Herpes zoster
Encyclopedia
Herpes zoster commonly known as shingles and also known as zona, is a viral disease characterized by a pain
ful skin rash with blister
s 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. Herpes zoster is not the same disease as herpes simplex
despite the name similarity (both the varicella zoster virus and herpes simplex virus
belong to the same viral subfamily Alphaherpesvirinae
).
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
, without causing any symptoms. Years or decades after a chickenpox infection, the virus may break out of nerve cell bodies and travel down nerve axon
s to cause viral infection of the skin in the region of the nerve. The virus may spread from one or more ganglia along nerves of an affected segment
and infect the corresponding dermatome
(an area of skin supplied by one spinal nerve) causing a painful rash. Although the rash usually heals within two to four weeks, some sufferers experience residual nerve pain for months or years, a condition called postherpetic neuralgia
. Exactly how the virus remains latent in the body, and subsequently re-activates is not understood.
Throughout the world the incidence rate
of herpes zoster every year ranges from 1.2 to 3.4 cases per 1,000 healthy individuals, increasing to 3.9–11.8 per year per 1,000 individuals among those older than 65 years. Antiviral drug
treatment can reduce the severity and duration of herpes zoster if a seven-to-ten day course of these drugs is started within 72 hours of the appearance of the characteristic rash.
, fever
, and malaise
, are nonspecific, and may result in an incorrect diagnosis. 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.
Herpes zoster in children is often painless, but older people are more likely to get zoster as they age, and the disease tends to be more severe.
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. Zoster sine herpete ("zoster without herpes") describes a patient who has all of the symptoms of herpes zoster except this characteristic rash.
Later the rash becomes vesicular, forming small blister
s 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.
Herpes zoster may have additional symptoms, depending on the dermatome
involved. Herpes zoster ophthalmicus
involves the orbit of the eye
and occurs in approximately 10–25% of cases. It is caused by the virus reactivating in the ophthalmic division of the trigeminal nerve
. In a few patients, symptoms may include conjunctivitis
, keratitis
, uveitis
, and optic nerve
palsies
that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain. Herpes zoster oticus, also known as Ramsay Hunt syndrome type II, involves the ear
. It is thought to result from the virus spreading from the facial nerve
to the vestibulocochlear nerve
. Symptoms include hearing loss and vertigo
(rotational dizziness).
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. 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 been previously infected with VZV; although it can occur at any age, approximately half of the cases in the USA occur in those aged 50 years or older. 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 axon
s 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.
As with chickenpox and/or other forms of herpes, direct contact with an active 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).
If the rash has appeared, identifying this disease (making a differential diagnosis
) requires only 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 test
s are available to diagnose herpes zoster. The most popular test detects VZV-specific IgM
antibody
in blood; this appears only during chickenpox or herpes zoster and not while the virus is dormant. In larger laboratories, lymph
collected from a blister is tested by 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.
for VZV exists, marketed as Zostavax
. In a 2005 study of 38,000 older adults it prevented half the cases of herpes zoster and reduced the number of cases of postherpetic neuralgia by two-thirds. A 2007 study found that the zoster vaccine is likely to be cost-effective in the U.S., projecting an annual savings of $82 to $103 million in healthcare costs with cost-effectiveness ratios ranging from $16,229 to $27,609 per quality-adjusted life year gained. In October 2007 the vaccine was officially recommended in the U.S. for healthy adults aged 60 and over. Adults also receive an immune boost from contact with children infected with varicella (chicken pox), a boosting method that prevents about a quarter of herpes zoster cases among unvaccinated adults, but that is becoming less common in the U.S. now that children are routinely vaccinated against varicella. The shingles vaccination can cut the risk of the severe disease by 55 percent.
The Centers for Disease Control and Prevention
recommends shingle vaccine for use in people 60 years old and older to prevent shingles, but it is not recommended to treat active shingles or post-herpetic neuralgia (pain after the rash is gone) once it develops.
In the United Kingdom
and other parts of Europe, population-based varicella immunization is not practised. The rationale is that until the entire population could be immunized, adults who have previously contracted VZV would instead derive benefit from occasional exposure to VZV (from children), which serves as a booster to their immunity to the virus, and may reduce the risk of shingles later on in life. The UK Health Protection Agency
states that, while the vaccine is licensed in the UK, there are no plans to introduce it into the routine childhood immunization scheme, although it may be offered to healthcare workers who have no immunity to VZV.
A 2006 study of 243 cases and 483 matched controls found that fresh fruit is associated with a reduced risk of developing shingles–people who consumed less than one serving of fruit a day had a risk three times as great as those who consumed more than three servings, after adjusting for other factors such as total energy intake. For those aged 60 or more, vitamins and vegetable intake had a similar association.
