Reye Syndrome

Reye Syndrome: Excerpt from The 5-Minute Pediatric Consult

Andrew E. Mulberg, MDSeth L. Ness, MD, PhD

Reye Syndrome - BASICS

Reye Syndrome - description

• Acute encephalopathy and fatty degeneration of the liver
• The US Centers for Disease Control and Prevention description is of an illness that meets all the following criteria:
  • Acute, noninflammatory encephalopathy that is documented clinically by (a) an alteration in consciousness and, if available, (b) a record of the CSF containing ≤8 leukocytes/mm³ or a histologic specimen demonstrating cerebral edema without perivascular or meningeal inflammation
  • Hepatopathy documented by either (a) a liver biopsy or an autopsy considered to be diagnostic of Reye syndrome or (b) a 3-fold or greater increase in the levels of the serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), or serum ammonia
  • No more reasonable explanation for the cerebral and hepatic abnormalities

Reye Syndrome - epidemiology

• Peak incidence age 6 years
• Most children range from 4–12 years of age.
• Association with ingestion of aspirin-containing medicines by children with varicella or influenza B
• In 1982, the US Surgeon General issued an advisory on the use of salicylates and Reye syndrome.

Reye Syndrome - incidence

• Peak incidence of 555 cases in children in the US in 1980
• From 1994–1997, there were no more than 2 cases of Reye syndrome annually.

Reye Syndrome - pathophysiology

• Mitochondrial injury of unknown etiology in a viral-infected host results in dysfunction of oxidative phosphorylation and fatty acid oxidation.
• Mitochondrial toxins, usually salicylates, exacerbate the condition when ingested after mitochondrial injury.

Postmortem:

• Liver: Grossly yellowish-white, due to increased triglyceride levels; foamy cytoplasm with increased microvesicular fat, decreased glycogen
• Brain: Marked edema with increased intracellular fluid and loss of neurons
• Abnormal-looking mitochondria can be detected in many tissues.

Reye Syndrome - DIAGNOSIS

Reye Syndrome - signs & symptoms

• Slight liver enlargement without jaundice
• Absence of focal neurologic signs
• Neurologic examination varies with stage of disease:
  • Stage 0: Alert, wakeful
  • Stage 1: Difficult to arouse, lethargic, sleepy
  • Stage 2: Delirious, combative, with purposeful or semipurposeful motor responses
  • Stage 3: Unarousable, with predominantly flexor motor responses, decorticate
  • Stage 4: Unarousable, with predominantly extensor motor responses, decerebrate
  • Stage 5: Unarousable, with flaccid paralysis, areflexia, and pupils unresponsive
  • Stage 6: Treated with curare or equivalent drug, and therefore unclassifiable

Reye Syndrome - history

• Prodromal illness: Upper respiratory infection (73%)—influenza B, influenza A, and varicella
• Abrupt-onset vomiting within 47 days of initial illness
• Natural history: Neurologic deterioration in which delirium may progress to seizures, coma, or death

Reye Syndrome - tests

Reye Syndrome - lab

• Ammonia test: Result may be normal at the onset of vomiting. Serum level exceeding 45 ์g/dL suggests higher mortality.
• CSF: Normal except for elevated intracranial pressure

Reye Syndrome - imaging

EEG: Characteristic of metabolic encephalopathy with generalized slow-wave abnormalities

Reye Syndrome - diag proced-surgery

• Liver and muscle function testing: Elevated levels of transaminases, creatinine kinase, lactate dehydrogenase, and ammonia; increased PT
• Metabolic workup: Abnormalities of organic and amino acids may be present if symptoms caused by a metabolic disorder

Reye Syndrome - differencial diagnosis

• It is important to distinguish between so-called classic Reye syndrome, associated with aspirin (acetylsalicylic acid) therapy, and Reye-like syndromes, often due to metabolic disorders and other causes, as mentioned subsequently.
• Metabolic diseases: In a report by Hou et al., Reye-like syndrome was secondary to hereditary organic acidemias (n = 13), urea cycle defects (n = 4), mitochondrial disorders (n = 3), fulminant hepatitis (n = 2), tyrosinemia (n = 1), and valproate-associated hepatotoxicity (n = 1). In the United Kingdom, 12% of Reye syndrome cases between 1981 and 1996 were subsequently reclassified as metabolic disorders.
• CNS infections (e.g., meningitis, encephalitis)
• Toxins
• Drug ingestion (e.g., salicylates, valproate)

