Possible case of procainamide-induced intrahepatic cholestatic jaundice

To describe a possible case of procainamide-induced intrahepatic cholestatic jaundice that was recognized six weeks after the initiation of procainamide therapy and to summarize the five previously reported cases.

A 77-year-old woman with a history of hypertension, insulin-dependent diabetes mellitus, temporal arteritis, and Wolff-Parkinson-White syndrome who had taken procainamide for six weeks presented to the hospital with disorientation and acute renal and hepatic dysfunction. In addition to disorientation, scleral icterus, and diffuse maculopapular rash, her physical examination was generally normal. There was no evidence of fever, nausea, vomiting, lymphadenopathy, or eosinophilia. Her liver enzyme concentrations increased significantly from baseline (beginning of procainamide therapy). Her N-acetylprocainamide (NAPA) concentration was elevated to 52 mg/L upon admission. Procainamide was discontinued and her NAPA concentration returned to within normal limits in two days. Diagnostic tests were performed to rule out active hepatitis, vasculitis, and liver malignancies. After procainamide was discontinued and prednisone treatment was started, she became more oriented and her liver enzyme concentrations slowly improved.

Only five cases of procainamide-induced liver abnormalities have been previously reported; these included granulomatous hepatitis and intrahepatic cholestasis. The mechanism for liver dysfunction is not known; however, it is proposed to be a delayed hypersensitivity reaction. Clinical hallmarks of hypersensitivity include fever, eosinophilia, rash, and lymphadenopathy; nausea and vomiting also may be present. Of the five reported cases, all experienced fever and only one experienced pruritus. No patients had eosinophilia or lymphadenopathy. Because of the temporal increase in liver enzyme concentrations after six weeks of procainamide therapy, we believe that this case represents another possible procainamide-induced hypersensitivity reaction.

Procainamide-induced liver dysfunction can occur from one day to six weeks after initiation of the drug and may subside one day to several weeks after discontinuation of therapy. Symptoms may include nausea, vomiting, rash, and fever. Liver enzyme concentrations are abnormal. It is important to recognize the possibility of such a reaction early so that procainamide therapy can be discontinued promptly to avoid further liver damage.