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. 1991 Jan;4(1):129–135. doi: 10.1128/cmr.4.1.129

Severe chronic active Epstein-Barr virus infection syndrome.

M Okano 1, S Matsumoto 1, T Osato 1, Y Sakiyama 1, G M Thiele 1, D T Purtilo 1
PMCID: PMC358181  PMID: 1848476

Abstract

Reports of unusually severe lymphoproliferative disorders associated with extremely high antibody titers against Epstein-Barr virus (EBV) have recently increased. The syndrome, which we designated severe chronic active EBV infection syndrome, is characterized by persistent or intermittent fever, lymphadenopathy, and hepatosplenomegaly and primarily affects children and young adults. Polyclonal gammopathy and bone marrow suppression are generally observed, and some patients develop B-cell or T-cell lymphoproliferation or lymphoma. Frequently, EBV genomes are detectable in tissues infiltrated with lymphoid cells. Additionally, it is difficult to establish spontaneous or B95-8 EBV-induced cell lines despite the expression of an activated EBV infection. We review and report here the published medical literature and our own experience regarding patients with severe chronic active EBV infection syndrome in an attempt to understand this enigmatic syndrome and the possible pathogenetic mechanism(s) responsible for this disorder.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alfieri C., Ghibu F., Joncas J. H. Lytic, nontransforming Epstein-Barr virus (EBV) from a patient with chronic active EBV infection. Can Med Assoc J. 1984 Nov 15;131(10):1249–1252. [PMC free article] [PubMed] [Google Scholar]
  2. Alfieri C., Joncas J. H. Biomolecular analysis of a defective nontransforming Epstein-Barr virus (EBV) from a patient with chronic active EBV infection. J Virol. 1987 Oct;61(10):3306–3309. doi: 10.1128/jvi.61.10.3306-3309.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DuBois R. E., Seeley J. K., Brus I., Sakamoto K., Ballow M., Harada S., Bechtold T. A., Pearson G., Purtilo D. T. Chronic mononucleosis syndrome. South Med J. 1984 Nov;77(11):1376–1382. doi: 10.1097/00007611-198411000-00007. [DOI] [PubMed] [Google Scholar]
  4. Hellmann D., Cowan M. J., Ammann A. J., Wara D. W., Chudwin D., Chang R. S. Chronic active Epstein-Barr virus infections in two immunodeficient patients. J Pediatr. 1983 Oct;103(4):585–588. doi: 10.1016/s0022-3476(83)80592-7. [DOI] [PubMed] [Google Scholar]
  5. Henle W., Henle G., Andersson J., Ernberg I., Klein G., Horwitz C. A., Marklund G., Rymo L., Wellinder C., Straus S. E. Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. Proc Natl Acad Sci U S A. 1987 Jan;84(2):570–574. doi: 10.1073/pnas.84.2.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ishihara S., Tawa A., Yumura-Yagi K., Murata M., Hara J., Yabuuchi H., Hirai K., Kawa-Ha K. Clonal T-cell lymphoproliferation containing Epstein-Barr (EB) virus DNA in a patient with chronic active EB virus infection. Jpn J Cancer Res. 1989 Feb;80(2):99–101. doi: 10.1111/j.1349-7006.1989.tb02273.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Joncas J. H., Ghibu F., Blagdon M., Montplaisir S., Stefanescu I., Menezes J. A familial syndrome of susceptibility to chronic active Epstein-Barr virus infection. Can Med Assoc J. 1984 Feb 1;130(3):280–284. [PMC free article] [PubMed] [Google Scholar]
