Reye’s syndrome, that is, acute encephalopathy combined with visceral steatosis patient syndrome, is a group of syndromes characterized by cerebral edema and liver dysfunction caused by visceral fat infiltration, named because it was first reported by Reye in 1963. The disease occurs mostly in infants and children from 6 months to 15 years of age contraindicated or children with a mean age of 6 years, rare in oral adults, and predominantly in infants and children in China.
Clinical features are symptoms of brain damage such as vomiting, impaired consciousness and convulsions, as well as abnormal liver function and metabolic disorders, following a prodromal viral infection. The etiology is unknown and is mostly thought to be related to viral infection, but may also be related to aflatoxin, salicylic acid agents or environmental and genetic factors. In particular, it should be noted that studies have found that children who have taken salicylic acid preparations such as aspirin while suffering from viral infectious diseases with fever are more likely to have Reye’s syndrome.
The pathology of this disease is characterized by acute cerebral edema and steatosis of the liver, kidneys, pancreas, heart muscle and other organs, with the main ultrastructural alteration being mitochondrial abnormalities. The incidence of Reye’s syndrome is relatively low compared with that of intracranial infectious diseases, but the onset is fierce and the mortality rate is high. Untreated or severe cases can die within days or even within 24 hours, but mild cases or those treated promptly can stop the progression of the disease in its early stages and gradually recover, therefore, early diagnosis and timely treatment are important.
Clinicians should be more alert to this disease, be familiar with and master its clinical diagnosis and treatment measures, and improve the level of cognition and prevention in order to maximize the success rate of rescue and treatment and reduce the disability and death rate of children with the disease.
I. Clinical diagnosis and evaluation
1, diagnostic clues to understand the factors associated with the occurrence of the disease and clinical manifestations, can provide clinicians with diagnostic clues.
2. Pathogenetic factors: The exact etiology of the development of Reye’s syndrome is not completely clear, and the relevant research literature suggests that the etiology of its development is multifactorial.
It is generally believed to be related to the following factors.
(1) Infections: Most children with pre-morbid viral infections, manifested as respiratory or gastrointestinal symptoms. The causative agents may be influenza virus, coxsackievirus, herpes virus, EBV, varicella, parainfluenza, and enterovirus. However, there is no evidence to date that the disease is due to direct infection by viruses.
(2) Drugs: There is more evidence that children who take salicylates (aspirin) at the time of viral infection are more likely to develop the disease later. In recent years, the incidence of this disease has decreased after the reduction or discontinuation of salicylic acid in the United Kingdom and the United States. In addition, the antiepileptic drug sodium valproate can also cause the same symptoms as Richter’s syndrome.
(3) toxins: aflatoxin, organic pesticides and other contaminated food poisoning can appear the same symptoms as this disease.
(4) Genetic metabolic disease: Some children have a family history of the disease. Some congenital metabolic abnormalities can cause the manifestation of Reye’s syndrome, sometimes called Reye-like syndrome, such as systemic carnitine deficiency, ornithine carbamoyltransferase deficiency caused by hyperammonemia. As genetic technology advances, more Reye-like syndromes will yield specific diagnoses of genetic metabolic diseases.
3, prodromal oral symptoms: in the 2 weeks before the disease often have upper respiratory tract and liver disease digestive liver cancer virus infection oral prodromal oral symptoms, such as fever, cough, runny nose, vomiting, diarrhea and other signs, or suffer from chickenpox and other viral infectious diseases.
4.Digestive system symptoms: children start with frequent vomiting, sometimes it may be accompanied by vomiting blood.
5, liver damage symptoms: the characteristic clinical manifestations of Richter’s syndrome, which is characterized by liver dysfunction but mostly without jaundice. The child’s liver is enlarged and has an abnormal texture. Brain damage is the most prominent manifestation of the disease. When the prodromal oral symptoms improve, frequent vomiting and severe headache may suddenly appear, starting with excitement and irritability, confusion and drowsiness, and then turning into convulsions, coma, respiratory incoherence, etc., and even a deafferentation state.
