Highlights

New Chickenpox Immunization Schedule

In 2007, the U.S. Centers for Disease Control (CDC) updated the immunization schedule for the chickenpox vaccine. The CDC now recommends that children receive two doses of the vaccine. Children should receive:

• The first dose when they are 12 – 15 months old
• The second dose when they are 4 – 6 years old

If your child has been previously vaccinated, make sure that the pediatrician administers a second “catch-up” dose. It is clear that one dose of chickenpox vaccine does not provide complete protection against chickenpox. Adults who are at high risk of contracting chickenpox should also receive two doses of the chickenpox vaccine.

Shingles Vaccine

In 2006, the FDA approved the first shingles vaccine (Zostavax). The CDC now recommends that all adults with intact immune systems who are age 60 years and older receive this vaccine to help prevent herpes zoster (shingles). This includes adults who have previously had a shingles attack. Evidence indicates that Zostavax can help prevent the occurrence of shingles by about 50%. The vaccine can also help prevent the development of post-herpetic neuralgia (the nerve pain that can follow shingles) by 67%.

Scientists Identify Varicella-Mediating Protein

The varicella-zoster virus causes both chickenpox and shingles. After a chickenpox attack, the virus can lie dormant in the body for many years. Once reactivated, the virus quickly travels through nerve cells, causing rash and nerve pain. In 2006, scientists at the U.S. National Institutes of Health identified a specific protein that causes the virus to spread throughout cells in the body. Researchers hope that this important discovery may lead to new drug treatments for shingles.

Investigational Treatments for Postherpetic Neuralgia

Intravenous antiviral drug treatment, followed by oral antiviral drugs, may help reduce postherpetic neuralgia pain, according to a small study published in the Archives of Neurology.

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 varicella 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. In 2006, scientists at the U.S. Institutes of National Health identified a specific protein, called insulin-degrading enzyme, which causes the varicella-zoster virus to spread throughout cells in the body. The scientists hope that this discovery may eventually help in developing new drug therapies for treating shingles.

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

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. [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 10 - 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 - 7 days, and the entire disease process lasts 7 - 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.

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 - 5 days before the infection becomes active and the skin rash erupts. Occasionally, the pain can last 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 - 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 - 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 - 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.

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 U.S. in 1995, however, the incidence of disease and hospitalizations due to chickenpox has declined by nearly 90%.

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 - 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.

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 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. Recurrence of chickenpox is possible, but uncommon. One episode of chickenpox usually means lifelong 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.

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 - 7 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 Syndrome. Reye 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. Inflammation can also occur 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.

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 - 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. Either 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.

Elderly people. The older the patient, the higher the risk for complications from either chickenpox or shingles. Adults who smoke are at particularly higher risk for pneumonia from chickenpox.

Patients with Compromised Immune Systems. People with suppressed immune systems from diseases such as AIDS, leukemia, or those who take immunosuppressive drugs, are at the highest risk for severe and even unusual forms of VZV. Examples include chronic chickenpox with persistent sores, or disseminated varicella-zoster (in which the infection spreads to internal organs).

Patients with Serious Illnesses. People with serious illnesses may be at risk for complications of the varicella-zoster virus. Patients with diseases, such as Hodgkin's disease, who receive bone marrow or stem cell transplants are at higher risk for herpes zoster and its complications. An inactivated vaccine given before the procedure may be helpful.

Pregnant Women. Pregnant women who become infected with the varicella-zoster virus, whether in the form of chickenpox or shingles, are at increased risk for serious pneumonia.

• The risk for the infant is lower or higher depending on when the mother became infected.
• Chickenpox in the mother during early pregnancy poses a slightly increased risk for birth defects in the infant, but it is not usually viewed as grounds for terminating a pregnancy.
• The highest risk for birth defects is about 2%, which usually occurs if the mother has chickenpox between the 13th and 20th week. Even in such cases, birth defects may only result in minor skin abnormalities. More serious defects include a smaller than normal head, eye problems, low birth weight, and mental retardation.
• If women develop chickenpox (not shingles) within 5 days before and 2 days after delivery, their newborns are at risk for life-threatening varicella.

Newborns and Infants. Chickenpox in newborns is a life-threatening condition. Although chickenpox can still be very dangerous in older infants, most are protected by antibodies in breast milk from mothers who have had chickenpox. Children under age 1 who develop chickenpox are at higher risk for childhood shingles. All infants should have as little exposure as possible to people with chickenpox.

