Cytomegalovirus (HHV5)

Key Points

• Cytomegalovirus (CMV)
  • Characteristics
    • Member of Herpesvirus family
      • Also known as human herpesvirus 5 (HHV-5)
      • Enveloped DNA virus with double-stranded, linear DNA 
        • Herpesviruses are unique in that they get their envelope by budding from nuclear membrane of host cell
  • Transmission
    • Can occur through many routes
      • Blood/tissue exposure (transplant recipients)
      • Sexual exposure
      • Close contact
      • Occupational exposure (e.g. urine, bodily fluids)
      • Perinatal exposure
  • Pathophysiology
    • Can establish latency (like other herpesviruses)
      • Clinical symptoms may result from primary infection or reactivation
  • Presentation
    • In immunocompetent patients
      • Mononucleosis syndrome
        • Fever, malaise, myalgia, lymphadenopathy, atypical lymphocytosis
        • Often causes morbilliform/maculopapular rash
          • Contrast vs. EBV, where rash is rare except after administration of penicillin
        • Tonsil/pharynx involvement is usually not seen
          • Contrast vs. EBV, where pharyngitis is classic
        • Negative heterophile antibodies (Monospot test)
          • Contrast vs. EBV, where Monospot is diagnostic
    • In immunocompromised patients (e.g. AIDS)
      • Retinitis
        • Hemorrhage, cotton-wool exudates, vision loss
        • Typically occurs in AIDS CD4+ <50 cells/µL
        • May be complicated by retinal detachment
      • Colitis
        • Common in AIDS patients
        • Ulcers and mucosal erosions
        • Abdominal pain, weight loss, and diarrhea may be seen
      • Esophagitis
        • Presents as dysphagia or odynophagia
        • Common cause of AIDS esophagitis
        • Shallow linear ulcers seen on biopsy
          • Biopsy aids definitive diagnosis
      • Pneumonitis
        • Especially after lung transplant
        • Fever, shortness of breath, cough
        • Interstitial pneumonitis may be difficult to distinguish from acute rejection
      • May cause widespread organ failure (tissue-invasive CMV)
    • Congenital CMV
      • Only 10% of affected infants symptomatic (90% asymptomatic)
        • Nonspecific symptoms (petechiae, jaundice, hepatosplenomegaly, small size for gestational age, and microcephaly)
      • May be complicated by hearing loss
  • Diagnosis
    • Histopathology
      • Classic “owl’s eye” appearance
        • Enlarged cells, with intranuclear inclusions surrounded by clear halos
    • PCR or anti-CMV antibodies (IgM or IgG) are diagnostic
      • Low-yield due to inability to test without giving you the answer
    • Peripheral blood smear shows atypical lymphocytosis
    • Negative monospot test
  • Treatment
    • In immunocompetent patients, no pharmacotherapy is indicated
    • In severe disease or immunocompromised patients
      • Ganciclovir/Valganciclovir are widely used in AIDS or transplant recipients
      • Foscarnet also used in CMV retinitis
      • Cidofovir is rarely added as adjunct therapy
      • Acyclovir and related drugs are not effective
        • Due to lack of needed viral thymidine kinase for drug activation