Infectious mononucleosis


  • Caused by Epstein-Barr virus
    • CMV and HHV-6 may cause mononucleosis-like illnesses
  • Infects B lymphocytes which causes dissemination
    • T lymphocytes fight infection
    • In patients with decreased T cell function, can lead to continued proliferation and neoplastic transformation

Clinical Features

  • Triad of:
  • Symptoms
    • Abrupt or insidious
    • Headache, fever, and malaise common, sore throat and lymphadenopathy follow
    • Rash in 10-15% usually between 4th-6th day of illness
      • Red macular or maculopapular morbilliform rash of trunk & upper arms
      • Occasionally involves face, thigh and legs, periorbital & eyelid edema in 50% of cases
  • Previously treated as strep pharyngitis
  • Illness typically 2-4 weeks, but malaise and fatigue may last for months

Differential Diagnosis

Acute Sore Throat

Bacterial infections

Viral infections



Pediatric Rash



  • Heterophile antibody (monospot) test vs EBV IgM Assay
  • CBC
    • Lymphocytosis (≥50% lymphocytes)
      • 10% or more atypical lymphocytes
      • Hypersegmented neutrophils
    • Thrombocytopenia
  • LFTs
    • Elevations in AST and ALT is expected up to 5x
  • Suspected mononucleosis during pregnancy (also need to rule out other pathology):


  • Heterophile antibody (monospot) test
    • Up to 25% of patients in 1st week of symptoms may have false negative test[3]
    • 10% of adult patients with EBV infection will be persistently negative
    • Up to 50% of pediatric patients will be persistently negative[4]
  • EBV IgM Assay
    • Carries 97% sensitivity and 94% specificity at symptom onset[5]


  • Supportive
  • Avoid contact sports for 1-2 months[6] (decrease risk of splenic rupture)


  • Discharge


  1. Luzuriaga K and Sullivan JL. Infectious mononucleosis. N Engl J Med. 2010; 362:1993-2000.
  2. Melio, Frantz, and Laurel Berge. “Upper Respiratory Tract Infection.” In Rosen’s Emergency Medicine., 8th ed. Vol. 1, n.d.
  3. Pitetti RD, Laus, S, and Wadowsky, RM. Clinical evaluation of a quantitative real time polymerase chain reaction assay for diagnosis of primary Epstein-Barr virus infection in children. Pediatr Infect Dis J. 2003; 22:736–739.
  4. Papesch M and Watkins R. Epstein-Barr virus infectious mononucleosis. Clin Otolaryngol Allied Sci. 2001; 26(1):3-8.
  5. Bruu, AL, et al. Evaluation of 12 commercial tests for detection of Epstein-Barr virus-specific and heterophile antibodies. Clin Diagn Lab Immunol. 2000; 7:451–456.
  6. O'Connor TE, Skinner LJ, Kiely P, Fenton JE. Return to contact sports following infectious mononucleosis: the role of serial ultrasonography. Ear Nose Throat J. 2011 Aug;90(8):E21-4.
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