ABSTRACT
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455 Clinical Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456
Drug-Induced Lupus-Like Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456 Autoimmune Hemolytic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457 Autoimmune Thrombocytopenia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458 Drug-Induced Pemphigus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458 Autoimmune Liver Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459
Possible Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460 Covalent Binding and the Hapten Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . 460 Danger Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 462 Interference with Tolerance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463 Other Pharmacologic Mechanisms Leading to Autoimmunity . . . . . . . . . . . 463
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
Drug-induced hypersensitivity is a major clinical problem, and it also signifi cantly increases the uncertainty of drug development. Between the years 1975 and 2000, over 10% of newly approved drugs either had to be withdrawn from the market or achieved “Black Box” warnings because of adverse reactions that were not predicted by preclinical testing and clinical trials [1].
