Varicella Zoster Virus

Aka: Varicella Zoster Virus, Chickenpox, Chicken Pox, VZV, Human Herpesvirus 3, Varicella-Zoster Virus

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II. Epidemiology

  1. Peak onset ages 5 to 9 years old
  2. Outbreak time: January to May
  3. Incidence: 3.7 Million cases/year in U.S. 1980-1990
  4. Varicella Immunity
    1. Adults (U.S): 95% immune
    2. Adults (U.S.) without known VZV history: 75% immune

III. Etiology

  1. Herpes Varicella Zoster Virus
  2. Human Herpes Virus (Herpesviridae)

IV. Pathophysiology

  1. Incubation Period: 10-21 days (after respiratory transmission)
  2. Transmission
    1. Transplacental (vertical transmission)
    2. Direct contact or Respiratory droplet
      1. Household contact transmission: 90%
      2. Limited exposure: 10-35%

V. Symptoms

  1. Viral Prodrome (prodrome is often absent in children, who have rash at onset)
    1. Fever
    2. Anorexia
    3. Malaise
    4. Headache
    5. Myalgia
    6. Upper Respiratory Infection
  2. Pruritic rash
    1. See signs for description

VI. Signs

  1. Generalized Lymphadenopathy
  2. Rash (present in 100% of cases)
    1. Crops of small, Red Papules or Vesicles
      1. Start as Macules and transition to Papules, Vesicles and then Pustules
        1. In vaccinated patients, lesions remain maculopapular (not vesicular)
        2. If Immunocompromised, may develop progressive and extensive lesions
          1. May also appear septic, with multisystem organ involvement
      2. Lesions are in various stages of healing (contrast with Smallpox in which lesions at same stage)
      3. No longer contagious when all lesions have crusted (typically after 4-5 days)
    2. Develop into "Dew Drop on a rose petal" appearance
      1. Oval, "teardrop" Vesicles
      2. Erythematous base
    3. Spread centripetally from head to trunk
      1. Starts on face and scalp and spreads to trunk and back
      2. Minimal limb involvement
      3. May involve oral or vaginal mucosa
    4. Images
      1. DermVaricellaZoster.jpg

VII. Differential Diagnosis

  1. Herpes Simplex Virus
  2. Herpes Zoster Virus (Shingles)
  3. Impetigo
  4. Coxsackie virus
  5. Papular Urticaria
  6. Scabies
  7. Dermatitis Herpetiformis
  8. Drug rash
  9. Smallpox
    1. Vesicular lesions that are all in the same stage

VIII. Labs: Diagnosis

  1. Varicella is typically a clinical diagnosis (and formal testing is not typically needed)
    1. However, consider testing when diagnosis is unclear, especially in pregnancy, Immunocompromised patients
  2. Varicella PCR
    1. Preferred diagnostic test when needed
    2. Sample sources
      1. Vesicle (punture with needle or unroof and swab the base)
      2. Lesion crust
  3. Other tests
    1. Varicella tissue culture
      1. Lower Test Sensitivity than PCR, and longer wait
    2. Vesicular fluid exam (Tzanck Smear)
      1. Multinucleated giant cells
      2. Epithelial cells with Eosinophilic inclusion bodies
      3. Virus
    3. Varicella Serology
      1. Varicella IgG titers (obtain acute and convalescent titers)

IX. Labs: Other

  1. Complete Blood Count (CBC)
    1. Slight Leukocytosis
  2. IgG Antibody to VZV (ELISA)
    1. Immunity testing indicated in pregnancy

X. Management: General

  1. Reduction of Pruritus
    1. Calamine Lotion
    2. Oatmeal Bath (Aveeno)
    3. Atarax at bedtime
  2. Prevention of Superinfection
    1. Apply Bacitracin to denuded lesions until scab forms
  3. Hospitalization Indications
    1. Immunocompromised state or pregnancy <20 weeks gestation (see IV protocol below)
    2. Malignancy (e.g. Leukemia)
      1. Mortality rates are as high as 30%
    3. Varicella Complications (e.g. Pneumonia)
  4. Close observation and consider hospitalization
    1. Children <1 year old
    2. Adults with primary varicella (consider admission)
      1. Mortality >25 fold over that of children

