Epstein-Barr Virus (EBV)

Virology

Member of Herpesvirus Family (see Herpesviruses)

  • xxxx

Epidemiology

  • xxx

Diagnosis

Mono Spot Test (see xxxx)

  • Positive

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

  • Chronic interstitial lung disease due to Epstein-Barr virus infection in two infants. Eur Respir J. 2000 Apr;15(4):803-6 [MEDLINE]
  • The role of Epstein-Barr virus in pleural effusions of unknown aetiology: an interesting clinical perspective. Eur Respir J 2005; 26:566-568 [MEDLINE]
  • A possible role for Epstein-Barr virus in the pathogenesis of pleural effusion. Eur Respir J 2005;26:662 666 [MEDLINE]

Clinical

  • Infectious-mononucleosis-like disease with negative heterophil agglutination test. Clinical features in relation to Epstein-Barr virus and cytomegalovirus antibodies. J Infect Dis. 1970;121(6):608 [MEDLINE]
  • Infectious mononucleosis. Prim Care. 1975;2(2):295 [MEDLINE]
  • Heterophil-negative infectious mononucleosis and mononucleosis-like illnesses. Laboratory confirmation of 43 cases. Am J Med. 1977;63(6):947 [MEDLINE]
  • Heterophil antibody in adults with sore throat: frequency and clinical presentation. Ann Intern Med. 1982;96(4):505 [MEDLINE]
  • Infectious mononucleosis in patients aged 40 to 72 years: report of 27 cases, including 3 without heterophil-antibody responses. Medicine (Baltimore). 1983;62(4):256 [MEDLINE]
  • Clinical picture of primary HIV infection presenting as a glandular-fever-like illness. BMJ. 1988;297(6660):1363 [MEDLINE]
  • The spectrum of clinical and laboratory findings resulting from human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not resulting from Epstein-Barr virus or cytomegalovirus. Am J Clin Pathol. 1990;93(6):776 [MEDLINE]
  • Infectious mononucleosis in older adults. Am Fam Physician. 1990 Dec;42(6):1599-606 [MEDLINE]
  • Spontaneous rupture of the spleen in patients with infectious mononucleosis. Mayo Clin Proc. 1992;67(9):910 [MEDLINE]
  • Isolation of human herpesvirus 7 from a child with symptoms mimicking chronic Epstein-Barr virus infection. Br J Haematol. 1993;84(3):545 [MEDLINE]
  • Infectious mononucleosis hepatitis: report of two patients. Indian J Gastroenterol. 1997;16(3):113 [MEDLINE]
  • Necrotizing genital ulcerations in a premenarcheal female with mononucleosis. Obstet Gynecol. 1998;92(4 Pt 2):642 [MEDLINE]
  • Ascites and severe hepatitis complicating Epstein-Barr infection. Am J Gastroenterol. 1999;94(1):236 [MEDLINE]
  • Peritonsillar abscess and infectious mononucleosis: an association or a different presentation of the same condition. Ir Med J. 1999;92(2):278 [MEDLINE]
  • Infectious mononucleosis in middle age. JAMA. 1999;281(5):454 [MEDLINE]
  • Epstein-Barr virus-related gastric pseudolymphoma in infectious mononucleosis. Gastrointest Endosc. 2000;52(2):290 [MEDLINE]
  • Acute renal failure: unusual complication of Epstein-Barr virus-induced infectious mononucleosis. Clin Infect Dis. 2000;31(6):1519 [MEDLINE]
  • Oropharyngotonsillitis associated with nonprimary Epstein-Barr virus infection. Arch Otolaryngol Head Neck Surg. 2000;126(2):185 [MEDLINE]
  • Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. J Am Board Fam Pract. 2001;14(4):234 [MEDLINE]
  • Just another simple case of infectious mononucleosis? Lancet. 2003;361(9364):1182 [MEDLINE]
  • Herpes simplex virus and Epstein-Barr virus infections in pregnancy: consequences of neonatal or intrauterine infection. Reprod Toxicol. 2006;21(4):436 [MEDLINE]
  • Epstein-Barr virus infection in pregnancy–a prospective controlled study. Reprod Toxicol. 2008;25(4):468 [MEDLINE]
  • Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis. 2013;207(1):80 [MEDLINE]
  • Do penicillins really increase the frequency of a rash when given during Epstein-Barr Virus primary infection? Clin Infect Dis. 2013;57(11):1661 [MEDLINE]
  • Splenic rupture in infectious mononucleosis: A systematic review of published case reports. Injury. 2016 Mar;47(3):531-8 [MEDLINE]
  • Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection – Systematic review of the literature. J Clin Virol. 2016;82:51 [MEDLINE]
  • Splenic Infarction in Acute Infectious Mononucleosis. J Emerg Med. 2016 Jan;50(1):e11-3 [MEDLINE]
  • Antibiotic-Induced Rash in Patients With Infectious Mononucleosis. Ann Pharmacother. 2017;51(2):154 [MEDLINE]
  • Chronic Active Epstein-Barr Virus Disease. Front Immunol. 2017;8:1867 [MEDLINE]
  • Incidence of Antibiotic-Related Rash in Children with Epstein-Barr Virus Infection and Evaluation of the Frequency of Confirmed Antibiotic Hypersensitivity. Int Arch Allergy Immunol. 2018;176(1):33 [MEDLINE]
  • Clinical warning of hemophagocytic syndrome caused by Epstein-Barr virus. Ital J Pediatr. 2021;47(1):3 [MEDLINE]