Drug-induced and toxic granulomatous hepatitis

The ability to induce granulomatous hepatitis has been attributed to numerous drugs; some sixty causative drugs have been culled from the literature for this review. Additionally, granulomas or granulomatoid lesions have resulted from occupational exposure to toxic substances (e.g. silica, copper sulphate, beryllium compounds), and particulate material from various therapeutic or diagnostic procedures (e.g. reactions to starch, talc, suture material, polyvinyl pyrrolidone, silicone, barium sulphate, thorium dioxide) or from intravenous drug abuse (e.g. talc). Clinically, patients with drug-induced or toxic granulomatous hepatitis may be asymptomatic. More frequently, the presentation is that of an acute febrile illness, with or without a rash and eosinophilia, followed by jaundice and biochemical evidence of hepatic dysfunction. The diagnosis of drug-induced granulomatous hepatitis is based largely on ruling out other aetiologies. Liver biopsy plays a key role in diagnosis. Recovery is the rule following withdrawal of the drug. Morphologically, drug-induced granulomas may be impossible to distinguish from those due to other causes. Associated lesions suggesting a drug aetiology include significant tissue eosinophilia, unicellular hepatocytic degeneration and necrosis, cholestasis and acute cholangitis or vasculitis. Special stains, polarizing and phase contrast microscopy, transmission and scanning electron microscopy and energy dispersive X-ray microanalysis all play a role in the aetiologic diagnosis of some types of granulomas.