Overview
Reye’s syndrome describes acute, rare, life-threatening, non-inflammatory encephalopathy and fatty liver infiltration and dysfunction due to mitochondrial damage. It is associated with the use of aspirin under 16 years old and viral infections.
The risk of Reye’s syndrome is why aspirin and salicylates should never be given to children <16 years old unless the benefits outweigh the risks (for example, in Kawasaki disease).
Pathophysiology
Although the exact cause is unknown, viral infections and aspirin use in susceptible individuals lead to impaired mitochondrial function and lipid metabolism in the brain, liver, and kidneys. This can lead to hypoglycaemia and hyperammonaemia resulting in cerebral oedema.
Epidemiology
- The restriction of the use of aspirin in children has reduced the incidence of Reye’s syndrome
- Reye’s syndrome is generally rare in >18 year-olds and the peak incidence is 5-14 years old.
Presentation
- There may be a preceding viral infection or aspirin use
- Encephalopathy:
- As time goes on, the patient deteriorates
- Hypoglycaemia may be present
- Liver dysfunction is present, but jaundice is not typically present
Investigations
Overview
Initial investigations for Reye’s syndrome include:
- Blood glucose:
- Low – hypoglycaemia suggests a severe case and should be treated urgently
- Liver function tests (LFTs):
- Nearly always shows elevated AST/ALT
- Bilirubin is usually normal, hyperbilirubinaemia may suggest an alternate diagnosis
- Prothrombin time may be slightly prolonged in around 50% of cases
- Serum ammonia levels:
- Elevated
- Salicylate levels:
- May be elevated if aspirin use was the trigger
- Urinalysis:
- May show ketonuria and elevated specific gravity
- Urea and electrolytes (U&Es) and blood gases:
- May show metabolic acidosis and may be mixed with respiratory alkalosis
Other investigations may include:
- CT head:
- May show cerebral oedema, but may be normal
- Lumbar puncture – only if there are no contraindications (such as elevated intracranial pressure):
- To rule out other causes such as meningitis
- Usually normal but may show low glucose
- Electroencephalogram (EEG):
- Shows generalised slowing and flattening of waves
- Liver biopsy:
- Shows fatty infiltration
Diagnosis
Reye’s syndrome is diagnosed if there are no other explanations for the signs and symptoms seen. There are no specific tests, but some diagnostic criteria have been proposed:
- Non-inflammatory and acute encephalopathy
- Hepatic dysfunction and a liver biopsy showing fatty infiltration
- No other explanation for cerebral oedema or hepatic dysfunction
- Cerebrospinal fluid is sterile and has a maximum of <9 white cells/cm3 or a brain biopsy shows only cerebral oedema without inflammation
Management
Overview
Treatment is supportive and is aimed at correcting metabolic abnormalities and controlling elevated intracranial pressure. This may include maintaining oxygen saturation, correcting hypoglycaemia, treating hyperammonaemia, using anticonvulsants, and correcting coagulopathy.
Early discussion with specialists and admission to paediatric intensive care units should be sought.
Complications
- Neurological complications are the most likely:
- Brain herniation
- Seizures
- Long-term complications (e.g. learning difficulties, behavioural changes, memory problems, speech and language difficulties, hearing and visual loss)
- Acute respiratory failure
- Aspiration pneumonia
- Cardiovascular collapse
- Gastrointestinal bleeding – due to coagulopathy
- Acute kidney injury – due to fatty infiltration
- Pancreatitis – due to fatty infiltration
- Sepsis
Prognosis
- Early diagnosis and management are associated with a better prognosis, however, the mortality rate is around 20%.
- Around 20% of patients are left with persistent neurological complications
- Factors associated with a poorer prognosis are hyperammonaemia, <5 years old, and more advanced illness.
