VARICELLA


See also "Varicella Vaccine"

An enveloped DS-DNA virus in the Herpesvirus family

I. Epidemiology

  1. 8.3-9.1% of U.S. kids < 10yo get varicella each year
  2. Annual incidence 3.5-4 million cases
  3. 5-10% of adults are nonimmune (3)
  1. In persons over 18yo and no h/o or unknown h/o varicella, >70% are seropositive (3)
  1. 80-92% of people who think they've never had chicken pox are actually seropositive
  2. $399 in annual health care costs (including time off work) (3)

II. Natural acute infection ("Chicken Pox")

  1. Natural history
  1. Transmitted through direct contact with skin lesions and by airborne resp. droplet infection
  2. Seems to confer lifelong immunity
  3. Rare before age 6mo
  4. 300-500 vesicles, usually crust 5-6d after onset of rash
  5. Fever, headache, malaise
  6. Us. lasts about 5d
  7. Contagious from 1-2d before rash appears until all vescles are crusted over
  8. Lose average of 8.7 days of school; caretakers lose avg 0.5-1.8 days of work (3)
  9. After acute infection, the virus remains dormant in sensory-nerve ganglia

 

  1. Diagnosis
    1. Primarily clinical
    2. DFA of fluid from unroofed lesion can confirm; has largely replaced older "Tzank prep"
    3. For VZV meningitis/encephalitis, PCR of CSF can confirm
  1. Complications of acute infection
  1. 9000 hosps, 50-100 deaths/yr, mostly in kids
  2. Hosp. occurs in about 4/10,000 cases in kids, 30/10,000 cases in adults (13)
  3. Incidence of complications is higher for pts > 15yo or < 1yo; immunocompromised, or premature or low-birth-weight infants
  4. Bacterial superinfection of skin lesions (<5yo)--Usually staph or group A strep
    1. Group A Strep necrotizing fasciitis--risk was significantly associated with use of ibuprofen in one case-control study (Peds. 103:783, 1999--JW)
  1. Encephalitis (>5yo)
  2. Reye’s syndrome (5-14yo)
  3. Pneumonia (<5yo, >15yo)--"Ground-glass" apperance on x-ray typical
  4. Glomerulonephritis
  5. Arthritis
  1. Treament of Chicken Pox
  1. Supportive tx--Analgesics, antipyretics, antipruritics-Avoid ASA which can precipitate Reye's syndrome
  2. Acyclovir 20mg/kg (max 800mg) PO QID x 5d may reduce duration/severity; in immunocompromised, 10mg/kg IV Q8h x 7d
  3. Acyclovir-resistant--Can use Forscarnet 40mg/kg IV Q8h x 10d
  1. Chicken pox in pregnancy
  1. Congenital infection
  1. A low-grade teratogen (4% cong. defects; although this figure is disputed and actual risk is unclear) when infection occurs <16wks
  2. Typical abnormalities inc. limb defects, cataracts, chorioretinitis, cutaneous scars, cortical atrophy, microcephaly, IUGR (3)
  3. Occurs in 2% of infants born to women who contract varicella in 1st or 2nd trimester
  4. Mortality as high as 30% in severe cases (6)
  1. Maternal disease in pregnancy:
  1. Can also be associated with preterm labor
  2. 10-30% of women will get varicella pneumonia, with mortality up to 40%. Acyclovir may help if given early after onset of respiratory symptoms (<72h)
  1. Management of infection in pregnancy:
  1. Not an indication for termination
  2. VZIG administration for exposure of women who have no known clinical h/o varicella is controversial: many of these women are actually seropositive & wouldn't benefit from it; if you're going to give it, do so <96h post-exposure.
  3. Check for dermatomal limb defects by US
  4. Herpes zoster is not of perinatal significance
  5. With maternal varicella where rash appears 2d before to 5d after birth, there is a risk of neonatal varicella; VZIG is indicated in this situation because of the high mortality associated with neonatal varicella.
  1. Postexposure prophylaxis
    1. Acyclovir and Varicella vaccine have been used
    2. Varicella-Zoster Immune Globulin (VZIG, VariZIG)--Can reduce severity of Varicella if given up to 7-10d after exposure. Recommended for:
      1. Immunosuppressed pts exposed to Varicella or disseminated Herpes Zoster
      2. Nonimmune pregnant women exposed to Varicella or desseminated Herpes Zoster
      3. Neonates whose mother developed Varicella between 7d prior to and 28d after delivery

