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Varicella-Zoster virus (VZV) infections

The varicella-zoster virus causes varicella (chickenpox) and shingles (herpes zoster). It is very contagious. Chickenpox is usually a childhood infection that begins with a prodrome of fever, headache, and malaise followed by a generalized vesicular rash. It is characterized by the appearance of papules and pruritic vesicles that evolve to pustules and crusts. Lesions typically begin on the face and scalp, spreading inferiorly to the trunk and extremities. Herpes zoster is a painful vesicular eruption that usually occurs in adults. After affecting a patient early in life, the varicella-zoster virus lies dormant in a dorsal root ganglion until reactivation occurs. The rash is unilateral and limited to one or more adjacent dermatomes. Management includes symptomatic treatment and antiviral therapy. | MedComic/Jorge Muniz

Varicella zoster virus is one of the herpesviruses and it causes two diseases – varicella or chickenpox, and herpes zoster also known as shingles.

  • Naturally infects humans
  • No animal reservoir
  • Main targets: T lymphocytes, epithelial cells and ganglia

Epidemiology

Epidemiology of VZV infections
Epidemiology of VZV infections | Mueller, N. H., Gilden, D. H., Cohrs, R. J., Mahalingam, R., & Nagel, M. A. (2008). Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency. Neurologic Clinics, 26(3), 675–viii. https://doi.org/10.1016/j.ncl.2008.03.011
  • Worldwide incidence and is endemic in populations of sufficient size to sustain year-round transmission, with epidemics occurring every 2–3 years.
  • Strong seasonal pattern (peak incidence during winter and spring or during the cool, dry season)

Microbiology

Varicella-zoster virus (VZV, also known as human herpesvirus 3) is a ubiquitous alphaherpesvirus with a double-stranded DNA genome.

Varicella (Chickenpox) Virus
Electron micrograph of a Varicella (Chickenpox) Virus. Varicella or Chickenpox, is an infectious disease caused by the varicella-zoster virus, which results in a blister-like rash, itching, tiredness and fever. | By Photo Credit:Content Providers(s): CDC/Dr. Erskine Palmer/B.G. Partin – This media comes from the Centers for Disease Control and Prevention’s Public Health Image Library (PHIL), with identification number #1878.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−, Public Domain, https://commons.wikimedia.org/w/index.php?curid=816522

Presentation

Disease course:

  1. Varicella (chickenpox) infection
  2. Latent phase
  3. Zoster (shingles)
Different phases of VZV infection
Different phases of VZV infection: Primary infection with varicella zoster virus (VZV) in susceptible individuals causes varicella, which usually is harmless in healthy children whose immune system controls the infection. VZV establishes latency in ganglionic neurons, and reactivation of viral replication and spread of the virus to the skin innervated by these neurons causes zoster. Increasing age and compromised immune function are risk factors for complications of VZV infections. However, some of these complications, such as postherpetic neuralgia, can also occur without these predisposing factors | Mueller, N. H., Gilden, D. H., Cohrs, R. J., Mahalingam, R., & Nagel, M. A. (2008). Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency. Neurologic Clinics, 26(3), 675–viii. https://doi.org/10.1016/j.ncl.2008.03.011

Varicella (Chickenpox)

Chickenpox, also known as varicella, is a highly contagious disease caused by the initial infection with Varicella-Zoster virus (VZV).
Varicella zoster: Chicken pox
The Calgary Guide | http://calgaryguide.ucalgary.ca/

Maculopapular rash and vescicles

Diffuse prurititic, vescicular rash most priminent on face and chest that appears 24-48 hr after the prodromal symptoms as intensely pruritic erythematous macules. Rash becomes non-contageous after crusting of lesions
Clinical manifestation of herpes zoster
Clinical manifestation of herpes zoster. | Wood MJ, Easterbrook P. Shingles, scourge of the elderly: the acute illness. In: Sacks SL, Straus SE, Whitley RJ, Griffiths PD, eds. Clinical Management of Herpes Zoster. Amsterdam, Netherlands: IOS Press; 1995:193-209.

