gms | German Medical Science

30. Jahrestagung der Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie (GAA)

Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie

09.11. - 10.11.2023, Köln

Controversy from pharmacovigilance of acetylsalicylic acid as a suspect causative agent for appearance and disappearance of Reye’ Syndrome in children

Meeting Abstract

  • Alexandra Bernd - Uni Mainz, Mainz, Germany
  • Eva-Maria Möser - Uni Mainz, Mainz, Germany
  • Dagmar Vogel - Uni Mainz, Mainz, Germany
  • Katharina Wofram - Uni Mainz, Mainz, Germany
  • Oksana Ivonchyk - Uni Mainz, Mainz, Germany
  • corresponding author presenting/speaker Hubert Heuer - experts4pharma, Schwabenheim, Germany

Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie e.V. (GAA). 30. Jahrestagung der Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie. Köln, 09.-10.11.2023. Düsseldorf: German Medical Science GMS Publishing House; 2023. Doc23gaa04

doi: 10.3205/23gaa04, urn:nbn:de:0183-23gaa044

Published: November 7, 2023

© 2023 Bernd et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at



Background: Reye’s syndrome was first described in 1963 when Reye et al. presented in the Lancet 21 children from Australia between 1951 and 1962 with a disease they called ‘Encephalopathy with fatty degeneration of the viscera’ with a high lethality, called thereafter Reye syndrome [1].

Materials and methods: The Reye’s syndrome was a rare disease in children which appeared suddenly in the early 1950s and disappeared just as suddenly in the late 1980s. An association between Reye’s syndrome and the ingestion of aspirin (acetylsalicylic acid) was claimed, although a causation by means of pharmacovigilance was difficult to prove.

Results: The presence of salicylates in the blood or urine of Reye’s syndrome patients has not been clearly demonstrated (though expsure was assumed). Further more no animal model of Reye’s syndrome has been developed where aspirin causes the disease. Sufficient evidence for disprove from epidemiological data that the incidence of Reye’s syndrome was decreasing well before warning labels were placed on aspirin products may not be a valid argument in view of potential less exposure in childrens by the alertness of the medical community from the Lancet article before. Reye’s syndrome disappeared from countries where aspirin was not used in children as well as from countries which continued to use aspirin in children (to be balanced vs. unkown alertness from Lancet article [1], leading to non-use earlier).

Conclusion: Also the argument has been raised, that Reye’s syndrome was probably either a viral mutation which spontaneously disappeared, or a conglomeration of metabolic disorders that had not been recognized or described at that time. Therefore further evaluation on other methodolocigal (including correct diagnosis) or confounding factors appears necessary.


Reye RD, Morgan G, Baral J. Encephalopathy and fatty degeneration of the viscera. A disease entity in childhood. Lancet. 1963 Oct 12;2(7311):749-52. DOI: 10.1016/s0140-6736(63)90554-3 External link