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Virological and immunological characteristics of fatal Epstein-Barr virus mononucleosis in a 17-year-old Caucasian male presenting with meningoencephalitis and hemophagocytic syndrome

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Abstract

In this report, the authors present a detailed immunological and virological assessment of an immunocompetent 17-year-old Caucasian male with a fatal Epstein-Barr virus (EBV) infectious mononucleosis presenting with meningoencephalitis and hemophagocytic syndrome. The patient with serologically confirmed EBV infectious mononucleosis was admitted to the hospital because of 3 weeks’ fever. Fine-needle aspiration of lymph nodes showed reactive hyperplasia with prominent hemophagocytosis. Percentages of intracellular interferon-gamma (IFN-γ) in CD4+ and CD8+ T cells in the peripheral blood progressively increased during the course of disease (10.2% and 8.5% on day 35; 30.1% and 53.2% on day 44; 42.2% and 75.2% on day 50; 36.1% and 50.6% on day 59, respectively). On day 50, the patient developed meningoencephalitis. Brain computed tomography (CT) was normal. Brain magnetic resonance imaging (MRI) showed multifocal inflammatory lesions in frontal and temporal cortex of the right hemisphere as well as severe perivascular inflammatory reaction. The patient was treated with steroids, cyclosporin A, and methotrexate intratecally. Following treatment, EBV viremia in the blood and cerebrospinal fluid (CSF) decreased from pretreatment values (54,490 copies of EBV DNA/ml and 39,500 copies/ml, respectively) to 8715 copies/ml in the blood and 14,690 in the CSF. Despite treatment, the patient remained unconscious and died of sepsis and pneumonia 3 months after initial symptoms. Immunohistochemical staining showed the presence of EBV in both perivascular infiltrates and grey matter. Enhanced Th1 response as shown by high levels of IFN-γ in peripheral blood lymphocytes may be a predictor of severe complications during acute EBV infection. Early implementation of immunosuppressive therapy in these patients should be considered.

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References

  • Attarbaschi T, Willheim M, Ramharter M, Hofmann A, Wahl K, Winkler H, Graninger W, Winkler S (2003). T cell cytokine profile during primary Epstein-Barr virus infection (infectious mononucleosis). Eur Cytokine Netw 14: 34–39.

    PubMed  CAS  Google Scholar 

  • Christensen T (2006). The role of EBV in MS pathogenesis. Int Mult Scler J 13: 52–57.

    CAS  Google Scholar 

  • Doja A, Bitnun A, Jones EL, Richardson S, Tellier R, Petric M, Heurter H, Macgregor D (2006). Pediatric Epstein-Barr virus-associated encephalitis: 10-year review. J Child Neurol 21: 385–391.

    PubMed  Google Scholar 

  • Drebber U, Kasper HU, Krupacz J, Haferkamp K, Kern MA, Steffen HM, Quasdorff M, zur Hausen A, Odenthal M, Dienes HP (2006). The role of Epstein-Barr virus in acute and chronic hepatitis. J Hepatol 44: 879–885.

    Article  PubMed  CAS  Google Scholar 

  • Francisci D, Sensini A, Fratini D, Moretti MV, Luchetta ML, Di Caro A, Stagni G, Baldelli F (2004). Acute fatal necrotizing hemorrhagic encephalitis caused by Epstein-Barr virus in a young adult immunocompetent man. J Neuro Virol 10: 414–417.

    Google Scholar 

  • Hinedi TB, Koff RS (2003). Cholestatic hepatitis induced by Epstein-Barr virus infection in an adult. Dig Dis Sci 48: 539–541.

    Article  PubMed  Google Scholar 

  • Hiroshima K, Iyoda A, Isobe K, Ishii G, Toyozaki T, Shibuya K, Shimamura F, Haga Y, Okimoto Y, Horie H, Harigaya K, Ohwada H (2003). Fatal infectious mononucleosis with evidence suggestive of the developmenot of B cell lymphoma. Pathol Int 53: 642–648.

    Article  PubMed  Google Scholar 

  • Hislop AD, Annels NE, Gudgeon NH, Leese AM, Rickinson AB (2002). Epitope-specific evolution of human CD8+ T cell responses from primary to persistent phases of Epstein-Barr virus infection. J Exp Med 195: 893–905.

