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Reye's
syndrome is a rare form of acute encephalopathy and fatty
infiltration of the liver that tends to follow some acute viral
infections, particularly when salicylates are used. Diagnosis is
clinical. Treatment is supportive.
The
cause of Reye's syndrome is unknown, but many cases seem to follow
infection with influenza A or B or varicella. Using salicylates
during such illness increases the risk by as much as 35-fold. This
finding has led to a marked decrease in salicylate use in the US
since the mid-1980s (except when specifically indicated such as in
juvenile RA and Kawasaki disease), and a corresponding decrease in
the incidence of Reye's from several hundred annual cases to <
20. The syndrome occurs almost exclusively in children <
18 yr. In the US, most cases occur in late fall and winter.
The
disease affects mitochondrial function, causing disturbance in
fatty acid and carnitine metabolism. Pathophysiology is similar to
a number of inherited metabolic disorders.
Symptoms
and Signs
The
disease varies greatly in severity but is characteristically
biphasic. Initial viral symptoms (URI or sometimes chickenpox) are
followed in 5 to 7 days by pernicious nausea and vomiting and a
sudden change in mental status. The changes in mental status may
vary from a mild amnesia and lethargy to intermittent episodes of
disorientation and agitation, which can progress rapidly to
deepening stages of coma manifested by progressive
unresponsiveness, decorticate and decerebrate posturing, seizures,
flaccidity, fixed dilated pupils, and respiratory arrest. Focal
neurologic findings are usually not present. Hepatomegaly occurs
in about 40% of cases, but jaundice is absent.
Complications
include electrolyte and fluid disturbances, increased intracranial
pressure (ICP), diabetes insipidus, syndrome of inappropriate ADH
secretion, hypotension, arrhythmias, bleeding diatheses
(especially GI), pancreatitis, respiratory insufficiency,
hyperammonemia, aspiration pneumonia, and poor temperature
regulation.
Diagnosis
Reye's
syndrome should be suspected in any child exhibiting the acute
onset of an encephalopathy (without known heavy metal or toxin
exposure) and pernicious vomiting associated with hepatic
dysfunction. Liver biopsy provides the definitive diagnosis,
showing microvesicular, fatty changes, and is especially useful in
sporadic cases and in children < 2
yr. The diagnosis may also be made when the typical clinical
findings and history are associated with the following laboratory
findings: increased liver transaminases (AST, ALT >
3 times normal), normal bilirubin, increased blood ammonia level,
and prolonged PT. CSF examination usually shows increased
pressure, < 8 to 10 WBCs/μL,
and normal protein levels; the CSF glutamine level may be
elevated. Hypoglycemia and hypoglycorrhachia occur in 15% of
cases, especially in children < 4
yr; they should be screened for metabolic disease. The condition
is staged from I to V according to severity.
Signs
of metabolic derangement include elevated serum amino acid levels,
acid-base disturbances (usually with hyperventilation, mixed
respiratory alkalosis–metabolic acidosis), osmolar changes,
hypernatremia, hypokalemia, and hypophosphatemia.
Differential
diagnosis includes other causes of coma and hepatic dysfunction,
such as sepsis or hyperthermia (especially in infants);
potentially treatable inborn abnormalities of urea synthesis (eg,
ornithine transcarbamylase deficiency) or of fatty acid oxidation
(eg, systemic carnitine deficiency, medium chain acyl-CoA
dehydrogenase deficiency); phosphorus or carbon tetrachloride
intoxication; acute encephalopathy caused by salicylism or other
drugs - eg, valproate
()
- or poisons; viral encephalitis or meningoencephalitis; and acute
hepatitis. Illnesses such as idiopathic steatosis of pregnancy and
tetracyclineTETRACYN)
liver toxicity may show similar light microscopic findings.
Prognosis
Outcome
is related to the duration of cerebral dysfunction, severity and
rate of progression of coma, severity of the increased ICP, and
degree of blood ammonia elevation. Progression from stage I to
higher stages is likely when the initial blood ammonia level is > 100 μg/dL
(> 60 μmol/L)
and the PT is ≥ 3 sec longer
than that of the control. In fatal cases, the mean time from
hospitalization to death is 4 days. Fatality rates average 21% but
range from < 2% among patients in
stage I to > 80% in patients in
stage IV or V. Prognosis for survivors usually is good, and
recurrences are rare. However, the incidence of neurologic
sequelae (mental retardation, seizure disorders, cranial nerve
palsies, motor dysfunction) is as high as 30% among those who
developed seizures or decerebrate posturing during illness.
Treatment
Treatment
is supportive, with particular attention paid to control of ICP
and to blood glucose, because glycogen depletion is common.
Treatment of elevated ICP includes intubation, hyperventilation,
fluid restriction of 1500 mL/m2/day, elevating the head
of bed, and osmotic diuretics. Infusion of 10 or 15% dextrose is
common to maintain euglycemia. Coagulopathy may require fresh
frozen plasma or vitamin K. Other treatments (eg, exchange
transfusion, hemodialysis, and induction of deep coma with the use
of barbiturates) have not been proved effective but are sometimes
used.
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