However, a study on untreated herpes zoster shows that, once the rash has cleared, postherpetic 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. 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. Administering gabapentin
along with antivirals may offer relief of 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.
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. 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. However, when comparing cessation of herpes zoster-associated pain or post herpetic neuralgia, there was no difference between aciclovir plus prednisone and simply aciclovir alone. Because of the risks of corticosteroid treatment, it is recommended that this combination of drugs only be used in people more than 50 years of age, due to their greater risk of postherpetic neuralgia.
is similar to standard treatment for herpes zoster at other sites. A recent trial comparing aciclovir with its prodrug, valaciclovir, demonstrated similar efficacies in treating this form of the disease. The significant advantage of valciclovir over aciclovir is its dosing of only 3 times/day (compared with aciclovir's 5 times/day dosing), which could make it more convenient for patients and improve adherence with therapy.
, 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.
Although herpes zoster typically resolves within 2 weeks, certain complications may arise:
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Varicella zoster virus (VZV) has a high level of infectivity
and has a worldwide prevalence. Herpes zoster is a re-activation of latent VZV infection: this means that zoster can only occur in someone who has previously had chickenpox (varicella).
Herpes zoster has no relationship to season and does not occur in epidemics. There is, however, a strong relationship with increasing age. The incidence rate of herpes zoster ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years, and incidence rates worldwide are similar.
This relationship with age has been demonstrated in many different countries, and is attributed to the fact that cellular immunity declines as people grow older.
Another important risk factor is immunocompromise
: HIV is an important example of immune compromise). Other risk factors include psychological stress
. Blacks are at lower risk of shingles than white caucasians. It is unclear whether the risk is increased in females. Other potential risk factors include mechanical trauma
, and exposure to immunotoxin
s.
There is not strong evidence for a genetic link or a link to family history. A 2008 study showed that people with close relatives who have had shingles are twice as likely to develop it themselves, but a study performed in Italy was not able to prove that family history is not a risk factor or evidence for a link to genetic factors.
Adults with latent VZV infection who are exposed intermittently to children with chickenpox receive an immune boost. This periodic boost to the immune system helps to prevent shingles in older adults. When routine chickenpox vaccination was introduced in the US, the concern was that because older adults would no longer receive this natural, periodic boost, this would result in an increase in the incidence of shingles in the US.
Multiple studies and surveillance data, at least when viewed superficially, demonstrate no consistent trends in incidence in the U.S. since the chickenpox vaccination program began in 1995. However, upon closer inspection, the two studies that showed no increase in shingles incidence were conducted among populations where varicella vaccination was not as yet widespread in the community. A recent study by Patel et al. concluded that since the introduction of the chickenpox vaccine, hospitalization costs for complications of shingles have increased by more than $700 million annually for those over 60 years. Another study by Yih et al. reported that as varicella vaccine coverage in children increased, the incidence of varicella decreased and the occurrence of shingles among adults increased 90%. The results of a further study by Yawn et al. showed a 28% increase in shingles incidence from 1996 to 2001. It is likely that incidence rate will change in the future, due to the aging of the population, changes in therapy for malignant and autoimmune diseases, and changes in chickenpox vaccination rates; a wide adoption of zoster vaccination could dramatically reduce the incidence rate.
In one study, it was estimated that 26% of patients who contract herpes zoster eventually present with complications. Postherpetic neuralgia arises in approximately 20% of patients. A study of 1994 California data found hospitalization rates of 2.1 per 100,000 person-years, rising to 9.3 per 100,000 person-years for ages 60 and up. An earlier Connecticut study found a higher hospitalization rate; the difference may be due to the prevalence of HIV
in the earlier study, or to the introduction of antivirals in California before 1994.
, ergotism
, and erysipelas
. It was only in the late eighteenth century that William Heberden
established a way to differentiate between herpes zoster and smallpox, and only in the late nineteenth century that herpes zoster was differentiated from erysipelas
. In 1831, Richard Bright
hypothesized that the disease arose from the dorsal root ganglion, and this was confirmed in an 1861 paper by Felix von Bärunsprung.
The first indications that chickenpox and herpes zoster were caused by the same virus were noticed at the beginning of the 20th century. Physicians began to report that cases of herpes zoster were often followed by chickenpox in the younger people who lived with the shingles patients. The idea of an association between the two diseases gained strength when it was shown that lymph from a sufferer of herpes zoster could induce chickenpox in young volunteers. This was finally proved by the first isolation of the virus in cell cultures, by the Nobel laureate Thomas Huckle Weller
, in 1953.
