Varicella-Zoster Virus (HHV3)

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