title: Severe degenerative change of multiple organs mediated by chronic active Epstein-Barr virus infection with infected T-cell expansion.
abstract: We here report the case of a young Japanese woman diagnosed with chronic active Epstein-Barr virus (EBV) infection. Intensive therapy with the CHOP regimen was partially able to control virus expansion, but various central nervous system symptoms appeared and gradually progressed. EBV-encoded RNA, detected using in situ hybridization, disclosed the presence of EBV in liver and bone marrow tissue, and real-time PCR revealed the presence of EBV in the cerebrospinal fluid (CSF) and serum. CD3+CD4+CD8-CD56- T-cell expansion in the peripheral blood (PB) and CSF was also observed. Atrophic brain changes were progressive, and the patient died of central nervous system disturbance and pulmonary hemorrhage a year after diagnosis. Autopsy revealed that EBV-infected T lymphocytes with a phenotype similar to those seen in PB and CSF had infiltrated multiple organs: the lymph nodes, bone marrow, endocardium, pericardium, myocardium, spleen, liver, and spinal cord. There have been few previous reports of severe degenerative changes in the myocardium, liver, and spinal cord in patients with EBV infection. Although EBV occasionally infiltrates the central nervous system and brain, atrophic changes mediated by EBV are rare. The autopsy results of this case suggest the possibility of EBV-mediated, severe degenerative changes in multiple organs.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan. tokuhira@saitama-med.ac.jp.
authors.forename: Michihide
authors.initials: M
authors.lastname: Tokuhira
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iizuka
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Saitama Medical Center, Kawagoe, Saitama, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sekiguchi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Sato
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Chen-Kang
authors.initials: CK
authors.lastname: Chien
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Sekiguchi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hanzawa
authors.affiliation: Department of Pathology, Saitama Medical Center, Kawagoe, Saitama, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Tamaru
authors.affiliation: Department of Pathology, Saitama Medical Center, Kawagoe, Saitama, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Itoyama
authors.affiliation: Transfusion Center, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Saitama Medical Center, Kawagoe, Saitama, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Mori
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical Center, 1981 Kamodatsujido, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kizaki
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001344:Autopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D020031:Epstein-Barr Virus Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011241:Prednisone / Q000008:administration & dosage; D012367:RNA, Viral / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D012367:RNA, Viral; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone