Herpes zoster commonly known as shingles and also known as zona, is a viral disease

characterized by a painful skin rash with blisters in a limited area on one side of the body,
often in a stripe. The initial infection with varicella zoster virus (VZV) causes the acute
(short-lived) illness chickenpox which generally occurs in children and young people.
Once an episode of chickenpox has resolved, the virus is not eliminated from the body
but can go on to cause shingles—an illness with very different symptoms—often many
years after the initial infection.

Varicella zoster virus can become latent in the nerve cell bodies and less frequently in
non-neuronal satellite cells of dorsal root, cranial nerve or autonomic ganglion,[1]
without causing any symptoms.[2] Years or decades after a chickenpox infection, the
virus may break out of nerve cell bodies and travel down nerve axons to cause viral
infection of the skin in the region of the nerve.

Signs and symptoms

The earliest symptoms of herpes zoster, which include headache, fever, and malaise, are
nonspecific, and may result in an incorrect diagnosis.[5][10] These symptoms are
commonly followed by sensations of burning pain, itching, hyperesthesia
(oversensitivity), or paresthesia ("pins and needles": tingling, pricking, or numbness).The
pain may be mild to extreme in the affected dermatome, with sensations that are often
described as stinging, tingling, aching, numbing or throbbing, and can be interspersed
with quick stabs of agonizing pain.[12] Herpes zoster in children is often painless.

In most cases after 1–2 days, but sometimes as long as 3 weeks, the initial phase is
followed by the appearance of the characteristic skin rash. The pain and rash most
commonly occurs on the torso, but can appear on the face, eyes or other parts of the body.
At first the rash appears similar to the first appearance of hives; however, unlike hives,
herpes zoster causes skin changes limited to a dermatome, normally resulting in a stripe
or belt-like pattern that is limited to one side of the body and does not cross the midline.
[11] Zoster sine herpete ("herpes without zoster") describes a patient who has all of the
symptoms of herpes zoster except this characteristic rash.

Later the rash becomes vesicular, forming small blisters filled with a serous exudate, as
the fever and general malaise continue. The painful vesicles eventually become cloudy or
darkened as they fill with blood, crust over within seven to ten days; usually the crusts
fall off and the skin heals, but sometimes, after severe blistering, scarring and discolored
skin remain
Pathophysiology

Progression of herpes zoster. A cluster of small bumps (1) turns into blisters (2). The
blisters fill with lymph, break open (3), crust over (4), and finally disappear. Postherpetic
neuralgia can sometimes occur due to nerve damage (5),

The causative agent for herpes zoster is varicella zoster virus (VZV), a double-stranded
DNA virus related to the Herpes simplex virus group. Most people are infected with this
virus as children, and suffer from an episode of chickenpox. The immune system
eventually eliminates the virus from most locations, but it remains dormant (or latent) in
the ganglia adjacent to the spinal cord (called the dorsal root ganglion) or the ganglion
semilunare (ganglion Gasseri) in the base of the skull.[15] Repeated attacks of herpes
zoster are rare, and it is extremely rare for patients to suffer more than three recurrences.

Herpes zoster occurs only in people who have had chickenpox, and although it can occur
at any age, the majority of sufferers are more than 50 years old. The disease results from
the virus reactivating in a single sensory ganglion. In contrast to Herpes simplex virus,
the latency of VZV is poorly understood. The virus has not been recovered from human
nerve cells by cell culture and the location and structure of the viral DNA is not known.
Virus-specific proteins continue to be made by the infected cells during the latent period,
so true latency, as opposed to a chronic low-level infection, has not been proven.
Although VZV has been detected in autopsies of nervous tissue, there are no methods to
find dormant virus in the ganglia in living people.

Unless the immune system is compromised, it suppresses reactivation of the virus and
prevents herpes zoster. Why this suppression sometimes fails is poorly understood, but
herpes zoster is more likely to occur in people whose immune system is impaired due to
aging, immunosuppressive therapy, psychological stress, or other factors. Upon
reactivation, the virus replicates in the nerve cells, and virions are shed from the cells and
carried down the axons to the area of skin served by that ganglion. In the skin, the virus
causes local inflammation and blisters. The short- and long-term pain caused by herpes
zoster comes from the widespread growth of the virus in the infected nerves, which
causes inflammation.
The symptoms of herpes zoster cannot be transmitted to another person.[21] However,
during the blister phase, direct contact with the rash can spread VZV to a person who has
no immunity to the virus. This newly-infected individual may then develop chickenpox,
but will not immediately develop shingles. Until the rash has developed crusts, a person
is extremely contagious. A person is also not infectious before blisters appear, or during
postherpetic neuralgia (pain after the rash is gone). The person is no longer contagious
after the rash has disappeared.

Diagnosis

Herpes zoster on the chest

If the rash has appeared, identifying this disease (making a differential diagnosis) only
requires a visual examination, since very few diseases produce a rash in a dermatomal
pattern (see map). However, herpes simplex virus (HSV) can occasionally produce a rash
in such a pattern. The Tsanck smear is helpful for diagnosing acute infection with a
herpes virus, but does not distinguish between HSV and VZV.

When the rash is absent (early or late in the disease, or in the case of zoster sine herpete),
herpes zoster can be difficult to diagnose.Apart from the rash, most symptoms can occur
also in other conditions.