As the disease progresses, the manifestations of impaired consciousness and increased intracranial pressure progressively worsen, and finally brain herniation and brainstem dysfunction occur, and death may occur due to respiratory and circulatory failure. Neurological signs and meningeal stimulation signs are not obvious in this disease. Hypoglycemia and hyperammonia Most children have symptoms of hypoglycemia and hyperammonia, and a few have water-electrolyte metabolism disorders such as dehydration and metabolic acidosis.
6. Blood routine: total white blood cell count is mostly significantly increased, and the classification is mainly based on neutrophil elevation.
7.Liver function test: increased serum alanine aminotransferase, prolonged prothrombin time.
8.Blood biochemical examination: blood ammonia, plasma free fatty protein acid and short chain fatty protein acid are elevated. Blood glucose is mostly reduced, and some children have normal blood glucose.
9.Cerebrospinal fluid examination: except for the online pressure is painfully elevated, the cell count and protein are mostly within the normal range.
10.Electroencephalography: moderate to severe diffuse abnormality in the online.
11.Imaging: cranial CT and MRI examination online helps to exclude brain occupying lesions.
12.Liver biopsy: The definitive diagnosis of the disease relies on biopsy of the liver, which shows characteristic changes such as large fat droplets in the hepatocytes and electron microscopic observation of mitochondrial expansion and reduction or disappearance of dense bodies.
Diagnosis and differential diagnosis
1. Diagnosis: The diagnosis is based on medical history, clinical manifestations and auxiliary examinations. The possibility of Reye’s syndrome should be considered according to the characteristics of the child with antecedent viral infection and later acute progressive brain symptoms, such as vomiting, convulsions, and impaired consciousness, but without focal neurological signs, high cerebrospinal fluid pressure but without inflammatory changes.
The diagnosis of the disease is then supported by biochemical metabolic features such as high early blood ammonia, low blood glucose, prolonged prothrombin time, elevated serum transaminases, and low blood bilirubin. For the diagnosis of this disease, clinicians should be vigilant enough, if early diagnosis and timely treatment can be made, the development of severe manifestation of late stage of severe intracranial pressure increase, brain herniation and central brainstem compression may be avoided.
2. Differential diagnosis: Reye’s syndrome is often misdiagnosed, partly because it is very uncommon and may be misdiagnosed as encephalitis, meningitis, diabetes mellitus, overdose or poisoning, etc. Therefore, differential diagnosis is important. The prominent clinical manifestations of Reye’s syndrome are liver damage and brain damage in two parts, and clinicians need to pay attention to differential diagnosis with other diseases with similar clinical manifestations when making the diagnosis of the disease.
3, central nervous system infection diseases: such as viral encephalitis, septic meningitis, etc. The main difference between these diseases and Richter’s syndrome is that their cerebrospinal fluid has inflammatory changes.
4, genetic metabolic diseases: there are many genetic metabolic diseases with clinical manifestations similar to those of Reye’s syndrome, such as defects in the enzyme system of the urea cycle (ornithine carbamoyltransferase deficiency, etc.), systemic carnitine deficiency, some organic aciduria, medium and long chain fatty acid acyl coenzyme dehydrogenase defects, etc. Many of these genetic metabolic disorders are associated with hyperammonemia, and some with dicarboxylic aciduria.
They are characterized by a family history, early onset and recurrent or periodic occurrence of the same symptoms, a small liver, delayed growth and development, and often triggered by eating large amounts of food that they cannot metabolize, e.g., patients with congenital hyperammonemia may have sudden onset of symptoms similar to Reye’s syndrome due to eating large amounts of protein. The diagnosis of genetic metabolic diseases depends on biochemical metabolic analysis, enzyme assays, and genetic analysis.