  8. Joncas J., Monczak Y., Ghibu F., Alfieri C., Bonin A., Ahronheim G., Rivard G. Brief report: killer cell defect and persistent immunological abnormalities in two patients with chronic active Epstein-Barr virus infection. J Med Virol. 1989 Jun;28(2):110–117. doi: 10.1002/jmv.1890280211. [DOI] [PubMed] [Google Scholar]
  9. Jones J. F., Ray C. G., Minnich L. L., Hicks M. J., Kibler R., Lucas D. O. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985 Jan;102(1):1–7. doi: 10.7326/0003-4819-102-1-. [DOI] [PubMed] [Google Scholar]
  10. Jones J. F., Shurin S., Abramowsky C., Tubbs R. R., Sciotto C. G., Wahl R., Sands J., Gottman D., Katz B. Z., Sklar J. T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections. N Engl J Med. 1988 Mar 24;318(12):733–741. doi: 10.1056/NEJM198803243181203. [DOI] [PubMed] [Google Scholar]
  11. Kawa-Ha K., Franco E., Doi S., Yumura K., Ishihara S., Tawa A., Yabuuchi H. Successful treatment of chronic active Epstein-Barr virus infection with recombinant interleukin-2. Lancet. 1987 Jan 17;1(8525):154–154. doi: 10.1016/s0140-6736(87)91980-5. [DOI] [PubMed] [Google Scholar]
  12. Kikuta H., Nakanishi M., Sakiyama Y., Matsumoto S. Chronic active Epstein-Barr virus (EBV) infection is associated with clonotypic intracellular terminal regions of the EBV. J Infect Dis. 1989 Sep;160(3):546–547. doi: 10.1093/infdis/160.3.546a. [DOI] [PubMed] [Google Scholar]
  13. Kikuta H., Taguchi Y., Tomizawa K., Kojima K., Kawamura N., Ishizaka A., Sakiyama Y., Matsumoto S., Imai S., Kinoshita T. Epstein-Barr virus genome-positive T lymphocytes in a boy with chronic active EBV infection associated with Kawasaki-like disease. Nature. 1988 Jun 2;333(6172):455–457. doi: 10.1038/333455a0. [DOI] [PubMed] [Google Scholar]
  14. Kuis W., Roord J. J., Zegers B. J., Rickinson A. B., Kapsenberg J. G., The H., Stoop J. W. Heterogeneity of immune defects in three children with a chronic active Epstein-Barr virus infection. J Clin Immunol. 1985 Nov;5(6):377–385. doi: 10.1007/BF00915334. [DOI] [PubMed] [Google Scholar]
  15. Masucci M. G., Szigeti R., Ernberg I., Björkholm M., Mellstedt H., Henle G., Henle W., Pearson G., Masucci G., Svedmyr E. Cell-mediated immune reactions in three patients with malignant lymphoproliferative diseases in remission and abnormally high Epstein-Barr virus antibody titers. Cancer Res. 1981 Nov;41(11 Pt 1):4292–4301. [PubMed] [Google Scholar]
  16. Miller G., Grogan E., Fischer D. K., Niederman J. C., Schooley R. T., Henle W., Lenoir G., Liu C. R. Antibody responses to two Epstein-Barr virus nuclear antigens defined by gene transfer. N Engl J Med. 1985 Mar 21;312(12):750–755. doi: 10.1056/NEJM198503213121204. [DOI] [PubMed] [Google Scholar]
  17. Miller G., Grogan E., Rowe D., Rooney C., Heston L., Eastman R., Andiman W., Niederman J., Lenoir G., Henle W. Selective lack of antibody to a component of EB nuclear antigen in patients with chronic active Epstein-Barr virus infection. J Infect Dis. 1987 Jul;156(1):26–35. doi: 10.1093/infdis/156.1.26. [DOI] [PubMed] [Google Scholar]
  18. Okano M., Thiele G. M., Davis J. R., Grierson H. L., Purtilo D. T. Epstein-Barr virus and human diseases: recent advances in diagnosis. Clin Microbiol Rev. 1988 Jul;1(3):300–312. doi: 10.1128/cmr.1.3.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Okano M., Thiele G. M., Davis J. R., Nauseef W. M., Mitros F., Purtilo D. T. Adenovirus type-2 in a patient with lethal hemorrhagic colonic ulcers and chronic active Epstein-Barr virus infection. Ann Intern Med. 1988 May;108(5):693–699. doi: 10.7326/0003-4819-108-5-693. [DOI] [PubMed] [Google Scholar]