Until the 1940s, the disease was considered benign, and serious complications were thought to be very rare. However, by 1942, it was recognized that herpes zoster was a more serious disease in adults than in children, and that it increased in frequency with advancing age. Further studies during the 1950s on immunosuppressed individuals showed that the disease was not as benign as once thought, and the search for various therapeutic and preventive measures began. By the mid-1960s, several studies identified the gradual reduction in cellular immunity in old age, observing that in a cohort of 1,000 people who lived to the age of 85, approximately 500 (i.e., 50%) would have at least one attack of herpes zoster, and 10 (i.e., 1%) would have at least two attacks.
In historical shingles studies, shingles incidence generally increased with age. However, in his 1965 paper, Dr. Hope-Simpson was first to suggest, “The peculiar age distribution of zoster may in part reflect the frequency with which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody protection have their attacks of zoster postponed.”
Lending support to this hypothesis that contact with children with chickenpox boosts adult cell-mediated immunity to help postpone or suppress shingles, is the study by Thomas et al., which reported that adults in households with children had lower rates of shingles than households without children. Also, the study by Terada et al. indicated that pediatricians reflected incidence rates from 1/2 to 1/8 that of the general population their age.
The family name of all the herpesviridae
is derived from the Greek word herpein ("to creep"), referring to the latent, recurring infections typical of this group of viruses. Zoster comes from Greek zōstēr, meaning "belt" or "girdle", after the characteristic belt-like dermatomal rash. The common name for the disease, shingles, derives from the Latin cingulus, a variant of Latin cingulum meaning "girdle".
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
ful skin rash with blister
Blister
A blister is a small pocket of fluid within the upper layers of the skin, typically caused by forceful rubbing , burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid called serum or plasma...
s in a limited area on one side of the body, often in a stripe. The initial infection with varicella zoster virus
Varicella zoster virus
Varicella zoster virus is one of eight herpes viruses known to infect humans . It commonly causes chicken-pox in children and Herpes zoster in adults and rarely in children.-Nomenclature:...
(VZV) causes the acute (short-lived) illness chickenpox
Chickenpox
Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring...
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. Herpes zoster is not the same disease as herpes simplex
Herpes simplex
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...
despite the name similarity (both the varicella zoster virus and herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
belong to the same viral subfamily Alphaherpesvirinae
Alphaherpesvirinae
Alphaherpesvirinae is a subfamily of Herpesviridae primarily distinguished by reproducing more quickly than other subfamilies of Herpesviridae. In animal virology the most important herpesviruses belong to the Alphaherpesvirinae...
).
Varicella zoster virus can become latent
Virus latency
Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection...
in the nerve cell bodies
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
and less frequently in non-neuronal satellite cells
Satellite cells
Myosatellite cells or satellite cells are small mononuclear progenitor cells with virtually no cytoplasm found in mature muscle. They are found sandwiched between the basement membrane and sarcolemma of individual muscle fibers, and can be difficult to distinguish from the sub-sarcolemmal nuclei...
of dorsal root
Dorsal root ganglion
In anatomy and neuroscience, a dorsal root ganglion is a nodule on a dorsal root that contains cell bodies of neurons in afferent spinal nerves.-Unique unipolar structure:...
, cranial nerve
Cranial nerves
Cranial nerves are nerves that emerge directly from the brain, in contrast to spinal nerves, which emerge from segments of the spinal cord. In humans, there are traditionally twelve pairs of cranial nerves...
or autonomic
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
ganglion
Ganglion
In anatomy, a ganglion is a biological tissue mass, most commonly a mass of nerve cell bodies. Cells found in a ganglion are called ganglion cells, though this term is also sometimes used to refer specifically to retinal ganglion cells....
, without causing any symptoms. Years or decades after a chickenpox infection, the virus may break out of nerve cell bodies and travel down nerve axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s to cause viral infection of the skin in the region of the nerve. The virus may spread from one or more ganglia along nerves of an affected segment
Segmentation (biology)
Segmentation in biology refers to either a type of gastrointestinal motility or the division of some animal and plant body plans into a series of repetitive segments. This article will focus on the segmentation of animal body plans, specifically using the examples of the phyla Arthropoda,...
and infect the corresponding dermatome
Dermatomic area
A dermatome is an area of skin that is mainly supplied by a single spinal nerve.There are eight cervical nerves ,twelve thoracic nerves,five lumbar nerves and five sacral nerves....
