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Shingles
Specialty	Infectious diseases, dermatology, neurology

Herpes zoster, commonly known as shingles, is a disease caused by the reactivation of a varicella-zoster virus (VZV or HHV-3) infection, also known as chickenpox. Once reactivated, this virus causes painful blisters over the area of a dermatome (a skin area supplied by a single spinal nerve).

After an attack of chickenpox, the varicella-zoster virus retreats to nerve cells within the ganglion or the spinal cord, where it lies dormant for months or even decades. When aging, stress, or disease cause the virus to reactivate and reproduce, it travels along the path of a nerve to the skin's surface, where it causes shingles.

Treatment is generally with antiviral drugs such as aciclovir (Zovirax), famciclovir (Famvir) or valaciclovir (Valtrex). These are most effective if given within 72 hours of the appearance of definitive symptoms.

Signs and symptoms

The earliest symptoms of shingles include headache, fever, and malaise. These may be followed by itching, burning, and hypersensitivity. The pain may be extreme in the affected nerve, where the rash will later develop, and can be characterized as stinging, tingling, aching, numbing, or throbbing, and can be pronounced with quick stabs of intensity. During this phase, herpes zoster infections are often misdiagnosed as a heart attacks, renal colic, or other diseases with similar symptoms. Some symptomatic patients do not develop the characteristic rash (a condition known as zoster sine herpete); this may delay diagnosis and treatment.

In most cases, the initial phase is followed by development of the characteristic skin rashes of herpes zoster. The rash (and preceding pain) most commonly occurs on the torso, but can also appear on the face, eyes or other parts of the body. The rash at first is visually similar to the first appearance of hives. Unlike hives, however, shingles causes skin changes limited to a single dermatome (an area of skin supplied by one spinal nerve), with a stripe or belt-like pattern limited to one side of the body and not crossing the midline.

The rash evolves into small blisters filled with serous fluid (vesicles), which are generally painful. Their development is often associated with the occurrence of anxiety and further flu-like symptoms, such as fever, tiredness, and generalized pain. The vesicles eventually become cloudy or darkened as they fill with blood, and crust over within seven to ten days. After the crusts fall off, patients are typically left with scarring and discolored skin.

• Day 1.
• Day 2.
• Day 5.
• Day 6, with characteristic purple color.

Causes

Shingles can only arise in individuals who have been previously exposed to chickenpox (varicella-zoster). The disease arises from various events which depress the immune system, such as aging, severe emotional stress, severe illness, immunosuppression or long-term use of corticosteroids. The cellular and immunological events that lead to reactivation are poorly understood. Although shingles can affect people with cancer (more often in those afflicted with leukemias or lymphomas than in cases involving solid tumors), it is not a risk factor for having an underlying cancer problem, so there is no need for cancer investigations simply because of shingles.

Transmission

Most people are infected with VZV in childhood, as it causes chickenpox. The immune system eventually eliminates the virus from most locations, but it remains dormant in the ganglia adjacent to the spinal cord (called the dorsal root ganglion) or the trigeminal ganglion in the base of the skull.

Usually, the immune system suppresses reactivation of the virus. In the elderly, whose immune response generally tends to deteriorate, as well as in those patients whose immune system is being suppressed, this process is compromised. Viral replication commences in the nerve cells, and newly formed viruses are carried down the axons to the area of skin served by that ganglion (a dermatome). Here, the virus causes local inflammation in the skin, with the formation of blisters.

Shingles cannot be caught from another person. However, during the blister phase, direct contact with the rash can spread VZV to a person who has no immunity to the virus (either from previous chickenpox or its vaccine). The exposed person may then develop chickenpox, not shingles. The virus is not spread through airborne transmission, such as sneezing or coughing. Once the rash has developed crusts, the person is no longer contagious. A person is not infectious before blisters appear or with post-herpetic neuralgia (pain after the rash is gone).

