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What is Reye's Syndrome?

Reye’s syndrome, also called Reye syndrome, is a rare but potentially fatal children’s disease. This rare condition affects children and adolescents. Most cases occur in children between the ages of 4 and 12 years. There are rare reports of Reye’s syndrome in infants, older children, and young adults.

According to the National Reye’s Syndrome Foundation, the condition is most commonly linked to the use of drugs called salicylates, particularly aspirin and aspirin-containing medicines, during viral illnesses such as an upper respiratory tract infection (influenza) or varicella (chickenpox). Less commonly, Reye’s syndrome occurs in association with other viral infections such as rubella, herpes simplex, and Epstein-Barr.

Reye’s syndrome was first described by an Australian pathologist called R.D.K. Reye in 1963. National surveillance of Reye syndrome began in the United States in the early 1970s, leading to strict warnings against the use of aspirin in children.

Early Signs and Symptoms of Reye Syndrome

Reye’s syndrome causes swelling in the brain and liver. Early signs and symptoms of Reye’s syndrome include:

• Lack of energy, listlessness, sluggishness, or sleepiness

• Vomiting that doesn’t stop or keeps happening again and again

• Changes in personality, such as irritability, aggression, irrational behavior, or combativeness

• Diarrhea and rapid breathing (in children younger than 2 years of age)

As the condition progresses, it can cause:

• Disorientation or confusion

• Hallucinations (seeing or hearing things that are not there)

• Delirium (altered attention and thinking abilities)

• Weakness of the limbs (inability to move the arms or legs)

• Seizures or convulsions

• Loss of consciousness

The symptoms of Reye’s syndrome develop due to cerebral edema (swelling in the child’s brain) and changes in liver function due to fat deposition. Therefore, it is called an acute noninflammatory encephalopathy and fatty degeneration of the liver. 

Early symptoms of Reye’s syndrome can rapidly progress to more severe symptoms, coma, and death. However, early detection and treatment for Reye’s syndrome can result in a full recovery.

What is the Main Cause of Reye's Syndrome? 

Common Triggers

The exact cause of Reye’s syndrome is unknown. However, it’s been linked to the use of acetylsalicylic acid (aspirin) in children and teens during a viral illness. Therefore, caution is advised when giving aspirin to children and adolescents to treat pain or fever. 

What Medication Causes Reye's Syndrome?

Medications called salicylates, most notably aspirin and salicylate-containing medicines such as Pepto-Bismol (bismuth subsalicylate), can cause Reye’s syndrome, especially in children and teenagers who are recovering from a viral infection. 

Genetic and Environmental Influences

Sometimes, Reye's syndrome is not linked to the use of aspirin but rather to underlying metabolic disorders called fatty acid oxidation disorders (FAODs). Specifically, it has been linked to medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. These are rare, inherited, inborn errors of metabolism in which the body cannot break down fatty acids due to an absent or dysfunctional enzyme. People with fatty acid oxidation disorders are more likely to develop Reye’s syndrome after taking aspirin during a viral illness, such as influenza or chickenpox. Your child’s doctor can order a screening test to find out if they have a fatty acid oxidation disorder.

Additionally, exposure to certain toxins, such as herbicides, insecticides, and paint thinner, can also cause a Reye-like syndrome with similar symptoms. Keep in mind that these toxins do not cause Reye’s syndrome.

How is Reye's Syndrome Diagnosed?

There is no specific test to diagnose Reye’s syndrome. Laboratory findings in children with Reye syndrome may include low blood sugar, elevated levels of ammonia and acidity in the blood, and elevated liver enzymes. A diagnosis is made based on the symptoms a child experiences, their medical history, and physical examination while ruling out other causes. 

Some of the diagnostic tests done to exclude other causes of liver and brain problems in children experiencing symptoms similar to Reye syndrome include:

• Blood tests

• Urine tests.

• Spinal tap or lumbar puncture to obtain a sample of cerebrospinal fluid to rule out infection in the brain and spinal cord such as meningitis.

• A liver biopsy is done to look for signs of fat buildup in liver cells or other problems with the liver. 

• CT scan or MRI scan to look for causes of decreased alertness and check for swelling in the brain. 

How Quickly Does Reye's Syndrome Progress?

