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•	Introduction
•	Symptoms
•	Risk Factors
•	Complications
•	Vaccination
•	Diagnosis
•	Treatment for Chickenpox...
•	Treatment for an Acute Shin...
•	Treatment for Postherpetic ...
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Shingles and Chickenpox (Varicella-Zoster Virus)

Highlights

Drug Approvals

• Proquad is a new vaccine that combines measles, mumps, rubella, and varicella (chickenpox) protection. It is the first vaccine to provide one-shot immunization against all four diseases.
• Pregabalin (Lyrica) has been approved for treatment of postherpetic neuralgia. The anticonvulsant drug is similar to gabapentin (Neurontin).

Chickenpox Vaccine

• In 2005, the U.S. Centers for Disease Control and Prevention (CDC) expanded its recommendations for chickenpox vaccination. The CDC now recommends the vaccine for all patients age 13 years and older who do not have immunity to chickenpox. Patients should receive two doses spaced 1 to 2 months apart.
• The vaccine has reduced hospitalizations for chickenpox by 88%, according to a study in the Journal of the American Medical Association.
• Deaths from chickenpox have also dramatically declined since the vaccine became available in 1995, suggests a study in the New England Journal of Medicine.

Shingles Vaccine

• The FDA has approved the use of a shingles vaccine, called Zostavax. The vaccine is a stronger version of the chickenpox vaccine.
• The Zostavax vaccine is the first vaccine for prevention of shingles (herpes zoster). The vaccine is for patients age 60 years and older.
• In a clinical trial, patients who received the vaccine had half the number of shingles cases as patients who received placebo, and two-thirds fewer cases of postherpetic neuralgia than those taking placebo. Results of the trial were published in the New England Journal of Medicine.

Postherpetic Neuralgia

Epidural (spinal) injections do not help prevent postherpetic neuralgia, according to a study in the Lancet. Researchers found that the injections helped slightly to relieve shingles pain, but the effect did not last longer than a month.

Introduction

Shingles and chickenpox were once considered separate disorders. Researchers now know that they are both caused by a single virus of the herpes family known as varicella-zoster virus (VZV). The word herpes is derived from the Greek word "herpein," which means "to creep," a reference to a characteristic pattern of skin eruptions. VZV is still referred to by separate terms:

• Varicella: The primary infection that causes chickenpox
• Herpes zoster: The reactivation of the virus that causes shingles

Varicella (Chickenpox). When patients with chickenpox cough or sneeze, they expel tiny droplets that carry the virus. If a person who has never had chickenpox or been vaccinated inhales these particles, the virus enters the lungs. From here it passes into the bloodstream. When it is carried to the skin it produces the typical rash of chickenpox.

Chickenpox is caused by the varicella-zoster virus, a member of the herpes virus family. The same virus also causes herpes zoster, shingles, in adults. Chickenpox is extremely contagious, and can be spread by direct contact, droplet transmission, and airborne transmission. Symptoms range from fever, headache, stomach ache, or loss of appetite before breaking out in the classic pox rash. The rash can consist of several hundred small, itchy, fluid-filled blisters over red spots on the skin. The blisters often appear first on the face, trunk, or scalp and then spread to other parts of the body

Herpes Zoster (Shingles). The virus also travels to nerve cells called dorsal root ganglia. These are bundles of nerves that transmit sensory information from the skin to the brain. Here, the virus can hide from the immune system for years, often for a lifetime. This inactivity is called latency.

Click the icon to see an image of shingles.

If the virus becomes active after being latent, it causes the disorder known as shingles. The virus in this later form is referred to as herpes zoster. The virus spreads in the ganglion and to the nerves connecting to it. Nerves most often affected are those in the face or the trunk. The virus can also spread to the spinal cord and into the bloodstream.

It is not clear why the virus reactivates in some people and not in others. In many cases, the immune system has become impaired or suppressed from certain conditions such as AIDS or other immunodeficient diseases, or from certain cancers or drugs that suppress the immune system. Aging itself increases the risk for shingles.

Other Herpes Viruses

The varicella-zoster virus belongs to a group of herpes viruses that includes eight human viruses (it also includes animal viruses as well). Herpes viruses are similar in shape and size and reproduce within the structure of a cell. The particular cell depends upon the specific virus. The human herpes viruses are:

• Herpes Simplex Virus 1 (HSV-1; causes cold sores and sometimes genital herpes)
• Herpes Simplex Virus 2 (HSV-2; causes genital herpes and sometimes cold sores)
• Varicella-zoster Virus (VZV; causes chickenpox and shingles)
• Cytomegalovirus (CMV; causes mononucleosis and retinitis)
• Epstein-Barre Virus (EBV; causes mononucleosis
• Human Herpesvirus 6 (HHV6; causes roseola)
• Human Herpesvirus 7 (HHV7; causes roseola)
• Human Herpesvirus 7 (HHV8; causes Kaposi's sarcoma)

All herpes viruses share some common properties, including a pattern of active symptoms followed by latent inactive periods that can last for months, years, or even for a lifetime. [For more information, see In-Depth Report #52: Herpes Simplex.]

Symptoms

The time between exposure to the virus and eruption of symptoms is called the incubation period. For chicken pox, this period is between 10 and 20 days. The patient often develops fever, headache, swollen glands, and other flu-like symptoms before the typical rash appears. While fevers are low grade in most children, some can reach up to 105° F.

These symptoms subside once the rash breaks out. One or more tiny raised red bumps appear first, most often on the face, chest or abdomen. They become larger within a few hours and spread quickly, eventually forming small blisters on a red base. The numbers of blisters vary widely; some patients have only a few spots, others can develop hundreds. Each blister is filled with clear fluid that becomes cloudy in several days. It takes about 4 days for each blister to dry out and form a scab. During its course, the rash itches, sometimes severely. Usually separate crops of blisters occur over 4 to 7 days, and the entire disease process lasts between 7 and 10 days.

Chickenpox itself usually occurs only once, although mild second infections, marked by the telltale rash, have been reported in older children years after their first infection.

