MD Nexus

Epstein-Barr Virus (EBV)

Virology

Member of Herpesvirus Family (see Herpesviruses)

Epidemiology

Diagnosis

Mono Spot Test (see xxxx)

Clinical Presentations

Classic Infectious Mononucleosis

General Comments

  • While Infectious Mononucleosis Can Affect Any Organ System, Classic Infectious Mononucleosis Has a Characteristic Pattern of Involvement

Cardiovascular Manifestations

  • Bradycardia (see xxxx)
    • Epidemiology
      • Bradycardia Occurs in 35-50% of Cases
  • Chest Pain (see Chest Pain)
    • Epidemiology
      • Chest Pain Occurs in 5-10% of Cases
  • Myocarditis (see Myocarditis)
    • Epidemiology
      • Case Reports

Dermatologic Manifestations

  • Rash
    • Epidemiology
      • Rash Occurs in 3-6% of Cases
      • It was Previously Thought that the Maculopapular Rash was Associated with the Administration of Amoxicillin/Ampicillin
      • However, the Rash Can Occur in the Absence of Antibiotic Exposure or with the Use of Other Antibiotics (Including Azithromycin, Levofloxacin, Piperacillin/Tazobactam, and Cephalexin) (Clin Infect Dis, 2013) [MEDLINE] (Ann Pharmacother, 2017) [MEDLINE] ( Int Arch Allergy Immunol, 2018) [MEDLINE]
    • Physiology
      • Mechanism May Involve a Transient Virus-Mediated Immune Alteration, Resulting in a Delayed Hypersensitivity-Type Reaction
      • Of Note, This May Not Be a True Allergy, Since Many of the Patients with Infectious Mononucleosis-Associated Rash with the Use of Amoxicillin/Ampicillin Can Subsequently Tolerate Amoxicillin/Ampicillin without Any Adverse Events (Rash, etc)
    • Clinical
  • Sweats
    • Epidemiology
      • Sweats Occur in 80-95% of Cases

Gastrointestinal Manifestations

  • Acalculous Cholecystitis (see Acalculous Cholecystitis)
    • Epidemiology
      • Case Reports (J Clin Virol, 2016) [MEDLINE]
  • Acute Pancreatitis (see Acute Pancreatitis)
    • Epidemiology
      • Case Reports (J Clin Virol, 2016) [MEDLINE]
  • Anorexia (see Anorexia)
    • Epidemiology
      • Anorexia Occur in 50-80% of Cases
  • Gastric Pseudolymphoma
    • Epidemiology
      • Case Report (Gastrointest Endosc, 2000) [MEDLINE]
  • Hepatitis/Cholestasis
    • Epidemiology
      • Cases Have Been Reported (Indian J Gastroenterol, 1997) [MEDLINE] (Am J Gastroenterol, 1999) [MEDLINE]
    • Clinical
    • Prognosis
      • Fatalities Associated with Hepatitis Have Been Reported (Indian J Gastroenterol, 1997) [MEDLINE]
  • Hepatomegaly (see Hepatomegaly)
    • Epidemiology
      • Hepatomegaly Occur in 15-25% of Cases
  • Jaundice/Hyperbilirubinemia (see Hyperbilirubinemia)
    • Epidemiology
      • Jaundice Occur in 5-10% of Cases
  • Mesenteric Adenitis
    • Epidemiology
      • Case Report
  • Nausea (see Nausea and Vomiting)
    • Epidemiology
      • Nausea Occur in 50-70% of Cases

