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1/300. Subacute painful lumbosacral polyradiculoneuropathy in immunocompromised patients.

    The syndrome of inflammatory subacute lumbosacral polyradiculoneuropathy (SLP) has been reported in acquired immunodeficiency syndrome (AIDS) patients in association with cytomegalovirus infection and is only partially amenable to anti-viral therapy. We report three cases of relatively benign inflammatory painful SLP in two non-AIDS, immunosuppressed patients and one who hiv-seroconversed at the time of clinical presentation. SLP developed: (1) in association with hiv seroconversion; (2) during ECHO virus infection in a patient with common variable immune deficiency; and (3) after a severe systemic infection that induced transient immunosuppression due to Epstein-Barr virus reactivation. This report expands the spectrum of viruses associated with acute and subacute lumbosacral polyradiculoneuropathy and may shed light on its possible pathogenesis.
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2/300. Systemic granulomatous arteritis associated with Epstein-Barr virus infection.

    A 61-year-old woman initially presented with symptoms and findings reminiscent of infectious mononucleosis, and her illness then took a rapidly fatal course. autopsy revealed widespread granulomatous arteritis, with multinucleated giant cells but without eosinophils and fibrinoid necrosis, affecting small arteries and arterioles and infiltration of haemophagocytic histiocytes into many organs. in situ hybridization with Epstein-Barr virus (EBV)-specific oligonucleotide probes showed positive signals in the infiltrating immune cells and epithelial and endothelial cells of the affected organs. EBV-associated haemophagocytic syndrome (EBV-AHS) with systemic granulomatous arteritis was diagnosed. From the immunophenotypes of the infiltrating immune cells, a possible role of CD4 T-cells in the pathogenesis of this haemophagocytic syndrome and granulomatous vasculitis was suggested.
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3/300. Characterization of Epstein-Barr virus (EBV)-infected natural killer (NK) cell proliferation in patients with severe mosquito allergy; establishment of an IL-2-dependent NK-like cell line.

    The clinical evidence of a relationship between severe hypersensitivity to mosquito bite (HMB) and clonal expansion of EBV-infected NK cells has been accumulated. In order to clarify the mechanism of EBV-induced NK cell proliferation and its relationship with high incidence of leukaemias or lymphomas in HMB patients, we studied clonally expanded NK cells from three HMB patients and succeeded in establishing an EBV-infected NK-like cell line designated KAI3. immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses revealed that KAI3 cells as well as infected NK cells exhibited an EBV latent infection type II, where EBV gene expression was limited to EBNA 1 and LMP1. As KAI3 was established by culture with IL-2, IL-2 responsiveness of peripheral blood NK cells from patients was examined. The results represented markedly augmented IL-2-induced IL-2R alpha expression in NK cells. This characteristic property may contribute to the persistent expansion of infected NK cells. However, KAI3 cells as well as the NK cells from patients were not protected from apoptosis induced by either an anti-Fas antibody or NK-sensitive k562 cells. Preserved sensitivity to apoptosis might explain the relatively regulated NK cell numbers in the peripheral blood of the patients. To our knowledge, KAI3 is the first reported NK-like cell line established from patients of severe chronic active EBV infection (SCAEBV) before the onset of leukaemias or lymphomas. KAI3 cells will contribute to the study of EBV persistency in the NK cell environment and its relationship with high incidence of leukaemias or lymphomas in HMB patients.
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4/300. poliomyelitis-like syndrome associated with Epstein-Barr virus infection.

    A 20-month-old male presented with an acute clinical syndrome resembling poliomyelitis, characterized by a flaccid monoplegia, areflexia of the involved limb, and preserved sensation. Electrophysiologic studies supported a neuronopathic localization involving the anterior horn cells. Although laboratory evidence for a poliovirus infection was absent, serologic and polymerase chain reaction studies documented an active central nervous system infection with Epstein-Barr virus, indicating that a poliomyelitis-like syndrome may be produced by infectious agents other than enteroviruses.
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5/300. The association of latent Epstein-Barr virus infection with hydroa vacciniforme.

    patients with hydroa vacciniforme (HV)-like eruptions and malignant potential have been reported from asia and mexico, and those patients frequently had an associated latent Epstein-Barr virus (EBV) infection. In order to elucidate the association of latent EBV infection with HV, we studied six children with typical manifestations of HV by detection of EBV genes and EBV-related RNAs in biopsy specimens from cutaneous lesions. Cutaneous lesions of all six children with typical HV contained EBV-encoded small nuclear rna (EBER) cells in 3-10% of the dermal infiltrates, whereas no Bam HI-H, l-fragment (BHLF) mRNA, or transcripts encoding EA-D antigen, were detected. No EBER cells were detected in other inflammatory or benign lymphoproliferative skin disorders tested. polymerase chain reaction amplification confirmed the presence of EBV dna sequences in five of six biopsy specimens from the patients. Latent EBV infection is associated with the development of cutaneous lesions of HV.
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6/300. Epstein-Barr virus (EBV) associated B-cell lymphoproliferative disease following HLA identical sibling marrow transplantation for aplastic anaemia in a patient with an EBV seronegative donor.

