search for


Case Report
A Boy with Chronic Active EBV Infection Presented as Mosquito Bite Hypersensitivity Progressed to Fatal Hemophagocytic Lymphohistiocytosis due to NK Cell Neoplasm
Clin Pediatr Hematol Oncol 2019;26:95-8.
Published online October 31, 2019
© 2019 Korean Society of Pediatric Hematology-Oncology

Jin Ah Lee1, Seung Beom Han1,2, Nack Gyun Chung1, Jin Han Kang1,2, Myungshin Kim3,4 and Dae Chul Jeong1,2

1Department of Pediatrics, 2Vaccine Bio-research Institute, 3Department of Laboratory Medicine, 4Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
Correspondence to: Dae Chul Jeong
Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
Tel: +82-2-2258-6180
Fax: +82-2-537-4544
Received September 10, 2019; Revised October 7, 2019; Accepted October 17, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Chronic active Epstein-Barr virus (CAEBV) infection is characterized by recurrent infectious mononucleosis (IM)-like symptoms and an unusual pattern of anti-EBV antibodies. We report a boy with CAEBV who progressed to aggressive hemophagocytic lymphohistiocytosis (HLH) with NK cell neoplasm. A 19-year-old adolescent boy was admitted with fever and a history of recurrent IM-like symptoms following mosquito bites since the age of 6 years. His condition was diagnosed as CAEBV with atypical lymphocytosis and an unusual pattern of anti-EBV antibodies. His symptoms subsided during treatment with steroids and cyclosporine, although the EBV genome load kept increasing for several years. He was re-admitted after follow-up loss for 8 years, and his clinical and laboratory findings confirmed HLH and high titer of the EBV genome. Bone marrow analysis with flow cytometry showed hemophagocytosis with compatible NK cell neoplasm. He rapidly progressed to pulmonary infection and expired soon after. We conclude that hematopoietic stem cell transplantation may be a potential therapeutic modality for treating CAEBV before serious EBV manifestations.
Keywords: Chronic active Epstein-Barr virus infection, Hemophagocytic lymphohistiocytosis, NK cell neoplasm, Mosquito bite hypersensitivity
  1. Williams H, Crawford DH. Epstein-Barr virus: the impact of scientific advances on clinical practice. Blood 2006;107:862-9.
    Pubmed CrossRef
  2. Cohen JI, Kimura H, Nakamura S, Ko YH, Jaffe ES. Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008. Ann Oncol 2009;20:1472-82.
    Pubmed KoreaMed CrossRef
  3. Kimura H, Hoshino Y, Kanegane H, et al. Clinical and virologic characteristics of chronic active Epstein-Barr virus infection. Blood 2001;98:280-6.
    Pubmed CrossRef
  4. Okano M, Kawa K, Kimura H, et al. Proposed guidelines for diagnosing chronic active Epstein-Barr virus infection. Am J Hematol 2005;80:64-9.
    Pubmed CrossRef
  5. Kimura H. Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Rev Med Virol 2006;16:251-61.
    Pubmed CrossRef
  6. Sangueza-Acosta M, Sandoval-Romero E. Epstein-Barr virus and skin. An Bras Dermatol 2018;93:786-99.
    Pubmed KoreaMed CrossRef
  7. Tokura Y, Ishihara S, Tagawa S, Seo N, Ohshima K, Takigawa M. Hypersensitivity to mosquito bites as the primary clinical manifestation of a juvenile type of Epstein-Barr virus-associated natural killer cell leukemia/lymphoma. J Am Acad Dermatol 2001;45:569-78.
    Pubmed CrossRef
  8. Straus SE, Cohen JI, Tosato G, Meier J. NIH conference. Epstein-Barr virus infections: biology, pathogenesis, and management. Ann Intern Med 1993;118:45-58.
    Pubmed CrossRef
  9. Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD. The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol 2015;33:787-821.
    Pubmed CrossRef
  10. Kimura H, Hoshino Y, Hara S, et al. Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection. J Infect Dis 2005;191:531-9.
    Pubmed CrossRef
  11. Tokura Y, Matsuoka H, Koga C, et al. Enhanced T-cell response to mosquito extracts by NK cells in hypersensitivity to mosquito bites associated with EBV infection and NK cell lymphocytosis. Cancer Sci 2005;96:519-26.
    Pubmed CrossRef
  12. Sawada A, Inoue M, Kawa K. How we treat chronic active Epstein-Barr virus infection. Int J Hematol 2017;105:406-18.
    Pubmed CrossRef
  13. Savoldo B, Huls MH, Liu Z, et al. Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection. Blood 2002;100:4059-66.
    Pubmed CrossRef
  14. Kanegane H, Nomura K, Miyawaki T, Tosato G. Biological aspects of Epstein-Barr virus (EBV)-infected lymphocytes in chronic active EBV infection and associated malignancies. Crit Rev Oncol Hematol 2002;44:239-49.
    Pubmed CrossRef
  15. Kimura H, Morishima T, Kanegane H, et al. Prognostic factors for chronic active Epstein-Barr virus infection. J Infect Dis 2003;187:527-33.
    Pubmed CrossRef

October 2019, 26 (2)
Full Text PDF
Send to a friend

Cited By Articles
  • CrossRef (0)

Author ORCID Information
  • Dae Chul Jeong