congenital giant cell inclusion disease
Introduction
Introduction to congenital giant cell inclusion disease Giant cell inclusion body infection is caused by a congenital or acquired systemic infection syndrome caused by cytomegalovirus (CMV). As infected cells become larger, inclusion bodies appear in the nucleus and cytoplasm. This disease is also known as cytomegalic inclusion disease. There are two types, one is salivary adenovirus, which is an asymptomatic and limited infection, and most of them become invisible or chronic infection of the salivary glands and persist for a long time. The other is a systemic disease, which is relatively rare and mainly invades small babies. It is characterized by the discovery of large cells containing intranuclear and intracytoplasmic inclusions in many organ tissues, accompanied by systemic symptoms, which are caused by intrauterine virus infection. One of the important causes of fetal malformation. basic knowledge The proportion of the disease: the incidence rate is about 0.001% -0.002% Susceptible people: infants and young children Mode of transmission: mother-to-child transmission Complications: interstitial pneumonia, retinitis, optic atrophy, dysmotility
Cause
Causes of congenital giant cell inclusion disease
CMV is a double-stranded DNA virus belonging to the herpes virus group. Its morphology is similar to that of other herpes viruses. It has obvious species-specificity to host or tissue culture cells. Human CMV can only be isolated and cultured in human embryonic fibroblasts. The stained cells became round and gradually enlarged, and the intracytoplasmic eosinophilic inclusions and eosinophilic or amphotropic inclusions were the main features. The inclusion bodies in the nucleus (8-10 m diameter) accounted for most of the central region of the nucleus. It is purple-red stained with hematoxylin, and there is a well-defined bright circle separated from the nuclear membrane. Similar to the owl eye, the intracytoplasmic inclusions (about 4 m in diameter) generally gather on one side of the cytoplasm (Fig. 18- 14), CMV is unstable in hot, acidic environment and fat solvent, can be inactivated after 30 minutes at 56 °C or 5 minutes after UV irradiation, can withstand cold, can be kept in the refrigerator at -60 ~ -80 °C Its infectivity, human CMV has only one serotype, but at least three serum "subtype" strains, the relationship between them is very close, almost can not be distinguished by neutralization test, AD169 strain has a wide range of antigenicity, so often as Representative strains were used for serological tests.
When the mother is suffering from primary CMV infection, the virus is widely present in various organs of the host, and can infect the fetus with blood flow through the placenta, especially within 4 months of pregnancy, which is more likely to cause fetal damage. The cellular immune tolerance of the cells allows the virus to proliferate slowly in the cells, causing organ damage. If the consequences are severe, it may cause miscarriage, stillbirth, and light birth weight or deformity. Infants' congenital infections often have obvious The danger of leaving damage, especially the central nervous system.
The severity of congenital infection is related to the lack of ability to produce antibodies and the response of T cells to CMV. In children and adults infected with CMV, activated T lymphocytes with cytotoxic phenotype are present in the peripheral blood, if the host The function of the T cells is impaired, and the latent virus may resurrect and cause multiple syndromes.
Recurrent infection during pregnancy does not necessarily lead to congenital infection of the fetus. At this time, the amount of maternal virus is less than that of the original. When the baby is infected with the cervix, there is a high risk of infection in the first few months of life. Most acquired acquired infections are asymptomatic. However, the virus is discharged continuously or intermittently, and the symptoms are mild at the time of onset.
After the human body suffers from giant cell inclusion disease, the pathogen can be widely distributed in various organs of the body, causing cellular inflammatory reactions. Typical inclusion bodies appear in the giant cells of various tissues, which are common in the lung, liver, central nervous system, salivary gland, and Including kidney, intestine, adrenal gland, bladder, pancreas, thyroid, parathyroid gland, testis, epididymis, ovary, myocardium, eyeball, bone, blood vessels, skin, etc., can cause chronic interstitial nephritis, pneumonia, focal hepatic necrosis, brain Necrotic granuloma, extensive calcification (including cerebral wall calcium deposition), extrahepatic hematopoiesis such as liver and spleen, ulcerative enteritis.
