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BASICS

  • EBV: Human herpesvirus 4, gamma herpesvirus family.
  • Subtypes: ST1 predominates in Western Hemisphere and Southeast Asia; ST1 and ST2 equally prevalent in Africa.
  • Primary Infection: Mostly asymptomatic in childhood; symptomatic IM in adolescents/young adults.
  • EBV is classified as a group I carcinogen due to its association with malignancies.

EPIDEMIOLOGY

  • High-risk groups: Military recruits, college students, crowded living conditions.
  • Incidence: ~500/100,000 in the US; highest in ages 15-24 years.
  • Prevalence: 95% seropositive by adulthood worldwide.
  • Seroconversion: Earlier in developing countries; delayed and variable by ethnicity in the US.

ETIOLOGY AND PATHOPHYSIOLOGY

  • EBV replicates in nasopharyngeal epithelium; infects B-cells and epithelial cells.
  • Causes viremia and immune response with atypical lymphocytosis.
  • Latent infection maintained via immune evasion; lytic phase causes clinical disease.
  • Risk factors for clinical disease include genetics, smoking, BMI, low vitamin D.
  • Immunosuppression predisposes to lymphoproliferative disorders.

RISK FACTORS

  • Age (adolescents and young adults).
  • Crowded living conditions.
  • Close intimate contact (e.g., deep kissing).
  • Immunosuppression.
  • Possible fomite transmission.

GENERAL PREVENTION

  • Avoid close contact with symptomatic persons.
  • Good hygiene and handwashing.
  • Standard precautions for blood exposure.
  • EBV vaccines under development but none available yet.

COMMONLY ASSOCIATED CONDITIONS

  • Infectious mononucleosis (IM) syndrome.
  • X-linked lymphoproliferative syndrome.
  • EBV-related lymphomas and malignancies (Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin lymphoma).
  • Chronic active EBV infection.
  • Post-transplant lymphoproliferative disorder.
  • Neurologic, hematologic, and pulmonary complications in immunocompromised hosts.

DIAGNOSIS

HISTORY

  • Insidious or abrupt onset of fatigue, malaise, sore throat.
  • Fever (up to 40-40.6°C), lasting 7-10 days or more.
  • Rash, conjunctivitis, chest pain (rare myocarditis/pericarditis).

PHYSICAL EXAM

  • Fever, cervical lymphadenopathy (>50% cases).
  • Pharyngitis with gray-white tonsillar exudates.
  • Palatal petechiae (~60% cases).
  • Bilateral upper eyelid edema (Hoagland sign).
  • Splenomegaly (~50%).
  • Maculopapular or petechial rash (3-16%).

DIFFERENTIAL DIAGNOSIS

  • Streptococcal pharyngitis
  • Diphtheria
  • Viral hepatitis, CMV
  • Toxoplasmosis
  • Acute HIV infection

LABORATORY TESTS

  • CBC: lymphocytosis with atypical lymphocytes up to 70%.
  • Monospot (heterophile antibody): sensitivity 70-90%; false-negatives early or in young children.
  • EBV-specific serologies: viral capsid antigen (VCA) IgM & IgG.
  • LFTs: mild transaminitis common; jaundice rare.
  • Imaging: chest X-ray for hilar adenopathy if indicated; ultrasound rarely needed except for splenomegaly assessment in athletes.

TREATMENT

  • Supportive care: rest, hydration, analgesics (NSAIDs or acetaminophen).
  • Avoid strenuous activity for 4 weeks to prevent splenic rupture.
  • Antibiotics only for confirmed streptococcal co-infection.
  • Corticosteroids: reserved for severe airway obstruction; limited evidence for routine use.
  • Antivirals (acyclovir): small studies suggest symptomatic benefit; not routinely recommended.
  • Transplant recipients: may need immunosuppression adjustment and rituximab.

ISSUES FOR REFERRAL

  • Airway compromise due to oropharyngeal edema.
  • Severe complications or atypical presentations.
  • Hematologic or neurologic complications.

SURGERY/OTHER PROCEDURES

  • Splenectomy for refractory thrombocytopenia.
  • Hematopoietic stem cell transplantation for X-linked lymphoproliferative syndrome.

ONGOING CARE

  • Avoid contact sports and heavy exertion until spleen size normalizes.
  • Monitor symptoms; fatigue may persist for months.
  • Eliminate hepatotoxic substances until liver function normalizes.

PROGNOSIS

  • Most recover within ~4 weeks.
  • Fatigue may persist for months.
  • Serious complications are rare but can include splenic rupture and neurologic sequelae.

COMPLICATIONS

  • Neurologic: aseptic meningitis, encephalitis, Bell palsy, Guillain-Barré syndrome.
  • Hematologic: thrombocytopenia, hemolytic anemia.
  • Splenic rupture (0.1% incidence).
  • Pneumonitis, airway obstruction.

REFERENCES

  1. Yu H, Robertson ES. Epstein-Barr virus history and pathogenesis. Viruses. 2023;15(3):714.
  2. Houen G, Trier NH. Epstein-Barr virus and systemic autoimmune diseases. Front Immunol. 2021;11:587380.
  3. Cai X, Ebell MH, Haines L. Accuracy of signs, symptoms, and hematologic parameters for the diagnosis of infectious mononucleosis: a systematic review and meta-analysis. J Am Board Fam Med. 2021;34(6):1141-1156.
  4. Gomes K, Goldman RD. Corticosteroids for infectious mononucleosis. Can Fam Physician. 2023;69(2):101-102.

ICD10

  • B27.00 Gammaherpesviral mononucleosis without complication
  • B27.09 Gammaherpesviral mononucleosis with other complications
  • B27.01 Gammaherpesviral mononucleosis with polyneuropathy

CLINICAL PEARLS

  • 98% of patients present with fever, sore throat, cervical lymphadenopathy, and tonsillar hypertrophy.
  • Monospot may be falsely negative in first 10-14 days.
  • Lymphocytosis with atypical lymphocytes is characteristic but not specific.
  • Treatment is supportive; avoid strenuous activities to prevent splenic rupture.