First Sign of Reye Syndrome in Infants
The earliest clinical sign of Reye syndrome in infants is persistent vomiting, which typically begins 3-5 days after a prodromal viral illness (most commonly influenza or varicella) and precedes neurological deterioration. 1, 2
Clinical Presentation Timeline
Prodromal Phase
- A viral illness (influenza A or B, or varicella) occurs first, followed by an apparent recovery period of 3-5 days 3, 1
- The child initially appears to be improving from the viral infection before Reye syndrome symptoms emerge 1
Initial Warning Sign: Vomiting
- Persistent, severe vomiting is the hallmark early sign that distinguishes Reye syndrome from simple viral illness recovery 1, 2
- The vomiting is characteristically protracted and unusually severe, lasting 24-96 hours before serious neurological signs develop 2
- Any child with history of influenza or varicella within 1 week who develops vomiting lasting more than 12 hours, especially if associated with lethargy, should be evaluated for Reye syndrome 2
Important Distinction for Infants
In infants specifically, the presentation may be more subtle and atypical compared to older children: 1
- Diarrhea may be present instead of or in addition to vomiting 1
- Respiratory disturbances can occur 1
- Seizures may be an early manifestation 1
- The classic vomiting pattern seen in school-age children may be less prominent 1
Progression After Initial Vomiting
Neurological Deterioration
- Following the vomiting phase, neurological changes develop, including altered mental status, lethargy, and encephalopathy 3, 1
- Brain dysfunction manifests as disturbed consciousness and increased intracranial pressure without inflammatory signs 3
Associated Metabolic Findings
- Liver dysfunction with elevated transaminases (SGPT/ALT) is consistently present 2
- Metabolic acidosis is always detected 3
- Elevated blood ammonia levels (>45 μg/dL) are associated with worse prognosis 4
- Hypoglycemia may occur but is not universal 5
Critical Clinical Pitfalls
Recognition Challenges
- The biphasic nature creates a false sense of security - parents and clinicians may believe the child is recovering from the viral illness when vomiting begins 1
- In infants under 5 years, the case fatality rate is significantly higher (relative risk 1.8), making early recognition even more critical 4
- Symptoms in infants are more subtle than in older children, requiring higher clinical suspicion 1
Diagnostic Urgency
- Any infant with persistent vomiting (>12 hours) following influenza or varicella within the preceding week should have immediate liver function testing (SGPT/ALT) 2
- The vomiting precedes serious brain signs by 24-96 hours, creating a narrow window for intervention before irreversible neurological damage 2
- Early diagnosis and treatment in Stage I (non-comatose) cases significantly reduces morbidity and mortality 2
Modern Context
The incidence of Reye syndrome has declined dramatically since warnings about aspirin use in children with viral illnesses were issued in the 1980s, with fewer than 36 cases per year reported since 1987 4. However, the syndrome still occurs and carries a 31% overall case fatality rate 4. Given its rarity, any suspected case should prompt extensive investigation to rule out treatable inborn metabolic disorders that can mimic Reye syndrome 4.