Infectious Mononucleosis (IM) in Emergency Medicine

Updated: Nov 11, 2022
  • Author: Michael S Omori, MD; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
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Infectious mononucleosis (IM) is a clinical syndrome. IM represents the immunopathologic expression that occurs under a specific set of circumstances and in response to infection with the Epstein-Barr virus (EBV). [1]

These circumstances primarily relate to the age and immunocompetency of the patient when the infection is acquired.

IM was first described in 1920. In 1932, the association between the disease syndrome and a positive heterophile antibody test was recognized. It was not until 1968 that EBV was identified as the most likely causative agent of IM. [1]



Epstein-Barr virus (EBV) is a member of the family Herpesviridae, which includes other human pathogens (eg, herpes simplex viruses, herpes varicella-zoster viruses, cytomegalovirus, human herpes viruses 6 and 7). [2]

Herpes viruses contain double-stranded DNA, and they have an icosahedral capsid and a glycoprotein-containing envelope. They are relatively fragile and do not survive long outside the human host fluids.

EBV is ubiquitous. It is estimated that more than 90% of adult humans demonstrate serologic evidence of a prior infection with EBV. Most cases of IM are due to EBV, but the vast majority of EBV infections do not result in infectious mononucleosis. In industrialized nations and among higher socioeconomic groups, infection with EBV tends to occur in adolescents and young adults. It is in this age group that the ensuing immunopathology gives rise to the characteristic clinical syndrome.

The most common mode of transmission of EBV is through exposure to infected saliva from asymptomatic individuals, often as a result of kissing.

Following exposure, EBV infects epithelial cells of the oropharynx and salivary glands. B lymphocytes may become infected through exposure to these cells or may be directly infected in the tonsillar crypts. B-cell infection allows viral entry into the bloodstream, which systemically spreads the infection.

In the immunocompetent patient, the proliferation of infected B cells results in massive activation and proliferation of cytotoxic T lymphocytes, leading to the characteristic lymphoid hyperplasia. Clinically, this is observed as tonsillitis, lymphadenopathy, and hepatosplenomegaly.

The T-cell response is largely responsible for the rise in the absolute lymphocyte count and for the finding of atypical lymphocytes. These atypical lymphocytes (ie, Downey cells) actually are CD8 cytotoxic T cells.

B-cell infection caused by EBV leads to the transformation of the B cells to immortal plasmacytoid cells, which secrete a wide variety of immunoglobulins (eg, heterophile antibodies). Antibodies against specific EBV antigens and a number of autoantibodies also are produced.

Other disease states that are associated with EBV include African Burkitt lymphoma, Hodgkin lymphoma, and certain nasopharyngeal cancers. An association has also been suggested between EBV infections and subsequent development of multiple sclerosis. [3, 2]




United States

The incidence of infectious mononucleosis (IM) as a recognizable clinical syndrome due to Epstein-Barr virus (EBV) is estimated at 45 per 100,000 patients.


The worldwide incidence of infectious mononucleosis is unknown, but in developing countries, 90% of children experience an asymptomatic Epstein-Barr virus infection when younger than 5 years and are not susceptible to mononucleosis that is associated with Epstein-Barr virus.


Fatalities secondary to infectious mononucleosis (IM) are rare and most often are the result of splenic rupture. Other fatal occurrences have been attributed to secondary bacterial infection, hepatic failure, and myocarditis.

Airway obstruction can occur due to massive edema of the Waldeyer ring.

Serious nonfatal complications also are rare and may include involvement of the CNS or the hematologic system.

CNS complications can include meningitis, encephalitis, hemiplegia, psychosis, cranial nerve palsies, Guillain-Barré syndrome, transverse myelitis, and peripheral neuritis. Evidence also exists to suggest Epstein-Barr virus infection as an adult is a risk factor for the development of multiple sclerosis. [3, 4]

Hematologic complications can include development of autoimmune hemolytic anemia, pancytopenia, red cell aplasia, severe thrombocytopenia, or agranulocytopenia.


No known ethnic or racial predilections exist; however, in developed countries, it is more common in persons of a higher socioeconomic class.


No predilection exists for either sex.

The only sex-related factor is the complication of splenic rupture; more than 90% of these cases occur in males.


The syndrome of infectious mononucleosis most often is an immunopathologic response to an infection with Epstein-Barr virus. The clinical expression of that response is influenced greatly by the age of the infected individual.

The highest occurrence rate is in those aged 15-25 years. It is estimated that 1-3% of college students are affected annually.

In children younger than 4 years, the infection is most often asymptomatic, but they may present with atypical symptoms (eg, irritability, failure to thrive, abdominal pain due to mesenteric adenopathy or splenomegaly, upper respiratory infection [URI] symptoms).

Elderly patients with Epstein-Barr virus infection usually present with nonspecific complaints (eg, fever, fatigue, malaise, myalgias).



Infectious mononucleosis is a self-limited illness. Spontaneous resolution typically occurs in 3-4 weeks. [1]

While malaise and fatigue may persist for several months, the vast majority of patients fully recover with no significant permanent sequelae.


Patient Education

Patients diagnosed with infectious mononucleosis should be educated as to the expected prognosis and time course of their illness.

They should be instructed to avoid participation in contact sports and to refrain from vigorous physical activity for at least 1 month in order to minimize the possibility of splenic rupture.

Routine follow-up care should be arranged to monitor patients for improvement or for the development of symptoms that are suggestive of complications.

For patient education resources, see the Bacterial and Viral Infections Center and Ear, Nose, and Throat Center, as well as Mononucleosis and Tonsillitis.