What is the management of Epstein Barr virus (EBV) infection?

Management of Epstein-Barr Virus (EBV) Infection

For EBV infections, management should focus on supportive care for uncomplicated cases, while rituximab therapy is recommended for reactivated EBV with persistent symptoms, along with reduction of immunosuppression when possible. 1

Diagnosis Confirmation

• Confirm EBV infection through:
  • Heterophile antibody testing (Monospot)
  • EBV-specific antibody panel (VCA IgM, VCA IgG, EBNA IgG)
  • Quantitative EBV PCR viral load for suspected reactivation 1
• EBER-ISH (EBV-encoded RNA in situ hybridization) is essential for confirming EBV in lymphoma tissue (90% sensitivity, 95% specificity) 1

Management of Uncomplicated EBV Infection (Infectious Mononucleosis)

1. Supportive Care:

   • Rest and adequate hydration
   • NSAIDs for symptomatic relief (fever, sore throat, general fatigue)
     • May be particularly effective in patients with atopic predispositions 2
   • Acetaminophen for pain and fever

2. Activity Restrictions:

   • Avoid contact sports for at least 3-4 weeks due to risk of splenic rupture
   • Consider ultrasonic assessment of spleen size to guide return to physical activities 3

3. Monitoring for Complications:

   • Hepatitis: Monitor liver function tests in symptomatic cases 3
   • Splenic rupture: Most cases occur within 3 weeks of diagnosis 3
   • Airway compromise: Assess for tonsil enlargement causing respiratory difficulty 3

Management of Specific Complications

1. Airway Compromise:

   • Systemic corticosteroids during hospitalization for significant tonsillar hypertrophy 3

2. Hepatitis:

   • Usually self-limiting; monitor liver tests in symptomatic cases 3

3. Splenic Rupture:

   • Rare but serious complication
   • Immediate hospitalization and surgical consultation 3

Management of Reactivated EBV Infection

1. First-line Treatment:

   • Rituximab 375 mg/m² IV once weekly until EBV DNA-emia negativity (80% response rate)
   • Reduction of immunosuppression if possible 1

2. Monitoring:

   • Regular EBV DNA quantification
   • Validated fatigue assessment tools
   • Follow-up every 4-8 weeks to monitor symptoms and laboratory findings 1

Management of Chronic Active EBV Disease (CAEBV)

1. Diagnosis:

   • EBV DNA load ≥ 10,000 IU/mL in whole blood
   • Confirmation of EBV-infected T or NK cells 4

2. Treatment:

   • Hematopoietic stem cell transplantation (HSCT) is the only curative treatment
   • Chemotherapy to control disease activity before HSCT 4
   • First-line immunomodulative therapy with prednisolone and cyclosporine A with/without etoposide to control disease activity before transplantation 1

Special Considerations for Immunocompromised Patients

1. Monitoring:

   • More aggressive monitoring with regular EBV DNA-emia quantification
   • Watch for lymphadenopathy, hepatosplenomegaly, worsening cytopenias 1

2. Transplant Patients:

   • Pre-transplant: EBV serology for all recipients and donors
   • Post-transplant: Weekly EBV DNA monitoring for high-risk patients for at least 4 months 1

3. EBV-Associated Lymphoproliferative Disease:

   • Reduction of immunosuppression
   • Rituximab therapy
   • Consider EBV-specific cytotoxic T lymphocytes or donor lymphocyte infusion as second-line options 1

Important Caveats

• Standard antiviral drugs (acyclovir, valacyclovir) have limited efficacy against latent EBV 1, 5
• Acyclovir may inhibit oropharyngeal EBV replication but has minimal effect on clinical symptoms 5
• Consider CAEBV as a differential diagnosis in patients with persisting symptoms of infectious mononucleosis for more than 3 months 3
• Rising EBV DNA levels correlate with increased risk of lymphoproliferative disorders in immunocompromised patients (hazard ratio of 2.5) 1