(an area of skin supplied by one spinal nerve) causing a painful rash. Although the rash usually heals within two to four weeks, some sufferers experience residual nerve pain for months or years, a condition called postherpetic neuralgia
Postherpetic neuralgia
Postherpetic neuralgia is a neuralgia caused by the varicella zoster virus. Typically, the neuralgia is confined to a dermatomic area of the skin and follows an outbreak of herpes zoster in that same dermatomic area...
. Exactly how the virus remains latent in the body, and subsequently re-activates is not understood.
Throughout the world the incidence rate
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of herpes zoster every year ranges from 1.2 to 3.4 cases per 1,000 healthy individuals, increasing to 3.9–11.8 per year per 1,000 individuals among those older than 65 years. Antiviral drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
treatment can reduce the severity and duration of herpes zoster if a seven-to-ten day course of these drugs is started within 72 hours of the appearance of the characteristic rash.
Signs and symptoms
The earliest symptoms of herpes zoster, which include headacheHeadache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, and malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
, are nonspecific, and may result in an incorrect diagnosis. These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia
Hyperesthesia
Hyperesthesia is a condition that involves an abnormal increase in sensitivity to stimuli of the sense. "When a non-noxious stimulus causes the sensation of pain the area will be termed hyperaesthetic". Stimuli of the senses can include sound that one hears, foods that one tastes, textures that...
(oversensitivity), or paresthesia
Paresthesia
Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
("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.
Herpes zoster in children is often painless, but older people are more likely to get zoster as they age, and the disease tends to be more severe.
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
Dermatomic area
A dermatome is an area of skin that is mainly supplied by a single spinal nerve.There are eight cervical nerves ,twelve thoracic nerves,five lumbar nerves and five sacral nerves....
, normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline. Zoster sine herpete ("zoster without herpes") describes a patient who has all of the symptoms of herpes zoster except this characteristic rash.
Later the rash becomes vesicular, forming small blister
Blister
A blister is a small pocket of fluid within the upper layers of the skin, typically caused by forceful rubbing , burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid called serum or plasma...
s 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.
| Day 1 | Day 2 | Day 5 | Day 6 |
|---|---|---|---|
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 |
 |
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Herpes zoster may have additional symptoms, depending on the dermatome
Dermatome
Dermatome may refer to:*Dermatome , a surgical instrument used to produce thin slices of skin*Dermatome , an area of skin that is supplied by a single pair of dorsal roots*Dermatome...
involved. Herpes zoster ophthalmicus
Ophthalmic nerve
The ophthalmic nerve is one of the three branches of the trigeminal nerve, the fifth cranial nerve. The ophthalmic nerve carries only sensory fibers.-Branches:*Nasociliary nerve**sensory root of ciliary ganglion**posterior ethmoidal nerve...
involves the orbit of the eye
Orbit (anatomy)
In anatomy, the orbit is the cavity or socket of the skull in which the eye and its appendages are situated. "Orbit" can refer to the bony socket, or it can also be used to imply the contents...
and occurs in approximately 10–25% of cases. It is caused by the virus reactivating in the ophthalmic division of the trigeminal nerve
Trigeminal nerve
The trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system...
. In a few patients, symptoms may include conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
, keratitis
Keratitis
Keratitis is a condition in which the eye's cornea, the front part of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves impaired eyesight.-Types:...
, uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, and optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
palsies
Palsy
In medicine, palsy is the paralysis of a body part, often accompanied by loss of sensation and by uncontrolled body movements, such as shaking. Medical conditions involving palsy include cerebral palsy , brachial palsy , and Bell's palsy ....
that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain. Herpes zoster oticus, also known as Ramsay Hunt syndrome type II, involves the ear
Ear
The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....
. It is thought to result from the virus spreading from the facial nerve
Facial nerve
The facial nerve is the seventh of twelve paired cranial nerves. It emerges from the brainstem between the pons and the medulla, and controls the muscles of facial expression, and functions in the conveyance of taste sensations from the anterior two-thirds of the tongue and oral cavity...
to the vestibulocochlear nerve
Vestibulocochlear nerve
The vestibulocochlear nerve is the eighth of twelve cranial nerves, and is responsible for transmitting sound and equilibrium information from the inner ear to the brain...
. Symptoms include hearing loss and vertigo
Vertigo (medical)
Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
(rotational dizziness).
Pathophysiology
Varicella zoster virus
Varicella zoster virus is one of eight herpes viruses known to infect humans . It commonly causes chicken-pox in children and Herpes zoster in adults and rarely in children.-Nomenclature:...
(VZV), a double-stranded DNA virus
DNA virus
A DNA virus is a virus that has DNA as its genetic material and replicates using a DNA-dependent DNA polymerase. The nucleic acid is usually double-stranded DNA but may also be single-stranded DNA . DNA viruses belong to either Group I or Group II of the Baltimore classification system for viruses...
related to the Herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
group. Most people are infected with this virus as children, and suffer from an episode of chickenpox
Chickenpox
Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring...
