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Cytomegalovirus (HHV5)

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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