Reye's syndrome (Reye): what is it, symptoms, causes, treatment, prognosis

general information

Reye's syndrome, Reye's syndrome (acute liver failure and encephalopathy) is a rare childhood disease. The disease strikes first persons under the age of 18, especially children between the ages of about 4 and 12. In rare cases, it can affect babies or adults.

The cause of the disease is unknown. However, there seems to be a link between the onset of Reye's syndrome and the use of aspirin-containing drugs (salicylates) in children or adolescents with certain viral diseases, in particular upper respiratory tract infections (for example, influenza B) or, in some cases, chickenpox (chickenpox smallpox).

Although the disease can affect any organ, Reye's syndrome is primarily characterized by characteristic fatty changes in the liver and sudden (acute) cerebral edema. Associated symptoms and signs may include:

• sudden onset of severe, persistent vomiting;
• increased levels of certain liver enzymes in the blood (hepatic transaminases);
• unusually high blood ammonia (hyperammonemia);
• disturbances of consciousness;
• sudden episodes of uncontrolled electrical activity in the brain (epilepsy);
• and / or other abnormalities, leading in some cases to potentially life-threatening complications.

Due to the potential association between the use of aspirin-containing drugs and the development of Reye's syndrome it is recommended to avoid the use of such drugs for persons under the age of 18 who suffer from viral infections, such as flu or chickenpox.

Signs and symptoms

Symptoms of Reye's syndrome usually begin after a viral illness, especially an upper respiratory tract infection (eg, influenza B virus) or, in some cases, chickenpox. Less commonly, Reye's syndrome can develop after infection with other viral agents, such as influenza A or rubella.

Approximately 3-5 days after the onset of a viral infection, sick children develop sudden, persistent, uncontrolled vomiting. Further, disturbances of consciousness arise, they can begin at the same time or develop within several hours. Such disorders of consciousness often include:

• irritability;
• anxiety;
• disorientation;
• lethargy and memory impairment.

Some children may remain lethargic without progression to loss of consciousness. In other cases, neurological deterioration can be rapidly progressive, resulting in:

• apparent lack of environmental awareness (stupor);
• a state of unconsciousness and indifference (coma);
• dilated pupils (mydriasis);
• rapid, shallow breathing (tachypnea);
• heart palpitations (tachycardia);
• loss of certain reflexes (eg, deep tendons, pupils, oculocephalic (doll's head and eyes phenomenon)).

Severe neurological dysfunction can also lead to:

• episodes of uncontrolled electrical disturbances in the brain (epilepsy);
• abnormal posture (decerebration and decortication rigidity), indicating damage to certain areas of the brain;
• potentially life-threatening complications.

Signs associated with fatty liver degeneration may include an enlarged liver (hepatomegaly) and abnormally elevated levels of certain liver enzymes (hepatic transaminases), indicating liver dysfunction. However, jaundice, often associated with liver dysfunction, is usually absent or minimal in those with the disorder.

Jaundice - a condition in which the skin, sclera of the eyes and mucous membranes acquire a yellowish color due to the excessive accumulation of bilirubin pigment in the blood.

In people with Reye's syndrome, the severity of the disease can be highly variable. According to reports in the medical literature, some patients may have mild symptoms without progression of the disease. However, as discussed above, other people with the disorder can develop rapid neurological deterioration, leading to potentially life-threatening consequences.

Scientists have proposed a clinical staging system based on different levels of disease severity, with I, II and Stage III indicate relatively mild to moderate illness, and stages IV and V indicate more severe disease.

Reye's syndrome causes

The exact cause of Reye's syndrome remains unknown. However, according to scientists, there is a connection between the onset of the disease and the intake of aspirin-containing drugs (salicylates) in children or adolescents with certain viral diseases. These are usually upper respiratory tract infections caused by the influenza B virus or chickenpox (chickenpox). Less commonly, the development of Reye's syndrome has been reported in association with other viral infections, including influenza A, herpes simplex virus, rubella or Epstein-Barr virus.

