From the Guidelines
To evaluate for Epstein-Barr virus (EBV) in a patient with cervical lymphadenopathy, the recommended blood tests include a heterophile antibody test (monospot) and EBV-specific antibody panel, with a focus on viral capsid antigen (VCA) IgM and IgG, early antigen (EA) antibodies, and Epstein-Barr nuclear antigen (EBNA) antibodies, as indicated by 1. The monospot test provides rapid results but has lower sensitivity in children and early infection. The EBV-specific antibody panel is crucial for distinguishing between acute, past, and reactivated EBV infections. Key points to consider when interpreting these tests include:
- Acute infection is characterized by positive VCA IgM, positive VCA IgG, and negative EBNA antibodies.
- Past infection shows negative VCA IgM, positive VCA IgG, and positive EBNA antibodies. Additional tests that may be valuable in the evaluation of EBV infection include:
- Complete blood count (CBC) with differential, as atypical lymphocytes are often present in EBV infection.
- Liver function tests to assess for hepatic involvement, which is common in EBV infections, as noted in 1 and 1. These tests collectively help distinguish between acute infection, past infection, or reactivation of EBV, which is important for proper management of cervical lymphadenopathy, and are supported by the guidelines outlined in 1.
From the Research
Blood Tests for Epstein-Barr Virus (EBV) Evaluation
To evaluate for Epstein-Barr virus (EBV) in a patient with cervical lymphadenopathy, several blood tests can be ordered. These tests are based on the detection of various antibodies and antigens associated with EBV infection.
- Immunoglobulin G (IgG) and IgM antibodies to the viral capsid antigen (VCA): These antibodies are key markers for diagnosing EBV infection. IgM antibodies to VCA indicate a recent or current infection, while IgG antibodies suggest a past infection 2.
- Heterophile antibodies: These antibodies are also used to diagnose EBV infection, particularly in the context of infectious mononucleosis. Their presence can help differentiate between primary EBV infection and reactivation 3.
- IgG antibodies to the EBV early antigen-diffuse (EA-D) and nuclear antigen (EBNA-1): These antibodies can help determine the stage of EBV infection. EA-D antibodies are often associated with reactivation, while EBNA-1 antibodies typically indicate a past infection 2.
- IgG avidity determination: This test measures the binding strength of IgG antibodies to EBV antigens. High avidity indices suggest a past infection, while low avidity indices indicate a recent infection 4.
Interpretation of EBV Serological Patterns
The interpretation of EBV serological patterns can be complex, with 32 possible patterns resulting from the combination of five markers (VCA IgG, VCA IgM, heterophile antibodies, EA-D IgG, and EBNA-1 IgG). However, only 12 of these patterns occur frequently enough to be considered interpretable 2. The use of easy-to-use tables and IgG avidity determination can help simplify the interpretation of EBV serological results 2, 4.
Additional Diagnostic Tools
In some cases, additional diagnostic tools such as real-time EBV PCR may be used to confirm primary EBV infections or reactivation, particularly when serological results are inconclusive 5. However, the utility of EA titers for diagnosing EBV reactivation has been questioned, and PCR may be a more reliable method for detecting EBV DNA in serum 5.