What are the symptoms, diagnosis, and treatment of Epstein-Barr Virus (EBV) infection?

Epstein-Barr Virus (EBV): Symptoms, Diagnosis, and Treatment

Epstein-Barr virus infection typically presents with fever, lymphadenopathy, and hepatosplenomegaly, requires serological testing for diagnosis, and is primarily managed with supportive care in immunocompetent individuals.

Symptoms

EBV infection commonly manifests as infectious mononucleosis with the following symptoms:

• Primary symptoms:

  • Fever (persistent or intermittent)
  • Lymphadenopathy (swollen lymph nodes)
  • Hepatosplenomegaly (enlarged liver and spleen)
  • Sore throat with exudative tonsillitis
  • Debilitating fatigue

• Additional symptoms:

  • Headache
  • Myalgia (muscle pain)
  • Arthralgia (joint pain)
  • Palatal petechial rash
  • Lymph node tenderness and pain 1

• Potential complications:

  • Hematological abnormalities
  • Digestive tract disorders
  • Neurological complications
  • Pulmonary issues
  • Ocular problems
  • Dermal manifestations
  • Cardiovascular disorders (including aneurysm and valvular disease) 1, 2
  • Splenic rupture (0.1-0.5% of cases) 2

Diagnosis

Laboratory Testing

1. Initial diagnostic approach:

   • Heterophile antibody test (Monospot): Detectable between 6-10 days after symptom onset, peaks at 2-3 weeks. Approximately 85% of mononucleosis cases can be diagnosed with this test 1, 3
   • Complete blood count: Elevated white blood cell count with increased percentage of atypical lymphocytes 1
   • Liver function tests: Often shows elevated liver enzymes 2

2. Serological testing (when heterophile test is negative):

   • EBV-specific antibodies:

     • Viral capsid antigen (VCA) IgM and IgG
     • Early antigen (EA) antibodies
     • Epstein-Barr nuclear antigen (EBNA) antibodies 1, 2

   • Interpretation:

     • Recent primary infection: VCA IgM (with or without VCA IgG) present, EBNA antibodies absent
     • Past infection (>6 weeks): EBNA antibodies present 1
     • Typical pattern in active infection: VCA-IgG ≥1:640 and EA-IgG ≥1:160 1

3. Molecular testing:

   • Quantitative PCR: Detects EBV DNA in peripheral blood
     • Active infection threshold: >10^2.5 copies/mg DNA in peripheral blood mononuclear cells 1, 2
   • In situ hybridization: Detects EBV-encoded RNAs (EBERs) in tissue samples 1

Special Considerations

• False-negative heterophile antibody results occur in approximately 10% of patients, especially in children younger than 10 years 1
• False-positive heterophile results may occur in patients with leukemia, pancreatic carcinoma, viral hepatitis, and CMV infection 1
• In immunocompromised patients, serological testing may have limited utility; PCR-based viral load assessment is preferred 2, 4

Treatment

Immunocompetent Patients

• Supportive care is the mainstay of treatment:

  • Adequate hydration
  • Rest
  • Antipyretics for fever
  • Analgesics for pain relief 2

• Activity restrictions:

  • Avoid contact sports for at least 3-4 weeks from symptom onset
  • Longer restrictions if splenomegaly persists to prevent splenic rupture 2

• Antiviral therapy:

  • Not routinely recommended for immunocompetent patients
  • Acyclovir, ganciclovir, and other antivirals have not shown efficacy against EBV in immunocompetent individuals 2

Immunocompromised Patients

• Monitoring:

  • Regular monitoring of EBV viral load 2
  • Prospective monitoring after high-risk transplantation 2

• Management strategies:

  • Reduction of immunosuppression when applicable 2
  • Rituximab for significant EBV DNA-emia without clinical symptoms 2
  • For EBV-associated post-transplant lymphoproliferative disorder (PTLD):
    • First-line: Reduce immunosuppression and rituximab
    • Second-line: EBV-specific cytotoxic T lymphocytes or donor lymphocyte infusion
    • Third-line: Chemotherapy ± rituximab 2

• In severe cases:

  • Consider ganciclovir or foscarnet despite limited evidence 2

Prevention

• No vaccine is currently available 5
• In transplant settings:
  • Pre-transplant EBV serology screening
  • Post-transplant monitoring of EBV DNA levels in high-risk patients 2
  • Consider antiviral prophylaxis for high-risk immunocompromised patients 2

Monitoring for Complications

• Regular follow-up to assess resolution of symptoms
• Monitor for development of lymphoproliferative disorders in immunocompromised patients
• Consider imaging studies (PET-CT) to assess disease extent in complicated cases 2