Aspirin and Reye Syndrome
Reye syndrome is an extremely rare but severe and often fatal disease. Death occurs in about 30–40% of cases from brainstem dysfunction. The disease typically is preceded by a viral infection with an intermediate disease-free interval of 3–5 days. The biochemical explanation for Reye-like symptoms is a generalized disturbance in mitochondrial metabolism, eventually resulting in metabolic failure in the liver and other tissues.
The etiology of ‘classical’ Reye syndrome is unknown. Hypothetically, the syndrome may result from an unusual response to the preceding viral infection, which is determined by host genetic factors but can be modified by a variety of exogenous agents. Thus, several infections and diseases might present clinically with Reye-like symptoms. Exogenous agents involve a number of toxins, drugs (including aspirin [acetylsalicylic acid]), and other chemicals.
The ‘rise and fall’ in the incidence of Reye syndrome is still poorly understood and unexplained. With a few exceptions, there were probably no new Reye-like diseases reported during the last 10 years that could not be explained by an inherited disorder of metabolism or a misdiagnosis. This may reflect scientific progress in the better understanding of cellular and molecular dysfunctions as disease-determining factors. Alternatively, the immune response to and the virulence of a virus might have changed by alteration of its genetic code.
The suggestion of a defined cause-effect relationship between aspirin intake and Reye syndrome in children is not supported by sufficient facts. Clearly, no drug treatment is without side effects. Thus, a balanced view of whether treatment with a certain drug is justified in terms of the benefit/risk ratio is always necessary. Aspirin is no exception.
KeywordsInfluenza Aspirin Acetaminophen Salicylate Kawasaki Disease
Funding for the preparation of this review was provided by Bayer HealthCare, Leverkusen, Germany. The author would like to thank Ertan Mayatepek (University Clinics Düsseldorf, Department of Pediatrics, Düsseldorf, Germany) for his critical comments and valuable advice as well as Erika Lohmann for her assistance in preparing this manuscript.
The author has not received income from patents, royalties, or stocks, or received any other financial or material gain that are directly related to the subject matter of this review. The author has received research grants from and been involved with the advisory boards of the following companies: Astra-Zeneca GmbH, Bayer HealthCare, Sanofi-Aventis, Schering AG, and Schwarz Pharma GmbH.
The author receives current project support from the following companies: Bayer HealthCare, Schering AG, and Schwarz Pharma GmbH. The author consults for Astra-Zeneca GmbH, Bayer HealthCare, Boehringer Ingelheim Pharma GmbH & Co. KG, BBraun Melsungen AG, Schering AG, and Sanofi-Aventis. The author’s work on the side effects of drugs is supported by grants from BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte).
- 2.Mowat AP. Reye’s syndrome and aspirin. In: Vane JR, Botting RM, editors. Aspirin and other salicylates. London: Chapman & Hall Medical, 1992: 531–47Google Scholar
- 7.Weiner DL. Pediatrics, Reye syndrome, 2001 [online]. Available from URL: http://www.emedicine.com/EMERG/topic399.htm [Accessed 2003 Dec 22]
- 11.Schrör K. Acetylsalicylic acid. Frechen, Germany: Dr. Schrör Verlag — Nature & Science. In pressGoogle Scholar
- 24.Hall SM, Lynn R. Reye syndrome. In: Guy M, Nicoll A, Lynn R, editors. British Paediatric Surveillance Unit, 12th annual report. London: RCPCH, 1998Google Scholar
- 28.Desschamps D, Fisch C, Fromenty B, et al. Inhibition by salicylic acid of the activation and thus oxidation of long chain fatty acids: possible role in the development of Reye’s syndrome. J Pharmacol Exp Ther 1991; 259: 894–904Google Scholar
- 29.Troll MM, Menten ML. Salicylate poisoning: report of four cases. Am J Dis Child 1945; 69: 37–43Google Scholar
- 54.Yamashita F, Eiichiro O, Kimura A, et al. Reye’s syndrome in Asian countries. In: Pollack JD, editor. Reye’s syndrome. 4th ed. Bryon (OH): National Reye’s Syndrome Foundation, 1985: 47–60Google Scholar
- 58.Sengupta CH, Steffen R, Schar M. Das Reye-Syndrom in der Schweiz. Schweiz Rundsch Med 1987; 76: 1114–6Google Scholar
- 61.Starko KM, Ray CG, Dominguez LB, et al. Reye’s syndrome and salicylate use. Pediatrics 1980; 66: 854–64Google Scholar
- 66.Hall SM. Reye’s syndrome and aspirin: areview. J Royal Soc Med 1986; 79: 596–8Google Scholar
- 67.Consensus conference: diagnosis and treatment of Reye’s syndrome. JAMA 1981; 246: 2441–4Google Scholar
- 74.Gladtke E, Schauseil-Zipf U. Reye’s syndrome. Monatsschr Kinderheilk 1987; 135: 699–704Google Scholar
- 77.Orlowski JP, Campbell P, Goldstein S. Reye’s syndrome: a case control study of medication use and associated viruses in Australia. Cleve Clin Med 1990; 57: 323–9Google Scholar