Reye Syndrome – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

  • 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

Epidemiology

Incidence

  • 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

Risk Factors

  • 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]

Genetics

No known genetic pattern

General Prevention

  • 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.

Etiology

Unknown; mitochondrion is major site of injury.

Diagnosis

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]

History

  • Recent aspirin use
  • Sleepiness, lethargy, or confusion
  • Vomiting

Physical Exam

  • Vital signs
  • Complete physical exam, especially a thorough neurologic exam, to evaluate different criteria in the clinical staging system

Diagnostic Tests & Interpretation

Lab

  • Hypoglycemia
  • 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)

Diagnostic Procedures/Surgery

  • Lumbar puncture with cerebrospinal fluid (CSF) fluid pressure measurement: Increased CSF pressure without pleocytosis (<8 leukocytes/mm3)
  • Liver biopsy

Pathological Findings

  • 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

Differential Diagnosis

  • Acute encephalopathy without hepatic abnormalities:
    • Encephalitis
    • Meningitis
    • Drug overdose
    • Poisoning
    • 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
      • Fructosemia
    • 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)

Pediatric Considerations

  • 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].

Treatment

Medication

  • 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
      • Barbiturates
  • 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.

Additional Treatment

General Measures

  • 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

Surgery/Other Procedures

Decompression craniotomy may be necessary.

In-Patient Considerations

Initial Stabilization

Medical emergency requiring immediate hospitalization and frequent monitoring, often in an intensive-care setting

Ongoing Care

Follow-Up Recommendations

Complete bed rest

Patient Monitoring

Depends on specific residual effects; may require care of physicians, nurses, psychologists, and/or physical, occupational, and/or speech therapists

Diet

n.p.o. during the acute phase

Patient Education

  • 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

Prognosis

  • 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.

Complications

  • Aspiration pneumonia
  • Respiratory failure
  • Cardiac dysrhythmia/arrest
  • Inappropriate vasopressin excretion
  • Diabetes insipidus
  • Cerebral edema
  • Seizures
  • Death

References

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.

Additional Reading

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

Codes

ICD9

331.81 Reye’s syndrome

Snomed

74351001 Reye’s syndrome (disorder)

Clinical Pearls

  • 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.

Jean-Paul Marat

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