Herpes Zoster 

Varicella-zoster virus (VZV) is the agent causing varicella, otherwise known as chickenpox, the common childhood infection. Following resolution of chickenpox, VZV lies dormant in the spinal dorsal root ganglia until a decrease in cellular immunity triggers the reactivation of the virus, resulting in herpes zoster, otherwise known as shingles. (See Etiology.)

Shingles is a syndrome characterized by a painful, vesicular rash that is usually restricted to a unilateral dermatomal distribution. At times, especially in the immunosuppressed patient, the infection may spread and produce severe systemic illness, with involvement of multiple visceral organs and multiple dermatomes (disseminated zoster). The shingles-associated rash is seen in the images below. (See Etiology and Pathophysiology.)

Shingles usually has a benign course, but complications may occur, ranging from mild to life threatening. In properly selected patients, early treatment with antivirals and corticosteroids has been shown to decrease the duration of symptoms and to possibly prevent or ameliorate some complications. (See Pathophysiology and Treatment and Management.)

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

Go to Pediatric Herpes Zoster for more complete information on this topic.

Preeruptive 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, photophobia, and, uncommonly, fever.

Acute eruptive phase

This phase is marked by the emergence of vesicular eruptions. As in the preeruptive phase, patients may also experience such symptoms as malaise, myalgia, headache, and fever. Lesions begin as erythematous macules and papules (seen in the image below) that quickly develop into vesicles. New lesions tend to form over a period of 3-5 days, sometimes coalescing to form bullae.

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 in the eruptive phase 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.

Patients are infectious until the lesions have 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.

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. It is the most frequent complication of herpes zoster, observed in 9-45% of all cases of zoster.^[1]

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 the pain may require an extended period of time. Pain lasting longer than 12 months has been described in nearly 50% of patients older than 70 years.^[2]

The prevalence of postherpetic neuralgia in herpes zoster cases increases with age, with a 14.7-fold higher prevalence in patients older than 50 years compared with their younger counterparts.^[3]

VZV reactivation causes inflammation in the dorsal root ganglion, accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. The distribution of the rash corresponds to the sensory fields of the infected neurons within a specific ganglion. The anatomic location of the involved dermatome often determines the specific manifestations (eg, herpes zoster ophthalmicus [HZO], causing ocular complications, when the trigeminal ganglion is involved).

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 pseudo-obstruction.

Wider involvement of the spinal cord can produce Guillain-Barré syndrome, transverse myelitis, and myositis.

In severely ill or immunocompromised patients, general central nervous system (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.^[4] Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis without elevated protein. These infections can be life threatening.

Herpes zoster ophthalmicus

This is potentially the most devastating form of acute zoster.

Herpes zoster ophthalmicus (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 of the ocular and periocular structures.

Polymerase chain reaction (PCR) nerve studies have shown latent trigeminal VZV in up to 87% of patients.^[5] Clinical disease has been reported in as few as 8% and as many as 56% of patients in studies focused on ophthalmic involvement.^[6]

Ramsay Hunt syndrome

Also known as herpes zoster oticus, geniculate neuralgia, or herpes zoster auricularis, Ramsay-Hunt syndrome is caused by VZV reactivation involving the facial and auditory nerves. Go to Herpes Zoster Oticus for more complete information on this topic.

Vesicular eruptions may manifest on the pinna, tragus, or tympanic membrane or in the auditory canal, as well as anywhere in the facial nerve distribution.

The patient may experience hearing impairment, nystagmus, vertigo, or facial nerve palsy (mimicking Bell palsy).^[7] Patients may lose taste sensation in the anterior two thirds of the tongue.^[7]

Ramsay Hunt syndrome may go unnoticed and be difficult to diagnose, especially in elderly patients.

VZV is an enveloped, double-stranded deoxyribonucleic acid (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.

Exactly why VZV reactivates from latency is not fully understood. However, cell-mediated, VZV-specific immunity has been shown to be a major factor in determining reactivation of VZV. Cell-mediated, VZV-specific immunity decreases with age and in patients with certain malignancies. These groups have much higher rates of herpes zoster. Patients with hypogammaglobulinemia (a defect of humoral, but not cellular, immunity) do not have a higher rate of zoster. This supports the concept of an important role for cell-mediated immunity in the pathogenesis of VZV infection.

No identifiable environmental, genetic, or social risk factors exist for the development of the reactivation of VZV.