Herpes zoster (Shingles)

Shingles, also known as herpes zoster, is a viral disease characterised by a painful skin rash with blisters in a localised area.
Herpes zosters: Shingles
The Calgary Guide | http://calgaryguide.ucalgary.ca/
A case of shingles that demonstrates the typical dermatomal distribution, in this case C8/T1
A case of shingles that demonstrates the typical dermatomal distribution, in this case C8/T1 | By James Heilman, MD – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=14082247
  • Affected dermatome (eg. Thoracic dermatome (M/C)):
    • Burning discomfort
    • Discrete vesicles (3-4 days later)

Complications

Neurologic complications of varicella zoster virus reactivation
Neurologic complications of varicella zoster virus reactivation. | Mueller, N. H., Gilden, D. H., Cohrs, R. J., Mahalingam, R., & Nagel, M. A. (2008). Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency. Neurologic Clinics, 26(3), 675–viii. https://doi.org/10.1016/j.ncl.2008.03.011

Cutaneous complications:

Seen in both chicken pox and shingles
  • Secondary bacterial infections of the skin lesions (common)
  • Necrotizing fasciitis (rare)

Neurologic complications:

  • Cranial nerve palsy
  • Myelitis
  • Encephalitis
  • Granulomatous cerebral angiitis: Cerebrovascular complication leading to stroke-like syndrome in association with shingles (esp. in ophthalmic distribution)
  • Post-herpetic neuralgia (M/C): Persistence of pain for ≥ 1-6 months following healing of rash
  • Geniculate ganglion:
    • Ramsay Hunt syndrome/Herpes zoster oticus
      • TRIAD: Ipsilateral facial paralysis + Ear pain + Vescicles (on face, on/in the ear)
  • Sacral nerve root involvement:
    • Bowel & bladder dysfunction

Ramsay Hunt syndrome:

Shingles in ophthalmic division of Trigeminal
  • Vescicles on cornea → Ulceration → Blindness
  • URGENT OPHTHALMOLOGY REVIEW required

Progressive varicella syndrome

Seen in immunocompromised individuals
  • Continued development of lesions
  • Hemorrhagic lesions
  • Coagulopathy and visceral organ involvement (including hepatitis, pneumonia and encephalitis)

Congenital varicella syndrome

Following infection in the 1st & 2nd trimester at a frequency of 0.4-2%
  • Cicatrix: Characteristic zigzag skin scarring in a dermatomal distribution
  • Malformed extremities
  • Cataracts and brain abnormalities (e.g. aplasia, calcifications)
  • If the disease occurs in the mother 5 days before to 2 days after delivery: Severe and often fatal neonatal disease

Diagnosis

  • In atypical cases,
    • Diagnosis is made on Tzanck smear of the lesions
      • Shows multinucleated cells
    • IgM antibodies to varicella

Differential diagnosis:

  • Vesicular exanthemata (eg. Herpes simplex)
  • Enteroviral infections (hand-foot-mouth disease)
  • Insect bites
  • Drug reactions
Comparison of the epidemiology, clinical features, complications, and clinical course among the three herpes viruses
Comparison of the epidemiology, clinical features, complications, and clinical course among the three herpes viruses | Abbreviations: HSV, herpes simplex virus; VZV, varicella-zoster virus; CMV, cytomegalovirus; va, cranial nerve V1; KP, keratic precipitate; AC, anterior chamber; IOP, intraocular pressure.

Management

Symptomatic management:

  • Antipyretics
  • Antipruritic agents
  • Good hygiene

Medical management:

Aspirin is contraindicated due to the risk of Reye syndrome. Management of shingles is same as chickenpox but with duration of 7-10 days
  • Adult/child:
    • Oral aciclovir 800mg 5 times daily for 5 days
    • Famciclovir 500mg 3 times daily for 5 days
    • Valaciclovir 1g 3 times daily for 5 days
  • Immunocompromised/pregnant host:
    • IV Aciclovir 5mg/kg daily
      • If improves, switch to oral therapy

Post-exposure prophylaxis:

  • Varicella zoster immune globulin (YZIG)

Prevention:

  • Live attenuated vaccine (Oka strain)
Varicella zoster virus (VZV)
Varicella zoster virus (VZV) causes varicella (chickenpox) and, upon reactivation following latency, zoster (shingles). The development of vaccines to reduce the disease burden, particularly in at-risk populations (for example, pregnant women and the elderly), are a current focus. | Gershon, A. A., Breuer, J., Cohen, J. I., Cohrs, R. J., Gershon, M. D., Gilden, D., … Yamanishi, K. (2015). Varicella zoster virus infection. Nature Reviews Disease Primers, 1, 15016. Retrieved from https://doi.org/10.1038/nrdp.2015.16

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