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Reye Syndrome

Reyes' Syndrome

Reye syndrome is a potentially fatal disease of childhood, characterized by a combination of acute encephalopathy and fatty infiltration of the internal organs. The etiology is unknown, but it is almost always associated with a previous viral infection.


Presentation

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:

  • 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.
Fever
  • Patients with fever took salicylate more frequently than control subjects with fever (P .01). In addition, salicylate consumption was correlated with severity of Reye's syndrome (P .05).[ncbi.nlm.nih.gov]
  • It is most often associated with use of aspirin during the fever, and for this reason aspirin and aspirin-containing products are not recommended for people under the age of 19 during fever.[encyclopedia.com]
Fatigue
  • Reye's syndrome Pathology Type Syndrome Cause(s) Interaction of aspirin with influenza Symptoms Stage 1: Vomiting, drowsiness, fatigue, loss of energy Stage 2: Aggression, irritation, befuddlement, delirium, seizures, weakness, and coma Mortality Rate[house.wikia.com]
  • Symptoms of Reye's Syndrome Severe nausea and vomiting Drowsiness; lethargy Mental confusion, hyperexcitability, disorientation, irritability, or memory loss Severe symptoms: seizures, loss of consciousness, cessation of breathing Irritability Fatigue[healthcommunities.com]
  • Sindrom khronicheskoy ustalosti: sovremennye predstavleniya ob etiologii Abstract About the authors References Statistics Abstract Chronic fatigue syndrome is a disease of unexplained feeling of profound fatigue lasting for more than 6 months.[endojournals.ru]
  • […] dementia without behavioral disturbance ( F02.80 ) Reye's syndrome G93.7 Syndrome - see also Disease Reye's G93.7 ICD-10-CM Codes Adjacent To G93.7 G93.1 Anoxic brain damage, not elsewhere classified G93.2 Benign intracranial hypertension G93.3 Postviral fatigue[icd10data.com]
High Fever
  • A seven-month-old girl was admitted to the Pediatrics Department of Mackay Memorial Hospital with the following symptoms and signs: (1) high fever for more than five days; (2) injection of bilateral conjunctiva; (3) bright red lips with strawberry tongue[ncbi.nlm.nih.gov]
Hyperpnea
  • Examination may reveal a positive Babinski sign and hyperreflexia, consistent with cerebral edema; dilated, sluggish pupils, and hyperpnea with irregular respirations. Hepatomegaly is sometimes present, but splenomegaly is absent.[web.archive.org]
  • Examination may reveal a positive Babinski sign and hyperreflexia, as well as signs consistent with cerebral edema: dilated, sluggish pupils, and hyperpnea with irregular respirations (5).[hawaii.edu]
Vomiting
  • For example, vomiting may be replaced with diarrhea and infants may display irregular breathing.[web.archive.org]
  • Convert to ICD-10-CM : 331.81 converts directly to: 2015/16 ICD-10-CM G93.7 Reye's syndrome Clinical Information A form of encephalopathy with fatty infiltration of the liver, characterized by brain edema and vomiting that may rapidly progress to seizures[icd9data.com]
  • The syndrome often begins with vomiting. It may last for many hours. The vomiting is quickly followed by irritable and aggressive behavior. As the condition gets worse, the child may be unable to stay awake and alert.[nlm.nih.gov]
Nausea
  • It may follow an upper respiratory infection or chickenpox, and has symptoms of nausea, vomiting, seizures, confusion, and lethargy. As the disease worsens, the child may be unable to stay awake and alert.[health.utah.gov]
  • Symptoms include nausea and vomiting listlessness personality change - such as irritability, combativeness or confusion delirium convulsions loss of consciousness if these symptoms occur soon after a viral illness, seek medical attention immediately.[icd9data.com]
  • Other symptoms of Reye syndrome: Confusion Lethargy Loss of consciousness or coma Mental changes Nausea and vomiting Seizures Unusual placement of arms and legs ( decerebrate posture ).[nlm.nih.gov]
  • A physician should be consulted before giving a child any aspirin or anti-nausea medicines during a viral illness, which can mask the symptoms of RS. Is there any treatment? There is no cure for RS.[web.archive.org]
Persistent Vomiting
  • Homepage Rare diseases Search Search for a rare disease Reye syndrome Disease definition A rare, systemic disease characterized by persistent vomiting with confusion, lethargy, disorientation, hyperreflexia, hyperventilation, and tachycardia, with rapid[orpha.net]