. The immune system eventually eliminates the virus from most locations, but it remains dormant (or latent) in the ganglia
Ganglion
In anatomy, a ganglion is a biological tissue mass, most commonly a mass of nerve cell bodies. Cells found in a ganglion are called ganglion cells, though this term is also sometimes used to refer specifically to retinal ganglion cells....
adjacent to the spinal cord (called the dorsal root ganglion
Dorsal root ganglion
In anatomy and neuroscience, a dorsal root ganglion is a nodule on a dorsal root that contains cell bodies of neurons in afferent spinal nerves.-Unique unipolar structure:...
) or the ganglion semilunare (ganglion Gasseri) in the base of the skull. 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 been previously infected with VZV; although it can occur at any age, approximately half of the cases in the USA occur in those aged 50 years or older. The disease results from the virus reactivating in a single sensory ganglion. In contrast to Herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
, the latency of VZV is poorly understood. The virus has not been recovered from human nerve cells by cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
and the location and structure of the viral DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
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
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
, 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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
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 axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s to the area of skin served by that ganglion. In the skin, the virus causes local inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
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.
As with chickenpox and/or other forms of herpes, direct contact with an active 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).
Diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
) requires only a visual examination, since very few diseases produce a rash in a dermatomal pattern (see map)
Dermatomic area
A dermatome is an area of skin that is mainly supplied by a single spinal nerve.There are eight cervical nerves ,twelve thoracic nerves,five lumbar nerves and five sacral nerves....
. However, herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
(HSV) can occasionally produce a rash in such a pattern. The Tsanck smear
Tzanck test
In dermatopathology, the Tzanck test, also Tzanck smear, is scraping of an ulcer base to look for Tzanck cells. It is sometimes also called the Chickenpox skin test and the herpes skin test....
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 test
Medical test
A diagnostic test is any kind of medical test performed to aid in the diagnosis or detection of disease. For example:* to diagnose diseases, and preferably sub-classify it regarding, for example, severity and treatability...
s are available to diagnose herpes zoster. The most popular test detects VZV-specific IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
in blood; this appears only during chickenpox or herpes zoster and not while the virus is dormant. In larger laboratories, lymph
Lymph
Lymph is considered a part of the interstitial fluid, the fluid which lies in the interstices of all body tissues. Interstitial fluid becomes lymph when it enters a lymph capillary...
collected from a blister is tested by polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
for VZV DNA, or examined with an electron microscope
Electron microscope
An electron microscope is a type of microscope that uses a beam of electrons to illuminate the specimen and produce a magnified image. Electron microscopes have a greater resolving power than a light-powered optical microscope, because electrons have wavelengths about 100,000 times shorter than...
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
Viral culture
Viral culture is a laboratory test in which samples are placed with a cell type that the virus being tested for is able to infect. If the cells show changes, known as cytopathic effects, then the culture is positive....
. 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
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
. Overall testing for herpes simplex and herpes zoster using PCR showed a 60.4% improvement over viral culture.
Prevention
A live vaccineVaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
for VZV exists, marketed as Zostavax
Zostavax
Zostavax is a live vaccine developed by Merck & Co. which has been shown to reduce the incidence of herpes zoster by 51.3% in a study of 38,000 adults aged 60 and older who received the vaccine. The vaccine also reduced by 66.5% the number of cases of postherpetic neuralgia and reduced the...
. In a 2005 study of 38,000 older adults it prevented half the cases of herpes zoster and reduced the number of cases of postherpetic neuralgia by two-thirds. A 2007 study found that the zoster vaccine is likely to be cost-effective in the U.S., projecting an annual savings of $82 to $103 million in healthcare costs with cost-effectiveness ratios ranging from $16,229 to $27,609 per quality-adjusted life year gained. In October 2007 the vaccine was officially recommended in the U.S. for healthy adults aged 60 and over. Adults also receive an immune boost from contact with children infected with varicella (chicken pox), a boosting method that prevents about a quarter of herpes zoster cases among unvaccinated adults, but that is becoming less common in the U.S. now that children are routinely vaccinated against varicella. The shingles vaccination can cut the risk of the severe disease by 55 percent.
The Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
recommends shingle vaccine for use in people 60 years old and older to prevent shingles, but it is not recommended to treat active shingles or post-herpetic neuralgia (pain after the rash is gone) once it develops.
