Guideline sources The following summarized guidelines for the evaluation and management of infectious mononucleosis (IM) are prepared by our editorial team based on guidelines from the American Medical Society for Sports Medicine (AMSSM 2023) and the American Association of Family Physicians (AAFP 2004). 1 2 3 4 4 4 5 6 Definition IM, also known as mono or "kissing disease", is an acute infection characterized by fever, lymphadenopathy, and pharyngitis. 4 Epidemiology IM is most frequently caused by the EBV (EBV) transmitted through infected saliva during kissing. EBV. 5 Pathophysiology The incidence of IM in the United States is estimated at 500 cases per 100,000 population per year, with the peak incidence between ages 15-24 years. However, over 90% of adults globally are EBV seropositive. 4 https://web.pathway.md/diseases/recG23DgLnhmiaNYg 1/5 6/24/23, 2:34 PM Infectious mononucleosis Pathway Disease course Young children are often asymptomatic, and symptoms frequently occur in adolescents and young adults. Clinical manifestations include pharyngitis, bilateral cervical lymphadenopathy, fever, generalized muscle aches, hepatosplenomegaly, maculopapular rash, jaundice, arthritis, conjunctivitis, and edema. Complications include hematological complications (hemolytic anemia, thrombocytopenia, aplastic anemia, TTP, HUS, and DIC), neurologic complications (Guillain-Barre syndrome, facial paralysis, meningoencephalitis, aseptic meningitis, transversal myelitis, peripheral neuritis, cerebellitis, and optical neuritis), splenic rupture, airway obstruction, pneumonia, hemophagocytic lymphohistiocytosis (prolonged fever, lymphadenopathy, hepatosplenomegaly, exanthem, hepatic dysfunction, and cytopenia). 4 Prognosis and risk of recurrence Most patients achieve complete resolution within weeks, and mortality rates are low (5.3%). EBV remains dormant post-recovery, but symptomatic reactivation is rare. 6 Guidelines 1. Screening and diagnosis Diagnosis: suspect IM in 10-30 years old patients presenting with sore throat and significant fatigue, palatal petechiae, posterior cervical or auricular lymphadenopathy, marked axillary lymphadenopathy, or inguinal lymphadenopathy. B 2. Classification and risk stratification Risk of splenic rupture: Recognize that splenic rupture is a rare complication of IM with an incidence of < 0.5%. B Recognize that most splenic ruptures occur in the first 2 days of illness and are exceedingly rare after 28 days from the onset of IM. B Risk of chronic fatigue: Insufficient evidence to recommend specific tests or examination findings to estimate the risk of chronic fatigue due to IM. I Recognize that fatigue, myalgias, and need for sleep may persist for several months after the acute infection has resolved. B 3. Diagnostic investigations Clinical assessment: https://web.pathway.md/diseases/recG23DgLnhmiaNYg 2/5 6/24/23, 2:34 PM Infectious mononucleosis Pathway Recognize that clinical manifestations of IM can be nonspecific and physical examination techniques have poor sensitivity and specificity in identifying relative splenic enlargement, and inter-rater reliability for physical examination is also poor. A Avoid relying on physical examination to assess for the presence or absence of splenomegaly. D Laboratory tests: Consider obtaining laboratory confirmation of IM. B Recognize that atypical lymphocytosis of at least 20% or atypical lymphocytosis of at least 10% and lymphocytosis of at least 50% may signal IM. B Splenic imaging: do not obtain splenic imaging in the routine management of patients with IM unless splenic injury and/or rupture is suspected. Recognize that most, if not all, athletes have at least some degree of splenic enlargement early in their illness, and there are no data that correlate spleen size to splenic rupture. D Show 2 more 4. Medical management Supportive care: offer supportive care for the treatment of uncomplicated IM. B Corticosteroids: Insufficient evidence to support the use of oral corticosteroids to reduce the time until return to sport in patients with IM. I Administer corticosteroids in patients with IM complicated by impending airway obstruction, hemolytic anemia, severe thrombocytopenia, or myocarditis. B Do not use corticosteroids in the acute