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Question:

A previously healthy 2-year-old girl is in the intensive care unit due to coma and respiratory failure.  The patient began having a headache and confusion a day ago.  This morning, her parents brought her to the emergency department due to vomiting.  In the emergency department, the patient began having generalized tonic-clonic seizures.  She was intubated and sedated.  The patient and her older brother had fever, cough, and pharyngitis last week.  The nanny gave the child over-the-counter medications for fever, but the parents do not know exactly what.  The patient's older sister had a cold sore on her lip 2 weeks ago.  Temperature is 37.1 C (98.8 F).  On examination, the girl is unresponsive and intubated.  Pupils are equal and have a sluggish reaction to light.  The sclera is nonicteric, and the neck is supple.  Mild hepatomegaly is palpated on abdominal examination.  Laboratory studies are as follows:

Liver function studies

  •     Total bilirubin

0.5ml/dL

  •     Aspartate aminotransferase

906 U/L

  •     Alanine aminotransferase

1214 U/L

 

        Cerebral spinal fluid

  •     Opening pressure

320 mm of H2O

  •     Glucose

53 mg/dL

  •     Protein

32 mg/dL

  •     Leukocytes                        2/mm3

 

CT scan of the brain reveals diffuse cerebral edema.  Which of the following is the most likely diagnosis in this patient?

 
Answers:

A.  Anticholinergic toxicity

Your reply:

B. Bacterial meningitis

C.  Hepatitis A infection

Correct answer:

D. Reye syndrome

E. Viral encephalitis

Explanation:

(Choice A)  Anticholinergic toxicity (eg, diphenhydramine overdose) presents with dry mouth and skin, blurry vision, hyperthermia, and urinary retention.  These findings are not present in this child.

 

(Choices B and E)  Children with encephalopathy should be evaluated for encephalitis.  However, this patient is unlikely to have infection of the central nervous system, given the normal cerebrospinal fluid findings and absence of fever and nuchal rigidity.

 

(Choice C)  Hepatitis A infection presents with fever, vomiting, and diarrhea.  Patients typically have elevated liver function tests, including bilirubin, but not increased intracranial pressure.  This child has markedly increased intracranial pressure, a normal bilirubin level, and no jaundice.

 

Explanation

This child's rapid onset of encephalopathyhepatic dysfunction, cerebral edema, and increased intracranial pressure is concerning for Reye syndrome.  Reye syndrome is a rare illness seen exclusively in young children treated with salicylates (eg, aspirin) for a viral infection (eg, influenzavaricella).  Reye syndrome was once relatively common, but the identification of aspirin exposure as a risk factor led to recommendations to avoid it in the management of pediatric fever and, consequently, there was a significant reduction in the incidence of Reye syndrome.  However, sporadic cases have been linked to unintentional administration of aspirin when caregivers are unaware of the contents of over-the-counter medications.

Presenting signs include vomiting and abnormal behavior, which progress rapidly to seizures and lethargy.  Characteristic laboratory findings of hepatic injury include marked elevations in aminotransferases, hyperammonemia, and prolonged PT.  Hypoglycemia may result from depletion of glucose stores and increased use.  Despite the degree of liver involvement, total bilirubin is usually normal or minimally elevated, and icterus is unusual.  Treatment is supportive.  Elevated intracranial pressure is a major cause of death in Reye syndrome.

Educational objective: Reye syndrome presents with vomiting, encephalopathy, hepatic dysfunction, and abnormal behavior leading to seizures and lethargy.  Caregivers should avoid administering aspirin to children with viral infection.

 

(Choices B and E)  Children with encephalopathy should be evaluated for encephalitis.  However, this patient is unlikely to have infection of the central nervous system, given the normal cerebrospinal fluid findings and absence of fever and nuchal rigidity.

 
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