In the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
and other parts of Europe, population-based varicella immunization is not practised. The rationale is that until the entire population could be immunized, adults who have previously contracted VZV would instead derive benefit from occasional exposure to VZV (from children), which serves as a booster to their immunity to the virus, and may reduce the risk of shingles later on in life. The UK Health Protection Agency
Health Protection Agency
The Health Protection Agency, or, in Welsh, Yr Asiantaeth Diogelu Iechyd is a statutory corporation. It is an independent UK organisation that was set up by the government in 2003 to protect the public from threats to their health from infectious diseases and environmental hazards...
states that, while the vaccine is licensed in the UK, there are no plans to introduce it into the routine childhood immunization scheme, although it may be offered to healthcare workers who have no immunity to VZV.
A 2006 study of 243 cases and 483 matched controls found that fresh fruit is associated with a reduced risk of developing shingles–people who consumed less than one serving of fruit a day had a risk three times as great as those who consumed more than three servings, after adjusting for other factors such as total energy intake. For those aged 60 or more, vitamins and vegetable intake had a similar association.
Treatment
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, once the rash has cleared, postherpetic 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-counterOver-the-counter drug
Over-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
analgesics. Topical lotions containing calamine
Calamine
Calamine is a mixture of zinc oxide with about 0.5% ferric oxide . It is the main ingredient in calamine lotion and is used as an antipruritic to treat mild pruritic conditions such as sunburn, eczema, rashes, poison ivy, chickenpox, and insect bites and stings...
can be used on the rash or blisters and may be soothing. Occasionally, severe pain may require an opioid medication, such as morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
. Once the lesions have crusted over, capsaicin
Capsaicin
Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...
cream (Zostrix) can be used. Topical lidocaine
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
and nerve blocks may also reduce pain. Administering gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...
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 neuralgiaPostherpetic neuralgia
Postherpetic neuralgia is a neuralgia caused by the varicella zoster virus. Typically, the neuralgia is confined to a dermatomic area of the skin and follows an outbreak of herpes zoster in that same dermatomic area...
. Of these drugs, acyclovir has been the standard treatment, but the new drugs valaciclovir and famciclovir
Famciclovir
Famciclovir is a guanine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster . It is a prodrug form of penciclovir with improved oral bioavailability...
demonstrate similar or superior efficacy and good safety and tolerability. The drugs are used both as prophylaxis (for example in AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
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
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
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 corticosteroidsGlucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
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
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
with aciclovir
Aciclovir
Aciclovir or acyclovir , chemical name acycloguanosine, abbreviated as ACV,is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax, Zovirax, and Zovir...
improved healing time and quality of life. 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
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
agents, return to usual activities and have uninterrupted sleep. However, when comparing cessation of herpes zoster-associated pain or post herpetic neuralgia, there was no difference between aciclovir plus prednisone and simply aciclovir alone. Because of the risks of corticosteroid treatment, it is recommended that this combination of drugs only be used in people more than 50 years of age, due to their greater risk of postherpetic neuralgia.
Herpes zoster ophthalmicus
Treatment for herpes zoster ophthalmicusOphthalmic zoster
Ophthalmic zoster is a cutaneous condition, a specific type of herpes zoster affecting the ophthalmic division of the fifth cranial nerve.- See also :* Disseminated herpes zoster* Inflammatory skin lesions following zoster infection...
is similar to standard treatment for herpes zoster at other sites. A recent trial comparing aciclovir with its prodrug, valaciclovir, demonstrated similar efficacies in treating this form of the disease. The significant advantage of valciclovir over aciclovir is its dosing of only 3 times/day (compared with aciclovir's 5 times/day dosing), which could make it more convenient for patients and improve adherence with therapy.
Prognosis
The rash and pain usually subside within three to five weeks, but about one in five patients develops a painful condition called postherpetic neuralgiaPostherpetic neuralgia
Postherpetic neuralgia is a neuralgia caused by the varicella zoster virus. Typically, the neuralgia is confined to a dermatomic area of the skin and follows an outbreak of herpes zoster in that same dermatomic area...
, 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
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
. This condition may involve complications that affect several levels of the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
and cause multiple cranial
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
neuropathies, polyneuritis, myelitis
Myelitis
Myelitis is a disease involving inflammation of the spinal cord, which disrupts central nervous system functions linking the brain and limbs. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation....
, or aseptic meningitis
Aseptic meningitis
Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings...
. Other serious effects that may occur in some cases include partial facial paralysis
Bell's palsy
Bell's palsy is a form of facial paralysis resulting from a dysfunction of the cranial nerve VII that results in the inability to control facial muscles on the affected side. Several conditions can cause facial paralysis, e.g., brain tumor, stroke, and Lyme disease. However, if no specific cause...
