Is aspirin use in children with viral infections associated with Reye syndrome?

Reye Syndrome and Aspirin Use in Children

Yes, aspirin use in children with viral infections, particularly influenza and varicella (chickenpox), is strongly associated with Reye syndrome, a rare but potentially fatal disease characterized by encephalopathy and fatty liver degeneration. 1, 2

The Evidence for This Association

The link between aspirin and Reye syndrome is well-established and has fundamentally changed pediatric practice since the 1980s. After warnings were issued about aspirin use in children with viral infections beginning in 1980, reported cases of Reye syndrome declined sharply from a peak of 555 cases in 1980 to no more than 36 cases per year since 1987. 3 This dramatic 93% reduction following public health warnings and FDA-required product labeling in 1986 provides compelling evidence of causation. 3, 4

• Among children with Reye syndrome, 82% had detectable blood salicylate levels, further supporting the association. 3
• The overall case fatality rate for Reye syndrome is 31%, with the highest mortality in children under 5 years of age. 3

Current Clinical Guidelines

All major medical organizations explicitly contraindicate aspirin use in children and adolescents with viral infections, particularly influenza and varicella. 1

Specific Contraindications

• Children and adolescents aged 6 months to 18 years receiving aspirin or other salicylates should not receive live attenuated influenza vaccine (LAIV) because of the association of Reye syndrome with wild-type influenza virus infection. 1
• The FDA drug label explicitly warns that children and teenagers who have or are recovering from chickenpox or flu-like symptoms should not use aspirin products. 2
• Children and adolescents receiving long-term aspirin therapy are at risk for developing Reye syndrome after influenza infection and require special precautions. 1

When Aspirin Must Be Used in Children

There are limited circumstances where aspirin benefits outweigh risks in pediatric patients, but these require specific monitoring:

Kawasaki Disease

• Aspirin at 80-100 mg/kg per day is used during the acute phase of Kawasaki disease, but children on long-term aspirin therapy must receive annual influenza vaccination. 1, 5
• Parents must be instructed to contact their physician immediately if the child develops symptoms of or exposure to influenza or varicella. 1, 5
• Reye syndrome has been documented in patients taking high-dose aspirin for prolonged periods after Kawasaki disease. 1, 5

Pediatric Stroke Prevention

• For stroke prevention, aspirin at 3-5 mg/kg per day is reasonable, but annual influenza vaccination and varicella vaccination verification are mandatory. 1, 6
• Aspirin should be halted during suspected influenza or varicella infections, though there is no consensus about discontinuation during other febrile illnesses. 1

Long-term Aspirin Therapy Considerations

• It remains unclear whether low-dose aspirin therapy (used for antiplatelet effects) increases Reye syndrome risk, but vigilance is still required. 1
• Some physicians substitute alternative antiplatelet medications (such as clopidogrel) for aspirin during the 6-week period after varicella vaccination. 1

Critical Clinical Pitfalls to Avoid

• Do not assume aspirin is safe during "minor" viral illnesses—the risk applies to all viral infections, particularly influenza and varicella. 2, 7
• Do not overlook adolescents and older children, as Reye syndrome is now more prevalent in this age group who may self-medicate with aspirin. 7, 8
• In infants, Reye syndrome symptoms may be subtle (diarrhea, respiratory disturbances, seizures) rather than the classic presentation of vomiting and altered mental status. 7
• Use acetaminophen or non-steroidal anti-inflammatory drugs (not aspirin) for fever relief in children with suspected viral infections. 1
• Never use aspirin-containing products like bismuth subsalicylate (Pepto-Bismol) in children aged ≤18 years with suspected influenza. 1

The Pathophysiology Context

Reye syndrome is a biphasic illness where a prodromal viral illness (frequently influenza A or B or varicella) is followed by protracted vomiting and neurologic changes 3-5 days later, just when the child seems to be recovering. 7, 8 Aspirin has been identified as a contributing factor to the metabolic disorder that occurs, involving severe brain edema, increased intracranial pressure, hypoglycemia, and fatty infiltration of the liver. 8