Presenting Symptoms of Mononucleosis
Mononucleosis typically presents with the classic triad of fever (often reaching 40°C), tonsillar pharyngitis with sore throat, and cervical lymphadenopathy, accompanied by profound fatigue that can persist for weeks to months. 1, 2
Core Clinical Features
Primary Symptoms
- Fever: High-grade and persistent, potentially reaching 40°C (104°F), may be unresponsive to antipyretics in severe cases 1, 2
- Pharyngitis: Sore throat with tonsillar involvement is a hallmark feature 1, 3
- Lymphadenopathy: Swollen lymph nodes, particularly in the cervical region 1, 3
- Fatigue: Profound and characteristic, typically resolving within three months but can be prolonged 3
Physical Examination Findings
- Hepatosplenomegaly: Splenomegaly occurs in approximately 50% of cases, hepatomegaly in 10% 1, 2, 3
- Periorbital/palpebral edema: Typically bilateral, present in one-third of patients 3
- Maculopapular rash: Occurs in 10-45% of cases, usually widely scattered and erythematous, particularly common (up to 90%) in patients treated with antibiotics like ampicillin 2, 3
Laboratory Abnormalities
Blood work characteristically shows peripheral leukocytosis with lymphocytes comprising at least 50% of the white blood cell differential, and atypical lymphocytes constituting more than 10% of total lymphocyte count. 4, 2, 3
- Elevated white blood cell count with increased percentage of atypical lymphocytes 4
- Mild elevations in liver function tests are common 1
- Hematologic complications: Anemia, thrombocytopenia, and neutropenia can occur in severe cases 1, 2
Less Common but Important Manifestations
Neurological Symptoms
Other Complications
- Myalgia and arthralgia may be present 2
- Interstitial pneumonitis can develop in some cases 1, 2
- Cardiovascular disorders: Including coronary aneurysms or valvular disease in chronic cases 2
- Digestive tract, pulmonary, ocular, and dermal complications are possible 2
Age-Related Variations
In children younger than 10 years, primary EBV infection is usually asymptomatic or presents with nonspecific symptoms, making diagnosis more challenging. 5
In adults over age 40, the presentation differs significantly: fever remains nearly universal, but lymphadenopathy, pharyngitis, splenomegaly, lymphocytosis, and atypical lymphocytes are often absent. Jaundice and hepatomegaly occur more commonly in older patients, creating diagnostic confusion with lymphoma, leukemia, or biliary obstruction. 6
Critical Pitfalls to Avoid
- Heterophile antibody (Monospot) testing has approximately 10% false-negative rate, particularly early in infection (before 6-10 days) and in children under 10 years 4, 2, 7
- When clinical suspicion remains high despite negative heterophile testing, EBV-specific serologic testing (VCA IgM, VCA IgG, and EBNA antibodies) should be performed 4, 7
- The presence of VCA IgM without EBNA antibodies indicates recent primary infection, while EBNA antibodies indicate infection more than 6 weeks prior 4, 7
- Consider alternative diagnoses when tests are negative, including CMV infection, HIV, Toxoplasma gondii, and adenovirus infection 4, 7