Heart Disease Induced by Toxins Adverse reactions to drugs and other substances can affect the heart in different ways These can be classified as hypersensitivity myocarditis, toxic myocarditis, cardiomyopathy, or endocardial fibrosis (Boxes 59.2 to 59.4) Box 59.2 Drugs Producing Hypersensitivity Myocarditis Acetazolamide Amitriptyline Amphotericin (amphotericin B) Carbamazepine Chloramphenicol Clozapinea Indomethacin (indometacin) Isoniazid Methyldopa Minocyclinea Para-aminosalycilic acid Penicillin Phenindione Phenylbutazone Phenytoin (diphenylhydantoin) Smallpox vaccine Spironolactone Streptomycin Sulfonamides Sulfonylureas Tetracyclines Thiazide diuretics Tetanus toxoid aUpdated to include clozapine and minocycline.377 Modified from Billingham ME Morphologic changes in drug-induced heart disease In: Bristow MR ed Drug-Induced Heart Disease Amsterdam: Elsevier; 1980:127–149; and Taliercio CP, Olney BA, Lie JT Myocarditis related to drug hypersensitivity Mayo Clin Proc 1985;60:463–468 Box 59.3 Drugs and Agents Producing Toxic Myocarditis Antimony Anthracycline antibiotics Arsenicals Barbiturates Caffeine Catecholamines Cyclophosphamide Emetine 5-Fluorouracil Lithium carbonate Hydralazine Paraquat Phenothiazines Plasmocid Quinidine Rapeseed oil Modified from Billingham ME Morphologic changes in drug-induced heart disease In: Bristow MR, ed Drug-Induced Heart Disease Amsterdam: Elsevier; 1980:127–149 Box 59.4 Drugs and Agents Producing Endocardial Fibrosis Serotonin Methysergide Mercury Busulfan Irradiation Modified from Billingham ME Morphologic changes in drug-induced heart disease In: Bristow MR, ed Drug-Induced Heart Disease Amsterdam: Elsevier, 1980:127–149 The list of drugs in connection with which hypersensitivity myocarditis has been described is very long (see Box 59.2) The true incidence is unknown, since hypersensitivity myocarditis is rarely recognized clinically and therefore tends to be a postmortem finding Inappropriate sinus tachycardia, mild radiographic cardiomegaly, and ST-segment and T-wave changes on the ECG in the presence of other allergic reactions and hypereosinophilia should raise suspicion for clinical diagnosis Diagnosis is important, since sudden death from heart block or ventricular tachycardia can occur.350 Hypersensitivity myocarditis is not dosedependent and can occur at any time during the administration of drugs A delayed hypersensitivity reaction is the accepted mechanism Histopathologic examination reveals an interstitial inflammatory infiltrate with eosinophils, atypical lymphocytes, and plasma cells; this mainly affects the ventricles Myocytic damage is seen but necrosis is uncommon Severe cases may exhibit a nonnecrotizing vasculitis These lesions are reversible upon stopping the drug Fibrosis, therefore, is not seen Treatment is centered on discontinuing the offending drug combined with use of corticosteroids or immunosuppressive therapy Many substances have been implicated in the production of toxic myocarditis This is a dose-related condition in which the effects are cumulative Clinical presentation is that of acute myocarditis Extensive cellular necrosis occurs over a short period Histopathologic signs include myocardial damage, inflammatory