- Viral infection (an essential component of the theorized pathophysiology of Reye syndrome) is usually varicella or influenza, although rotavirus and respiratory viruses have also been recognized as inciting factors as well as some bacteria and, in certain cases, microbial toxins.
- The use of salicylates during the infection has been strongly associated with development of Reye syndrome. Other medications and chemicals such as phenothiazines, valproic acid, NSAIDs, plant toxins, fruit toxins, and some antibiotics and antineoplastic drugs have also been associated. The inciting drug may be responsible for the mitochondrial dysfunction due to the depression of cytochrome P450 present in this disease.
- Reye-like syndrome mimics Reye syndrome but is generally a result of inborn errors of metabolism. Pre-existing metabolic disorders such as beta-oxidation defects, fatty acid metabolism defects, organic acidurias, and urea cycle disorders can predispose to the mitochondrial dysfunction that occurs with Reye syndrome. Any patient diagnosed with Reye syndrome should undergo investigation for inborn errors of metabolism as well.
Reye syndrome is very rare and affects children more often than adults. Incidence in the United States for individuals under the age of 18 is less than 0.3-1/100 000, with a mean age of 9 years. In other countries, the mean age is generally lower, and there tends to be a lack of association with influenza virus as compared with the United States. Peak incidence occurs during the winter and spring months when respiratory viral infections are more common.
The CDC has created diagnostic criteria for Reye syndrome:
- Acute noninflammatory encephalopathy with an altered level of consciousness
- Hepatic dysfunction with a liver biopsy showing fatty metamorphosis without inflammation or necrosis or a greater than 3-fold increase in alanine aminotransferase, aspartate aminotransferase
- No other explanation for cerebral edema or hepatic abnormality
- Cerebrospinal fluid with a white blood cell count of 8 cells/µL or fewer (usually lymphocytes); note that lumbar puncture should not be performed in patients who are hemodynamically unstable and/or those in whom increased intracranial pressure is a concern
- Brain biopsy with findings of cerebral edema but lacking signs of inflammation or necrosis