Chickenpox (Varicella Zoster)

Chickenpox (Varicella Zoster) is a topic covered in the 5-Minute Clinical Consult.

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Basics

Description

  • Highly contagious, generalized exanthem characterized by crops of pruritic vesicles on the skin and mucous membranes following exposure to varicella-zoster virus (VZV)
  • VZV is spread by respiratory (airborne) droplets and direct contact with vesicles.
  • VZV establishes latency in the dorsal root ganglia; reactivation results in herpes zoster (shingles).
  • Chickenpox outbreaks tend to occur late winter through early spring in temperate climates.
  • Usual incubation period is 14 to 16 days (range: 10 to 21 days) after exposure to varicella OR herpes zoster (shingles) rash. Patients are infectious from ~48 hours before appearance of vesicles until the final lesions have crusted.
  • Historically, most people acquired chickenpox during childhood and developed lifelong immunity. The varicella vaccine became available in 1995 (1). Varicella is currently part of recommended primary vaccination schedule for children.
  • System(s) affected: nervous, skin/exocrine
  • Synonym(s): varicella

Epidemiology

  • Peak incidence 3 to 9 years but may occur at any age
  • Predominant gender: male = female

Incidence
  • Decreasing incidence since routine vaccination; estimated 3.5 million cases annually prior to vaccine, with an incidence of 8–9% in children age 1 to 9 years
  • Reported U.S. varicella cases: 1991: 147,076; 2017: 8,775 cases (1)
  • Prior to vaccine, ~100 deaths per year were reported in the US; in 2015, there were 6 reported deaths (1).
  • U.S. rates: 1994, prior to vaccine: 136/100,000 persons; 2013 to 2014: <0.001/100,000 persons
  • Rates of varicella in the United States dropped after vaccine introduction until mid-2000s when they plateaued; second dose of vaccine recommended in 2006 and rates have again declined
  • In developing countries, varicella is still associated with a severe disease burden.
  • Susceptible (immunologically naive) individuals exposed to varicella are at risk to develop disease and are also potentially infectious for 21 days.

Etiology and Pathophysiology

  • Viral particles are inhaled via respiratory droplets where they invade respiratory epithelium. Replication in regional respiratory tract lymph nodes are followed by primary viremia (4 to 6 days after exposure). A second phase of viral replication and a secondary viremia (14 to 16 days after exposure) contribute to epidermal invasion and the characteristic skin lesions.
  • Skin lesions are histologically identical to herpes simplex virus.
  • In fatal cases, intranuclear inclusions are found in vascular endothelium and most organs.
  • VZV is a double-stranded DNA virus of the α-Herpesviridae subfamily.
  • Humans are primary disease reservoir.

Risk Factors

  • For primary disease: no history of prior varicella infection or immunization, immunocompromised (especially children with leukemia/lymphoma in remission or receiving high-dose corticosteroids), pregnancy

Geriatric Considerations

  • Infection is more severe in adults.
  • Reactivation of latent infection causes herpes zoster (shingles).
  • The CDC recommends vaccinating all immunocompetent adults >50 years old with recombinant varicella vaccine (Shingrix). The live attenuated vaccine (Zostavax) is no longer available for use in the United States as of November 18, 2020.
  • The recombinant zoster vaccine (Shingrix) is administered as a 2-dose series separated by 2 to 6 months. This vaccine can be given to patients with a history of shingles or who have already had a dose of the live attenuated zoster vaccine.
  • Primary viral pneumonia is the most common cause of death from varicella.

Pediatric Considerations

  • Neonates born to mothers who develop chickenpox from 5 days before to 2 days after delivery are at risk for serious disease and should receive varicella-zoster immune globulin (VZIG).
  • Newborns are at highest risk for severe disease during the 1st month of life, especially if mother is seronegative.
  • Delivery prior to 28 weeks increases risk.
  • Varicella bullosa is seen mainly in children <2 years. Lesions appear as bullae instead of vesicles. The clinical course is otherwise similar.
  • Septic complications and encephalitis are the most common causes of death from zoster in children.
  • Avoid aspirin/acetylsalicylic acid in children because of link to Reye syndrome.

Pregnancy Considerations

  • 25% risk of transplacental infection after maternal infection
  • Congenital malformations are seen in 2% of patients when the fetus is infected during the 1st or 2nd trimester, characterized by limb atrophy, cutaneous scarring, and occasional CNS and eye manifestations.
  • Morbidity (e.g., pneumonia) is increased in women infected during pregnancy.

