Infectious mononucleosis

Last updated: July 27, 2023

Summarytoggle arrow icon

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).

Epidemiologytoggle arrow icon

  • 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.

Etiologytoggle arrow icon


Pathophysiologytoggle arrow icon

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

Clinical featurestoggle arrow icon

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.

Diagnosticstoggle arrow icon

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

Pathologytoggle arrow icon

Differential diagnosestoggle arrow icon

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.

Treatmenttoggle arrow icon

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)

Complicationstoggle arrow icon

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

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

Referencestoggle arrow icon

  1. Houldcroft CJ, Kellam P. Host genetics of Epstein–Barr virus infection, latency and disease. Rev Med Virol. 2014; 25 (2): p.71-84.doi: 10.1002/rmv.1816 . | Open in Read by QxMD
  2. Jarrett RF. Risk factors for Hodgkin's lymphoma by EBV status and significance of detection of EBV genomes in serum of patients with EBV-associated Hodgkin's lymphoma.. Leuk Lymphoma. 2003; 44 Suppl 3: p.S27-32.doi: 10.1080/10428190310001623801 . | Open in Read by QxMD
  3. González Saldaña N, Monroy Colín VA, Piña Ruiz G, Juárez Olguín H. Clinical and laboratory characteristics of infectious mononucleosis by Epstein-Barr virus in Mexican children.. BMC research notes. 2012; 5: p.361.doi: 10.1186/1756-0500-5-361 . | Open in Read by QxMD
  4. Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med. 2010; 362 (21): p.1993-2000.doi: 10.1056/nejmcp1001116 . | Open in Read by QxMD
  5. Dunmire SK, Grimm JM, Schmeling DO, Balfour HH Jr, Hogquist KA. The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events.. PLoS Pathog. 2015; 11 (12): p.e1005286.doi: 10.1371/journal.ppat.1005286 . | Open in Read by QxMD
  6. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Updated: May 1, 2013. Accessed: March 17, 2017.
  7. Sangueza-Acosta M, Sandoval-Romero E. Epstein-Barr virus and skin.. An Bras Dermatol. 2018; 93 (6): p.786-799.doi: 10.1590/abd1806-4841.20187021 . | Open in Read by QxMD
  8. Rubin E, Reisner HM. Essentials of Rubin's Pathology. Lippincott Williams & Wilkins ; 2009
  9. Infectious mononucleosis: histopathologic aspects. Updated: January 1, 1975. Accessed: March 17, 2017.
  10. Wright DH, Addis BJ, Leong ASY. Diagnostic Lymph Node Pathology. Hachette UK Company ; 2011
  11. Infectious mononucleosis. The spectrum of morphologic changes simulating lymphoma in lymph nodes and tonsils.. Updated: February 1, 1987. Accessed: March 17, 2017.
  12. Mononucleosis-Like Syndrome. Updated: March 3, 2017. Accessed: March 17, 2017.
  13. Becker JA, Smith JA. Return to play after infectious mononucleosis.. Sports health. 2014; 6 (3): p.232-8.doi: 10.1177/1941738114521984 . | Open in Read by QxMD
  14. Epstein-Barr Virus and Infectious Mononucleoisis. Updated: September 14, 2016. Accessed: March 28, 2017.
  15. Bar-Or A, Pender MP, Khanna R, et al. Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies. Trends Mol Med. 2019; 26 (3): p.296-310.doi: 10.1016/j.molmed.2019.11.003 . | Open in Read by QxMD
  16. Larroche C. Hemophagocytic lymphohistiocytosis in adults: diagnosis and treatment.. Joint bone spine. 2012; 79 (4): p.356-61.doi: 10.1016/j.jbspin.2011.10.015 . | Open in Read by QxMD
  17. Oliveira C, Chacim S, Ferreira I, Domingues N, Mariz JM. Secondary Hemophagocytic Syndrome: The Importance of Clinical Suspicion. Case Reports in Hematology. 2014; 2014: p.1-5.doi: 10.1155/2014/958425 . | Open in Read by QxMD
  18. Pannone G, Zamparese R, Pace M, et al. The role of EBV in the pathogenesis of Burkitt’s Lymphoma: an Italian hospital based survey. Infect Agent Cancer. 2014; 9 (1): p.34.doi: 10.1186/1750-9378-9-34 . | Open in Read by QxMD

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