Infectious Mononucleosis

Updated: Oct 19, 2016
  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Overview

Background

Infectious mononucleosis was first described by Sprunt and Evans in the Bulletin of the Johns Hopkins Hospital in 1920. [1] They described the clinical characteristics of Epstein-Barr virus (EBV) infectious mononucleosis. At the time, their article was entitled "Mononuclear leukocytosis in reaction to acute infection (infectious mononucleosis)," because the causative organism, EBV, had yet to be described.

Since the 1800s, infectious mononucleosis has been recognized as a clinical syndrome consisting of fever, pharyngitis, and adenopathy. The term glandular fever was first used in 1889 by German physicians and was termed Drüsenfieber. The association between infectious mononucleosis and EBV was described in the late 1960s.

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Pathophysiology

EBV is transmitted via intimate contact with body secretions, primarily oropharyngeal secretions. EBV infects the B cells in the oropharyngeal epithelium. The organism may also be shed from the uterine cervix, implicating the role of genital transmission in some cases. On rare occasion, EBV is spread via blood transfusion.

Circulating B cells spread the infection throughout the entire reticular endothelial system (RES), ie, liver, spleen, and peripheral lymph nodes. EBV infection of B lymphocytes results in a humoral and cellular response to the virus. The humoral immune response directed against EBV structural proteins is the basis for the test used to diagnose EBV infectious mononucleosis. However, the T-lymphocyte response is essential in the control of EBV infection; natural killer (NK) cells and predominantly CD8+ cytotoxic T cells control proliferating B lymphocytes infected with EBV.

The T-lymphocyte cellular response is critical in determining the clinical expression of EBV viral infection. A rapid and efficient T-cell response results in control of the primary EBV infection and lifelong suppression of EBV.

Ineffective T-cell response may result in excessive and uncontrolled B-cell proliferation, resulting in B-lymphocyte malignancies (eg, B-cell lymphomas).

The immune response to EBV infection is fever, which occurs because of cytokine release consequent to B-lymphocyte invasion by EBV. Lymphocytosis observed in the RES is caused by a proliferation of EBV-infected B lymphocytes. Pharyngitis observed in EBV infectious mononucleosis is caused by the proliferation of EBV-infected B lymphocytes in the lymphatic tissue of the oropharynx.

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Epidemiology

Frequency

United States

EBV infectious mononucleosis is a common cause of viral pharyngitis in patients of all ages, but it is particularly frequent in young adults. In the United States, approximately 50% of the population seroconverts before age 5 years, with much of the rest seroconverting in adolescence or young adulthood. Approximately 12% of susceptible college-aged young adults convert each year, half of whom develop acute infectious mononucleosis.

International

See United States.

Mortality/Morbidity

Patients with EBV infection who present clinically with infectious mononucleosis invariably experience accompanying fatigue. Fatigue may be profound initially but usually resolves gradually in 3 months. Some patients experience prolonged fatigue and, after initial recovery, enter a state of prolonged fatigue without the features of infectious mononucleosis.

Mortality and morbidity rates due to uncomplicated primary EBV infectious mononucleosis are low. The rare cases of attributed mortality are usually related to spontaneous splenic rupture. Splenic rupture may be the initial presentation of EBV mononucleosis.

Most cases of EBV infectious mononucleosis are subclinical, and the only manifestation of EBV infection is a serological response to EBV surface proteins discovered with EBV serological tests. Airway obstruction and central nervous system (CNS) mononucleosis are also responsible for increased morbidity in infectious mononucleosis. Selective immunodeficiency to EBV, which occurs in persons with X-linked lymphoproliferative syndrome, may result in severe, prolonged, or even fatal infectious mononucleosis.

Hepatic necrosis caused by extensive EBV proliferation in the RES of the liver is the usual cause of death in affected males. EBV is the main cause of malignant B-cell lymphomas in patients receiving organ transplants.

Most instances of posttransplant lymphoproliferative disorder (PTLD) are associated with EBV. EBV in PTLD is acquired from an EBV-positive donor organ. The likelihood of PTLD is directly proportional to the degree of immunosuppressive drugs administered to the transplant patient.

Depending on the intensity, rapidity, and completeness of the T-lymphocyte response, malignancy may result if EBV-induced B-lymphocyte proliferation is uncontrolled. Hodgkin disease and non-Hodgkin lymphoma (NHL) may result. Other EBV-related malignancies include oral hairy leukoplakia in patients with HIV infection.

Leiomyomas and leiomyosarcomas in immunocompromised children, nasopharyngeal carcinoma, and Burkitt lymphoma are among other neoplasms caused by EBV.

Age

Although primarily a disease of young adults, EBV infectious mononucleosis may occur from childhood to old age.

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