Further Outpatient Care

Monitor patients to be sure that the infection is improving over time. Serial CBC counts should document the increase in lymphocytes as well as atypical lymphocytes, and this may be monitored on a weekly basis until these values normalize.

Patients with positive heterophile tests should not be monitored with serial testing because the heterophile test may remain positive for as much as 1 year after infection.

Serial specific Epstein-Barr virus (EBV) antibody testing is usually not necessary in patients with acute infection. Caution patients that increased IgG, VCA, and EBNA levels persist for life. Also, inform patients that titers vary and that IgG titers have no relationship to disease activity or to how the patient feels.

Patients should be advised that fatigue may take some time to resolve, and some patients may develop a state of chronic fatigue that is induced, but not caused by, EBV infectious mononucleosis.

Further Inpatient Care

Patients with extreme tonsillar enlargement may require extended care if intubation is required.

Deterrence/Prevention

Avoid close contact with body fluid secretions, particularly saliva.

Complications

Extreme enlargement of the tonsils may result in airway obstruction.

Encephalitis and myocarditis are rare complications.

Splenic rupture is a rare, but potentially lethal, complication of EBV infectious mononucleosis.

Rare patients with EBV infectious mononucleosis develop lymphoma.

Prognosis

If splenic rupture is recognized and expeditiously treated surgically, the prognosis is good.

Patients with EBV infectious mononucleosis who become asplenic as the result of splenic rupture and/or surgical removal should be treated as other patients with asplenia.

Patient Education

Counsel patients to refrain from strenuous physical activity for the first 3 weeks of illness.

Patients should avoid exposing other people to their body secretions because EBV remains viable in patients with EBV infectious mononucleosis for months after the initial infection.

For excellent patient education resources, visit eMedicineHealth's Bacterial and Viral Infections Center and Back, Ribs, Neck, and Head Center. Also, see eMedicineHealth's patient education articles Mononucleosis and Chronic Fatigue Syndrome.

