Reye syndrome

Definition

Reye syndrome is a serious, potentially fatal condition that strikes children and adolescents who have just recovered from a viral infection, especially when that illness has been treated with aspirin or aspirin-containing products. Reye syndrome causes damage to the liver and brain.

Description

Reye syndrome is a relatively rare disease. Since the late 1980s, when concern regarding aspirin use in children became more widely publicized, fewer than 20 cases of Reye syndrome have been reported annually. This is down from a peak of over 600 cases in 1980. Although researchers have not been able to state this definitively, the decreased incidence of Reye syndrome has been commonly attributed to a greatly decreased use of aspirin-containing products in children.

When Reye syndrome strikes, it can be a devastating illness. The death rate from the disease used to be as high as 50–60%. Better, faster methods of diagnosis have allowed earlier identification of the disorder, allowing the death rate to drop to 30–35%. Younger children seem to have a higher risk of death. Even those children who recover may be faced with lifelong disability, depending on the degree of brain damage suffered. Long-term problems may include behavior problems, attention disorders, mental retardation , blindness, seizures , varying degrees of paralysis, and learning difficulties.

Demographics

Reye syndrome primarily strikes children and adolescents who have recently recovered from a viral infection, particularly chicken pox or influenza. Because the frequency of most viral infections peaks in the winter months, Reye syndrome is most common in January, February, and March. In the United States, the most common age for Reye syndrome is six to eight years. Reye syndrome is extremely rare in individuals over the age of 18.

Causes and symptoms

Scientists do not feel convinced that the true cause of Reye syndrome has been defined. Although there is a clear-cut association between recent viral infection and the disease, and between use of aspirin-containing products and the disease, the actual mechanism of the condition has not been fully delineated. There may also be an association between the development of Reye syndrome and exposure to pesticides and/or aflatoxin (a toxin produced by a fungus that infests grains, peanuts, soybeans, and corn that have been stored in warm, moist conditions).

The underlying problem in Reye syndrome seems to be dysfunction of the small, energy-producing structures within the body's cells (the mitochondria). The blood becomes more acidic, ammonia levels increase, and sugar levels drop. Large quantities of fat are deposited throughout many organs of the body, most significantly, the liver. The fatty deposits in the liver interfere with normal liver functioning. Swelling and increased pressure in the brain puts pressure on the delicate brain tissues, resulting in damage.

Reye syndrome begins within about a week of recovery from a viral illness. Vomiting and listlessness are some of the earliest symptoms, although they are not necessarily universal in every patient. Children tend to become sleepy, disoriented, confused, and even combative. Reye syndrome can progress very quickly. Within hours, symptoms can become more severe, with loss of consciousness, seizures, stupor, and coma, all signaling critical illness.

Reye syndrome is graded I through V at the time of diagnosis, in order to determine a level of severity. Grades I through III are considered mild to moderate, while grades IV and V are considered critically ill. Criteria for this grading is as follows:

• Grade I: Child is quiet, sleepy, vomiting, and there is some blood evidence of a drop in liver functioning.
• Grade II: Child is confused, delirious, combative, with overly-active reflexes, breathing quickly.
• Grade III: Child is in a light coma, may have seizures, pupils still responsive to light, is in decorticate posture (stiff, rigid posture indicative of damage to nerve tracts that run between spinal cord and brain).
• Grade IV: Child is in a deepening coma, experiencing seizures, pupils nonresponsive to light, has abnormal reflexes, is in decerebrate posture (stiff, rigid posture indicative of severe damage to brain stem).
• Grade V: Child is in a deep coma, pupils are fixed and dilated (abnormally enlarged, do not constrict when exposed to light), no normal reflexes, alternates between decerebrate posture and completely limp, flaccid muscles, cannot breathe independently, EEG reading lacks normal waves.

Diagnosis

There is no specific test to diagnose Reye syndrome. Diagnosis is suggested by a number of different abnormalities, including:

• extremely elevated liver enzymes (20–30 times normal)
• increases in blood ammonia (three times normal)
• low blood sugar
• high blood acidity
• blood clotting abnormalities
• abnormal electroencephalogram (EEG, a test in which electrodes applied to the scalp allow the electrical activity of the brain to be recorded)
• abnormal liver biopsy , revealing large quantities of fat deposited within the liver

Treatment team

Children with Reye syndrome are usually cared for in a hospital, with more severely ill children requiring care in an intensive care unit. Health care providers may include pediatric intensivists, neurologists, and gastroenterologists (to closely monitor liver function).

Treatment

There is no cure for Reye syndrome. Treatment is considered supportive, meaning that treatment is given to address the specific complications, in order to try to prevent progression of the liver and brain damage and permanent effects.

Medications such as steroids and/or diuretics may be given to try to relieve brain swelling; at the same time, fluid intake should be restricted to prevent further swelling. Glucose is given to increase blood sugar levels. Vitamin K, platelet transfusions, and frozen plasma may be given to improve a bleeding disorder. Seriously ill patients will probably need to be on a ventilator.

Recovery and rehabilitation

Even children who seem to have made a complete recovery may actually demonstrate significant neuropsychological deficits with specific testing. Depending on the actual deficits, physical therapy, occupational therapy, speech and language therapy, and educational interventions may be necessary.

Prognosis

Prognosis depends on the severity of the brain swelling. The liver functioning is usually fully recovered, but brain damage will leave permanent deficits. When Reye syndrome is diagnosed earlier in its course, aggressive treatment can be started to slow the progress of damaging brain swelling, improving the patient's chance of complete recovery. There is a higher risk of death or of permanent damage when there is a delay in diagnosis and therefore in treatment. When Reye syndrome is not diagnosed and treated quickly, death can occur within only days of the syndrome's onset. Death rates from Reye syndrome are currently about 30–35%.

Special concerns

Reye syndrome can be almost completely prevented by parental awareness of the dangers of administering any aspirin-containing substances to their children. This includes aspirin itself, as well as various cold and flu preparations that may contain salicylates or salicylic acid (the chemical names for aspirin). Many common over-thecounter medications for upset stomach also contain salicylates. Parents should carefully read the list of active ingredients and/or consult a physician or pharmacist before giving their children over-the-counter medicines. Making sure that children are immunized yearly against the flu (influenza vaccine) and considering giving children the chicken pox vaccine may also help decrease the risk of Reye syndrome.

Resources

BOOKS

Gascon, Generoso G., and Pinar T. Ozand. "Aminoacidopathies and Organic Acidopathies, Mitochondrial Enzyme Defects, and Other Metabolic Errors." In Textbook of Clinical Neurology, edited by Christopher G. Goetz. Philadelphia: W.B. Saunders Company, 2003.

Rudolph, Jeffrey A., and William F. Balistreri. "Reye Syndrome and the Mitochondrial Hepatopathies." In Nelson Textbook of Pediatrics, edited by Richard E. Behrman, et al. Philadelphia: W.B. Saunders Company, 2004.

Wachtel, Tom J. "Reye's Syndrome." In Ferri's Clinical Advisor: Instant Diagnosis and Treatment, edited by Fred F. Ferri. St. Louis: Mosby, 2004.

WEBSITES

National Institute of Neurological Disorders and Stroke (NINDS). Reye Syndrome Fact Sheet. (April 27, 2004). <http://www.ninds.nih.gov>.

ORGANIZATIONS

National Reye's Syndrome Foundation, Inc. (419) 636-2679 or (800) 233-7393; Fax: (419) 636-9897. nrsf@reyessyndrome.org. <http://www.reyessyndrome.org/default.htm>.

Rosalyn Carson-DeWitt, MD