Symptoms of a Typical Shingles (Herpes Zoster) Attack

Shingles nearly always occurs in adults. It develops on one side of the body. Usually two, and sometimes three, identifiable symptom stages occur:

• The first is known as the prodrome, a cluster of warning symptoms that appear before the outbreak of the infection.
• The second stage comprises the symptoms of the active infection itself.
• In many patients, a third syndrome known as postherpetic neuralgia develops.

One form of shingles is known as zoster sine herpes, in which pain occurs first without a rash. Pain is so common to all stages of herpes zoster that doctors often refer to all syndromes with a single term: Zoster-Associated Pain (ZAP).

Prodrome (Pain).

• Pain is the primary early symptom for shingles, and it occurs in all patients. The pain most often occurs in the skin at the site of the re-activated virus. The pain may be experienced as sharp, aching, piercing, tearing, or similar to an electric shock.
• The affected skin may itch, feel numb, and be unbearably sensitive to touch. Often the patient experiences a combination of these sensations along with pain.
• In addition, some patients may have flu-like symptoms such as muscle aches. (Some people have fever, but it is uncommon.)

The prodrome stage lasts 1 to 5 days before the infection becomes active and the skin rash erupts. Occasionally, the pain can last for weeks or even months before the rash erupts.

Active Shingles. The rash that marks the active infection follows the same track of inflamed nerves as the prodrome pain. Between 50 - 60% of cases occur on the trunk. The second most common site is the head, particularly on one side of the face. It may also erupt on the neck or lower back. If the face is affected, there is a danger that the infection can spread to the eye or mouth. A rash that follows the side of the nose is a warning that the cornea of the eye is in danger.

This is a picture of herpes zoster (shingles) on the neck and cheek. The same virus that causes chickenpox is responsible for outbreaks of shingles. Outbreaks of shingles often follow the distribution of nerves in the skin. This distribution pattern is called a dermatome (see the "dermatomes" picture).

The active infection is typically marked by the following sequence:

• A rash appears, starting as well-defined, small, red, clear spots.
• Within 12 to 24 hours, these pimples develop into small fluid-filled blisters.
• The blisters grow, merge, and become pus-filled.
• Pain is common during the active infection.
• Within about 7 to 10 days (as with chickenpox), the blisters form crusts and heal. In some cases it may take as long as a month before the skin clears completely. Healing takes even longer in patients who have impaired immune systems, and, in such cases, the blisters may persist for months.

Zoster Sine Herpete. Sometimes pain develops without a rash, a condition known as zoster sine herpete. This usually occurs in elderly patients. Symptoms include burning or shooting pain, numbness, tingling, itching, headache, fever, chills, and nausea. An accurate early diagnosis of shingles in such cases is often difficult. Some evidence suggests that some cases of Bell's palsy (in which part of the face becomes paralyzed) might actually be an indication of zoster sine herpete.

Postherpetic Neuralgia. Postherpetic neuralgia (PHN) is pain that persists for longer than a month after the onset of herpes zoster. (Some experts define persistent pain as subacute herpetic neuralgia if it lasts between 1 and 3 months, and as PHN if it lasts beyond 3 months.) PHN occurs in approximately 10 - 20% of patients who have shingles.

Risk for Recurrence of Shingles. Shingles can recur, but the risk is low (1 - 5%). Some evidence suggests that a first zoster episode boosts the immune system to ward off another attack. To support this theory, some elderly people with zoster who are exposed to children with chickenpox appear to have extra protection against a second zoster attack. In people with impaired immune systems, such as those with AIDS, a booster effect does not occur. These patients are at particular risk for multiple recurrences of shingles.

Risk Factors

The varicella-zoster virus is responsible for both chickenpox and herpes zoster, but its method of infection is different in both diseases.

• Both the active varicella and zoster form of the virus can cause chickenpox.
• The shingles virus in its latent (inactive) form is never infectious.

Catching Chickenpox. Most people get chickenpox from exposure to other people with chickenpox. It is most often spread through sneezing, coughing, and breathing. It is so contagious that few nonimmunized people escape this common disease when they are exposed to someone else with the disease.

People can also catch chickenpox from direct exposure to a shingles rash if they have not been immunized by vaccination or a previous bout of chickenpox. In such cases, transmission happens during the active phase when blisters have erupted but have not formed dry crusts. Herpes zoster spreads only from the rash. A person with shingles cannot transmit the virus by breathing or coughing.

Developing Shingles. Shingles itself can develop only from a reactivation of the varicella-zoster virus in a person who has previously had chickenpox. In other words, shingles itself is never transmitted from one person to another either in the air or through direct exposure to the blisters.

Risk Factors for Chickenpox (Varicella)

Between 75 - 90% of chickenpox cases occur in children under 10 years of age. Before the introduction of the vaccine, about 4 million cases of chickenpox were reported in the U.S. each year. Since a varicella vaccine became available in the US in 1995, however, the incidence of disease and hospitalizations due to chickenpox has declined by nearly 90%. Experts expect the disease to become a rarity in the US.

The disease usually occurs in late winter and early spring months. It can also be transmitted from direct contact with the open sores. (Clothing, bedding, and such objects do not usually spread the disease.)

A patient with chickenpox can transmit the disease from about 2 days before the appearance of the spots until the end of the blister stage. This period lasts about 5 to 7 days. Once dry scabs form, the disease is unlikely to spread.

Most schools allow children with chickenpox back 10 days after onset. Some require children to stay home until the skin has completely cleared, although this is not necessary to prevent transmission.

Risk Factors for Shingles (Herpes Zoster)

About 500,000 cases of shingles occur each year in the U.S. Anyone who has had chickenpox has risk for shingles later in life, which means that 90% of adults in the U.S. are at risk for shingles. Shingles occurs, however, in between 10 - 20% of these adult over the course of their lives, so certain factors must exist to increase the risk for such outbreaks.

The Aging Process. The risk for herpes zoster increases as people age, and the overall number of cases will undoubtedly increase as the baby boomer generation gets older. One study estimated that a person who reaches age 85 has a 50% chance of having herpes zoster. The risk for postherpetic neuralgia (PHN) is also highest in older people with the infection and increases dramatically after age 50. PHN is persistent pain and is the most feared complication of shingles.