General Prevention

  • Isolate hospitalized patients.
  • When indicated, administer passive immunization using VZIG within 96 hours (can be as long as up to 10 days) after exposure. VZIG recommended for:
    • Patients exposed to chickenpox or shingles who are immunocompromised, newborns of mothers with onset of chickenpox <5 days before delivery or <2 days after delivery, premature infants (<28 weeks) exposed in neonatal period either whose mothers are not immune, or babies who weigh <1,000 g regardless of maternal immunity
  • Active immunization prevents or reduces the severity of varicella if given within 72 hours of exposure.
  • Active immunization: varicella virus vaccine (Varivax): live attenuated vaccine recommended by ACIP for immunization of healthy patients ≥12 months who have not had chickenpox
    • 12 months to 12 years: initial dose 0.5 mL SC at age 12 to 15 months; second dose at age 4 to 6 years. Single dose is 85–94% effective in preventing severe disease. The 2-dose regimen is 96–98% effective. Breakthrough disease generally has <50 lesions, shorter duration, and lower fever incidence (2)[A].
    • ≥13 years: two 0.5 mL SC doses 4 to 8 weeks apart, seroconversion rates 78–82% after 1 dose, 99% after 2 doses; adult efficacy in lower end of this range
    • 2014 U.S. estimate: 91% one or more-dose vaccine coverage for children 19 to 35 months (3)
    • Vaccine side effects are pain and redness at the vaccine site (19% of children; 24% of teens and adults). 1 in 10 develops fever. 1 in 25 will develop a mild varicella-like rash up to 1 month after vaccination.
    • Vaccine contraindications
      • Severe allergic reaction (e.g., anaphylaxis) to a previous dose or vaccine component
      • Severe immunodeficiency (e.g., HIV patients with very low CD4 counts, chemotherapy, congenital immunodeficiency, long-term immunosuppressive therapy)
      • Pregnancy
  • MMRV vaccine, combines the measles, mumps, and rubella vaccine with varicella, is equally effective. There are rare reports of an increased risk of febrile seizures 5 to 12 days after vaccination in 1/2,300 to 2,600 patients.
  • May be considered for a subset of HIV-positive children in CDC class I with CD4 >25%
    • Vaccine recipients who develop a rash should avoid contact with immunocompromised people, pregnant women who have never had chickenpox, and their newborns.
    • Allow at least 3 months between doses 1 and 2 in children needing catch-up vaccination.

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Basics

Description

  • Highly contagious, generalized exanthem characterized by crops of pruritic vesicles on the skin and mucous membranes following exposure to varicella-zoster virus (VZV)
  • VZV is spread by respiratory (airborne) droplets and direct contact with vesicles.
  • VZV establishes latency in the dorsal root ganglia; reactivation results in herpes zoster (shingles).
  • Chickenpox outbreaks tend to occur late winter through early spring in temperate climates.
  • Usual incubation period is 14 to 16 days (range: 10 to 21 days) after exposure to varicella OR herpes zoster (shingles) rash. Patients are infectious from ~48 hours before appearance of vesicles until the final lesions have crusted.
  • Historically, most people acquired chickenpox during childhood and developed lifelong immunity. The varicella vaccine became available in 1995 (1). Varicella is currently part of recommended primary vaccination schedule for children.
  • System(s) affected: nervous, skin/exocrine
  • Synonym(s): varicella

Epidemiology

  • Peak incidence 3 to 9 years but may occur at any age
  • Predominant gender: male = female

Incidence
  • Decreasing incidence since routine vaccination; estimated 3.5 million cases annually prior to vaccine, with an incidence of 8–9% in children age 1 to 9 years
  • Reported U.S. varicella cases: 1991: 147,076; 2017: 8,775 cases (1)
  • Prior to vaccine, ~100 deaths per year were reported in the US; in 2015, there were 6 reported deaths (1).
  • U.S. rates: 1994, prior to vaccine: 136/100,000 persons; 2013 to 2014: <0.001/100,000 persons
  • Rates of varicella in the United States dropped after vaccine introduction until mid-2000s when they plateaued; second dose of vaccine recommended in 2006 and rates have again declined
  • In developing countries, varicella is still associated with a severe disease burden.
  • Susceptible (immunologically naive) individuals exposed to varicella are at risk to develop disease and are also potentially infectious for 21 days.

