Reye’s syndrome usually begins a few days after onset of a viral illness, most often one of the influenza viruses or varicella. The disease predominantly affects children and young adolescents, with a peak incidence between ages 5 and 15 years. Onset of the disease is manifested by symptoms of encephalitis (e.g., confusion, lethargy, or aggressive behavior), without focal neurologic signs, that accompany or follow onset of protracted or recurrent vomiting. Temperature is usually normal. There is laboratory evidence of liver cell injury, with AST or ALT more than 3 times the upper limit of the reference range, with some patients exceeding 20 or even 25 times the upper limit. Serum total bilirubin is usually normal, and clinical jaundice is rare. Nevertheless, the PT is usually elevated, and blood ammonia level is frequently elevated. Routine CSF test results are usually normal. Creatine phosphokinase level is markedly abnormal, and phosphorus level is decreased, indicating muscle involvement. Fatty liver is frequently found on biopsy or autopsy. Although exact etiology is not known, influenza A and B, especially B, have been associated with the majority of cases, with chickenpox next most frequent and other viruses also implicated on occasion. There is also very strong association with aspirin use during a viral infection.

Conditions that may simulate Reye’s syndrome and that can be ruled out by assay of serum levels or other tests include salicylate or acetaminophen overdose, valproic acid toxicity, encephalitis from other causes (e.g., herpes simplex virus) with superimposed creatine phosphokinase elevation due to intramuscular injection, denatured alcohol poisoning, and acute lead poisoning. Certain rare inborn errors of metabolism (e.g., deficiency of ornithine transcarbamylase) may be manifested by symptoms that suggest Reye’s syndrome.