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• Reye Syndrome: an outdated notion
  Maria Casteels-Van Daele
  Published on: 9 January 2022

• Published on: 9 January 2022

  Reye Syndrome: an outdated notion

  • Maria Casteels-Van Daele, Professor of Pediatrics
  • Other Contributors:
    • Ephrem Eggermont

  Dear Editor

  We would like to comment on the paper by Dr J Glasgow and Dr B Middleton on “Reye syndrome- insights on causation and prognosis” [1]. Although the authors agree that the “diagnostic criteria (of Reye syndrome) are non-specific” they ignore the logical consequences of a non- specific definition. This non-specificity implies that the epidemiological studies suggesting a link with aspirin have been performe...

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  Dear Editor

  We would like to comment on the paper by Dr J Glasgow and Dr B Middleton on “Reye syndrome- insights on causation and prognosis” [1]. Although the authors agree that the “diagnostic criteria (of Reye syndrome) are non-specific” they ignore the logical consequences of a non- specific definition. This non-specificity implies that the epidemiological studies suggesting a link with aspirin have been performed on groups of children with heterogeneous disorders. This bias, in addition to other ones, weakens the validity of these case-control studies, since the definition of a “case subject” must be specific for the case control study to be valid and reliable [2]. Even the more rigorous Yale study gives evidence for the non-specificity of their cases: of the 25 patients with “definite Reye syndrome” only 8 had undergone liver biopsy and only 12 were partially screened for inborn errors of metabolism, the screening being limited to biochemical analyses of urine samples only [3]. Another logical consequence of the non-specific definition of Reye syndrome is its so-called decline. Medicine is not static. Nowadays, 39 years after the description of Reye syndrome, we are much better equipped to identify and correctly diagnose infectious diseases, metabolic and toxic disorders; we no longer use a vague descriptive term for updated and well-defined heterogeneous diseases or disorders [4]. This is shown in several series of Reye syndrome meeting the diagnostic criteria as put forward by the Centers for Disease Control, in which the percentage of definite diagnosis versus presumptive diagnosis varies between 0% and 62% [4,5]. It is surprising that Dr. Glasgow persists in disregarding the role of antiemetics in some patients diagnosed as Reye syndrome, neglecting again his own data which unfortunately were not reported in the UK risk factor study but which indicate that not only the use of aspirin but also that of antiemetics was significantly higher in Reye syndrome-patients than in controls [6,7]. We appreciate the question marks, suggestions and speculations of the authors in the paragraph discussing the hypothesis whether there is a biological difference between control and “Reye syndrome cells”. Progress of science indeed depends on clear data.

  References:
  (1) Glasgow JFT, Middleton B. Reye syndrome-insights on causation and prognosis. Arch Dis Child 2001;85:351-3.
  (2) Moyer VA. Confusing conclusions and the clinician: an approach to evaluating case-control studies. J Pediatr 1994;124:671-4.
  (3) Forsyth BW, Horwitz RI, Acampora D, Shapiro ED et al. New epidemiological evidence confirming that bias does not explain the aspirin/Reye’s syndrome association. JAMA 1989;261:2517-24.
  (4) Casteels-Van Daele M, Van Geet C, Wouters C, Eggermont E. Reye syndrome revisited: a descriptive term covering a group of heterogeneous disorders. Eur J Pediatr 2000;159:641-8.
  (5) Gauthier M, Guay J, Lacroix J, Lortie A. Reye’s syndrome. A reappraisal of diagnosis in 49 presumptive cases. Am J Dis Child 1989;143:1181-5.
  (6) Casteels-Van Daele M, Eggermont E. Reye’s syndrome. BMJ 1994;308:919- 20.
  (7) Casteels-Van Daele M, Eggermont E. Reye’s syndrome. BMJ 1994;309:1443.

  The authors never had nor have any ongoing affiliation or financial involvement with any pharmaceutical company nor with any other entity with a financial interest in the subject matter.

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  Conflict of Interest:
  None declared.

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