Varicella-Zoster Virus

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Practice Essentials

Varicella-zoster virus (VZV) causes chickenpox and herpes zoster (shingles). Chickenpox follows initial exposure to the virus and is typically a relatively mild, self-limited childhood illness with a characteristic exanthem, but can become disseminated in immunocompromised children. 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).

Essential update: New CDC guidelines for varicella-zoster virus immune globulin use

In July 2013, the CDC issued updated recommendations for the use of varicella-zoster immune globulin (VariZIG) to reduce the severity of VZV infection, extending the window for postexposure prophylaxis for those at high risk for severe varicella.[1, 2] The FDA's original approval of VariZIG recommended use within 4 days, but subsequent studies have shown that the treatment is effective for up to 10 days after exposure.

Other recommendations include the use of VariZIG in the following patients:

Signs and symptoms

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. Pain occurs in 41% of patients, itching in 27%, and paresthesias in 12%.

During the acute illness, patients may experience the following:

Herpes zoster (shingles)

Zoster multiplex

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.[3]

Central nervous system deficits

Ramsay-Hunt syndrome

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

Keratitis (herpes ophthalmicus)

See Clinical Presentation for more detail.

Diagnosis

When the presentation includes the typical dermatomal rash, additional studies are not required. Studies to consider in specific situations include the following:

See Workup for more detail.

Management

Treatment options are based on the following:

Antiviral medications decrease the duration of symptoms 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.[4] High- risk groups include the following:

See Treatment and Medication for more detail.

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

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 exanthem.

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.

Pathophysiology

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, 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.

Frequency

United States

The rate of occurrence is about 5 persons per 1000 population. Immunosuppression increases this risk. The risk of postherpetic neuralgia increases with age. Approximately 50% of patients older than 60 years may have temporary or prolonged pain syndrome.

The frequency of VZV infection may decrease as the immunized children become adults.

International

VZV infection occurs with the same frequency in the United States and internationally.

Mortality/Morbidity

Race

The vesicular eruption of VZV infection may be more difficult to diagnose in patients with darker skin.

Sex

VZV infection occurs with equal frequency in males and females.

Age

History

Physical

Causes

Immunosuppression increases the risk of both typical shingles and atypical presentations, such as myelitis, encephalitis, disseminated disease, and visceral involvement.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Medical Care

Surgical Care

Surgical care may be required for complications of zoster, such as necrotizing fasciitis.

Consultations

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Current research is considering whether the varicella vaccine may also prove efficacious as treatment for active varicella-zoster virus (VZV) infection.

Acyclovir (Zovirax)

Clinical Context:  Patients experience less pain and faster resolution of cutaneous lesions when used within 48 h from rash onset. May prevent recurrent outbreaks.

Valacyclovir (Valtrex)

Clinical Context:  Prodrug rapidly converted to the active drug acyclovir. More expensive but has a more convenient dosing regimen than acyclovir.

Famciclovir (Famvir)

Clinical Context:  Prodrug that, when biotransformed into active metabolite penciclovir, may inhibit viral DNA synthesis/replication.

Class Summary

Three medications may help reduce pain and symptoms and the incidence of postherpetic neuralgia. All need to be used with caution in patients with renal compromise. Hemolytic uremic syndrome is rare but has been reported. All 3 agents may be used for 7-10 d, depending on response. Only acyclovir is available in an intravenous form.

Varicella virus vaccine (Varivax)

Clinical Context:  A live attenuated varicella virus prepared from the Oka/Merck strain. It is propagated in human diploid cell cultures (MRC-5). Each 0.5-mL dose (when reconstituted) contains 1350 PFU of varicella, sucrose, and gelatin; residual components of MRC-5 DNA and protein; and trace quantities of neomycin and fetal bovine serum. Indicated for vaccination against varicella in individuals >1 y.

Varicella zoster vaccine (Zostavax)

Clinical Context:  This is a lyophilized preparation of the Oka/Merck strain of live, attenuated varicella-zoster virus (VZV). It has been shown to boost immunity against herpes zoster virus (shingles) in older patients. It reduces the occurrence of shingles in individuals older than 60 years by about 50%. For individuals aged 60-69 years, it reduces the occurrence by 64%. In the ZEST trial, the vaccine significantly reduced the risk by 70% in subjects aged 50-59 years. It also slightly reduces pain compared with no vaccination in those who develop shingles. It is indicated for the prevention of herpes zoster in patients who have no contraindications.