Immunosuppression. People whose immune systems are impaired from diseases such as AIDS or childhood cancer have a risk for herpes zoster that is much higher than those with healthy immune systems. Herpes zoster in people who are HIV-positive may be a sign of full-blown AIDS. Certain drugs used for HIV, called protease inhibitors, may also increase the risk for herpes zoster.

Cancer. Cancer places people at risk for herpes zoster. At highest risk are those with Hodgkin's disease (13 - 15% of these patients develop shingles). About 7 - 9% of patients with lymphomas, and between 1 - 3% of patients with other cancers, have herpes zoster. Chemotherapy itself increases the risk for herpes zoster.

Immunosuppressant Drugs. Patients who take certain drugs that suppress the immune system are at risk for shingles (as well as other infections). They include:

• Azathioprine (Imuran)
• Chlorambucil (Leukeran)
• Cyclophosphamide (Cytoxan)
• Cyclosporine (Sandimmune, Neoral)
• Cladribine (Leustatin)

These drugs are used for patients who have undergone organ transplantation and are also used for severe autoimmune diseases caused by the inflammatory process. Such disorders include rheumatoid arthritis, systemic lupus erythematosus, diabetes, multiple sclerosis, Crohn's disease, and ulcerative colitis.

Lack of Exposure to Children Infected with Chickenpox. Interestingly, one study suggested that previously infected adults who are exposed to children with chickenpox may receive an extra boost in antibody production, which can actually help them fight off herpes zoster. This means that as more children are vaccinated against chickenpox, more adults may be at risk for herpes zoster.

Risk Factors for Shingles in Children. Although most common in adults, shingles occasionally develops in children. One study reported that only 5% of cases occur in those under age 15. Children with immune deficiencies are at highest risk. Children with no immune problems but who had chickenpox before they were 1 year old also have a higher risk for shingles.

Complications

Chickenpox (varicella) rarely causes complications, but it is not always harmless. It can cause hospitalization and, in rare cases, death. Fortunately, since the introduction of the vaccine in 1995, hospitalizations have declined by nearly 90%, and there have been few fatal cases of chickenpox.

Adults have the greatest risk for dying from chickenpox, with infants having the next highest risk. Males (both boys and men) have a higher risk for a severe case of chickenpox than females. Children who catch chickenpox from family members are likely to have a more severe case than if they caught it outside the home. The older the child the higher the risk for a more severe case. But even in such circumstances, chickenpox is rarely serious in children. Other factors put individuals at specifically higher risk for complications of chickenpox.

Recurrence of Chickenpox and Reactivation as Shingles

Recurrence of Chickenpox. Recurrence of chickenpox is possible, but uncommon. One episode of chickenpox usually means life-long immunity against a second attack. However, people who have had mild infections may be at greater risk for a breakthrough infection later on.

Reactivation of the Virus as Shingles (Herpes Zoster). The major long-term complication of varicella is the later reactivation of the herpes zoster virus and the development of shingles. Shingles occurs in about 20% of people who have had chickenpox.

Specific Complications of Chickenpox (Varicella)

Aside from itching, the complications described below are very rare.

Itching. Itching, the most common complication of the varicella infection, can be very distressing, particularly for small children. Certain home remedies are available that can alleviate the discomfort (see Treatment for Chickenpox section).

Secondary Infection and Scarring. Small scars may remain after the scabs have fallen off, but they usually clear up within a few months. In some cases, a secondary infection may develop at sites which the patient has scratched. The infection is usually caused by the bacteria Staphylococcus aureus or Streptococcus pyogenes. Permanent scarring may occur as a result. Children with chickenpox are at much higher risk for this complication than adults are, possibly because they are more likely to scratch.

Ear Infections. Some children are at higher risk for ear infections from chickenpox. Hearing loss is a very rare result of this complication.

A middle ear infection is also known as otitis media. It is one of the most common of childhood infections. With this illness, the middle ear becomes red, swollen, and inflamed because of bacteria trapped in the eustachian tube.

Bacterial Superinfection. Bacterial superinfection of the skin caused by group A streptococcus is the most common serious complication of chickenpox (but it is still rare). The infection is usually mild, but if it spreads in deep muscle, fat, or in the blood, it can be life threatening. Infection can cause serious conditions such as necrotizing fasciitis (the so-called flesh-eating bacteria) and toxic shock syndrome (TSS).

Symptoms include:

• A persistent or recurrent high fever
• Redness, pain, and swelling in the skin and the tissue beneath

Pneumonia. Pneumonia is suspected if coughing and abnormally rapid breathing develop in patients who have chickenpox. Adults and adolescents with chickenpox are at some risk for serious pneumonia. Pregnant women, smokers, and those with serious medical conditions are at higher risk for pneumonia if they have chickenpox. Oxygen and intravenous acyclovir are key treatments for this condition. Pneumonia that is caused by varicella can result in lung scarring, which may impair oxygen exchange over the following weeks, or even months.

Click the icon to see an image of pneumonia.

Effects on the Brain and Central Nervous System.

• Inflammation in the Brain. Encephalitis and meningitis, infections or inflammation in the central nervous systems, have occurred in a few varicella patients, both children and adults. This condition can be very dangerous, causing coma and even death. Fortunately, it is extremely rare. Symptoms vary; the patient may become over-agitated or may exhibit loss of coordination and poor balance.
• Stroke. Although stroke in children is extremely rare, a condition called cerebral vasculitis, in which blood vessels in the brain become inflamed, has been associated with varicella-zoster. Varicella may be a factor in some cases of stroke in young adults.

Effects During Pregnancy. The risk for chickenpox in a pregnant woman is very low (1 to 7 cases cases in 10,000). However, chickenpox places the woman at risk for life-threatening pneumonia. Infection in the pregnant woman in the first trimester also poses a 1 - 2% chance for infecting the developing fetus, which is an extremely serious condition. (Herpes zoster is even rarer in pregnant women, and there is almost no risk for the unborn child in such cases.)

