Clinical features of adult-onset chronic active Epstein–Barr virus infection: a retrospective analysis

  • Ayako Arai
  • Ken-Ichi Imadome
  • Yuko Watanabe
  • Mayumi Yoshimori
  • Takatoshi Koyama
  • Takeharu Kawaguchi
  • Chiaki Nakaseko
  • Shigeyoshi Fujiwara
  • Osamu Miura
Original Article


We performed a retrospective analysis of patients with adult-onset chronic active Epstein–Barr virus infection (CAEBV). First, we analyzed five patients (aged 28–72) diagnosed at our hospitals with EBV-infected clonally proliferating T cells. Four patients were administered cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) chemotherapy, but no remarkable decrease of viral load was observed in three of the patients. The other patient died 19 days after initiation of CHOP treatment due to disease progression. Addition of high-dose cytarabine to the regimens of two of the patients was discontinued shortly after administration, due to the development of grade 4 pericardial effusion. Together, these regimens may be insufficient for treating adult-onset CAEBV. We next reviewed 23 adult-onset CAEBV patients, adding 18 previously reported patients to the five patients described in the present study. T cells were frequently infected (87%), whereas NK- and T-cell types are known to be almost equally prevalent in childhood-onset cases. The time duration from the onset of disease to initiation of treatment averaged 20 months. Reports showed that 12 patients died; seven patients died at an average of 8 months after initiation of treatment. Patients’ disease courses seemed to be rapidly progressive and more aggressive than those of childhood-onset cases. More cases must be studied to clarify clinical features and establish an optimal treatment strategy.


Chronic active Epstein–Barr virus infection Adult-onset EBV-positive T-cell lymphoproliferative disorders of childhood Chemotherapy Clinical features 


