Mononucleosis in Emergency Medicine Clinical Presentation

Updated: Mar 16, 2017
  • Author: Michael S Omori, MD; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
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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 commonly are affected, but generalized adenopathy also may occur.

Patients often complain of headache.

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.

Erythema nodosum and erythema multiforme also have been associated with infectious mononucleosis, but these complications are not common.

Petechiae may occur.

Jaundice may occur.

Severe abdominal pain is uncommon in patients with infectious mononucleosis, and it should prompt immediate attention to a possible splenic rupture.

In older adults, nonspecific symptoms (eg, fever, fatigue, myalgia, malaise) predominate, making it difficult to establish a specific diagnosis.



Fever usually does not exceed 102°F in infectious mononucleosis, but it may be as high as 104°F.

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.

Petechiae of the palate, occurring at the junction of the hard and soft palate, may occur in up to one third of cases. Petechiae are not pathognomonic, but evidence of them is highly suggestive of infectious mononucleosis.

Jaundice may occur.



Numerous etiologies exist.

In more than 90% of cases, infectious mononucleosis is secondary to Epstein-Barr virus (EBV) infection.

Other infectious causes include the following:

Noninfectious causes of heterophile negative infectious mononucleosis – like syndrome include medications (eg, phenytoin, sulfas) and malignancy (eg, lymphomas, leukemias).

Risk factors include the following:

  • Being a college or high school student

  • Kissing

  • Blood transfusion