cytomegalovirus uveitis
Introduction
Introduction to cytomegalovirus uveitis Cytomegalovirus (CMV) is a herpes virus that generally does not cause disease in people with normal immune function. It can cause gastrointestinal diseases, central nervous system diseases, lung diseases and retinitis in immunosuppressed patients. Retinitis is the most common disease and the most common cause of opportunistic infection and blindness in acquired immunodeficiency syndrome. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: non-infectious Complications: retinal detachment optic neuritis optic atrophy
Cause
Cause of cytomegalovirus uveitis
(1) Causes of the disease
Cytomegalovirus is an enveloped double-stranded DNA virus that has been named by the International Committee of Virology and Taxonomy as human herpesvirus type 5 (Table 1). It has species specificity and is found to be large in addition to human CMV. Mice, mice, guinea pig CMV, morphologically, CMV has a DNA-containing nucleus surrounded by a capsid composed of 162 viral shells, the outermost envelope of which is the largest in the herpes virus. It consists of 230,000 base pairs with a molecular weight of 15106 Da. The genome can encode 80 kinds of proteins. In the process of genomic protein synthesis of CMV, it often appears as a cascade reaction. The earliest synthesis of a group of alpha proteins (called immediate-early protein) This histone initiates the transcription of the second group of protein protein (called early protein) mRNA, and finally the third group of protein protein (called late protein), immediately after the virus penetrates into the cell - early protein expression In the host cell nucleus, the presence of this protein is the only evidence that the virus infects the cell but does not replicate. Almost all immediate-early proteins, early proteins are not structural proteins, and most late proteins are structural proteins.
(two) pathogenesis
CMV infection is divided into two major categories: congenital infection and acquired infection. The main infection methods are as follows: 1 Infection through close contact, contact with body fluids containing virus (such as saliva, urine, cervical secretions, semen, tears, breast milk) And articles contaminated by feces, etc.) can cause infection; 2 sexual contact infections, especially homosexuals are more likely to spread through this route; 3 by entering blood, blood products and organ transplants containing the virus; 4 intrauterine infection or Infected by a virus during childbirth, like other herpesviruses, the virus tends to lie in certain tissues or cells after the primary infection. The latent parts are secretory glands, white blood cells and kidneys. Stimulation, especially in the presence of immunodeficiency syndrome or the use of immunosuppressive drugs to cause immune deficiencies can cause viral activation and cause a variety of pathological changes.
Prevention
Cytomegalovirus uvitis prevention
The focus of prevention is on neonates, especially prevention of congenital infections, as well as immunocompromised patients, especially organ transplants. Pregnancy should be discontinued when the mother is diagnosed with a primary CMV infection during pregnancy, especially in early pregnancy.
Complication
Cytomegalovirus uveitis complications Complications retinal detachment optic neuritis optic atrophy
CMV retinitis can cause rhegmatogenous retinal detachment, the incidence rate is 13.2% to 29%; a few patients may have serous retinal detachment; nearly one-third of patients have optic neuritis, and optic atrophy may occur later, the disease is generally not Causes macular changes.
Symptom
Cytomegalovirus uveal inflammation symptoms common symptoms deafness mental retardation sore throat pre-shadow immune dysfunction jaundice abortion liver splenomegaly fundus changes edema
Congenital or childhood infection
Congenital CMV infection can cause fetal death and miscarriage, survivors often have low body weight, hepatosplenomegaly, jaundice, ecchymosis, respiratory distress, microcephaly, mental retardation, deafness, epilepsy, dyskinesia and behavioral abnormalities, eyes The department can be expressed as no eyeball, small eyeball, retinitis or retinal choroiditis, and in rare cases can cause iridocyclitis.
2. Acquired infection
Acquired infections are seen in acquired immunodeficiency syndrome and immunosuppression caused by various causes. Systemic manifestations of fever, headache, muscle pain, sore throat, hepatosplenomegaly, lymphadenopathy, esophagitis, colitis or gyrus Enteritis, interstitial pneumonia, hepatitis, encephalitis, myocarditis, arthritis, peripheral neuropathy, thrombocytopenia, etc.
The eye changes are mainly manifested as retinitis. Patients usually complain of blurred vision, dark spots, dark shadows, flashing sensation or decreased vision. Fundus examination can reveal scattered yellow-white necrotizing retinal lesions, usually accompanied by mild vitreous Inflammation and retinal hemorrhage.
CMV retinitis can be divided into two types, one is explosive or edema type, the lesions are mostly distributed along the retinal large blood vessels, the appearance is dense, the fusion is white turbid, often accompanied by retinal hemorrhage and retinal vascular sheath, difficult to see The choroid to the corresponding site; the other is lazy or granular, showing mild to moderate granulosa retinal opacity, densely distributed lesions, but not related to retinal blood vessels, bleeding is rare, retinal vascular sheath is also relatively rare.
Both types of retinitis have a dry appearance and a granular edge, and the advancing edge of the lesion is usually sharp. In the absence of effective treatment, it usually progresses continuously, and full-thickness retinal necrosis occurs within a few weeks. CMV retinitis It can be accompanied by iridocyclitis and frosty dendritic vasculitis.
