Jump to comment:

• Aspirin, Reye Syndrome, Kawasaki disease, and allergies; a reconsideration of the links
  Susan M Hall
  Published on: 22 March 2016

• Published on: 22 March 2016

  Aspirin, Reye Syndrome, Kawasaki disease, and allergies; a reconsideration of the links

  • Susan M Hall, medical epidemiologist

  Dear Editor,

  Van Bever et al suggest that “it is time to rethink whether there is any causal link between aspirin and Reye’s syndrome (RS)” and that paediatricians should consider returning to aspirin as “their first choice antipyretic/analgesic in children” [1]. The proposal appears to originate in the hypothesis that the decline in its use is responsible for the increase in allergic disorders. They do no...

  Show More

  Dear Editor,

  Van Bever et al suggest that “it is time to rethink whether there is any causal link between aspirin and Reye’s syndrome (RS)” and that paediatricians should consider returning to aspirin as “their first choice antipyretic/analgesic in children” [1]. The proposal appears to originate in the hypothesis that the decline in its use is responsible for the increase in allergic disorders. They do not specify how the occasional use of aspirin for a febrile illness might reverse this increase.

  The virtual disappearance of RS following the warning labels on aspirin for children and teenagers has been described as a “public health triumph” in terms of the death and disability avoided [2]. Compelling evidence of benefit must be presented to justify reinstatement of aspirin in the routine treatment of febrile illness in children.

  The authors argue that RS is extremely rare in patients on both short and long term aspirin treatment for Kawasaki disease (KD) and therefore aspirin may not be causally associated with RS. They state that only one case of RS associated with KD has ever been reported, and that only in the Japanese literature. However, a basic Medline search reveals another report –from Taiwan [3].Furthermore, 14 of 361 patients reported to the National Reye’s Syndrome Surveillance System in the USA between 1980 and 1997 for whom data on aspirin use were available, were on long term salicylate medication for either KD or juvenile chronic arthritis [4]. The authors of this report also cite two other studies showing a higher attack rate of RS among children on long term salicylates for juvenile chronic arthritis.

  Bever et al’s argument fails to take account of the fact that Reye’s syndrome has a multifactorial aetiopathogenesis: besides aspirin, the other associated risk factors for which there is both epidemiological and laboratory evidence are a prodromal viral infection, typically influenza or varicella, and an innate susceptibility[5]. The latter is reflected in the rarity of Reye’s syndrome: even in the years before aspirin warnings the annual reported incidence was at most 1 per 100 000 children under 18 in the USA. The chances of a child even on long term aspirin having these other two risk factors must be very small indeed and probably explains the dearth of reports of RS in these patients. Furthermore, most cases of KD occur in children under five whereas most cases of idiopathic RS were in the over fives [4]. There is in fact a small excess risk of RS in children receiving long term aspirin and, because of this, it is recommended practice in the USA to vaccinate such patients against influenza and varicella[4]. Perhaps paediatricians in Japan and other countries where there is a high incidence of KD disease do the same.

  It is true that the biological mechanism underlying the link between aspirin and RS is not understood, but evidence for the association is substantial[5] and has convinced regulatory authorities in the UK, USA, Europe and many other countries. There are alternative, equally effective drugs for symptomatic relief in children with febrile illnesses, which have not been associated with this lethal condition. It is irresponsible to encourage doctors to ignore the current guidelines on the basis of a hypothesis for which there is no robust evidence.

  References

  (1). van Bever HP, Quek SC, Lim T. Aspirin, Reye syndrome, Kawasaki disease, and allergies; a reconsideration of the links. Arch Dis Child 2004; 89: 1178

  (2). Monto AS. The disappearance of Reye’s syndrome – a public health triumph. New Engl. J Med 1999; 340: 1423-1424

  (3). Lee JH, Hung HY, Huang FX. Kawasaki disease with Reye’s syndrome: report of one case. Zhonghua Min Guo Xiao Er Ke Yi Xue HuiZa Zhi 1992; 33: 67-71

  (4). Belay ED, Bresee JS, Holman RC, et al. Reye’s syndrome in the United States from 1981 through 1997. New Engl J Med 1999; 340: 1377-1382

  (5). Glasgow JFT, Hall SM. Reye’s syndrome and aspirin. In Rainsford KD (ed) Aspirin and related Drugs, Taylor and Francis, London 2004; 555- 585

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top