  • Symptoms of Reye Syndrome include: Unusual sleepiness or lack of energy Diarrhea and rapid breathing in infants and toddlers Persistent vomiting in children and teenagers Changes in personality or behaviour such as confusion, irritability or aggression[healthlinkbc.ca]
  • The persistent vomiting classically seen with Reye's syndrome can result in electrolyte abnormalities and dehydration, especially in young children.[ebmconsult.com]
  • Symptoms include: persistent vomiting lethargy or sleepiness in infants, diarrhea and rapid breathing In the later stages, a child may exhibit irrational behavior, confusion, severe weakness, seizures, and loss of consciousness.[siloisd.org]
  • 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.[symptoma.com]
Recurrent Vomiting
  • However, it can also occur in the absence of aspirin use Rare, acute, sometimes fatal disease of childhood, most often occurring as a sequel of varicella or a viral upper respiratory infection of childhood; marked by recurrent vomiting and elevated serum[icd9data.com]
  • Symptoms of RS include persistent or recurrent vomiting, listlessness, personality changes such as irritability or combativeness, disorientation or confusion, delirium, convulsions, and loss of consciousness.[web.archive.org]
  • The symptoms of RS include persistent or recurrent vomiting; listlessness; personality changes such as irritability or combativeness and disorientation or confusion; delirium, convulsions, and loss of consciousness.[sharecare.com]
  • Symptoms include persistent or recurrent vomiting, listlessness, personality changes such as irritability or combativeness, disorientation, delirium, convulsions, and loss of consciousness.[liverfoundation.org]
Abdominal Pain
  • A previously well 8-year-old boy presented with repeated episodes of vomiting and abdominal pain followed by altered sensorium and tonic spasms. This occurred 5 days after upper respiratory tract infection.[ncbi.nlm.nih.gov]
  • Edmondson and Can Ficicioglu, An 8-Year-Old Girl With Abdominal Pain and Mental Status Changes, Pediatric Emergency Care, 31, 6, (459), (2015).[dx.doi.org]
Hepatomegaly
  • A 2-year-old boy had acute fever, malaise, and somnolence with hepatomegaly, increased blood ammonia content (338 microM), high SGOT, low blood glucose content, and mild acidosis.[ncbi.nlm.nih.gov]
  • Hepatomegaly, acute hepatic steatosis, fatty liver degeneration and multiple laboratory abnormalities are associated.[orpha.net]
  • * Stupor * Agitated delirium * Screaming * Drug reaction-like behavior * Extensor spasms * Decerebrate rigidity * Aspirin poisoning-like symptoms * Coma * Vomiting, think Reye's * Emergency SGOT-SGPT (SAT-ACT) * Elevated blood NH3 * Hypoglycemia and hepatomegaly[web.archive.org]
  • Liver function is impaired, sometimes with slight hepatomegaly but without jaundice.[patient.info]
Confusion
  • Other symptoms of Reye syndrome: Confusion Lethargy Loss of consciousness or coma Mental changes Nausea and vomiting Seizures Unusual placement of arms and legs ( decerebrate posture ).[nlm.nih.gov]
  • Homepage Rare diseases Search Search for a rare disease Reye syndrome Disease definition A rare, systemic disease characterized by persistent vomiting with confusion, lethargy, disorientation, hyperreflexia, hyperventilation, and tachycardia, with rapid[orpha.net]
  • In the later stages, a child may behave irrationally; be confused; or have severe muscle weakness, seizures, and loss of consciousness. There usually is no fever.[bestonlinemd.com]
  • Take your child to the emergency room immediately, if you see signs of: confusion lethargy other mental symptoms[healthline.com]
Seizure
  • Complications may include: Coma Permanent brain damage Seizures When untreated, seizures and coma may be life threatening.[nlm.nih.gov]
  • Convert to ICD-10-CM : 331.81 converts directly to: 2015/16 ICD-10-CM G93.7 Reye's syndrome Clinical Information A form of encephalopathy with fatty infiltration of the liver, characterized by brain edema and vomiting that may rapidly progress to seizures[icd9data.com]
  • A child also might get: small amounts of insulin to increase glucose metabolism corticosteroids to reduce brain swelling diuretics to get rid of excess fluid If seizures happen, they'll be treated with medicines.[kidshealth.org]
