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Emergency And Acute Medicine – Reye Syndrome
Reye syndrome is a rare but potentially fatal, reversible clinicopathologic syndrome characterized by acute noninflammatory encephalopathy and hepatic dysfunction with fatty infiltration. It is believed to involve primary mitochondrial injury leading to impaired oxidative phosphorylation and decreased activity of enzymes involved in the Krebs cycle, gluconeogenesis, and urea synthesis. The result is hyperammonemia, hypoglycemia, and hepatic dysfunction without significant inflammation. Rapid neurologic deterioration is due to cerebral cytotoxic edema and increased intracranial pressure (ICP), with herniation being the most common cause of death. Survivors often recover normal liver and neurologic function.
The condition primarily affects children, with peak incidence between ages 4 and 11 years and an average age of 7 years. It is extremely rare in individuals older than 18 years. Fewer than 10% of cases occur before age 1 year. Incidence is highest in winter and early spring and has historically been associated with antecedent viral infections such as influenza A or B and varicella. Epidemiologic evidence strongly links exposure to salicylates during viral illness as a major risk factor. Genetic susceptibility and other environmental factors may contribute. Reye-like syndromes describe similar presentations due to inborn errors of metabolism or toxic exposures affecting fatty acid oxidation and urea metabolism.
Patients typically present with a biphasic illness. An initial viral prodrome is followed several days later by persistent, profuse vomiting and rapid onset of neurologic symptoms. The patient is usually afebrile at presentation. Early manifestations include lethargy, behavioral changes, irritability, confusion, delirium, and combativeness. As cerebral edema worsens, patients may develop hyperventilation, decorticate or decerebrate posturing, seizures, and coma. Hepatomegaly is present in about 40% of cases. No focal neurologic deficits are typically found. Infants may present atypically with tachypnea, apnea, hypoglycemia, irritability, or seizures.
Laboratory evaluation demonstrates elevated liver transaminases (at least three times normal), elevated serum ammonia, hypoglycemia (particularly in infants), prolonged prothrombin time due to decreased clotting factor synthesis, and elevated blood urea nitrogen. Serum bilirubin is usually normal or only mildly elevated. Ammonia levels often peak 24 to 48 hours after onset of neurologic symptoms; levels greater than 300 μg/dL are associated with poor prognosis. Platelet count and peripheral smear are usually normal. Toxicology screening should be performed to exclude other causes. Head CT may demonstrate diffuse cerebral edema. Lumbar puncture is not contraindicated but typically shows fewer than 8 leukocytes/mm³. Liver biopsy confirms the diagnosis by demonstrating microvesicular fatty infiltration but should not delay treatment.
The differential diagnosis includes inborn errors of metabolism (urea cycle defects, fatty acid oxidation disorders, organic acidemias), toxin exposures, drug intoxications such as acetaminophen or salicylates, hypoglycemia, sepsis, meningitis, encephalitis, and head trauma.
Management is supportive and aimed primarily at controlling intracranial pressure and correcting metabolic derangements. All patients require intensive care admission in a facility capable of ICP monitoring. Airway protection with rapid-sequence intubation is indicated for significant encephalopathy. Supplemental oxygen and cardiorespiratory monitoring are essential. Intravenous glucose should be administered promptly for altered mental status, and serum glucose should be maintained between 125 and 175 mg/dL with careful monitoring. Overhydration should be avoided.
Elevated ICP is managed with head elevation, controlled hyperventilation, osmotic therapy such as mannitol, and, in severe cases, barbiturate coma. Intracranial pressure monitoring via subarachnoid bolt or intraventricular catheter may be required in advanced stages. Vitamin K is administered if prothrombin time is prolonged, and fresh-frozen plasma may be given for severe coagulopathy or bleeding. Diuretics such as furosemide may be used adjunctively. Treatment should be initiated promptly without waiting for liver biopsy confirmation.
All children with suspected Reye syndrome should be admitted to the intensive care unit. Discharge decisions are individualized and depend on stabilization of mental status and laboratory values. Long-term follow-up with hepatology and neurology is recommended, including neuropsychological assessment.
A critical preventive point is the avoidance of aspirin and salicylate-containing products in children and adolescents with viral illnesses. Clinicians must maintain vigilance for alternative diagnoses and aggressively manage intracranial pressure, as neurologic complications are the primary determinant of outcome.
