Varicella

What is varicella?

Varicella (commonly known as chickenpox) is caused by varicella-zoster virus. It usually occurs in childhood and is characterized by a generalized pruritic vesicular rash and fever.1

What are the symptoms of varicella zoster and its manifestations?

Symptoms that develop prior to the onset of rash include malaise, pruritus, anorexia, and listlessness.1,2

Skin manifestations in varying stages of evolution consist of maculopapules, vesicles, pustules, and scabs.1,2

At first, the lesions contain clear fluid, pustulating and scabbing over a short period of time. Rash initially appears on the trunk and face, quickly spreading to other areas of the body. Successive crops of lesions generally continue over a period of 2 to 4 days. Crusts completely fall off within 1 to 2 weeks after infection begins and can leave a slightly depressed area in the skin.1,2

How is varicella transmitted?

The most common mode of transmission of varicella-zoster virus is believed to be person to person from infected respiratory tract secretions containing the varicella-zoster virus that come into contact with the mucosa of the upper respiratory tract or the conjunctiva of the eye.1 The virus is believed to replicate at the site entry in the nasopharynx and in regional lymph nodes. Varicella is usually contagious from 1 to 2 days before onset of rash until lesions have formed crusts.1

What are the clinical features of varicella over time?

Pathogenesis of varicella

 1. INFECTION
DAY 0 
Varicella-zoster virus infects the mucosa of the upper respiratory tract or the conjunctiva of the eye. The virus is thought to replicate in the nasopharynx and regional lymph nodes of the head and neck.1,3,4
Clinical Features of Varicella Over Time
2. PRIMARY VIREMIA
DAY 4–6
Infected T-cells enter the blood stream causing a primary viremia characterized by malaise, fever, and aching back/extremities. Infected T-cells then move to the viscera and sensory ganglia. On the sensory ganglia, a second round of viral replication takes place.1,2,3,4
Clinical Features of Varicella Over Time
 3. SECONDARY VIREMIA
~DAY 14 (can range from 10–21 days) 
Varicella-zoster virus spreads to the skin by way of a secondary viremia, leading to a generalized, pruritic vesicular rash.1,2,3,4
Clinical Features of Varicella Over Time
How is varicella diagnosed?

A varicella diagnosis can be typically based on:

Age of the patient1
Exposure to someone with varicella or herpes zoster within the last 2–3 weeks1,5
Season during which the rash occurs (In the United States, the incidence of varicella is highest between March and May.)1

Rash that:

  • Is itchy (pruritic)1
  • Is accompanied by pain and low-grade fever2
  • Is characterized by lesions that are scattered vs clustered and are located initially on the head and then spread to the trunk, with relative sparing of the extremities1,5
  • Progresses quickly from macules to papules, vesicles, pustules, and finally crusts1,5
What are the complications of varicella?
Possible Varicella Complications
Cutaneous Neurologic Pneumonic
  • Bacterial skin infections that can lead to more serious infections such as bacteremia, toxic shock syndrome, and necrotizing fasciitis5,6
  • Acute cerebellar ataxia and encephalitis1,5
  • Other rare neurologic complications include:
    • Reye’s syndrome1,5
    • Transverse myelitis1
    • Guillain-Barré syndrome1
    • Possible increased risk of stroke7
  • Varicella pneumonia occurs more frequently in healthy adults and is characterized by5,8:
    • Cough
    • Dyspnea
    • High fever
  • These symptoms may also be accompanied by pleuritic chest pain or hemoptysis5,8
Possible Varicella Complications
Cutaneous
  • Bacterial skin infections that can lead to more serious infections such as bacteremia, toxic shock syndrome, and necrotizing fasciitis5,6
Neurologic
  • Acute cerebellar ataxia and encephalitis1,5
  • Other rare neurologic complications include:
    • Reye’s syndrome1,5
    • Transverse myelitis1
    • Guillain-Barré syndrome1
    • Possible increased risk of stroke7
Pneumonic
  • Varicella pneumonia occurs more frequently in healthy adults and is characterized by5,8:
    • Cough
    • Dyspnea
    • High fever
  • These symptoms may also be accompanied by pleuritic chest pain or hemoptysis5,8

Populations at increased risk of severe varicella illness and/or complications1,9:

  • Healthy adults
  • Immunocompromised individuals
  • Children with lymphoma, leukemia, or HIV
  • Pregnant women
  • Developing fetuses
  • Susceptible infants and neonates
What happens if a pregnant woman contracts varicella?