Disseminated Varicella. Disseminated varicella, chickenpox that spreads to organs in the body, is extremely serious and is a major problem for patients with compromised immune systems. An immune system may become compromised as a result of diseases such as AIDS, inherited conditions, or certain drugs. For example, disseminated varicella occurs in up to 35% of children with chickenpox who are taking cancer chemotherapy. In such cases, mortality rates are between 7 - 30%.

Reye's Syndrome. Reye's syndrome, a disorder that causes sudden and dangerous liver and brain damage, is a complication of chickenpox and other viruses in children who take aspirin. The disease can lead to coma and is life-threatening. Symptoms include rash, vomiting, and confusion beginning about a week after the onset of the disease. Because of the strong warnings against children taking aspirin, this condition is, fortunately, nearly nonexistent.

Other Rare Complications of Chickenpox. Other extremely rare complications of varicella include problems in blood clotting, and inflammation of the nerves in the hands and feet, and in other areas of the body, such as the heart, testicles, liver, joints, or kidney. Children should never be given aspirin when they have a viral infection.

Complications of Shingles (Herpes Zoster)

Pain. The pain and discomfort of the active herpes zoster infection is the primary symptom and complication of herpes zoster. The pain usually takes one of these forms:

• Continuous burning or aching pain
• Periodic piercing pain
• Spasm similar to electric shock

Such experiences may also be more intense than even normal responses, defined in the following ways:

• Allodynia is pain caused by factors, such as a light touch of clothing or a cold wind, which occurs from very little stimulation.
• Hyperalgesia is a more intense painful response to a normally painful experience.

The pain tends to be more severe at night. Temperature changes can also affect pain. The pain may extend beyond the areas of the initial zoster attack. In most cases, it does not affect daily life. Rarely, however, the pain of herpes zoster affects sleep, mood, work, and overall quality of life. This can lead to fatigue, loss of appetite, depression, social withdrawal, and impaired daily functioning.

Itching. Many patients report itching (postherpetic itch) as the primary symptom, rather than pain. In rare cases, it can be disabling.

Postherpetic Neuralgia (PHN). Postherpetic neuralgia (PHN) is pain that persists for longer than a month after the onset of herpes. It is the most common severe complication of shingles. It is not clear why PHN occurs. Some theories for its development are:

• The herpes zoster virus appears to produce persistent inflammation in the spinal cord that causes long-term damage, including nerve scarring.
• Nerves that are injured in the initial attack may regrow abnormally and provoke an exaggerated response in the brain that signals intense sensitivity or pain.

In people with herpes zoster, the risk of developing PHN ranges from 10 - 70%. In general, however, the risk is likely to be in the lower range. People with impaired immune systems do not seem to be at any higher risk for persistent PHN than those with normal immune systems.

The following are risk factors for PHN:

• Age. PHN affects about 25% of herpes zoster patients over 60 years old. The older a person is, the longer PHN is likely to last. It rarely occurs in people under age 50.
• Gender. Some studies suggest that women may be at slightly higher risk for PHN than men.
• Severe or Complicated Shingles. People who had prodromal symptoms or a severe attack (numerous blisters and severe pain) during the initial shingles episode are also at high risk for PHN. The rate is also higher in people whose eyes have been affected by zoster.

In most cases, PHN resolves within 3 months. Some experts define persistent pain after a herpes zoster attack as subacute herpetic neuralgia if it lasts between 1 and 3 months and as PHN only if it lasts beyond 3 months. Studies report that only about 10% of patients experience pain after a year. Unfortunately, when PHN is severe and treatments have not been very effective, the persistent pain and abnormal sensations can be profoundly frustrating and depressing for patients.

Secondary Infection in the Blisters. If the blistered area is not kept clean and free from irritation, it may become infected with Streptococcus A or Staphylococcus bacteria. If the infection is severe, scarring can occur.

Guillain-Barre Syndrome. Guillain-Barre syndrome is caused by inflammation of the nerves and has been associated with a number of viruses, including herpes zoster. The arms and legs become weak, painful, and, sometimes, even paralyzed. The trunk and face may be affected. Symptoms vary from mild to severe enough to require hospitalization. The disorder resolves in a few weeks to months. Other viruses ( C. jejuni, cytomegalovirus, and Epstein-Barr) may have a stronger association to this syndrome than herpes zoster. One study, in fact, found no higher incidence of herpes zoster virus in patients with Guillain-Barre than in the general population.

Effects on Face and Ears.

• Ramsay Hunt syndrome. Ramsay Hunt syndrome occurs when herpes zoster causes facial paralysis and rash on the ear (herpes zoster oticus) or in the mouth. Symptoms include severe ear pain and hearing loss, ringing in the ear, loss of taste, nausea, vomiting, and dizziness. Ramsay Hunt Syndrome may also cause a mild inflammation in the brain. The dizziness may last for a few days or even for weeks, but usually resolves. Severity of hearing loss varies from partial to total; however, this too usually always goes away. Facial paralysis, on the other hand, may be permanent.
• Bell's Palsy. Bell's palsy is partial paralysis of the face. There is some indication that this syndrome may suggest a reactivation of herpes zoster, even if no rash appears.

In some cases, it is difficult to distinguish between Bell's palsy and Ramsay Hunt syndrome, particularly in the early stages. Ramsay Hunt syndrome tends to be more severe than Bell's palsy. Although evidence is weak on treating facial involvement of herpes zoster, some experts recommend oral prednisone (a corticosteroid) and an antiviral drug within 7 days of symptom onset. Even though nearly all cases of Bell's palsy and the majority of Ramsay Hunt syndrome resolve without problems, the possibility of residual symptoms with Ramsay Hunt and the early resemblance between the two syndromes warrants this treatment.

Effects on the Brain. Inflammation of the membrane around the brain (meningitis) or in the brain itself (encephalitis) is a rare complication in people with herpes zoster. The encephalitis is generally mild and resolves in a short period. In rare cases, particularly in patients with impaired immune systems, it can be severe and even life-threatening.

