Shingles, also known as herpes zoster or zona, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. Two to four days before the rash occurs, there may be tingling or local pain in the area. Other common symptoms are fever, headache, and tiredness. The rash usually heals within four weeks, but some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.
Shingles is caused by the varicella zoster virus (VZV) that also causes chickenpox. In the case of chickenpox, also called varicella, the initial infection with the virus typically occurs during childhood or adolescence. Once the chickenpox has resolved, the virus can remain dormant (inactive) in human nerve cells (dorsal root ganglia or cranial nerves) for years or decades, after which it may reactivate and travel along nerve bodies to nerve endings in the skin, producing blisters. During an outbreak of shingles, exposure to the varicella virus found in shingles blisters can cause chickenpox in someone who has not yet had chickenpox, although that person will not develop shingles, at least on the first infection. How the virus subsequently re-activates is not well understood.
The disease has been recognized since ancient times. Risk factors for reactivation of the dormant virus include old age, poor immune function, and having contracted chickenpox before 18 months of age. Diagnosis is typically based on the signs and symptoms presented. Varicella zoster virus is not the same as herpes simplex virus, although they both belong to the alpha subfamily of herpesviruses.
Shingles vaccines reduce the risk of shingles by 50–90%, depending on the vaccine used. Vaccination also decreases rates of postherpetic neuralgia, and, if shingles occurs, its severity. If shingles develops, antiviral medications such as aciclovir can reduce the severity and duration of disease if started within 72 hours of the appearance of the rash. Evidence does not show a significant effect of antivirals or steroids on rates of postherpetic neuralgia. Paracetamol, NSAIDs, or opioids may be used to help with acute pain.
It is estimated that about a third of people develop shingles at some point in their lives. While shingles is more common among older people, children may also get the disease. According to the US National Institutes of Health, the number of new cases per year ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals to 3.9 to 11.8 per 1,000 person-years among those older than 65 years of age. About half of those living to age 85 will have at least one attack, and fewer than 5% will have more than one attack. Although symptoms can be severe, risk of death is extremely low: 0.28 to 0.69 deaths per million.
Signs and symptoms
The earliest symptoms of shingles, which include headache, fever, and malaise, are nonspecific, and may result in an incorrect diagnosis. Revised June 2005. These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia (oversensitivity), or paresthesia ("pins and needles": tingling, pricking, or numbness). Pain can be mild to severe 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.
Shingles in children is often painless, but people are more likely to get shingles as they age, and the disease tends to be more severe.
In most cases, after one to two days, and sometimes as long as three weeks, the initial phase is followed by the appearance of the characteristic skin rash. The pain and rash most commonly occur on the torso but can appear on the face, eyes, or other parts of the body. At first, the rash appears similar to hives; however, unlike hives, shingles causes skin changes limited to a dermatome, typically resulting in a stripe- or belt-like pattern on one side of the body that does not cross the midline. Zoster sine herpete ("zoster without herpes") describes a person who has all of the symptoms of shingles 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 and 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. The blister fluid contains varicella zoster virus, which can be transmitted through contact or inhalation of fluid droplets until the lesions crust over, which may take up to four weeks.
+ Development of the shingles rash Day 1 Day 2 Day 5 Day 6
Face Shingles may have additional symptoms, depending on the dermatome involved. The trigeminal nerve is the most commonly involved nerve, of which the ophthalmic division is the most commonly involved branch. When the virus is reactivated in this nerve branch, it is termed zoster ophthalmicus. The skin of the forehead, upper eyelid, and orbit of the eye may be involved. Zoster ophthalmicus occurs in approximately 10–25% of cases. In some people, symptoms may include conjunctivitis, keratitis, uveitis, and optic nerve palsies, which can sometimes cause chronic ocular inflammation, vision loss, and debilitating pain.
Shingles 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).
