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The Broad Spectrum of EBV Disease

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Medical Author: Melissa Conrad Stoppler, MD Medical Editor: William C. Shiel Jr., MD, FACP, FACR The Epstein-Barr virus (EBV), a member of the herpesvirus family, is found throughout the world. Studies show that up to 95% of all adults have antibodies against this common virus, meaning that they were infected at some point in their lives. Even though most infections with EBV go unnoticed or produce only very mild symptoms, in some cases, it can be associated with the development of serious conditions, including several types of cancer. Even mild or non-life-threatening infection with EBV can, occasionally, be associated with the development of serious complications from the infection. Although the virus typically targets lymphocytes, a particular blood cell involved in the immune response, almost all organs systems can ultimately be affected by EBV infection. EBV is transmitted by close person-to-person contact. Primary, or initial, infection with EBV may not produce symptoms or there can be a number of different symptoms, especially in young children. The manifestations of primary EBV infection include: ●Infectious mononucleosis (IM): This is the most common medical condition associated with EBV. IM is characterized by extreme fatigue, tonsillitis and/or inflamed throat (pharyngitis), enlarged, tender lymph nodes in the neck, and moderate to high fever. Although the fever and sore throat typically resolve within two weeks, fatigue may persist for months after the infection.
●Other mild childhood illnesses: EBV infection in young children has also been linked to ear infections, diarrhea, other gastrointestinal symptoms, and cold symptoms in addition to the classic symptoms of IM.
●In rare cases, primary infection with EBV has been associated with neurologic disturbances including Guillain-Barre syndrome and meningoencephalitis. Other rare manifestations of primary infection are abnormalities of the blood or coagulation systems such as anemia, thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS), and disseminated intravascular coagulation (DIC). Complications of primary EBV infection are not common but may be life-threatening if not treated. Rupture of the spleen (which may be enlarged in patients with IM) occurs in one to two cases per 1,000 cases of IM, almost always in males. A second potentially fatal but treatable complication is obstruction of the airway due to enlargement of lymph nodes and swelling of inflamed tissues surrounding the airway. EBV generally persists throughout life in most people who are infected and rarely causes any problems. In some cases, however, EBV has been linked to the development of cancers and serious conditions, including the following: ●Burkitt's lymphoma: This tumor is the most common childhood malignancy in equatorial Africa. Tumors are characteristically located in the jaw. Genetic studies have shown that in equatorial Africa (where over 95% of children have been infected with EBV by age 3), the vast majority of Burkitt lymphomas originate from an EBV-infected lymphocyte, a type of blood cell targeted by the virus.
●Hodgkin lymphoma : In 1987, the finding of EBV genetic material was reported in up to 50% of cases of Hodgkin lymphoma, also known as Hodgkin's disease, in certain geographic areas and patient populations.
●Nasopharyngeal carcinoma: This cancer is rare in almost all populations, but it occurs as one of the most common cancers in southern China. Numerous studies have shown that these cancers are related to EBV infection and that EBV genetic material is contained in these cancers. Still, the majority of people in China who have been infected with EBV do not develop nasopharyngeal carcinoma.
●EBV-associated non-Hodgkin lymphomas (usually B-cell lymphomas) have also been described in people infected with the HIV virus.
●Rare cases of T-cell lymphomas have also been linked to EBV infection.
●Post-transplant lymphoproliferative disease (PTLD) refers to a category of conditions that develop in people taking immunosuppressive medications following an organ transplant. The EBV virus has been implicated in the majority of cases of PTLD. Manifestations can vary, ranging from an increased number of lymphocytes in the bloodstream to blood-cell malignancies such as B-cell lymphoma.
●Rare hematologic conditions: EBV has also been found to be associated with the development of certain rare conditions causing abnormal growth and function of specific components of the blood. Examples of these conditions are hemophagocytic lymphohistiocytosis and lymphomatoid granulomatosis. Despite the diverse and potentially grave conditions that have been linked to EBV, the vast majority of people will experience no symptoms or have a self-limited illness such as IM when they contract the virus. It is likely that additional factors are necessary to predispose individuals to the development of cancers and other serious conditions as a result of EBV infection, and the reasons why EBV causes cancers in certain individuals and not in the majority of infected people are not fully understood. Research is underway to further characterize the broad spectrum of EBV-associated medical conditions.

The Broad Spectrum of EBV Disease

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