Prevention
Congenital giant cell inclusion disease prevention
(1) The prevention goal is to prevent high-risk serum antibody-negative persons from infecting CMV as much as possible, and to minimize the CMV reactivation of serum antibody-positive persons;
(2) There is currently no effective method to prevent CMV activation during pregnancy. Careful hand washing is the best way to reduce CMV infection in pregnant women. The use of high titer immunoglobulins is under investigation. Antiviral drugs have no preventive effect;
(3) Nursery schools and kindergartens are important places for the spread of this disease, causing infections among children and HIV-negative staff and parents. Infant chamber workers who are negative for serum antibodies are also susceptible to infection by exposure to infected infants (diapers, urine, saliva, etc.). The most effective prevention method is good hygiene habits, such as hand washing; (4) Prevention of sexual transmission is also an important measure;
(5) The virus can be transmitted through blood transfusion, so it is advisable to avoid unnecessary blood transfusion. Serum CMV antibody-negative blood products (at least IgM negative) or no blood cells are used as far as possible for premature infants, neonates, immunodeficiency patients, organ transplant recipients, and pregnant women. The transplanted organ may be a source of infection of CMV, and serum-antibody-negative organs or tissues should be used whenever possible.
Complication
Congenital giant cell inclusion disease complications Complications interstitial pneumonia, retinitis, optic atrophy, dyskinesia
Can cause interstitial pneumonia, hepatitis, retinitis, optic atrophy, deafness, mental retardation, movement disorders, paralysis.
Symptom
Congenital giant cell inclusion disease symptoms Common symptoms Bacterial infection Septic lymph node enlargement Immunity reduced jaundice Liver splenomegaly Skin bleb herpes Peripheral neuritis convulsion
The clinical manifestations of this disease vary in severity. Systemic giant cell inclusion disease mainly occurs in neonates and infants. In this case, jaundice, hepatosplenomegaly, skin defects, microcephaly, intracranial calcification, etc. should be seen. Note that with toxoplasmosis, sepsis, congenital biliary obstruction, infantile hepatitis, systemic herpes simplex, congenital leukemia, congenital rubella syndrome, etc., mental retardation, dyskinesia, cerebral palsy and other symptoms are generally in older babies be found.
When you have the following conditions in childhood, consider the possibility of acquiring giant cell inclusion disease:
1 chronic liver disease or persistent interstitial pneumonia that cannot be explained by other causes;
2 clinically similar to infectious mononucleosis, but the anti-EB virus capsid antigen is negative for heterophilic agglutination test, often occurs after surgery (especially happy surgery) to receive a large number of fresh blood;
3 Children with chronic wasting diseases treated with immunosuppressive drugs (such as leukemia, malignant tumors), recipients of organ transplants, such as severe pneumonia, are often caused by CMV infection.
In the case of the above, virological and serological tests are required to confirm the diagnosis.
Most CMV infections are not dominant, and the performance after infection is diverse. Symptoms are divided into two types:
1. About 10% of congenital infections have obvious symptoms after birth, which are manifested as hepatosplenomegaly, persistent jaundice, skin defects, microcephaly, chorioretinitis, mental retardation and dyskinesia, etc. The performance of the item can exist alone, and may be accompanied by slow growth, irritability, and sometimes fever. The body temperature is slightly warmed to 40 ° C, but only a small number of children have clinical symptoms at birth, so most of them cannot be diagnosed, such as after birth. Symptoms that appear only for months to years can also manifest as hearing loss, mild neurological symptoms and developmental disorders, which can affect learning. Children with congenital giant cell inclusion disease can develop various congenital malformations. Status, bilateral paralysis, epileptiform convulsions, optic atrophy, deafness (about 10% of children with deafness), and increased sensitivity to bacterial infection, some children with asymptomatic congenital CMV infection, although physical development is normal There may still be congenital malformations and hearing impairment, but the incidence and severity are lower than those with symptoms.
