Signs and Symptoms of Mononucleosis
Mononucleosis typically presents with the classic triad of fever, pharyngitis (sore throat), and posterior cervical lymphadenopathy, most commonly affecting adolescents and young adults aged 15-24 years. 1
Classic Presenting Features
The hallmark symptoms include:
- Fever: Often high-grade, reaching up to 40°C, and may be persistent 2
- Pharyngitis: Severe sore throat is a dominant complaint 1
- Lymphadenopathy: Posterior cervical lymph node enlargement is characteristic; may also see auricular, marked generalized, or inguinal adenopathy 3, 1
- Profound fatigue: Significant and often debilitating exhaustion that distinguishes mononucleosis from simple pharyngitis 3, 4
Additional Common Manifestations
Beyond the classic triad, patients frequently develop:
- Hepatosplenomegaly: Enlargement of both liver and spleen occurs commonly 2, 3
- Palatal petechiae: Small hemorrhagic spots on the palate support the diagnosis 3
- Prolonged symptom duration: The illness typically lasts 2-3 weeks, though fatigue and myalgias may persist for several months 3, 5
Laboratory Abnormalities
Blood work reveals characteristic patterns that aid diagnosis:
- Atypical lymphocytosis: At least 20% atypical lymphocytes, or at least 10% atypical lymphocytes plus total lymphocytosis of at least 50% strongly supports the diagnosis 3, 1
- Elevated white blood cell count: With increased percentage of atypical lymphocytes 6, 2
- Mild liver enzyme elevations: Transaminases are often mildly elevated 2, 1
Less Common but Important Complications
Clinicians should remain vigilant for:
- Maculopapular rash: Particularly in patients inadvertently treated with antibiotics (especially ampicillin/amoxicillin) 2
- Neurological symptoms: Headache is common; rare severe complications including encephalitis can occur 2
- Hematologic complications: Anemia, thrombocytopenia, and neutropenia may develop in severe cases 2
- Respiratory complications: Interstitial pneumonitis can develop 2
- Peritonsillar abscess: Rare bacterial superinfection complication 7
- Splenic complications: Including splenic infarction, which may remain asymptomatic 7
Red Flag Symptoms Requiring Urgent Evaluation
Seek immediate medical attention for:
- Persistent high fever unresponsive to antipyretics 2
- Respiratory compromise or severe pharyngeal edema (may require corticosteroids) 3
- Signs of splenic rupture (abdominal pain, particularly left upper quadrant)
- Severe hematologic abnormalities
Clinical Pitfalls to Avoid
The heterophile antibody test (Monospot) has important limitations: False-negative results occur in approximately 10% of patients, are especially common in children younger than 10 years, and may be negative early in the illness (first week) 6, 1. The test has 87% sensitivity and 91% specificity 1. When clinical suspicion is high but heterophile testing is negative, consider EBV-specific antibody testing: VCA IgM presence (with or without VCA IgG) in the absence of EBNA antibodies indicates recent primary infection 6, 2.
Do not overlook alternative diagnoses when heterophile testing is negative, including cytomegalovirus, toxoplasmosis, HIV, adenovirus, or streptococcal pharyngitis 6, 3.