Reye Syndrome

What happens in Reye syndrome

Reye syndrome damages the mitochondria, the energy-producing parts of cells, particularly in the liver and brain. The liver fills with tiny fat droplets and cannot process ammonia and other waste products properly. Ammonia builds up in the blood, blood sugar may drop, and the brain swells within the skull. Swelling raises pressure inside the skull, which can cause seizures, coma and death if not treated quickly.

Unlike most liver diseases, Reye syndrome usually does not cause yellow skin or eyes (jaundice), which can make it harder to recognize.

Causes and the aspirin link

The exact cause is unknown, but the strongest known risk is taking aspirin (acetylsalicylic acid) or other salicylates during a viral infection, especially:

• Influenza (flu), both types A and B
• Chickenpox (varicella)
• Less often, other viral infections such as colds and stomach bugs

In the 1980s, after public health warnings, labeling changes and campaigns telling parents not to give aspirin to children, Reye syndrome cases in the US fell from hundreds per year to only a few. This dramatic decline strongly supports the link.

Salicylates are found in more products than many people realize:

• Aspirin and some combination cold, flu and pain products
• Bismuth subsalicylate (Pepto-Bismol, Kaopectate in some formulations)
• Some teething gels in certain countries (choline salicylate)
• Oil of wintergreen (methyl salicylate) and some topical muscle rubs, in large amounts

Some children with Reye-like illness turn out to have an inherited metabolic disorder, such as a fatty acid oxidation disorder or a urea cycle defect. Doctors test for these, especially in younger children or those without aspirin exposure.

Symptoms

Symptoms usually begin 3 to 5 days after the start of a viral illness, often just as the child seems to be recovering.

Early signs

• Sudden, repeated vomiting
• Lethargy, sleepiness or loss of energy
• In infants: diarrhea and rapid breathing instead of vomiting

Later signs

• Confusion, disorientation or hallucinations
• Irritability, aggressive or irrational behavior
• Weakness or paralysis of the arms or legs
• Seizures
• Decreasing consciousness, leading to coma
• Abnormal stiff posturing of the body

Stages

Doctors grade severity from stage I to V:

Children diagnosed and treated at stage I or II have a much better outlook.

Diagnosis

There is no single test. Doctors look for the combination of brain and liver involvement after a viral illness, and exclude other causes such as meningitis, encephalitis, poisoning and metabolic disorders:

• Blood tests: raised liver enzymes (AST, ALT) and ammonia, low blood sugar, prolonged clotting times, normal or only slightly raised bilirubin
• Salicylate level if aspirin exposure is possible
• Lumbar puncture to rule out infection
• CT or MRI of the brain to look for swelling and other causes
• Liver biopsy, occasionally, to show the typical small fat droplets
• Metabolic screening for inherited disorders

Treatment

There is no cure, so treatment supports the body while the illness runs its course, usually in a pediatric intensive care unit:

• Reducing brain swelling: head elevation, medicines such as mannitol or hypertonic saline, controlled breathing on a ventilator, and pressure monitoring in severe cases
• IV glucose to correct and prevent low blood sugar
• Fluids and electrolytes, carefully balanced to avoid worsening brain swelling
• Vitamin K and plasma to correct clotting problems
• Seizure control
• Close monitoring of breathing, heart rhythm and blood pressure

Outlook

Outcome depends mostly on how severe the brain swelling becomes. Children treated early, before coma, usually recover fully. Deeper coma carries a high risk of death or lasting brain damage, such as learning difficulties, speech or movement problems and seizures. Historically, the death rate was about 20% to 30% or higher in severe cases. Early recognition has improved survival.

Prevention

• Do not give aspirin or salicylate-containing medicines to children or teenagers under 19, unless a doctor prescribes it for a specific condition, such as Kawasaki disease.
• Check labels for "aspirin", "acetylsalicylic acid", "salicylate", "salicylic acid" or "subsalicylate".
• Use acetaminophen (paracetamol) or ibuprofen for fever and pain in children, following the label dose.
• Keep children up to date with flu and chickenpox vaccines.
• Children who must take long-term aspirin should get a yearly flu vaccine and their doctor should be contacted promptly if they are exposed to flu or chickenpox.

Frequently asked questions

Why can't children take aspirin?

Aspirin taken during a viral infection such as flu or chickenpox is linked to Reye syndrome, a rare but dangerous illness that causes brain swelling and liver damage. For this reason, aspirin and salicylates are avoided in anyone under 19 unless a doctor specifically prescribes them.

What are the first signs of Reye syndrome?

The first signs are sudden, persistent vomiting and unusual sleepiness or lethargy, typically 3 to 5 days into a viral illness. These can quickly progress to confusion, irritability, aggressive behavior and seizures. Infants may have diarrhea and fast breathing instead.

Can adults get Reye syndrome?

It is very rare in adults. Most cases occur in children and teenagers, especially between 4 and 14. A few adult cases have been reported. The general advice to avoid aspirin applies to people under 19.

Is Reye syndrome still a problem today?

It is now very rare in countries where parents avoid giving aspirin to children. US cases dropped from hundreds per year in the 1980s to a handful. It still occurs occasionally, so the advice to avoid aspirin in children remains important.

Is Pepto-Bismol safe for children?

Standard Pepto-Bismol contains bismuth subsalicylate, a salicylate related to aspirin, and is not recommended for children and teenagers recovering from flu or chickenpox. Check the label and ask a pharmacist for a child-specific alternative.