  20. Okano M., Thiele G. M., Purtilo D. T. Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection. Am J Pediatr Hematol Oncol. 1990 Summer;12(2):168–173. doi: 10.1097/00043426-199022000-00008. [DOI] [PubMed] [Google Scholar]
  21. Risdall R. J., McKenna R. W., Nesbit M. E., Krivit W., Balfour H. H., Jr, Simmons R. L., Brunning R. D. Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis. Cancer. 1979 Sep;44(3):993–1002. doi: 10.1002/1097-0142(197909)44:3<993::aid-cncr2820440329>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  22. Schooley R. T., Carey R. W., Miller G., Henle W., Eastman R., Mark E. J., Kenyon K., Wheeler E. O., Rubin R. H. Chronic Epstein-Barr virus infection associated with fever and interstitial pneumonitis. Clinical and serologic features and response to antiviral chemotherapy. Ann Intern Med. 1986 May;104(5):636–643. doi: 10.7326/0003-4819-104-5-636. [DOI] [PubMed] [Google Scholar]
  23. Steinberg A. D., Seldin M. F., Jaffe E. S., Smith H. R., Klinman D. M., Krieg A. M., Cossman J. NIH conference. Angioimmunoblastic lymphadenopathy with dysproteinemia. Ann Intern Med. 1988 Apr;108(4):575–584. doi: 10.7326/0003-4819-108-4-575. [DOI] [PubMed] [Google Scholar]
  24. Straus S. E., Tosato G., Armstrong G., Lawley T., Preble O. T., Henle W., Davey R., Pearson G., Epstein J., Brus I. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985 Jan;102(1):7–16. doi: 10.7326/0003-4819-102-1-7. [DOI] [PubMed] [Google Scholar]
  25. Sullivan J. L., Woda B. A., Herrod H. G., Koh G., Rivara F. P., Mulder C. Epstein-Barr virus-associated hemophagocytic syndrome: virological and immunopathological studies. Blood. 1985 May;65(5):1097–1104. [PubMed] [Google Scholar]
  26. Tobi M., Morag A., Ravid Z., Chowers I., Feldman-Weiss V., Michaeli Y., Ben-Chetrit E., Shalit M., Knobler H. Prolonged atypical illness associated with serological evidence of persistent Epstein-Barr virus infection. Lancet. 1982 Jan 9;1(8263):61–64. doi: 10.1016/s0140-6736(82)90210-0. [DOI] [PubMed] [Google Scholar]
  27. Tobi M., Straus S. E. Chronic Epstein-Barr virus disease: a workshop held by the National Institute of Allergy and Infectious Diseases. Ann Intern Med. 1985 Dec;103(6 ):951–953. doi: 10.7326/0003-4819-103-6-951. [DOI] [PubMed] [Google Scholar]
  28. Virelizier J. L., Lenoir G., Griscelli C. Persistent Epstein-Barr virus infection in a child with hypergammaglobulinaemia and immunoblastic proliferation associated with a selective defect in immune interferon secretion. Lancet. 1978 Jul 29;2(8083):231–234. doi: 10.1016/s0140-6736(78)91744-0. [DOI] [PubMed] [Google Scholar]
  29. Weiss L. M., Movahed L. A., Warnke R. A., Sklar J. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease. N Engl J Med. 1989 Feb 23;320(8):502–506. doi: 10.1056/NEJM198902233200806. [DOI] [PubMed] [Google Scholar]
  30. Yokochi T., Yanagawa A., Kimura Y., Mizushima Y. High titer of antibody to the Epstein-Barr virus membrane antigen in sera from patients with rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol. 1989 Aug;16(8):1029–1032. [PubMed] [Google Scholar]

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