Reye's syndrome and the aspirin warning

In 1963 R. D. Reye, G. Morgan and J. Baral described in the Lancet an illness of children combining encephalopathy with fatty degeneration of the viscera. Reye syndrome began with vomiting and lethargy and could progress to delirium and coma, most often in a child recovering from a viral infection, particularly influenza or chickenpox. In 1982 the CDC estimated 600 to 1,200 cases a year in the United States, with death in 20 to 30 percent of reported cases and brain damage in some survivors.

Case-control studies by state health departments in Arizona, Michigan and Ohio found an association between the syndrome and salicylates such as aspirin taken during the illness before it. In one Michigan study all 12 patients had taken a salicylate product, compared with 12 of 29 matched controls. In February 1982 the CDC advised physicians and parents of the possible risk, and the American Academy of Pediatrics advised in June that salicylates be avoided in children with influenza or chickenpox. An FDA working group audited the raw data from the Michigan and Ohio studies, and a public meeting held by the FDA, CDC and National Institutes of Health on 24 May 1982 agreed that the new analysis supported the association.

On 11 June 1982 the MMWR published the Surgeon General's advice against giving salicylates to children with influenza or chickenpox. Doubts about the methods of the state studies led the Secretary of Health and Human Services to set up a Public Health Service task force study. Its main phase, run from January 1985 to May 1986, compared 27 patients with 140 matched controls and found an odds ratio of 40 for salicylate use.

Since 1986 the labels of all aspirin-containing medicines in the United States have had to warn of the risk. National surveillance recorded a peak of 555 cases in children in 1980 and no more than 36 a year from 1987. Of 1,207 cases reported from December 1980 to November 1997, 31 percent were fatal.