Reye syndrome
Post-viral vomiting and encephalopathy with hepatic dysfunction, hyperammonemia, hypoglycemia, and often little or no jaundice.
GI
Reye Syndrome
After a viral illness, recurrent vomiting and altered behavior can signal a mitochondrial liver-brain emergency.
- Connect salicylate exposure after viral illness to mitochondrial hepatic dysfunction and encephalopathy.
- Recognize vomiting, hypoglycemia, hyperammonemia, coagulopathy, and microvesicular steatosis.
- Exclude infectious, toxic, and inherited metabolic mimics while initiating ICU supportive care.
Rounds dashboard
See the whole liver patient
The dashboard keeps injury pattern, function, complications, and next action visible together.
Quick check
An 8-year-old is recovering from influenza when persistent vomiting develops, followed by irritability and confusion. A caregiver gave aspirin for fever. Glucose is 48 mg/dL, ammonia is elevated, and CSF has no pleocytosis.
Which diagnosis is most likely?
Reason it through
- What is the temporal clue?Encephalopathy follows a viral prodrome.
- What exposure raises risk?Aspirin or another salicylate given to a child with viral illness.
- Which laboratory pair points to hepatic mitochondrial failure?Hypoglycemia and hyperammonemia.
Trend severity, not one diagnostic cutoff
Reye syndrome has no single confirmatory number; direction and neurologic stage matter.
Serial ammonia, glucose, blood gas, electrolytes, AST, ALT, PT/INR, mental status, pupils, and cardiorespiratory status reveal progression.
A rising ammonia level or worsening neurologic stage is more concerning than an isolated stable elevation.
Place the clinical measures along a progression axis.
Alert with vomiting
Lethargy or irritability
Confusion or combativeness
Seizures or abnormal posturing
Coma or loss of brainstem responses
Neurologic decline is an ICU escalation signal even before every laboratory result returns.
A syndrome of exclusion with a distinctive pattern
Reye syndrome is uncommon, so recognition depends on pattern plus active exclusion of dangerous mimics.
The classic setting is a child recovering from influenza or varicella who received salicylate and then develops abrupt vomiting and progressive encephalopathy.
Mitochondrial dysfunction impairs fatty-acid oxidation and the urea cycle, producing microvesicular steatosis, hyperammonemia, hypoglycemia, and cerebral edema.
Compare Reye syndrome with its closest alternatives.
Salicylate poisoning
Tachypnea, mixed respiratory alkalosis and metabolic acidosis, tinnitus, fever, and a measured salicylate burden may dominate.
Meningitis or encephalitis
Fever, meningeal signs, focal findings, seizures, inflammatory CSF, or pathogen testing can identify CNS infection.
Inborn error of metabolism
Urea-cycle, fatty-acid oxidation, and organic-acidemia disorders may mimic Reye syndrome, especially with recurrence, fasting triggers, unusual age, or family history.
Aspirin exposure supports Reye syndrome but does not replace toxicology and metabolic evaluation.
From viral recovery to cerebral edema
The clinical evolution can be rapid and staged by worsening neurologic dysfunction.
Persistent vomiting is often the first warning after the viral prodrome, followed by irritability, confusion, combativeness, delirium, seizures, and coma.
Ammonia and cerebral swelling can rise as hepatic mitochondrial metabolism fails, even when bilirubin is not strikingly elevated.
Order the typical progression.
Influenza, varicella, or another viral syndrome begins to improve.
Aspirin during the illness increases risk; exposure may need a careful caregiver and medication-history review.
Recurrent emesis marks the transition from ordinary recovery to possible metabolic disease.
Irritability, lethargy, disorientation, or combativeness signals encephalopathy.
Seizures, abnormal posturing, loss of brainstem responses, and coma indicate cerebral edema and critical illness.
Recognize the biochemical constellation
No single result confirms Reye syndrome, but the cluster should trigger immediate care.
Expected findings include elevated ammonia and aminotransferases, prolonged PT/INR, hypoglycemia, and acid-base or electrolyte abnormalities.
Liver histology, when needed, shows diffuse microvesicular fatty change with minimal inflammation rather than the necroinflammatory pattern of viral hepatitis.
Identify the finding most consistent with Reye syndrome.
Hyperammonemia with hypoglycemia and encephalopathyThis reflects impaired hepatic mitochondrial metabolism and is a classic emergency pattern.