Click the icon to see an image of the meninges of the brain.

Effects in the Urinary Tract. In rare situations, herpes zoster can infect the urinary tract and cause difficulty in urination. The condition is temporary but may require a catheter for patients who have trouble urinating.

Click the icon to see an image of the male urinary tract.

Infections in the Eye. If shingles occurs in the face, the eyes are at risk, particularly if the path of the infection follows the side of the nose. If the eyes become involved (called herpes zoster ophthalmicus), a severe infection can occur that is difficult to treat and can threaten vision. AIDS patients may be at particular risk for a chronic infection in the cornea of the eye.

Click the icon to see an image of the eye.

Herpes zoster can also cause a devastating infection in the retina called imminent acute retinal necrosis syndrome. In such cases, visual changes develop within weeks or months after the herpes zoster outbreak has resolved. Although this complication usually follows a herpes outbreak in the face, it can occur after an outbreak in any part of the body. Prompt treatment with acyclovir can often halt its progress, at least in people with healthy immune systems. Acyclovir or valacyclovir, a similar drug, may prevent other eye complications, such as conjunctivitis (pink-eye), inflammation of the cornea, and pain.

Disseminated Herpes Zoster. As with disseminated chickenpox, disseminated herpes zoster, which spreads to other organs, can be serious to life-threatening, particularly if it affects the lungs. People with compromised immune systems are at greatest danger, with risk of 5 - 25%. It is very rare in people with healthy immune systems.

In very rare cases, herpes zoster has been associated with Stevens-Johnson syndrome, an extensive and serious condition in which widespread blisters cover mucous membranes and large areas of the body.

Vaccination

A live-virus vaccine (Varivax) produces persistent immunity against chickenpox. Data show that the vaccine can prevent chickenpox or reduce the severity of the illness if it is used within 3 days, and possibly up to 5 days, after exposure to the infection.

The vaccine against chickenpox is now recommended in the U.S .for all children between the ages of 18 months and adolescents who have not yet had chickenpox. Children are given one dose of the vaccine. (A new vaccine [Proquad] for children ages 1 – 12 years combines measles, mumps, rubella, and varicella in one product.) Two doses, 1 to 2 months apart, are given to children age 13 years and older.

Recommendations for the Vaccine in Adults

The U.S. Centers for Disease Control and Prevention (CDC) recommends that every healthy adult without a known history of chickenpox be vaccinated. Adults in the following groups should strongly consider vaccination:

• Those with high risk of exposure or transmission (hospital or day care workers, parents of young children).
• People in contact with those who have compromised immune systems.
• Nonpregnant women of childbearing age.
• International travelers.

As with other live-virus vaccines, the chickenpox vaccine is not recommended for:

• Women who are pregnant or who may become pregnant within 30 days of vaccination.
• People whose immune systems are compromised by disease or drugs (such as after organ transplantation). Experts report that the vaccine is safe in children with acute lymphoblastic leukemia (ALL). Certain children who are HIV-positive may be candidates for the vaccine. An inactivated chickenpox vaccine may be safe for patients undergoing bone marrow transplants when given before and after the operation.

Patients who cannot be vaccinated but who are exposed to chickenpox receive immune globulin antibodies against varicella virus. This helps prevent complications of the disease if they become infected.

Side Effects of the Varicella (Chickenpox) Vaccine

• Discomfort at the Injection Site. About 20% of vaccine recipients have pain, swelling, or redness at the injection site.
• Severe Side Effects. Only about 5% of adverse reactions are serious. Such events include seizures, pneumonia, anaphylactic reaction, encephalitis, Stevens-Johnsons syndrome, neuropathy, herpes zoster, and blood abnormalities.
• Risk of Transmission. The vaccine may produce a mild rash within about a month of the vaccination, which can transmit chickenpox to others. Individuals who have recently been vaccinated should avoid close contact with anyone who might be susceptible to severe complications from chickenpox until the risk for a rash passes.
• Later Infection. Months or even years after the vaccination, some people develop a mild infection termed modified varicella-like syndrome (MVLS). The condition appears to be less contagious and has fewer complications than naturally acquired chickenpox.

Vaccine Long-Term Effectiveness and Possible Need for a Booster

There is currently intense debate over the long-term protection of the vaccine. Such controversy is stimulated by the incidence of breakthrough infections after vaccination. However, evidence clearly shows  improvements in quality of life and better survival rates since the introduction of the vaccine. Any negative studies to date on long-term effectiveness simply raise the question of the need for booster or higher doses -- not the elimination of the vaccine altogether.

Breakthrough Infections and Waning Protection in Vaccinated Children. Studies report that more than 15% of vaccinated children still develop chickenpox (called breakthrough infections). Reasons for this include:

• Waning Immunity. Studies on children in day care centers report that nearly half of children who had been previously vaccinated develop chickenpox. In one study, children vaccinated within three years had a much lower risk than those whose vaccinations had occurred later. Another study reported a higher risk for breakthrough infections in children who were immunized before 15 months.
• Oral Steroids. Children on oral steroids are also at higher risk for a breakthrough infection. (Children taking inhaled steroids, such as for asthma, do not appear to have this risk.)

If vaccinated children develop chickenpox, the cases are nearly always mild and usually less contagious. In such children, the infection appears to be caused by a wild virus, not a reactivation of the vaccine.

This does not necessarily mean that children who are vaccinated eventually lose total immunity. A breakthrough infection is often due to issues with the primary vaccine (improper storage, low potency) or the child's history (having asthma, being less than 14 months at the time of vaccination). Nevertheless, some evidence suggests that either having the vaccination or even having chickenpox itself is not as protective against a later infection as experts have previously thought.

Long-Term Protection in Vaccinated Adults. The protective effect for adults is even less clear. An encouraging study of adults reported that although 9% developed chickenpox months to years after their last vaccination, in all cases, infection was mild, with none of the serious complications of adult chickenpox. A 2003 study on booster shots in older adults suggests that revaccination with the live virus is safe and effective.

