Infectious mononucleosis

Last updated: December 13, 2021

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Infectious mononucleosis (IM), also called "mono" or the "kissing disease", is an acute condition caused by the Epstein-Barr virus (EBV). The disease is highly contagious and spreads via bodily secretions, especially saliva. Infection frequently goes unnoticed in children; mainly adolescents and young adults exhibit symptoms. Symptomatic individuals typically first experience fever, malaise, and fatigue, which is later accompanied by acute pharyngitis, tonsillitis, lymphadenopathy, and/or splenomegaly lasting up to a month. IM is also sometimes associated with a measles-like exanthem, especially in individuals who are falsely diagnosed with bacterial tonsillitis and given ampicillin or amoxicillin. To avoid misdiagnosis, suspected cases are confirmed with a heterophile antibody test (monospot test), or in some cases, positive serology. Patients exhibit lymphocytosis, often with atypical T lymphocytes on a peripheral smear. IM is treated symptomatically, as it is usually self-limiting. Although complications are rare, IM is associated with atraumatic splenic rupture due to splenomegaly and multiple malignancies (e.g., Hodgkin's lymphoma, Burkitt lymphoma).

  • General: Approx. 90–95% of adults are EBV-seropositive worldwide. [1]
  • Peak incidence: (of symptomatic disease): 15–24 years of age [2]
  • Incidence: 5/1000 per year [3]

Epidemiological data refers to the US, unless otherwise specified.


“You must Be (B lymphocytes) 21 (CD21) to drink in a BAR (Epstein-BARr virus).”

Splenomegaly can lead to a potentially life-threatening splenic rupture!

In most cases, a maculopapular rash occurs due to empiric administration of aminopenicillins, and not due to EBV infection.

Clinical suspicion of IM is confirmed via antibody testing.

Serology Past infection Primary infection
anti-VCA IgM negative positive
anti-VCA IgG positive positive
Anti-EBNA-1 IgG positive negative

Tonsillitis is an important differential diagnosis that is often treated with aminopenicillins (e.g., ampicillin). However, if given to a patient with IM, the patient often develops a macular erythematous rash after 5–9 days.

The differential diagnoses listed here are not exhaustive.

Therapy of IM is mainly symptomatic.

  • Avoid physical activity because of the risk of splenic rupture.
    • Patients should avoid strenuous physical activities for at least 21 days after initial symptoms develop. [13]
    • Patients should avoid high-contact sports (e.g., football, wrestling) for at least 4 weeks
  • Fluids (IV administration if necessary)
  • Analgesics/antipyretics (e.g., acetaminophen), viscous lidocaine for throat pain
  • Steroids are not recommended for routine use but may be considered in complicated cases.
  • Contact persons should avoid direct contact to the patient's bodily fluids (e.g., no sharing of food, drinks, personal items, no kissing)

Immunocompromised patients have a higher risk of developing complications. [14]

We list the most important complications. The selection is not exhaustive.

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  12. Mononucleosis-Like Syndrome. Updated: March 3, 2017. Accessed: March 17, 2017.
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  14. Epstein-Barr Virus and Infectious Mononucleoisis. Updated: September 14, 2016. Accessed: March 28, 2017.
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