Reye Syndrome

Reye syndrome is a rare but serious condition that causes swelling in the liver and brain, primarily affecting children and teenagers recovering from a viral infection. The syndrome was first described by Dr. Ralph Douglas Kenneth Reye in 1963.

Key Points

• Acute, non-inflammatory encephalopathy with fatty degeneration of the liver
• Typically occurs following viral illness treated with aspirin
• Medical emergency with rapid progression
• Mortality rate: 20-40% without early intervention
• Significant decrease in incidence since aspirin warning labels

Epidemiology & Risk Factors

Demographics

• Peak age: 5-14 years
• Rare in adults and infants
• Equal gender distribution
• Seasonal pattern correlating with viral infections

Risk Factors

• Primary Risk Factors:
  • Aspirin use during viral illness
  • Recent influenza B or varicella infection
  • Upper respiratory tract infections
  • Gastroenteritis
• Additional Risk Factors:
  • Genetic predisposition
  • Metabolic disorders
  • Fatty acid oxidation disorders
  • Organic acidemias

Historical Trends

• Peak incidence: 1970s (555 cases in 1980)
• Current incidence: <2 cases per year in US
• Dramatic decrease after aspirin warnings in 1980s

Pathophysiology

Cellular Mechanisms

• Mitochondrial dysfunction:
  • Disruption of oxidative phosphorylation
  • Impaired fatty acid β-oxidation
  • Accumulation of fatty acids in hepatocytes
• Metabolic derangements:
  • Increased ammonia levels
  • Elevated intracranial pressure
  • Impaired glucose metabolism

Organ System Effects

• Brain:
  • Cerebral edema
  • Altered neurotransmitter function
  • Disrupted blood-brain barrier
• Liver:
  • Microvesicular fatty infiltration
  • Preserved hepatic architecture
  • Minimal inflammation
  • Reversible changes if treated early

Clinical Presentation

Classic Presentation Pattern

• Phase 1: Viral Prodrome
  • Respiratory or varicella infection
  • Apparent recovery phase
  • Duration: 3-7 days
• Phase 2: Reye Syndrome Onset
  • Sudden behavioral changes
  • Persistent vomiting
  • Rapid neurological deterioration

Detailed Symptoms

• Neurological:
  • Personality changes
  • Lethargy progressing to delirium
  • Seizures
  • Decerebrate/decorticate posturing
  • Papilledema
  • Altered reflexes
• Gastrointestinal:
  • Protracted vomiting
  • Right upper quadrant pain
  • Hepatomegaly

Clinical Staging

Stage I

• Lethargy
• Vomiting
• Laboratory abnormalities

Stage II

• Delirium
• Combativeness
• Hyperventilation
• Hyperreflexia

Stage III

• Obtundation
• Light coma
• Decorticate rigidity
• Seizures may begin

Stage IV

• Deeper coma
• Decerebrate rigidity
• Fixed pupils
• Minimal response to pain

Stage V

• Deep coma
• Loss of brainstem reflexes
• Flaccidity
• Seizures
• Death possible

Diagnostic Approach

Laboratory Studies

• Essential Tests:
  • Liver function tests (↑AST, ALT)
  • Ammonia levels (↑↑)
  • Coagulation profile (↑PT, PTT)
  • Blood glucose
  • Comprehensive metabolic panel
• Additional Studies:
  • Complete blood count
  • Blood gas analysis
  • Cerebrospinal fluid analysis
  • Toxicology screen
  • Metabolic screening

Imaging

• Brain imaging:
  • CT scan: cerebral edema
  • MRI: exclude other diagnoses
• Liver imaging:
  • Ultrasound
  • CT if needed

Differential Diagnosis

• Metabolic disorders:
  • Medium-chain acyl-CoA dehydrogenase deficiency
  • Organic acidemias
  • Urea cycle disorders
• Other conditions:
  • Viral encephalitis
  • Toxic ingestion
  • Drug reaction
  • Intracranial hemorrhage

Management

Initial Stabilization

• Airway management:
  • Early intubation if needed
  • Maintain adequate oxygenation
• Hemodynamic support:
  • IV fluid resuscitation
  • Blood pressure maintenance
  • Cardiac monitoring

Specific Interventions

• ICP Management:
  • Head elevation
  • Osmotic therapy (mannitol/hypertonic saline)
  • Temperature control
  • Seizure prophylaxis
• Metabolic Management:
  • Glucose control
  • Correction of coagulopathy
  • Ammonia reduction measures

Monitoring

• Neurological status:
  • Frequent assessments
  • ICP monitoring if indicated
• Laboratory monitoring:
  • Serial ammonia levels
  • Liver function tests
  • Coagulation parameters

Prevention & Prognosis

Prevention Strategies

• Primary Prevention:
  • Avoid aspirin in children under 16
  • Use alternative antipyretics
  • Public health education
• Secondary Prevention:
  • Early recognition of symptoms
  • Prompt medical attention
  • Genetic counseling if indicated

Prognosis

• Factors Affecting Outcome:
  • Stage at presentation
  • Time to treatment initiation
  • Severity of cerebral edema
  • Associated complications
• Long-term Outcomes:
  • Complete recovery possible with early treatment
  • Neurological sequelae in severe cases
  • Stage-dependent mortality rate