2, acquired infections The disease is a self-limiting disease, the clinical manifestations are generally lighter, although most infants are subclinical infections, but the incidence of symptoms is still higher than adults, manifested as liver, spleen and lymph nodes, rash , bronchitis or pneumonia, etc., hepatitis can also occur, and children with congenital infections are rarely violated by the nervous system, childhood infections are often obtained through the respiratory tract, often not dominant, but become long-term carriers, even Prolonged hepatitis or interstitial pneumonia may occur, and children who have received fresh blood transfusions may also develop this disease, which may resemble infectious mononucleosis, but the heterophilic agglutination of EBV capsid antigen And IgM antibodies are always negative, can also cause hemolytic anemia or infectious peripheral neuritis, the activation of non-dominant CMV infection often occurs in a variety of factors, so that the body's immunity is reduced, the potential viral infection can be activated and the disease These factors include pregnancy, organ transplantation, application of immunosuppressants or antimetabolites, surgery, giant blood disease, tumors, etc., which can cause pneumonia, hepatitis, retinitis, Pneumonitis is the most serious consequence of CMV infection in bone marrow transplant recipients. The incidence rate is 40%, and the mortality rate is 90%. Children with AIDS have a high CMV infection rate, which is characterized by prolonged viremia. Progressive development is often the most common cause of death.
Examine
Examination of congenital giant cell inclusion disease
1, blood and liver function
There may be anemia and thrombocytopenia, clinically similar to children with infectious mononucleosis, more abnormal lymphocytes can be seen on peripheral blood smears, serum bilirubin increased in children with jaundice, accompanied by elevated serum transaminase, Diagnosis can be confirmed by virology and serological examination.
2. Etiology
(1) Detection of CMV: Inoculation into human embryonic lung fibroblasts with urine, bronchoalveolar lavage, saliva, liver biopsy or pharyngeal secretions, CMV can be cultured, usually with a swollen round cell lesion within 1 week, but It takes 4-6 weeks to spread the whole single layer of cells. Due to the high conditions required for virus isolation and the slow growth of CMV, it is not suitable for promotion. It is necessary to dye fresh morning urine sediment smears and find giant cells with inclusion bodies. One method, but the detection rate of this kind of cells is low, and it is necessary to check carefully. The concentrated urine can be seen under the electron microscope. CMV can also be used. In situ hybridization, monoclonal antibody indirect immunofluorescence, ELISA sandwich Method and flow cytometry to detect CMV antigen in clinical specimens.
(2) Detection of CMV-DNA: CMV-DNA in pregnant women can be examined by DNA-DNA hybridization; CMV-DNA in urine of children is detected by polymerase chain reaction; CMVDNA is detected by probe labeled with digoxigenin .
3. Serology
Second, serum antibody testing: the most commonly used complement binding test (CF), indirect immunofluorescence test (IIF), immunoenzyme test (EIA), indirect hemagglutination test (IHA) and radioimmunoassay (RIA) test CMV- IgG and IgM antibodies, commonly used complement binding assay to determine IgG antibody, the titer of this antibody in the recovery period serum is 4 times more acute than the diagnostic value, so it can not be used for early diagnosis, in recent years, fluorescent antibody indirect staining, Indirect ELISA, radioimmunoautoradiography, capture ELISA, indirect enzyme labeling, etc., detection of CMV-IgM antibodies in the serum of children, is helpful for early diagnosis.
Diagnosis
Diagnosis and diagnosis of congenital giant cell inclusion body disease
Should pay attention to with toxoplasmosis, sepsis, congenital biliary obstruction, infantile hepatitis, systemic herpes simplex, congenital leukemia, congenital rubella syndrome, etc., mental retardation, dyskinesia, cerebral palsy and other symptoms are generally in the larger baby Can be discovered.