Class Summary

These agents are used to induce active immunity.

The combined MMRV vaccine (ProQuad) has been shown to be associated with an increased risk of febrile seizure occurring 5-12 days following vaccination at a rate of 1 in 2300-2600 in children aged 12-23 months compared with separate MMR vaccine and varicella vaccine administered simultaneously.[10, 11] As a result, the CDC Advisory Committee on Immunization Practices (ACIP) recommends that separate MMR and varicella vaccines be used for the first dose, although providers or parents may opt to use the combined MMRV for the first dose after counseling regarding this risk.[12] MMRV is preferred for the second dose (at any age) or the first dose if given at age 48 months or older.

Data from postlicensure studies do not suggest that children aged 4-6 years who received the second dose of MMRV vaccine had an increased risk for febrile seizures after vaccination compared with children the same age who received MMR vaccine and varicella vaccine administered as separate injections at the same visit.[12]

Capsaicin transdermal patch (Qutenza)

Clinical Context:  Transient receptor potential vanilloid-1 (TRPV1) agonist indicated for neuropathic pain associated with postherpetic neuralgia. TRPV1 is an ion channel–receptor complex expressed on nociceptive skin nerve fibers. Topical capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain relief by reduction in TRPV1-expressing nociceptive nerve endings. Neuropathic pain may gradually recur over several months (thought to be caused by TRPV1 nerve fiber reinnervation of treated area).

Class Summary

Topical analgesics that contain capsaicin are effective in decreasing neuropathic pain caused by postherpetic neuralgia.

Varicella zoster immune globulin, human (VariZIG)

Clinical Context:  Varicella zoster immune globulin (VZIG) contains immunoglobulin G (IgG) varicella-zoster antibodies. It provides passive immunization to exposed individuals at high risk of complications from varicella. High- risk groups include immunocompromised children and adults, newborns of mothers with varicella shortly before or after delivery, premature infants, infants < 1 year, adults without evidence of immunity, and pregnant women. Administer by deep IM injection, preferably in deltoid muscle. For neonates or infants, administer IM in anterolateral aspect of thigh.

Class Summary

The specific immune globulin with IgG varicella zoster antibodies provides passive immunization for susceptible individuals when administered within 10 days (ideally within 96 hours) of exposure.

Further Inpatient Care

Further Outpatient Care

Deterrence/Prevention

Complications

Prognosis

Author

Wayne E Anderson, DO, FAHS, Assistant Professor of Internal Medicine/Neurology, College of Osteopathic Medicine of the Pacific Western University of Health Sciences; Clinical Faculty in Family Medicine, Touro University College of Osteopathic Medicine; Clinical Instructor, Departments of Neurology and Pain Management, California Pacific Medical Center

Disclosure: Teva Honoraria Speaking and teaching; Allergan Grant/research funds Other; Insys Honoraria Speaking and teaching; DepoMed Honoraria Speaking and teaching

Specialty Editors

Maria D Mileno, MD, Associate Professor of Medicine, Division of Infectious Diseases, The Warren Alpert Medical School of Brown University

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Gordon L Woods, MD, Consulting Staff, Department of Internal Medicine, University Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of prior coauthor Amar Safdar, MD, to the development and writing of this article.

References

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

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

Human herpesvirus (HHV) type 3. Intraoral herpes zoster closely resembles recurrent HHV-1 infection, but the lesions generally follow a dermatome and stop sharply at the midline, as shown here. However, the rules for common sites of occurrence of HHV-1 and HHV-3 often do not apply to patients who are immunocompromised. Courtesy of Sheldon Mintz, DDS.

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

Human herpesvirus (HHV) type 3. Intraoral herpes zoster closely resembles recurrent HHV-1 infection, but the lesions generally follow a dermatome and stop sharply at the midline, as shown here. However, the rules for common sites of occurrence of HHV-1 and HHV-3 often do not apply to patients who are immunocompromised. Courtesy of Sheldon Mintz, DDS.