Reye Syndrome

Reye syndrome is a neurological (brain) and hepatic (liver) dysfunction disorder most often seen in children treated with aspirin just after recovery from a [Page 1491]viral infection. First recognized in the early 1960s, the cause of Reye syndrome has yet to be identified; however, it is believed that the use of aspirin and preceding viral illness are precipitating factors. Although a firm correlation has not been determined between the use of aspirin after viral illness and Reye syndrome, since the Centers for Disease Control and Prevention warned parents not to use aspirin in children (without physician notification and approval), cases of Reye syndrome have drastically declined. Now, cases have been limited to approximately two cases per year since the mid-1990s.

Reye syndrome occurs most frequently in children 4 to 12 years of age. It occurs equally in males and females and is strongly associated with the use of aspirin during a viral illness, most specifically the flu (caused by influenza A or B) and the chicken pox (caused by the Varicella Zoster) viruses. Typically, a child has just recovered from a viral illness four to seven days previously and then has a sudden onset of vomiting. Twenty-four to thirty-six hours after the onset of vomiting, children have mental status changes including confusion, lethargy, irritability, restlessness, increased combativeness, or disorientation. As the illness progresses, coma, seizures, respiratory arrest, and death can occur.

Children with Reye syndrome have elevation of liver enzymes (alanine aminotransferase and aspartate aminotransferase) typically without jaundice (yellowing of the skin) and fatty degeneration of their liver, which causes metabolic disturbances. Patients also develop noninflammatory cerebral edema (swelling), which elevates the intracranial pressure and puts pressure on the brain causing neurological symptoms. The usual cause of death from Reye syndrome is herniation of the brain from increased intracranial pressure from cerebral edema.

The pathophysiology and criteria for diagnosis of Reye syndrome have not been determined. Pathology theories for Reye syndrome involving mitochondrial (a part of each cell that makes energy) damage and hepatic metabolic disturbances have been explored, although evidence is weak. Reye syndrome is a diagnosis of exclusion, meaning many other illnesses should be ruled out as a cause of the symptoms before the diagnosis of Reye syndrome can be made. The patient history of viral illness and aspirin use is helpful information. A thorough physical exam, several laboratory tests, head imaging, and liver biopsy are also done at the physician's discretion.

Symptoms of Reye syndrome were staged in 1981 by the National Institutes of Health. Stage 1 describes the patient as lethargic, following verbal commands with normal posture, response to pain, and pupillary responses. Stage 2 describes combative behavior with inappropriate verbalizations, normal posture, normal or abnormal response to pain, and sluggish pupillary reactions. Stage 3 describes the patient as being in a coma with abnormal posturing, response to pain, and pupillary reaction. Stage 4 describes stage 3 with increased pupillary and ocular response abnormalities. Stage 5 indicates the patient is nonreactive in all ways including pupillary/ocular responses.

All patients with Reye syndrome should be admitted to the hospital for evaluation and categorized into one of the five stages listed above. Treatment in stages 1 and 2 include constant observation and evaluation of neurological status, as well as supportive treatment of electrolyte abnormalities and fluid replacement. Patients in stages 3 to 5 are placed under constant monitoring of breathing and tissue perfusion, metabolic disturbances are identified and corrected, and great care is taken to decrease cerebral edema. Reduction of the increased intracranial pressure is a high priority because its decline can directly influence the patient's survival. Recommendations include placing a device (catheter) in the patient's brain to monitor pressure. Treatments for elevated intracranial pressure include medications such as steroids, mannitol, and furosemide, or use of the inserted catheter to release small amounts of fluid from around the brain.

...