What parents should know about Reye’s syndrome

What is Reye’s syndrome? | Symptoms | Diagnosis | Treatments | Prevention

If you’re a parent, you may know that you should never give aspirin to a child with chickenpox or the flu. The reason for this is to decrease the risk of a serious condition and potentially fatal disorder called Reye’s syndrome, or Reye syndrome, which can cause liver dysfunction and swelling in the brain and has been linked to the use of aspirin in children and teens with viral infections like influenza, varicella (which causes chickenpox), upper respiratory tract infections, and COVID-19, which is caused by the novel coronavirus.

In 1980, the Centers for Disease Control and Prevention (CDC) recorded 555 cases of Reye’s syndrome in the United States. Fortunately, that same year widespread warnings about aspirin use for children started, and since 1994 fewer than two cases have been reported each year nationwide.

“In the ’80s, about 1 in every 100,000 kids got it—now, it’s about 1 in a million,” says Amy Cram, MD, a pediatrician with Northeast Medical Group. “That’s largely because we know that using aspirin as a fever reducer or anti-inflammatory increases the risk.”

Most children (about 80%) who get Reye’s syndrome survive, but it needs to be treated immediately, often in a hospital’s intensive care unit. If left untreated, Reye’s syndrome can lead to permanent brain damage or death in just a few days. 

RELATED: What’s the best pain reliever or fever reducer for kids?

What is Reye’s syndrome?

Reye’s syndrome is an illness that is almost always found in children and adolescents under the age of 18—most commonly those aged 4 to 12—but it can affect people of any age. Doctors don’t know exactly what causes Reye’s syndrome, but it always follows another illness and is usually linked to the use of medicines that contain aspirin in children who have a viral infection.

Aspirin, also known as acetylsalicylic acid, salicylic acid, or acetylsalicylate, is the most-utilized pain-relieving drug in history. It works by inhibiting the body’s production of prostaglandins, which are compounds produced by enzymes in the body that play a key role in the body’s inflammatory response to an infection or injury. 

When it is used for a viral illness, aspirin can affect a person’s mitochondria, which are tiny structures in the cells called that generate the power to run the cell.  

“Aspirin in the setting of a viral illness, such as influenza or chickenpox, causes liver mitochondrial injury,” says Nathan Friday, Pharm.D., a pharmacist with Kroger. And this causes liver dysfunction. 

This mitochondrial dysfunction can lead to a buildup of ammonia—a byproduct of metabolism—in the bloodstream. This condition, called hyperammonemia, can lead to swelling in the brain and increased pressure on the brain as it presses against the skull. The amount of swelling and pressure determine the severity of an individual’s neurologic symptoms.   

Reye’s syndrome symptoms

Although it affects all the body’s organs, Reye’s syndrome does the most harm to the brain and liver. That’s why, in medical terms, it’s defined as: “acute noninflammatory encephalopathy with fatty liver failure.” Encephalopathy, a condition that alters the brain’s function or structure, is the most dangerous symptom of Reye’s syndrome, but it’s very hard to recognize until the damage is already being done to the brain and the signs of the illness become apparent.

Signs typically appear three to five days after the onset of a viral infection and usually start with sudden, continuous vomiting, although in children under 2 years of age, the first sign may be diarrhea. The vomiting is usually followed by increased lethargy or unusual sleepiness; however, children less than 12 months may present without vomiting. Neurologic symptoms then start to appear within the next 24 to 48 hours and may include:

• irritability
• restlessness
• disorientation
• personality changes
• impaired memory

As the illness rapidly progresses and the brain continues to deteriorate due to swelling and pressure, further symptoms can include:

• dilated pupils
• confusion or disorientation
• hallucinations
• shallow or rapid breathing
• rapid heart rate
• loss of consciousness

In addition to its neurologic symptoms, Reye’s syndrome can also cause massive accumulations of fat in the liver and other organs. The severity of symptoms and the prognosis for recovery vary widely and depend on the amount of damage done to the brain. Some people have mild symptoms and make a full recovery. Others are left with some degree of mental or physical impairment.

In severe cases, damage to the brain can lead to seizures, paralysis in the arms and legs, coma, and eventually death. The mortality rate of Reye’s syndrome was once about 50%, but that number has decreased to less than 20% in recent years.