(usually temporary), ear damage, or encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
. 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
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
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.
Although herpes zoster typically resolves within 2 weeks, certain complications may arise:
- Secondary bacterial infection
- Motor involvement - incl. weakness especially in "motor herpes zoster"
- Eye involvement - trigeminal nerveTrigeminal nerveThe trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system...
involvement (as seen in herpes ophthalmicus) should be treated early and aggressively as it may lead to blindness. Involvement of the tip of the nose in the zoster rash is a strong predictor of herpes ophthalmicus. - Postherpetic neuralgiaPostherpetic neuralgiaPostherpetic neuralgia is a neuralgia caused by the varicella zoster virus. Typically, the neuralgia is confined to a dermatomic area of the skin and follows an outbreak of herpes zoster in that same dermatomic area...
- a condition of chronic pain following herpes zoster
Epidemiology
Varicella zoster virus (VZV) has a high level of infectivity
Infectivity
In epidemiology, infectivity refers to the ability of a pathogen to establish an infection. More specifically, infectivity is a pathogen's capacity for horizontal transmission that is, how frequently it spreads among hosts that are not in a parent-child relationship...
and has a worldwide prevalence. Herpes zoster is a re-activation of latent VZV infection: this means that zoster can only occur in someone who has previously had chickenpox (varicella).
Herpes zoster has no relationship to season and does not occur in epidemics. There is, however, a strong relationship with increasing age. The incidence rate of herpes zoster ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years, and incidence rates worldwide are similar.
This relationship with age has been demonstrated in many different countries, and is attributed to the fact that cellular immunity declines as people grow older.
Another important risk factor is immunocompromise
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
: HIV is an important example of immune compromise). Other risk factors include psychological stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
. Blacks are at lower risk of shingles than white caucasians. It is unclear whether the risk is increased in females. Other potential risk factors include mechanical trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
, and exposure to immunotoxin
Immunotoxin
An immunotoxin is a human-made protein that consists of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell...
s.
There is not strong evidence for a genetic link or a link to family history. A 2008 study showed that people with close relatives who have had shingles are twice as likely to develop it themselves, but a study performed in Italy was not able to prove that family history is not a risk factor or evidence for a link to genetic factors.
Adults with latent VZV infection who are exposed intermittently to children with chickenpox receive an immune boost. This periodic boost to the immune system helps to prevent shingles in older adults. When routine chickenpox vaccination was introduced in the US, the concern was that because older adults would no longer receive this natural, periodic boost, this would result in an increase in the incidence of shingles in the US.
Multiple studies and surveillance data, at least when viewed superficially, demonstrate no consistent trends in incidence in the U.S. since the chickenpox vaccination program began in 1995. However, upon closer inspection, the two studies that showed no increase in shingles incidence were conducted among populations where varicella vaccination was not as yet widespread in the community. A recent study by Patel et al. concluded that since the introduction of the chickenpox vaccine, hospitalization costs for complications of shingles have increased by more than $700 million annually for those over 60 years. Another study by Yih et al. reported that as varicella vaccine coverage in children increased, the incidence of varicella decreased and the occurrence of shingles among adults increased 90%. The results of a further study by Yawn et al. showed a 28% increase in shingles incidence from 1996 to 2001. It is likely that incidence rate will change in the future, due to the aging of the population, changes in therapy for malignant and autoimmune diseases, and changes in chickenpox vaccination rates; a wide adoption of zoster vaccination could dramatically reduce the incidence rate.
In one study, it was estimated that 26% of patients who contract herpes zoster eventually present with complications. Postherpetic neuralgia arises in approximately 20% of patients. A study of 1994 California data found hospitalization rates of 2.1 per 100,000 person-years, rising to 9.3 per 100,000 person-years for ages 60 and up. An earlier Connecticut study found a higher hospitalization rate; the difference may be due to the prevalence of HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
in the earlier study, or to the introduction of antivirals in California before 1994.
History
Herpes zoster has a long recorded history, although historical accounts fail to distinguish the blistering caused by VZV and those caused by smallpoxSmallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
, ergotism
Ergotism
Ergotism is the effect of long-term ergot poisoning, traditionally due to the ingestion of the alkaloids produced by the Claviceps purpurea fungus which infects rye and other cereals, and more recently by the action of a number of ergoline-based drugs. It is also known as ergotoxicosis, ergot...
, and erysipelas
Erysipelas
Erysipelas is an acute streptococcus bacterial infection of the deep epidermis with lymphatic spread.-Risk factors:...