    BACKGROUND: B-cell lymphoproliferative disorders (BLPD*) caused by Epstein-Barr virus (EBV) occurring after allogeneic bone marrow transplantation (BMT) are usually of donor origin. Treatment such as discontinuation of immunosuppression may be successful in some cases, but infusion of donor T cells results in successful eradication of EBV BLPD in most cases. methods AND RESULTS: We report a case of EBV positive aggressive BLPD after HLA matched sibling BMT for aplastic anaemia. The tumour completely regressed after withdrawal of cyclosporin and donor lymphocyte infusion. However, although the tumor was of donor origin, the donor serum was negative for antibodies to EBV antigens and no EBV-specific cytotoxicity was detected in donor peripheral blood mononuclear cells. The recipient was seropositive for EBV before BMT. CONCLUSIONS: We speculate that a 'second primary' EBV infection occurred involving donor cells in the recipient during BMT immunosuppression, with subsequent outgrowth of donor-derived BLPD. EBV infection may have been by an endogenous EBV isolate, from external sources, or from third party transfusions.
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7/300. Interferon gamma (IFN-gamma) deficiency in generalized Epstein-Barr virus infection with interstitial lymphoid and granulomatous pneumonia, focal cerebral lesions, and genital ulcers: remission following IFN-gamma substitution therapy.

    A 26-year-old previously healthy woman developed granulomatous pneumonitis, encephalitis, and genital ulceration during primary Epstein-Barr virus (EBV) infection. EBV dna was demonstrated by polymerase chain reaction analysis of serum, lung tissue, and genital ulcer specimens. serology verified primary EBV infection. The patient lacked lymphocytes cytotoxic to autologous EBV-transformed B lymphocytes. No spontaneous or in vitro EBV-induced interferon gamma (IFN-gamma) production was evident in peripheral blood. The cells had normal IFN-gamma production when stimulated with staphylococcus aureus exotoxin A. In the bone marrow and peripheral blood, the number of large granular CD56 lymphocytes (natural killer cells) increased 39%-55%, but no CD4 or CD8 cell lymphocytosis was initially found. A partial clinical response was achieved with treatment with acyclovir, corticosteroids, and intravenous gamma-globulin. Because of persistent granulomatous central nervous system and lung involvement, subcutaneous IFN-gamma therapy was started but was discontinued after 3 months because of development of fever, pancytopenia, and hepatitis. This therapy initiated a complete clinical recovery, which occurred parallel to development of EBV-specific cytotoxic CD8 T lymphocytes and normalization of natural killer cell lymphocytosis. These findings provide evidence for an EBV-induced lymphoproliferative disorder due to a T lymphocyte dysfunction associated with a selective lack of IFN-gamma synthesis.
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8/300. Tubulointerstitial nephritis and uveitis in association with Epstein-Barr virus infection.

    The case of a 13.5-year-old girl with acute tubulointerstitial nephritis and uveitis (TINU syndrome) is presented. The etiology of this rare syndrome, which in most cases involves female adolescents and usually regresses spontaneously, is still unknown. An infection-triggered pathological immune reaction has been considered to play a role in the pathogenesis of this disorder. Here we report for the first time the association of TINU syndrome and Epstein-Barr virus infection.
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9/300. Subacute sensory neuropathy associated with Epstein-Barr virus.

    A 35-year-old man experienced severe sensory loss, pseudoathetosis, and areflexia during recovery from a severe viral illness. Sensory nerve action potentials were absent, motor conduction velocities were mildly slowed, and blink reflexes were normal. magnetic resonance imaging (MRI) revealed abnormal signal within the central and dorsal aspects of the thoracic cord. Acute and convalescent Epstein-Barr virus (EBV) titers suggested EBV as the etiology. Subacute sensory neuropathy, with peripheral and central nervous system involvement, is a rare complication of EBV infection.
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10/300. Peripheral T-cell lymphoma with Reed-Sternberg-like cells of B-cell phenotype and genotype associated with Epstein-Barr virus infection.

    We report three cases of nodal peripheral T-cell lymphoma (PTCL) with Reed-Sternberg-like (RS-like) cells of B-cell pheno- and/or genotype. Histologic analysis in all cases revealed diffuse nodal effacement by atypical lymphoid cells of variable size. Two of the three cases had features of angioimmunoblastic T-cell lymphoma (AILT). Large mononuclear and binucleated cells with prominent eosinophilic nucleoli and abundant cytoplasm resembling classic RS cells and mononuclear variants were scattered throughout all biopsies. The lymphoma cells in the three cases were of T-cell lineage (CD3 , CD43 , and CD45RO ). The RS-like cells from all cases were CD30 and CD15 positive. In contrast to the neoplastic T cells, the RS-like cells lacked all T-cell markers and in two cases were positive for CD20. Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) and EBER 1 (2/2) were detected in the RS-like cells in all cases. The neoplastic T cells were negative for EBV. polymerase chain reaction (PCR) analysis demonstrated clonal rearrangements of the T-cell receptor gamma chain gene in the three cases. PCR analysis of microdissected RS-like cells for immunoglobulin heavy chain gene rearrangements in cases 1 and 3 showed an oligoclonal pattern. The presence of RS-like cells in PTCL represents a diagnostic pitfall, because in one case this observation led to a misdiagnosis of Hodgkin's disease (HD). The oligoclonal expansion of EBV-infected cells may be related to underlying immunodeficiency associated with T-cell lymphomas and AILT in particular. This phenomenon may provide the basis for some cases of Hodgkin's disease after T-cell lymphomas and suggests that they are clonally unrelated neoplasms. The expression of LMP1 appears to be crucial for the immunophenotype and probably for the morphology of the RS and RS-like cells appearing in diverse lymphoid malignancies, including HD, chronic lymphocytic leukemia, and PTCL.
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