Epstein Barr Virus (EBV)

EBV is a DNA virus. Epstein-Barr virus (EBV) (HHV-4) is highly prevalent; serologic studies show evidence of previous EBV infection in almost all adults. It is most commonly transmitted by saliva and is the main cause of infectious mononucleosis in children and adolescents. Patients present with fever, severe fatigue, pharyngitis, cervical and axillary lymphadenopathy, and splenomegaly. Atypical lymphocytosis and aminotransferase level elevations are clues to the diagnosis, which is established by the presence of heterophile antibodies (Monospot test) or IgM to the EBV viral capsid antigen. The Monospot test result may be negative in the first week of illness. Treatment is supportive; glucocorticoids may be given to patients with autoimmune hemolytic anemia, central nervous system involvement, or tonsillar enlargement with a compromised airway. EBV is associated with the development of T-cell and B-cell lymphomas, Hodgkin and Burkitt lymphoma, nasopharyngeal carcinoma, and posttransplant lymphoproliferative disease in solid organ transplantation. [1]

Reactivation disease is not a prominent issue with EBV, in contrast to other common herpesviruses, but it has been associated with an aggressive lymphoproliferative disorder in transplant recipients. [2]

EBV is a Herpesvirus. 

Herpesvruses [1]

Approximately 90 to 95 percent of adults are EBV antibody seropositive; however, studies suggest that primary EBV infection may be occurring at a later age in children residing in the developed world. As an example, in a large public university in the United States, the seroprevalence of EBV antibodies among entering freshman declined from 64 percent in 2006 to 52 percent in 2022. [2]

 IgG antibodies to antiviral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA) are present for life in patients with prior EBV exposure and are not markers of an active process suggesting true chronic active EBV infection. [2]

EBV is associated with the development of T-cell and B-cell lymphomas, Hodgkin and Burkitt lymphoma, nasopharyngeal carcinoma, and posttransplant lymphoproliferative disease in solid organ transplantation. [1]

Case series suggest that there may be an association between infectious mononnucleosis (IM) and subsequent Lemierre's disease. As an example, in one series that evaluated five patients diagnosed with Lemierre’s disease over a six-year period, three had evidence of acute EBV infection, including one related to Fusobacterium necrophorum. However, in a larger series that evaluated 23 patients with Lemierre's syndrome related to F. necrophorum, only one patient had evidence of concomitant mononucleosis. In that series, another patient who died from Lemierre's syndrome had a high number of EBV copies in the CSF and serum; however, it was unclear if the patient had acute EBV since anti-EBV antibodies were not obtained. [2]

Chronic active Epstein-Barr virus (CAEBV) infection is a rare, life-threatening lymphoproliferative disorder that may involve B lymphocytes, T lymphocytes, or NK cells. The syndrome is characterized by a persistent infectious mononucleosis (IM)-like syndrome and EBV viremia. Clinical manifestations may include fever, swelling of lymph nodes, and hepatosplenomegaly along with liver function test abnormalities and cytopenias. Patients with untreated T cell CAEBV often develop systemic organ disease due to T cell infiltration of tissues, hemophagocytic lymphocytosis, liver failure, or coronary artery aneurysms. [2]

Diagnostic criteria are not well defined, but the presence of persistent viremia and hypogammaglobulinemia, as well as the detection of a clonal proliferation of B, T, or NK cell population, support the diagnosis. A common misconception is to label patients with fatigue alone as having chronic EBV based only upon positive serologic markers without any of the above abnormalities. However, IgG antibodies to antiviral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA) are present for life in patients with prior EBV exposure and are not markers of an active process suggesting true chronic active EBV infection. [2]

While the pathogenesis is not well understood, EBV infection of hematopoietic stem cells may be the initiating factor in CAEBV. EBV sequencing studies have found that certain intragenic deletions are associated with CAEBV and NK lymphoproliferative disorders. Early data suggest the effect of the deletions is to simultaneously promote more efficient lytic cycle reactivation, avert cell lysis, and drive lymphomagenesis. [2]

The only treatment regimen that has been curative is hematopoietic stem cell transplantation. Other treatment options that have been used include high-dose corticosteroids or antiviral therapy (eg, ganciclovir) used individually or in combination with proteasome inhibitors (eg, bortezomib) or histone deacetylase inhibitors. [2]

EBV infection has received a great deal of attention as a possible etiologic agent for chronic fatigue syndrome (CFS). [2]

Supportive. [1]

Corticosteroids for swollen tonsils, autoimmune hemolytic anemia, or CNS involvement. [1]