Reye syndrome

Reye syndrome progresses through five stages:[5][6][7]

• Stage I
  • Vasoconstrictive rash on palms of hands and feet
  • Persistent, heavy vomiting that is not relieved by not eating
  • Generalized lethargy
  • Confusion
  • Nightmares (possible symptom)
  • No fever usually present[8]
  • Headaches
• Stage II
  • Stupor
  • Hyperventilation
  • Fatty liver (found on biopsy)
  • Hyperactive reflexes
• Stage III
  • Continuation of Stage I and II symptoms
  • Possible coma
  • Possible cerebral edema
  • Rarely, respiratory arrest
• Stage IV
  • Deepening coma
  • Dilated pupils with minimal response to light
  • Minimal but still present liver dysfunction
• Stage V
  • Very rapid onset following stage IV
  • Deep coma
  • Seizures
  • Multiple organ failure[9]
  • Flaccidity
  • Hyperammonemia (above 300 mg/dL of blood)
  • Death

The cause of Reye syndrome is unknown.[2] It usually begins shortly after recovery from a viral infection, such as influenza or chickenpox.[1] About 90% of cases in children are associated with aspirin (salicylate) use.[2] Inborn errors of metabolism are also a risk factor.[3]

The association with aspirin has been shown through epidemiological studies. The diagnosis of Reye syndrome greatly decreased in the 1980s, when genetic testing for inborn errors of metabolism was becoming available in developed countries.[10] A retrospective study of 49 survivors of cases diagnosed as Reye syndrome showed that the majority of the surviving patients had various metabolic disorders, particularly a fatty-acid oxidation disorder medium-chain acyl-CoA dehydrogenase deficiency.[11]

Treatment is supportive.[1] Mannitol may be used to help with the brain swelling.[2]

Documented cases of Reye syndrome in adults are rare. The recovery of adults with the syndrome is generally complete, with liver and brain function returning to normal within two weeks of onset.

In children, mild to severe permanent brain damage is possible, especially in infants. Over thirty percent of the cases reported in the United States from 1981 through 1997 resulted in fatality.

Reye syndrome occurs almost exclusively in children. While a few adult cases have been reported over the years, these cases do not typically show permanent neural or liver damage. Unlike in the United Kingdom, the surveillance for Reye syndrome in the United States is focused on people under 18 years of age.

In 1980, after the CDC began cautioning physicians and parents about the association between Reye syndrome and the use of salicylates in children with chickenpox or virus-like illnesses, the incidence of Reye syndrome in the United States began to decline, prior to the FDA's issue of warning labels on aspirin in 1986.[10] In the United States between 1980 and 1997, the number of reported cases of Reye syndrome decreased from 555 cases in 1980 to about two cases per year since 1994. During this time period 93% of reported cases for which racial data were available occurred in whites and the median age was six years. In 93% of cases a viral illness had occurred in the preceding three-week period. For the period 1991–1994, the annual rate of hospitalizations due to Reye syndrome in the United States was estimated to be between 0.2 and 1.1 per million population less than 18 years of age.

During the 1980s, a case-control study carried out in the United Kingdom also demonstrated an association between Reye syndrome and aspirin exposure.[16] In June 1986, the United Kingdom Committee on Safety of Medicines issued warnings against the use of aspirin in children under 12 years of age and warning labels on aspirin-containing medications were introduced. United Kingdom surveillance for Reye syndrome documented a decline in the incidence of the illness after 1986. The reported incidence rate of Reye syndrome decreased from a high of 0.63 per 100,000 population less than 12 years of age in 1983–1984 to 0.11 in 1990–1991.

From November 1995 to November 1996 in France, a national survey of pediatric departments for children under 15 years of age with unexplained encephalopathy and a threefold (or greater) increase in serum aminotransferase and/or ammonia led to the identification of nine definite cases of Reye syndrome (0.79 cases per million children). Eight of the nine children with Reye syndrome were found to have been exposed to aspirin. In part because of this survey result, the French Medicines Agency reinforced the international attention to the relationship between aspirin and Reye syndrome by issuing its own public and professional warnings about this relationship.[17]

The syndrome is named after Douglas Reye, who, along with fellow physicians Graeme Morgan and Jim Baral, published the first study of the syndrome in 1963 in The Lancet.[18] In retrospect, the occurrence of the syndrome may have first been reported in 1929. Also in 1964, George Johnson and colleagues published an investigation of an outbreak of influenza B that described 16 children who developed neurological problems, four of whom had a profile remarkably similar to Reye syndrome. Some investigators refer to this disorder as Reye-Johnson syndrome, although it is more commonly called Reye syndrome. In 1979, Karen Starko and colleagues conducted a case-control study in Phoenix, Arizona, and found the first statistically significant link between aspirin use and Reye syndrome.[19] Studies in Ohio and Michigan soon confirmed her findings[20] pointing to the use of aspirin during an upper respiratory tract or chickenpox infection as a possible trigger of the syndrome. Beginning in 1980, the CDC cautioned physicians and parents about the association between Reye syndrome and the use of salicylates in children and teenagers with chickenpox or virus-like illnesses. In 1982 the U.S. Surgeon General issued an advisory, and in 1986 the Food and Drug Administration required a Reye syndrome-related warning label for all aspirin-containing medications.[21]

• NINDS Reye's Syndrome Information Page