    Article  PubMed  CAS  Google Scholar 

  • Holmoy T, Kvale EO, Vartdal F (2004). Cerebrospinal fluid CD4+ T cells from a multiple sclerosis patients cross-recognize Epstein-Barr virus and myelin basic protein. J NeuroVirol 10: 278–283.

    Article  PubMed  CAS  Google Scholar 

  • Imashuku S (2002). Clinical features and treatment strategies of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Crit Rev Oncol Hematol 44: 259–272.

    Article  PubMed  Google Scholar 

  • Kasahara Y, Yachie A, Takei K, Kanegane C, Okada K, Ohta K, Seki H, Igarashi N, Maruhashi K, Katayama K, Katoh E, Terao G, Sakiyama Y, Koizumi S (2001). Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Blood 98: 1882–1888.

    Article  PubMed  CAS  Google Scholar 

  • Khamma S, Kumar A (2003). Infectious mononucleosis presenting as acute hepatitis, with marked leukocytosis and renal involvement. Indian J Gastroenterol 22: 62.

    Google Scholar 

  • Kivisakk P, Trebst C, Liu Z, Tucky BH, Sorensen TL, Rudick RA, Mack M, Ransohoff RM. (2002). T cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking. Clin Exp Immunol 129: 510–518.

    Article  PubMed  CAS  Google Scholar 

  • Kobbervig C, Norback D, Kahl B (2003). Infectious mononucleosis progressing to fatal malignant lymphoma: a case report and review of the literature. Leuk Lymphoma 44: 1215–1221.

    Article  PubMed  CAS  Google Scholar 

  • Kumakura S (2005). Hemophagocytic syndrome. Intern Med 4: 278–280.

    Article  Google Scholar 

  • Lay JD, Tsao CJ, Chen JY, Kadin ME, Su IJ (1997). Up-regulation of tumor necrosis factor-α gene by Epstein-Barr virus and activation of macrophages in Epstein-Barr virus-infected T cells in the pathogenesis of hemophagocytic syndrome. J Clin Invest 100: 1969–1979.

    Article  PubMed  CAS  Google Scholar 

  • Lehrnbecher T, Chittka B, Nanan R, Seidenspinner S, Kreth HW, Schuster V (1996). Activated T lymphocytes in the cerebrospinal fluid of a patient with Epstein-Barr virus-associated meningoencephalitis. Pediatr Infect Dis 15: 631–363.

    Article  CAS  Google Scholar 

  • Majid A, Galetta SL, Sweeney CJ, Robinson C, Mahalingam R, Smith J, Forghani B, Gliden DH (2002). Epstein-Barr virus myeloradiculitis and encephalomyeloradiculitis. Brain 125: 159–165.

    Article  PubMed  Google Scholar 

  • Markin RS (1994). Manifestations of Epstein-Barr virus-associated disorders in liver. Liver 14: 1–13.

    PubMed  CAS  Google Scholar 

  • Merelli E, Bedin R, Sola P, Gentilini M, Pietrosemoli P, Meacci M, Portolani M (1997). Encephalomyeloradiculopathy associated with Epstein-Barr virus: primary infection or reactivation? Acta Neurol Scand 96: 416–420.

    Article  PubMed  CAS  Google Scholar 

  • Mizuno I, Takanashi Y, Onodera H, Shigeta M, Tanaka N, Yuya H, Kitaichi M, Nakajima K (2003). A case of lymphomatoid granulomatosis/angiocentric immunoproliferative lesions with long clinical course and diffuse brain involvement. J Neurol Sci 213: 67–76.

    Article  PubMed  Google Scholar 

  • Negro F (2006). The paradox of Epstein-Barr virus-associated hepatitis. J Hepatol 44: 839–841.

    Article  PubMed  Google Scholar 

  • Neuenburg JK, Cho TA, Nilsson A, Bredt BM, Hebert SJ, Grant RM, Price RW (2005). T-cell activation and memory phenotypes in cerebrospinal fluid during HIV infection. J Acquir Immune Defic Syndr 39: 16–22.

