Reye Syndrome – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
- An acute encephalopathy with cerebral edema and fatty infiltration of the liver
- Occurs in previously healthy children and is often associated with an antecedent viral infection such as varicella or influenza (1)[C]
- Markedly decreased in incidence since the late 1970s, when association with aspirin use was determined (2,3)[B]
- Most current cases are actually Reyelike syndrome caused by an inborn error of metabolism or toxin (see Differential Diagnosis).
- System(s) affected: Gastrointestinal; Nervous
- Synonym: White liver disease
- Predominant age:
- Infants, children, adolescents
- Peak incidence at 6 years of age
- Most cases between 4 and 12 years of age
- Predominant sex: Male = Female
- Currently very rare
- Pediatric age group
- Rural and suburban areas
- Viral illnesses such as varicella and influenza A
- Use of preparations containing aspirin, salicylates, and/or salicylamides (4)[C]
No known genetic pattern
- Avoid salicylates in children with viral illnesses because the drug appears to act as a cofactor in susceptible individuals.
- A physician should be consulted before giving any child aspirin or antinausea medicines during a viral illness, especially influenza A.
- Recognize early symptoms of the disease.
Unknown; mitochondrion is major site of injury.
Symptoms reflected in clinical staging system:
- I: Vomiting, sleepiness, lethargy
- II: Confusion, delirium, hyperpnea, irritability, combativeness, hyper-reflexia, altered muscle tone
- III: Obtundation, light coma and seizures, decorticate rigidity, loss of oculocephalic reflexes, intact pupillary reflex
- IV: Coma, decerebrate posturing spontaneously or in response to painful stimuli, seizures, fixed pupils
- V: Coma, flaccid paralysis, loss of deep tendon reflexes, seizures, respiratory arrest, isoelectric electroencephalogram (2)[C]
- Recent aspirin use
- Sleepiness, lethargy, or confusion
- Vital signs
- Complete physical exam, especially a thorough neurologic exam, to evaluate different criteria in the clinical staging system
Diagnostic Tests & Interpretation
- Severe elevations of aspartate aminotransferase/alanine aminotransferase
- Normal or slightly elevated bilirubin or alkaline phosphatase
- Elevated ammonia
- Prolonged prothrombin time: Often not responsive to vitamin K
- Mixed respiratory alkalosis and metabolic acidosis
- Hyperaminoacidemia (glutamine, alanine, lysine)
- Lumbar puncture with cerebrospinal fluid (CSF) fluid pressure measurement: Increased CSF pressure without pleocytosis (<8 leukocytes/mm3)
- Liver biopsy
- Slightly enlarged, firm, yellow liver with fat droplets throughout
- Characteristic liver biopsy (may need special preparation) shows foamy cytoplasm with microvesicular fat
- Uniformly severe mitochondrial injury
- Acute encephalopathy without hepatic abnormalities:
- Drug overdose
- Psychiatric illness
- Diabetes mellitus
- Reyelike syndrome: Acute toxic encephalopathy with hepatic abnormalities (4)[C] due to either metabolic disorders or drug or toxin ingestions, including:
- Inherited metabolic disorders: Organic acidurias with defects in hepatic fatty acid oxidation; fatty acid metabolism defects
- Acyl-CoA dehydrogenase, carnitine deficiency:
- Urea cycle defects
- Carbamyl phosphate synthetase, ornithine transcarbamylase
- The most commonly diagnosed metabolic disorder in association with Reyes syndrome (RS) is medium-chain acyl coenzyme A dehydrogenase deficiency.
- Drug ingestions: Valproate, aspirin
- Toxin ingestions: Margosa oil, hopantenate, aflatoxin, hypoglycin (akee fruit; Jamaican vomiting sickness)
- It is essential to make the correct diagnosis, especially in infants <2 years of age.
- Rule out other causes of Reyelike syndrome (3,4)[C].
- All treatment is supportive and may include:
- Glucose 10–15% IV
- Vitamin K
- For increased intracranial pressure:
- Mannitol 0.5–1.0 g/kg IV as long as there is adequate urine output
- Dexamethasone 0.5 mg/kg/d
- Contraindications: Do not use mannitol if patient has no renal output.
- Precautions: Mannitol and poor renal output may result in vascular overload and pulmonary edema.
- Significant possible interactions: Refer to the manufacturers’ literature.
- Supportive care dictated by the severity of illness
- IV glucose and frequent monitoring of serum glucose (to prevent severe hypoglycemia)
- Hyperventilation, mannitol, and barbiturates to reduce intracranial pressure (ICP)
- Minimization of noise and other central nervous system stimulation to prevent increases in ICP
- Vitamin K, fresh-frozen plasma, and platelets as needed
- Mechanical ventilation as needed
- Dialysis to reduce high ammonia levels and/or residual salicylate
Decompression craniotomy may be necessary.
Medical emergency requiring immediate hospitalization and frequent monitoring, often in an intensive-care setting
Complete bed rest
Depends on specific residual effects; may require care of physicians, nurses, psychologists, and/or physical, occupational, and/or speech therapists
n.p.o. during the acute phase
- National Reye Syndrome Foundation, P.O. Box 829, Byron, OH 43506-0829, (800) 233-7393; http://www.reyessyndome.org
- National Institute of Health: http://www.ninds.nih.gov/disorders/reyes_syndrome/reyes_syndrome.htm
- Overall prognosis is related to degree of cerebral edema and ammonia level on admission.
- Outcomes range from a mild illness without progression and complete resolution to a critical illness with significant lasting sequelae.
- Possible neurologic sequelae include brain damage and disability, including problems with attention, concentration, speech, language, and fine and gross motor skills.
- Sequelae are more common with higher stages.
- Aspiration pneumonia
- Respiratory failure
- Cardiac dysrhythmia/arrest
- Inappropriate vasopressin excretion
- Diabetes insipidus
- Cerebral edema
1. Schror K. Aspirin and Reye syndrome: A review of the evidence. Pediatr Drugs. 2007;9:195–204.
2. Monto AS. The disappearance of Reye’s syndrome–a public health triumph. N Engl J Med. 1999;340:1423–4.
3. Belay ED, Bresee JS, Holman RC, et al. Reye’s syndrome in the United States from 1981 through 1997. N Engl J Med. 1999;340:1377–82.
4. Glasgow JF, Middleton B. Reye syndrome–insights on causation and prognosis. Arch Dis Child. 2001;85:351–3.
Gosalakkal JA, Kamoji V. Reye syndrome and reye-like syndrome. Pediatr Neurol. 2008;39:198–200.
Green A, Hall SM. Investigation of metabolic disorders resembling Reye’s syndrome. Arch Dis Child. 1992;67:1313–7.
Pugliese A, Beltramo T, Torre D et al. Reye’s and Reye’s-like syndromes. Cell Biochem. Funct. 2008;26:741–6.
See Also (Topic, Algorithm, Electronic Media Element)
Encephalitis, Viral; Hepatic Encephalopathy
331.81 Reye’s syndrome
74351001 Reye’s syndrome (disorder)
- RS is a rare acute metabolic encephalopathy largely affecting children and adolescents.
- Associations include antecedent viral infection and aspirin use.
- Most current cases of RS are actually Reyelike syndrome, caused by an inborn error of metabolism or a toxin.
- All treatment is supportive.
- Prognosis is related to the degree of cerebral edema and ammonia level on admission, and ranges from complete resolution to persistent neurologic sequelae.