The symptomatology of Reye syndrome typically surfaces after 3 to 5 days from onset of the viral infections of the respiratory tract. The following system wise presentation of signs and symptoms is commonly seen in patients with Reye syndrome:

• General Appearance: Patients may be brought in lethargic, week and sleepy due to hyperammonemia and impending brain edema. This could also make the child aggressive and agitated with irrational behavior due to the high ammonia levels in the brain. 
• Chest and heart: Tachypnea may present with due to an enlarging liver that limits the intrathoracic space.

• Abdomen: Persistent vomiting in teenagers may be an early sign of brain edema. Diarrhea may heralding sign of Reye syndrome among children below 2 years old due to metabolic defects in fat oxidation. Hepatomegaly may present in almost half of all Reye syndrome cases due to hepatic edema.
• Neurologic: Weakness and paralysis of the legs and arms may be a presenting neurologic sign with cerebral damage. Patients may brought in to the emergency room in seizure due to hyperammonemia and brain edema.

The diagnosis of Reye syndrome conforms with the diagnostic criteria established by the CDC which in includes: acute altered state of consciousness, hepatic dysfunction, CSF white blood cell count of less than 8 cells/uL, and histologic signs of cerebral edema [7]. Reye syndrome does not have a specific test to clinch its definitive diagnosis. However, there are laboratory tests that may correlate with the syndrome and aid the management of cases. The following laboratory examinations and tests are done in patients with relative risk for Reye syndrome:

• Blood and urine test for the diagnosis of fatty acid oxidation defects and metabolic disorders.
• Lumbar tap (spinal tap): This procedure is done to rule out other disorders that may present like Reye syndrome (i.e. meningitis and encephalitis).
• Liver biopsy: Hepatocyte tissues may be harvested from the liver to demonstrate the histologic changes typical of Reye syndrome.
• Imaging: Cranial computed tomography and magnetic resonance imaging can elucidate detailed images of the brain to rule out other organic brain causes that may mimic the signs of Reye syndrome.
• Skin biopsy: Fatty acid oxidation disorders and other metabolic disorders can be diagnosed using skin biopsy methods performed inside a clinic.

Patients suffering from Reye syndrome are always treated as an in-patient case in the hospital although severe cases may require intensive care. The following specific treatments are implored in the treatment of Reye syndrome among admitted patients:

• Intravenous solutions: Intravenous fluids may replace imbalances in glucose and other electrolytes among patients with Reye syndrome.
• Osmotic diuretics: Diuretics like mannitol may be used to decrease the intracranial pressure in patients with brain edema [8]. Hypertonic saline at 3% may also decrease the level of brain edema [9].
• Medications that prevent bleeding: Hepatic damage in Reye syndrome may require exogenous sources of Vitamin K, plasma and platelet concentrates to prevent bleeding problems that may occur. 
• Liver transplant: Liver transplantation may be the last option in cases of severe irreversible liver damage among infants presenting with encephalopathy and fulminant hepatitis [10].

Prognosis and mortality rates greatly improve with the prompt diagnosis and treatment of Reye syndrome. The majority of deaths in Reye syndrome is due to cerebral edema; thus, any signs of increased intracranial pressure precludes a poor prognosis [6].

Age related risk for mortality is marked below 5 years of age. Serum ammonia levels beyond 45 mcg/dl have a relative risk of 3.4. Hypoglycemia and hyponatremia are considered early predictors of poor prognosis.

Complications

The following clinical conditions are established complications of Reye syndrome:

• Electrolyte and fluid imbalance
• Increased intracranial pressure
• Hypotension
• Cardiac Arrhythmias
• Gastrointestinal bleeding
• Pancreatitis
• Respiratory insufficiency
• Hyperammonemia
• Aspiration pneumonia
• Uncal herniation
• Death

The definitive etiology of Reye syndrome is vaguely understood. However, salicylates like aspirin and viral infections like influenza and varicella are identified as a triggering factor in the onset of the disease among teenagers and children [3].

Inborn error of metabolism like the medium-chain-acyl-dehydrogenase and the long-chain-acyl-dehydrogenase deficiency has been proven to cause Reye syndrome among patients [4]. The exposure to toxins like insecticides, herbicides and paint thinner have also been implicated in the occurrence of Reye syndrome.

