Reye's syndrome in the United States from 1981 through 1997

N Engl J Med. 1999 May 6;340(18):1377-82. doi: 10.1056/NEJM199905063401801.


Background: Reye's syndrome is characterized by encephalopathy and fatty degeneration of the liver, usually after influenza or varicella. Beginning in 1980, warnings were issued about the use of salicylates in children with those viral infections because of the risk of Reye's syndrome.

Methods: To describe the pattern of Reye's syndrome in the United States, characteristics of the patients, and risk factors for poor outcomes, we analyzed national surveillance data collected from December 1980 through November 1997. The surveillance system is based on voluntary reporting with the use of a standard case-report form.

Results: From December 1980 through November 1997 (surveillance years 1981 through 1997), 1207 cases of Reye's syndrome were reported in patients less than 18 years of age. Among those for whom data on race and sex were available, 93 percent were white and 52 percent were girls. The number of reported cases of Reye's syndrome declined sharply after the association of Reye's syndrome with aspirin was reported. After a peak of 555 cases in children reported in 1980, there have been no more than 36 cases per year since 1987. Antecedent illnesses were reported in 93 percent of the children, and detectable blood salicylate levels in 82 percent. The overall case fatality rate was 31 percent. The case fatality rate was highest in children under five years of age (relative risk, 1.8; 95 percent confidence interval, 1.5 to 2.1) and in those with a serum ammonia level above 45 microg per deciliter (26 micromol per liter) (relative risk, 3.4; 95 percent confidence interval, 1.9 to 6.2).

Conclusions: Since 1980, when the association between Reye's syndrome and the use of aspirin during varicella or influenza-like illness was first reported, there has been a sharp decline in the number of infants and children reported to have Reye's syndrome. Because Reye's syndrome is now very rare, any infant or child suspected of having this disorder should undergo extensive investigation to rule out the treatable inborn metabolic disorders that can mimic Reye's syndrome.

MeSH terms

  • Adolescent
  • Age Factors
  • Ammonia / blood
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Incidence
  • Infant
  • Male
  • Population Surveillance
  • Reye Syndrome / blood
  • Reye Syndrome / epidemiology*
  • Reye Syndrome / etiology
  • Reye Syndrome / mortality
  • Risk Factors
  • Salicylates / blood
  • Seasons
  • Severity of Illness Index
  • United States / epidemiology
  • Virus Diseases / complications
  • Virus Diseases / epidemiology


  • Salicylates
  • Ammonia