III. Herpes zoster ("Shingles")--A recurrence of latent VZV infection

  1. See also under "Varicella Vaccine"
  2. More common elderly & immunocompromised
  3. Unilateral vesicular eruption w/dermatomal distribution
  4. Natural history in 2 phases:
    1. Prodromal--1-4d of burning/stabbing pain in the affected dermatome, possibly w/malaise and fever
    1. Acute--Dermatomal rash starting as erythematous papules, coalescing and forming clumps of vesicles, pustules, and crusts
      1. Herpes zoster ophthalmicus
        1. Involvement of ophthalmic division of the trigeminal nerve (CN V)
        2. Can be associated with keratitis which can cause blindness (prompt treatment may reduce risk)
        3. Suspect if lesions are on tip of nose
      2. In rare cases (esp. immunocompromised pts) can get disseminated VZV infection as a complication of Herpes Zoster
      3. Treatment
        1. Corticosteroids do not alter incidence or duration of postherpetic neuralgia--208 immunocompetent adults >50yo with herpes zoster for < 72h randomized to 21d of Acyclovir (800mg 5x/d), Prednisone (60mg/d tapering to 15/d), one or the other plus placebo, or 2 placebos (Ann Int. Med 125:376, 1996-JW). Quicker healing of rash and resolution of pain with both drugs than with either alone; persistence of pain at 6 mos didn't differ between combination and single-drug groups. No sig. difference in troublesome sx (e.g. GI sx).
        2. Antivirals may help--Meta-analysis of 5 randomized, placebo-controlled trials involving 792 pts with herpes zoster (avg. age bout 60) who got acyclovir 800mg QID starting < 72h after onset of rash found OR 0.54 for any pain at 6mos; Criticized by varied definitions & reporting of pain in different studies(Arch. Int. Med 157:909, 1997-JW)
    2. NOTE--Some cases of Bell's palsy are ass'd with positive salivary PCR for VZV *Neurol. 55:708, 2000--JW)
  1. Postherpetic Neuralgia--Chronic pain in affected dermatome
    1. Risk of severe pain from postherpetic neuralgia was 0% and mild-moderate pain from postherpetic neuralgia was 3.3% in a series of 421 pts followed after their first episode of herpes zoster; 96% received no antiviral drugs (BMJ 321:794, 2000--JW)
    2. More likely in older pts
    3. In a series of 201 pts with Herpes Zoster, # of lesions and intensity of pain were both ass'd with risk of postherpetic neuralgia (J. Inf. Dis. 179:9, 1999--JW)
    4. Treatment of postherpetic neuralgia (us. defined as pain > 3mos after resolution of rash)
      1. Tricyclic antidepressants more effective than placebo
      2. Gabapentin (Gralise and others)
        1. 229 pts with postherpetic neuralgia randomized to gabapentin (300-1200mg TID titrated upward at weekly intervals) vs. placebo x 8 weeks; sig. greater improvement in pain with gabapentin (JAMA 280:1837, 1998)
      3. Valproic Acid
        1. In a study in about 40 pts with pain from post-herpetic neuralgia x > 6mos randomized to divalproex sodium 1g/d vs. placebo, at 8wks, the divalproex was associated with sig. greater reductions in pain  (QJM 98:29, 2005--AFP)
      4. Intrathecal methylprednisolone ass'd with sig. greter relief of pain than placebo in a randomized trial in 277 pts with > 1y of intractable pain from postherpetic neuralgia (NEJM 343:1514, 2000--JW)
      5. Pregabalin (Lyrica) 50-200mg TID
        1. May cause drowsiness
        2. PDR mentions thrombocytopenia, peripheral edema, myopathy, PR interval prolongation, and "possible tumorigenic potential."
      6. In a systematic review of 206 papers on treatment of postherpetic neuralgia, gabapentin, opioids, pregabalin, topical lidocaine, and tricyclic antidepressants were all felt to have good evidence for efficacy at reducing symptoms (Neurol. 63:959, 2004--JW)
  2. Varicella-zoster Virus Vasculopathy
    1. A rare but serious complication of herpes zoster
    2. Can be associated with CVA (usually ischemic; sometimes hemorrhagic)
    3. In a retrospective study of pts with herpes zoster ophthalmicus, 1y incidence of CVA was 8.1% (compared with 1.7% of control pts); no sig. diff. in CVA incidence between pts who received antiretrovirals c/w those who didn't (Neurol. 74:792, 2010-JW)