The peak annual incidence of Reye syndrome in the United States reached 555 cases between 1979 and 1980 according to the Centers of Disease and Control (CDC). The national prevalence in the United States is 15 to 88 cases per 10 million population.

Prevalence of Reye syndrome correlates well during the outbreaks of influenza and chicken pox. In the United Kingdom, the incidence of Reye syndrome occurs among children ages 12 and below at 63 cases per 10 million population [5].

Peak age incidence of Reye syndrome is at 6 years old with age range incidence at 5 to 14 years old. Reye syndrome rarely affects the newborns and those beyond the age of 18 years old. The white race shares 93% of cases while the black African American race has only 5% of the cases.

The exact pathophysiology of Reye syndrome is still unclear although mitochondrial injury and dysfunction has been closely implicated. There is a marked inhibition of the oxidative phosphorylation and the fatty acid beta oxidation in cells which were previously infected by the flu and chicken pox virus.

Mitochondrial dysfunction are further aggravated by toxins like salicylates. The progressive damage of the hepatic mitochondria leads to hyperammonemia causing astrocyte and cerebral edema causing an increased in intracranial pressure in the brain.

Extreme precautions should be observed in giving aspirin to children especially those recovering from a recent viral infection. Newborn screening can detect inborn errors of metabolism that can greatly predispose the child to Reye syndrome. A careful examination of the drug labels should be a prudent practice to prevent inadvertent intake of aspirin during viral infections. The active immunization against varicella and influenza can greatly lower the incidence of Reye syndrome among children.

Reye syndrome is a rare and serious clinical disease characterized by the progressive swelling of the liver and the brain. This syndrome commonly affects children and teenagers with recent viral infection like influenza and varicella [1].

Patients may appear unconscious in the emergency room which requires immediate care of this potentially fatal disease [2]. Aspirin is commonly associated with Reye syndrome; thus, prudent caution should be observed when giving this type of medications to pediatric cases who are undergoing a viral infection.

Definition

Reye syndrome is a serious clinical disorder characterized by brain and liver swelling.

Cause

Influenza and varicella infection, inborn errors of fat metabolism, and salicylates are the most common causes.

Symptoms

Altered state of consciousness, neurologic deficits, seizures, abdominal distention, vomiting and weakness may occur.

Diagnosis

A good clinical history and neurologic examination, blood tests, liver and skin biopsy, and imaging methods are used to diagnose Reye syndrom. 

Treatment and follow-up

Correction of electrolyte imbalance, medical decompression with the use of diuretics, and the use of medications that prevent bleeding. Liver transplant may be an option for severe liver damage.

1. Belay ED, Bresee JS, Holman RC, Khan AS, Shahriari A, Schonberger LB. Reye's syndrome in the United States from 1981 through 1997. N Engl J Med. May 6 1999; 340(18):1377-82.
2. Tanret I, Duh D. The Reye syndrome. J Pharm Belg. 2011; (1):13-5 
3. Selves A, Ruiz S, Crognier L, Conil JM, Bonneville F. Aspirin and its danger: Reye syndrome in young adult. Ann Fr Anesth Reanim. 2013; 32(11):814-6 
4. Gosalakkal JA, Kamoji V. Reye syndrome and reye-like syndrome. Pediatr Neurol. Sep 2008; 39(3):198-200.
5. New World Encyclopedia. Reye's syndrome. Last updated September 5, 2008
6. Link A, Kaplan BT, Böhm M. 21-year-old woman with Reye's syndrome after influenza .Dtsch Med Wochenschr. 2012; 137(38):1853-6 
7. CDC. Reye syndrome surveillance--United States, 1989. MMWR Morb Mortal Wkly Rep. Feb 8 1991; 40(5):88-90.
8. Chesnut RM. Medical management of severe head injury: present and future. New Horiz. Aug 1995; 3(3):581-93.
9. Brenkert TE, Estrada CM, McMorrow SP, Abramo TJ. Intravenous hypertonic saline use in the pediatric emergency department. Pediatr Emerg Care. Jan 2013; 29(1):71-3.
10. Cağ M, Saouli AC, Audet M, Wolf P, Cinqualbre J. Reye syndrome and liver transplantation. Turk J Pediatr. 2010; 52(6):662-4