Incidence in the United States

Approximately 95% of adults, and 99.5% of adults aged 40 years or older, in the United States have antibodies to VZV and are vulnerable to reactivation of infection.^[8] A person of any age with a prior varicella infection may develop zoster, but incidence increases with advancing age due to declining immunity. Approximately 4% of patients with zoster will develop a recurrent episode later in life.^[9]

Prior to the advent of widespread vaccination, an estimated 4 million cases of primary VZV infection occurred annually in the United States alone.^[8] Infection was nearly universal by the end of the teenage years, with studies showing only 10% of persons older than age 15 years remaining susceptible to infection.^[9] Cumulative over a lifetime, 10-20% of those with primary infections went on to experience episodes of herpes zoster.^[10] High-risk groups, such as elderly populations and immunocompromised people, might experience cumulative incidences as great as 50%.^[11] The estimated annual number of herpes zoster cases in the United States is approximately 1 million.^[12]

Widespread vaccination for varicella has reduced the incidence of primary VZV infection in the United States by up to 90% since its introduction in 1995.^[8] However, the effect of both this vaccination, and the more recently approved vaccination for herpes zoster, on the current and future incidence of herpes zoster is still uncertain.

International incidence

Epidemiological data is limited, but the international incidence appears similar to that in the United States.^[13]

Race predilection

Research indicates that blacks are one-fourth as likely as whites to develop herpes zoster.

Sex predilection

Retrospective and prospective research has indicated that elderly black adults are up to 75% less likely to develop herpes zoster than elderly white adults.^[11] Similar findings have been demonstrated in children.^[14] Conversely, in a meta-analysis of controlled herpes zoster clinical trials in a nonwhite racial group was found to be associated with a younger age at zoster onset.^[15]

Age predilection

The incidence of herpes zoster increases with age. In the general population, the lifetime incidence rate of herpes zoster is 10-20%, which rises to 50% in those individuals surviving to age 85 years.^[11]

The rash usually resolves within 10-15 days. The prognosis for younger and otherwise healthy patients is excellent. Elderly people have a significantly increased risk of complications, including postherpetic neuralgia, bacterial infections, and scarring.

Morbidity in herpes zoster

A common complication of herpes zoster is postherpetic neuralgia, which is pain that persists for longer than 1 month following resolution of the vesicular rash. Its incidence increases dramatically with age (ie, 3-4% in those aged 30-50 y; 34% in those >80 y).^[11] }

Postherpetic neuralgia may develop as a continuation of pain that accompanies acute zoster, or it may develop following apparent resolution of the initial zoster reactivation. The pain of postherpetic neuralgia may extend for months to years.^[2]

Herpes zoster may be associated with a secondary bacterial infection at the site of the rash (typically streptococcal or staphylococcal).

Herpes zoster involving the ophthalmic branch of the trigeminal nerve may be associated with conjunctivitis, keratitis, corneal ulceration, iridocyclitis, glaucoma, and blindness.

Complications of the Ramsay Hunt syndrome (zoster involving cranial nerves V, IX, and X) may include peripheral facial nerve weakness and deafness.

Meningoencephalitis secondary to herpes zoster is more likely to be seen in immunocompromised patients than in immunocompetent patients. Other CNS complications may include myelitis, cranial nerve palsies, and granulomatous angiitis. Granulomatous angiitis may result in the development of a cerebrovascular accident.

Disseminated zoster may be seen in immunocompromised patients. In such cases, hematogenous spread may result in the involvement of multiple dermatomes. Visceral involvement can also occur.

Mortality in herpes zoster

Herpes zoster rarely causes fatalities in patients who are immunocompetent, but it can be life threatening in immunocompromised patients. Disseminated zoster in immunocompromised patients can lead to death from encephalitis, hepatitis, or pneumonitis. Patients with active lymphoproliferative malignancies are at particular risk. The mortality rate from disseminated herpes zoster is between 5% and 15%.^[10]

Inform patients about the natural progression of herpes zoster and its potential complications.

During the acute phase, patients are infective to others and should be instructed to avoid contact with elderly people, people who are immunocompromised, pregnant women, or people with no history of chickenpox infection.

Patients should be instructed to not scratch the lesions, which may predispose them to secondary bacterial infections.

For patient education information, visit eMedicine's Bacterial and Viral Infections Center, as well as Shingles and Chickenpox.