How is Reye syndrome in a 4‑14‑year‑old child after influenza or varicella treated and prevented, especially when aspirin was used for fever?

Reye Syndrome: Treatment and Prevention

Immediate Management

There is no specific treatment for Reye syndrome; management focuses on correcting metabolic imbalances and reducing intracranial pressure with intensive supportive care. 1

Critical Supportive Interventions

• Immediately discontinue all aspirin and salicylate-containing products upon recognition or suspicion of Reye syndrome, as aspirin is a proven contributing factor to this metabolic disorder 1, 2

• Correct metabolic derangements including hypoglycemia, hyperammonemia (the most frequent laboratory abnormality occurring 24-48 hours after mental status changes), and coagulopathy 1

• Manage elevated intracranial pressure aggressively, as brain edema is the primary cause of mortality; this has reduced mortality from 50% to less than 20% through earlier diagnosis and more intensive therapy 1

• Consult a specialist in metabolic medicine immediately, as many children presenting with Reye-like symptoms have an underlying inborn error of metabolism that requires specific treatment 1

Clinical Presentation to Recognize

• Protracted vomiting followed by encephalopathy in an afebrile patient 24-48 hours after the vomiting begins, typically occurring 3-5 days after a viral illness (particularly influenza B or varicella) 1, 3

• Lethargy as the first neurological manifestation in older children; diarrhea and hyperventilation may be the first signs in children younger than 2 years 1, 3

• Hepatomegaly in 50% of patients with minimal or absent jaundice, plus threefold elevation in ALT/AST and elevated ammonia levels 1

Prevention Strategies

Primary Prevention: Avoid Aspirin in Children

The dramatic fall in Reye syndrome incidence following warnings about aspirin use in children provides the strongest evidence for prevention. 1, 2

• Never use aspirin for fever control in children with influenza or varicella, as the association between aspirin therapy and Reye syndrome is clear and consistent, with 82% of reported cases having detectable blood salicylate levels 1, 2

• Use acetaminophen or ibuprofen as alternative antipyretics during viral illnesses in children under 18 years of age 3

• Since 1980, reported cases declined from a peak of 555 cases annually to no more than 36 cases per year since 1987 following public health warnings about aspirin use 2

Special Considerations for Children on Long-Term Aspirin Therapy

For children requiring chronic aspirin therapy (e.g., Kawasaki disease, stroke prevention), specific precautions are essential:

• Administer annual influenza vaccination to all children on long-term aspirin therapy to reduce the risk of influenza infection 1, 4

• Verify varicella vaccination status and consider vaccination, weighing theoretical vaccine risks against known risks of wild-type varicella infection in children on salicylate therapy 1, 4

• Immediately discontinue aspirin during suspected influenza or varicella infections and instruct parents to contact their physician promptly if the child develops symptoms of or exposure to these viruses 1, 4

• Consider halting aspirin during other febrile illnesses, though consensus is lacking; some experts recommend discontinuation or dose reduction during any febrile illness given the apparent increased stroke risk during such illnesses 1

Alternative Management When Aspirin Cannot Be Used

• Administer IVIG 2 g/kg as a single infusion without aspirin in conditions like Kawasaki disease when Reye syndrome develops or influenza/varicella complicates treatment 5

• Substitute clopidogrel (1 mg/kg per day) as an alternative antiplatelet agent if antiplatelet therapy is needed after Reye syndrome resolves, though adequate safety data in children are lacking 1, 5

Critical Pitfalls to Avoid

• Do not assume the diagnosis is Reye syndrome without extensive investigation to rule out treatable inborn metabolic disorders that can mimic Reye syndrome, as the condition is now very rare 2

• Do not overlook that children on long-term aspirin therapy remain at risk even during low-dose maintenance phases, not just during high-dose therapy 4

• Do not miss that case fatality rate is highest (relative risk 1.8) in children under 5 years of age and in those with serum ammonia above 45 μg/dL (relative risk 3.4) 2

• Do not confuse Reye syndrome with acute necrotizing encephalopathy, which occurs predominantly in Japan, affects children aged 1-5 years, has fewer than 10% survival, and shows bilateral thalamic involvement on MRI 1, 6

Prognosis and Outcomes

• Overall case fatality rate is 31%, with death occurring from brainstem dysfunction secondary to cerebral edema 1, 2, 7

• Among survivors, 26% have residual neurological deficits and 43% achieve full recovery based on Japanese surveillance data 1

• Early recognition and aggressive supportive care are associated with decreased morbidity and mortality 3