From the Guidelines
Mononucleosis is typically diagnosed using a combination of laboratory tests, including the heterophile antibody test (Monospot), EBV-specific serologic testing, complete blood count (CBC), and liver function tests. To diagnose mononucleosis, the following laboratory tests are recommended:
- Heterophile antibody test (Monospot) to detect heterophile antibodies produced in response to Epstein-Barr virus (EBV) infection 1
- EBV-specific serologic testing, including IgM antibodies to viral capsid antigen (VCA-IgM) and IgG antibodies to VCA and Epstein-Barr nuclear antigen (EBNA), to determine the stage of infection 1
- Complete blood count (CBC) to show an elevated white blood cell count with a high percentage of atypical lymphocytes (more than 10%), which is characteristic of mono 1
- Liver function tests to detect mild liver inflammation with elevated liver enzymes, which is often caused by mono 1 If EBV tests are negative but mono is still suspected, testing for cytomegalovirus (CMV) may be performed, as it can cause a similar illness 1. It's essential to note that the Monospot test may be negative early in the illness or in children under 4 years old, and false-negative results may occur in approximately 10% of patients 1. In such cases, EBV-specific serologic testing can provide a definitive diagnosis 1.
From the Research
Laboratory Tests for Diagnosing Mononucleosis
To diagnose mononucleosis, several laboratory tests can be used, including:
- Complete blood count (CBC) with differential to assess for greater than 40% lymphocytes and greater than 10% atypical lymphocytes 2
- Rapid heterophile antibody test, which has a sensitivity of 87% and specificity of 91% 2
- Epstein-Barr viral capsid antigen-antibody testing, which is more sensitive and specific but more expensive and takes longer to process than the rapid heterophile antibody test 2, 3
- Serologic testing for antibodies to viral capsid antigens, which is recommended when confirmation of the diagnosis is required in patients with a negative mono-spot test 4
- Testing for specific IgM and IgG antibodies against viral capsid antigens, early antigens, and EBV nuclear antigen proteins 5
Interpretation of Laboratory Results
When interpreting laboratory results, it is essential to consider the following:
- The heterophile antibody test can have a false-negative result in children younger than five years and in adults during the first week of illness 2
- The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result 2
- The diagnosis of infectious mononucleosis may be made when IgG-VCA, IgM-VCA, and anti-D antibodies are present and EBNA antibodies are absent 3
- The lymphocyte to white cell count ratio is not sufficient to diagnose or exclude infectious mononucleosis 6