Diagnosis (development)

Emma's case has received a diagnosis of Infectious mononucleosis (IM). Some further aspects of this diagnosis are explored below.

How is the diagnosis of IM made?

In the primary care setting a clinical diagnosis alone may be sufficient to allow adequate management of a patient. The possibility of HIV seroconversion illness should be considered, so this diagnosis is not missed. Clinical follow up is important, to ensure resolution of lymphadenopathy and other manifestations.

Infectious mononucleosis due to primary EBV infection, may be diagnosed in patients with atypical lymphocytosis with or without elevated transaminases, using the heterophile antibody (monospot) blood test. This tests for heterophile IgM antibodies, detected by the agglutination of horse red cells in a latex agglutination assay. The monospot is not a test for EBV-specific antibodies but for a surrogate marker for acute EBV infection. This is because primary EBV infection stimulates polyclonal antibody production by infected B-lymphocytes including a heterogeneous group of circulating heterophile (IgM) antibodies that cross-react with antigens found on sheep and horse red cells.

What other tests can be done to confirm the diagnosis when the heterophile antibody test is negative?

A definitive diagnosis of EBV infection can be made by testing for specific IgM and IgG antibodies against viral capsid antigens, early antigens, and EBV nuclear antigens (summarised in the table here):

 

EBV VCA IgM

EBV VCA IgG

EBV EBNA IgG

Acute infection

Detected

Detected/Not detected

Not detected

Previous infection

Not detected

Detected

Detected

EBV virus capsid antigen (VCA) IgM is usually detectable at clinical presentation with symptoms, and persists for several weeks. EBV IgM antibodies are not detected in association with chronic infection, so their presence is virtually diagnostic of current or recent primary EBV infection. EBV VCA IgG levels also appear during primary infection and generally persist for the rest of the patient’s life. EBNA (Epstein-Barr nuclear antigen) IgG is another EBV-specific IgG antibody. This IgG only appears in convalescence, or even several months later. The detection of EBV IgM and absence of EBNA IgG confirm primary EBV infection. The absence of Epstein-Barr VCA IgM and the detection of EBNA IgG indicate past infection.