eMedicine Specialties > Infectious Diseases > Viral Infections

Herpes Zoster

Author: James E Moon, MD, Clinical Investigator, Department of Clinical Trials, Walter Reed Army Institute of Research and Assistant Professor, Department of Medicine, Uniformed Service University of Health Sciences
Coauthor(s): Duane R Hospenthal, MD, PhD, Chief, Infectious Disease Service, San Antonio Military Medical Center, Brooke Army Medical Center; Professor of Medicine, Uniformed Services University of the Health Sciences
Contributor Information and Disclosures

Updated: Nov 23, 2009

Introduction

Background

Herpes zoster (shingles) is 1 of 2 distinctive manifestations of human infection with the varicella-zoster virus (VZV), the other being varicella (chickenpox). Chickenpox is the primary infection, whereas herpes zoster represents reactivation of a previous infection. Herpes zoster has been known since ancient times and, in fact, still carries the name used by Hippocrates. Understanding the connection between herpes zoster, chickenpox, and VZV, however, is the product of more recent research done in the 19th and 20th centuries.

Chickenpox is a common and generally benign illness of childhood that is characterized by an exanthematous vesicular rash. Following resolution of this primary infection, VZV becomes latent in dorsal root ganglia until such time as a decrease in cellular immunity triggers the reactivation of the virus.

Herpes zoster typically manifests as a vesicular rash in a unilateral dermatomal distribution associated with pain. Without treatment, symptoms usually resolve over several weeks to a month. However, up to 20% of patients may experience prolonged and sometimes debilitating sequelae, chiefly postherpetic neuralgia.

Pathophysiology

VZV is an enveloped double-stranded DNA virus belonging to the Herpesviridae family. In humans, primary infection with VZV occurs when the virus comes into contact with the mucosa of the respiratory tract or conjunctiva. From these sites, it is distributed throughout the body via mononuclear cells in the blood stream. In tissue, VZV spreads from cell to cell via direct contact to produce its effects.

After primary infection, the virus migrates along sensory nerve fibers to the satellite cells of dorsal root ganglia where it becomes dormant. This dormancy may be permanent, or the virus may become reactivated by conditions of decreased cellular immunity, resulting in herpes zoster.

Frequency

United States

Prior to the advent of widespread vaccination, an estimated 4 million cases of primary VZV infection occurred annually in the United States alone. Infection was nearly universal by the end of the teenaged years, with studies showing less than 5% of adults aged 20-29 years remaining susceptible to infection. Cumulative over a lifetime, 15-30% of those with primary infections went on to experience episodes of herpes zoster. High-risk groups, such as elderly populations and immunocompromised people, might experience cumulative incidences as great as 50%. Estimated annual incidence of herpes zoster in the United States was at least 500,000 cases.

In 1995, a vaccine to prevent VZV infection was licensed in the United States and was thereafter added to the schedule of routine childhood vaccinations in the United States, as well in many other countries. Since the introduction of widespread vaccination, the incidence of primary infection has been reduced in certain populations by as much as 90%. However, the effect of childhood vaccination on the incidence of herpes zoster has yet to be adequately quantified. So far, various studies and surveillance data have failed to indicate any consistent trend in incidence rates.

Further complicating the issue of zoster frequency is the recently licensed (2006) adult vaccine (Zostavax) to prevent herpes zoster. A major study in adults aged 60 years and older demonstrated that a single dose of this vaccine reduced the incidence of herpes zoster by 51.3% over a median 3-year surveillance period compared with placebo.¹ However, the effects of this vaccine on herpes zoster in the general population have yet to be quantified.

International

No accurate data are available, but incidence likely is similar to that in the United States.

Mortality/Morbidity

Herpes zoster rarely causes fatalities in patients who are immunocompetent, but it can be life threatening in immunocompromised patients.

• One study demonstrated a mortality rate of nearly 10% among bone marrow transplant recipients who later developed herpes zoster.²
• Long-term complications of ophthalmic zoster with corneal involvement occur in over 20% of such patients and may result in blindness.

Race

No clear predominance exists among any race or ethnic group.

Sex

No significant sex predominance has been observed in herpes zoster.

