How is fever in Epstein-Barr virus (EBV) infectious mononucleosis (mono) distinguished from fever associated with other conditions?

Updated: Sep 20, 2018
  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Fever is rarely the sole manifestation of Epstein-Barr virus (EBV) infectious mononucleosis. Because most patients with EBV infectious mononucleosis usually have fever, pharyngitis, and lymphadenopathy, the differential diagnoses are those of an infectious mononucleosis–like illness, which include infectious mononucleosis due to cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), acute HIV disease, toxoplasmosis, and anicteric viral hepatitis.

These infectious diseases, which have presentations similar to those of infectious mononucleosis, have also been termed heterophile-negative infectious mononucleosis because the heterophile test and EBV serology findings are negative in these patients. In rare cases, EBV infection has been reported as a cause of fever of unknown origin (FUO).

Fevers due to EBV infectious mononucleosis may reach 103-104°F but are usually less than 102°F. Relative bradycardia is a rare finding in patients with EBV mononucleosis and suggests myocardial involvement (eg, myocarditis). Persistent fever or a recrudescence of fever after clinical recovery should suggest an alternate diagnosis.

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