Case reports indicate that most children and teens develop Reye syndrome 3-5 days after the onset of a viral infection. Once the symptoms develop, the condition progresses quickly and can result in deep coma and death. Early diagnosis and treatment are, therefore, vital to prevent brain damage and death.

Conditions Similar to Reye's Syndrome

Conditions that can cause symptoms similar to Reye’s syndrome include:

• Rare inborn errors of metabolism, such as ornithine transcarbamylase (OTC) deficiency and glutaric aciduria type I (GA1), also known as glutaryl-CoA dehydrogenase deficiency (GCDH).

• Urea cycle disorders.

• Fatty acid oxidation disorders.

• Organic acidurias.

• Central nervous system infections, including encephalitis and meningitis (inflammation in the brain).

Treatment and Management

Immediate Medical Interventions

As noted, there can be rapid progression in Reye’s syndrome, resulting in life-threatening health complications. Therefore, if there is suspicion of Reye’s syndrome, the patient needs to seek medical care immediately in the emergency room.  Severe cases of Reye’s syndrome may require close monitoring in an intensive care unit (ICU). Immediate treatment consists of:

• Close monitoring of the child’s blood pressure, heart rate, and other vital signs 

• Mental status and intracranial pressure monitoring

• Intravenous (IV) fluids and glucose support with insulin and dextrose-containing IV fluids

• Diuretics (water pills) for increased intracranial pressure as these medicines help to decrease pressure on the brain by increasing fluid elimination from the body through urine

• Corticosteroids to help with inflammation and brain swelling

• Vitamin K, plasma, and platelets to treat  bleeding due to liver problems

• Cooling blankets to maintain the child’s body temperature at a desirable range

• Ventilator for breathing support, if needed

What Are the Long-Term Effects of Reye's Syndrome?

Most children and teenagers who develop Reye's syndrome make a full recovery. However, some children are left with varying degrees of brain damage, delayed cognitive development, epilepsy, nerve damage, and muscle weakness. These conditions may require long-term management and rehabilitation. In the absence of a proper diagnosis and treatment, Reye's syndrome can be fatal within a few days.

Prevention Strategies

Public Health Recommendations

Case reports show that children and teenagers recovering from a viral respiratory infection or chickenpox who took aspirin developed Reye syndrome. Because of these medication reactions, public health recommendations are that you should not give a child aspirin or salicylate-containing medications such as Pepto-Bismol if they are recovering from a flu-like illness or chickenpox. 

Some medical facilities perform screening for fatty acid oxidation disorders in newborns. Children diagnosed with fatty acid oxidation disorders should not take aspirin or salicylate-containing medicines.

The only exception to the general rule about aspirin use in children and teenagers is in those with Kawasaki disease and other chronic conditions that require long-term treatment with aspirin-containing drugs. In these cases, it is important to make sure that the child’s vaccinations are up-to-date. 

Safe Medication Practices

Check medication labels before giving them to children, especially herbal remedies and over-the-counter (OTC) drugs available without a prescription. Salicylate is an ingredient in many OTC products, including Alka-Seltzer and Pepto-Bismol.

Be aware of the different names of aspirin, such as salicylic acid, salicylate, acetylsalicylic acid, and acetylsalicylate.

Aspirin is approved for use in children older than 3 years of age. However, you should avoid giving aspirin to children and adolescents of any age to treat pain and fever. There are safer alternatives such as acetaminophen (Tylenol) or ibuprofen (Motrin, Advil) that are specially formulated for children.

Make sure your child is up-to-date on recommended vaccinations, including two doses of the chickenpox vaccine and the annual flu vaccine. These two viral illnesses are most closely linked to Reye's syndrome. Preventing them can prevent Reye’s syndrome or reduce your child’s risk of developing this dangerous condition.

Resources and Support

Support Groups and Community Resources

• National Reye’s Syndrome Foundation (NRSF)

• National Organization for Rare Disorders (NORD)

Educational Materials for Parents and Caregivers

• National Institute of Neurological Disorders and Stroke NINDS (Reye’s Syndrome)

• National Library of Medicine (Reye Syndrome)

Professional Guidelines for Healthcare Providers

• Medscape (Reye’s Syndrome)