Reye Syndrome



  • A serious, acute noninflammatory encephalopathy associated with cerebral edema and fatty infiltration of the liver classically noted in children taking aspirin during a viral infection (1)
  • Occurs primarily in children and teenagers <18 years (1)
  • Reye syndrome (RS) is typically biphasic, often initially presenting with symptoms of viral or bacterial infection (i.e., in order of association influenza A or B, varicella, parainfluenza, measles, adenovirus, coxsackieviruses, parechovirus, CMV, EBV, HIV, hepatitis A or B, Mycoplasma, and Chlamydia), 1 to 5 days without symptoms, followed by onset of severe vomiting, altered mental status, and signs of acute encephalopathy (2).
  • RS is currently very rare since warning statements by the CDC and American Academy of Pediatrics in 1982 were issued for use of aspirin in children, followed by black box warning in 1986 against use of aspirin in children and teenagers with recent viral illness (1,3).
  • System(s) affected: gastrointestinal, nervous, muscular, and cardiac
  • Synonym(s): white liver disease



  • Predominant age (1,3)
    • <18 years old
    • Peak incidence at 1 to 3 years old
  • Predominant sex: male = female (4)
  • Currently very rare. In the United States, <0.1/100,000 annually. Prior to issued warnings about aspirin use in children, the United States documented 555 case reports in 1980. Most recent U.S. statistics noted no more than 2 cases per year between 1994 and 1997 (1).
  • Mortality rate 20–40%, males > females (2)

Etiology and Pathophysiology

Specific etiology is unknown but appears to be secondary to multiple synergistic factors causing acute mitochondrial injury from significant inhibition of fatty acid oxidation limiting gluconeogenesis causing hypoglycemia, elevated ammonia, acute transaminitis, and hepatic fatty infiltration (1).

Possible genetic factors that lead to predisposition for development of RS but currently no known genetic pattern (2)

Risk Factors

  • Pediatric age group
  • Prodromal illnesses
    • Viral: influenza A and B, varicella, parainfluenza, measles, adenovirus, coxsackievirus, parechovirus, EBV, CMV, HIV, hepatitis A and B, or rotavirus
    • Bacterial: Mycoplasma, Chlamydia, Salmonella, Shigella (2)
  • Use of preparations containing aspirin, salicylates, and/or salicylamides (1)
  • Other exogenous agents with less significant association: valproic acid, aflatoxin in Thailand, bongkrekate in Indonesia, margosa oil in Southern Asia, unripe ackee fruit in Jamaica, hopentanate in Japan, and insecticides in Canada (1)

General Prevention

  • Avoid salicylates in children with viral illnesses because the drug appears to act as a cofactor in susceptible individuals (1).
  • A physician should be consulted before giving any child aspirin or antinausea medicines (containing salicylates) during a viral illness, especially influenza A (3).
  • Recognize early symptoms of the disease for prompt initiation of supportive treatment (4).

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