Vaccine's Effect on Shingles. It is not yet clear if the chickenpox vaccine protects against the later development of shingles. Vaccination began in 1995, so it may take years for scientists to better understand its effect on shingles. However, in 2006 a shingles vaccine was approved for use in the United States. The zoster vaccine (Zostavax) is a stronger version of the chickenpox vaccine. Study results published in 2005 suggested that the zoster vaccine could prevent about half of all shingles cases and two-thirds of postherpetic neuralgia cases. The vaccine was tested in adults age 60 years and older.

Varicella-Zoster Immune Globulin

Varicella-zoster immune globulin (VZIG) is a substance that triggers an immune response against the varicella-zoster virus. It is used to protect high-risk patients who are exposed to chickenpox, or those who cannot receive a vaccination of the live virus. Such groups include:

• Pregnant women with no history of chickenpox
• Newborns under 4 weeks who are exposed to chickenpox or shingles
• Premature infants
• Immunocompromised children and adults with no antibodies to VZV
• Recipients of bone-marrow transplants (even if they have had chickenpox)
• Patients with a debilitating disease (even if they have had chickenpox)

VZIG should be given within 96 hours and no later than 10 days after exposure to someone with chickenpox.

Diagnosis

Both chickenpox (varicella) and shingles (zoster) can usually be diagnosed by symptoms alone. If a diagnosis is still unclear after a physical examination, diagnostic tests may be required.

Ruling Out Other Disorders

Either variation of the virus may be confused with other disorders.

Ruling out Disorders that Resemble Chickenpox. Chickenpox, particularly in early stages, may be confused with herpes simplex (the disorder more commonly referred to as "herpes"), or impetigo, insect bites, and scabies.

Ruling out Disorders that Resemble Shingles. The early prodrome stage of shingles can cause severe pain on one side of the lower back, chest, or abdomen before the rash appears. It therefore may be mistaken for disorders, such as gallstones, that cause acute pain in internal organs.

In the active rash stage, shingles may be confused with herpes simplex, particularly in young adults if the blisters occur on the buttocks or around the mouth. Herpes simplex, however, does not usually generate chronic pain.

A diagnosis may be difficult if herpes zoster takes a non-typical course, such as with Bell's palsy or Ramsay Hunt syndrome in the face, or if it affects the eye, or causes fever and delirium.

Test to Identify the Virus

In most cases of chickenpox and shingles, the symptoms alone are sufficient to make a diagnosis. In some patients, such as those who are immunosuppressed, if the symptoms are not straightforward the doctor performs one or more additional tests to detect the virus itself. The tests usually aim to distinguish between varicella-zoster and herpes simplex viruses.

Virus Culture. A viral culture uses specimens taken from the blister, fluid in the blister, or sometimes spinal fluid. They are sent to a laboratory, where it takes between 1 and 14 days to detect the virus in the preparation made from the specimen. It is also sometimes used in vaccinated patients to determine if a varicella-like infection is caused by a natural virus or by the vaccine. This test is useful, but it is sometimes difficult to recover the virus from the samples.

Immunofluorescence Assay. Immunofluorescence is a diagnostic technique used to identify antibodies to a specific virus. In the case of herpes zoster, the technique uses ultraviolet rays applied to a preparation composed of cells taken from the zoster blisters. The specific characteristics of the light as seen through a microscope will identify the presence of the antibodies. This test is less expensive than a culture, more accurate, and results are faster.

Polymerase Chain Reaction (PCR). Polymerase chain reaction (PCR) techniques use a piece of the DNA of the virus, which is then replicated millions of times until the virus is detectable. This technique is expensive but is useful for unusual cases, such as identifying infection in the central nervous system.

Treatment for Chickenpox

Acetaminophen. Patients with chickenpox do not have to stay in bed unless fever and flu symptoms are severe. To relieve discomfort, a child can take acetaminophen (Tylenol), with doses determined by the doctor. A child should never be given aspirin or medications containing aspirin, which increase the risk for a dangerous condition called Reye's syndrome.

Soothing Baths. Frequent baths are particularly helpful in relieving itching, when used with preparations of finely ground (colloidal) oatmeal. Commercial preparations (Aveeno) are available in drugstores, or one can be made at home by grinding or blending dry oatmeal into a fine powder. Use about two cups per bath; the oatmeal will not dissolve, and the water will have a scum. One-half to one cup of baking soda in a bath may also be helpful.

Lotions. Calamine lotion and similar over-the-counter preparations can be applied to the blisters to help dry them out and soothe the skin.

Antihistamines. For severe itching diphenhydramine (Benadryl) is useful and may help children sleep.

Preventing Scratching. Small children may have to wear mittens so that they don't scratch the blisters and cause a secondary infection. All patients with varicella, including adults, should have their nails trimmed short.

Acyclovir for Chickenpox

Acyclovir is an antiviral drug that may be used in adult varicella patients or those of any age with a high risk for complications and severe forms of chickenpox. The drug may also benefit smokers with chickenpox, who are at higher than normal risk for pneumonia. Some experts recommend its use for children who catch chickenpox from other family members because such patients are at risk for more serious cases. To be effective, oral acyclovir must be taken within 24 hours of the onset of the rash. Early intravenous administration of acyclovir is essential treatment for chickenpox pneumonia.

Treatment for an Acute Shingles Attack

The treatment goals for an acute attack of herpes zoster include:

• Reduce pain
• Reduce discomfort
• Hasten healing of blisters
• Prevent the disease from spreading

Over-the-counter (OTC) remedies are often effective in reducing the pain of an attack. Antiviral drugs (acyclovir and others), oral corticosteroids, or both are sometimes given to patients with severe symptoms, particularly if they are older and at risk for postherpetic neuralgia. In addition, psychologic therapies aimed at coping and reducing the effects of pain may be useful.

Home Remedies for Shingles

Applied Cold. Cold compresses soaked in Burrow's solution (an OTC remedy) and cool baths may help relieve the blisters. It is important not to break blisters as this can cause infection. Experts advise against warm treatments, which can intensify itching. Patients should wear loose clothing and use clean loose gauze coverings over the affected areas.

