Reye syndrome is a rare, possibly life-threatening condition that primarily affects children – most often those under 15 years old. Nearly half of all reported cases involve children under 5 years old, according to the Centers for Disease Control and Prevention (CDC).

The cause of Reye syndrome is unknown, although the use of aspirin or salicylate-containing medications in children and teenagers to treat viral infections (e.g., cold, flu, chickenpox) is associated with onset of the condition. It primarily causes damage to the brain and liver. Death occurs in 20 to 30 percent of reported cases.

Reye syndrome was identified in 1963, though the disease was first diagnosed as a unique illness in 1929, and the number of cases peaked in the 1960s and 1970s. Since 1980, the number of reported cases has dropped dramatically. Beginning in the 1980s, physicians warned parents away from using aspirin in children recovering from viral infections. This may have prevented some cases of Reye syndrome. In addition, other disorders now classified as inborn errors of metabolism have since been identified with similar symptoms. Children with these conditions might have been diagnosed with Reye syndrome in earlier decades.

Within a week of a viral illness, a child’s or teenager’s condition may appear to worsen. Symptoms of Reye syndrome include continual vomiting, lethargy and changes in a person’s mental status (e.g., disorientation, confusion, irritation, argumentative and/or aggressive behavior). Vomiting may not occur in infants with Reye syndrome, although additional symptoms (e.g., diarrhea, irregular breathing) may occur.

Parents and other caregivers who believe a child may have Reye syndrome should seek immediate medical attention because symptoms may progress rapidly. Early identification can help reduce the risk of long-term complications (e.g., brain damage, coma) and death. Diagnosis may be made if a child has recently had a viral illness, has taken aspirin, there is evidence of liver dysfunction and changes in mental status and other conditions have been ruled out. Many laboratory tests may be involved in the diagnosis, especially to rule out metabolic causes. Tests may include liver function tests, serum ammonia test (blood test that measures the levels of the waste product ammonia) liver biopsy, spinal tap and/or imaging tests.

There is no known cure for Reye syndrome. Most often, supportive care for patients with the syndrome is provided in a hospital. The type of treatment depends on the condition of the patient and may include efforts to reduce swelling of the brain, balance the patient’s nutrient and fluid levels, and aid breathing in cases of respiratory difficulty. Each patient’s level of recovery depends on the severity of the symptoms.

Reye (pronounced “rye”) syndrome is a rare, potentially life-threatening illness. It primarily affects the brain and liver, causing inflammation and pressure inside the head (with corresponding cognitive or behavioral symptoms) and dysfunction of the liver, leading to a dangerous buildup of toxins in the body.

Reye syndrome occurs almost exclusively in children and teenagers recovering from viral illnesses such as a cold, the flu or chickenpox. The use of aspirin or aspirin-containing medication (presumably to treat the viral infection) has been associated with onset of the syndrome.

People of all ages may be affected, but Reye syndrome occurs most often among those under 15 years old. Nearly half of all reported cases have occurred in children under 5 years old, according to the Centers for Disease Control and Prevention (CDC). It is estimated to occur in 1 out of every 100,000 children under the age of 18.

The syndrome is named after an Australian pathologist, Dr. R. Douglas Reye, who along with North Carolina physician George Johnson, published the first study of the syndrome in 1963. Outbreaks of Reye syndrome occurred in the United States during the 1960s and 1970s. Since the early 1980s, the number of cases reported has dropped dramatically. This may be related to increased publicity during the early 1980s warning people about the danger of using aspirin and aspirin-containing medication in children. In addition, several other conditions known as inborn errors of metabolism have since been identified that have symptoms similar to Reye syndrome. Some earlier suspected Reye syndrome cases actually may have been these metabolic conditions.

In 1982, the surgeon general advised against use of these medications in children with influenza or chickenpox. In 1986, the Food and Drug Administration (FDA) ruled that all over-the-counter aspirin and aspirin-containing products must carry a warning label about Reye syndrome. Another warning stating that children and teenagers who have chicken pox or flu symptoms, or are recovering from these illnesses, should not use aspirin became effective in 2004.

Reye syndrome primarily affects the brain and liver. It causes swelling and accumulation of fat in the liver. The liver fails to function as it should, and may cause poor blood clotting and increased bleeding. Patients with Reye syndrome tend to have high levels of ammonia and acidity in their blood and low levels of blood sugar (glucose). 

Reye syndrome may cause brain damage due to accumulation of fluids in the brain, which causes the brain to swell and pressure in the head to increase. This can result in life-threatening seizures, coma and brain damage. Reye syndrome may also affect other organs in the body.

The death rate among patients with Reye syndrome was initially 40 percent, but has decreased to between 20 and 30 percent of reported cases, according to the CDC. Most children with Reye syndrome survive and many have no long-terms complications.

