IgE-mediated drug fever due to histamine H2-receptor blockers

Drug-induced fever due to histamine H2-receptor blockers was experienced by a 55-year-old man. The patient became febrile 5 days after receiving cimetidine, and continued to be febrile until the drug was stopped. His maximum body temperature was above 40 degrees C. Challenge tests with cimetidine and ranitidine showed that the fever was caused by the H2-blocker. The patient's serum IgE concentration increased markedly to 2590 IU/ml 10 days after admission, and skin tests for cimetidine and ranitidine were positive. Lymphocyte stimulation tests were positive for both drugs (stimulation indices: 193% for cimetidine and 325% for ranitidine). Cimetidine-induced fever has generally been thought to be due to a direct effect on the thermoregulatory centre in the hypothalamus, on the basis of experimental studies of the injection of cimetidine to the cerebral ventricles. However, clinical evidence has not excluded an allergic involvement in this type of drug-induced fever. This patient's fever was proven to be due to administration of the H2-blocker, and the mechanism of action was IgE-mediated.