Pathogenesis.
1. in individual cases, in individuals without clear immune dysfunction, EBV infection can be followed by chronic or recurrent transmission of symptoms accompanied by abnormal changes in EBV antibodies, called chronic active EBV infection (CAEBV).
2, the exact etiology is unknown, the following aspects are related: host immune abnormalities, perforin gene mutations, CD40 ectopic expression, and among them, immune dysfunction is the most important
3. The age of onset of CAEBV varies, from infants to adults, but it is most common in children under 12 years of age. The prognosis of the disease is poor.
CAEBV pathogenesis.
The pathogenesis of CAEBV is not well understood and is thought to be related to the following: host immune abnormalities, mutations in the perforin gene, and ectopic expression of CD40, of which immune dysfunction is the most important cause of its pathogenesis.
The most important causes of proliferation are.
1, functional defects of EBV-specific cytotoxic T lymphocytes (CTL)/natural killer cells (NK) and untimely apoptosis of activated T cells , are the most important causes of sustained EBV proliferation.
2, EBV infection of T and NK cells and their clonal proliferation is the key to pathogenesis.
1, three prominent manifestations: fever, liver, spleen enlargement
2. there may also be enlarged lymph nodes, anemia, rash, jaundice, and diarrhea
3, there may also be regular or persistent fatigue, sore throat, lymph node tenderness, anemia, muscle aches, arthralgia, cowpox-like blisters and mosquito allergy.
4. The disease is often misdiagnosed as tuberculosis infection, connective tissue disease, lymphoma, sepsis, etc. due to persistent or recurrent fever and enlarged liver and spleen lymph nodes.
Diagnostic criteria for CAEBV.
These include clinical manifestations of EBV-related disease, duration, abnormal increase in EBV viral load and evidence of histopathological damage associated with EBV infection. 2005 Japanese scholar Okano proposed new diagnostic criteria.
1. Persistent or recurrent IM-like symptoms, including fever, lymph node enlargement, hepatosplenomegaly, along with other systemic morbidities such as: hematologic, gastrointestinal, neurologic, pulmonary, ocular, cutaneous and/or cardiovascular (including aneurysms and vascular lesions).
2. Abnormal anti-EBV antibodies, including elevated anti-VCA and EA antibodies: high titers of VCA-IgG (+), EA-IgG (+), VCA-IgA (+) and elevated EBV-DNA copy number in peripheral blood/ or positive EBV-DNA detected in affected tissue.
3. The chronic course of the disease cannot be explained by other diseases. All of the above 3 criteria were met to make the diagnosis, and the duration of disease greater than 6 months was no longer emphasized compared to the past. It is noted that increased anti-EBV antibodies (anti-VCA and anti-EA), but VCA-IgG ≥ l:640 and EA-IgG > 1:160 are sufficient, and laboratory methods to detect EBV-DNA and RNA in tissues and peripheral blood and histopathology and immunology are also recommended.
Treatment.
1. There is no satisfactory treatment available and no regular treatment strategy has been developed. Antiviral therapy, immunochemotherapy (including pedialyte glycosides, glucocorticoids, cyclosporine A, gammaglobulin, etc.), cytokine application (alpha-interferon or gamma-interferon), and antitumor drugs (CHOP regimen or other equivalent therapeutic regimens), which have limited efficacy and may result in a one-time remission of symptoms.
2. Radical treatment, early and aggressive measures should be taken for active immune reconstitution and complete elimination of virally infected or clonally proliferating lymphocytes. Hematopoietic stem cell transplantation should be a promising treatment; this therapy can awaken EBV-specific cellular immune responses in immunodeficient patients, improve CAEBV-related symptoms, and normalize viral immune serology.
3. patients with CAEBV often have multi-organ damage and severe complications, and the risk of complications after stem cell transplantation is high.
4. retrospective analysis showed that older age, high plasma EBV-DNA load, thrombocytopenia, hypoalbuminemia and long time from primary infection to diagnosis of CAEBV are risk factors for poor prognosis in CAEBV patients. Recently, it has been found that low-dose unrelated allogeneic bone marrow transplantation may be an optional option as most patients with CAEBV have multi-organ dysfunction and are more prone to transplantation-related complications.
Clinical prognosis.
Overall, the prognosis is poor, related to the severity of their infection and genetic aspects, characterized by severe fever, hepatosplenomegaly, and extensive lymphadenopathy with hepatitis, myocarditis, or pulmonary failure. Long-term follow-up reveals that about half of the children die after 4-5 years, about half of them due to organ failure. Other more common causes of death are malignancy, opportunistic infections and virus-associated hemophagocytic syndrome.