Itch Relief. In general, to prevent or reduce itching, home treatments are similar to those used for chickenpox. Patients can try antihistamines, (particularly Benadryl), oatmeal baths, and calamine lotion.

Over-the-Counter Pain Relievers. For an acute shingles attack, patients may take over-the-counter pain relievers:

• Children should take acetaminophen. (Shingles is very rare in children.)
• Adults may take aspirin or other nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil). Such remedies, however, are not very effective for postherpetic neuralgia.

Nucleoside Analogues and Other Anti-Viral Drugs

Nucleoside Analogues. The best class of drugs developed against varicella-zoster are those known as nucleoside, or guanosine, analogues, which are able to block viral reproduction. None of these drugs can actually destroy the virus and cure the disease, but they can significantly reduce the severity of the attack, hasten healing, and reduce the duration. There is some evidence that early treatment with these drugs can reduce the risk for postherpetic herpes.

These anti-viral drugs are usually taken for 7 days. Ideally they should be started within 72 hours of the onset of infection. The earlier they are given the more effective these drugs are, but they can be helpful even if treatment is started after 3 days. Combinations of antiviral therapy with other drugs, such as tricyclic antidepressants or anticonvulsant drugs are under investigation

Acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex) are approved for shingles. Acyclovir is the oldest, most studied of these drugs, but either famciclovir (Famvir) or valacyclovir (Valtrex), which are both metabolized into acyclovir, are now preferred for herpes zoster for most patients. They relieve symptoms better than acyclovir and require fewer daily doses (typically three) than the five doses needed with acyclovir.

Because herpes zoster tends to resolve fairly quickly in young adults, these drugs are generally reserved for patients at greatest risk for complications or persistent pain. They include:

• Elderly people
• Those with infections that threaten the eye
• Patients who are HIV positive or immunocompromised in other ways
• Patients whose infection covers a larger-than-average surface area of the skin
• Those with very severe pain

These drugs appear to have little or no harmful effect on healthy cells and can penetrate most body tissues, including cerebrospinal fluid. Evidence to date suggests that they are safe during pregnancy.

Possible side effects of nucleoside analogues include rash, headache, fatigue, tremor, nausea and vomiting. Seizures are a very rare side effect. Patients with AIDS or other diseases that compromise the immune system are at increased risk for kidney damage and blood clots. Patients with suppressed immune systems are also more likely to have viral resistance to these drugs. These drugs are safe to take during pregnancy.

Foscarnet. Foscarnet (Foscavir) is a powerful antiviral drug known as a pyrophosphate analogue. It is used in cases of VZV strains that have become resistant to acyclovir and similar drugs. Administered intravenously, the drug can have toxic effects. It can impair kidney function (which is reversible) and cause seizures. Fever, nausea, and vomiting are common side effects. It can also cause ulcers on genital organs. As with other drugs, it does not cure shingles.

Brivudin. Brivudin (Helpin, Zostex) is another anti-viral drug, but it is not available in the U.S. It only needs to be taken once a day.

Oral Corticosteroids

Oral corticosteroids, including prednisolone or prednisone, are powerful anti-inflammatory medications. They have some benefit for reducing pain and accelerating healing in acute attacks when used with acyclovir. (They are not recommended without acyclovir.) They also may be helpful for improving symptoms of Bell's palsy and Ramsay Hunt syndrome. Corticosteroids do not appear to prevent a further shingles attack or reduce the risk for PHN. Side effects of corticosteroids can be severe, and patients should take oral steroids at as low a dose and for as short a time as possible. (Injected or intravenous steroids, however, may offer specific relief for PHN without significant side effects.)

Epidural Blocks

Epidural blocks are injections of local anesthetics and steroids outside the tough membrane surrounding the spinal cord (the dura matter). The injected drugs block the nerves and may offer relief from acute herpes zoster pain for some people. A 2006 study found that a single epidural injection helps slightly to relieve shingles pain for a month, but the effect does not last any longer. The injection does not help prevent postherpetic neuralgia.

Treatment for Postherpetic Neuralgia

Postherpetic neuralgia (PHN) is difficult to treat. Once PHN develops, a patient may need a multidisciplinary approach that involves a pain specialist, psychiatrist, primary care physician, and other health care providers.

In 2004, the American Academy of Neurology (AAN) issued treatment guidelines for postherpetic neuralgia based on an extensive review of published studies. The AAN recommends:

• Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine, maprotiline)
• Anticonvulsants (gabapentin and pregabalin)
• Lidocaine skin patches
• Opioids (oxycodone, methadone, morphine)

Topical Substances for Postherpetic Neuralgia

Topical Pain Relievers. Creams, patches, or gels containing various substances can provide some pain relief.

• Lidocaine and Other Anesthetic Patches. A patch that contains the anesthetic lidocaine (Lidoderm) is approved specifically for postherpetic neuralgia (PHN). One to four patches can be applied over the course of 24 hours. Another patch (EMLA) contains both lidocaine and prilocaine, a second anesthetic. The most common side effects are skin redness or rash.
• Capsaicin (Zostrix) is prepared from the active ingredient in hot chili peppers. An ointment form has been approved for postherpetic neuralgia. Its benefits are limited, however. A patch form that uses a higher than standard dose may work better. In one study, it reduced pain by 33% in nearly half of patients. Capsaicin should not be used until the blisters have completely dried out and are falling off the skin. Capsaicin ointment should be handled using a glove, and applied to affected areas three or four times daily. The patient will usually experience a burning sensation when the drug is first applied, but this sensation diminishes with use. It may take up to 6 weeks for the patient to experience its full effect, and about a third of patients cannot tolerate the burning sensation.
• Topical Aspirin. Topical aspirin, known chemically as triethanolamine salicylate (Aspercreme) may bring relief.
• Menthol-Containing Preparations. Topical drugs containing menthol, such as high-strength Flexall 454, may be helpful.

