Reye's Syndrome

Reye syndrome is a rare but serious illness that results from aspirin use during a viral infection. It affects all organs of the body but is most harmful to the brain and the liver. Brain damage results from increased pressure within the brain, and fat accumulates in the liver and many other organs. Reye syndrome is primarily a children's disease, although it can occur at any age.

Other Names

• Reye’s syndrome
• Reye-Johnson syndrome.

Signs and Symptoms

Symptoms of Reye syndrome usually occur about a week after a viral infection such as the chicken pox, a cold or flu. The first symptoms to appear are:

• Diarrhea
• Lethargy
• Persistent vomiting
• Rapid breathing

As the syndrome progresses, patients may develop:

• Irritable, aggressive or irrational behavior
• Confusion
• Weakness or paralysis in the arms and legs
• Seizures
• Loss of consciousness

The late stages of the syndrome are characterized by extensive liver and brain damage, convulsions, and coma. The syndrome can be fatal.

Causes

Reye syndrome is defined as a two-phase illness because it generally occurs in conjunction with a previous viral infection, such as the flu or chicken pox. Frequently the syndrome occurs during recovery from a viral infection, although it can also develop three to five days after the onset of the viral illness.

Exactly how salicylates and a viral infection work together to cause Reye syndrome is not known. Some evidence suggests that salicylates and viral infections work in tandem to damage mitochondria. Mitochondria reside in the cytoplasm of cells and produce ATP, which is the energy that cells use.

Salicylates are not the only drugs to be linked to Reye syndrome. Some association between the syndrome and zidovudine (Retrovir), didanosine (Videx), and valproic acid has been suggested. Some toxins, herbicides, pesticides, paint thinners, and paint have been linked to the syndrome as well.

Diagnosis

The symptoms of Reye syndrome are shared among numerous illnesses. Thus, the syndrome is often misdiagnosed as encephalitis, meningitis, diabetes, drug overdose, poisoning, sudden infant death syndrome, or psychiatric illness. Diagnosis is based on exclusion of other conditions.

There is no single test for Reye syndrome. Screening usually begins with blood and urine tests. These may show a higher than normal blood glucose level, abnormal liver function tests, and elevated ammonia level. Sometimes more invasive diagnostic tests are needed to evaluate other possible causes of liver problems and investigate any neurological abnormalities. For example:

• A lumbar puncture (spinal tap) can help to rule out other diseases such as infection of the lining that surrounds the brain and spinal cord (meningitis) or inflammation or infection of the brain (encephalitis). During a spinal tap, a needle is inserted through the lower back into a space below the end of the spinal cord. A small sample of cerebrospinal fluid is removed and sent to a lab for analysis.
• A liver biopsy can help the doctor identify conditions that may be affecting the liver. During a liver biopsy, a needle is inserted through the skin on the upper right side of the abdomen and into the liver. A small sample of liver tissue is removed and sent to a lab for analysis.
• Computed tomography (CT) scan or Magnetic resonance imaging (MRI) of the brain may help to identify or rule out other causes of behavior changes or decreased alertness. A CT scan uses a sophisticated X-ray machine linked to a computer to produce detailed, two-dimensional images of the brain. An MRI scan uses magnetic fields and radio waves to generate images of the brain.

Treatment

No treatments exist that specifically treat Reye syndrome. Supportive treatment is aimed at protecting the brain against irreversible damage by reducing brain swelling, reversing the injury, preventing complications in the lungs, and anticipating cardiac arrest. These supportive treatments may include:

• Administration of intravenous (IV) fluids, especially glucose (evidence suggests that intravenous dextrose can slow the progression of the syndrome)
• Insulin to increase the metabolism of sugar
• Corticosteroids to reduce swelling in the brain
• Diuretic medications to increase the output of urine
• Hyperventilation (mechanical ventilation) may be needed in extreme cases to decrease pressure in the brain.

Blood transfusion, hemodialysis, and induction of deep coma with the use of barbiturates are treatments that are sometimes used although not scientifically proven to be effective.

Outcome

Recovery from Reye syndrome is directly related to the severity of the swelling of the brain. Some people recover completely, while others may sustain varying degrees of brain damage. In rapidly progressing disease that results in a coma, outcome is poor. Chances of recovery are greatest if a diagnosis is made early and treatment is initiated.

Epidemiology

Between 1980 and 1998, 1,207 cases of Reye syndrome were diagnosed in children under 18 years of age in the United States.^[1] The incidence of Reye syndrome has dropped since the association between the illness and aspirin use in children had been made. In 1980, 555 cases had been diagnosed and, since 1987 no more than 36 cases per year had been reported between 1987 and 1997.^[1] Another reason for the decline was the recognition of other conditions that cause the same symptoms as Reye syndrome.

Clinical Trials

A list of ongoing trials is available at Clinical Trials.gov: Reye syndrome trials

Research

Much of the research on RS focuses on answering fundamental questions about the disorder such as how problems in the body's metabolism may trigger the nervous system damage characteristic of RS and what role aspirin plays in this life-threatening disorder. The ultimate goal of this research is to improve scientific understanding, diagnosis and medical treatment of RS.

History

Reye syndrome was first described in the British journal Lancet. in 1963 by Australian pathologist Dr. Ralph Douglas Kenneth Reye and his colleagues. ^[2] Dr. Reye reported a described a syndrome in young children in which acute encephalopathy (brain disease) and fatty degeneration of the liver followed an acute febrile illness, usually influenza or chickenpox. He noticed the liver and brain damage after autopsies of children who became ill (usually with vomiting) and died after a viral illness. The syndrome was further described in British Medical Journal in 1966. ^[3]

By 1980, aspirin had been identified as a major risk factor for the genesis of the syndrome. Recommendations to eliminate aspirin use in children during an infection has dramatically reduced the incidence of Reye syndrome in recent years.

Public Health

The U.S. Food and Drug Administration (FDA) mandated a warning label on all salicylate products in June of 1986 due to the proposed link between aspirin use in children after a viral illness and Reye syndrome. The label was modified in 1986 and was made permanent on all non-prescription aspirin products. ^[4] It reads as follows: "Warning: Children and teenagers should not use this medicine for chickn pox or flu symptoms before a doctor is consulted about Reye syndrome, a rare but serious illness reported to be associated with aspirin."

References

1. ↑ ^{1.0 1.1} Belay ED, Bresee JS, Holman RC, Khan AS, Shahriari A, Schonberger LB. Reye's Syndrome in the United States from 1981 through 1997. N Engl J Med. 1999 May 6;340(18):1377-82. Abstract | Full Text | PDF
2. ↑ Reye RD, Morgan G, Baral J. ENCEPHALOPATHY AND FATTY DEGENERATION OF THE VISCERA. A DISEASE ENTITY IN CHILDHOOD. Lancet. 1963 Oct 12;2(7311):749-52. Abstract
3. ↑ Becroft D. Syndrome of encephalopathy and fatty degeneration of viscera in New Zealand children. Br Med J. 1966 Jul 16;2(5506):135-40. Full Text
4. ↑ American Academy of Pediatrics. AAP News. 1988 Sep; 4(9): 1988: p.2 Abstract

External Links

National Reye's Syndrome Foundation (US)

National Reyes Syndrome Foundation UK