INTRODUCTION

Pemoline (Cylert) is a central nervous system stimulant first introduced into clinical trials in the 1970s. Currently, it is most commonly used to treat children with attention deficit disorder (ADD).^1,2 There have been scattered reports of hepatotoxicity with pemoline usually involving transient elevation of liver chemistries.^3-6 Overt liver failure has been rarely reported.^7-10 During the last 3 years we encountered four cases of marked liver dysfunction in children on pemoline. Two of these progressed to fulminant hepatic failure requiring liver transplantation. In those cases where autoantibodies were measured, there was evidence for autoimmune activation (see Tables 1 and 2).

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Table Removed (Available Only in the Full Text)

	CASE REPORTS

Case 1

This patient was an adopted 14-year-old girl with ADD unresponsive to methylphenidate. Pemoline, 37.5 mg per day, was instituted with some improvement in school performance. Liver chemistries were not routinely monitored. Six months later, jaundice and fatigue developed. Physical examination was notable for jaundice and no organomegaly. Liver transaminases were in the 1000 IU/L range with a total bilirubin of 8 mg/dL with a direct fraction of 6 mg/dL. The serum albumin level was normal but the prothrombin time was elevated to 17 seconds (normal <13 seconds) and was unresponsive to subcutaneous vitamin K. Pemoline was immediately discontinued. Serologic evaluation for Hepatitis A,B,C as well as cytomegalovirus and Epstein Barr virus (EBV) gave negative results. Serum ceruloplasmin and -1-antitrypsin levels and phenotype were normal. Abdominal ultrasound showed nonspecific heterogeneity of the liver parenchyma. Antinuclear antibody (ANA) measured positive 1:80 with a speckled pattern and antiparietal cell antibodies were isolated. Antismooth muscle, antimitochondrial, and liver-kidney microsomal antibodies were all negative. Over the next 3 weeks, the patient developed worsening jaundice and coagulopathy. She developed grade IV hepatic encephalopathy and underwent orthotopic liver transplantation. The explanted liver was shrunken and weighed 563 g. Histology showed submassive necrosis with microvesicular steatosis, cholestasis, regenerative nodules, and chronic active hepatitis. The . . . [Full Text of this Article]