Reye Syndrome

Snapshot

  • A 7-year-old girl is brought to the emergency room for lethargy and altered mental status. She was born at full term and previously healthy. She recently complained of feeling muscle soreness, headaches, and some nausea. A few of her classmates at school had tested positive for influenza A, and she was instructed to stay home from school during this time. Her parents gave her an aspirin herself this morning for her symptoms. On physical exam, she is noted to be obtunded and had hepatomegaly. On laboratory evaluation, she had elevated liver enzymes. She is admitted to the intensive care unit for supportive care and careful monitoring of her intracranial pressure.

Introduction

  • Clinical definition
    • acute non-inflammatory hepatic encephalopathy resulting in fatty liver and cerebral edema 
  • Epidemiology
    • demographics
      • children
      • very rare
    • risk factors
      • viral infection treated with aspirin
        • varicella
        • influenza
        • gastroenteritis
        • rarely, vaccination with live viruses
  • Pathogenesis
    • aspirin metabolites inhibit mitochondrial enzymes
      • disrupts oxidative phosphorylation and fatty acid beta-oxidation pathways
      • microvesicular fatty changes in the liver
  • Prognosis
  • mortality < 20%

Presentation

  • Symptoms
    • nausea and sudden-onset vomiting
    • diarrhea
    • lethargy
    • irritability
    • restlessness
    • delirium
    • seizures
    • coma
  • Physical exam
    • hepatomegaly
    • minimal jaundice
    • obtunded
    • in severe cases
      • permanent neurologic damage
      • fixed and dilated pupils
  • loss of oculovestibular reflexes

Imaging

  • Computed tomography (CT) of the brain
    • indication
      • all patients
    • findings
  • diffuse brain swelling

Studies

  • Diagnostic approach
    • other causes of encephalopathy must be ruled out, including central nervous system infections
  • Serum labs
    • ↓ blood glucose
    • ↑ ammonia
    • ↑ hepatic enzymes
    • ↑ long chain free fatty acid levels
  • Invasive studies
    • liver biopsy
      • indication
        • confirm diagnosis
      • findings
        • non-inflammatory fatty changes
  • microvesicular steatosis 

Differential

  • Inborn errors of metabolism, e.g., fatty acid oxidation defects, urea cycle defects, etc.
    • distinguishing factors
      • typically presents in infancy
      • genetic testing
  • normal liver size

Treatment

  • Management approach
    • avoid use of aspirin in children, except when necessary 
      • e.g., Kawasaki disease
    • treatment is largely supportive and neuro-protective
  • Medical
    • neuro-protection
      • indication
        • all patients
      • modalities
        • mannitol
        • glycerol
  • dexamethasone

Complications

  • Permanent brain damage
  • Death