Questions

Sprunt TPV, Evans FA. Mononuclear leukocytosis in reaction to acute infection (infectious mononucleosis). Bulletin of the Johns Hopkins Hospital. Baltimore, 1920. 31:410-417.
Balfour HH, Holman CJ, Hokanson KM, et al. A prospective clinical study of Epstein-Barr virus and host interactions during acute infectious mononucleosis. J Infect Dis. 2005 Nov 1. 192(9):1505-12. [QxMD MEDLINE Link].
About Epstein-Barr virus. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/epstein-barr/about-ebv.html. Accessed: April 21, 2021.
Dowd JB, Palermo T, Brite J, McDade TW, Aiello A. Seroprevalence of Epstein-Barr virus infection in U.S. children ages 6-19, 2003-2010. PLoS One. 2013. [QxMD MEDLINE Link].
Smatti MK, Al-Sadeq DW, Ali NH, Pintus G, Abou-Saleh H, Nasrallah GK. Epstein-Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update. Front Oncol. 2018. 8:211. [QxMD MEDLINE Link].
Candy B, Chalder T, Cleare AJ, Wessely S, White PD, Hotopf M. Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review. Br J Gen Pract. 2002 Oct. 52 (483):844-51. [QxMD MEDLINE Link].
Balfour HH Jr, Odumade OA, Schmeling DO, Mullan BD, Ed JA, Knight JA, et al. Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis. 2013 Jan 1. 207 (1):80-8. [QxMD MEDLINE Link].
Vetsika EK, Callan M. Infectious mononucleosis and Epstein-Barr virus. Expert Rev Mol Med. 2004 Nov 5. 6 (23):1-16. [QxMD MEDLINE Link].
Sawyer RN, Evans AS, Niederman JC, McCollum RW. Prospective studies of a group of Yale University freshmen. I. Occurrence of infectious mononucleosis. J Infect Dis. 1971 Mar. 123 (3):263-70. [QxMD MEDLINE Link].
Moretti M, Lava SAG, Zgraggen L, Simonetti GD, Kottanattu L, Bianchetti MG, et al. Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: Systematic review. J Clin Virol. 2017 Jun. 91:12-17. [QxMD MEDLINE Link].
Dunmire SK, Verghese PS, Balfour HH Jr. Primary Epstein-Barr virus infection. J Clin Virol. 2018 May. 102:84-92. [QxMD MEDLINE Link].
Yonese I, Sakashita C, Imadome KI, Kobayashi T, Yamamoto M, Sawada A, et al. Nationwide survey of systemic chronic active EBV infection in Japan in accordance with the new WHO classification. Blood Adv. 2020 Jul 14. 4 (13):2918-2926. [QxMD MEDLINE Link].
Hoagland RJ. Infectious mononucleosis. Prim Care. 1975 Jun. 2 (2):295-307. [QxMD MEDLINE Link].
Young LS, Yap LF, Murray PG. Epstein-Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer. 2016 Dec. 16 (12):789-802. [QxMD MEDLINE Link].
Shannon-Lowe C, Rickinson AB, Bell AI. Epstein-Barr virus-associated lymphomas. Philos Trans R Soc Lond B Biol Sci. 2017 Oct 19. 372 (1732):[QxMD MEDLINE Link].
Okuno Y, Murata T, Sato Y, Muramatsu H. Defective Epstein-Barr virus in chronic active infection and haematological malignancy. Nat Microbiol. 2019 Mar. 4 (3):404-413. [QxMD MEDLINE Link].
Blum KA, Lozanski G, Byrd JC. Adult Burkitt leukemia and lymphoma. Blood. 2004 Nov 15. 104 (10):3009-20. [QxMD MEDLINE Link].
Burkitt D. A sarcoma involving the jaws in African children. Br J Surg. 1958 Nov. 46 (197):218-23. [QxMD MEDLINE Link].
Robbiani DF, Deroubaix S, Feldhahn N, Oliveira TY, Callen E, Wang Q, et al. Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma. Cell. 2015 Aug 13. 162 (4):727-37. [QxMD MEDLINE Link].
Renné C, Hinsch N, Willenbrock K, Fuchs M, Klapper W, Engert A, et al. The aberrant coexpression of several receptor tyrosine kinases is largely restricted to EBV-negative cases of classical Hodgkin's lymphoma. Int J Cancer. 2007 Jun 1. 120 (11):2504-9. [QxMD MEDLINE Link].
Raghupathy R, Hui EP, Chan AT. Epstein-Barr virus as a paradigm in nasopharyngeal cancer: from lab to clinic. Am Soc Clin Oncol Educ Book. 2014. 149-53. [QxMD MEDLINE Link].
Andersson-Anvret M, Forsby N, Klein G, Henle W. Relationship between the Epstein-Barr virus and undifferentiated nasopharyngeal carcinoma: correlated nucleic acid hybridization and histopathological examination. Int J Cancer. 1977 Oct 15. 20 (4):486-94. [QxMD MEDLINE Link].
Castillo JJ, Beltran BE, Miranda RN, Paydas S, Winer ES, Butera JN. Epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly: what we know so far. Oncologist. 2011. 16 (1):87-96. [QxMD MEDLINE Link].
Pitjadi T, M, Grayson W. Epstein-Barr Virus-Associated Smooth Muscle Tumour: A Case Series with a Significant Proportion of Tumours Showing Proclivity for Cutaneous Soft Tissues. Dermatopathology. 2019. 6:133-146.
McClain KL, Leach CT, Jenson HB, Joshi VV, Pollock BH, Parmley RT, et al. Association of Epstein-Barr virus with leiomyosarcomas in young people with AIDS. N Engl J Med. 1995 Jan 5. 332 (1):12-8. [QxMD MEDLINE Link].
Bhatia K, Shiels MS, Berg A, Engels EA. Sarcomas other than Kaposi sarcoma occurring in immunodeficiency: interpretations from a systematic literature review. Curr Opin Oncol. 2012 Sep. 24 (5):537-46. [QxMD MEDLINE Link].
Kawamoto K, Miyoshi H, Seto M, Kimura H, Ohshima K. [Clinical features of adult-onset chronic active Epstein-Barr virus infection]. Rinsho Ketsueki. 2019. 60 (8):944-952. [QxMD MEDLINE Link].
Morscio J, Tousseyn T. Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders. World J Transplant. 2016 Sep 24. 6 (3):505-16. [QxMD MEDLINE Link].
Ebell MH. Epstein-Barr virus infectious mononucleosis. Am Fam Physician. 2004 Oct 1. 70 (7):1279-87. [QxMD MEDLINE Link].
Marshall-Andon T, Heinz P. How to use … the Monospot and other heterophile antibody tests. Arch Dis Child Educ Pract Ed. 2017 Aug. 102 (4):188-193. [QxMD MEDLINE Link].
Schumacher HR, Austin RM, Stass SA. False-positive serology in infectious monoucleosis. Lancet. 1979 Mar 31. 1 (8118):722. [QxMD MEDLINE Link].
Epstein-Barr Virus and Infectious Mononucleosis: Laboratory Testing. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/epstein-barr/laboratory-testing.html. Accessed: April 21, 2021.

