Intended for healthcare professionals

Letters

Reye's syndrome

BMJ 1994; 308 doi: https://doi.org/10.1136/bmj.308.6933.919b (Published 02 April 1994) Cite this as: BMJ 1994;308:919
  1. M Casteels-van Daele,
  2. E Eggermont
  1. Department of Paediatrics, University Hospital Gasthuisberg, University of Leuven, 3000 Leuven, Belgium.

    EDITOR, - We agree with John F T Glasgow and Raymond Moore that Reye's syndrome is a heterogeneous disorder.1 Indeed, it is a non- specific clinicopathological entity, the microvesicular lipid accumulations evident in the liver on light microscopy now being considered to be a non- specific finding for which there are many other causes.1,2 Electron microscopy is now recommended, but in the epidemiological studies reported it has been done in relatively few cases. With regard to aetiology, it is clear that the diagnosis of Reye's syndrome has been revised recently in favour of an inherited metabolic disorder in many patients; other patients are nowadays more correctly diagnosed as having viral disease or an escalation of symptoms induced by antiemetics, whose side effects are now better recognised.2

    This improved diagnosis, however, implies that the American and British epidemiological studies that suggested a link between Reye's syndrome and aspirin were done on a heterogeneous group of children with different diseases. This fact alone weakens their hypothesis. In the studies carried out by the Centers for Disease Control only the drugs used before the onset of severe vomiting were registered; thus drugs - for example, antiemetics - given between the onset of vomiting and admission to hospital were excluded. Moreover, the Ohio survey first started by registering all drugs taken throughout the illness, but when these data indicated that not only the use of aspirin but also that of phenothiazines and trimethobenzamide hydrochloride was significantly greater in cases of Reye's syndrome than controls the questionnaire was revised.3 Only the drugs given before the onset of vomiting were then registered, and thus the same bias was introduced as in the other surveys.

    Defining the day of onset of severe vomiting as the onset of Reye's syndrome is arbitrary and results in incorrect data on use of drugs. This arbitrary definition is the key to the whole theory. Indeed, there is no proof that vomiting reflects the early stages of cerebral oedema or the onset of Reye's syndrome; vomiting is often a symptom inherent to the viral infection.2 And in some patients the “encephalopathy” was misleading extrapyramidal reactions induced by antiemetics.2

    In the British risk factor study the use of antiemetics was significantly higher in patients with Reye's syndrome than in the comparison group.4 Indeed, of 106 patients with Reye's syndrome, 33 had taken at least one antiemetic or antihistamine, or both, before admission compared with 17 of the 185 control patients (P<0.0001); of these, 15 patients with Reye's syndrome versus three controls had taken an antiemetic such as metoclopramide (P=0.0001).5 (S Hall, personal communication). The British data and the analysis of the Ohio study3 show that not only the use of aspirin but also the use of antiemetics, phenothiazines, or other antihistamines is significantly greater in cases than controls.

    Why then do people repeat that the only link is the one between aspirin and Reye's syndrome? Would it not be more logical to point to the antiemetics known to be neurotoxic? Their possible role was suggested by the Food and Drug Administration in 1976.5 The apparent decline of Reye's syndrome is not a factor in favour of a link with aspirin as increased recognition of metabolic, viral, or toxic diseases may explain this “pseudo decline.”1,2In conclusion, Reye's syndrome should be reassessed.

    References