The primary symptoms and outcomes associated with Reye's syndrome appear to be the result of characteristic fatty liver changes, impaired functioning liver and abnormal accumulation of fluid in the brain tissue (cerebral edema), which can lead to increased fluid pressure and potential compression of brain tissue brain. In people with Reye's syndrome, degenerative liver changes are associated with abnormal infiltration of liver cells (hepatocytes) with fatty compounds (such as triglycerides). In addition, fatty infiltration of the spleen can be observed to a lesser extent, pancreas, voluntary (skeletal) muscles, heart muscle (myocardium) and / or tubular structures in the kidneys that collect and conduct urine (renal tubules).

Scientists suggest that the primary underlying defect of Reye's syndrome is abnormal mitochondrial function with reduced activity of hepatic mitochondrial enzymes (for example, ornithine transcarbamylase, carbamyl phosphate synthetase, pyruvate dehydrogenase). However, the cause of this mitochondrial dysfunction remains unknown. Mitochondria are tiny rod-like structures (organelles) outside the nuclei of cells that function in cellular metabolism and other processes. They contain various enzymes and serve as the primary site for the generation of cellular energy. Enzymes are proteins that accelerate the rate of specific chemical reactions. The term "metabolism" refers to all the chemical processes that take place in the body.

Current research has shown that certain metabolic disorders or congenital metabolic disorders can lead to the appearance of symptoms that mimic those associated with Reye's syndrome (the so-called "diseases like Rhea "). Metabolic disorders causing symptoms and signs similar to those seen in the syndrome Rhea, include certain disorders of the urea cycle, organic aciduria and disorders of fat metabolism acids.

Affected populations

Reye's syndrome is a rare condition that affects men and women in relatively equal numbers. The disease occurs almost exclusively in people under the age of 18. Most cases occur around 6 years of age, with most affected individuals between about 4 and 12 years of age. However, there have been rare cases of Reye's syndrome affecting infants and adults. Evidence suggests that children and adolescents in rural and peri-urban areas are more likely to be affected than in urban areas.

The disorder was initially recognized as a separate disease in 1963 with several reported cases in the United States and Australia. Observation of Reye's syndrome has shown that the disorder tends to occur in outbreaks associated with viral infection (for example, influenza B, chickenpox, various other viral infections) or can sometimes occur more sporadically (singularly), also in connection with these viral infections.

Since the late 1980s, the incidence in the world, including in Russia, has dropped sharply. During 1974-1984, between 200 and 550 cases were reported annually in the United States. In Russia, their number is unknown. However, since 1988, fewer than 20 cases have been reported annually. Many researchers attribute this to increased public awareness of the potential link between Reye's syndrome and the use of aspirin-containing drugs for certain viral infections and the recognition that some children suspected of having Reye's syndrome do have a congenital error metabolism.

Diagnostics

Reye's syndrome should be suspected in any infants, children, or adolescents who experience severe, persistent vomiting due to evidence of unexplained acute cerebral edema, the researchers said. The condition can be diagnosed based on the patient's complete medical history, careful clinical assessment, characteristic physical findings and results of specialized laboratory research.

Initial tests may include liver enzyme tests (ALT, AST) that show elevated levels of certain liver enzymes (eg, aspartate transaminase [AST], alanine transaminase [ALT]) in blood. The results of these tests are usually available within a few hours, and high levels of these enzymes strongly suggest Reye's syndrome.

In some people with Reye's syndrome, analysis of cerebrospinal fluid (CSF) can confirm an increase in blood pressure.

Liquor - a watery protective fluid circulating through the four cavities (ventricles) of the brain, the canal containing the spinal cord (vertebral canal), and the space between the layers of protective membranes (meningia) surrounding the brain and spinal cord (i.e., the subarachnoid space).