Age

People of all ages can be affected, but incidence increases with age, presumably through the general decrease in immune function that occurs with aging. The following data are the incidence rates from 1996:

• People younger than 20 years - 0.4-1.6 cases per 1000 persons
• People aged 20-50 years - 2-3 cases per 1000 persons
• People older than 80 years - 4.5-11 cases per 1000 persons

Clinical

History

The clinical manifestations of herpes zoster can be divided into the pre-eruptive phase (preherpetic neuralgia), acute eruptive phase, and chronic phase (postherpetic neuralgia).

• Pre-eruptive phase
  • This phase is characterized by unusual skin sensations or pain within the affected dermatome that heralds the onset of lesions by 48-72 hours.
  • During this time, patients may also experience other symptoms such as malaise, myalgia, headache, and fever.
• Eruptive phase
  • This phase is marked by the emergence of vesicular eruptions. As in the pre-eruptive phase, patients may also experience symptoms such as malaise, myalgia, headache, and fever.
  • Lesions begin as erythematous macules and papules that quickly develop into vesicles. New lesions tend to form over a period of 3-5 days, sometimes coalescing to form bullae.
    
    

    

    Maculopapular rash due to herpes zoster in a child with a history of leukemia. Courtesy of the CDC.

    [ CLOSE WINDOW ]

    

    Maculopapular rash due to herpes zoster in a child with a history of leukemia. Courtesy of the CDC.

  • After they form vesicles, lesions progress through stages in which they rupture, release their contents, ulcerate, and finally crust over and become dry.
  • Almost all adult patients experience pain (ie, acute neuritis) during the eruptive phase. A few experience severe pain without any evidence of a vesicular eruption (ie, zoster sine herpete), and a small number of patients have a characteristic eruption but do not experience pain.
  • Symptoms and lesions tend to resolve over 10-15 days. However, lesions may require up to a month to completely heal, and the associated pain may become chronic (see below).
  • Patients are infectious until lesions are dried. Anyone who has not previously had varicella is at risk of acquiring this readily transmitted virus. Pregnant women and immunosuppressed patients have the highest risk of serious sequelae.
  • Herpes zoster in persons younger than 50 years may be an indicator of an immunocompromised state. Therefore, younger patients with zoster should be assessed for evidence of immunodeficiency, including HIV.
• Chronic phase (postherpetic neuralgia)
  • Postherpetic neuralgia is persistent or recurring pain lasting 30 or more days after the acute infection or after all lesions have crusted.
  • Most people report a deep burning or aching pain, paresthesia, dysesthesia, hyperesthesia, or electric shock–like pains. The pain can be severe and incapacitating.
  • Resolution of pain may require months or even years.
  • The incidence of postherpetic neuralgia increases with age, occurring in the following:
    • 2% of untreated adults younger than 40 years
    • 21% of adults aged 40-60 years
    • 40% or more of adults older than 60 years
• Age is also a risk factor for pain persistence.
  • Up to 50% of patients older than 50 years have pain that persists for more than a month.
  • Pain lasting for more than 1 year occurs in 48% of patients older than 70 years.

Physical

Presentation with a characteristic rash facilitates making the diagnosis of herpes zoster. Other findings can include lymphadenopathy and sensory changes.