Skin Coolants. Ethyl chloride (Chloroethane) and fluori-methane are chemicals that cool the blood vessels in the skin. Sprays that contain these chemicals are not anesthetics, but are used to inactivate the sensitive areas. To use the spray, the patient must be in a comfortable position. The spray bottle is held upside-down, about 12 to 18 inches from the targeted area, and the face must be covered if the spray is being used near the head.

Tricyclic Antidepressants

Tricyclic antidepressants relieve pain in up to two-thirds of patients. These drugs not only relieve depression, which can be common in PHN sufferers, but certain tricyclics specifically block sodium channels, which play a role in causing pain in PHN. Nortriptyline (Pamelor, Aventyl), amitriptyline (Elavil, Endep), and desipramine (Norpramin) are standard drugs.

According to one study, two-thirds of patients obtain pain relief if they take tricyclics within 3 months to a year after a herpes zoster attack. The drugs are less successful when taken after that. It may take several weeks for the drugs to become fully effective. They do not work as well in patients who experience burning pain or allodynia (pain that occurs with normally non-painful stimulus, such as a light touch or wind).

Unfortunately, tricyclics have side effects that are particularly severe in the elderly, who are also more likely to have PHN. Desipramine and nortriptyline have fewer side effects than amitriptyline and are preferred for older patients. Side effects include dry mouth, blurred vision, constipation, dizziness, difficulty urinating, disturbances in heart rhythms, and an abrupt drop in blood pressure when standing up.

Anticonvulsant (Anti-Seizure) Drugs

Certain anticonvulsant drugs have effects that block over-excitation of nerve cells and may be helpful for PHN patient. (Anticonvulsant drugs are also known as anti-seizure drugs.)

Gabapentin. Gabapentin (Neurontin) was the first anticonvulsant drug approved for PHN. Studies suggest significant pain relief in patients with PHN and reduction in the use of opioids. Many patients also report improved quality of life, including better sleep. Gabapentin is also showing promise in combination with valacyclovir for reducing pain from an acute herpes zoster attack.

Side effects include skin rashes, increased risk for infection, headache, dizziness, sleepiness, swelling, and upset stomach. Some people experience visual disturbances, ringing in the ears, agitation, or odd movements when drug levels are at their peak. These side effects may limit their value in older people who are at risk of falling. In general, however gabapentin is safer than tricyclic antidepressants for elderly patients.

Pregabalin. Pregabalin (Lyrica) is similar to gabapentin. Like gabapentin, side effects can include sleepiness and dizziness

Other Anticonvulsant Drugs. The AAN guidelines found insufficient evidence to recommend carbamazepine (Tegretol).

Opioids and Opioid-like Drugs

Opioids. Patients with severe pain that does not respond to tricyclic antidepressants may need powerful painkilling opioid drugs. They may be taken by mouth or delivered through a skin patch. Oxycodone is the standard opioid for PHN. Morphine is also used. Methadone (Dolophine) may also be helpful. A 2005 study found that morphine worked best when combined with the anticonvulsant gabapentin. Constipation, drowsiness, and dry mouth are common side effects of opioids.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea but not severe gastrointestinal problems, as NSAIDs can. Studies suggest it might be very helpful for PHN patients, particularly those with heart problems or other conditions that restrict tricyclic antidepressants.

Other Medical Treatments

Intrathecal Corticosteroid Injections. Epidural (also called intrathecal) injections of corticosteroids are administered within the the tough membrane surrounding the spinal cord. The corticosteroids are sometimes combined with anesthetics. Some older studies indicated that these injections may relieve PHN pain, but this treatment is still under investigation and is not common medical practice. A 2006 study reported that epidural injections may provide slight temporary relief for acute shingles attacks, but they do not prevent PHN.

Surgery. Certain surgical techniques in the brain or spinal cord attempt to block nerve centers associated with postherpetic neuralgia. These methods carry risk for permanent damage, however, and should be used only as a last resort when all other methods have failed and the pain is intolerable. Most studies indicate that surgery does not relieve PHN pain.

Psychologic Approaches

Stress Reduction Techniques. A number of relaxation and stress-reduction techniques may be helpful for managing chronic pain. They include meditation, deep breathing exercises, biofeedback, and muscle relaxation. Such techniques may apply to those with severe pain from acute infection and from persistent long-term postherpetic neuralgia. [For more information, see In-Depth Report #31: Stress.]

Behavioral Cognitive Therapy. Behavioral cognitive therapy is showing benefit in enhancing patients' beliefs in their own abilities for dealing with pain. Using specific tasks and self-observation, patients gradually shift their fixed ideas that they are helpless against the pain that dominates their lives to the perception that it is a manageable experience. The skill of the therapist is very important to its success.

Alternative Remedies

Many people with chronic pain such as PHN turn to alternative treatments for relief. Aside from hypnosis, little evidence indicates that these treatments work for PHN. Remedies include:

• Hypnosis
• Topical use of diluted apple cider vinegar
• Acupuncture
• Colostrum (a pre-milk fluid produced by mammals)
• Pantothenic acid (Vitamin B5)

Resources

• www.cdc.gov -- Centers for Disease Control and Prevention
• www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
• www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
• www.aan.com -- American Academy of Neurology
• www.neuropathy.org -- Neuropathy Association
• www.vzvfoundation.org -- VZV Research Foundation

References

Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352(13):1324-1334.

Hempenstall K, Nurmikko TJ, Johnson RW, A'Hern RP, Rice AS. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med. 2005;2(7):e164.

Nguyen HQ, Jumaan AO, Seward JF. Decline in mortality due to varicella after implementation of varicella vaccination in the United States. N Engl J Med. 2005;352(5):450-458.

Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271-2284.

van Wijck AJ, Opstelten W, Moons KG, van Essen GA, Stolker RJ, Kalkman CJ, et al. The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial. Lancet. 2006;367(9506):219-224.

Vazquez M, Shapiro ED. Varicella vaccine and infection with varicella-zoster virus. N Engl J Med. 2005;352(5):439-440.

Zhou F, Harpaz R, Jumaan AO, Winston CA, Shefer A. Impact of varicella vaccination on health care utilization. JAMA. 2005;294(7):797-802.

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