. It was only in the late eighteenth century that William Heberden
William Heberden
William Heberden , English physician, was born in London, where he received the early part of his education.At the end of 1724 he was sent to St John's College, Cambridge, where he obtained a fellowship, around 1730, became master of arts in 1732, and took the degree of MD in 1739...
established a way to differentiate between herpes zoster and smallpox, and only in the late nineteenth century that herpes zoster was differentiated from erysipelas
Erysipelas
Erysipelas is an acute streptococcus bacterial infection of the deep epidermis with lymphatic spread.-Risk factors:...
. In 1831, Richard Bright
Richard Bright (physician)
Richard Bright was an English physician and early pioneer in the research of kidney disease.He was born in Bristol, Gloucestershire, the third son of Sarah and Richard Bright Sr., a wealthy merchant and banker. Bright Sr. shared his interest in science with his son,encouraging him to consider it...
hypothesized that the disease arose from the dorsal root ganglion, and this was confirmed in an 1861 paper by Felix von Bärunsprung.
The first indications that chickenpox and herpes zoster were caused by the same virus were noticed at the beginning of the 20th century. Physicians began to report that cases of herpes zoster were often followed by chickenpox in the younger people who lived with the shingles patients. The idea of an association between the two diseases gained strength when it was shown that lymph from a sufferer of herpes zoster could induce chickenpox in young volunteers. This was finally proved by the first isolation of the virus in cell cultures, by the Nobel laureate Thomas Huckle Weller
Thomas Huckle Weller
Thomas Huckle Weller was an American virologist. He, John Franklin Enders and Frederick Chapman Robbins were awarded a Nobel Prize in Physiology or Medicine in 1954 for showing how to cultivate poliomyelitis viruses in a test tube, using tissue from a monkey.Weller was born and grew up in Ann...
, in 1953.
Until the 1940s, the disease was considered benign, and serious complications were thought to be very rare. However, by 1942, it was recognized that herpes zoster was a more serious disease in adults than in children, and that it increased in frequency with advancing age. Further studies during the 1950s on immunosuppressed individuals showed that the disease was not as benign as once thought, and the search for various therapeutic and preventive measures began. By the mid-1960s, several studies identified the gradual reduction in cellular immunity in old age, observing that in a cohort of 1,000 people who lived to the age of 85, approximately 500 (i.e., 50%) would have at least one attack of herpes zoster, and 10 (i.e., 1%) would have at least two attacks.
In historical shingles studies, shingles incidence generally increased with age. However, in his 1965 paper, Dr. Hope-Simpson was first to suggest, “The peculiar age distribution of zoster may in part reflect the frequency with which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody protection have their attacks of zoster postponed.”
Lending support to this hypothesis that contact with children with chickenpox boosts adult cell-mediated immunity to help postpone or suppress shingles, is the study by Thomas et al., which reported that adults in households with children had lower rates of shingles than households without children. Also, the study by Terada et al. indicated that pediatricians reflected incidence rates from 1/2 to 1/8 that of the general population their age.
Etymology
The family name of all the herpesviridae
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...
is derived from the Greek word herpein ("to creep"), referring to the latent, recurring infections typical of this group of viruses. Zoster comes from Greek zōstēr, meaning "belt" or "girdle", after the characteristic belt-like dermatomal rash. The common name for the disease, shingles, derives from the Latin cingulus, a variant of Latin cingulum meaning "girdle".
See also
- Disseminated herpes zosterDisseminated herpes zosterDisseminated herpes zoster is an infection caused by the Herpes varicella zoster virus. This is the same virus that causes herpes zoster and chickenpox...
- Inflammatory skin lesions following zoster infectionInflammatory skin lesions following zoster infectionInflammatory skin lesions following zoster infection is a cutaneous condition that may occur following zoster, characterized by skin lesions within the affected dermatome....
External links
- NINDS Shingles Information Page, National Institute of Neurological Disorders and StrokeNational Institute of Neurological Disorders and StrokeThe National Institute of Neurological Disorders and Stroke is a part of the U.S. National Institutes of Health . It conducts and funds research on brain and nervous system disorders and has a budget of just over US$1.5 billion...
- Links to pictures of Shingles (Hardin MD) University of IowaUniversity of IowaThe University of Iowa is a public state-supported research university located in Iowa City, Iowa, United States. It is the oldest public university in the state. The university is organized into eleven colleges granting undergraduate, graduate, and professional degrees...
- Facts About The Cornea and Corneal Disease: Herpes Zoster (Shingles), National Eye InstituteNational Eye InstituteThe National Eye Institute is one of the US National Institutes of Health that was established in 1968. The mission of NEI is to prolong and protect the vision of the American people. The NEI conducts and performs research into treating and preventing diseases affecting the eye or vision....