Reye's syndrome
Introduction
Introduction to Lai's syndrome Reyes Syndrome (RS) is an acute progressive encephalopathy, also known as encephalopathy with visceral steatosis, Reye syndrome, viral infectious encephalopathy syndrome, hepatic massive steatosis - acute encephalopathy syndrome, vomiting, liver Lipidosis and the like. This syndrome is an unexplained syndrome with acute encephalopathy and hepatic steatosis as the main clinical features. It was first reported by Australian pediatric pathologist Reye in 1963. Reye syndrome is a critical illness, often preceded by a virus. Symptoms of encephalopathy such as acute intracranial hypertension, disturbance of consciousness, and convulsions after infection, often accompanied by severe cerebral edema, and abnormal liver function and metabolic disorders. In most cases, severe intracranial pressure and cerebral palsy cause death, or serious neurological sequelae. basic knowledge The proportion of sickness: 0.0004%-0.001% Susceptible people: no special people Mode of infection: non-infectious Complications: arrhythmia cerebral palsy
Cause
Cause of Lyue's syndrome
(1) Causes of the disease
The etiology and pathogenesis of this disease have not been known so far, but it has been confirmed to be closely related to viral infection and taking aspirin. It is generally considered to be related to the following factors, but it is not the only reason.
Infection
Common viral infections before the disease, manifested as respiratory or digestive tract symptoms, the pathogen may be influenza virus, chickenpox, parainfluenza, enterovirus, Epstein-Barr virus, etc.
2. Drugs
There is more evidence (such as epidemiology) that patients who take salicylate (aspirin) during viral infection are more likely to develop this disease later, and it has been confirmed to have multiple inhibitory effects on mitochondria. In recent years, the incidence of this disease has decreased in the United States, the United States and other countries to reduce or stop the application of salicylic acid. In addition, the anti-epileptic drug valproic acid can also cause the same symptoms as Reye's syndrome.
It has recently been reported that Reye syndrome usually occurs after flu or chickenpox, and if the incidence of aspirin is significantly increased, there is a significant correlation between the two, the Atlanta Center for Prevalence Control has been caused by oral administration of aspirin in chickenpox and flu. The same performance as Reye syndrome is called "aspirin syndrome". Aspirin Pharmaceuticals and Aspirin in the United States have been affixed to aspirin vials since 1985. Children with flu or chickenpox need to be approved by the physician before taking it. Warning label and delete the word flu as an indication for aspirin.
Toxin
Aflatoxin, organic phosphorus and organic oxygen and other insecticides, dirt and other contaminated foods or contact with it, may appear the same symptoms as this disease.
4. Inherited metabolic diseases
Some children have a family history, some congenital metabolic abnormalities can cause the manifestation of Reye's syndrome, sometimes called Reye-like syndrome, such as systemic carnitine deficiency, liver enzyme damage and In the urinary circulation, ornithine transcarbamylase (OTC) and carbamyl phosphate synthase (CPS) deficiency caused by hyperammonemia, etc., with the advancement of genetic technology, there will be more Wright's synthesis A specific diagnosis of inherited metabolic diseases was obtained.
The above various reasons are also affected by the inherent susceptibility of the body. Lassick et al believe that this symptom is caused by the excessive release of tumor necrosis factor (TNF), which is known to be caused by viral infection, endotoxin and phagocytic cells. Increased release of activated macrophages, non-hormonal anti-inflammatory drugs can release macrophages to excessive concentrations of TNF, arterial experiments suggest that young animals are more sensitive to TNF, thus causing a hypothesis, namely Some specific young children treated with aspirin can increase TNF release leading to the development of Reye syndrome.
(two) pathogenesis
Pathogenesis
The pathogenesis of RS has not been known so far. The study found that there is abnormal mitochondrial morphology in RS patients, and the enzyme activity in liver mitochondria is decreased, while the in vitro enzyme activity of mitochondria remains normal, the mitochondrial GOT in serum increases, and the dicarboxylic acid in urine increases, suggesting the presence of acute fatty acid . Oxidative disorders, clinical observations also found that the symptoms of RS are similar to genetic metabolic diseases with mitochondrial abnormalities, and mitochondrial inhibitors or toxins (such as salicylate, echinoderma oil, etc.) can cause similar clinical pathological changes, so most scholars believe that this The disease is associated with viral infection or other factors that induce mitochondrial damage.