  • In the later stages, a child may behave irrationally; be confused; or have severe muscle weakness, seizures, and loss of consciousness. There usually is no fever.[web.archive.org]
Lethargy
  • Other symptoms of Reye syndrome: Confusion Lethargy Loss of consciousness or coma Mental changes Nausea and vomiting Seizures Unusual placement of arms and legs ( decerebrate posture ).[nlm.nih.gov]
  • Homepage Rare diseases Search Search for a rare disease Reye syndrome Disease definition A rare, systemic disease characterized by persistent vomiting with confusion, lethargy, disorientation, hyperreflexia, hyperventilation, and tachycardia, with rapid[orpha.net]
  • It may follow an upper respiratory infection or chickenpox, and has symptoms of nausea, vomiting, seizures, confusion, and lethargy. As the disease worsens, the child may be unable to stay awake and alert.[health.utah.gov]
Agitation
  • We report the case of a 17-month-old white girl whose 1-day history of vomiting and agitation followed by generalized unresponsiveness caused her to be brought to a local emergency department.[ncbi.nlm.nih.gov]
  • However, then he abruptly starts to vomit repeatedly and frequently every one or two hours over a twenty-four to thirty-six-hour period, becoming lethargic or sleepy, which then turns into agitation, delirium, or anger.[healthychildren.org]
  • Parents should look for behavior changes, such as confusion, agitation, and delirium. Other common symptoms include frequent vomiting, sleepiness or lack of energy, diarrhea, and rapid breathing.[bundoo.com]
  • […] such as a flu-like upper respiratory infection or chicken pox (usually no diarrhea) Elevated SGOT-SGPT (SAT-ACT) [usually 200 or more units] in the absence of jaundice Signs of disturbed brain function characterized by: * Lethargy * Staring * Stupor * Agitated[web.archive.org]
Headache
  • Both chickenpox and the flu can cause headaches. That is why it is important to not use aspirin to treat a child's headache. Your child may have an undetected viral infection and be at risk of developing Reye’s syndrome.[healthline.com]
  • Patients during the prodrome and control subjects had similar rates of sore throat, coryza, cough, headache, and gastrointestinal complaints except for documented fever which occurred significantly more often in patients than in control subjects (P .05[ncbi.nlm.nih.gov]
  • Do not give ASA or Aspirin to anyone under 18 years of age to manage symptoms such as fever, headache and muscle aches. Instead, use acetaminophen for anyone under 18 years of age.[healthlinkbc.ca]
  • Aspirin is in many over-the-counter and prescription drugs, including drugs for headache, fever, menstrual cramps, muscle pain, nausea, upset stomach, and arthritis. It may be used in drugs taken orally or by suppository.[encyclopedia.com]

Workup

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.
Prothrombin Time Prolonged
  • Prothrombin time: prolonged. A CT scan of the brain is obtained which shows cerebral edema. His neurologic symptoms rapidly worsen and he becomes unresponsive. He is intubated and put on mechanical ventilation. Reye syndrome is suspected.[web.archive.org]
  • Prothrombin time: prolonged. A CT scan of the brain is obtained which shows diffuse cerebral edema. His neurologic symptoms rapidly worsen, and he becomes unresponsive. He is intubated and put on mechanical ventilation. Reye syndrome is suspected.[hawaii.edu]
Hyponatremia
  • Hypoglycemia and hyponatremia are considered early predictors of poor prognosis.[symptoma.com]
Liver Biopsy
  • The muscle biopsy results were compared with those of liver biopsies in 7 patients including one patient with definite RS and 6 with mimicking RS. In 3 clinical RS patients, only a muscle biopsy was performed.[ncbi.nlm.nih.gov]

Treatment

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

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:

Etiology

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.

Epidemiology

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.

Sex distribution
Age distribution

Pathophysiology

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.

Prevention

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.

Summary

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.

Patient Information

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.

References

Article

  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 

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Last updated: 2019-07-11 22:15