management of IM without complications, such as laryngeal edema or hematologic complications. D Do not use corticosteroids in the routine management of IM. D Consider administering corticosteroids in patients with respiratory compromise or severe pharyngeal edema. C Antiviral therapy: Insufficient evidence to support the use of antiviral agents to reduce the time until return to sport in patients with IM. I Do not use acyclovir in the routine management of IM. D Antihistamines: do not use antihistamines in the routine management of IM. D 5. Nonpharmacologic interventions Exercise restriction: https://web.pathway.md/diseases/recG23DgLnhmiaNYg 3/5 6/24/23, 2:34 PM Infectious mononucleosis Pathway Advise athletes with IM to refrain from sports activity until afebrile, asymptomatic, and well- hydrated. B Advise patients with IM to restrict participation in contact or collision sports for at least 4 weeks after the onset of symptoms and until asymptomatic. B 6. Follow-up and surveillance Return to sport: consider advising a trial of supervised, nonimpact, low-intensity activity 2 weeks from the onset of symptoms in afebrile athletes with an adequate energy level and improving clinical examination findings. Consider delaying return to sport in the presence of ongoing clinical signs/symptoms, lack of athlete readiness, and/or IM-associated complications. C Show 2 more Likelihood Ratios Pertinent positives The following findings increase the probability of infectious mononucleosis in adults. -1 Finding LR+ Value Increased blood lymphocyte count 15 (11-21) Increased atypical lymphocytes ( 10%) 11 (2.7-35) Increased lymphocyte count-to-WBC count ratio (> 0.40) 5.3 (4.2-6.6) Presence of posterior cervical lymphadenopathy 3.1 (1.6-5.9) Show 9 more Pertinent negatives The following findings decrease the probability of infectious mononucleosis in adults. -1 Finding LR- Value blood lymphocyte count not increased 0.17 (0.09-0.32) Absence of generalized lymphadenopathy 0.23-0.44 lymphocyte count-to-WBC count ratio not increased ( 0.40) 0.30 (0.26-0.35) atypical lymphocytes not increased (< 10%) 0.37 (0.26-0.51) Show 8 more References 1. Mark H Ebell. Epstein-Barr virus infectious mononucleosis. Am Fam Physician. 2004 Oct 1;70 7 1279 87. Open https://web.pathway.md/diseases/recG23DgLnhmiaNYg 4/5 6/24/23, 2:34 PM Infectious mononucleosis Pathway 2. Becker JA, Smith JA. Return to Play After Infectious Mononucleosis. Sports Health. 2014 May;6 3 232 8. Open 3. Margot Putukian, Christopher A McGrew, Holly J Benjamin et al. American Medical Society of Sports Medicine Position Statement: Mononucleosis and Athletic Participation. Clin J Sport Med. 2023 May 15. Online ahead of print. Open 4. Napoleon Gonzalez Saldana, Victor Antonio Monroy Colin, Georgina Pina Ruiz et al. Clinical and laboratory characteristics of infectious mononucleosis by Epstein-Barr virus in Mexican children. 2012 Jul 20;5 361.2012 Jul 20;5 361. Open 5. Katherine Luzuriaga, John L Sullivan. Infectious mononucleosis. N Engl J Med. 2010 May 27;362 21 1993 2000. Open 6. Pierre Tattevin, Yves Le Tulzo, Sophie Minjolle et al. Increasing incidence of severe Epstein-Barr virus- related infectious mononucleosis: surveillance study. 2006 May;44 5 1873 4.2006 May;44 5 1873 4. Open 7. American Medical Society for Sports Medicine. Choosing Wisely AMSSM recommendations. Choosing Wisely. 2014. Open 8. Henry H Balfour Jr, Samantha K Dunmire, Kristin A Hogquist. Infectious mononucleosis. Clin Transl Immunology. 2015 Feb 27;4 2):e33. Open 9. Napole n Gonz lez Salda a, Victor Antonio Monroy Col n, Georgina Pi a Ruiz et al. Clinical and laboratory characteristics of infectious mononucleosis by Epstein-Barr virus in Mexican children. BMC Res Notes. 2012 Jul 20;5 361. Open 10. Pierre Tattevin, Yves Le Tulzo, Sophie Minjolle et al. Increasing incidence of severe Epstein-Barr virus- related infectious mononucleosis: surveillance study. J Clin Microbiol. 2006 May;44 5 1873 4. Open 11. Jason Womack, Marissa Jimenez. Common questions about infectious mononucleosis. Am Fam Physician. 2015 Mar 15;91 6 372 6. Open 12. Mark H Ebell. Epstein-Barr virus infectious mononucleosis. Am Fam Physician. 2004 Oct 1;70 7 1279 87. Open https://web.pathway.md/diseases/recG23DgLnhmiaNYg 5/5