The exact cause of Reye syndrome is unknown. Viral infections (e.g., colds, the flu, chickenpox) combined with the use of aspirin or aspirin-containing medication appear to be related to the onset of the syndrome.

Aspirin, a type of nonsteroidal anti-inflammatory drug (NSAID), may also be referred to as salicylic acid, salicylate, acetylsalicylic acid or acetylsalicylate. Aspirin has anti-inflammatory, pain-relieving (analgesic), and fever-reducing (antipyretic) properties – but appears to have a toxic effect in children and teens with viral illnesses. Various medications may contain aspirin, including antidiarrheals, antacids, antinausea drugs and a variety of cold and flu medications. Bismuth subsalicylate is an example of an over-the-counter medication for upset stomach that contains aspirin.

Certain factors are associated with an increased risk of Reye syndrome. These risk factors include:

• Use of aspirin to treat viral infections. Aspirin (or any medication derived from salicylic acid) used to treat viral illnesses has been associated with an increased risk of Reye syndrome.
  
  
• Age. Most cases of Reye syndrome occur in children and teenagers – especially those under 15 years old. Almost half of all cases in children occur in those under 5 years of age, according to the Centers for Disease Control and Prevention (CDC).
  
  
• Season. Reye syndrome occurs more often in the winter months when viral illnesses are more easily spread due to close contact indoors with others.

Early identification of Reye syndrome is crucial. Prompt medical attention can save a child’s life, especially since symptoms may progress rapidly to seizures, coma and death within hours or days. However, most children with Reye syndrome have mild cases that do not worsen.

Reye syndrome usually occurs in a person who has recently contracted a viral illness (e.g., the flu, chickenpox). Signs of Reye syndrome typically appear within a week after onset of the initial infection – at a time when a child appears to be recovering from the original illness.

Symptoms may be mild to severe. When they are mild, the condition may go unnoticed, symptoms do not worsen and the syndrome resolves without treatment, usually within five to 10 days. However, when symptoms are severe, they can progress to death within hours.

Early signs and symptoms of Reye syndrome include:

• Vomiting that is sudden and protracted over many hours
• Lethargy, unusual sleepiness, difficult to awaken
• Disorientation (e.g., confusion, irrational behavior)
• Irritability, aggression, combative behavior
• Hyperventilation
• Liver dysfunction (e.g., swollen, high triglyceride content)

The early signs of Reye syndrome may differ in infants. For example, vomiting may not occur in infants with the syndrome, whereas diarrhea and irregular breathing may appear. 

Additional, more severe signs of Reye syndrome include:

• Delirium
• Weakness in arms/legs, muscle function loss, paralysis
• Unusual posture (arms/legs extended, toes pointed downward)
• Sluggish breathing
• Seizures
• Fixed pupils
• Respiratory arrest
• Coma

The following are NOT symptoms of Reye syndrome:

• Jaundice. Does not usually occur in patients with Reye syndrome. If it occurs, it may indicate a metabolic disorder not associated with Reye syndrome.
  
  
• Fever. Although Reye syndrome does not produce a fever, it may be present in children with the syndrome, since it often accompanies the viral infections (e.g., flu, chickenpox) that precede Reye syndrome.

Parents and caregivers who believe a child may have Reye syndrome should seek immediate medical attention. Early identification can help reduce the risk of long-term complications (e.g., brain damage, coma) and death.

The first step in diagnosing Reye syndrome is a thorough medical history. This may include questions by a pediatrician about recent viral illnesses (e.g., colds, the flu, chickenpox) and all medications taken recently (e.g., aspirin or any medication containing salicylic acid) by a child. Parents and other adults may be asked about any unusual changes in the mental alertness of the child.

A physical examination may be performed to look for any other signs of illness. A neurological examination may be performed to rule out disorders of the central nervous system. In addition, the following tests may be performed to diagnose Reye syndrome or to rule out other conditions:

• Liver function tests. These are blood tests that identify levels of certain substances (e.g., liver enzymes, glucose, ammonia) that may indicate dysfunction of the liver, which may indicate the presence of Reye syndrome or another condition.
  
  
• Liver biopsy. A tissue sample (taken by needle inserted through abdomen and into the liver) is analyzed for fat accumulation, a sign of Reye syndrome. This test is also used to rule out other possible diseases that may affect the liver.
  
  
• Spinal tap. Analysis of cerebral spinal fluid (CSF). This may help rule out other conditions, such as meningitis or encephalitis.
  
  
• Imaging tests. These may include computed axial tomography (CAT scan) or magnetic resonance imaging (MRI) of the head to rule out other potential causes of symptoms. A CAT scan may also show brain swelling associated with Reye syndrome.

