Varicella-Zoster Virus (VZV)

Updated: Oct 01, 2021
  • Author: Zartash Zafar Khan, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Overview

Practice Essentials

Varicella-zoster virus (VZV) causes chickenpox and herpes zoster (shingles). Varicella is characterized by a pruritic, maculopapular, vesicular rash that evolves into noninfectious dried crusts over a 3- to 7-day period. Reactivation of the dormant virus results in the characteristic painful dermatomal rash of herpes zoster, which is often followed by pain in the distribution of the rash (postherpetic neuralgia). 

Typical zoster in the vicinity of right popliteal Typical zoster in the vicinity of right popliteal fossa in a vertebral nerve L4 distribution.

Signs and symptoms

Chicken pox

In children, chicken pox is manifested with fever and irritability, followed by vesicular rash erruption. Rash eventually crusts and heals. 

Chicken pox also can occur in adults without natural or vaccine induced immunity to VZV. 

Herpes zoster (shingles)

  • The most common presentation is the shingles vesicular rash, which most commonly affects a thoracic dermatome. Pain and paresthesia are typically the first symptoms of VZV infection. Until the characteristic vesicular rash erupts, diagnosis may be difficult. A prodromal period during which symptoms may vary is common. 

  • After a prodromal illness of pain and paresthesias, erythematous macules and papules develop and progress to vesicles within 24 hours

  • The vesicles eventually crust and resolve

  • Pain and sensory loss are the usual symptoms

  • Motor weakness also may occurs and is frequently missed on examination

  • Cases of actual monoplegia due to VZV brachial plexus neuritis have been reported

Zoster multiplex

  • Shingles may appear in multiple dermatomes, both contiguous and noncontiguous, on either side of the body

  • Immunocompromised individuals are more susceptible

  • Terminology depends on the number of involved dermatomes and on whether the condition is unilateral or bilateral (eg, zoster duplex unilateralis refers to the involvement of two unilateral dermatomes)

  • Cases of zoster simultaneously occurring in seven noncontiguous dermatomes have been reported

Zoster sine herpete

VZV infection may reactivate without causing cutaneous vesicles. These patients have severe dermatomal pain, possible motor weakness and possible hypesthesia, but no visible rash or vesicles.

VZV infection may present as acute peripheral facial palsy in 8-25% of patients who have no cutaneous vesicles. This is more common in immunosuppressed patients who use acyclovir (or other agents) as zoster prophylaxis. [1]

Central nervous system disease

  • VZV continues to be associated with CNS disease, with meningitis being the most frequent clinical presentation. CNS VZV disease often presented without accompanying zoster rash. [50]

Ramsay-Hunt syndrome

This syndrome occurs when the geniculate ganglion is involved. The clinical presentation includes the following:

  • A peripheral facial palsy

  • Pain in the ear and face

  • Vesicles in the external ear canal (not always present)

  • Additional auditory and vestibular symptoms in some cases

Keratitis (herpes ophthalmicus)

  • Caused by reactivation of VZV infection in the ophthalmic division of the trigeminal nerve.

  • The presentation may include conjunctivitis or corneal ulcers

  • Complications include blindness

  • Vesicles do not have to be present

  • Rarely, the virus migrates along the intracranial branches of the trigeminal nerve, causing thrombotic cerebrovasculopathy with severe headache and hemiplegia

See Clinical Presentation for more detail.

Diagnosis

Diagnosis of chicken pox or herpes Zoster is typically clinical. 

If in doubt laboratory tests can be performed. PCR to detect VZV DNA is the most reliable and sensitive method. Direct immunofluorescence (DFA) to detect VZV antigen is the second choice; sensitivity is only 60–70% of cases detectable by PCR. Other methods to confirm VZV infection, which are less preferable and less commonly used. Viral culture of VZV is possible but is insensitive, time-consuming and expensive because it requires special media.

  • In cases of acyclovir-resistant VZV, detections of mutations in thymidine kinase can be determined by PCR and sequence analysis

  • MRI may be useful if myelitis, meningitis or encephalitis is suspected

  • Lumbar puncture may be helpful if signs suggest myelitis, meningitis or encephalitis

See Workup for more detail.

Management

Treatment options are based on the following:

  • Patient age

  • Patient immune state

  • Duration of symptoms

  • Presentation

Antiviral medications decrease symptom duration and the likelihood of postherpetic neuralgia, especially when initiated within 2 days of the onset of rash. Oral acyclovir may be prescribed in otherwise healthy patients who have typical cases. Compared with oral acyclovir, other medications (eg, valacyclovir, penciclovir, famciclovir) may decrease the duration of the patient's pain.