Marked conjugated hyperbilirubinemia as the required defining featureJaundice is often absent or modest and is not required.
Neutrophilic CSF pleocytosis as the usual findingInflammatory CSF points toward CNS infection rather than classic Reye syndrome.
Macrovesicular steatosis with dense portal inflammationReye syndrome classically produces microvesicular steatosis with little inflammation.
The brain can be critically ill while the child looks only mildly jaundiced.
One mitochondrial insult, several compartments
Management follows the organs threatened by energy failure and swelling.
The liver loses effective fatty-acid oxidation, ureagenesis, glucose homeostasis, and clotting-factor production.
The brain is threatened by hyperammonemia, osmotic shifts, cerebral edema, seizures, and reduced perfusion.
Map the compartment to the bedside threat.
Hepatic mitochondria
Impaired beta-oxidation produces microvesicular fat and reduced ATP-dependent metabolism.
Urea cycle
Impaired ammonia disposal contributes to hyperammonemia and encephalopathy.
Blood glucose
Limited glycogen and impaired hepatic metabolism can cause dangerous hypoglycemia, especially in younger children.
Cerebral compartment
Edema raises intracranial pressure and can reduce cerebral perfusion or cause herniation.
Coagulation system
Prolonged PT/INR reflects hepatic dysfunction; bleeding risk and procedure planning require repeated assessment.
Stabilize while proving what it is not
Diagnostic work and treatment occur together in a pediatric ICU.
Secure airway, breathing, and circulation; check glucose immediately; obtain ammonia, electrolytes, blood gas, liver tests, PT/INR, toxicology, and targeted infectious studies.
Correct hypoglycemia, avoid hypotonic fluid, maintain oxygenation and perfusion, control fever and seizures, elevate the head, minimize noxious stimulation, and manage intracranial hypertension with critical-care guidance.
Reveal the purpose behind each action.
Restore cerebral fuel while avoiding large glucose swings.
Use frequent bedside glucose checks.
Protect a declining child and maintain oxygenation.
Intubation is indicated when consciousness or protective reflexes deteriorate.
Exclude structural and infectious mimics without provoking herniation.
Defer lumbar puncture when intracranial pressure is unsafe.
Exclude fatty-acid oxidation defects, urea-cycle disorders, organic acidemias, and ingestions.
Save blood and urine early because treatment can alter the signature.
Provide meticulous supportive neurocritical care.
There is no proven therapy that reverses the mitochondrial lesion; early physiologic support is decisive.
Do not delay glucose correction or neuroprotection while awaiting a definitive exclusion diagnosis.
Stage 1 of 3: Overview
Overview
Reye Syndrome
The clinical evolution can be rapid and staged by worsening neurologic dysfunction.
Rounds question
Name today’s management pivot
Choose the clue that changes what the team does on this round.
Which diagnosis is most likely?
- Key finding. An 8-year-old is recovering from influenza when persistent vomiting develops, followed by irritability and confusion. A caregiver gave aspirin for fever. Glucose is 48 mg/dL, ammonia is elevated, and CSF has no pleocytosis.
- Answer. Reye syndrome
- Why. The post-viral course, salicylate exposure, vomiting, encephalopathy, hypoglycemia, and hyperammonemia form the classic pattern.
- Board rule. Post-viral vomiting plus behavior change is a metabolic emergency, not routine gastroenteritis.
Run the liver cases
Five pediatric presentations test recognition, mimic exclusion, laboratory interpretation, cerebral protection, and prevention.
Cross out premature plans and highlight the finding that changes management. Each case separates injury, function, and complication.
A 10-year-old recovering from influenza develops repeated vomiting and unusual aggression. His parent reports giving aspirin-containing cold medicine. Glucose is 54 mg/dL and ammonia is elevated.
What is the best immediate disposition?
Reason it through
- Which symptom is more than post-viral nausea?New aggression is encephalopathy.
- Which exposure links the pattern?An aspirin-containing product.
- Why ICU rather than routine observation?Neurologic decline, hypoglycemia, and cerebral edema can progress rapidly.
Which symptom is more than post-viral nausea?Which exposure links the pattern?
- Which symptom is more than post-viral nausea?New aggression is encephalopathy.
- Which exposure links the pattern?An aspirin-containing product.