  1. 1.
    Okano M, Kawa K, Kimura H, Yachie A, Wakiguchi H, Maeda A, et al. Proposed guidelines for diagnosing chronic active Epstein–Barr virus infection. Am J Hematol. 2005;80:64–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Quintanilla-Martinez L, Kimura H, Jaffe ES. EBV-positive T-cell lymphoproliferative disorders of childhood. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008. p. 278–80.Google Scholar
  3. 3.
    Ohshima K, Kimura H, Yoshino T, Kim CW, Ko YH, Lee SS, et al. Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD. Pathol Int. 2008;58:209–17.PubMedCrossRefGoogle Scholar
  4. 4.
    Sato E, Ohga S, Kuroda H, Yoshiba F, Nishimura M, Nagasawa M, et al. Allogeneic hematopoietic stem cell transplantation for Epstein–Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan. Am J Hematol. 2008;83:721–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Imadome K, Shimizu N, Arai A, Miura O, Watanabe K, Nakamura H, et al. Coexpression of CD40 and CD40 ligand in Epstein–Barr virus-infected T and NK cells and their role in cell survival. J Infect Dis. 2005;192:1340–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Koyama M, Takeshita Y, Sakata A, Sawada A, Yasui M, Okamura T, et al. Cytotoxic chemotherapy successfully induces durable complete remission in 2 patients with mosquito allergy resulting from Epstein–Barr virus-associated T-/natural killer cell lymphoproliferative disease. Int J Hematol. 2005;82:437–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Fujii N, Takenaka K, Hiraki A, Maeda Y, Ikeda K, Shinagawa K, et al. Allogeneic peripheral blood stem cell transplantation for the treatment of chronic active Epstein–Barr virus infection. Bone Marrow Transplant. 2000;26:805–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Sato-Matsumura KC, Matsumura T, Kobayashi H, Fujimoto K, Itoh T, Shimizu M, et al. Marked swollen erythema of the face together with sicca syndrome as a sign for chronic active Epstein–Barr virus infection. Br J Dermatol. 2000;143:1351–3.PubMedCrossRefGoogle Scholar
  9. 9.
    Kimura H, Hoshino Y, Kanegane H, Tsuge I, Okamura T, Kawa K, et al. Clinical and virologic characteristics of chronic active Epstein–Barr virus infection. Blood. 2001;98:280–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Hauptmann S, Meru N, Schewe C, Jung A, Hiepe F, Burmester G, et al. Fatal atypical T-cell proliferation associated with Epstein–Barr virus infection. Br J Haematol. 2001;112:377–80.PubMedCrossRefGoogle Scholar
  11. 11.
    Ogawa J, Koike R, Sugihara T, Hagiyama H, Nishio J, Kohsaka H, et al. An autopsied case of chronic active Epstein–Barr virus infection complicated in systemic lupus erythematosus and antiphospholipid antibody syndrome. Nihon Rinsho Meneki Gakkai Kaishi. 2002;25:458–65.PubMedGoogle Scholar
  12. 12.
    Shirasaki F, Taniuchi K, Matsushita T, Hamaguhi Y, Takata M, Takehara K. Epstein–Barr virus-associated T-cell lymphoma: a case of eyelid swelling and intramuscular infiltration mimicking dermatomyositis. Br J Dermatol. 2002;147:1244–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Yoshiba F, Hagihara M, Tazume K, Ogawa Y, Kishi K, Higuchi A, et al. Complete resolution of severe chronic active Epstein–Barr virus infection by cultured, activated donor T lymphocyte infusion after nonmyeloablative stem cells allografting. Bone Marrow Transplant. 2003;32:107–10.PubMedCrossRefGoogle Scholar
  14. 14.
    Ogata M, Imamura T, Mizunoe S, Ohtsuka E, Kikuchi H, Nasu M. Natural killer cell-type body cavity lymphoma following chronic active Epstein–Barr virus infection. Am J Hematol. 2003;73:126–30.PubMedCrossRefGoogle Scholar
  15. 15.
    Shibuya A, Tsuchihashi T, Watanabe M, Nakazawa T, Takeuchi A, Sakurai K, et al. Severe chronic active Epstein–Barr virus infection associated with multiple necrotic lesions in the liver. Hepatol Res. 2003;25:447–54.PubMedCrossRefGoogle Scholar
  16. 16.
    Uchiyama T, Arai K, Yamamoto-Tabata T, Hirai K, Kishimoto K, Nakamura Y, et al. Generalized myositis mimicking polymyositis associated with chronic active Epstein–Barr virus infection. J Neurol. 2005;252:519–25.PubMedCrossRefGoogle Scholar
  17. 17.
    Kobayashi Z, Tsuchiya K, Takahashi M, Yokota O, Sasaki A, Bhunchet E, et al. An autopsy case of chronic active Epstein–Barr virus infection (CAEBV): distribution of central nervous system (CNS) lesions. J Neurol Sci. 2008;275:170–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Sonke GS, Ludwig I, van Oosten H, Baars JW, Meijer E, Kater AP, et al. Poor outcomes of chronic active Epstein–Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients. Clin Infect Dis. 2008;47:105–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Gotoh K, Ito Y, Shibata-Watanabe Y, Kawada J, Takahashi Y, Yagasaki H, et al. Clinical and virological characteristics of 15 patients with chronic active Epstein–Barr virus infection treated with hematopoietic stem cell transplantation. Clin Infect Dis. 2008;46:1525–34.PubMedCrossRefGoogle Scholar
  20. 20.
    Takano H, Nakagawa K, Ishio N, Daimon M, Kobayashi Y, Hiroshima K, et al. Active myocarditis in a patient with chronic active Epstein–Barr virus infection. Int J Cardiol. 2008;130:e11–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Imashuku S, Azuma N, Kanegane H, Kasahara Y. M-protein-positive chronic active Epstein–Barr virus infection: features mimicking HIV-1 infection. Int J Hematol. 2009;90:235–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Kimura H, Morishima T, Kanegane H, Ohga S, Hoshino Y, Maeda A, et al. Prognostic factors for chronic active Epstein–Barr virus infection. J Infect Dis. 2003;187:527–33.PubMedCrossRefGoogle Scholar
  23. 23.
    Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, et al. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin’s lymphoma. N Engl J Med. 1998;339:21–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Capizzi RL, Davis R, Powell B, Cuttner J, Ellison RR, Cooper MR, et al. Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia—a Cancer and Leukemia Group B Study. J Clin Oncol. 1988;6:499–508.PubMedGoogle Scholar
  25. 25.
    Ek T, Jarfelt M, Mellander L, Abrahamsson J. Proinflammatory cytokines mediate the systemic inflammatory response associated with high-dose cytarabine treatment in children. Med Pediatr Oncol. 2001;37:459–64.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  • Ayako Arai
    • 1
  • Ken-Ichi Imadome
    • 2
  • Yuko Watanabe
    • 1
  • Mayumi Yoshimori
    • 3
  • Takatoshi Koyama
    • 3
  • Takeharu Kawaguchi
    • 4
  • Chiaki Nakaseko
    • 4
  • Shigeyoshi Fujiwara
    • 2
  • Osamu Miura
    • 1
  1. 1.Department of HematologyTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Department of Infectious DiseasesNational Research Institute for Child Health and DevelopmentTokyoJapan
  3. 3.Department of Laboratory Molecular Genetics of HematologyTokyo Medical and Dental UniversityTokyoJapan
  4. 4.Department of HematologyChiba University HospitalChibaJapan

Personalised recommendations