What are the clinical manifestations of Reye's syndrome?

Symptoms of Reye's Syndrome

Reye's syndrome presents with protracted vomiting followed 24-48 hours later by acute encephalopathy in an afebrile child, typically after a viral illness, with minimal or absent jaundice and hepatomegaly in 50% of cases. 1

Clinical Presentation Timeline

The syndrome follows a characteristic two-phase pattern:

Phase 1: Gastrointestinal Symptoms

• Protracted, persistent vomiting is the hallmark initial symptom
• Occurs following a viral illness (particularly influenza B or varicella)
• Patient becomes afebrile at this stage (important distinguishing feature)
• In children younger than 2 years, diarrhea and hyperventilation may be the first signs 1

Phase 2: Neurological Deterioration (24-48 hours after vomiting onset)

• Lethargy is usually the first neurological manifestation 1
• Progressive altered level of consciousness ranging from confusion to coma
• Agitated delirium may occur 2
• Seizures can develop
• Behavioral disturbances and personality changes
• In severe cases: obtundation and coma 2

Physical Examination Findings

• Hepatomegaly in 50% of patients 1
• Minimal or absent jaundice (despite liver dysfunction) 1
• No fever at presentation (distinguishes from encephalitis)
• Signs of increased intracranial pressure in advanced stages
• Cerebral edema 3, 2

Laboratory Abnormalities

The diagnostic triad comprises 1:

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 with:
   • More than threefold increase in ALT and AST
   • Fatty metamorphosis on liver biopsy

Additional findings include:

• Hypoglycemia 3
• Metabolic acidosis 4
• Prolonged prothrombin time
• Normal or minimally elevated bilirubin

Critical Clinical Context

The syndrome typically follows a viral illness (especially influenza B or varicella) and has strong association with aspirin use in children 1, 5. There is characteristically a 3-5 day disease-free interval between the viral illness and onset of Reye's syndrome symptoms 5.

Important Caveats

• The absence of fever at presentation is a key distinguishing feature from infectious encephalitis
• CSF may show increased opening pressure but WBCs are typically fewer than 9/ml (usually lymphocytes) 1
• Head CT may reveal cerebral edema but is often normal initially 1
• Any child with recurrent episodes should be investigated for inborn errors of metabolism, as several metabolic disorders can present with "Reye-like" syndromes 6, 7

The mortality has decreased from 50% to less than 20% with earlier diagnosis and aggressive management of metabolic imbalance and intracranial pressure 1.