2. Pathology
The pathological changes of RS are mainly manifested in the brain and liver.
The pathological changes of the brain are mainly cerebral edema, the appearance is swollen, the weight is increased, the cerebral gyrus is flattened, the sulci is shallow, narrowed, and the occipital foramen or cerebellar incision is visible. Neuron damage can be seen under light microscope. It may be a secondary lesion of cerebral edema and cerebral ischemia. Under electron microscope, diffuse neuronal mitochondrial swelling, astrocytic edema, reduced particles, and vacuoles can be seen.
The appearance of the liver is light yellow to white, suggesting an increase in fat content. Hepatic steatosis can be seen under light microscopy. Mitochondrial swelling and deformation can be seen by electron microscopy. Mitochondrial sputum can disappear, and many small fat droplets can be seen in liver cytoplasm. Liver biopsy revealed The above typical mitochondrial changes are important pathological criteria for determining diagnosis.
Prevention
Lai syndrome prevention
The prevention of hereditary diseases mainly depends on genetic counseling and prenatal diagnosis. Since most cases of this syndrome are sporadic, the development of prenatal diagnosis is not currently widespread.
1. Prevent infection
Especially for viral infectious diseases, do a variety of vaccination work.
2. Use or disable certain drugs with caution
Children with viral infection should stop taking salicylate and use anti-epileptic drug valproic acid with caution.
3. Avoid all kinds of toxins.
4. Do a good job in the prevention and treatment of hereditary diseases.
Complication
Lyric syndrome complications Complications arrhythmia cerebral palsy
The disease is caused by multiple organs, and various clinical manifestations, such as liver enlargement, liver and spleen dysfunction, arrhythmia, heart failure, oliguria, anuria, etc., advanced brain damage or cerebral palsy may occur, and breathing may occur. Functional failure.
Symptom
Symptoms of Rei 's Syndrome Common Symptoms Irritability, Hemorrhagic Tendency, Sore Throat, Increased Intracranial Pressure, Diarrhea, Abnormal Respiratory, Abnormal Hepatic Function, Disorder, Drowsiness
The disease is the beginning of the above respiratory tract infection or mild gastrointestinal disorders, so the prodromal period may have fever, cough, runny nose, sore throat and skin herpes or diarrhea, this period generally lasts 3 to 5 days occasionally 2 to 3 Weeks, after hours to days of asymptomatic intermittent period into the extreme period, severe vomiting indicates the onset of encephalopathy, the typical clinical manifestations of encephalopathy are rapid vomiting, quickly enter a highly irritating state, irritability, in the middle Toxic sputum, accompanied by fever, hyperhidrosis, tachycardia, rapid breathing, dilated pupils and other sympathetic nerve excitability, no meningeal or focal neurological disorders, the severity of encephalopathy and the rate of progression, individual differences, light clinical I can't see the obvious symptoms of the central nervous system. I only suspected this due to liver dysfunction. The severe ones quickly entered the coma after repeated vomiting for several hours. About half of the patients may have mild to moderate hepatic stenosis, but no jaundice and bleeding tendency. .
The classification criteria for Reye syndrome was first proposed by Huttenlocher in 1972. Devivo was slightly modified in 1984 and is now divided into 5 levels:
Grade 0: Clinical manifestations without neurological symptoms, with liver dysfunction.
Level 1: Dementia, lethargy, disorientation, amnesia, vomiting, liver dysfunction.
Level 2: inflammatory sputum, stupor, dull or shallow coma, accompanied by de-cortical state, sympathetic excitation, rapid breathing, liver dysfunction.
Level 3: Coma, going to the brain, overexcited sympathetic, and liver dysfunction.
Grade 4: somatic relaxation, apnea, circulatory failure, dilated pupils, loss of light reflex, liver dysfunction.
Examine
Examination of Lai's syndrome
1. Blood examination: The total number of white blood cells is significantly increased, and granulocytes are the majority.
