Herpes Zoster

Aka: Herpes Zoster, Shingles, Zoster Sine Herpete

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II. Epidemiology

  1. Incidence: 1 Million cases in United States annually
    1. Lifetime risk: 30%
  2. Age: Peak onset at 50-79 years old
  3. Gender predominance: Women account for 60% of cases

III. Pathophysiology

  1. Reactivation of latent virus from dorsal root Ganglion
    1. Initial Varicella Zoster Virus infection (Chicken Pox) recedes to cranial and dorsal root ganglia
    2. Occurs in 10-20% of people previously exposed to Chicken Pox
  2. Typically occurs when T cell mediated Immunity decreases (e.g. advancing age, Immunocompromised)
    1. Risk increases 20 to 100 fold over age-matched controls
  3. Inflammation to acute viral ID in segmental nerve
  4. Contagious to non-immune persons
    1. Avoid contact until rash heals

IV. Risk Factors

  1. Age over 50 years old
  2. Chicken Pox at age <1 year old
  3. Altered T cell-mediated Immunity (especially if onset in a younger patient)
    1. HIV Infection
    2. Malignancy (esp. lymphoproliferative disorders)
    3. Organ transplant status
    4. Immunosuppressant use

V. Symptoms: Prodrome

  1. Timing
    1. May be precede rash by 1-5 days
  2. Most common symptoms
    1. Fever (variably present)
    2. Headache
    3. Photophobia
    4. Paresthesias
      1. Pain within Dermatome occurs first
      2. Examples: itching, burning, hyperesthesia
    5. Malaise

VI. Signs: Rash

  1. Timing
    1. Develops after 48-72 hours (up to 5 days before rash)
    2. Lesions heal within 2-4 weeks
  2. Distribution
    1. Follows 1-2 Dermatomes and uncommonly crosses the mid-line (although may occur on back)
    2. Lesions appear proximally first, then distally
    3. Most common regions
      1. Back (esp. T1 to L2)
      2. Face (esp. ophthalmic branch of Trigeminal Nerve, accounting for 15% of cases)
  3. Characteristics
    1. Starts as erythematous, maculopapular rash
    2. Clear Vesicles develop
    3. Vessicles turn cloudy within 3-5 days
    4. Crust over within 7-10 days
    5. Residual scar or pigmentation changes are common
  4. Associated Findings
    1. Tender regional Lymph Nodes
  5. Variants
    1. Zoster Sine Herpete (zoster without a rash)
      1. Zoster without rash is uncommon but does occur
      2. Gilden (2010) Curr Top Microbiol Immunol 342: 243–53 +PMID:20186614 [PubMed]
    2. Hutchinson's Sign (Vesicle on the tip of nose)
      1. Associated with Herpes Zoster Ophthalmicus
      2. Stain the eye for Fluorescein and observe for Dendrites
      3. Exercise high level of suspicion for ocular involvement
    3. Ramsay Hunt Syndrome (Vesicle in ear)
      1. Associated with Bell's Palsy
      2. Course may be more prolonged
  6. Images
    1. DermHerpesZosterEarly.jpg
    2. DermHerpesZosterLate.jpg

VII. Labs: Vesicle fluid testing

  1. Indications
    1. Not routinely indicated (as Shingles is typically a clinical diagnosis)
    2. Recurrent lesions with suspected herpes simplex
    3. Suspected Zoster Sine Herpete (zoster without a rash)
    4. Widely disseminated rash in an immunocompomised patient
    5. Distinguish from other Vesiculobullous Rash (see differential diagnosis below)
  2. Zoster PCR (preferred)
    1. Test Sensitivity: 95%
    2. Test Specificity: 99%
  3. Direct immunofluorescent Antigen staining
    1. Test Sensitivity: 82%
    2. Test Specificity: 76%
  4. Virus Culture
    1. Test Sensitivity: 20%
    2. Test Specificity: 99%
  5. Tzanck Smear of lesion base (Multinucleated giant cells)
    1. Rarely performed now in United States
  6. References
    1. Sauerbrei (1999) J Clin Virol 14(1): 31-36 [PubMed]

VIII. Differential Diagnosis

  1. Cellulitis
  2. Vesicular dermatitis
    1. See Vesiculobullous Rash
  3. Painful serious condition (prior to dermatitis appearance)
    1. Acute Abdomen
    2. Acute Coronary Syndrome

