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Varicella-Zoster Virus (HHV3)

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Key Points

  • Varicella-Zoster virus (VZV)
    • Characteristics
      • Member of Herpesvirus family
        • Also known as human herpesvirus 3 (HHV-3)
        • 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
      • Respiratory droplets
      • Direct contact with infected lesions
    • Pathogenesis and Presentation
      • Primary infection
        • Replicates inside T-cells, which disseminate through body to cause viremia
        • Chickenpox (varicella zoster)
          • Generalized pruritic vesicular rash
          • Usually seen in children
          • Encephalitis
            • Cerebellar ataxia or diffuse encephalitis are possible
          • Pneumonia
            • Rare, but accounts for majority of deaths in adults
            • Dry cough and progressive shortness of breath
      • Dormancy in sensory ganglia
        • Enters sensory nerves and moves by retrograde transport
        • Usually resides in dorsal root ganglion or trigeminal ganglia
      • Reactivation
        • Often precipitated by immunocompromise (elderly, stress, etc.)
          • Rarely occurs in healthy individuals
        • Virus replicates in ganglion and is transported by anterograde transport to skin
        • Shingles (herpes zoster)
          • Affects single dermatome (or connected dermatomes)
          • Burning/stabbing nerve pain
            • Caused by acute neuritis in sensory nerve
            • Usually precedes rash by 2-3 days
            • Often complicated by postherpetic neuralgia (PHN)
              • “Stabbing” or “burning” pain in same distribution that may last months after resolution
              • Thought to result from inflammation and necrosis from viral replication in ganglia
          • Unilateral vesicular rash
            • Rupture of vesicles produces ulcers that crust over weeks
            • Contagious until ulcers are dry (7-10 days)
          • Blindness (rare)
            • CN V1 branch involvement  (herpes zoster ophthalmicus) can lead to visual impairment
            • Retinal necrosis can also cause blindness
          • Ramsay-Hunt syndrome (rare)
            • Describes ear involvement and facial paralysis
    • Diagnosis
      • Diagnosis is mainly clinical; PCR is the gold standard for confirming unclear cases
      • Tzank smear of lesions
        • Epithelial cells scraped from lesion, prepared on Wright-Giemsa stain
        • Multinuclear giant cells
          • intranuclear inclusions (Cowdry type A bodies)
        • High yield; but not used clinically due to poor sensitivity/specificity
    • Treatment
      • Chickenpox is usually not treated pharmacologically
        • symptomatic relief (soothing creams, etc.)
      • Shingles is treated using acyclovir, famciclovir, or valacyclovir
        • Guanosine analog that inhibit viral DNA polymerase (viral DNA synthesis)
        • Requires herpes viral thymidine kinases (phosphorylation) for conversion into their active form
      • Analgesics may be used to control nerve pain