2. Urine examination: ketone bodies can appear in the urine, and dicarboxylic acids appear.
3. Blood examination: abnormal liver function, serum aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase (CPK) value increased significantly after the disease, returned to normal within 1 week, blood ammonia increased significantly in the early stage of the disease, can be increased 300g / dl or more, also returned to normal blood ammonia within 1 week, prothrombin decreased, other metabolic disorders showed a significant decrease in blood glucose, cholesterol and total blood lipids decreased, while free fatty acid concentration increased, infants often have hypoglycemia, may appear Low carnitineemia, hypocholesterolemia, hypolipoproteinemia and dicarboxylate blood (urine), dicarboxylic acid in serum, blood lactic acid in some children, increased pyruvate, and decreased activity of mitochondrial enzyme complex.
4. Cerebrospinal fluid examination: cerebrospinal fluid pressure is significantly increased, cerebrospinal fluid routine examination is mostly normal, cell number and protein are normal, such as no hypoglycemia, normal sugar, hypoglycemia, the sugar content is correspondingly reduced, some children with cerebrospinal fluid lactic acid and pyruvate The level is increased and the activity of the mitochondrial enzyme complex is reduced.
5. Liver biopsy: A typical RS liver change can be found.
6. EEG examination: early normal, abnormal after 2 years old, EEG showed diffuse encephalopathy, see slow wave increase, irregular electrical activity, etc., may also have epileptiform discharge (spin wave), sleep When the spindle wave disappears, the background wave is widely and slowly, and the degree of EEG changes is not completely consistent with the clinical manifestations.
2. Brain CT, MRI examination: Should be done brain CT examination, can be found cerebral edema, midline shift and other changes, showing frontal atrophy, corpus callosum dysplasia, brain stem narrowing, ventricle enlargement.
Diagnosis
Diagnostic identification of Lai's syndrome
Diagnostic criteria
According to the above clinical characteristics combined with the relevant examinations and tests can make a diagnosis, because the clinical symptoms of the brain first, the liver enlargement is not obvious, generally no jaundice, it is easy to ignore.
1. Anyone who meets the following conditions can make a diagnosis
(1) Age is under 16 years old, especially infants and young children.
(2) History of a precursor infection or history of taking salicylate before the illness.
(3) Sudden onset, symptoms of cerebral edema and increased intracranial pressure, but no signs of the nervous system, cerebrospinal fluid examination, except for increased pressure, other normal.
(4) Blood ammonia exceeds the normal value by 1.5 times, serum transaminase exceeds the normal value by 3 times, blood sugar is lowered, prothrombin time is prolonged, and serum bilirubin is not high.
(5) Liver biopsy is of great significance for clinical diagnosis.
Partin's experience in 2300 liver biopsy in 15 years is the only specific diagnostic marker for this disease. The main changes are smooth endoplasmic reticulum proliferation, loss of glycogen, peroxisome proliferative and hepatocyte mitochondrial changes. It is still not clear that the disease has been diagnosed by electron microscopy. Even if a liver biopsy is performed, it is still difficult to have a pathologist who is familiar with the electron microscopy technique.
2. Diagnostic criteria established by the CDC
The most commonly used standard in clinical practice is the diagnostic criteria established by the Centers for Disease Control and Prevention (CDC), which mainly include:
(1) Clinically diagnosed RS (CRS):
1 acute non-inflammatory encephalopathy: disturbance of consciousness, cerebrospinal fluid examination except for increased pressure, the rest are normal, except for central nervous system infection or histology confirmed.
2 laboratory examination: transient liver dysfunction, that is, transaminase, blood ammonia or prothrombin measurement normal value × 3, but should be seized at the time of the attack, or return to normal 2 to 7 days after the onset; blood Increased ammonia, acute fatty liver, may be associated with blood lactic acid, increased pyruvate, decreased prothrombin, increased CK, infants often have hypoglycemia.
3 Except other diseases: except for other similar diseases, such as acute poisoning, inherited metabolic diseases, fulminant hepatitis and so on.
RS (CRS) called clinical diagnosis if liver biopsy or autopsy is not performed in accordance with the above clinical diagnostic criteria.
(2) Confirmed RS (DRS): If the liver biopsy or autopsy meets the RS diagnostic criteria, it is called a confirmed RS (DRS).
