Drug hypersensitivity syndrome is relatively rare. It mainly affects adults and is equal in incidence in males and females. Genetic susceptibility and HLA associations have been found for several causative drugs.

The most common drugs to cause this reaction are a number of anti-epilepsy drugs (particularly carbamazepine, phenobarbital and phenytoin), the anti-gout drug, allopurinol, olanzapine, and the sulphonamide group of antibiotics. It has been estimated that at least 1 in every 10,000 patients treated with an anticonvulsant will develop drug hypersensitivity syndrome.

The risk of drug hypersensitivity syndrome in patients on allopurinol depends on the dose of allopurinol. It is greater if the patient has kidney disease and if they are also taking thiazide diuretics.

It has also been rarely reported to be due to other medicines. It can be very difficult to determine the exact cause of drug hypersensitivity syndrome if several medicines have been commenced in preceding weeks. In about 10% of cases, the causative drug is never identified.