Reye syndrome is a rare but potentially fatal, reversible clinicopathologic syndrome characterized by acute noninflammatory encephalopathy and hepatic dysfunction with fatty infiltration. It is believed to involve primary mitochondrial injury leading to impaired oxidative phosphorylation and decreased activity of enzymes involved in the Krebs cycle, gluconeogenesis, and urea synthesis. The result is hyperammonemia, hypoglycemia, and hepatic dysfunction without significant inflammation. Rapid neurologic deterioration is due to cerebral cytotoxic edema and increased intracranial pressure (ICP), with herniation being the most common cause of death. Survivors often recover normal liver and neurologic function.
The condition primarily affects children, with peak incidence between ages 4 and 11 years and an average age of 7 years. It is extremely rare in individuals older than 18 years. Fewer than 10% of cases occur before age 1 year. Incidence is highest in winter and early spring and has historically been associated with antecedent viral infections such as influenza A or B and varicella. Epidemiologic evidence strongly links exposure to salicylates during viral illness as a major risk factor. Genetic susceptibility and other environmental factors may contribute. Reye-like syndromes describe similar presentations due to inborn errors of metabolism or toxic exposures affecting fatty acid oxidation and urea metabolism.
Patients typically present with a biphasic illness. An initial viral prodrome is followed several days later by persistent, profuse vomiting and rapid onset of neurologic symptoms. The patient is usually afebrile at presentation. Early manifestations include lethargy, behavioral changes, irritability, confusion, delirium, and combativeness. As cerebral edema worsens, patients may develop hyperventilation, decorticate or decerebrate posturing, seizures, and coma. Hepatomegaly is present in about 40% of cases. No focal neurologic deficits are typically found. Infants may present atypically with tachypnea, apnea, hypoglycemia, irritability, or seizures.
Laboratory evaluation demonstrates elevated liver transaminases (at least three times normal), elevated serum ammonia, hypoglycemia (particularly in infants), prolonged prothrombin time due to decreased clotting factor synthesis, and elevated blood urea nitrogen. Serum bilirubin is usually normal or only mildly elevated. Ammonia levels often peak 24 to 48 hours after onset of neurologic symptoms; levels greater than 300 μg/dL are associated with poor prognosis. Platelet count and peripheral smear are usually normal. Toxicology screening should be performed to exclude other causes. Head CT may demonstrate diffuse cerebral edema. Lumbar puncture is not contraindicated but typically shows fewer than 8 leukocytes/mm³. Liver biopsy confirms the diagnosis by demonstrating microvesicular fatty infiltration but should not delay treatment.
The differential diagnosis includes inborn errors of metabolism (urea cycle defects, fatty acid oxidation disorders, organic acidemias), toxin exposures, drug intoxications such as acetaminophen or salicylates, hypoglycemia, sepsis, meningitis, encephalitis, and head trauma.
Management is supportive and aimed primarily at controlling intracranial pressure and correcting metabolic derangements. All patients require intensive care admission in a facility capable of ICP monitoring. Airway protection with rapid-sequence intubation is indicated for significant encephalopathy. Supplemental oxygen and cardiorespiratory monitoring are essential. Intravenous glucose should be administered promptly for altered mental status, and serum glucose should be maintained between 125 and 175 mg/dL with careful monitoring. Overhydration should be avoided.
Elevated ICP is managed with head elevation, controlled hyperventilation, osmotic therapy such as mannitol, and, in severe cases, barbiturate coma. Intracranial pressure monitoring via subarachnoid bolt or intraventricular catheter may be required in advanced stages. Vitamin K is administered if prothrombin time is prolonged, and fresh-frozen plasma may be given for severe coagulopathy or bleeding. Diuretics such as furosemide may be used adjunctively. Treatment should be initiated promptly without waiting for liver biopsy confirmation.
All children with suspected Reye syndrome should be admitted to the intensive care unit. Discharge decisions are individualized and depend on stabilization of mental status and laboratory values. Long-term follow-up with hepatology and neurology is recommended, including neuropsychological assessment.
A critical preventive point is the avoidance of aspirin and salicylate-containing products in children and adolescents with viral illnesses. Clinicians must maintain vigilance for alternative diagnoses and aggressively manage intracranial pressure, as neurologic complications are the primary determinant of outcome.
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