• Pre-eruptive phase  
  • Paresthesia or other sensory changes over a dermatomal distribution
  • Lymphadenopathy
• Eruptive phase  
  • The initial rash manifests as a swath of erythematous swollen plaques and patches from which clusters of small vesicles arise. This eruption is virtually diagnostic of shingles.
  • The extent of dermatomal involvement varies among patients and may involve all or part of a dermatome.
  • It usually affects a single unilateral dermatome and rarely crosses the body midline. Involvement of multiple dermatomes or bilateral aspects of the same dermatome (ie, crossing the midline) may indicate disseminated disease or another etiology such as herpes simplex virus (HSV).
  • Variation in vesicle size is common.
  • Only a few vesicles may be present initially, but successive eruptions for 3-5 days may occur.
  • Vesicles either umbilicate or erupt prior to drying and crusting. Crusts generally fall off within 3 weeks.
  • In elderly and immunocompromised patients, the eruptive phase is commonly longer and more extensive. It occasionally results in hemorrhagic blisters, skin necrosis, and secondary bacterial infections.
  • In an uncertain number of cases, zoster may manifest without rash or vesicles, with only pain in a dermatomal distribution (ie, zoster sine herpete).
• Central nervous system involvement  
  • While zoster is classically described in sensory (dorsal root) ganglia, it can spread to affect any portion of the nervous system.
  • Involvement of the anterior horn cells can produce muscular weakness, cranial nerve palsies, diaphragmatic paralysis, neurogenic bladder, and colon pseudoobstruction.
  • Wider involvement of the spinal cord can produce Guillain-Barré syndrome, transverse myelitis, and myositis.
  • In severely ill or immunocompromised patients, general CNS involvement can be observed in the form of meningoencephalitis or encephalitis. Such presentations are indistinguishable from other forms of meningoencephalitis, although other evidence of acute zoster usually is present.³ CSF studies frequently reveal pleocytosis without elevated protein. These infections can be life threatening.
• Herpes zoster ophthalmicus (HZO)  
  • This is potentially the most devastating form of acute zoster.
  • HZO results from the reactivation of varicella-zoster virus (VZV) in the trigeminal (fifth cranial) nerve. Any branch of the nerve may be affected, although the frontal branch within the first division of the trigeminal nerve is most commonly involved. This branch innervates nearly all the ocular and periocular structures.
  • Polymerase chain reaction (PCR) nerve studies have shown latent trigeminal VZV in up to 87% of patients.⁴ However, clinical disease has been reported in only 8-56% of patients in studies focused on ophthalmic involvement.
  • Presentations of HZO are diverse. In addition to the classic symptoms and lesions of herpes zoster, other common manifestations include conjunctivitis, scleritis, episcleritis, keratitis iridocyclitis, Argyll-Robertson pupil, glaucoma, retinitis, choroiditis, optic neuritis, optic atrophy, retrobulbar neuritis, exophthalmos, lid retraction, ptosis, and extraocular muscle palsies.
  • HZO may appear weeks to months after the resolution of other symptoms.
  • Postherpetic neuralgia and long-term sequelae may result.
  • When the nasociliary branch is involved, vesicles may appear on the tip or side of the nose (Hutchinson sign). Such a presentation is a predictor for possible serious complications such as ocular inflammation and corneal denervation.
• Ramsay-Hunt syndrome  
  • Also known as herpes zoster oticus, geniculate neuralgia, or herpes zoster auricularis, it is caused by VZV reactivation involving the facial and auditory nerves.
  • Vesicular eruptions may manifest on the pinna, tragus, in the auditory canal, and on the tympanic membrane, as well as anywhere in the facial nerve distribution.
  • The patient may experience hearing impairment, nystagmus, vertigo, or facial nerve palsy (mimicking Bell palsy).
  • Patients may lose taste sensation in the anterior two thirds of the tongue.
  • It accounts for more than 50% of the cephalic motor neuropathies.
  • It may be unnoticed and difficult to diagnose, especially in elderly patients.

Causes

• Herpes zoster is caused by the reactivation of VZV.
• No identifiable environmental, genetic, or social factors exist.

• Search for CME/CE on This Topic »

• Herpes Zoster (Emergency Medicine)
• Herpes Zoster (Ophthalmology)
• Herpes Zoster Oticus (Emergency Medicine)
• Herpes Zoster Ophthalmicus (Emergency Medicine)

• Bacterial and Viral Infections Center
• Chickenpox Symptoms
• Chickenpox Treatment
• Chickenpox Overview
• Chickenpox Causes
• Shingles Overview

• Herpes Zoster Ophthalmicus Associated With Increased Risk of Stroke
• Herpes Zoster Attacks Increase Stroke Risk By 30%
• More Zoster Vaccine May Help Protect Elderly Patients

• Short-term and Long-term Effects of Highly Active Antiretroviral Therapy on the Incidence of Herpes Zoster in HIV-infected Children
• Type I Boston Keratoprosthesis With Cataract Extraction and Intraocular Lens Placement for Visual Rehabilitation of Herpes Zoster Ophthalmicus: The "KPro Triple"
• New Viral Prophylactic Vaccines: Dermatology Perspective and Update