Reye Syndrome Clinical Presentation

Updated: Apr 02, 2015
  • Author: Debra L Weiner, MD, PhD; Chief Editor: Kirsten A Bechtel, MD  more...
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Presentation

History

According to Centers for Disease Control and prevention (CDC) surveillance statistics for 1980-1997, 93% of 1160 patients had at least 1 viral illness in the 3 weeks preceding the onset of Reye syndrome. [4] Illnesses included viral upper respiratory illness or influenza in 73%, varicella in 21%, gastroenteritis in 14%, and other illness with exanthem in 5%. [4] Salicylates were detectable in the blood of 82% of patients. [4]

Influenza B (most common), influenza A, and varicella-zoster virus (VZV) are the viral pathogens most often involved. Parainfluenza, adenovirus, coxsackieviruses A and B, echovirus, Epstein-Barr virus (EBV), rubella virus, measles virus, cytomegalovirus (CMV), herpes simplex virus (HSV), parainfluenza virus, and poliomyelitis virus are less commonly associated. Reye syndrome can occur after vaccination with live viral vaccines.

Abrupt onset of pernicious vomiting occurs 12 hours to 3 weeks (mean, 3 days) after symptoms of viral illness have resolved. Neurologic symptoms usually occur 24-48 hours after the onset of vomiting. Lethargy is typically the first neurologic manifestation. Diarrhea and hyperventilation may be the first signs in children younger than 2 years. Irritability, restlessness, delirium, seizures, and coma occur.

Obtain an appropriate history in any child who presents with symptoms similar to those of Reye syndrome to determine whether an inborn error of metabolism (IEM) should be considered.

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Physical Examination

Signs and symptoms of Reye syndrome include protracted vomiting, with or without clinically significant dehydration; hepatomegaly in 50%; minimal or absent jaundice; and lethargy progressing to encephalopathy, obtundation, coma, seizures, and paralysis. Notably, patients are afebrile. Some postulate that antiemetics mask early symptoms, and others propose that antiemetics may further predispose the individual to the disease.

Lovejoy initially divided Reye syndrome into clinical stages 1-5 [6] ; Hurwitz subsequently developed a modified classification that divided the syndrome into stages 0-5, including a nonclinical stage (ie, stage 0). The CDC uses the Hurwitz classification but adds stage 6. Stage 0 does not meet the CDC case definition, because it does not meet the criteria for encephalopathy (see DDx). The stages used in the CDC classification of Reye syndrome are as follows:

  • Stage 0 - Alert, abnormal history and laboratory findings consistent with Reye syndrome, and no clinical manifestations
  • Stage 1 - Vomiting, sleepiness, and lethargy
  • Stage 2 - Restlessness, irritability, combativeness, disorientation, delirium, tachycardia, hyperventilation, dilated pupils with sluggish response, hyperreflexia, positive Babinski sign, and appropriate response to noxious stimuli
  • Stage 3 - Obtunded, comatose, decorticate rigidity, and inappropriate response to noxious stimuli
  • Stage 4 - Deep coma, decerebrate rigidity, fixed and dilated pupils, loss of oculovestibular reflexes, and dysconjugate gaze with caloric stimulation
  • Stage 5 - Seizures, flaccid paralysis, absent deep tendon reflexes (DTRs), no pupillary response, and respiratory arrest
  • Stage 6 - Patients who cannot be classified because they have been treated with curare or another medication that alters the level of consciousness

Diagnostic criteria

The CDC developed the following diagnostic criteria for Reye syndrome [7, 8] :

  • Acute noninflammatory encephalopathy with an altered level of consciousness
  • Hepatic dysfunction with a liver biopsy showing fatty metamorphosis without inflammation or necrosis or a greater than 3-fold increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or ammonia levels
  • No other explanation for cerebral edema or hepatic abnormality
  • Cerebrospinal fluid (CSF) with a white blood cell (WBC) count of 8 cells/µL or fewer (usually lymphocytes); note that lumbar puncture should not be performed in patients who are hemodynamically unstable and/or those in whom increased intracranial pressure (ICP) is a concern
  • Brain biopsy with findings of cerebral edema without inflammation or necrosis

When these criteria were developed, specific testing for other conditions was not required. Other etiologies, particularly inborn errors of metabolism (IEMs), should be ruled out before a definitive diagnosis is made.

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Complications

Complications of Reye syndrome include the following:

  • Brain herniation, status epilepticus, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and diabetes insipidus
  • Acute respiratory failure and aspiration pneumonia
  • Cardiac arrhythmias
  • Myocardial infarction
  • Cardiovascular collapse
  • Gastrointestinal bleeding and pancreatitis
  • Acute renal failure
  • Sepsis
  • Death
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