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.

An autopsy case of chronic active Epstein–Barr virus infection (CAEBV): Distribution of central nervous system (CNS) lesions

“…To date, CNS involvement in patients with CAEBV has hardly been reported [6][7][8][9]. Although two autopsy cases of CAEBV with CNS lesions have been reported [8,9], details of neuropathological findings were not described.…”

“…Although two autopsy cases of CAEBV with CNS lesions have been reported [8,9], details of neuropathological findings were not described.…”

Hepatocellular apoptosis associated with cytotoxic T/natural killer‐cell infiltration in chronic active EBV infection

“…Patients with EBV infection often present with liver disturbance. While IM is often accompanied by mild hepatitis, several groups have reported that patients with CAEBV progressed to hepatic failure, 2,18 and that 7.5–33% of patients with CAEBV died due to hepatic failure 20,21 …”

“…EBV is a ubiquitous herpes virus that usually causes asymptomatic infection during early childhood. Infectious mononucleosis (IM) is a symptomatic acute EBV infection occurring more often in adolescents and young adult than in children, and is usually a benign self‐limiting disease 1,2 . It is thought that EBV remains latent for life in the B cells of normal hosts after primary infection, 3,4 and that T‐cell immunity, including immunity against cytotoxic T cells and natural killer (NK) cells, primarily regulates the proliferation of EBV‐infected B cells 1,3 …”

“…Chronic active EBV infection (CAEBV) is clinically characterized by persistent or recurrent IM‐like symptoms: fever, lymphadenitis, rash, hepatosplenomegaly, and hepatitis 2,5 . The clinical course of CAEBV varies.…”