Etiology and Pathophysiology

  • Viral particles are inhaled via respiratory droplets where they invade respiratory epithelium. Replication in regional respiratory tract lymph nodes are followed by primary viremia (4 to 6 days after exposure). A second phase of viral replication and a secondary viremia (14 to 16 days after exposure) contribute to epidermal invasion and the characteristic skin lesions.
  • Skin lesions are histologically identical to herpes simplex virus.
  • In fatal cases, intranuclear inclusions are found in vascular endothelium and most organs.
  • VZV is a double-stranded DNA virus of the α-Herpesviridae subfamily.
  • Humans are primary disease reservoir.

Risk Factors

  • For primary disease: no history of prior varicella infection or immunization, immunocompromised (especially children with leukemia/lymphoma in remission or receiving high-dose corticosteroids), pregnancy

Geriatric Considerations

  • Infection is more severe in adults.
  • Reactivation of latent infection causes herpes zoster (shingles).
  • The CDC recommends vaccinating all immunocompetent adults >50 years old with recombinant varicella vaccine (Shingrix). The live attenuated vaccine (Zostavax) is no longer available for use in the United States as of November 18, 2020.
  • The recombinant zoster vaccine (Shingrix) is administered as a 2-dose series separated by 2 to 6 months. This vaccine can be given to patients with a history of shingles or who have already had a dose of the live attenuated zoster vaccine.
  • Primary viral pneumonia is the most common cause of death from varicella.

Pediatric Considerations

  • Neonates born to mothers who develop chickenpox from 5 days before to 2 days after delivery are at risk for serious disease and should receive varicella-zoster immune globulin (VZIG).
  • Newborns are at highest risk for severe disease during the 1st month of life, especially if mother is seronegative.
  • Delivery prior to 28 weeks increases risk.
  • Varicella bullosa is seen mainly in children <2 years. Lesions appear as bullae instead of vesicles. The clinical course is otherwise similar.
  • Septic complications and encephalitis are the most common causes of death from zoster in children.
  • Avoid aspirin/acetylsalicylic acid in children because of link to Reye syndrome.

Pregnancy Considerations

  • 25% risk of transplacental infection after maternal infection
  • Congenital malformations are seen in 2% of patients when the fetus is infected during the 1st or 2nd trimester, characterized by limb atrophy, cutaneous scarring, and occasional CNS and eye manifestations.
  • Morbidity (e.g., pneumonia) is increased in women infected during pregnancy.

General Prevention

  • Isolate hospitalized patients.
  • When indicated, administer passive immunization using VZIG within 96 hours (can be as long as up to 10 days) after exposure. VZIG recommended for:
    • Patients exposed to chickenpox or shingles who are immunocompromised, newborns of mothers with onset of chickenpox <5 days before delivery or <2 days after delivery, premature infants (<28 weeks) exposed in neonatal period either whose mothers are not immune, or babies who weigh <1,000 g regardless of maternal immunity
  • Active immunization prevents or reduces the severity of varicella if given within 72 hours of exposure.
  • Active immunization: varicella virus vaccine (Varivax): live attenuated vaccine recommended by ACIP for immunization of healthy patients ≥12 months who have not had chickenpox
    • 12 months to 12 years: initial dose 0.5 mL SC at age 12 to 15 months; second dose at age 4 to 6 years. Single dose is 85–94% effective in preventing severe disease. The 2-dose regimen is 96–98% effective. Breakthrough disease generally has <50 lesions, shorter duration, and lower fever incidence (2)[A].
    • ≥13 years: two 0.5 mL SC doses 4 to 8 weeks apart, seroconversion rates 78–82% after 1 dose, 99% after 2 doses; adult efficacy in lower end of this range
    • 2014 U.S. estimate: 91% one or more-dose vaccine coverage for children 19 to 35 months (3)
    • Vaccine side effects are pain and redness at the vaccine site (19% of children; 24% of teens and adults). 1 in 10 develops fever. 1 in 25 will develop a mild varicella-like rash up to 1 month after vaccination.
    • Vaccine contraindications
      • Severe allergic reaction (e.g., anaphylaxis) to a previous dose or vaccine component
      • Severe immunodeficiency (e.g., HIV patients with very low CD4 counts, chemotherapy, congenital immunodeficiency, long-term immunosuppressive therapy)
      • Pregnancy
  • MMRV vaccine, combines the measles, mumps, and rubella vaccine with varicella, is equally effective. There are rare reports of an increased risk of febrile seizures 5 to 12 days after vaccination in 1/2,300 to 2,600 patients.
  • May be considered for a subset of HIV-positive children in CDC class I with CD4 >25%
    • Vaccine recipients who develop a rash should avoid contact with immunocompromised people, pregnant women who have never had chickenpox, and their newborns.
    • Allow at least 3 months between doses 1 and 2 in children needing catch-up vaccination.

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