Severe degenerative change of multiple organs mediated by chronic active Epstein–Barr virus infection with infected T-cell expansion

• Published in: International journal of hematology Vol. 87; no. 5; pp. 520 - 526
• Main Authors: Tokuhira, Michihide, Iizuka, Atsushi, Watanabe, Reiko, Sekiguchi, Naoya, Sato, Norihide, Chien, Chen-Kang, Sekiguchi, Yasunobu, Nemoto, Tomoe, Hanzawa, Kyoko, Tamaru, Jun-ichi, Itoyama, Shinji, Suzuki, Hiroshi, Takeuchi, Tsutomu, Mori, Shigehisa, Kizaki, Masahiro
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.06.2008; Springer; Springer Nature B.V
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Autopsies; Autopsy; Biological and medical sciences; Bone marrow; Brain; Case Report; CD3 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD56 antigen; CD8 antigen; Central nervous system; Cerebrospinal fluid; Chronic infection; Cyclophosphamide - administration & dosage; Doxorubicin - administration & dosage; Epstein-Barr virus; Epstein-Barr Virus Infections - cerebrospinal fluid; Epstein-Barr Virus Infections - drug therapy; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - pathology; Female; Hematologic and hematopoietic diseases; Hematology; Hemorrhage; Herpesvirus 4, Human; Humans; Hybridization; Immunohistochemistry; Infections; Infectious diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Liver; Liver - immunology; Liver - metabolism; Liver - pathology; Liver - virology; Lymph nodes; Lymphatic diseases; Lymphocytes; Lymphocytes T; Medical sciences; Medicine; Medicine & Public Health; Myocardium; Myocardium - immunology; Myocardium - metabolism; Myocardium - pathology; Nervous system; Oncology; Organs; Pericardium; Peripheral blood; Phenotypes; Prednisone - administration & dosage; RNA, Viral - metabolism; Spinal cord; Spinal Cord - immunology; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord - virology; Spleen; Spleen - immunology; Spleen - metabolism; Spleen - pathology; Spleen - virology; Vincristine - administration & dosage; Viral diseases; Viruses; Degenerative change; Hepatitis; Lymphoproliferative disorder; Encephalomyelitis; Chronic active Epstein–Barr virus infection; Gammaherpesvirinae; Chronic active Epstein-Barr virus infection, Lymphoproliferative disorder, Degenerative change; Nervous system diseases; Hematology; Herpesviridae; Hepatic disease; Hemopathy; Epstein Barr virus; Cerebral disorder; Virus; Infection; Chronic; Hepatitis, Encephalomyelitis; Lymphoproliferative syndrome; Viral disease; Central nervous system disease; T-Lymphocyte; Digestive diseases; Infected cell; Spinal cord disease; Expansion; Organ
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-008-0069-4

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.