Varicella zoster immune globulin (VariZIG) is indicated for administration to high-risk individuals within 10 days (ideally within 4 days) of chickenpox (VZV) exposure. [2] High- risk groups include the following:

  • Immunocompromised children and adults

  • Newborns of mothers with varicella shortly before or after delivery

  • Premature infants

  • Infants less than younger than 1 year of age

  • Adults without evidence of immunity

  • Pregnant women

See Treatment and Medication for more detail.

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Background

Varicella-zoster virus (VZV) is the cause of chickenpox and herpes zoster (also called shingles). Chickenpox follows initial exposure to the virus and is typically a relatively mild, self-limited childhood illness with a characteristic vesicular rash.

Approximately 1 per 4000 children develops VZV encephalitis, an acute neurologic disorder with potentially severe complications. In addition, immunocompromised children (eg, those receiving chemotherapy for leukemia or those with advanced HIV infection) can develop disseminated VZV infection, a potentially fatal complication.

After primary infection, VZV remains dormant in sensory nerve roots for life. Upon reactivation, the virus migrates down the sensory nerve to the skin, causing the characteristic painful dermatomal rash. After resolution, many individuals continue to experience pain in the distribution of the rash (postherpetic neuralgia). In addition, reactivation of VZV infection can cause a spectrum of atypical presentations, ranging from self-limited radicular pain without rash to spinal cord disease with weakness.

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Pathophysiology

VZV is a human alphaherpesvirus that causes varicella (chickenpox) as the primary infection and establishes latency in sensory ganglia. Infectious virus is transmitted by aerosolized respiratory droplets or by contact with virus in varicella or zoster skin lesions. VZV in respiratory or conjunctival mucosal cells has the opportunity to interact with and infect local immune system cells and those in adjacent lymphoid tissues. Chickenpox rash develops after an incubation period of 10 to 21 days. [51]

The host immunologic mechanisms suppress replication of the virus. Reactivation can occur if host immune mechanisms are compromised. This may be caused by medications, illness, malnutrition, stress or by the natural decline in immune function with aging. Upon reactivation, the virus migrates along sensory nerves and produces sensory loss, pain, and other neurologic complications. If motor nerve roots are also involved, weakness can develop in addition to sensory changes. Leptomeningeal involvement is rare but may develop when the ophthalmic branch of the trigeminal nerve is involved.

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Frequency

United States

Varicella used to be very common in the United States. In the early 1990s, an average of 4 million people got varicella, 10,500 to 13,000 were hospitalized, and 100 to 150 died each year. Since introduction of the varicella vaccination program in 1995 in the United States, varicella morbidity (cases and hospitalizations) and mortality (deaths) has decreased by more than 90%.

Per CDC report; The incidence for herpes zoster is approximately 4 cases per 1,000 U.S. population annually. The incidence among people 60 years and older is about 1 case per 100 US population annually. 

In a meta-analysis of 69 studies from various countries it was found that, cumulative incidence of HZ ranging from 2.9 to 19.5 cases per 1,000 population and an incidence rate of HZ ranging from 5.23 to 10.9 cases per 1,000 person-years. Studies revealed a trend of increasing incidence of HZ with increasing age and over time. [54]

 

 

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Mortality/Morbidity

About 95% of patients with zoster experience severe pain during the illness. The risk of developing post herpetic neuralgia in patients with HZ varies from 5% to more than 30%, as recently reported in a systematic review of 130 studies in 26 countries. [53] The occurrence of both HZ and PHN increases with age.

Other presentations of zoster, including ocular (keratitis) and spinal cord (myelitis) presentations, may result in additional morbidity.

Bacterial superinfection (impetiginization) of vesicular skin lesions can occur.

Severe complications include secondary bacterial infections (most notably those caused by group A beta-hemolytic Streptococcus, e.g., cellulitis, necrotizing fasciitis, septicemia, and toxic shock syndrome), pneumonia, encephalitis, cerebellar ataxia, Reye syndrome, and death. [52]

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Epidemiology

The cumulative incidence (3.22–11.2 vs 2.44–8.0 cases per 1000 population) and incidence rates (6.05–12.8 vs 4.30–8.5 cases per 1000 person-years) were higher in females than males. Studies revealed a trend of increasing incidence of HZ with increasing age and over time.  [54]

Zoster mortality is presumably elevated in countries severely affected by the HIV/AIDS pandemic.

The lifetime risk of developing HZ is between 25% and 30%, rising to 50% in those aged at least 80 years. The estimated average overall incidence of HZ is about 3.4–4.82 per 1000 person years which increases to more than 11 per 1000 person years in those aged at least 80 years. [55]

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Prognosis

Since the varicella vaccination program was implemented in 1995, hospitalizations and deaths from varicella have declined in the United States 93% and 94%, respectively.

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