Unknown: Reye Syndrome

Definition

Reye syndrome is a rare but acute illness characterized by brain damage and liver failure following a viral infection, most commonly an infection of the upper respiratory tract, influenza, chickenpox, or a stomach disorder. It occurs most often in children but has been reported in adults. Adults, however, usually recover completely, whereas children who develop the syndrome have a high risk of lasting brain damage or death.

Description

Reye syndrome is a life-threatening condition marked by swelling of the brain and a buildup of fatty deposits in the liver. What triggers the syndrome is not fully understood. It is sometimes described as a two-phase illness because it is almost always preceded by a viral infection.

Demographics

Reye syndrome is most likely to occur in children between the ages of five and fifteen; it appears to be more common in Caucasians in the United States than in members of other racial groups. Reye syndrome is reportedly most likely to occur in January, February, or March, during

influenza season. Epidemics of chickenpox or flu were sometimes followed by a rise in the number of reported cases of Reye syndrome.

In general, however, the disorder is much less common in the United States in the early 2000s than it was in 1980, when 555 cases were reported to the Centers for Disease Control and Prevention (CDC). In 1999, the CDC reported that the annual number of cases had declined rapidly, to an average of thirty-seven each year between 1987 and 1993. Since 1994, only about two cases per year have been reported in the United States.

Causes and Symptoms

The cause of Reye syndrome is still unknown. It is known that the condition is not contagious. In addition, the reasons for the decline in the number of cases since 1980 are not clear. Some doctors think that there are fewer cases of Reye syndrome at present because parents have heeded the warnings required by law since 1986 on all packages containing aspirin. Others wonder whether Reye syndrome is triggered by a specific strain of chickenpox or influenza virus rather than by aspirin because the viruses that cause these diseases are constantly mutating, or changing. In 2004 some doctors in Florida argued that the syndrome was caused by “a viral mutation which spontaneously disappeared” or by inherited metabolic disorders that were not recognized in the 1950s and 1960s. In addition, several doctors in Japan have reported cases of Reye syndrome in children who had not been given aspirin.

The symptoms of Reye syndrome are linked to the buildup of fatty deposits in the liver and increased pressure on the brain. The liver is not able to get rid of ammonia, a substance that is produced during the digestion of proteins in food. The ammonia builds up in the blood, a condition called hyperammonemia. This condition in turn can be associated with brain damage.

The symptoms of Reye syndrome are sometimes classified into early and later symptoms. It is important to note, however, that not all children with Reye syndrome have all these symptoms or develop them in the same order. Another important fact to keep in mind is that fever is not usually present in Reye syndrome.

Early symptoms of the disorder include:

• Persistent or continuous vomiting
• In small children, diarrhea and rapid breathing
• Unusual sleepiness and loss of energy (This symptom usually appears about twenty-four hours after the beginning of the vomiting.)

The second stage of Reye syndrome is marked by personality changes and changes in level of consciousness:

• Irritability and aggressive behavior
• Mental confusion
• Weakness or paralysis of the arms and legs
• Seizures
• Loss of consciousness and coma

The Discovery of Reye Syndrome

Ralph Douglas Reye (1912–1977; name pronounced like rye) was a pathologist who worked at the Royal Alexandria Hospital for Children in Sydney, Australia, in the early 1950s. In 1951 a pediatrician brought him a case involving a ten-month-old boy who died after thirty hours of vomiting. The pediatrician thought it might have been an infection, but Dr. Reye found liver and brain damage of a type that he had never seen before when he performed an autopsy. Over the next decade Dr. Reye identified twenty more cases of this strange syndrome. In 1963 he published an article in a prestigious British medical journal about his cases. A link with aspirin was not made until two younger doctors who were working with Dr. Reye interviewed the families of the twenty-one children he had studied and found that eleven of the children had taken aspirin during their illness.

Dr. Reye's work was confirmed by Dr. George Johnson, an American doctor who reported on the deaths of 16 school-age children in North Carolina in the mid-1960s who had the same kind of liver and brain damage as the children that Dr. Reye had studied. By 1986, the Food and Drug Administration (FDA) required American drug manufacturers to place a warning about Reye syndrome on all bottles of aspirin produced in the United States and to remove aspirin from most over-the-counter products intended for children.

