What are the signs and symptoms of cytomegalovirus (CMV) mononucleosis and how is it differentiated from Epstein-Barr virus (EBV) infectious mononucleosis?

Updated: Jul 07, 2021
  • Author: Ricardo Cedeno-Mendoza, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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CMV may produce a mononucleosis syndrome similar to that caused by Epstein-Barr virus (EBV), primary toxoplasmosis, or acute HIV seroconversion. In a large study of 494 patients with infectious mononucleosis, 79% of cases were due to EBV, and, in the 73 heterophile antibody–negative patients, approximately half of these were CMV positive (rising complement-fixing antibodies). [34] In about a third of patients with CMV mononucleosis, a rash may also be present (macular, papular, maculopapular, rubelliform, morbilliform, or scarlatiniform). [35]

Both CMV and EBV may result in atypical lymphocytes in the blood. Other pertinent test results include negative findings on heterophil antibody studies, mildly or moderately elevated levels of aspartate aminotransferases, and evidence of subclinical hemolysis. [36] Hepatitis and atypical lymphocytes usually disappear after 6 weeks. Despite its great sensitivity, the CMV IgM test is limited by a one-way cross-reaction of acute EBV infectious mononucleosis sera. False-positive reactions have resulted from the presence of rheumatoid factors. [36]

CMV infection should be suspected in patients with clinical mononucleosis or fever of unknown origin. Most cases have a paucity of physical examination findings. Some studies have shown that, as a group, patients infected with CMV have less hepatomegaly, splenomegaly, and pharyngitis than those infected with EBV. Patients with CMV mononucleosis may be older, have a longer duration of fever, and have less cervical lymphadenopathy. However, such clinical findings are inadequate to differentiate between the two viruses.

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