What are the signs and symptoms of Epstein-Barr Virus (EBV) infection?

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Signs and Symptoms of Epstein-Barr Virus (EBV) Infection

EBV infection commonly presents with prolonged or intermittent fever, lymphadenopathy, and hepatosplenomegaly, often accompanied by debilitating fatigue, sore throat, lymph node tenderness, headache, myalgia, and arthralgia. 1

Primary EBV Infection (Infectious Mononucleosis)

Common Symptoms

  • Fever: Often persistent for 1-2 weeks
  • Sore throat: Typically severe and exudative
  • Lymphadenopathy: Primarily cervical, but can be generalized
  • Fatigue: Often profound and may persist for weeks to months
  • Hepatosplenomegaly: Present in many cases

Additional Clinical Manifestations

  • Pharyngitis: Often with tonsillar enlargement and exudates
  • Palatal petechiae: Characteristic finding
  • Periorbital edema: May be present
  • Maculopapular rash: Occurs in 5-15% of cases, more common if ampicillin or amoxicillin is administered 2
  • Splenomegaly: Present in up to 50% of cases, with risk of splenic rupture 2

Ocular Manifestations

  • Follicular conjunctivitis: Typically unilateral
  • Ipsilateral lymphadenopathy
  • Hemorrhagic conjunctivitis: With subconjunctival hemorrhage and periorbital edema
  • Conjunctival nodules: Uncommon finding 1

Laboratory Findings

  • Lymphocytosis: With atypical lymphocytes (>10% of white blood cells)
  • Mild to moderate elevation of liver enzymes: Common
  • Positive heterophile antibody test (Monospot): Approximately 85% detection rate, peaks 2-3 weeks after symptom onset 2
  • Elevated EBV-specific antibodies: VCA IgM and IgG, EA antibodies 2

Age-Related Differences

  • Children under 10 years: Usually asymptomatic or with nonspecific symptoms
  • Adolescents and young adults: Classic infectious mononucleosis syndrome
  • Adults: May have more severe presentations 3

Chronic Active EBV Infection (CAEBV)

CAEBV is characterized by:

  • Persistent or recurrent infectious mononucleosis-like symptoms lasting more than 6 months
  • Unusual pattern of anti-EBV antibodies: Elevated anti-VCA (≥1:640) and anti-EA (≥1:160) 1
  • High viral load: >10^2.5 copies/mg DNA in peripheral blood mononuclear cells 1, 2
  • Chronic illness not explained by other known diseases 1

Complications of CAEBV

  • Hematological disorders: Including hemophagocytic lymphohistiocytosis
  • T-cell or NK-cell lymphoproliferative disorders/lymphomas
  • Skin lesions: Including hypersensitivity to mosquito bites
  • Cardiovascular disorders: Coronary aneurysms or valvular disease 1

Rare Complications of EBV Infection

  • Cholestatic hepatitis: Presenting with jaundice and elevated liver enzymes 4
  • Hemophagocytic lymphohistiocytosis (HLH): Characterized by fever, hepatosplenomegaly, cytopenias, hyperferritinemia, and hypertriglyceridemia 4
  • Neurological complications: Including encephalitis, meningitis, Guillain-Barré syndrome
  • Airway obstruction: Due to severe tonsillar hypertrophy
  • Splenic rupture: Risk highest 2-3 weeks after symptom onset 2
  • Lymphoma development: EBV infection is associated with certain lymphomas including Hodgkin's lymphoma and Burkitt's lymphoma 5

Clinical Course

  • Incubation period: Unusually long, approximately 4-6 weeks 6
  • Symptomatic phase: Typically 2-4 weeks in uncomplicated cases
  • Resolution: Most symptoms resolve within 1-2 months
  • Fatigue: May persist for several months in some patients

Key Diagnostic Considerations

  • EBV infection should be considered in patients presenting with prolonged fever, pharyngitis, and lymphadenopathy
  • Diagnosis is confirmed by serological testing or PCR for EBV DNA
  • Differential diagnosis includes other viral infections, streptococcal pharyngitis, toxoplasmosis, and cytomegalovirus infection

Remember that while most EBV infections are self-limiting, recognition of potential complications and monitoring for their development is essential, particularly in immunocompromised patients.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Epstein-Barr Virus Infection Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

[Infectious mononucleosis--a "childhood disease" of great medical concern].

Medizinische Monatsschrift fur Pharmazeuten, 2013

Research

Two cases of EBV infection preceding lymphoma.

Journal of cancer research and clinical oncology, 2022

Research

Primary Epstein-Barr virus infection.

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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