XI. Management: Virus Suppression

  1. Antiviral therapy is routinely recommended only in patients at higher risk of complications
    1. Unvaccinated patients >12 years old
    2. Chronic skin conditions
    3. Chronic lung disease (e.g. Asthma, COPD, Cystic Fibrosis)
    4. Patients on Salicylates or Corticosteroids (including Inhaled Corticosteroids)
    5. Pregnancy (see protocol below)
    6. Immunocompromised patients (see protocol below)
  2. Normal host: Acyclovir (or Valacyclovir or Famciclovir)
    1. Dosing
      1. Acyclovir 20 mg/kg/dose (up to 800 mg/dose) 4 times per day for 5 days
    2. Efficacy
      1. Shortens time of viral shedding
      2. Most effective if started within 24 hours of rash (some effect up to 72 hours)
        1. Faster cessation of new lesions
        2. Fever duration reduced
        3. More rapid healing
    3. Indications
      1. Consider especially in large household
    4. Adverse effects
      1. Avoid if Dehydration present
      2. Not associated with short-term viral resistance
    5. References
      1. Balfour (2001) Pediatr Infect Dis J 20:219-26 [PubMed]
  3. Immunocompromised (including high dose Corticosteroids for >14 days) or pregnancy exposure <20 weeks gestation
    1. VZIG
      1. See postexposure protocol below
    2. Acyclovir
      1. Initiate as soon as possible with onset of rash
      2. Indicated within 10 days of rash onset
      3. Dose: 500 mg/m2/day IV divided q8 hours for 7 days

XII. Prevention: Preexposure

  1. Varicella Vaccine (Varivax)
    1. Vaccinated patients may become infected, but tend to have a milder course

XIII. Prevention: Postexposure Prophylaxis

  1. Indications
    1. Exposure between 2 days before rash onset and when all skin lesions have crusted (4 to 5 days) AND
    2. Not immune
      1. No history of Varicella Zoster Virus infection and negative Serology or
      2. Less than 2 doses of Varicella Zoster Virus Vaccine
  2. Healthy patients
    1. Varicella Vaccine within 3-5 days of exposure
  3. Immunocompromised, pregnant women, or newborns (mother with rash 5 days before or 2 days after delivery)
    1. Varicella zoster immune globulin (VZIG) 125 units per 10 kg IM
      1. Avoid delays (best within first 96 hours, but may be given up to 10 days postexposure)
    2. Immune globulin (IVIG) 400 mg/kg IV
      1. Give only if VZIG not available
  4. Oral Acyclovir
    1. Consider for 7-10 days after exposure in Immunocompromised children without Varicella Immunity
  5. References
    1. Marin (2007) MMWR Recomm Rep 56(RR-4): 1-40 [PubMed]

XIV. Course

  1. Incubation Period: 11-21 days
  2. Infectious
    1. Start: 1-3 days before rash
    2. End: Final lesion crusted (4-5 days after rash onset)

XV. Complications: General

  1. Highest complication rates are in infants age <1 year
    1. Teens and adults also have higher complication rates
    2. Lowest complication rates in young children and pre-teen (age 1 to 12 years)
  2. Progressive varicella (Immunocompromised patients)
    1. Extensive lesions developing over a longer course
    2. Sepsis and multiorgan involvement may occur
  3. Lung involvement (14-30% of adults)
    1. Viral PneumoniaIncidence 1 case per 400 adult cases
    2. Secondary Bacterial Pneumonia
  4. Encephalitis
    1. Occurs in 1.8 per 10,000 varicella infections
  5. Acute Cerebellar Ataxia
    1. Occurs in 1 per 4000 varicella infections in children <15 years old
  6. Herpes Zoster
    1. Unvaccinated children <18 years will develop zoster in 230 per 100,000 Varicella cases
  7. Secondary Bacterial Infection (superinfection) common (esp. if fever>5 days)
    1. Cellulitis
    2. Abscess
    3. Erysipelas
    4. Otitis Media
    5. Invasive Group A Beta-hemolytic Streptococcus
      1. Incidence: 5.2 cases per 100,000 VZV cases
      2. Increasing Incidence
      3. Suspect if fever persists >3-4 days after exanthem
    6. Septic Arthritis
    7. Osteomyelitis
    8. Staphylococcal pyomyositis
    9. Disseminated disease in Immunocompromised
  8. Reye's Syndrome
    1. Avoid concurrent Aspirin use in children
  9. Nephritis
  10. Varicella mortality
    1. Pre-Vaccine era (1987-1992)
      1. Deaths: 80-105 per year (mostly children), once every 4 days in U.S.
      2. Most deaths occur under age 20 years old, an often in otherwise healthy children
    2. Post-Vaccine era
      1. Deaths: 17 per year (2008 to 2011 in U.S.)

XVI. Complications: Congenital Syndrome (Pregnancy related)

  1. General
    1. Non-immune Mother exposed to Varicella Zoster Virus
    2. Congenital syndrome risk 13-20 weeks gestation (2% risk if mother has varicella)
    3. Not associated with Pregnancy loss
    4. Not associated with Preterm Labor
  2. Infant Findings
    1. Skin lesions
    2. Short limbs and digits
    3. Ocular abnormalities
    4. Muscular atrophy
    5. Intrauterine Growth Retardation

XVII. References

  1. Harrison and Ruttan (2019) Crit Dec Emerg Med 33(7): 3-12
  2. Harrison and Ruttan (2023) Crit Dec Emerg Med 38(2): 23-31
  3. Doctor (1995) Pediatrics 96:428-33 [PubMed]
  4. Spencer (2017) Am Fam Physician 95(12): 786-94 [PubMed]

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