There is a risk of congenital varicella syndrome if the mother contracts varicella in the first 20 weeks of pregnancy. Infant abnormalities include low birth weight, skin scarring, hypoplasia of an extremity, localized muscular atrophy, chorioretinitis, encephalitis, brain atrophy, and death.1,6

If the mother contracts varicella during the perinatal phase, varicella can infect the infant by transplacental viremia (intrauterine exposure), ascending infection during birth, or direct contact with infectious lesions after birth.10

Varicella during the first 12 days of life is attributed to intrauterine exposure, whereas infection after 12 days of birth is attributed to postnatal infection, given a rough 12-day incubation period in the neonate.10

Maternal disease between 20 to 6 days before delivery, or neonatal onset from 5 to 10 days post delivery has resulted in somewhat mild outcomes as infants have had a chance to acquire maternal antibodies to avoid long-term complications. However, maternal disease between 5 days before to 2 days after delivery, or neonatal onset from 5 to 10 days after delivery has resulted in fatal outcomes in 20%-23% of the cases reported.10

Premature neonates aged <28 weeks gestation at birth have a high risk of severe varicella during the first 6 weeks after birth as there appears to be no protective maternal antibodies because of reduced gestational period.10

How does geography affect the disease epidemiology of varicella?
In Regions With Warmer Summers and Cooler Winters, 90% of the Population Is Infected With Varicella Prior to Adolescence
Temperate
Climates

In regions with warmer summers and cooler winters, 90% of the population is infected with varicella prior to adolescence. Peak incidence of varicella typically occurs in the cooler months of the year (ie, winter or spring).1,11

In Tropical Climates, It's Adolescents and Adults Who More Commonly Get Varicella
Tropical
Climates

In tropical climates, adolescents and adults more commonly get varicella.11

Has the prevalence of varicella changed since the introduction of the varicella vaccine?

From 1995 to 2010 in the US surveillance sites of West Philadelphia, PA and Antelope Valley, CA, there was a12:

~98% decline in the number of varicella cases at both surveillance sites since 1995

>85% decline in the number of varicella-related hospitalizations in 2006-2010, compared with 1995-1998

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ref1

Reference

  1. Centers for Disease Control and Prevention (CDC). Varicella. In: Hamborsky J, Kroger A, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington, DC: Public Health Foundation; 2015:353–376. http://www.cdc.gov/vaccines/pubs/pinkbook/index.html. Accessed October 15, 2019.
ref2

Reference

  1. Whitley RJ. Chickenpox and herpes zoster (varicella-zoster virus). In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Vol 2. 9th ed. Philadelphia, PA: Elsevier; 2019:1849-1856.
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  1. Gershon AA, Marin M, Seward JF. Varicella vaccines. In: Plotkin SA, Orenstein WA, Offit PA, Edwards KM, eds. Plotkin’s Vaccines. 7th ed. Philadelphia, PA: Elsevier; 2018: 1145-1180e17.
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Reference

  1. Gershon AA, Gershon, MD. Varicella-zoster virus. In: Richman DD, Whitley RJ, Hayden FG. Clinical Virology. 4th ed. Washington, DC: ASM Press; 2017:459-480.
ref5

Reference

  1. Levin MJ, Schmader KE, Oxman MN. Varicella and Herpes Zoster. In: Kang S, Amagai M, Bruckner AL, et al. Fitpatrick’s Dermatology. 9th ed. McGraw-Hill; 2019:1-72.
ref6

Reference

  1. Centers for Disease Control and Prevention. Chickenpox (varicella): for healthcare professionals. https://www.cdc.gov/chickenpox/hcp/index.html#complications. Updated December 31, 2018. Accessed November 20, 2019.
ref7

Reference

  1. Amlie-Lefond C, Gilden D. Varicella Zoster Virus: A Common Cause of Stroke in Children and Adults. J Stroke Cerebrovasc Dis. 2016;25(7):1561-1569.
ref8

Reference

  1. Denny JT, Rocke ZM, McRae VA, et al. Varicella pneumonia: case report and review of a potentially lethal complication of a common disease. J Investig Med High Impact Case Rep. 2018;6:2324709618770230.
ref9

Reference

  1. Centers for Disease Control and Prevention. Chickenpox (varicella): complications. https://www.cdc.gov/chickenpox/about/complications.html. Updated December 31, 2018. Accessed November 20, 2019.
ref10

Reference

  1. Sauerbrei A. Review of varicella-zoster virus infections in pregnant women and neonates. Health. 2010;2(2):143–152.
ref11

Reference

  1. Heininger U, Seward JF. Varicella. Lancet. 2006;368:1365–1376.
ref12

Reference

  1. Bialek SR, Perella D, Zhang J, et al. Impact of a routine two-dose varicella vaccination program on varicella epidemiology. Pediatrics. 2013;132:e1134–e1140.

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