Infection with varicella zoster virus (VZV) results in two distinct clinical conditions: varicella (i.e., chickenpox), which is caused by primary VZV infection; and herpes zoster (i.e., shingles), which is caused by reactivation of VZV decades after the initial infection. Virtually all adults are infected with VZV, and approximately one in three persons will develop herpes zoster in his or her lifetime.

As with other members of the herpesvirus family, VZV is noninfectious in its latent form but can reactivate to form intact virions in the involved sensory neurons. These virions then migrate to the skin through axons, spread from cell to cell, and penetrate the epidermis. The triggers for reactivation of VZV are not known, but multiple factors probably are involved. Specific components of cell-mediated immunity have a role in controlling the development of herpes zoster by preventing reactivation within the neuron and by preventing the full clinical expression of reactivated VZV. The effectiveness of these protective factors is well maintained in immunocompetent persons during childhood and early adulthood, probably because of periodic immunologic boosting.

Clinical Features

Herpes zoster typically begins with a prodrome. Headache, photophobia, and malaise may be present; fever is less common. Abnormal skin sensations and pain are the most common symptoms. These symptoms can precede the zoster rash by days to weeks and may be the only clinical manifestation of VZV reactivation. Pain is described as aching, burning, stabbing, or shock-like. Altered sensitivity to touch, pain provoked by trivial stimuli, and unbearable itching are often reported.

A common and potentially debilitating consequence of herpes zoster is postherpetic neuralgia, a persistent pain after resolution of the rash that can last for weeks to years. Pathologic observations thought to distinguish postherpetic neuralgia include axonal and cell body degeneration, atrophy of the spinal cord dorsal horn, scarring of the dorsal root ganglion, and loss of epidermal innervation of the affected area. This neuronal damage may be caused by ongoing viral replication. The primary risk factor for the development of postherpetic neuralgia is age; persons 50 years and older are at highest risk.

In addition to postherpetic neuralgia, herpes zoster is associated with other complications. Up to 25 percent of persons with herpes zoster have eye involvement, called herpes zoster ophthalmicus (HZO). Keratitis occurs in approximately two thirds of persons with HZO, often causing corneal ulceration. Other complications of HZO include conjunctivitis, uveitis, episcleritis and scleritis, retinitis, choroiditis, optic neuritis, lid retraction, ptosis, and glaucoma. Prolonged or permanent sequelae of HZO include pain, facial scarring, and vision loss.

Prevention

A live, attenuated vaccine for prevention of herpes zoster (Zostavax) was approved by the U.S. Food and Drug Administration in 2006 for use in persons 60 years and older. It is a lyophilized preparation of the same strain of VZV used in the varicella vaccines. However, its minimum potency is at least 14 times that of single-antigen varicella vaccine.

In a large clinical trial, the vaccine partially prevented the development of herpes zoster and postherpetic neuralgia, and it partially reduced the severity and duration of pain. Vaccine efficacy for herpes zoster prevention decreased during the first year after vaccination but remained stable through the remaining three years of follow-up. Vaccine efficacy for postherpetic neuralgia prevention followed a similar pattern, with an initial decrease and subsequent stabilization.

Routine administration of one dose of herpes zoster vaccine is recommended for all persons 60 years and older who have no contraindications. Other indications include a previous episode of herpes zoster and chronic medical conditions (e.g., chronic renal failure, diabetes, rheumatoid arthritis). Vaccination is not indicated to treat acute herpes zoster, to prevent persons with herpes zoster from developing postherpetic neuralgia, or to treat ongoing postherpetic neuralgia.

Immunogenicity of herpes zoster vaccine and of trivalent inactivated influenza vaccine is not compromised when the vaccines are administered simultaneously. However, no data exist on administration of herpes zoster vaccine with other vaccines routinely recommended for persons 60 years and older. Simultaneous administration of live, attenuated and inactivated vaccines generally has not resulted in impaired immune response or an increased rate of adverse effects; therefore, herpes zoster vaccine can be administered with other indicated vaccines during the same visit.

Herpes zoster vaccine is not approved for persons younger than 60 years and is not recommended for persons of any age who have received varicella vaccine. Contraindications include allergy to vaccine components, primary or acquired immunodeficiency, and pregnancy.