Reye syndrome may be confused with a variety of rare metabolic disorders. Most of these disorders are hereditary and can be identified through blood tests and urine tests. They are sometimes referred to as mitochondrial diseases because problems involve the mitochondria (energy-making structures within cells). Urine tests may also rule out poisoning or drug overdose as the cause of a patient’s symptoms.

There is no known treatment that cures Reye syndrome. In most cases, patients are hospitalized and supportive care is provided. The type of care depends on the severity of the patient’s condition. Children with mild signs of Reye syndrome may simply be observed and their condition stabilized. Recovery in mild cases is usually quick and complete.

Children who appear at a hospital with severe signs of illness (e.g., seizures, loss of consciousness) may have long-term cognitive, motor and/or visual impairment even after release from the hospital. Symptoms may worsen very quickly in patients with Reye syndrome. Severe cases that are not treated often result in death, usually within a few days. Thus, immediate medical attention is required at the earliest signs of Reye syndrome.

Patients hospitalized with Reye syndrome may receive the following care:

• Efforts to reduce swelling/pressure in the head, such as:
  
  
• Corticosteroids may help reduce swelling of the brain and prevent brain damage
  
  
• Barbiturates may help decrease pressure in the head
  
  
• Diuretics (drugs that increase urine production) may help accumulated fluids leave the body
  
  
• Intravenous fluids, nutrients, medications. Patients with Reye syndrome are often provided intravenous fluids and nutrients (e.g., electrolytes, glucose) to maintain proper nutritional balance and help reverse metabolic injury suffered from the syndrome. Insulin may also be provided to aid a patient’s ability to metabolize sugar.
  
  
• Breathing aids. This may include intubation (tube inserted into windpipe to aid breathing) or use of a ventilator to mechanically induce breathing and help prevent lung complications or cardiac arrest.

Patients’ conditions may be monitored for the duration of their hospital stay. Catheters (tubes inserted into an artery or vein) may be used to continuously monitor blood pressure, as well as track and maintain adequate levels of nutrition, fluids, electrolytes and blood gas status (measurement of pH [acidity], oxygen and carbon dioxide content within the blood).

Reye syndrome can cause permanent brain damage in severe cases resulting in cognitive, motor and/or visual impairment for the affected child. In such cases, rehabilitative treatment including speech, physical or occupational therapy may be helpful. Parents and caregivers should discuss all treatment options with their child’s physician.

To reduce the risk of developing Reye syndrome, parents or other caregivers should avoid giving aspirin (or any medication derived from salicylic acid) to a child or teenager, unless advised to do so by a physician. There are other over-the-counter medications (e.g., acetaminophen) that may be used for a child’s aches, pains or fever. Parents should be careful to check the ingredient list on all medications given to children, because aspirin (salicylate) may be found in a variety of over-the-counter medications, such as those used to treat diarrhea and upset stomach, as well some cold and flu medications. Parents and caregivers should consult the child’s pediatrician before providing a child with any type of medication.  

Children or teens, especially those who must take aspirin, are encouraged to receive vaccinations against influenza and chickenpox to reduce the risk of contracting these viral infections that usually precede Reye syndrome. This includes children on long-term aspirin therapy for conditions such as juvenile rheumatoid arthritis or Kawasaki disease as well as healthy children between the ages of 6 months and 5 years (for annual flu shots) and children ages 12 months to 18 years (for chickenpox).

Mothers who are breastfeeding should also avoid any products that contain aspirin, because it may be passed to an infant through breast milk.

Preparing questions in advance can help patients and parents have more meaningful discussions with physicians regarding their or their child’s treatment options. The following questions related to Reye syndrome may be helpful:

1. If I shouldn’t use aspirin for my child’s aches, pains or fever, what type of over-the-counter medication should I use?
   
   
2. In what situations might it be safe for my child to take aspirin?
   
   
3. At what age can my child safely take aspirin?
   
   
4. When my child has a viral infection, what signs should I look for that may indicate he/she is getting worse? What signs may indicate Reye syndrome?
   
   
5. How soon should I get help when I notice these signs?
   
   
6. Will my child need to be hospitalized if these signs appear?
   
   
7. How will you or another physician be able to determine the severity of my child’s condition?
   
   
8. How likely is Reye syndrome to result in permanent disability in my child?
   
   
9. What type of treatment may my child need for Reye syndrome?
   
   
10. Are there vaccines my child can get to prevent the flu or chickenpox? When can my child receive these shots? Will getting these vaccines prevent my child from developing Reye syndrome?
    
    
11. Are there additional steps I can take to help reduce my child’s risk of developing Reye syndrome?