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Medical Author:

Mary Nettleman, MD, MS, MACP

Mary Nettleman, MD, MS, MACP

Mary D. Nettleman, MD, MS, MACP is the Chair of the Department of Medicine at Michigan State University. She is a graduate of Vanderbilt Medical School, and completed her residency in Internal Medicine and a fellowship in Infectious Diseases at Indiana University.

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Medical Editor:

Charles Patrick Davis, MD, PhD

Charles Patrick Davis, MD, PhD

Dr. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. He has a PhD in Microbiology (UT at Austin), and the MD (Univ. Texas Medical Branch, Galveston). He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications.

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The diagnosis of mononucleosis starts with a physical examination. The doctor will look for fever, an inflamed throat, swollen lymph nodes in the neck, and an enlarged spleen. Red dots (petechiae) may be seen on the palate. Up to half of infected people will have an enlarged spleen, and 10% will have an enlarged liver on abdominal examination. People with suspected mononucleosis will have a blood sample drawn for blood counts and a "mono spot" test. If the mono spot is positive, the diagnosis is confirmed. Mono spots may be falsely negative in children under the age of 4 years or in the elderly. Repeating the test at a later date may be helpful in these cases. Other viruses and pathogens may cause an illness that is similar to mononucleosis (for example, cytomegalovirus, adenovirus, and Toxoplasma), so additional blood may be drawn to test for other pathogens..

In infected people, the number of normal lymphocytes in the blood is usually increased and the cells may look unusual or "atypical" under the microscope. Approximately 1%-3% of people develop anemia, which is caused by destruction of the red blood cells (hemolysis). Platelet counts may be low in up to half of patients, although this does not usually result in bleeding. In some cases, blood cells may be destroyed by other blood cells (hemophagocytic syndrome). Mild elevations in liver enzymes in the blood are common.

Several antibody tests are available to determine if a person has had a past infection or a current/recent infection with EBV. Some antibodies occur early and are transient, thus indicating new or "acute" infection. These include IgM antibody to the viral capsid antigen (VCA). Some antibodies develop immediately and persist for life, such as the IgG antibody to the viral capsid antigen. Other antibodies develop three to four weeks into the illness and persist for life, including antibodies to the nuclear antigen (EBNA). Antibodies to early antigen (EA-DIgG) may arise during acute infection and may persist, go away, or recur. PCR tests that detect EBV DNA are available in some laboratories.

Many physicians use three laboratory criteria (lymphocytosis, 10% or more lymphocytes are atypical on a peripheral blood smear, and a positive serologic test for EBV) along with the history and physical findings listed above to confirm a diagnosis of acute infectious mononucleosis.

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