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Table 1. Differential Diagnoses of Infectious Mononucleosis

Clinical Parameters		Epstein-Barr Virus	Cyto-megalovirus	Toxoplasmosis	Viral Hepatitis
Symptoms	Fatigue	+++	+	+/-	+
	Malaise	++	+	-	+
	Mild sore throat	+	+	+/-	+/-
	Early maculopapular rash	±	-	-	+/-
Signs	Early bilateral upper eyelid edema	±	-	-	-
	Unilateral localized adenopathy	-	-	+	-
	Bilateral posterior cervical adenopathy	+	+	-	+/-
	Tender hepatomegaly	+/-	+/-	-	+
	Splenomegaly	+	+/-	+/-	-
Laboratory abnormalities	WBC count	N*/-	N/-	N	¯
	Elevated SGOT^†/SGPT^‡	++	+	+/-	+++
	Atypical lymphocytes (≥ 10%)	+	+	-	-
	Thrombocytopenia	+/-	+/-	-	+/-
	Elevated IgM^§ CMV titer	-	+	-	-
	Elevated IgM EBV VCA^II titer	+	-	-	-
	Elevated IgM toxoplasmosis titer	-	-	+	-
	Positive hepatitis (eg, A, B, D) test	-	-	-	+
*Normal ^† Serum glutamic-oxaloacetic transaminase ^‡ Serum glutamic-pyruvic transaminase ^§ Immunoglobulin M ^II Viral capsid antigen

Table 2. EBV Serologic Responses in EBV-Associated Diseases

EBV Diseases	EBV Antibody Responses
	Anti-VCA			Anti-EA
	IgM Monospot/ Heterophile	IgM	IgG	Diffuse EA	Restricted EA	Anti-EBNA
Acute EBV mononucleosis	+	+	+	+	-	-
Past EBV infection	-	-	+	-	-	+
Chronic active EBV infection	-	-	+++	+	+	+
Burkitt lymphoma	-	-	+++	+/-	+	+
Nasopharyngeal carcinoma	-	-	+++	+	+/-	+

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Author

Kartika Shetty, MD, FACP Program Director, Internal Medicine Residency Program, Sunrise GME; Facility Medical Director, TEAMHealth, Mountain View Hospital

Kartika Shetty, MD, FACP is a member of the following medical societies: American College of Physicians, Association of Program Directors in Internal Medicine, Medical Council of India

Disclosure: Nothing to disclose.

Coauthor(s)

Elizabeth Benge, MD Resident Physician, Department of Internal Medicine, Sunrise Health GME Consortium

Elizabeth Benge, MD is a member of the following medical societies: American College of Physicians, American Medical Women's Association

Disclosure: Nothing to disclose.

Vanessa E Josef, MD, MS Fellow in Pulmonary Disease and Critical Care Medicine, University of New Mexico School of Medicine

Vanessa E Josef, MD, MS is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Reza Vaghefi, MD Infectious Disease Physician, Infectious Disease Partners of Nevada (IDPN), Sunrise Health GME Consortium

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University School of Medicine in Shreveport; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Charles S Levy, MD Associate Professor, Department of Medicine, Section of Infectious Disease, George Washington University School of Medicine

Charles S Levy, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, Medical Society of the District of Columbia

Disclosure: Nothing to disclose.