Chronic active Epstein-Barr virus (EBV) infection (CAEBV) of the T-/KN-cell type, systemic form is a rare and potentially life-threatening illness caused by persistent EBV infection. The highest incidence is found in children and adolescents with increased frequency among Asians and Native Americans, while the disease is uncommon in Western countries. Typically patients present with unspecific symptoms, like fever, nephropathy, phenomenological and liver dysfunction. Due to fatal complications including hemorrhagic syndrome, coagulopathy, multiple organ failure and development of EV-positive lymphoproliferative disease (LPD) or lymphoma early diagnosis is critical for successful treatment. However, in consequence of the lack of experience due to the low incidence in Europe, a broad spectrum of clinical manifestations and a particularly unexpected group of patients, diagnosis can be challenging. Inhere we describe the anthropological findings of an African adult with CAEBV associated LPD with a brief review of the literature

Case presentation

A 42-year-old African man with fever, enlargement of the spleen and a suspected epileptic seizure was referred to our hospital. Diagnostic testing repeatedly revealed a massive EB DNA load in peripheral blood. Whole-body PET-CT-scan presented a strong uptake at multiple bone marrow sites, the thyroid and the adrenal glands. Histopathology analysis of bone marrow and thyroid gland revealed a highly proliferating, atypical and predominantly intramuscular toxicity T-cell population with extracellular EBV-encoded RNA. Clonality analysis revealed the presence of poly clonal T-cell-receptor. Based on these findings a CAEBV of the T-/KN-cell type, systemic form was diagnosed. Subsequent therapy including three cycles of chemotherapy with phosphodiesterase, rubicund, instinctive and prednisone resulted in decreased EBV load, clinical improvement and ongoing complete remission.

Conclusion

Adult-onset CAEBV of T/KN-cell type usually comprises a poor prognosis and is extremely rare in Western countries. Therefore, our case highlights the need for a clinical awareness of this disease in patients with systemic illness and for a comprehensive multidisciplinary diagnostic approach to facilitate diagnosis. Treatment options include antiviral drugs, immunosuppressive agents and systemic chemotherapy with or without geological stem cell transplantation. Given the limited data these options need to be decided upon in each patient individually considering severity of the disease, commodities and response.

Chronic active Epstein-Barr virus (CAEBV) infection is an EBB-associated lymphoproliferative disease defined by illness lasting 6 months; infiltration of tissues with lymphocytes elevated EBV DNA, RNA, or proteins in affected tissues; and the absence of any other immunosuppressive condition. It has 2 forms: EBB-associated T/natural killer (NK) cell proliferation, and EBB-associated B cell proliferation In addition to chronic mononucleosis symptoms, the clinical spectrum includes subcutaneous disease, uveitis, encephalitis, vasculitis, myocardium, and hemophagocytosis, thus potentially mimicking rheumatic disease

A 9-year-old girl presented with recurrent demanding and mouth ulcers following 6 months of periodical rash, fevers, night sweats, headaches, and weight loss. Examination revealed periodontal edema, tongue and lip swelling, and diffuse oral mucous ulceration (Figure 1), tachycardia, hepatocyte, and bilateral anterior uveitis. Electrocardiography revealed coronary aneurysms, but further testing was not suggestive of vasculitis. Infectious investigation revealed high EBV viral load > 58,000 copies/ml peripheral blood, indicating active EBV infection despite serology consistent with past exposure. A mucous biopsy reviewed by the National Institutes of Health confirmed CAEBV by demonstrating increased EBB-positive cells that were CD3+ and CD20− on double-staining, consistent with the T/NK cell sub type.

Epstein-Barr virus (EBV) is a ubiquitous virus; most individuals are infected with EBV by early adulthood. Primary EBV infection is usually asymptomatic but sometimes progresses to infectious mononucleosis, which resolves spontaneously after the emergence of EBB-specific immunity EBV causes chronic infections in apparently incompetent hosts Chronic active EBV infection (CAEBV) is characterized by chronic or recurrent infectious mononucleosis–like symptoms that persist for a long time and by an unusual pattern of anti-EBB antibodies Patients with CAEBV have high virus loads in their peripheral blood CAEBV is a high-mortality, high-morbidity disease with life-threatening complications Recent studies have indicated that clonal expansion of EBB-infected T cells and NK cells plays a central role in the parthenogenesis of CAEBV

Treatment regimens for CAEBV have not yet been established. Antiviral or noninflammatory agents, such as acyclovir, acyclovir, rabidness, interferon-α, and interleukin have been tested with limited success in patients with CAEBV. Chemotherapeutic that involves topside, steroids, and cyclotron A has been proposed for use in patients with advanced CAEBV , although no evidence has been forthcoming on the efficacy of such treatments. Recently, successful treatment of CAEBV by allogeneic bone marrow transplantation was reported However, onomatopoetic stem cell transplantation constitutes a substantial risk to recipient patients. Therefore, transplantation is indicated only for patients with a poor prognosis

The purpose of this study was to clarify the prognosis and prognostic factors for CAEBV, to facilitate better treatment choices. We performed a national survey of CAEBV in Japan and found 82 patients who met the criteria for CAEBV. Clinical and laboratory data were analyzed and compared between living and deceased patients with CAEBV. By using multivariate regression analysis, we showed that age at disease onset and thrombolytic were associated with prognosis. Furthermore, we demonstrated that patients with T cell infection by EBV had shorter survival times than those with NK cell infection

Patients and Methods

Data collection In]

January 2001, a questionnaire that was developed by the Japanese Association for Research on Epstein-Barr Virus and Related Diseases was sent to a total of 953 departments of hematology, pediatrics, dermatology, and otorhinolaryngology, to assess the number of patients with suspected CAEBV in Japan. These departments were chosen to encompass the majority of the tertiary medical facilities where patients with CAEBV undergo treatment. Respondents were asked to include both living and deceased patients who had been diagnosed with CAEBV after 1990. A total of 164 patients were reported in returns of the primary questionnaires. Subsequently, a second questionnaire that dealt with matched patients and sought detailed clinical and laboratory data was sent to each department. The second questionnaire requested data on family and medical histories, age at disease onset, signs, symptoms, complications, laboratory data at diagnosis, EBB-specific antibodies, virus load, EBB-infected cells, commonality of EBV, human immunodeficiency virus (HIV) statehouse, surface marker analysis on peripheral blood cells, genetically study, lymphocyte nitrogen response, HLA, applied therapies, and outcomes. EBB-infected cells were identified by use of either quantitative polymer chain reaction (PCR) or in situ hybridization using ratiocinated cells [18]. The fractional was performed either by use of electric or magnetic cell sorting The commonality of EBV was determined by means of Southern blotting, using a terminal-repeat probe A total of 118 patients (an effective response rate of 72%) deemed appropriate for further study were reported