Failure to recognize early and control or prevent cerebral edema—the immediate cause of death

Reye Syndrome - TREATMENT

Reye Syndrome - initial stabilization

• Should be tailored based on severity of presentation
• IV glucose to counteract effects of glycogen depletion
• Fluid restriction in patients with cerebral edema (1,500 mL/m²/d), along with mannitol to increase serum osmolality and induce cerebral dehydration

Reye Syndrome - general measures

Vitamin K, fresh-frozen plasma, and platelets as needed for treatment of secondary coagulopathy

Reye Syndrome - FOLLOW UP

Cerebral function at presentation is the best predictor of outcome.

Reye Syndrome - prognosis

• Most patients suffer only mild illness without progression.
• Patients with milder disease (stages 0, 1, 2) tend to recover completely.
• Patients with stage 3 disease are equally likely to recover completely or die.
• Patients with stage 4–5 disease usually do not survive.

Reye Syndrome - complications

• Elevated intracranial pressure secondary to cerebral edema
• Cardiovascular collapse
• Overall mortality of 31%

Reye Syndrome - bibliography

1. Belay ED, Bresee JS, Holman RC, et al. Reye’s syndrome in the United States from 1981 through 1997. N Engl J Med. 1999;340:1377–1382.
2. Chow EL, Cherry JD, Harrison R, et al. Related Articles, Reassessing Reye syndrome. Arch Pediatr Adolesc Med. 2003;157(12):1241–1242.
3. Duerksen DR, Jewell LD, Mason AL, et al. Co-existence of hepatitis A and adult Reye’s syndrome. Gut. 1997;41:121–124.
4. Glasgow JF, Middleton B. Reye syndrome—insights on causation and prognosis. Arch Dis Child. 2001;85:351–353.
5. Glasgow JF, Middleton B, Moore R, et al. The mechanism of inhibition of beta-oxidation by aspirin metabolites in skin fibroblasts from Reye’s syndrome patients and controls. Biochim Biophys Acta. 1999;1454:115–125.
6. Green CL, Blitzer MG, Shapiro E. Inborn errors of metabolism and Reye’s syndrome: Differential diagnosis. J Pediatr. 1988;113:156.
Hall SM, Lynn R. Reye’s syndrome. In Guy M, Nicoll A, Lynn R, eds. British Paediatric Surveillance Unit 11th annual report. London: Royal College of Paediatrics and Child Health: 1997;24–26.
7. Hou JW, Chou SP, Wang TR. Metabolic function and liver histopathology in Reye-like illnesses. Acta Paediatr. 1996;85:1053–1057.
8. Lichtenstein PK, Heubi JE, Dougherty CC, et al. Grade I Reye’s syndrome: A frequent cause of vomiting and liver dysfunction after varicella and upper respiratory tract infection. N Engl J Med. 1983;309:133.
9. Reye RDK, Morgan G, Baral J. Encephalopathy and fatty degeneration of the viscera: A disease entity in childhood. Lancet. 1963;2:749.
10. van Bever HP, Quek SC, Lim T. Related Articles, Aspirin, Reye syndrome, Kawasaki disease, and allergies: A reconsideration of the links. Arch Dis Child. 2004;89(12):1178.

Reye Syndrome - CODES

Reye Syndrome - icd9

331.81 Reye’s syndrome

Reye Syndrome - FAQ

• Q: Is Reye syndrome fatal?
• A: ~30% of children will die, usually due to cerebral edema. Mortality rates are best predicted by neurologic state at the onset of presentation.
• Q: How can the neurologic findings of Reye syndrome be differentiated from those of meningitis?
• A: Aside from elevated intracranial pressure, the lumbar taps of patients with Reye syndrome are at best unremarkable. Elevated leukocyte count is not seen in these cases.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Reye's Syndrome

• Back to disease: Reye's Syndrome: Introduction
• Next Book Extract About Reye's Syndrome: Hepatitis (Pediatric Infectious Disease)
• More Book Extracts: All Online Books for Reye's Syndrome

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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