Vaccination

There are two types of varicella vaccines:

• A chickenpox vaccine for vaccinating children, adolescents, and some adults
• A shingles vaccine for vaccinating adults age 60 years and older

A live-virus vaccine (Varivax) produces persistent immunity against chickenpox. [A vaccine (Proquad) for children ages 1 - 12 years now combines measles, mumps, rubella, and varicella in one product.] 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.

In 2007, the U.S. Centers for Disease Control’s Advisory Committee on Immunization Practices (ACIP) revised the immunization schedule for the chickenpox vaccine. The new schedule recommends that children receive TWO doses of the chickenpox vaccine with:

• The first dose administered when the child is 12 – 15 months years of age, and
• The second dose administered when the child is 4 – 6 years of age

As of 2007, all children should routinely receive these vaccinations. For children who have previously received one dose of the chickenpox vaccine, the ACIP recommends that they receive a “catch-up” second dose during their regular doctor’s visit. This second dose can be given at any time as long as it is at least 3 months after the first dose. Experts pushed for the new second-dose policy due to a number of recent chickenpox outbreaks among previously vaccinated schoolchildren.

A 2007 study in the New England Journal of Medicine also found that one dose of the vaccine may not be enough to provide complete immunity. Among 350,000 patients researchers studied over 10 years, 11,356 were reported to have chickenpox. A total of 1,080 of the patients had breakthrough disease, a modified form of chickenpox with a mild rash that can occur in some vaccinated people. According to the study, those most at risk were children ages 8 - 12 years who had been vaccinated at least 5 years before their current chickenpox infection.

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.

• 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.

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 can prevent about half of all shingles cases and two-thirds of postherpetic neuralgia cases. The CDC recommends that all adults age 60 years and older who have intact immune systems should receive this vaccine

Varicella-zoster immune globulin (VariZIG) 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
• Newborn infants whose mothers had signs or symptoms of chickenpox around the time of delivery (5 days before to 2 days after)
• 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)

For these patients, VariZIG should be given within 96 hours of exposure to someone with chickenpox. (Note: VariZIG is a new formulation of an older drug called VZIG, which is no longer being produced.)

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.

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.

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 1 - 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, as aspirin increases the risk for a dangerous condition called Reye 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 2 cups per bath. The oatmeal will not dissolve, and the water will have a scum. A 1/2 - 1 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 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 (PHN). In addition, psychological therapies aimed at coping and reducing the effects of pain may be useful.

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. 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 to treat herpes zoster in 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 needs to be taken only once a day.

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 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 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 - 18 inches from the targeted area, and the face must be covered if the spray is being used near the head.

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.

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. 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.

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.

Antiviral Drugs. Researchers are investigating whether treatment with antiviral drugs may help reduce the pain associated with postherpetic neuralgia. A small 2006 study suggested that a 2-week course of therapy with intravenous acyclovir, followed by 1-month treatment with oral valacyclovir, may help relieve pain.

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.

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. [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.

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

References

American Academy of Pediatrics Committee on Infectious Diseases. Recommended immunization schedules for children and adolescents--United States, 2007. Pediatrics. 2007 Jan;119(1):207-8.

Centers for Disease Control and Prevention (CDC). A new product (VariZIG) for postexposure prophylaxis of varicella available under an investigational new drug application expanded access protocol. MMWR Morb Mortal Wkly Rep. 2006 Mar 3;55(8):209-10.

Centers for Disease Control and Prevention (CDC). Varicella outbreak among vaccinated children--Nebraska, 2004. MMWR Morb Mortal Wkly Rep. 2006 Jul 14;55(27):749-52.

Chaves SS, Gargiullo P, Zhang JX, Civen R, Guris D, Mascola L, et al. Loss of Vaccine-Induced Immunity to Varicella over Time. N Engl J Med. 2007 Mar 15;356(11):1121-9.

Davis MM, Marin M, Cowan AE, Guris D, Clark SJ. Physician attitudes regarding breakthrough varicella disease and a potential second dose of varicella vaccine. Pediatrics. 2007 Feb;119(2):258-64.

Li Q, Ali MA, Cohen JI. Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread. Cell. 2006 Oct 20;127(2):305-16.

Lopez AS, Guris D, Zimmerman L, Gladden L, Moore T, Haselow DT, et al. One dose of varicella vaccine does not prevent school outbreaks: is it time for a second dose? Pediatrics. 2006 Jun;117(6):e1070-7.

Quan D, Hammack BN, Kittelson J, Gilden DH. Improvement of postherpetic neuralgia after treatment with intravenous acyclovir followed by oral valacyclovir. Arch Neurol. 2006 Jul;63(7):940-2.

Review Date:
3/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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