Examine
Inspection of cytomegalovirus uveitis
Serological examination
Serological tests can determine whether a newborn or infant has a recent or active infection. The complement fixation test is the most common method for determining anti-CMV antibodies, but this test does not identify IgG and IgM. The sensitivity of this method is 90%. However, immunofluorescence and enzyme-linked immunosorbent assays are more sensitive. Positive serum antibodies mean that the host has been infected with CMV, but it does not mean that there must be tissue lesions. Dynamic antibody assays found that IgG antibody titers increased 4 or 4 times. The above is of great value for diagnosis. Higher antibody levels have greater diagnostic value for active CMV infection. The presence of anti-CMV IgM antibodies suggests a recent infection, but it cannot be determined as a primary infection because it can be infected after infection. It lasts for several months and can also occur when the virus is activated. In addition, when the rheumatoid factor is positive, false positive results can also occur. It is worth noting that a large amount of IgG can lead to false negative results, because IgG and CMV antigens are highly Affinity, the combination of the two causes a decrease in serum IgG levels, especially in newborns, where neonates receive high levels of maternal IgG, false The results of up to 20%, IgM can not cross the placenta, IgM suggesting intrauterine infection in umbilical cord blood, smaller antibody titer in the adult sense, because most adults have a positive antibody titer.
2. Virus isolation and culture
Isolation and culture of viruses is an important basis for the diagnosis. Various specimens from patients such as blood, urine, saliva, vitreous specimens or retinal choroid biopsy specimens can be used for culture. Samples from any part of the body are found to be CMV. It is helpful for diagnosis, but since the infected individual can excrete the virus for several months to several years, the biopsy and culture results should be interpreted according to clinical symptoms and signs, and the specimens collected from the larynx and urine specimens are cultured. Most valuable, the patient's subretinal fluid, vitreous, salivary gland, milk, semen, cervical secretions, etc. can also find positive results, culture usually uses fibroblasts, virus formation characteristic cell changes generally take a long time, from Between several days and 6 weeks, but more than 2 to 3 weeks, a rapid culture system has been developed. The cells can be quickly and reliably diagnosed by using immunofluorescent monoclonal antibody technology to detect early and late proteins in cell culture for 8 to 32 hours. .
3. Nuclear
Molecular biology techniques have greatly assisted in the diagnosis of CMV retinitis. In situ hybridization or PCR can be used to determine the CMV genome in tissues. In situ hybridization is a sensitive technique for determining CMV DNA or RNA in tissues. CMV retinitis, this technique is both sensitive and specific, but for patients who have been treated, the diagnostic value of this technique is not very large due to no virus replication. PCR technology has been used to determine aqueous humor, vitreous, and subretinal CMV in formalin-fixed ocular tissue sections is of great value for the diagnosis of atypical cases. Antiviral therapy may have a certain effect on the positive rate of PCR. Gerna et al found that 12 patients were treated before treatment. PCR results in water were positive, but only 4 specimens were positive after treatment. McCan et al found that the sensitivity of PCR detection was 95% in untreated patients with CMV infection, but the sensitivity was only 48 after treatment. %, PCR technology is a very sensitive technology, any pollution can cause DNA amplification, false positive results, so special attention should be paid to specimen contamination during experimental operation. question.
4. Histopathological examination
Histological examination reveals giant cells with inclusions in the nucleus, occasionally granulated basophilic inclusion bodies, immunocytochemistry using antibodies to detect viral antigens, and electron microscopy or immunohistochemical staining to find neural retinas. The retinal pigment epithelium has anti-CMV antibody staining, which is of great help to the diagnosis.
Fluorescein fundus angiography: CMV retinitis usually shows delayed filling of the affected small arteries during fluorescein fundus angiography, and enhanced light transmission in the atrophic retinal pigment epithelium, but fluorescent obscuration is visible in the pigmented area. Significant vascular leakage occurred in some areas, while other areas showed relatively weak fluorescence (ie, in the white necrotic area), small arteriolar stenosis and scattered microangioma were also seen.
Diagnosis
Diagnosis and diagnosis of cytomegalovirus uveitis
The diagnosis of CMV retinitis is not difficult according to the characteristic fundus manifestation and the patient's immune dysfunction caused by various reasons. However, for suspicious and atypical fundus changes, laboratory examination and other auxiliary examinations are needed to confirm the diagnosis. .
Other viruses such as herpes simplex virus, varicella-zoster virus can cause similar retinopathy, other pathogen infections (such as Toxoplasma gondii, fungal infections), and some other types of uveitis and non-inflammatory diseases can also show Retinitis should be taken into account in the differential diagnosis. According to the clinical manifestations of different diseases, appropriate culture and serological examination can distinguish these diseases from CMV retinitis.
Acute retinal necrosis syndrome caused by varicella-zoster virus is usually accompanied by obvious uveitis and vitreous opacity in the early stage; necrotic lesions usually start in the peripheral retina and spread to the entire peripheral retina, and then advance to the posterior pole It is very rare to start from the posterior pole; patients usually have obvious retinal vasculitis, mainly arteritis; late retinal detachment, these characteristics are helpful to distinguish from CMV retinitis.
Retinitis lesions caused by toxoplasmosis are usually yellow-white, and the boundary of active lesions is unclear. It often appears around the old reticular scar of the retina, forming a so-called "satellite" lesion. The vitreous usually has obvious signs of inflammation, rarely With retinal hemorrhage, occasional signs of inflammation appear in the anterior segment of the eye, and inflammatory cell deposits along the retinal blood vessels may occur. Toxoplasma retinitis is usually not associated with systemic diseases and often occurs in individuals with normal immune function.
Fungal retinitis typically manifests as a single or multiple villi-like, scattered retinal damage that extends into the vitreous cavity. The retinal and vitreous lesions are yellow-white, with a dense, villous appearance at the center of the retina or near the retina. An abscess can form in the vitreous, inflammatory deposits can be seen along the blood vessels, endogenous Candida ocular infections are common in those with weak constitution, those with central venous indwelling catheters, those who use glucocorticoids or immunosuppressive drugs, Patients who abuse intravenous drug injections are prone to this disease.
