Reye syndrome

Description: a rare type of hepatic encephalopathy that is associated with aspirin use for viral illness in children < 19 years
Etiology: aspirin use in individuals < 19 years of age with a febrile illness
Pathophysiology
- Viruses alter the metabolism of salicylates → accumulation of salicylate metabolites in the liver → mitochondrial injury and reversible inhibition of enzymes required for fatty acid oxidation → failure of hepatic ATP production → acute hepatic failure → hyperammonemia, metabolic acidosis, and hepatic steatosis → acute encephalopathy
- Hyperammonemia → cerebral edema → ↑ ICP
Clinical features
- Preceding viral infection (e.g., influenza, varicella or viral gastroenteritis): The first symptoms of Reye syndrome usually begin 3–5 days after a viral illness.
- Acute encephalopathy
  - Severe vomiting
  - Altered mental status (ranging from lethargy to delirium and coma)
  - Neurological symptoms (e.g., seizures, fixed pupils)
- Liver failure
  - Fatty degeneration
  - Hepatomegaly
Prevention
- Aspirin should be avoided in individuals < 19 years of age, especially those with fever.
- Exception: children with Kawasaki disease

Differential diagnostics

Feature	Salicylate (ASA) Poisoning	Acetaminophen (APAP) Poisoning	Reye Syndrome
Classic Hx	Overdose (intentional/accidental)	Intentional OD; chronic EtOH use	Child after viral illness + ASA use
Pathophysiology	Uncouples ox-phos; Resp center stim; Direct ototoxicity	Glutathione depletion -> toxic metabolite (NAPQI) -> liver necrosis	Mitochondrial dysfunction -> fatty liver & encephalopathy
Presentation	Tinnitus, fever, hyperventilation, AMS	Asymptomatic initially -> RUQ pain -> fulminant liver failure	Profuse vomiting, delirium/coma, NO jaundice
Key Lab Finding	Mixed resp. alkalosis + metabolic acidosis	Massive AST/ALT elevation (>1000s)	Hyperammonemia, elevated LFTs, hypoglycemia
Antidote / Tx	IV Sodium Bicarbonate, Hemodialysis	N-acetylcysteine (NAC)	Supportive care (manage ICP, hypoglycemia)
Buzzword	"Mixed acid-base disorder"	"Rumack-Matthew nomogram"	"Child + virus + aspirin"