Hematologic Manifestations

  • Atypical Lymphocytosis
    • Diagnosis
      • XXXX
  • Hemophagocytic Lymphohistiocytosis (HLH) (see Hemophagocytic Lymphohistiocytosis)
    • Epidemiology
      • Epstein-Barr Virus Infection is the One Most Commonly Associated with HLH (and Which Has Been the Best Studied)
      • Study of Prognostic Factors in EBV-Associated HLH (Ital J Pediatr, 2021) [MEDLINE]
  • Splenomegaly (see Splenomegaly)
    • Epidemiology
      • Splenomegaly Occurs in 50-60% of Cases
    • Clinical
      • Splenic Rupture May Occur as a Rare Complication (Incidence: 1-2 Cases Per Thousand) (Mayo Clin Proc, 1992) [MEDLINE]
        • Approximately 70% of Splenic Ruptures Occur in Males, Typically <30 y/o (Injury, 2016) [MEDLINE]
        • Approximately 50% of Splenic Ruptures are Spontaneous (Typically Occurring Around 14 Days After Symptom Onset)
        • Due to the Risk of Splenic Rupture, Caution Regarding the Avoidance of Contact Sports is Critical
    • Treatment
      • Splenic Rupture is Treated by Standard Mangement (i.e. Splenectomy, etc)
    • Prognosis
      • Splenomegaly Usually Begins to Decrease by the 3rd Week of Disease
      • Mortality from Splenic Rupture is Rare
  • Splenic Infarction (see Splenic Infarction)
    • Epidemiology
      • Splenic Infarction May Occur in Some Cases (J Emerg Med, 2016) [MEDLINE]
    • Clinical
      • May Be Noted Incidentally or May Manifest with Abdominal Pain (see Abdominal Pain)

Neurologic Manifestations

  • General Comments
    • Neurologic Manifestations Occur 2-4 wks After the Initial Symptom Onset
  • Alice in Wonderland Syndrome
    • Epidemiology
      • XXX
    • Clinical
      • Distortions of Visual Perception, Body Image, and/or Experience of Time
  • Aseptic Meningitis (see Meningitis)
  • Encephalomyelitis
  • Facial Nerve Palsy (see xxxx)
  • Fatigue/Malaise (see Fatigue)
    • Epidemiology
      • Fatigue Occurs in 90-100% of Cases
  • Guillain-Barre Syndrome (see Guillain-Barre Syndrome)
  • Headache (see Headache)
    • Epidemiology
      • Headache Occurs in 40-70% of Cases
  • Meningoencephalitis (see Meningitis and Encephalitis)
  • Optic Neuritis (see Optic Neuritis)
    • Epidemiology
      • While an Association Between Infectious Mononucleosis and Multiple Sclerosis Has Been Described, a True Association is Unclear
  • Other Cranial Nerve Palsies (see xxxx)
  • Peripheral Neuritis (see Peripheral Neuropathy)
  • Photophobia (see Photophobia)
    • Epidemiology
      • Photophobia Occurs in 5-10% of Cases
  • Transverse Myelitis (see Transverse Myelitis)

Ophthalmologic Manifestations

  • Ocular Muscle Pain
    • Epidemiology
      • Ocular Muscle Pain Occurs in 10-20% of Cases
  • Periorbital Edema (see xxxx)
    • Epidemiology
      • Periorbital Edema Occurs in 25-40% of Cases

Otolaryngologic Manifestations

  • Cervical Lymphadenopathy (see Lymphadenopathy)
    • Epidemiology
      • Lymphadenopathy Occurs in 100% of Cases (Prim Care, 1975) [MEDLINE] (J Am Board Fam Pract, 2001) [MEDLINE]
    • Clinical
      • Lymphadenopathy is Typically symmetric and more commonly involves the posterior cervical and posterior auricular nodes than the anterior chains
      • The posterior cervical nodes are deep to the sternocleidomastoid muscles and must be carefully palpated
      • The nodes may be large and moderately tender
      • Lymphadenopathy may also become more generalized, which distinguishes IM from other causes of pharyngitis (Ann Intern Med, 1982) [MEDLINE]
      • Lymphadenopathy peaks in the first week and then gradually subsides over two to three weeks
  • Palatal Enanthem
    • Epidemiology
      • Palatal Enanthem Occurs in 25-35% of Cases
  • Pharyngitis (see Pharyngitis)
    • Epidemiology
      • Pharyngitis Occurs in 80-85% of Cases (Prim Care, 1975) [MEDLINE] (J Am Board Fam Pract, 2001) [MEDLINE]
    • Clinical
      • Sore Throat/Dysphagia
      • Tonsillar Exudates (may appear white, gray-green, or even necrotic)
      • Palatal petechiae with streaky hemorrhages and blotchy red macules are occasionally present (this finding may also be seen in patients with streptococcal pharyngitis)
      • May Rarely Be Complicated by peritonsillar abscess or airway occlusion secondary to edema of the soft palate and tonsils (Ir Med J, 1999) [MEDLINE]
  • Rhinitis (see xxxx)
    • Epidemiology
      • Rhinitis Occurs in 10-25% of Cases

