The classic triad associated with IM includes fever, pharyngitis, and cervical lymphadenopathy, with morbilliform rash and palatal petechiae appearing less commonly (3%-15% and 25%, respectively).1,2,9 In affected patients, a transient truncal rash manifests within the first few days of disease onset.7 Tonsillar enlargement is also a common, but not specific, sign of acute IM.2 Splenomegaly is found in 15% to 65% of patients, typically developing within three weeks of disease onset.1,5,9
Hematologic complications occur in 25% to 50% of cases.5 Mild thrombocytopenia is common; however, more severe complications—such as hemolytic anemia, hemolytic-uremic syndrome, aplastic anemia, and disseminated intravascular coagulation—have also been associated with IM.5 Fulminant and potentially fatal complications are more common in immunocompromised patients.1,2
Pediatric and geriatric patients (those older than 65) may present with atypical signs and symptoms. For example, children are commonly asymptomatic or may present with a nonspecific viral illness.1 In addition, pediatric and elderly populations can develop elevated aminotransferase levels, and 26% of elderly patients present with jaundice (compared with 8% of young adults).2,3,7
Heterophile antibody testing is the most efficient and least expensive diagnostic test to confirm IM (sensitivity, 63%-84%; specificity, 84%-100%).2 Within the first week of IM, however, 25% of patients will produce a false-negative antibody test; a complete blood count (CBC) with differential and peripheral smear are appropriate follow-up tests.1,2,5 Detecting 10% or more atypical lymphocytes on a peripheral smear has a specificity of 95% and sensitivity of 61.3% for detecting IM, and a CBC with a lymphocyte count of less than 4,000 mm has a 99% negative predictive value.2 Viral capsid IgM testing can confirm the diagnosis of IM in an unclear clinical situation, such as a negative heterophile antibody test with an absolute lymphocyte count > 4,000 mm or in which 10% or more atypical lymphocytes were detected.2
Pharyngitis is caused by group A streptococci in 15% to 30% of children and 10% of adults worldwide, and 30% of patients with IM have a concomitant infection with group A streptococci.1,5 Because pharyngitis is a common presenting symptom of IM, rapid antigen strep test is appropriate when working up these patients.2 In addition, HIV, cytomegalovirus, human herpesvirus-6, and Toxoplasma gondii should be considered in the differential for patients with pharyngitis, fatigue, malaise, and lymphadenopathy—especially if the group A streptococci/EBV workup is negative.1,2,5
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