Table 2.
(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].