Skip to main content
. 2021 Jan 15;9(1):180. doi: 10.3390/microorganisms9010180

Table 2.

Diagnostic criteria of Chronic active Epstein-Barr virus infection.

(1) Sustained or recurrent infectious mononucleosis-like symptoms persist for more than 3 months
(2) Elevated EBV genome load in the peripheral blood (PB) or the tissue lesion
(3) EBV infection of T or NK cells in the affected tissues or the PB
(4) Exclusion of other possible diagnoses: primary infection of EBV (infectious mononucleosis), autoimmune diseases, congenital immunodeficiencies, HIV, and other immunodeficiencies requiring immunosuppressive therapies or underlying diseases with potential immunosuppression
Patients who fulfilled criteria (1)–(4) were diagnosed with CAEBV

Supplementary explanation: (1) Infectious mononucleosis -like symptoms generally include fever, swelling of lymph nodes, and hepatosplenomegaly; additional complications include hematological, gastroenterological, neurological, pulmonary, ocular, dermal, and/or cardiovascular disorders (including aneurysm and valvular disease), which have mostly been reported in patients with IM. EBV-HLH accompanied by primary infection of EBV and HV, whose symptoms are limited to those in the skin, should be excluded. Even if EBV-HLH or EBV-positive T- or NK-cell lymphoma/leukemia develops during the disease course, the original diagnosis of CAEBV does not change. (2) A standard for elevated EBV DNA load by quantitative PCR in the PB is more than 102.5 copies/μg DNA. (3) For detection of EBV-infected cells, it is recommended to perform a combination analysis of detecting the phenotypes of the infected cells (immune fluorescent staining, immune histological staining, magnetic bead sorting) and detecting EBV (EBNA staining, EBV-encoded small RNA in situ hybridization, PCR for EBV DNA). (4)Patients who were diagnosed with congenital immune deficiencies, autoimmune diseases, collagen diseases; patients who were pathologically diagnosed with malignant lymphomas (Hodgkin lymphoma; extranodal NK/T-cell lymphoma, nasal type (ENKL); angioimmunoblastic T-cell lymphoma; peripheral T-cell lymphoma (PTCL); aggressive NK-cell leukemia (ANKL)); and patients who were diagnosed with an iatrogenic immunosuppressive condition, either concurrently or prior to CAEBV diagnosis, were also excluded from CAEBV [17].