Hypersensitivity myocarditis.

Autopsy tissue specimens of 69 cases of hypersensitivity myocarditis were studied to determine drug association, spectrum of histologic findings, distribution of infiltrates, and correlation between degree of infiltrates and cardiac symptoms. Hypersensitivity myocarditis was defined by the presence of eosinophils, a mixed lymphohistiocytic infiltrate along natural planes of separation, and an absence of fibrosis or granulation tissue in areas of infiltrate. Commonly implicated drugs were methyldopa, hydrochlorothiazide, ampicillin, furosemide, digoxin, tetracycline, aminophylline, phenytoin, benzodiazepines, and tricyclic antidepressants. Histiocytes composed the predominant cell type (in addition to eosinophils and lymphocytes). Lymphocytes were predominantly T cells in 12 cases studied immunohistochemically. Small foci of myocyte necrosis were present in 37 cases, and they correlated with the degree of infiltrate. A nonnecrotizing vasculitis was present in 28 cases. The right ventricle was involved in all but three cases. Cardiac arrhythmias or unexplained death occurred in 29 patients and did not correlate with the degree of myocardial infiltrate or presence of necrosis. Eosinophils were present in the livers of 30 of 58 patients, and their presence correlated with the degree of cardiac infiltration. A causative association between histologic findings and drugs is difficult to prove because of the common usage of many of the drugs implicated, multiple drug use, and the absence of clinical criteria of hypersensitivity. Symptoms do not appear related to the degree of infiltrate. In more than half the cases, infiltrates may be missed by endomyocardial biopsy due to focality of lesions.