What is the diagnosis and treatment for Epstein Barr virus (EBV) infection?

Diagnosis and Treatment of Epstein-Barr Virus (EBV) Infection

EBV infection diagnosis requires specific serological testing and treatment is primarily supportive, with targeted interventions only for severe complications or in immunocompromised patients. 1

Diagnostic Approach

Primary EBV Infection (Infectious Mononucleosis)

• Diagnosis is made through a combination of:
  • EBV-specific antibody panel:
    • Primary infection: VCA IgM positive, possible VCA IgG positive, EBNA antibodies negative 1
    • Past infection: VCA IgG positive, EBNA antibodies positive, VCA IgM negative 1
  • Heterophile antibody testing (Monospot) - positive in approximately 85% of mononucleosis cases 2

Chronic Active EBV Infection (CAEBV)

CAEBV must fulfill all three criteria 3:

1. Persistent or recurrent infectious mononucleosis-like symptoms
2. Unusual pattern of anti-EBV antibodies with raised anti-VCA and anti-EA, and/or detection of increased EBV genomes in affected tissues
3. Chronic illness that cannot be explained by other known disease processes

Laboratory Testing

• Quantitative EBV PCR viral load testing - especially important for:
  • Immunocompromised patients
  • Suspected chronic active infection
  • Monitoring for reactivation 1
• Additional testing for CAEBV may include 3:
  • PCR (quantitative) - >102.5 copies/mg DNA in peripheral blood mononuclear cells
  • In situ hybridization (EBERs)
  • Immunofluorescence for EBNA, LMP
  • Southern blotting (for EBV clonality)

Treatment Approach

Uncomplicated EBV Infection

• Supportive care is the mainstay of treatment 1:
  • Adequate hydration
  • Rest
  • Analgesics/antipyretics for symptom relief
• Standard antiviral drugs (acyclovir, ganciclovir) have limited efficacy against EBV and are not routinely recommended 1, 4

Severe EBV Infection or Complications

• For EBV-associated hemolytic anemia or biliary stasis: supportive care and cold avoidance 5
• For severe cases in immunocompromised patients 1:
  • Reduction of immunosuppression if possible
  • Consider antiviral therapy (ganciclovir or foscarnet) despite limited evidence
  • Rituximab (375 mg/m² IV weekly until EBV DNA-emia negativity) for EBV reactivation
  • Cellular therapy options for refractory cases:
    • EBV-specific cytotoxic T lymphocytes
    • Donor lymphocyte infusion

Monitoring in High-Risk Patients

• Weekly EBV DNA monitoring by quantitative PCR is recommended for:
  • Transplant recipients
  • Patients on significant immunosuppressive therapy 1
• Continue monitoring for at least 4 months post-transplant 1

Special Considerations

• No EBV vaccine is currently available 1
• Risk of EBV-related lymphoproliferative disease is significantly higher in immunocompromised patients 1, 6
• Consider imaging (preferably PET-CT) and possibly biopsy if EBV-associated lymphoproliferative disease is suspected 1
• In fulminant mononucleosis, combination therapy with acyclovir and corticosteroids may provide symptomatic relief 4

Common Pitfalls to Avoid

• Don't rely solely on heterophile antibody tests, as they can be negative in approximately 15% of infectious mononucleosis cases 2
• Don't routinely prescribe antivirals for uncomplicated EBV infections 1, 4
• Don't overlook potential complications such as splenic rupture, hemolytic anemia, and biliary stasis 5
• Don't forget to consider EBV in patients with elevated transaminases, direct hyperbilirubinemia, or evidence of hemolytic anemia with nonspecific viral symptoms 5
• Be aware that the incubation period for symptomatic primary EBV infection is unusually long (approximately six weeks) 7