(3) Excluding some diseases: The symptoms of RS can occur in many diseases similar to RS, so it is necessary to identify a number of diseases, such as acute central nervous system infection, toxic encephalopathy, and genetic metabolic diseases.
Because the above-mentioned RS diagnostic criteria are non-specific, even the light microscopy is not specific for "acute fatty liver", so liver biopsy should be performed as much as possible, and changes in hepatocyte mitochondria should be observed under electron microscope to confirm the diagnosis. Liver biopsy It should be carried out within 4 to 5 days after the onset of the disease. The autopsy specimens are not suitable for mitochondrial morphology or related metabolic tests.
3. 1988 International Reye Syndrome Diagnostic Criteria
In 1988, the International Reye Syndrome Diagnostic Criteria Development Group proposed new diagnostic criteria, with 9 required standards, 8 supporting standards, and 7 exclusion criteria, as follows:
(1) Required standards:
1 Normal before birth and perinatal period.
2 6 months after birth (can be up to 18 months) mental exercise is normal.
3 The head circumference is normal at birth.
45 months to 4 years old, head growth slowed down.
From 56 months to 30 months, the skills of the purposeful hand that have been acquired are lost, and the ability of social interaction is declining.
6 The ability to express and understand language is severely impaired, and severe mental retardation develops.
Stereotypes of 7 hands, such as twisting hands, picking up hands, clapping, tapping, biting, washing hands, etc., appear after the purposeful hand movement disappears.
At 81 to 4 years old, there is an ataxia gait and physical disability.
9 until 2 to 5 years old, can make a tentative diagnosis.
(2) Supporting standards:
1 abnormal breathing, awake time to stop apnea, intermittently hyperventilation; breath holding, gaze; forced spit saliva, insufflation.
2 abnormal EEG, slow background wave or paroxysmal slow rhythm; epileptiform discharge with or without clinical seizures.
3 horror.
4 muscle contracture, associated with muscle disuse and dystonia.
5 peripheral vascular movement is abnormal.
6 scoliosis.
7 growth retardation.
8 atrophic small feet.
(3) Exclusion criteria:
1 intrauterine growth retardation.
2 increased internal organs or other signs of accumulated disease.
3 retinopathy or optic atrophy.
4 small head at birth.
5 perinatal acquired brain injury.
6 There is a metabolic disease or other progressive neuropathy.
7 serious infection or sequelae of head trauma.
Differential diagnosis
Viral encephalitis
Encephalitis or meningitis developed by Japanese encephalitis, mumps, chickenpox, flu, enterovirus, etc., its development rate is not as fast as Reye syndrome, the number of cerebrospinal fluid cells increases, protein content increases, and sugar does not decrease. Liver function is normal, there is no glycogen deficiency and fatty degeneration in liver tissue.
2. Severe viral hepatitis
Vomiting is relatively light, the symptoms of encephalopathy develop slowly, there is jaundice, the liver brain is not enlarged but shrinks, often accompanied by serious peritonitis, gastrointestinal bleeding, uremia and other serious complications, blood bilirubin is significantly elevated, valley Abnormal c-enzyme, the value can be parallel with bilirubin, the liver tissue is massively necrotic rather than fatty.
3. Drug poisoning
Salicylate, acetaminophen, tetracycline, phenformin, alcohol sulphur, methyl bromide and aluminum poisoning can cause Reye syndrome-like manifestations, of which salicylate poisoning is most similar to Reye syndrome. Therefore, it is difficult to make a final diagnosis by general laboratory examination including clinical determination of serum salicylate content, and even light microscopy of liver biopsy specimens, but serum amino acid spectrum and liver tissue electron microscopy can provide differential diagnosis basis. Serum amino acid content was normal or decreased during salicylate poisoning. There was no abnormality in cytoplasmic mitochondria under electron microscope, while serum glutamate, alanine and lysine levels were significantly increased in Reye syndrome, and the increase was severe. The degree was positively correlated, and the cytoplasmic mitochondria were extensively damaged under electron microscope.
4. Other illnesses
Such as primary hypoglycemia, congenital metabolic defects, infantile beriberi, etc. should also be considered in the differential diagnosis.
