The OPEN minute newsletter / Infectious Mononucleosis
June 28, 2023

Infectious Mononucleosis

Infectious Mononucleosis, also called “mono,” is a contagious disease. Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis, but other viruses can also cause this disease (Cytomegalovirus, Adenovirus, Group A beta-hemolytic streptococci, Human immunodeficiency virus, etc.). It is common among teenagers and young adults, especially college students. 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.


Epstein-Barr virus (EBV) is a member of the family “Herpesviridae,” which includes other human pathogens. 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) are actually CD8 cytotoxic T cells.


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 the Epstein-Barr virus.

Clinical Presentation

Infectious mononucleosis may have a varied clinical presentation, but the symptoms usually consist of fever, pharyngitis, and lymphadenopathy.

The incubation period of infectious mononucleosis is 4-6 weeks. Patients usually do not recall a history of possible exposure.

Prodromal symptoms consisting of 1-2 weeks of fatigue, malaise, and myalgia are common. Patients may present during the prodrome, which makes specific diagnosis difficult, or they may present with clinical infectious mononucleosis and admit a history of antecedent prodromal symptoms. Abrupt onset of infectious mononucleosis symptoms with no prodrome may occur.

Low-grade fever usually is present and lasts 1-2 weeks, but it may persist for 4-5 weeks. Pharyngitis is one of the cardinal symptoms of infectious mononucleosis, and it may be severe and/or exudative, particularly during the first week of symptoms, with gradual improvement thereafter. Tonsillitis may be present. Lymphadenopathy is almost universal, and it lasts for 1-2 weeks. Posterior cervical nodes are commonly affected, but generalized adenopathy also may occur. A morbilliform or papular erythematous eruption of the upper extremities or trunk accompanies infectious mononucleosis in approximately 5% of cases. A macular erythematous rash may occur in patients with infectious mononucleosis who are treated with ampicillin. This usually occurs after 5-9 days of antibiotic treatment, and typically this rash is tan or brownish in color. Since the color is quite different than the typical very red allergic-type rash, this should not be misinterpreted as a penicillin allergy. However, because the shape and distribution of the rash of infectious mononucleosis plus antibiotics are similar to an allergic-type rash, they are often confused by patients and clinicians.


Fever usually does not exceed 39oC in infectious mononucleosis, but it may be as high as 40°C. Pharyngitis often is the most prominent physical finding. Tonsillar edema and erythema with a grayish or greenish exudate are common and are clinically indistinguishable from streptococcal pharyngitis. Affected lymph nodes usually are symmetrically enlarged, firm, mobile, and tender. The nodes usually do not demonstrate warmth or overlying erythema. Splenomegaly is present in most cases of infectious mononucleosis, but it may not be appreciated on physical examination. Hepatomegaly is found in 10-30% of cases. Periorbital edema occurs in 15-35% of patients with infectious mononucleosis.


Complications in patients with infectious mononucleosis are uncommon but may be serious. Airway obstruction may develop in patients with severe inflammation and swelling of the tonsils and adenoids. This complication may occur in 1 of every 100-1000 cases and most often occurs in younger patients with infectious mononucleosis. These patients should be identified and admitted. Corticosteroids are indicated in an effort to avoid intubation or the need for a surgical airway. Additionally, the development of a peritonsillar abscess or massive retropharyngeal lymphadenopathy secondary to EBV mononucleosis has been reported. Splenic rupture is a serious complication of infectious mononucleosis, but it occurs in fewer than 0.5% of cases. More than 90% of splenic rupture cases occur in male patients. In rare cases, splenic rupture has been reported in patients without other clinical symptoms of infectious mononucleosis. CNS complications may occur early in the course, often during the first few weeks of the illness, and may include meningitis, encephalitis, seizures, nerve palsies, cerebellar syndrome, coma, transverse myelitis, and Guillain-Barré syndrome. Autoimmune hemolytic anemia is present in approximately 2% of patients with IM. Other complications involving the hematologic system include the development of pancytopenia, severe thrombocytopenia, a granulocytopenia, red cell aplasia, and hemolytic-uremic syndrome. Ophthalmic complications include conjunctivitis, episcleritis, and uveitis. Dermatologic complications include dermatitis, urticaria, and erythema multiforme. Other complications include psychosis, malabsorption, glomerulonephritis, nephrotic syndrome, bullous myringitis, orchitis, parotitis, monoarticular arthritis, and jaundice. Additional rare complications include cardiac involvement with myocarditis, pericarditis and ECG changes, fulminant hepatic disease, pneumonia, interstitial nephritis, and presentation as a cecal mass.

Laboratory Studies

White blood cell count

The WBC count and differential can be useful in establishing a diagnosis of infectious mononucleosis. WBC count results usually show a modest elevation, with a peak of 10,000-20,000 during the second or third week of the illness. Findings consistent with infectious mononucleosis include a differential that demonstrates greater than 50% lymphocytes, an absolute lymphocyte count greater than 4500, or an elevated lymphocyte count with greater than 10% atypical lymphocytes.

Liver function tests (LFTs) are abnormal in more than 90% of patients with infectious mononucleosis.

EBV VCA IgM detected test is used to detect EBV.


Infectious mononucleosis is a self-limited illness. Spontaneous resolution typically occurs in 3-4 weeks. Treatment of patients with infectious mononucleosis (IM) generally is supportive, consisting primarily of rest, analgesics, and antipyretics. Because of the risk of splenic rupture, healthcare providers should avoid vigorous abdominal examination and palpation in patients with infectious mononucleosis. Certain clinical situations may warrant the administration of corticosteroids. Several studies have suggested that corticosteroids may be beneficial to patients with infectious mononucleosis, but the routine use of these agents in patients with uncomplicated disease should be avoided because these medications may adversely affect cell-medicated immune responses, thereby increasing the risk of bacterial superinfection. Patients with complications due to infectious mononucleosis who may benefit from corticosteroids include those with massive edema of the Waldeyer ring with the potential for airway obstruction, patients with autoimmune hemolytic anemia, or those with severe thrombocytopenia. Other complications that may warrant such therapy include severe involvement of the heart or central nervous system (CNS).


There is no vaccine to protect against infectious mononucleosis. You can help protect yourself by not kissing or sharing drinks, food, or personal items, like toothbrushes, with people who have infectious mononucleosis.


Hope this helps!

Best regards,

Dr. Hripsime Apresyan, the head of the infectious diseases department of “Muratsan” hospital
Dr. Suren Brutyan, an infectious disease specialist
Dr. Mark Grigoryan, a clinical resident of the Department of Infectious Diseases of YSUBU

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