Reye's Syndrome in Infants with Kawasaki Disease on High-Dose Aspirin
What is Reye's Syndrome
Reye's syndrome is a rare but life-threatening condition characterized by acute hepatic encephalopathy and fatty degeneration of the liver, occurring when children take salicylates during active viral infections (particularly influenza or varicella) or after prolonged high-dose aspirin therapy. 1
The syndrome presents with:
- Sudden onset of persistent vomiting 2, 3
- Altered mental status progressing from lethargy to confusion and coma 2, 3
- Hepatomegaly with elevated liver enzymes (AST/ALT) 2, 3
- Hyperammonemia (ammonia >45 μg/dL is associated with worse outcomes) 4
- Hypoglycemia 2, 3
- Coagulopathy (prolonged PT/PTT) 2, 3
The overall mortality rate is 31%, with infants under 5 years at highest risk (relative risk 1.8). 4
Detection and Monitoring Protocol
Clinical Surveillance
Parents must be instructed to contact their child's physician immediately if the infant develops symptoms of or is exposed to influenza or varicella. 1, 5
Monitor specifically for:
- Behavioral changes with nausea and vomiting (early warning signs per FDA labeling) 6
- Poor activity, poor appetite, lethargy 3
- Tachycardia and tachypnea 3
- Any neurologic deterioration 7
Laboratory Monitoring
When Reye's syndrome is suspected, obtain:
- Liver function tests (AST/ALT elevation) 2, 3
- Serum ammonia (levels >45 μg/dL predict poor outcomes) 4
- Blood glucose (hypoglycemia is characteristic) 2, 3
- Coagulation studies (PT/PTT) 2, 3
- Blood salicylate levels (detectable in 82% of cases) 4
Liver biopsy shows microvesicular steatosis, confirming the diagnosis. 2, 3, 7
Treatment Approach
Immediate Management
When Reye's syndrome is suspected, immediately discontinue aspirin and provide intensive supportive care. 2, 3
The treatment protocol includes:
- Admission to intensive care unit 2
- Correction of hypoglycemia with intravenous dextrose 3
- Management of elevated intracranial pressure 7
- Correction of coagulopathy with fresh frozen plasma or vitamin K 3
- Ammonia-lowering strategies if hyperammonemia is severe 4
- Supportive care for hepatic encephalopathy 7
Aspirin Management During Viral Illness
In infants with Kawasaki disease who develop influenza, administer high-dose IVIG without aspirin and use alternative antipyretic drugs (acetaminophen) for fever control. 1
- Substitute an alternative antiplatelet agent for a minimum of 2 weeks during active viral infection 1
- Resume aspirin only after complete resolution of viral illness 1
Prevention Strategies
Vaccination Requirements
All infants ≥6 months on aspirin therapy must receive annual inactivated influenza vaccine before leaving the hospital, as must family members. 1, 5
Critical vaccination points:
- Only inactivated influenza vaccine should be administered to children on aspirin 1
- Infants with acute Kawasaki disease during influenza season who haven't been immunized should receive vaccine before hospital discharge 1
- Family members must also be vaccinated to reduce exposure risk 1
Varicella Considerations
Physicians must weigh theoretical risks of varicella vaccine against known risks of wild-type varicella infection in infants on long-term salicylate therapy. 1
- Some physicians substitute another antiplatelet medication for aspirin during the 6-week post-vaccination period 1
- Verify varicella vaccination status 1
Critical Pitfalls to Avoid
Do not assume the risk exists only during high-dose aspirin therapy—Reye's syndrome has been reported in patients taking high-dose aspirin for prolonged periods after Kawasaki disease, though low-dose antiplatelet therapy has not been associated with Reye's syndrome. 1, 5
Additional pitfalls:
- Do not continue aspirin during active influenza or varicella infections—the benefits of aspirin do not outweigh Reye's syndrome risk during active viral illness. 1, 6
- Do not delay intensive care admission if Reye's syndrome is suspected—rapid progression to coma can occur within hours 2, 3
- Do not assume all cases are aspirin-related—investigate for treatable inborn metabolic disorders that mimic Reye's syndrome 4
Special Considerations for Infants Under 8 Months
Infants under 5 years have the highest case fatality rate (relative risk 1.8), making vigilant monitoring even more critical in this age group. 4
Two documented cases of Reye's syndrome occurred in infants (7 months and 10 months) on high-dose aspirin for Kawasaki disease, with one fatality despite intensive treatment. 2, 3 These cases occurred 1-3 days after transitioning from high-dose to low-dose aspirin, emphasizing that vigilance must continue throughout all phases of treatment. 2, 3