What is Reye's syndrome?

Reye's Syndrome: A Rare but Serious Childhood Condition

Reye's syndrome is a rare childhood acute encephalopathy associated with liver dysfunction that typically follows viral illnesses and has a strong association with aspirin use during these infections. 1

Clinical Presentation and Pathophysiology

Reye's syndrome is characterized by a biphasic illness pattern:

• Initial phase: Viral prodromal illness (commonly influenza, particularly influenza B, or varicella)
• Second phase: Occurs 3-5 days later, just as the child appears to be recovering 2
• Key clinical features:
  • Protracted vomiting (usually the first symptom)
  • Encephalopathy in afebrile patients
  • Minimal or absent jaundice
  • Hepatomegaly in 50% of patients 1

Neurological Progression

• Lethargy is typically the first neurological manifestation
• Neurological symptoms usually develop 24-48 hours after vomiting begins
• In children under two years, diarrhea and hyperventilation may be the first signs 1

Diagnostic Criteria

Reye's syndrome comprises:

1. Acute non-inflammatory encephalopathy with altered consciousness
2. Elevated ammonia levels 24-48 hours after mental status changes (most frequent laboratory abnormality)
3. Hepatic dysfunction evidenced by:
   • Liver biopsy showing fatty metamorphosis, or
   • More than threefold increase in liver enzymes (ALT, AST) 1

Additional Diagnostic Findings

• Head CT may reveal cerebral edema but is often normal
• EEG typically shows slow wave activity in early stages, progressing to flattened waves in advanced stages
• CSF may have increased opening pressure with minimal white blood cells (<9/ml, usually lymphocytes) 1

Risk Factors

The strongest risk factor is aspirin use during viral illnesses, particularly influenza and varicella:

• The incidence of Reye's syndrome declined dramatically after warnings about aspirin use in children were issued 3
• 82% of reported cases had detectable blood salicylate levels 3
• Children on long-term aspirin therapy for medical conditions may be at increased risk if they develop influenza 1

Prognosis and Mortality

Mortality has improved with earlier diagnosis and aggressive management:

• Historical mortality was over 50% but has fallen to less than 20% 1, 4
• Poor prognostic factors include:
  • Age under 5 years (relative risk 1.8)
  • Serum ammonia level above 45 μg/dL (relative risk 3.4) 3
• In a Japanese study of 202 children with encephalopathy, outcomes included:
  • Death: 31%
  • Residual neurological deficit: 26%
  • Full recovery: 43% 1

Management

There is no specific treatment for Reye's syndrome. Key management principles include:

1. Correction of metabolic imbalances
2. Reduction of intracranial pressure
3. Consultation with specialists in metabolic medicine 1
4. Aggressive treatment of hyperammonemia may include arginine chloride, sodium benzoate, and hemodialysis in severe cases 5

Prevention

The most important preventive measure is avoiding aspirin use in children with viral illnesses. Since FDA warnings were implemented in 1986 requiring labels on aspirin products, the incidence has decreased dramatically from 555 cases in 1980 to fewer than 36 cases per year since 1987 3.

Important Considerations

• Many children with Reye's syndrome have underlying inborn errors of metabolism 1
• Atypical presentations may occur without aspirin exposure 6
• Due to its rarity today, any child suspected of having Reye's syndrome should undergo extensive investigation to rule out treatable inborn metabolic disorders that can mimic this condition 3
• In older adolescents who may self-medicate, awareness of the aspirin-Reye's syndrome connection remains important 2