IX. Complications

  1. Hospitalization in 2-3% of cases
  2. Postherpetic Neuralgia
  3. Herpes Zoster Ophthalmicus
    1. Especially if Conjunctivitis or Vesicle at tip of nose
  4. Herpes Zoster Oticus (Ramsay Hunt Syndrome)
  5. Meningitis
  6. Encephalitis
  7. Granulomatous Angiitis with contralateral Hemiplegia
  8. Cutaneous dissemination in Lymphoma (40%)
  9. Diffuse involvement (including pneumonitis)
    1. Occurs in Immunocompromised patients
  10. Longterm increased cardiovascular and Cerebrovascular Disease risk
    1. Growing evidence for association
    2. Erskine (2017) PLoS One 12(7):e0181565 +PMID: 28749981 [PubMed]

X. Management: Antivirals

  1. Relative indications for Antivirals (maximal benefit)
    1. Onset within 72 hours of starting treatment
    2. Age 50 years and older
    3. More than 50 lesions
    4. Continued active Vesicle eruptions (even if delayed beyond the 72 hour window)
    5. Opthalmic or neurologic involvement (even if delayed beyond the 72 hour window)
      1. Includes facial involvement (due to associated risk of ocular involvement)
  2. Precautions
    1. Adjust dosing for Creatinine Clearance <50 ml/min (<60 ml/min for Famciclovir)
  3. Oral Antiviral Agents (oral guanosine analogues)
    1. Acyclovir
      1. Dose: 800 mg orally five times daily for 7-10 days
      2. Reduces healing time, pain, and rash dissemination
      3. Least expensive of all Antiviral options by an order of magnitude
      4. Valacyclovir appeared more effective in over age 50
        1. (1999) Med Lett Drugs Ther 41:113-20 [PubMed]
    2. Valacyclovir
      1. Dose: 1000 mg orally three times daily for 7 days
      2. Equivalent efficacy to Famciclovir
        1. Tyring (2000) Arch Fam Med 9:863-9 [PubMed]
    3. Famciclovir
      1. Dose: 500 mg orally three times daily for 7 days
      2. Lesions healed faster, more brief virus shedding
      3. Reduces Postherpetic Neuralgia duration by 2 months
      4. Reference
        1. Tyring (1995) Ann Intern Med 123:89-96 [PubMed]

XI. Management: Pain Management

  1. See Postherpetic Neuralgia
  2. Analgesics
    1. Schedule Analgesics around the clock (not prn)
    2. Mild to moderate pain
      1. Acetaminophen
      2. NSAIDs
    3. Moderate to severe pain
      1. Opioid Analgesics
    4. Refractory pain (agents used in Postherpetic Neuralgia)
      1. No evidence that these agents reduce acute Shingles pain or that they prevent Postherpetic Neuralgia
      2. Amitriptyline (Elavil)
      3. Gabapentin (Neurontin)
  3. Systemic Corticosteroids
    1. Use is controversial and not routinely recommended
    2. May be associated with increased complications (e.g. Bacterial superinfection)
    3. May reduce acute pain, inflammation and speed up healing
    4. Does not reduce risk of Postherpetic Neuralgia
    5. References
      1. Wood (1994) N Engl J Med 330:896-900 [PubMed]

XII. Management: Special Circumstances

  1. Zoster Ophthalmicus
    1. See Herpes Zoster Ophthalmicus
  2. Immunocompromised Patient
    1. Acyclovir 10 mg/kg IV every 8 hours for 10 days

XIII. Prophylaxis: Varicella Immune Globulin (VZIG) Indications

  1. Immunodeficient under age 15 years
    1. Give within 72-96 hours exposure
  2. Newborn of infected mother
    1. Exposure 5 days before delivery or 2 days after

XIV. Prevention

  1. Avoid contact with active Shingles or Chicken Pox
  2. Consider prophylaxis if exposure in high-risk groups
  3. Varicella Vaccine routinely in children, teens, and adults
    1. May reduce risk of developing Shingles
    2. Part of routine Primary Series
  4. Herpes Zoster Vaccine (Shingles Vaccine, Zostavax)
    1. Recommended in adults over age 50 years (if not contraindicated)
    2. Following a Shingles episode, delay Vaccination until acute Shingles has resolved prior to Vaccination (~8 weeks)
    3. Reduces risk of Herpes Zoster Incidence by 60% and Post-herpetic Neuralgia by 65%

XV. References

  1. Takhar in Majoewsky (2012) EM:Rap 12(11): 12
  2. Berger in Goldman (2000) Cecil Medicine, p. 2130-1
  3. Habif (1996) Dermatology, p. 351-9
  4. Gnann (2002) N Engl J Med 347:340-6 [PubMed]
  5. Fashner (2011) m Fam Physician 83(12): 1432-7 [PubMed]
  6. Saguil (2017) Am Fam Physician 96(10): 656-63 [PubMed]

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