Reye syndrome, first described in 1963, is an acute, life-threatening, postinfectious, metabolic encephalopathy that affects predominantly school-aged children, occasionally infants, and rarely adults. Over the years, the disease and its clinical manifestations have received widespread recognition.

Characteristically, a prodromal illness, most often influenza or varicella infection, is followed in 3 to 5 days by the onset of persistent and intractable vomiting. Initially, patients are well oriented but irritable and lethargic. Some patients have no change in consciousness and remain only lethargic, with no progression to unconsciousness. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are 3 to 30 times normal. The serum bilirubin level rarely exceeds 1 mg/dL. Serum ammonia concentrations are variable at presentation. As the encephalopathy worsens to a hyperexcitable state, the patient is intermittently out of contact with the environment. Further progression to a deeper comatose state is characterized by decerebrate and decorticate posturing, hyperventilation, and, finally, flaccid paralysis with loss of involuntary ventilatory control. The comatose patient uniformly has an elevated ammonia concentration ranging from 3 to 20 times normal. The encephalopathy typically persists for 24 to 96 hours, with gradual improvement occurring in survivors. Recovery of consciousness in patients with permanent neurologic impairment may require weeks.

Criteria for the case definition of Reye syndrome include the following: an acute, noninflammatory encephalopathy documented clinically by an alteration in consciousness and, if available, cerebrospinal fluid containing fewer than eight leukocytes per microliter; hepatopathy documented by liver biopsy on autopsy or a threefold or greater increase in the ALT, AST, or serum ammonia level; and no more reasonable explanation for the cerebral or hepatic abnormalities.

Accurately assessing the severity of the illness is important because the therapies for severely affected children are aggressive, invasive, and dangerous. Several staging systems have been developed, culminating in the National Institutes of Health Staging System (Box 405.1). The peak incidence of this disorder occurred in the 1960s and 1970s, and only rare cases have been reported since 1985.