Chronic Active Epstein-Barr Virus Disease.

Hiroshi Kimura,Jeffrey I Cohen

doi:10.3389/fimmu.2017.01867

Abstract

Chronic active Epstein–Barr virus (CAEBV) disease is a rare disorder in which persons are unable to control infection with the virus. The disease is progressive with markedly elevated levels of EBV DNA in the blood and infiltration of organs by EBV-positive lymphocytes. Patients often present with fever, lymphadenopathy, splenomegaly, EBV hepatitis, or pancytopenia. Over time, these patients develop progressive immunodeficiency and if not treated, succumb to opportunistic infections, hemophagocytosis, multiorgan failure, or EBV-positive lymphomas. Patients with CAEBV in the United States most often present with disease involving B or T cells, while in Asia, the disease usually involves T or NK cells. The only proven effective treatment for the disease is hematopoietic stem cell transplantation. Current studies to find a cause of this disease focus on immune defects and genetic abnormalities associated with the disease.

Highlights

Primary infection of adolescents and young adults often results in infectious mononucleosis with fever, lymphadenopathy, and sore throat [1]
A large clonal or oligoclonal expansion of CD8 cells is observed during infectious mononucleosis [6]
Former definitions required elevated levels of antibody to EBV viral capsid or early antigen in the blood [18]; we have found that elevated levels of EBV DNA in the blood are more specific for Chronic active Epstein–Barr virus (CAEBV) than elevated levels of EBV antibodies

Summary

INTRODUCTION

Primary infection of adolescents and young adults often results in infectious mononucleosis with fever, lymphadenopathy, and sore throat [1]. EBV is present in circulating B cells, and the level of EBV DNA is elevated in the blood for the first month of the illness Both the innate immune response (especially NK cells) and the acquired immune response (virus-specific CD4 and CD8 cells) have a critical role in clearing the infection [2]. Others develop a more chronic course with persistent or intermittent infectious mononucleosis-like symptoms including fever, persistent lymphadenopathy, splenomegaly, and EBV hepatitis. These patients are unable to control EBV infection and have infiltration of tissues by EBV positive T, NK, or less often B cells. Unlike healthy persons with infectious mononucleosis, patients with CAEBV disease often have low numbers of EBV-specific CD8 cells [10]. Many have extremely high levels of antibodies to EBV lytic proteins and lack antibody to EBNA1 [13]

CAEBV DEFINITION AND FEATURES

CAEBV IN THE UNITED STATES

CAEBV IN ASIA

Hydroa vacciniforme

Findings

TREATMENT AND PROGNOSIS