Infectious Mononucleosis: Symptoms and Treatment
Infectious mononucleosis presents with a classic triad of fever, tonsillar pharyngitis, and lymphadenopathy, with treatment being primarily supportive as antiviral therapy does not improve outcomes in otherwise healthy individuals. 1, 2
Clinical Symptoms
Cardinal Features
- Fever reaching as high as 40°C (104°F), typically lasting 1-2 weeks 3, 2
- Tonsillar pharyngitis with severe sore throat 2, 4
- Lymphadenopathy, particularly posterior cervical and auricular nodes 2, 5
- Profound fatigue that may persist for weeks to months after acute infection resolves 2, 5
Common Physical Findings
- Splenomegaly occurs in approximately 50% of cases 2
- Hepatomegaly occurs in approximately 10% of cases 2
- Periorbital or palpebral edema (typically bilateral) in one-third of patients 2
- Palatal petechiae 5
Skin Manifestations
- Maculopapular rash occurs in 10-45% of cases, particularly common if antibiotics (especially ampicillin) are administered 3, 2
Laboratory Abnormalities
- Peripheral blood leukocytosis with lymphocytes comprising at least 50% of the white blood cell differential 6, 2
- Atypical lymphocytosis constituting more than 10% of total lymphocyte count 1, 2
- Mild elevations in liver function tests 3
Diagnostic Approach
Initial Testing
- Heterophile antibody test (Monospot) is the most widely used initial diagnostic test, becoming positive between the 6th and 10th day after symptom onset 1, 6
- Test characteristics: 87% sensitivity and 91% specificity 6
Important Diagnostic Pitfalls
- False-negative heterophile results occur in approximately 10% of patients, especially common in children younger than 10 years and early in infection 1, 6
- False-positive results may occur in patients with leukemia, pancreatic carcinoma, viral hepatitis, or CMV infection 1, 6
Confirmatory Testing When Heterophile is Negative
When clinical suspicion remains high despite negative heterophile test, obtain EBV-specific antibody testing 1, 6:
- VCA IgM (with or without VCA IgG) in the absence of EBNA antibodies indicates recent primary EBV infection 1, 6
- EBNA antibodies indicate infection occurred more than 6 weeks prior, making EBV unlikely as the current cause 1
- EBNA antibodies develop 1-2 months after primary infection and persist for life 1
Differential Diagnosis to Consider
When testing is negative or atypical, consider 1, 6:
- Cytomegalovirus (CMV) infection
- HIV infection (acute retroviral syndrome)
- Toxoplasma gondii infection
- Adenovirus infection
- Streptococcal pharyngitis
Treatment
Standard Management for Immunocompetent Patients
Aciclovir therapy does not ameliorate the course of infectious mononucleosis in otherwise healthy individuals and is not recommended. 1, 6
Supportive Care
- Adequate hydration, analgesics, and antipyretics 5
- Activity modification guided by patient's energy level; enforced bed rest is not necessary 5
- Avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly persists due to risk of splenic rupture 2, 5
Corticosteroid Use
- Corticosteroids are NOT recommended for routine treatment 6, 5
- May be indicated for specific complications: airway obstruction or severe pharyngeal edema 1, 5
Special Populations: Immunocompromised Patients
For patients on immunomodulator therapy with suspected primary EBV infection 1, 6:
- Reduce or discontinue immunomodulator therapy if possible 1, 6
- In severe primary EBV infection, antiviral therapy with ganciclovir or foscarnet may be considered despite lack of supporting evidence 1, 6
- Seek specialist consultation for suspected lymphoproliferative disease 1, 6
Critical Complications to Monitor
Life-Threatening Complications
- Spontaneous splenic rupture occurs in 0.1-0.5% of patients and is potentially fatal 2
- Splenic infarction can occur due to transient hypercoagulable state or splenomegaly 7
- Airway obstruction from severe pharyngeal edema 1
- Peritonsillar abscess (rare) 7
Long-Term Sequelae
- Chronic fatigue syndrome (infectious mononucleosis is a recognized risk factor) 2
- Fatigue, myalgias, and increased sleep requirements may persist for several months after acute infection resolves 5