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Infectious Mononucleosis

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Other Names

  • Mono
  • Kissing virus
  • Kissing disease


  • This page covers Infectious mononucleosis (IM), often referred to as 'mono'



  • It is estimated that 30-50% of college freshman are susceptible to infection
    • Annual incidence is 1-3%[1]
  • Although most commonly seen in teenagers, eventually infects up to 90% of all adults[2]


  • Viral syndrome characterized by pharyngitis, posterior cervical lymphadenopathy, fatigue, fever, abdominal pain and sometimes rash
  • Most commonly caused by primary Epstein-Barr virus (EBV) infection in teenagers
    • Transmission occurs primarily through oral secretions, hence the popular description "kissing disease"
    • Also shared through coughing, sneezing, close contact
    • Less commonly through blood, solid organ transplantation, hematopoeitic cell transplant
    • EBV is a member of the herpes virus family
    • Less commonly caused by cytomegalovirus (CMV)
  • General
    • Illness is generally self limited
    • Classic triad of fever, pharyngitis and lymphadenopathy
    • Incubation period is between 30-50 days, which makes identifying initial exposure challenging
    • Patients who are immunocompromised can develop severe symptoms
  • No season variation
  • Acutely, increases risk of splenomegaly and rupture
  • Chronically, EBV is associated with certain cancers and autoimmune disease

Risk Factors

  • Needs to be updated

Differential Diagnosis

  • Non-EBV Viral Pharyngitis
  • Strep Pharyngitis
  • Post Nasal Drip
  • Allergic Reaction

Clinical Features

  • General
  • History
    • Incubation period is approximately 6 weeks
    • May have a viral prodrome of fever, headache, malaise for up to 3 weeks
    • Patients endorse sore throat, cervical lymphadenopathy, fever, tonsillar enlargement
  • Physical Exam
    • Pharygeal inflammation (80%)
    • Palatal petechiae (25%)
    • Rash on trunk and upper extremity (10-40%), more common if treated with antibiotics
    • Splenomegaly (up to 50%, need citation)
      • Ability to detect splenomegaly on exam is limited
      • Poor sensitivity, specificity and inter-rate reliability (need citation)
    • Older adults may develop jaundice
    • Less common: periorbital edema, CNS complications, myocarditis
  • Special Tests



  • CBC shows nonspecific leukocytosis, lymphocytosis
  • Heterophile antibody test positive
  • LFTs may or may not bee elevated

Imaging Spleen

  • CT, MRI and US have been used
  • CT
    • Benefits: Greater detail, better quantifcation of splenic size
    • Limitations: cost, radiation exposure, time
    • Indicated if splenic rupture is suspected
  • US
    • Readily available, inexpensive, no radiation
    • Technique
    • Measure length, breadth, thickness
    • Multiply all 3 dimensions, divide by 27[3]
    • Interpret an individual measurement with caution. Likely need serial measurements
    • Clear guidance on normative data not well established


  • N/A


Hoagland's Criteria

  • WBC: at least 50% lymphocytes and at least 10% atypical lymphocytes[4]
  • Presence of fever, pharyngitis, and adenopathy
  • Confirmatory serologic testing
  • Approximately 50% of patients meet


  • No specific treatment, self limited illness
  • Supportive treatment
  • Sore throat
    • Salt water gargles, anesthetic throat lozenges or sprays, or gargling with 2% lidocaine solution
  • Acyclovir
    • Short term supression of viral shedding, no significant clinical benefit[5]
  • Oral Corticosteroids
    • Some benefit for severe pharyngeal edema
    • Consider in athletes with: impending airway obstruction, hemolytic anemia, severe thrombocytopenia, or myocarditis
    • Chochrane review: decreased symptoms for 12 hours, benefits subsided at 2-4 days[6]
  • Avoid
    • Activity/ sports until cleared by physician
    • If given penicillin, up to 90% of patients will develop a maculopapular rash (need citation)
    • Aspirin due to risk of bleeding, thrombocytopenia
    • Acetaminophen, alcohol due to hepatotoxicity
  • Isolate from others if possible to minimize exposure and risk


  • If splenic rupture, splenectomy
  • Some case reports of nonoperative management of stable splenic injury
    • Discuss with surgical staff if patient is stable

Rehab and Return to Play


  • No specific rehabilitation
  • Athlete may require conditioning before return to sport

Return to Play

  • Return too quickly increases risk of splenic injury
    • Complicated by lack of clear correlation between splenomegaly and risk of rupture
    • Unreliability of physical exam also a challenge
    • Risk not well understood in athletes, estimated to be 0.1-0.5% extrapolating from general population (need citation)
    • Up to 86% of ruptures are atraumatic
  • Sylvester et al: Less than 75% of ruptures occur before 21 days, most occur by 31 days[7]
    • Case reports of splenic rupture up to 7 weeks (need citation)
  • Most physicians hold athletes for 4-6 weeks
    • Consider light, noncontact activities 3 weeks from symptom onset[8]
  • Return to contact activities is controversial
    • RTP must be individualized
    • Important to discuss risk/benefit with athlete


See Also


  1. Brodsky AL, Heath CW. Infectious mononucleosis; epidemiological patterns at United States colleges and universities. Am J Epidemiol. 1972;96:87–93.
  2. Baumgarten E, Herbst H, Schmitt M, et al. Life-threatening infectious mononucleosis: is it correlated with virus-induced T cell proliferation? J Clin Infect Dis. 1994;19:152–156.
  3. Pietri H, Boscaini M. Determination of a splenic volumetric index by ultrasonic scanning. J Ultrasound Med. 1984;3:19–23.
  4. Ebell MH. Epstein-Barr virus infectious mononucleosis. Am Fam Physician. 2004;70:1279–1287.
  5. Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand J Infect Dis. 1999;31:543.
  6. Candy B, Hotopf M. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst Rev. 2006;3:CD004402.
  7. Sylvester, J. E., Buchanan, B. K., Paradise, S. L., Yauger, J. J., & Beutler, A. I. (2019). Association of Splenic Rupture and Infectious Mononucleosis: A Retrospective Analysis and Review of Return-to-Play Recommendations. Sports Health, 11(6), 543–549.
  8. Putukian, Margot, et al. "Mononucleosis and athletic participation: an evidence-based subject review." Clinical Journal of Sport Medicine 18.4 (2008): 309-315.
Created by:
John Kiel on 13 June 2019 10:35:35
Last edited:
4 May 2020 19:52:43