- Why ICU rather than routine observation?Neurologic decline, hypoglycemia, and cerebral edema can progress rapidly.
A 6-year-old with suspected Reye syndrome becomes somnolent. Bedside glucose is 38 mg/dL, oxygen saturation is 96%, and blood pressure is stable.
Which intervention should occur first?
Reason it through
- What immediate reversible threat is present?Severe hypoglycemia.
- Which organ is most vulnerable?The brain.
- Does dextrose interfere with the need for diagnosis?No. Stabilization takes priority while samples are obtained.
What immediate reversible threat is present?Which organ is most vulnerable?
- What immediate reversible threat is present?Severe hypoglycemia.
- Which organ is most vulnerable?The brain.
- Does dextrose interfere with the need for diagnosis?No. Stabilization takes priority while samples are obtained.
A 9-year-old has fever, confusion, neck stiffness, focal weakness, and CSF neutrophilic pleocytosis. AST is mildly elevated after several days of illness.
Which diagnosis deserves priority over Reye syndrome?
Reason it through
- Which findings localize directly to CNS inflammation?Neck stiffness and neutrophilic CSF pleocytosis.
- Which finding is atypical for classic Reye syndrome?A focal neurologic deficit with inflammatory CSF.
- What is the safety lesson?Treat dangerous infectious mimics promptly while evaluating encephalopathy.
Which findings localize directly to CNS inflammation?Which finding is atypical for classic Reye syndrome?
- Which findings localize directly to CNS inflammation?Neck stiffness and neutrophilic CSF pleocytosis.
- Which finding is atypical for classic Reye syndrome?A focal neurologic deficit with inflammatory CSF.
- What is the safety lesson?Treat dangerous infectious mimics promptly while evaluating encephalopathy.
A 3-year-old has a second episode of fasting-related hypoglycemia, hyperammonemia, and encephalopathy. No salicylate exposure occurred, and a sibling died during an unexplained childhood illness.
What should be prioritized?
Reason it through
- What feature is unusual for a one-time post-viral syndrome?This is a recurrent fasting-triggered episode.
- What history raises inherited risk?A sibling died during a similar unexplained illness.
- When should blood and urine be saved?During the acute metabolic crisis, before treatment erases the pattern.
What feature is unusual for a one-time post-viral syndrome?What history raises inherited risk?
- What feature is unusual for a one-time post-viral syndrome?This is a recurrent fasting-triggered episode.
- What history raises inherited risk?A sibling died during a similar unexplained illness.
- When should blood and urine be saved?During the acute metabolic crisis, before treatment erases the pattern.
A 12-year-old with suspected Reye syndrome progresses from confusion to seizures and abnormal posturing. Pupils are sluggish, and ammonia is rising.
Which management priority is most appropriate?
Reason it through
- Which findings signal raised intracranial pressure?Posturing, pupillary change, seizures, and declining consciousness.
- What procedure may be unsafe?Lumbar puncture when intracranial pressure is elevated.
- What is the immediate physiologic goal?Protect airway, oxygenation, cerebral perfusion, and control swelling and seizures.
Which findings signal raised intracranial pressure?What procedure may be unsafe?
- Which findings signal raised intracranial pressure?Posturing, pupillary change, seizures, and declining consciousness.
- What procedure may be unsafe?Lumbar puncture when intracranial pressure is elevated.
- What is the immediate physiologic goal?Protect airway, oxygenation, cerebral perfusion, and control swelling and seizures.
Rapid review
Three questions to check
Which diagnosis is most likely?
Reye syndrome. The post-viral course, salicylate exposure, vomiting, encephalopathy, hypoglycemia, and hyperammonemia form the classic pattern.
Which symptom is more than post-viral nausea?
New aggression is encephalopathy.
Which exposure links the pattern?
An aspirin-containing product.
Medically reviewed
Fatima Ali, DO
PGY-1 Resident Physician in Psychiatry
University Hospitals, Columbia
DO from Kansas City University
Resident physician and founding medical reviewer at Bone Wizardry, focused on clinical accuracy, clear diagnostic reasoning, and practical board-oriented teaching across the curriculum.
Languages: English, Urdu
Primary reviewerFull physician profile
Medically reviewed
Sources
Bone Wizardry is a study resource for medical students. It is not medical advice.