What are the diagnostic criteria for Reye syndrome?

Diagnostic Criteria for Reye Syndrome

Reye syndrome is diagnosed based on the presence of acute non-inflammatory encephalopathy with altered level of consciousness, elevation of ammonia levels 24-48 hours after mental status changes, and hepatic dysfunction with fatty metamorphosis or significantly increased liver enzymes, typically following a viral illness with a clear association with aspirin therapy. 1

Clinical Presentation

• Initial prodromal viral illness (often influenza or varicella)
• Followed by protracted vomiting (a key early symptom)
• Encephalopathy in an afebrile patient
• Minimal or absent jaundice (distinctly uncommon in Reye syndrome)
• Hepatomegaly (present in approximately 50% of patients)

Diagnostic Criteria

Essential Features:

1. History of recent viral illness
2. Acute non-inflammatory encephalopathy with altered mental status
3. Hepatic dysfunction without jaundice
4. Absence of other explanations for cerebral and hepatic abnormalities

Laboratory Findings:

• Elevated serum aminotransferases (transaminases) - 3+ times normal
• Elevated blood ammonia levels (typically 24-48 hours after mental status changes)
• Prolonged prothrombin time
• Normal cerebrospinal fluid (CSF) with minimal white blood cells (<9/ml, usually lymphocytes) 1, 2
• Absence of hypoglycemia (though this may be present in some cases)

Histopathologic Confirmation:

• Microvesicular fatty infiltration of the liver
• Characteristic mitochondrial changes 2

Diagnostic Workup

Initial Assessment:

• Complete blood count
• Comprehensive metabolic panel including liver enzymes
• Coagulation studies
• Serum ammonia level
• Blood and urine toxicology screen (to rule out drug ingestion)
• CSF analysis (to rule out infection)
• Head CT or MRI (may show cerebral edema)
• EEG (may show slow wave activity) 1

Confirmatory Testing:

• Liver biopsy - typically mandatory in adults for definitive diagnosis 2

Differential Diagnosis

The diagnosis of Reye syndrome must exclude:

• Inborn errors of metabolism (particularly disorders of organic acid, ammonia, and carbohydrate metabolism)
• Drug or toxin ingestion (a common mimicker in adults)
• Acute liver failure from other causes
• Viral encephalitis
• Alcohol abuse
• Collagen vascular disease
• Hepatitis B infection 1, 2

Staging System

Reye syndrome is typically classified into five stages based on neurological status:

1. Stage I: Vomiting, lethargy, drowsiness
2. Stage II: Disorientation, delirium, combativeness, hyperventilation
3. Stage III: Coma, hyperventilation, decorticate rigidity
4. Stage IV: Deepening coma, decerebrate rigidity, large pupils with minimal response to light
5. Stage V: Seizures, loss of deep tendon reflexes, flaccidity, respiratory arrest

Important Clinical Considerations

• Patients with recurrent episodes should be thoroughly investigated for underlying inborn errors of metabolism 3
• In adults, Reye syndrome is more difficult to diagnose and should be suspected in patients with unexplained altered behavior following a viral illness and vomiting 2
• The strong association with aspirin use during viral illnesses is a critical diagnostic clue 1
• Early diagnosis and aggressive management have reduced mortality from over 50% to less than 20% 1, 4

The diagnosis of Reye syndrome requires a high index of suspicion, particularly in adults where it may be misdiagnosed as acute neurological disease or drug reactions 4. Prompt recognition and treatment are essential for improving outcomes.