Laboratory tests are available to diagnose herpes zoster. The most popular test detects
VZV-specific IgM antibody in blood; this only appears during chickenpox or herpes
zoster and not while the virus is dormant.In larger laboratories, lymph collected from a
blister is tested by the polymerase chain reaction for VZV DNA, or examined with an
electron microscope for virus particles.

In a recent study, samples of lesions on the skin, eyes, and lung from 182 patients with
presumed herpes simplex or herpes zoster were tested with real-time PCR or with viral
culture. In this comparison, viral culture detected VZV with only a 14.3% sensitivity,
although the test was highly specific (specificity=100%). By comparison, real-time PCR
resulted in 100% sensitivity and specificity. Overall testing for herpes simplex and herpes
zoster using PCR showed a 60.4% improvement over viral culture.
Treatment

Herpes zoster on lower back

The aims of treatment are to limit the severity and duration of pain, shorten the duration
of a shingles episode, and reduce complications. Symptomatic treatment is often needed
for the complication of postherpetic neuralgia. However, a study on untreated herpes
zoster shows that pain once the rash has cleared (post herpetic neuralgia) is very rare in
people under 50 and wears off in time; in older people the pain wore off more slowly, but
even in people over 70, 85% were pain free one year after their shingles outbreak

Analgesics

People with mild to moderate pain can be treated with over-the-counter analgesics.
Topical lotions containing calamine can be used on the rash or blisters and may be
soothing. Occasionally, severe pain may require an opioid medication, such as morphine.
Once the lesions have crusted over, capsaicin cream (Zostrix) can be used. Topical
lidocaine and nerve blocks may also reduce pain.[38] Administering gabapentin along
with antivirals may offer relief of postherpetic neuralgia.

Antivirals

Antiviral drugs inhibit VZV replication and reduce the severity and duration of herpes
zoster with minimal side effects, but do not reliably prevent postherpetic neuralgia. Of
these drugs, acyclovir has been the standard treatment, but the new drugs valaciclovir
and famciclovir demonstrate similar or superior efficacy and good safety and tolerability.
The drugs are used both as prophylaxis (for example in AIDS patients) and as therapy
during the acute phase. Antiviral treatment is recommended for all immunocompetent
individuals with herpes zoster over 50 years old, preferably given within 72 hours of the
appearance of the rash.Complications in immunocompromised individuals with herpes
zoster may be reduced with intravenous acyclovir. In people who are at a high risk for
repeated attacks of shingles, five daily oral doses of acyclovir are usually effective.

Steroids

Orally administered corticosteroids are frequently used in treatment of the infection,

despite clinical trials of this treatment being unconvincing. Nevertheless, one trial
studying immunocompetent patients older than 50 years of age with localized herpes
zoster, suggested that administration of prednisone with aciclovir improved healing time
and quality of life.[40] Upon one-month evaluation, aciclovir with prednisone increased
the likelihood of crusting and healing of lesions by about twofold, when compared to
placebo. This trial also evaluated the effects of this drug combination on quality of life at
one month, showing that patients had less pain, and were more likely to stop the use of
analgesic agents, return to usual activities and have uninterrupted sleep.
Prognosis

The rash and pain usually subside within three to five weeks, but about one in five
patients develops a painful condition called postherpetic neuralgia, which is often
difficult to manage. In some patients, herpes zoster can reactivate presenting as zoster
sine herpete: pain radiating along the path of a single spinal nerve (a dermatomal
distribution), but without an accompanying rash. This condition may involve
complications that affect several levels of the nervous system and cause multiple cranial
neuropathies, polyneuritis, myelitis, or aseptic meningitis. Other serious effects that may
occur in some cases include partial facial paralysis (usually temporary), ear damage, or
encephalitis. During pregnancy, first infections with VZV, causing chickenpox, may lead
to infection of the fetus and complications in the newborn, but chronic infection or
reactivation in shingles are not associated with fetal infection.

There is a slightly increased risk of developing cancer after a herpes zoster infection.
However, the mechanism is unclear and mortality from cancer did not appear to increase
as a direct result of the presence of the virus. Instead, the increased risk may result from
the immune suppression that allows the reactivation of the virus.

Epidemiology

Electron micrograph of Varicella zoster virus. Approx. 150,000-fold magnification.

Varicella zoster virus has a high level of infectivity and is prevalent worldwide, and has a
very stable prevalence from generation to generation.VZV is a benign disease in a
healthy child in developed countries. However, varicella can be lethal to individuals who
are infected later in life or who have low immunity. The number of people in this high-
risk group has increased, due to the HIV epidemic and the increase in
immunosuppressive therapies.[50] Infections of varicella in institutions such as hospitals
are also a significant problem, especially in hospitals that care for these high-risk
populations.

In general, herpes zoster has no seasonal incidence and does not occur in epidemics. In
temperate zones chickenpox is a disease of children, with most cases occurring during the
winter and spring, most likely due to school contact; there is no evidence for regular
epidemics. In the tropics chickenpox typically occurs among older people. Incidence is
highest in people who are over age 55, as well as in immunocompromised patients
regardless of age group, and in individuals undergoing psychological stress. Non-whites
may be at lower risk; it is unclear whether the risk is increased in females. Other potential
risk factors include mechanical trauma, genetic susceptibility, and exposure to
immunotoxins.