In addition, blood tests usually show elevated levels of certain muscle enzymes (such as creatine kinase) and the mitochondrial enzyme glutamate dehydrogenase. Blood ammonia levels (hyperammonemia) can also be significantly elevated, although this is a highly variable rate.

As noted above, ammonia is a byproduct of protein metabolism that can be toxic to the brain.

Blood tests can also reveal low levels of a certain clotting factor (hypoprothrombinemia).

According to reports in the medical literature, in individuals with significantly elevated blood ammonia levels and / or hypoprothrombinemia that do not respond to vitamin K treatment may increase the likelihood of developing coma.

In those with this disorder, laboratory tests also usually show a decrease in liver activity. mitochondrial enzymes such as pyruvate dehydrogenase (PDC), ornithine transcarbamylase (OTC), and carbamoyl phosphate synthetase (KFS). Scientists point out that the acquired decrease in the activity of the enzymes OTC and CPS can lead to an increase in the level of ammonia in the blood (hyperammonemia).

Laboratory tests can also confirm reductions in downtime. blood glucose (hypoglycemia), especially in young children. CSF analysis can also reveal low glucose (sugar) levels in the cerebrospinal fluid (hypoglycorchia), reflecting hypoglycemia. According to scientists, diagnostic screening tests should be performed on all young patients to help rule out or identify underlying metabolic disorders that may be present.

In addition, especially for children under 1–2 years of age, a liver biopsy may be recommended to help rule out or confirm an underlying metabolic or toxic liver disorder. A liver biopsy involves surgical removal (biopsy) and microscopic examination of small samples of removed liver tissue. In patients with Reye's syndrome, a liver biopsy usually reveals an abnormal accumulation of certain fatty compounds (eg triglycerides) in liver cells and structural changes in the liver mitochondria.

Reye's syndrome treatment

According to reports in the medical literature, treatment basics include:

• early diagnosis;
• rapid introduction of intensive care as needed;
• measures to correct metabolic disorders;
• measures to prevent or control increased pressure between the skull and the brain (intracranial pressure) secondary to cerebral edema.

Specific treatments can vary from person to person, depending on the severity of the disease and the progression. For example, in children with mild illness (eg, stage I), treatment may mainly consist of close observation. However, in cases with more severe illness, intensive emergency treatment may be required. Such measures may include:

• continuous monitoring of vital signs (eg, circulation, fluid / electrolyte balance, respiration);
• delivery of fluids, electrolytes and glucose through a vein (intravenous);
• using a respirator to facilitate breathing.

Intracranial pressure levels must also be closely monitored, and certain medications (eg, mannitol, dexamethasone) may be administered to help control cerebral edema and reduce intracranial pressure.

Additional measures may include:

• administration of an enema with an antibiotic (neomycin) and an agent that helps to remove ammonia from the blood (for example, lactulose);
• vitamin K treatment or blood transfusion (such as platelets or fresh frozen plasma) for bleeding disorders;
• using a cooling blanket or other methods to stabilize or prevent abnormally high body temperature (hyperthermia);
• and / or other measures.

For some patients with the disorder, additional symptomatic and supportive measures may be recommended.

Scientists point out that there seems to be a correlation between residual cognitive effects and the severity of neurological impairment after initiation of therapy.

People with mild illness (such as stage I) usually recover completely. However, people with more severe illness may have residual neurological symptoms such as mental retardation, difficulty forming thoughts and visual and motor functions, or other related anomalies.

Great care must be taken when prescribing pain medications to patients with suspected episodes of Reye's syndrome. Patients and their families should discuss with their doctors the reasons for choosing certain pain medications.

Forecast

Reye's syndrome occurs almost exclusively in children. Although several adult cases have been reported over the years, these cases generally did not show permanent damage to the nervous system or liver. Reye's syndrome in children is rarely fatal. However, it can cause varying degrees of permanent brain damage.