    Article  PubMed  Google Scholar 

  • Pelletier LL, Borel DM, Romig DA, Liu C (1976). Disseminated intravascular coagulation and hepatic necrosis. Complications of infectious mononucleosis. JAMA 235: 1144–1146.

    Article  PubMed  CAS  Google Scholar 

  • Riemer G, Stenvik O, Dahl OP, Slungaard S, Ringstad J, Bruu AL (2001). Encephalitis after acute Epstein-Barr virus infection. Tidsskr Nor Laegeforen 121: 1798–1800.

    PubMed  CAS  Google Scholar 

  • Sato S, Kawashima H, Oshiro H, Hasegawa D, Kashiwagi Y, Takekuma K, Hoshika A (2004). Virological and immunological characteristics of a 19-year-old Japanese female with fatal outcome with Epstein-Barr virus-associated hemophagocytic syndrome. J Clin Virol 31: 235–238.

    Article  PubMed  Google Scholar 

  • Schellinger PD, Sommer C, Leithauser F, Schwab S, Storch-Hagenlocher B, Hacke W, Kiessling M (1999). Epstein-Barr virus meningoencephalitis with a lymphoma-like response in an immunocompetent host. Ann Neurol 45: 659–662.

    Article  PubMed  CAS  Google Scholar 

  • Tselis A, Duman R, Storch GA, Lisak RP (1997). Epstein-Barr virus encephalomyelitis diagnosed by polymerase chain reaction: detection of the genome in the CSF. Neurology 48: 1351–1353.

    PubMed  CAS  Google Scholar 

  • Yamashita S, Murakami C, Izumi Y, Sawada H, Yamazaki Y, Yokota TA, Matsumoto N, Matsukura S (1998). Severe chronic active Epstein-Barr virus infection accompanied by virus-associated hemophagocytic syndrome, cerebellar ataxia and encephalitis. Psychiatry Clin Neurosci 52: 449–452.

    Article  PubMed  CAS  Google Scholar 

  • Zephir H, De Seze J, Ferriby D, Stojkovic T, Vermersch P (2002). Epstein-Barr meningoencephaloradiculitis in a immunocompetent woman. Rev Neurol 158: 830–832.

    PubMed  CAS  Google Scholar 

  • Židovec Lepej S, Vince A, Dakovic Rode O, Remenar A, Jeren T (2003). Increased numbers of CD38 molecules on bright CD8+ T lymphocytes in infectious mononucleosis caused by Epstein-Barr virus infection. Clin Exp Immunol 133: 384–390.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department for Viral Hepatitis and Laboratory for Molecular Diagnostics, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, Zagreb, Croatia

    Adriana Vince, Ivan Kurelac & Sanja Kozić

  2. Division of Cellular Immunology, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, Zagreb, Croatia

    Snježana Židovec Lepej

  3. Department of Neuroinfections and Intensive Care Medicine, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, Zagreb, Croatia

    Bruno Baršić & Igor Klinar

  4. Department of Neuropathology, School of Medicine, University of Zagreb, Clinical Medical Center Zagreb, Zagreb, Croatia

    Kamelia Žarković

  5. Laboratory for Molecular Diagnostics and Cellular Immunity, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, Mirogojska 8, 10 000, Zagreb, Croatia

    Snježana Židovec Lepej

Authors
  1. Adriana Vince
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  2. Snježana Židovec Lepej
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  3. Ivan Kurelac
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  4. Bruno Baršić
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  5. Sanja Kozić
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  6. Igor Klinar
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  7. Kamelia Žarković
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Corresponding author

Correspondence to Snježana Židovec Lepej.

Additional information

This study was supported by grants from the Croatian Ministry of Science, Education and Sports to Dr. Vince and Dr. Židovec Lepej (grants number 143-1080116-0097 and 143-0000000-0117).

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Vince, A., Lepej, S.Ž., Kurelac, I. et al. Virological and immunological characteristics of fatal Epstein-Barr virus mononucleosis in a 17-year-old Caucasian male presenting with meningoencephalitis and hemophagocytic syndrome. Journal of NeuroVirology 13, 389–396 (2007). https://doi.org/10.1080/13550280701447042

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  • DOI: https://doi.org/10.1080/13550280701447042

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