genetic susceptibility