Children with a febrile illness (eg, influenza, varicella) treated with salicylates (eg, aspirin) are at risk for developing Reye syndrome.  It is hypothesized that affected children may have an inborn metabolic error that renders them sensitive to the toxic effects of salicylates, particularly in virus-infected cells.  Aspirin in these individuals causes mitochondrial dysfunction, which results in impaired fatty acid metabolism and the two components of Reye syndrome:

• Hepatic dysfunction results from the mitochondrial insult and manifests with hepatomegaly, elevated transaminases, hyperammonemia, and prolonged PT and PTT.  Bilirubin is typically normal, and jaundice is rare.  Light microscopy of a liver specimen shows microvesicular steatosis (ie, small fat vacuoles in the cytoplasm of hepatocytes) without necrosis or inflammation.  Electron microscopy findings include swollen mitochondria.

• Encephalopathy is attributed to hepatic dysfunction and the toxic effect of hyperammonemia on the CNS, leading to cerebral edema.  Vomiting and confusion from cerebral swelling can rapidly progress to coma and potentially death.

To avoid the possibility of inducing Reye syndrome, aspirin should not be administered to children except in the management of Kawasaki disease and rheumatologic diseases (eg, juvenile idiopathic arthritis).

(Choices A and E)  Apoptosis of hepatocytes and periportal mononuclear inflammatory infiltration are microscopic findings seen in viral hepatitis.  In contrast to this patient's presentation, hepatic encephalopathy from viral hepatitis would develop gradually.

(Choice B)  Primary biliary cholangitis is characterized by bile duct destruction and periductal granulomatous inflammation.  Hepatic encephalopathy may occur as a late finding of chronic cirrhosis but would not present acutely, as Reye syndrome did in this patient.

(Choice C)  In congestive heart failure, which would manifest with peripheral edema rather than rapidly progressive encephalopathy, the liver shows centrilobular congestion and, in some cases, centrilobular necrosis.  Centrilobular necrosis can also be seen with acetaminophen toxicity, which is unlikely in this patient who received a single antipyretic tablet.

Educational objective:
Reye syndrome is characterized by liver failure and encephalopathy following salicylate (aspirin) administration in children with a febrile illness.  Aspirin-induced mitochondrial dysfunction causes impaired fatty acid metabolism and microvesicular steatosis of the liver.