Pulmonary Manifestations

  • Cough (see xxxx)
    • Epidemiology
      • Cough Occurs in 30-50% of Cases
  • Pleural Effusion (see xxxx)
    • Epidemiology
      • Case Reports
        • Case Reported with Small Bilateral Pleural Effusions (with No Pleural Chemistry Obtained), Associated with Ascites (Lancet, 2003) [MEDLINE]
  • Pneumonia (see Community-Acquired Pneumonia)
    • Epidemiology
      • Case Reports (Lancet, 2003) [MEDLINE]
      • Occurs in <3% of Cases

Renal/Genitourinary Manifestations

Rheumatologic Manifestations

  • Arthralgias (see Arthralgias)
    • Epidemiology
      • Arthralgias Occur in 5-10% of Cases
  • Myalgias (see Myalgias)
    • Epidemiology
      • Myalgias Occur in 12-30% of Cases
  • Myositis (see Myositis)
    • Epidemiology
      • Case Report

Other Manifestations

  • Chills (see Chills)
    • Epidemiology
      • Chills Occur in 40-60% of Cases
  • Fatigue (see Fatigue)
    • Epidemiology
      • Fatigue Occurs Commonly
  • Fever (see Fever)
    • Epidemiology
      • Fever Occurs in 80-98% of Cases (Prim Care, 1975) [MEDLINE] (J Am Board Fam Pract, 2001) [MEDLINE]

Variant Types of Infectious Mononucleosis

Mild Infectious Mononucleosis

  • General Comments
    • Associated with Acute EBV Infection
    • Study of 66 EBV-Seronegative University Students Who Developed Acute Primary EBV Infection (J Infect Dis, 2013) [MEDLINE]
      • Classic Infectious Mononucleosis Syndrome: 77% of Cases
      • Atypical Symptoms: 12% of Cases
      • Asymptomatic: 11% of cases
  • Clinical Manifestations
    • Pharyngitis/Tonsillitis in the Absence of the Full Classic Infectious Mononucleosis Syndrome (Arch Otolaryngol Head Neck Surg, 2000) [MEDLINE]

Typhoidal Form of Infectious Mononucleosis

  • Clinical Manifestations
    • Fever and Lymphadenopathy in the Absence of Pharyngitis
      • These Patients May Be Heterophile Antibody-Negative (i.e. Heterophile-Negative) Infectious Mononucleosis
      • Other Etiologies of Heterophile-Negative Infectious Mononucleosis Include the Following

Infectious Mononucleosis in Very Young/Older Patients

  • General Comments
    • Very Young or Adults Frequently Do Not Manifest the Classic Infectious Mononucleosis Syndrome (JAMA, 1999) [MEDLINE]
  • Clinical Manifestations
    • Study of Patients Age 40-78 with Infectious Mononucleosis (Medicine-Baltimore, 1983) [MEDLINE]
      • Pharyngitis and Myalgias were the Most Frequent Symptoms
      • Cervical Lymphadenopathy was Less Commonly Observed
    • Study of Older Patients with Infectious Mononucleosis (JAMA, 1999) [MEDLINE]
      • Fever is Common and Can Last for Several Weeks
      • Elevated Liver Function Tests (Transaminitis) is Common
  • Clinical Features Differ by Age (Am Fam Physician, 1990) [MEDLINE]
    • Age ≤35 y/o
      • Lymphadenopathy: 94%
      • Pharyngitis: 84%
      • Fever: 75%
      • Splenomegaly: 52%
      • Hepatomegaly: 12%
      • Jaundice: 9%
      • Rash: 10%
    • Age ≥40 y/o
      • Lymphadenopathy: 47%
      • Pharyngitis: 43%
      • Fever: 95%
      • Splenomegaly: 33%
      • Hepatomegaly: 42%
      • Jaundice: 27%
      • Rash: 12%

Chronic Active Epstein-Barr Virus Infection

Epstein-Barr Virus Infection During Pregnancy

  • Epidemiology
    • In Cases of Maternal Infectious Mononucleosis, There is Little Evidence of Teratogenic Risk to Fetus (Reprod Toxicol, 2008) [MEDLINE]
    • Transplacental Transmission of Epstein-Barr Virus Appears to Be Rare (Reprod Toxicol, 2006) [MEDLINE]

References

General

Clinical