How is Reye’s syndrome diagnosed?

Early diagnosis and treatment are vitally important with Reye’s syndrome, so any infant, child, or teen who has recently had a viral infection and exhibits any of the symptoms of Reye’s syndrome should be taken to a hospital emergency room as quickly as possible. For proper diagnosis, it’s important that caregivers provide a detailed medical history of all medications, including over-the-counter, supplements, and vitamins, that a patient took.

Diagnosis typically starts with blood tests and urine tests to check for things like elevated fatty-acid or ammonia levels in the blood. Liver chemistry tests, in particular, can be helpful. The results can be ready within a few hours, and the tests can detect elevated levels of certain liver-produced enzymes in the blood. High levels of these enzymes are a likely sign of Reye’s syndrome. 

A number of other disorders can cause symptoms that are similar to Reye’s syndrome, so part of the diagnosis will consist of ruling out conditions like:

• fatty-acid oxidation disorders and other liver function issues
• inborn errors of metabolism and other metabolic disorders
• substance use, ingestion, or exposure to toxins
• central nervous system infections such as encephalitis (inflammation of the brain) and meningitis (inflammation of the protective membranes surrounding the brain and spinal cord)
• psychiatric illness

In some cases, a spinal tap may be done to detect increased pressure in the body’s cerebrospinal fluid (CSF). In this procedure, also called a lumbar puncture, a needle is inserted through the lower back into a space alongside the spinal column, and a small amount of CSF is removed for testing. Increased intracranial pressure can also sometimes be detected by magnetic resonance imaging (MRI) or a computerized tomography (CT) scan, and doctors may order one of these tests in evaluating the cause. 

Reye’s syndrome treatments

Treatment for Reye’s syndrome should begin as soon as possible to help slow the progression of the illness. 

“By the time kids with Reye’s syndrome [or a child with any illness] have a change in their mental status (their level of alertness and awareness), they should go to the emergency room,” Dr. Cram says. “And then they’d probably end up in the intensive care unit being monitored and stabilized with around-the-clock care.”

There is no cure for Reye’s syndrome, so treatment is aimed at protecting the brain from further damage, trying to reverse the metabolic issues that are causing the brain to swell, ensuring the lungs continue to function through means like a breathing tube or ventilator, and reducing overall bodily stress that could precipitate cardiac arrest.

“You can use a ventilator to hyperventilate someone with Reye’s syndrome, which can help with brain swelling,” Dr. Cram says. “There are also medications (such as mannitol or dexamethasone) you can give them that can help with swelling. 

Treatment can help slow the progression of Reye’s syndrome, and mild cases that don’t progress may cause no long-term complications. 

How to prevent Reye’s syndrome

1. Drugs to avoid (in addition to aspirin)

It may not be possible to prevent all cases of Reye’s syndrome, as some cases aren’t linked to aspirin. However, the chances of contracting this rare illness go down significantly by making sure that children with viral infections don’t take any medications that contain acetylsalicylic acid, salicylic acid, acetylsalicylate, or salicylate compounds. In addition to aspirin, this includes these over-the-counter drugs:

• Alka-Seltzer
• Anacin
• Ascriptin
• Bufferin
• Doan’s
• Ecotrin
• Excedrin
• Kaopectate
• Maalox
• Pamprin
• Pepto-Bismol   

This is not a complete list. Talk to your children’s provider or pharmacist for additional information. It is important parents and adolescents read all labels for over-the-counter medications before taking them. 

2. Vaccinations

In addition to avoiding those medications, you can reduce your child’s risk of contracting a viral infection in the first place by immunizing your children against all vaccine-preventable illness, but particularly flu (influenza) or varicella (chickenpox) as these are two of the most common vaccine-preventable febrile illnesses. Children receive varicella vaccines at ages 12 months and 4 years and should receive a flu vaccine each year. 

3. Safe pain relievers and fever reducers

The exception to the no-aspirin rule are children with conditions that respond well to aspirin treatment, such as Kawasaki disease. In those cases, parents should consult a doctor before administering pain-killing or anti-inflammatory medications. For other children, acetaminophen (Tylenol) or ibuprofen (Motrin) are always recommended instead of aspirin, especially with viral illnesses.