From the Guidelines
Infectious mononucleosis should be diagnosed through a combination of clinical evaluation and laboratory testing, starting with a complete blood count (CBC) to identify lymphocytosis with atypical lymphocytes, followed by a heterophile antibody test (Monospot), and if necessary, specific EBV antibody tests such as VCA-IgM and EBNA-IgG for definitive diagnosis. The diagnosis typically begins with recognizing the classic triad of symptoms: fever, sore throat, and lymphadenopathy, often accompanied by fatigue 1. A healthcare provider will first perform a physical examination looking for these symptoms along with possible splenomegaly or hepatomegaly.
Some key points to consider in the diagnosis include:
- An elevated white blood cell count with an increased percentage of atypical lymphocytes is common in EBV-associated mononucleosis 1.
- Heterophile antibodies usually become detectable between the sixth and tenth day following symptom onset, but false-negative results are obtained in approximately 10% of patients, especially in children younger than 10 years 1.
- When rapid Monospot or heterophile test results are negative, additional laboratory testing may be considered to differentiate EBV infection from a mononucleosis-like illness caused by other pathogens, and EBV antibody testing for IgG and IgM to viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA) are recommended 1.
- The presence of VCA IgM (with or without VCA IgG) antibodies in the absence of antibodies to EBNA indicates recent primary infection with EBV, while the presence of EBNA antibodies indicates infection more than 6 weeks from the time of the sample and therefore not likely implicating EBV as a cause 1.
Liver function tests may also be performed as mild liver inflammation is common in infectious mononucleosis. Diagnosis is important because symptoms can mimic other conditions like streptococcal pharyngitis, and proper identification helps avoid unnecessary antibiotic treatment and allows appropriate management of potential complications like splenic rupture.
From the Research
Diagnostic Criteria for Infectious Mononucleosis
The diagnosis of infectious mononucleosis can be made based on a combination of clinical and laboratory findings. The clinical manifestations of infectious mononucleosis include:
- Fever
- Tonsillar pharyngitis
- Lymphadenopathy
- Fatigue
- Periorbital and/or palpebral edema
- Splenomegaly and hepatomegaly
- Skin rash
Laboratory Tests for Infectious Mononucleosis
The laboratory tests used to diagnose infectious mononucleosis include:
- Complete blood count (CBC) with differential to assess for lymphocytosis and atypical lymphocytes 2
- Rapid heterophile antibody test, such as the monospot test, to detect serum heterophile antibodies 3, 2, 4
- Epstein-Barr viral capsid antigen-antibody testing for confirmation of diagnosis in patients with a negative monospot test 3, 2
- Liver function tests to assess for elevated liver enzymes, which can increase clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result 2
Interpretation of Laboratory Results
The interpretation of laboratory results for infectious mononucleosis includes:
- The presence of greater than 40% lymphocytes and greater than 10% atypical lymphocytes on CBC with differential is suggestive of infectious mononucleosis 2
- A positive rapid heterophile antibody test result is indicative of infectious mononucleosis, but a negative result does not rule out the diagnosis 2
- The presence of elevated liver enzymes and lymphocytosis can increase clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result 2
Differential Diagnosis
The differential diagnosis for infectious mononucleosis includes:
- Cytomegalovirus (CMV) infection, which can present with similar symptoms and laboratory findings 5, 6
- Human immunodeficiency virus (HIV) infection, which can present with similar symptoms and laboratory findings 4
- Other viral and bacterial infections that can cause similar symptoms and laboratory findings 4