Diagnosis

The diagnosis is made on visual examination; very few other diseases mimic herpes zoster, especially in the localization of the rash, which is otherwise quite similar in appearance and initial effect to that of poison oak or poison ivy (although it may not be accompanied by the intense itching so characteristic of those rashes). Diagnostic tests may be performed in doubtful cases. These may be necessary because, depending on the affected sensory nerve, the pain that is experienced before the onset of the rash may be misdiagnosed as pleurisy, myocardial infarction, appendicitis, cholelithiasis, or a migraine headache.

Fluid from a blister may be taken and analyzed in a medical laboratory where it is tested by polymerase chain reaction (PCR) for the presence of VZV DNA or examined by electron microscopy for Herpes virus particles. A physician can also take a viral culture of lymph from a fresh lesion, or perform a microscopic examination of the blister base called a Tzanck test which although inferior to PCR, is a reliable diagnostic method. In a complete blood count there may be an elevated number of white blood cells, which is an indirect sign of infection. The presence of IgM antibody to the virus in the blood would also give indication of the virus’ reactivation.

VZV encephalitis, a rare and serious complication of shingles in immunocompromised people, can be rapidly confirmed by PCR testing of cerebro-spinal fluid.

Treatment

There is no cure available for herpes zoster, nor a treatment to effectively eliminate the virus from the body. However, there are some treatments that can mitigate the length of the disease and alleviate certain side effects.

Antiviral drugs

The antiviral drugs aciclovir, valaciclovir and famciclovir inhibit replication of viral DNA. They are used both as prophylaxis (for example, in patients with AIDS) and as therapy during the acute phase. Oral aciclovir is most effective in moderating the progress of the symptoms, and in preventing post-herpetic neuralgia, if started within 24 to 72 hours of the onset of symptoms. Immunocompromised patients may respond best to intravenous aciclovir. In patients who are at high risk for recurrences, an oral dose of aciclovir, taken five times daily, is usually effective.

The amino acid lysine has also been reported that to inhibit the replication of herpes zoster.

Other drugs

Cimetidine, a common component of over-the-counter heartburn medication, has been shown to lessen the severity of herpes zoster outbreaks in several different instances. This usage is considered an off-label use of the drug. In addition, cimetidine and probenecid have been shown to reduce the renal clearance of aciclovir. The study showed these compounds reduce the rate, but not the extent, at which valaciclovir is converted into aciclovir. Renal clearance of aciclovir was reduced by approximately 24% and 33% respectively. In addition, respective increases in the peak plasma concentration of aciclovir of 8% and 22% were observed. The authors concluded that these effects were "not expected to have clinical consequences regarding the safety of valaciclovir". Due to the tendency of aciclovir to precipitate in renal tubules, combining these drugs should only occur under the supervision of a physician.

Prognosis

The rash and pain usually subside within three to five weeks. Many patients develop a painful condition called postherpetic neuralgia, which is often difficult to manage. Herpes zoster can reactivate subclinically in some patients, with pain in a dermatomal distribution without an accompanying rash. This condition is known as zoster sine herpete, and may be more complicated, affecting multiple levels of the nervous system and causing multiple cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis. Sometimes serious effects including partial facial paralysis (usually temporary), ear damage, or encephalitis may occur.

Shingles on the upper half of the face may result in eye damage and require urgent ophthalmological assessment. Approximately 25% of Herpes zoster cases result in "Herpes zoster ophthalmicus" (of the eye), which occurs when the varicella-zoster virus is reactivated in the ophthalmic division of the trigeminal nerve. Patients with this condition exhibit a vesicular rash around the orbit of the eye distributed according to the affected dermatome. A minority of patients may also develop conjunctivitis, keratitis, uveitis, and optic nerve palsies. This can sometimes result in chronic ocular inflammation, loss of vision, and debilitating pain.

Reactivation of the Varicella-zoster virus along the Vestibulocochlear nerve (which innervates the hearing and balance organs in the inner ear) is responsible for "Herpes zoster oticus", also known as Ramsay Hunt syndrome type II. The virus is thought to spread from the neighbouring facial nerve. The symptoms of herpes zoster oticus include hearing loss and vertigo (rotational dizziness).

