A 21-year-old woman comes to the office due to a 7-day history of sore throat, extreme fatigue, myalgias, and headaches. She recently returned from a winter break vacation to Jamaica. The patient has no significant medical history and takes no medications. She smokes half a pack of cigarettes daily and occasionally consumes alcohol. Temperature is 38 C (100.4 F), heart rate is 78/min, blood pressure is 114/76 mm Hg, and respirations are 14/min. Examination of the oropharynx shows palatal petechiae and enlarged, erythematous tonsils with exudates. There is generalized lymphadenopathy and mild splenomegaly. Complete blood count is as follows:
| Hemoglobin | 13.5 g/dL |
| Platelets | 105,000/mm3 |
| Leukocytes | 16,000/mm3 |
| Neutrophils | 40% |
| Eosinophils | 2% |
| Lymphocytes | 55% |
| Monocytes | 3% |
Peripheral blood smear is performed. Rapid streptococcal antigen and heterophile antibody tests are negative. Which of the following is the most likely diagnosis in this patient?
Infectious mononucleosis | |
Etiology |
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Clinical features |
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Diagnostic findings |
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Management |
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Infectious mononucleosis (IM) is a common viral illness caused by the Epstein-Barr virus (EBV). EBV is transmitted primarily by close contact with infectious oropharyngeal secretions. Clinical manifestations of IM include marked fatigue, malaise, sore throat, fever, and lymphadenopathy. Splenomegaly and, less commonly, hepatomegaly are also seen.
Lymphoproliferation is a hallmark of IM, and hematologic studies reveal leukocytosis and atypical lymphocytes with a large, vacuolated cytoplasm, as seen on this patient's peripheral blood smear. The heterophile antibody (Monospot) test is specific for EBV and detects EBV antibodies that agglutinate to horse red blood cells. However, results may be negative early in the course of illness, especially during the first week of symptoms (25% false-negative rate in week 1). For this reason, a negative heterophile antibody test does not exclude the diagnosis of IM, as in this case. Repeating the test after several days or checking anti-EBV IgM and IgG antibodies can help establish the diagnosis.
(Choice A) Acute lymphoblastic leukemia may present with fever, fatigue, lymphadenopathy, splenomegaly, and lymphocytosis. However, it does not cause exudative pharyngitis, and blasts (rather than atypical lymphocytes) are seen on peripheral blood smear.
(Choice B) Adenovirus infection is a common cause of fever, exudative pharyngitis, malaise, and generalized lymphadenopathy. Lymphocytosis may be seen, but atypical lymphocytes are not characteristic.
(Choice C) Diphtheria typically presents with fever, malaise, pharyngitis, and lymphadenopathy. A gray pseudomembrane may cover the tonsils and oropharynx. Diphtheria does not cause splenomegaly or atypical lymphocytes.
(Choice D) Hodgkin lymphoma may present with asymptomatic lymphadenopathy, sometimes accompanied by prolonged B symptoms (eg, fever, weight loss, night sweats). Pharyngitis is not typical. Patients often have normal blood smears; atypical lymphocytes would not be seen.
(Choice F) Influenza virus commonly causes fever, fatigue, myalgia, pharyngitis, and lymphadenopathy and occurs during the winter months. Splenomegaly and atypical lymphocytes are not associated with influenza infection.
Educational objective:
Clinical manifestations of infectious mononucleosis include fatigue, sore throat, fever, lymphadenopathy, and splenomegaly. Atypical lymphocytes on peripheral smear are characteristic; heterophile antibodies, while specific for Epstein-Barr virus infection, may be negative early in the illness.