Diagnostic Considerations

EBV-negative Mononucleosis

Approximately 10 percent of mononucleosis-type cases are not caused by EBV. CMV, HIV, Toxoplasma, human herpesvirus type 6 (HHV-6), hepatitis B and HHV-7 present similarly to EBV induced IM and should be considered in a heterophile-negative mononucleosis-like syndrome.

Table 1. Differential Diagnoses of Infectious Mononucleosis (Open Table in a new window)

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

Workup

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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.

Sections Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono)
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
Tables
References

Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono) Differential Diagnoses

Diagnostic Considerations

EBV-negative Mononucleosis

References

Tables

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