In the United States, approximately 10,000 individuals are hospitalized as a result of Herpes zoster and approximately 100 deaths occur as a result of complications of the disease. Herpes zoster occurs mostly in individuals with decreased immunity (particularly those with HIV infection or those who are receiving immunosuppressive therapy), in the elderly or in early infancy. During pregnancy, primary infection with VZV (chickenpox) but not the local reactivation (shingles) may cause problems in newborns.

Prevention

Zostavax is a vaccine developed by Merck & Co. which has proven successful in preventing half the cases of herpes zoster in a study of 38,000 people who received the vaccine. The vaccine also reduced by two-thirds the number of cases of postherpetic neuralgia. However, prior to the vaccine, it has long been known that adults received natural immune boosting from contact with children infected with varicella. This helped to suppress the reactivation of herpes zoster. In Massachusetts, herpes zoster incidence increased 90%, from 2.77 per 1000 to 5.25 per 100 in the period of increasing varicella vaccination 1999–2003. The effectiveness of the varicella vaccine itself is dependent on this exogenous (outside) boosting mechanism. Thus, as natural cases of varicella decline, so has the effectiveness of the vaccine.

The intake of micronutrients, including antioxidant vitamins, A, C, E and vitamin B group, as well as fresh fruit, may reduce the risk of developing shingles. In one study, patients who consumed less than one serving of fruit a day had three times the risk as those who consumed over three servings per day. For those aged 60 or more, micronutrient and vegetable intake had a similar lowering of risk. A recent study evaluating the effects of Tai Chi and health education on healthy adults, who, after 16 weeks of the intervention, were vaccinated with a live attenuated Oka/Merck varicella-zoster virus vaccine (VARIVAX) concluded that Tai Chi may augment some laboratory parameters of immunity against the varicella zoster virus.

Epidemiology

Before implementation of the universal varicella vaccination program in the U.S., incidence of shingles increased with advancing age in association with a progressive decline in immunity to varicella-zoster virus. Shingles incidence is highest in persons who are over age 55, as well as in immunocompromised patients regardless of age group. The incidence rate of Herpes zoster in persons aged 65 or older is approximately 19 per 1000 individuals per year in the US. The incidence in this age group of a white ethnic background is approximately 3.5 times higher than in the same age group of a Hispanic ethnic background. It can also be seen in immunocompetent individuals undergoing severe emotional stress.

In the United States, herpes zoster affects about 10–20% of the population (although nearly 100% of the population has been exposed to varicella-zoster by age 60). The rate is approximately 131 per 100,000 person-years in white individuals. Similar rates of infection have been observed worldwide.

According to a review of the disease in the United States, one million consultations for herpes zoster occur per year; approximately 250,000 of the patients examined develop herpes zoster ophthalmicus. A subset of 50% of these patients develops complications of herpes zoster ophthalmicus. Ramsay Hunt syndrome is the cause of as many as 12% of all cases of facial paralysis.

History

Herpes zoster has a long recorded history although historical accounts fail to distinguish the blistering caused by VZV and those caused by smallpox. It was only in the late eighteenth century that William Heberden established a way to clinically differentiate between the two diseases. Until the 1940s, the disease was considered benign, and it was believed that serious complications were very rare.

By 1942, it was recognized that zoster was a more serious disease in adults than in children and that Herpes zoster increased in frequency with advancing age. Further studies during the 1950s on immunosuppressed individuals showed that the disease lost much of its benign characteristics and the search for various therapeutic and preventive measures was initiated. By the mid-1960s, several studies identified the gradual reduction in cellular immunity in old age by observing that in a cohort of 1000 people who lived to the age of 85, approximately 500 would have one attack of Herpes zoster and 10 would have two attacks.

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External links

• NINDS Shingles Information Page, National Institute of Neurological Disorders and Stroke
• Template:NHS
• Information about management of Shingles for physicians
• Links to pictures of Shingles (Hardin MD) University of Iowa
• After Shingles—Information about Shingles and Post-Herpetic Neuralgia
• The National Eye Institute (NEI)

• Infectious skin diseases
• Viral diseases
• Herpesviruses
• Viruses