SYSTEMIC TYPE EPSTEIN-BARR VIRUS-RELATED LYMPHOPROLIFERATIVE DISEASES IN CHILDREN AND YOUNG ADULTS: Challenges for Pediatric Hemato-Oncologists and Infectious Disease Specialists

Abstract

Involvement of Epstein-Barr virus (EBV) has long been known in the development of various tumor-forming proliferating diseases, such as nasopharyngeal carcinoma in adults. However, in children and young adults more attention should be focused on systemic, severe type EBV-related diseases, such as fatal infectious mononucleosis, hemophagocytic syndrome, or chronic active EBV infection (CAEBV). These disorders show the typical clinical features of hemophagocytic lymphohistiocytosis (HLH). Although viral infectious diseases are mostly taken care of by infectious disease specialists, pediatric hemato-oncologists need to intervene in the treatment of this kind of disease because of their clonal and neoplastic disease characteristics and of their hematologically problematic, rapid, and life-threatening clinical courses.

An autopsy case of chronic active Epstein–Barr virus infection (CAEBV): Distribution of central nervous system (CNS) lesions

“…We believed that the patient had presented with EBV-HLH during the course of CAEBV. Recently, EBV was demonstrated to infect T cells or NK cells to cause systemic lymphoproliferative diseases such as CAEBV, EBV-HLH, and/ or EBV + lymphoma [1]. Diagnostic criteria for CAEBV consists of (1) persistent or recurrent infectious mononucleosis-like symptoms, such as fever, hepatosplenomegaly, persistent hepatitis and extensive lymphadenopathy (2) an unusual pattern of anti-EBV antibodies with raised anti-VCA and anti-EA, and/or detection of increased EBV genomes in affected tissue including peripheral blood, and (3) chronic illness that cannot be explained by other known disease processes at diagnosis [2].…”

“…In IM, EBV-infected B cells trigger proliferation of cytotoxic T cells, which themselves are free of EBV. Recently, EBV is also demonstrated to infect T cells or natural killer (NK) cells to cause systemic lymphoproliferative diseases such as chronic active EBV infection (CAEBV), EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and/or EBV + lymphoma [1]. Here, we report an autopsy case of CAEBV with severe and extensive central nervous system (CNS) involvement.…”

Approach to Hemophagocytic Syndromes

“…Alemtuzumab suppresses T cells and histiocytes and has proven to be a successful salvage strategy, 4,32 but careful surveillance for opportunistic infections such as CMV is essential. Other published salvage therapies include antithrombin III, 32 infliximab (anti-TNF antibody), 33 and daclizumab (anti-CD25 antibody). 34 In MAS patients, IL1 and IL6 inhibition have been successful in some but not all patients.…”

A case of a girl presenting with fever, cytopenia, liver dysfunction, hepatosplenomegaly, and hemophagocytosis in the bone marrow

“…3,8,9,12,13 Rituximab is a humanized anti-CD20 monoclonal antibody which targets and depletes mature B cells within 48 h of therapy. In relation to HLH, the inclusion of rituximab may rapidly reduce the numbers of B cells containing EBV; it is these cells that are thought to drive the dysregulation of the inflammatory response.…”