Diagnosis

There is no single test that is specific for Reye syndrome. It is diagnosed primarily by excluding other possible causes of the child's symptoms. Because Reye syndrome is a serious illness, however, the doctor must consider it as

a possible diagnosis in any child with a history of a recent viral illness combined with severe vomiting and changes in the level of consciousness.

The doctor will give the child the following types of tests:

• Blood and urine tests. These can help the doctor rule out the possibility of accidental poisoning or exposure to a toxic substance.
• Spinal tap (also called a lumbar puncture) to take a sample of cerebrospinal fluid (CSF). CSF is the fluid that surrounds the brain and the spinal cord. Analyzing the sample can help to determine whether the illness is caused by a brain infection rather than Reye syndrome.
• Liver biopsy. This test is performed by inserting a needle into the right side of the child's abdomen and removing a small sample of liver tissue.
• Computed tomography (CT) or magnetic resonance imaging (MRI) scans. These tests provide images of the brain that can help the doctor rule out tumors, head injuries, or other causes of the child's changes in behavior or level of alertness.

Treatment

Treatment of a child thought to have Reye syndrome must begin as soon as possible to lower the risk of death or lasting damage to the nervous system. Children diagnosed with Reye syndrome require treatment in the intensive care unit (ICU) of a hospital. There is no specific drug or other type of treatment that is unique to Reye syndrome. The child is carefully monitored for changes in vital signs (blood pressure, pulse or heart rate, breathing rate, and temperature) and symptoms and may be given one or more of the following:

• Intravenous fluids containing glucose (sugar) to nourish the body as well as replace lost fluids
• Small amounts of insulin
• Steroid medications to reduce swelling of the brain tissue
• Diuretics, drugs that speed up urine output
• If necessary, a respirator to help the child breathe

Prognosis

Most children treated early make a full recovery, but about 20 percent of children with Reye syndrome will die even with prompt treatment. About 10 percent of survivors suffer some kind of permanent damage

to the nervous system; the extent of the damage depends on the ammonia level in the blood. If treatment is delayed, the death rate can rise substantially. Children under the age of five are at greatest risk of severe brain damage or death.

Prevention

The best way to prevent Reye syndrome is to have children vaccinated against influenza and chickenpox and to avoid giving aspirin to children and teenagers under the age of eighteen when they get a cold or flu-like illness.

The Future

Further research may shed light on either the cause of Reye syndrome or the reasons for the drop in the number of cases reported since the 1990s.

SEE ALSO Chickenpox; Influenza

WORDS TO KNOW

Ammonia : A chemical produced during the breakdown of protein in the body. It is usually converted in the liver to another chemical called urea and then discharged from the body in the urine.

Diuretics : Medications that speed up the production of urine.

Hyperammonemia : Overly high levels of ammonia in the blood; it often indicates liver damage.

Vital signs : Measurements taken to evaluate basic body functions. They are temperature, pulse rate, blood pressure, and breathing rate.

For more information

PERIODICALS

Altman, Lawrence K. “The Doctor's World: Tale of Triumph on Every Aspirin Bottle.” New York Times, May 11, 1999. Available online at http://query.nytimes.com/gst/fullpage.html?res=940DE3D8143FF932A25756C0A96F958260&sec=&spon=&pagewanted=all (accessed April 15, 2008). This is a profile of Dr. Ralph Reye, the Australian doctor who first reported the syndrome that bears his name.

WEB SITES

Mayo Clinic. Reye's Syndrome. http://www.mayoclinic.com/health/reyes-syndrome/DS00142/DSECTION=1 (accessed April 16, 2008).

National Institute of Neurological Disorders and Stroke (NINDS). Reye's Syndrome Information Page. Available online at http://www.ninds.nih.gov/disorders/reyes_syndrome/reyes_syndrome.htm (updated February 14, 2007; accessed April 15, 2008).