Review Question - QID 214348

This patient with symptoms of fevers, arthralgias, and cough with a heterophile-negative antibody test most likely has a mononucleosis syndrome caused by cytomegalovirus (CMV) infection.

Cytomegalovirus infection in immunocompetent patients is most commonly asymptomatic, but if symptomatic, often manifests as a mononucleosis syndrome with fevers, myalgias, arthralgias, and cough. CMV disease may result from either a primary infection or reactivation of a latent infection. The mononucleosis syndromes caused by Epstein-Barr virus (EBV) and CMV are similar, but fever and systemic symptoms predominate in CMV infection, and signs of cervical lymphadenopathy and tonsillitis are not as common in CMV as in EBV infection. Laboratory studies will reveal negative heterophile antibody test in CMV, in contrast with EBV. An absolute lymphocytosis with more than 10% atypical lymphocytes on peripheral blood smear is seen in mononucleosis due to both CMV and EBV. The mainstay of treatment in immunocompetent patients with mononucleosis syndrome caused by CMV is supportive care, as antiviral medications (ganciclovir or valganciclovir) are indicated for immunocompromised patients or patients with severe disease or organ damage.

Figure/Illustration A shows a peripheral blood smear with an atypical lymphocyte (black arrow), seen in infectious mononucleosis.

Incorrect Answers:
Answer 2: Epstein-Barr virus also causes infectious mononucleosis that clinically manifests similarly to mononucleosis due to CMV or HIV infection. Diagnostic testing is thus important to differentiate between viral etiologies, with reactive (positive) heterophile antibodies being diagnostic of EBV infection.

Answer 3: Influenza virus is a common cause of seasonal influenza, which characteristically presents with abrupt onset of fever, headache, myalgias, and malaise along with respiratory tract symptoms of cough, sore throat, and nasal discharge. Atypical lymphocytes seen on peripheral blood smear in this patient, however, suggests a non-influenza viral diagnosis. Rapid influenza antigen tests are now widely used for the diagnosis of influenza.

Answer 4: Norovirus is the most common cause of viral gastroenteritis, which this patient may have had during his travels 3 weeks prior to presentation. While post-infectious symptoms may include symptoms such as gastrointestinal reflux and constipation, a mononucleosis syndrome weeks after a norovirus infection is uncommon.

Answer 5: Parainfluenza virus can cause respiratory illness in adults, with clinical manifestations varying from acute bronchitis to pneumonia. Atypical lymphocytes seen on peripheral blood smear in this patient, however, suggest a non-parainfluenza viral diagnosis, with CMV or EBV being more likely.

Bullet Summary:
Cytomegalovirus can cause a heterophile-negative mononucleosis type syndrome in immunocompetent patients.