What is the recommended approach for testing and managing a patient suspected of having mononucleosis?

Approach to Testing and Managing Suspected Mononucleosis

For patients with suspected infectious mononucleosis, the recommended diagnostic approach includes serological testing with a complete blood count with differential and heterophile antibody testing (Monospot), followed by EBV-specific antibody testing if the Monospot is negative but clinical suspicion remains high. 1, 2

Diagnostic Testing Algorithm

First-Line Testing

1. Complete Blood Count (CBC) with differential

   • Look for:
     • Lymphocytosis (>40% lymphocytes)
     • Atypical lymphocytes (>10% of total lymphocyte count)
     • Peripheral blood leukocytosis 3, 2

2. Heterophile Antibody Test (Monospot)

   • Widely used rapid screening test
   • Becomes detectable 6-10 days after symptom onset
   • Sensitivity: 87%, Specificity: 91% 1, 2
   • Important limitations:
     • False negatives common in children under 10 years
     • May be negative in the first week of illness
     • Can miss approximately 10% of EBV cases 1, 4

3. Liver Function Tests

   • Elevated liver enzymes increase clinical suspicion when heterophile test is negative 2

Second-Line Testing (if Monospot negative but clinical suspicion remains)

1. EBV-specific Antibody Panel (more sensitive and specific but more expensive)
   • Viral Capsid Antigen (VCA) IgM
   • Viral Capsid Antigen (VCA) IgG
   • Epstein-Barr Nuclear Antigen (EBNA) IgG 1, 5, 4

Interpretation of EBV Serological Patterns

Pattern	Interpretation
VCA IgM (+), VCA IgG (+), EBNA IgG (-)	Acute primary infection (within 6 weeks)
VCA IgM (-), VCA IgG (+), EBNA IgG (+)	Past infection (>6 weeks)
VCA IgM (-), VCA IgG (-), EBNA IgG (-)	No previous EBV infection

Management Approach

Supportive Care

1. Rest and hydration

   • Recommend rest as tolerated
   • Ensure adequate hydration 1, 3

2. Symptomatic relief

   • Antipyretics for fever
   • Analgesics for sore throat and pain 1

3. Activity restrictions

   • Avoid contact sports or strenuous exercise for at least 8 weeks or while splenomegaly is present
   • Use shared decision-making for determining return to activity 1, 3, 2, 6

Monitoring for Complications

1. Splenomegaly

   • Present in approximately 50% of cases
   • Risk of spontaneous splenic rupture (0.1-0.5% of cases)
   • Consider serial ultrasonography for athletes before return to play 3, 6

2. Hepatomegaly

   • Present in approximately 10% of cases 3

3. Persistent symptoms

   • If symptoms persist beyond 6 months, evaluate for chronic active EBV infection
   • Consider quantitative EBV viral load by PCR for persistent or severe symptoms 1

Special Considerations

1. Avoid unnecessary antibiotics

   • Only use if bacterial co-infection is confirmed 1

2. Immunocompromised patients

   • Higher risk for severe disease and lymphoproliferative disorders
   • May require closer monitoring 1, 2

Common Pitfalls and Caveats

1. Relying solely on heterophile antibody testing

   • Can miss up to 10% of cases, especially in young children 1, 4

2. Misinterpreting negative early test results

   • Heterophile antibodies may not be detectable in the first week 2, 4

3. Premature return to physical activity

   • Risk of splenic rupture if contact sports resumed too early 1, 3, 6

4. Overlooking mononucleosis-like illnesses

   • Consider other causes if EBV testing is negative (CMV, toxoplasmosis, HIV) 4

5. Unnecessary use of antivirals or corticosteroids

   • Routine use not recommended for uncomplicated cases 2

By following this structured approach to testing and management, clinicians can effectively diagnose and treat patients with suspected infectious mononucleosis while minimizing complications and unnecessary interventions.