What are the diagnostic approaches and treatment options for a patient presenting with signs and symptoms of Epstein-Barr Virus (EBV) infection?

Diagnostic Approaches and Treatment Options for Epstein-Barr Virus (EBV) Infection

The diagnostic approach for EBV infection should include serological testing with EBV-specific antibodies (VCA IgG/IgM, EA, EBNA), PCR-based viral detection, and clinical evaluation of characteristic symptoms including fever, lymphadenopathy, and hepatosplenomegaly. Treatment is primarily supportive care, with specific interventions reserved for severe complications.

Clinical Presentation

Common Signs and Symptoms

• Fever (persistent or intermittent)
• Lymphadenopathy (particularly cervical)
• Hepatosplenomegaly
• Fatigue and malaise
• Sore throat
• Headache
• Myalgia and arthralgia 1

Less Common Manifestations

• Hematological complications (anemia, thrombocytopenia)
• Neurological symptoms
• Respiratory symptoms
• Dermatological manifestations
• Cardiovascular disorders (including aneurysms and valvular disease) 1
• Splenic rupture (rare but potentially life-threatening complication, occurring in 0.5% of cases) 2

Diagnostic Approach

Laboratory Testing

1. Serological Testing (first-line approach):

   • EBV-specific antibody panel:
     • VCA IgM and IgG (positive in acute infection)
     • EA-IgG (often elevated in acute infection)
     • EBNA IgG (typically negative in acute infection, appears weeks to months later) 1, 3
   • Typical pattern in acute infection: Positive VCA IgM, positive VCA IgG, negative EBNA IgG 3
   • Heterophile antibody tests (monospot) have suboptimal sensitivity and specificity 1

2. Molecular Testing:

   • PCR detection of EBV DNA in blood (high sensitivity and specificity)
   • Quantitative PCR for viral load assessment (>10^2.5 copies/mg DNA in peripheral blood mononuclear cells suggests active infection) 1

3. Additional Laboratory Findings:

   • Elevated liver enzymes
   • Lymphocytosis with atypical lymphocytes
   • Elevated inflammatory markers

Imaging

• Abdominal ultrasound or CT scan if complications such as splenic involvement are suspected 2
• PET-CT for suspected lymphoproliferative disorders or to assess disease extent in complicated cases 1

Tissue Diagnosis (when indicated)

• Lymph node or tissue biopsy with:
  • EBER in situ hybridization (gold standard for tissue diagnosis)
  • Immunohistochemistry for viral antigens (LMP1, EBNA1)
  • Flow cytometry 1

Treatment Options

Uncomplicated EBV Infection

• Supportive care is the mainstay of treatment:
  • Adequate hydration
  • Rest
  • Antipyretics and analgesics for symptom control
  • Avoidance of contact sports (due to risk of splenic rupture)

Management of Complications

1. Airway Obstruction:

   • Corticosteroids may be indicated for significant tonsillar hypertrophy causing airway compromise 1

2. Splenic Rupture:

   • Emergency surgical intervention (splenectomy) is typically required 2
   • Close monitoring for left hypochondrial pain, Kehr's sign (referred pain to left shoulder), and hemodynamic instability

3. Severe Hepatitis:

   • In severe cases, valganciclovir has been used with some success 4
   • Corticosteroids may be considered in severe cases

4. Hemophagocytic Lymphohistiocytosis (HLH):

   • High-dose corticosteroids
   • Intravenous immunoglobulins
   • Early recognition is crucial for favorable outcomes 5

5. Chronic Active EBV Infection (CAEBV):

   • Diagnosis requires:
     • Persistent/recurrent infectious mononucleosis-like symptoms
     • Unusual pattern of anti-EBV antibodies or increased EBV genomes in tissues
     • Chronic illness not explained by other diseases 1
   • Treatment often requires specialized hematology consultation

6. Post-Transplant Lymphoproliferative Disorders (PTLD):

   • Rituximab is recommended for treatment 1
   • Reduction of immunosuppression when possible 1

Special Considerations

Immunocompromised Patients

• More aggressive monitoring and earlier intervention may be necessary
• For transplant recipients:
  • Pre-transplant EBV serology screening
  • Post-transplant monitoring of EBV DNA levels in high-risk patients
  • Rituximab may be used for treatment or prophylaxis of EBV reactivation 1

Co-infections

• Consider testing for other viral infections (CMV, HIV) that may present similarly or co-exist 6
• PCR-based viral panels are recommended to diagnose active viral infections and reactivations 1

Prevention

• No specific prevention strategies for primary EBV infection
• For immunocompromised patients:
  • Consider antiviral prophylaxis in high-risk settings
  • EBV serology matching for transplant donors/recipients when possible 1

Follow-up

• Most patients recover completely within 2-4 weeks
• Monitor for resolution of symptoms and laboratory abnormalities
• Extended follow-up may be necessary for patients with severe complications or chronic active infection