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Reye Syndrome -- United States, 1984

For the 1984 surveillance year,* 190 cases of Reye syndrome (RS) meeting CDC's case definition** were reported. Although delayed reports will increase the number of cases for 1984 somewhat, the 1984 total is presently among the lowest annual totals reported through the National Reye Syndrome Surveillance System (NRSSS) since its initiation in December 1973 (Table 1).

Cases were reported from 42 states. The sex and race distributions were similar to previous years. Of patients for whom this information was reported, 51% were male; 94%, white; 3%, black; and 3%, of Asian or American Indian extraction. Most RS patients were school-aged children; 38% were 10-14 years of age; 29%, 0-4 years of age; 18%, 5-9 years of age; 13%, 15-19 years of age; and 2%, 20 years of age or older.

For 179 (94%) of the patients, a prodromal illness occurring within 2 weeks before the onset of vomiting or neurologic symptoms of RS was reported. This prodromal illness was characterized by respiratory symptoms (76%), varicella exanthem (15%), diarrhea without respiratory symptoms (2%), or other signs and symptoms, including fever alone (7%).

Most patients were hospitalized in the first 6 months of the surveillance year (Figure 1). This winter and spring seasonal distribution primarily reflected the incidence of respiratory virus infections among children, particularly influenza types A(H1N1) and B, the predominant influenza isolates during 1984. In addition, the small number of varicella-associated RS patients were hospitalized primarily during this period.

The largest percentages of patients were admitted to hospitals in the three precomatose stages of RS: stage I--38%; stage II--36%; or stage 0--8% (1). Of these, 56% progressed to coma. The short-term outcomes were reported for 173 (91%) of the RS patients; 45 died, for a case-fatality ratio of 26%.

Editorial Note

Editorial Note: The NRSSS is useful in providing crude annual comparisons of RS activity, although the number of cases reported is recognized to be an underestimate of the true incidence of RS. During 1982-1984, the annual incidence of RS was the lowest reported since the initiation of national surveillance. The incidence of RS in previous years has reflected, at least in part, the intensity and/or type of influenza activity. However, the influenza activity in 1984 appeared to be much greater than in the 2 previous years, with widespread school outbreaks of both influenza types A(H1N1) and B (2).

When analyzed by 10-year age groups, the decline in reported cases from 1981 to 1984 is accounted for by a consistent decline in the number of cases reported each year among children under 10 years of age. No such decrease has occurred in the number of patients 10-19 years of age; in 1984, the number of cases reported in this age group increased, consistent with the increased influenza activity.

Varicella-associated RS cases show an even larger decline (from 77 in 1981 to 26 in 1984) in the number of cases reported each year among children under 10 years of age. However, annual varicella activity in the United States remained relatively stable during this period. The reasons for the decline in incidence among children under 10 years of age is unclear, although it does not appear to be solely the result of annual differences in the incidence of either influenza or varicella.

One possible explanation for the reduced incidence among children under 10 years of age is that there has been a decline in the use of salicylates among younger children in recent years.

In 1982, the Surgeon General of the Public Health Service (PHS) advised against giving salicylates and salicylate-containing medications to children with influenza and chickenpox (3). This advice was based on the review of results of case-control studies that showed a statistically significant association of RS with the ingestion of salicylates during the antecedent illness (4-6). Because of concerns regarding methodologic issues and the limitations of these studies, the Secretary of Health and Human Services appointed a PHS Task Force comprised of members of the National Institutes of Health, Food and Drug Administration, and CDC to design and implement a new epidemiologic study concerning the nature of the possible relationship between RS and medications.

A pilot study was conducted between February and May 1984 to determine the study feasibility and establish methodology. The pilot study included 29 RS cases and 143 controls consisting of children admitted to the same hospital (IP) or emergency room (ER), attending the same school, or identified by random-digit dialing (RDD). Ninety-seven percent of case children were reported to have received salicylates during the respiratory or chickenpox illness before a clinically defined onset of RS, compared with 28% (ER), 23% (IP), 59% (school), and 55% (RDD) at any time during their matched illnesses. The risk defined in the pilot study was comparable to or greater than that determined in the previous studies. The Institute of Medicine (IOM), National Academy of Sciences, served to advise and critique the protocol, monitor the study progress, and review study analysis and results. Following a review of the data collection methodology in July 1984 and the data analysis in December 1984, the IOM, on January 8, stated:

"1. The PHS Task Force should proceed with the full study. "2. Results of the pilot study should be released promptly to the

public and to scientists for review and analysis. "3. Analysis of the pilot study data reveals a strong association

between the Reye syndrome and the use of aspirin; considering data from previous studies also show an association of use of aspirin and Reye syndrome, the Committee recommends that steps should be taken to protect the public health before the full study is completed. "4. Although it is impossible to know with certainty whether the

release of the pilot study data will harm the full study, the Committee suspects the effects of the attendant publicity will be no more damaging than the current climate of public opinion, which appears not to have impeded conduct of the pilot study." A report of the pilot study is currently being prepared for publication. In view of these preliminary findings, physicians, parents, and older children who self-medicate should continue to be advised of the probable increased risk of RS associated with the use of salicylates for children, including teenagers, with influenza-like illness or chickenpox. Reported by Div of Viral Diseases, Center for Infectious Diseases, CDC; the Reye Syndrome Task Force, consisting of members from U.S. Food and Drug Administration, National Institutes of Health, Office of the Assistant Secretary of Health, and CDC.


  1. Hurwitz ES, Nelson DB, Davis C, Morens D, Schonberger LS, National Surveillance for Reye syndrome: a five-year review. Pediatrics 1982;70:895-900.

  2. CDC. Influenza--United States, 1983-1984 season. MMWR 1984;33:417-8.

  3. CDC. Surgeon General's advisory on the use of salicylates and Reye syndrome. MMWR 1982;31:289-90.

  4. Starko KM, Ray CG, Dominguez LB, Stromberg WL, Wodall DF. Reye's syndrome and salicylate use. Pediatrics 1980;66:859-64.

  5. Waldman RJ, Hall WN, McGee H, Van Amburg G: Aspirin as a risk factor in Reye's syndrome. JAMA 1982;247:3089-94.

  6. Halpin TJ, Holtzhauer FT, Campbell RJ, et al: Reye's syndrome and medication use. JAMA 1982;248:687-91 *For the purposes of surveillance, Reye syndrome years extend from December 1 to November 30 (i.e. the 1984 year runs from December 1, 1983, to November 30, 1984). The data for 1984 are preliminary and include cases reported as of January 8, 1985. **The CDC case definition is (1) acute noninflammatory encephalopathy documented by the clinical picture of alteration in the level of consciousness and, if available, a record of cerebrospinal fluid containing eight leukocytes or less per mm((3)), or histologic sections of the brain demonstrating cerebral edema without perivascular or meningeal inflammation; (2) fatty metamorphosis of the liver diagnosed by either biopsy or autopsy or a threefold or greater rise in the levels of either the SGOT, SGPT, or serum ammonia; and (3) no known more reasonable explanation for the cerebral or hepatic abnormalities.

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