Shingles may occur in the mouth if the maxillary or mandibular division of the trigeminal nerve is affected, in which the rash may appear on the mucous membrane of the upper jaw (usually the palate, sometimes the gums of the upper teeth) or the lower jaw (tongue or gums of the lower teeth) respectively. Oral involvement may occur alone or in combination with a rash on the skin over the cutaneous distribution of the same trigeminal branch. As with shingles of the skin, the lesions tend to only involve one side, distinguishing it from other oral blistering conditions. In the mouth, shingles appears initially as 1–4 mm opaque blisters (vesicles), which break down quickly to leave ulcers that heal within 10–14 days. The prodromal pain (before the rash) may be confused with toothache. Sometimes this leads to unnecessary dental treatment. Post-herpetic neuralgia is uncommonly associated with shingles in the mouth. Unusual complications may occur with intra-oral shingles that are not seen elsewhere. Due to the close relationship of blood vessels to nerves, the virus can spread to involve the blood vessels and compromise the blood supply, sometimes causing ischemic necrosis. In rare cases, oral involvement causes complications such as osteonecrosis, tooth loss, periodontitis (gum disease), pulp calcification, pulp necrosis, periapical lesions and tooth developmental anomalies.
Disseminated shingles In those with deficits in immune function, disseminated shingles may occur (wide rash). It is defined as more than 20 skin lesions appearing outside either the primarily affected dermatome and directly adjacent dermatomes, or appearing on 3 or more dermatomes. Besides the skin, other organs, such as the liver or brain, may also be affected (causing hepatitis or encephalitis, respectively), making the condition potentially lethal. Disseminated shingles occurs in 2% of the general population, and 15-30% of immunocompromised individuals.
Pathophysiology
The causative agent for shingles is the varicella zoster virus (VZV)—a double-stranded DNA virus related to the herpes simplex virus and member of Herpesviridae. The complete sequence of the viral genome was published in 1986. Most individuals are infected with this virus as children, which causes 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 trigeminal ganglion in the base of the skull.
Shingles 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 United States occur in those aged 50 years or older. Shingles can recur. In contrast to the frequent recurrence of herpes simplex symptoms, repeated attacks of shingles are unusual. It is extremely rare for a person to have more than three recurrences.
The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. Due to difficulties in studying VZV reactivation directly in humans (leading to reliance on small-animal models), its latency is less well understood than that of the herpes simplex virus. Virus-specific proteins continue to be made by the infected cells during the latent period, so true latency, as opposed to chronic, low-level, active infection, has not been proven to occur in VZV infections. Although VZV has been detected in autopsies of nervous tissue, there are no methods to find dormant virus in the ganglia of living people.
Unless the immune system is compromised, it suppresses viral reactivation and prevents shingles outbreaks. Why this suppression sometimes fails is poorly understood, but shingles is more likely to occur in people whose immune systems are impaired due to aging, immunosuppressive therapy, psychological stress, or other factors. Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.
As with chickenpox and other alpha-herpesvirus infections, direct contact with an active rash can spread the virus to a person who lacks immunity. This newly infected individual may then develop chickenpox, but will not immediately develop shingles.
Diagnosis
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. However, herpes simplex virus (HSV) can occasionally produce a rash in such a pattern (zosteriform herpes simplex).
When the rash is absent (early or late in the disease, or in the case of ), shingles can be difficult to diagnose. Apart from the rash, most symptoms can also occur in other conditions.
Laboratory tests are available to diagnose shingles. The most popular test detects VZV-specific IgM antibody in blood; this appears only during chickenpox or shingles and not while the virus is dormant. In larger laboratories, lymph collected from a blister is tested by polymerase chain reaction (PCR) for VZV DNA, or examined with an electron microscope for virus particles. Molecular biology tests based on in vitro nucleic acid amplification (PCR tests) are currently considered the most reliable. Nested PCR test has high sensitivity, but is susceptible to contamination leading to false positive results. The latest real-time PCR tests are rapid, easy to perform, and as sensitive as nested PCR, and have a lower risk of contamination. They also have more sensitivity than viral cultures.
Differential diagnosis Shingles can be confused with herpes simplex, dermatitis herpetiformis and impetigo, and skin reactions caused by contact dermatitis, candidiasis, certain drugs and insect bites.
Prevention