Shingles and Chickenpox (Varicella-Zoster Virus)

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Shingles and Chickenpox (Varicella-Zoster Virus)

WHAT ARE SHINGLES AND CHICKENPOX (VARICELLA-ZOSTER VIRUS)?

Varicella-Zoster Virus

Shingles and chickenpox were once considered separate disorders. It is now known 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 (Chicken Pox). When patients with chickenpox cough or sneeze, they expel tiny droplets that carry the virus, which in this early form is referred to as varicella viru s. 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 blood stream. When it is carried to the skin it produces the typical rash of chickenpox.

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 has properties that allow it to hide from the immune system for years, often for a lifetime. This inactivity is called latency.

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. Those nerves most often affected are those in the face or the trunk. The virus, however, can also spread to the spinal cord and into the blood stream.

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 may increase the risk for shingles.

Other Herpes Viruses

The varicella-zoster virus belongs to a group of herpes viruses that includes seven 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 herpes virus. The human herpes viruses are:

Herpes Simplex virus (the most common).
Varicella-Zoster virus (VZV).
Cytomegalovirus (CMV).
Epstein-Barre virus (causes mononucleosis).
Human Herpesvirus type 6 (causes roseola).
Human Herpesvirus type 7 (HHV-7).

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.

WHO GETS CHICKENPOX AND SHINGLES?

How People Develop Chicken Pox or Shingles

The varicella-zoster virus is responsible for both chicken pox 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 chicken pox. 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 chicken pox. 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 only develop from a reactivation of the varicella-zoster virus in a person who has previously had chicken pox. 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% and 90% of chickenpox cases occur in children under 10 years of age. According to a 2001 study, about 10% of children between ages five and nine and about 2% of 10 to 14 year olds get chicken pox each year. Among 15 to 19 year olds, the rate is 1.2%, which is significantly higher than before vaccinations became common. This rate should begin to fall as vaccinated younger children get older.

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 two days before the appearance of the spots, to the end of the blister stage. This period lasts about five to seven days. Once dry scabs form, and the disease is unlikely to spread.

Most schools allow children with chickenpox back after ten days of 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)

Anyone who has had chicken pox has risk for shingles later in life. Shingles occurs in between 10% and 20% of those who have had chickenpox, but certain people have a higher risk for shingles than others. An estimated 600,000 to 850,000 Americans are afflicted with shingles each year and millions of older adults worldwide are stricken each year. The incidence of herpes zoster is almost 65% higher than it was 40 years ago. The incidence may be slightly higher in women than in men, although this is not clear.

Age. The risk for herpes zoster increases with age. One study estimated that a person who reaches 85 has a 50% chance of having herpes zoster. The risk for postherpetic neuralgia (PHN) is also highest in older people with the infection. In one study, the risk for PHN in zoster-infected adults under 49 was only 3% to 4%, but between 60 and 70 the risk climbed to 30%.

most common in adults, shingles can also develop children. One study reported that only 5% of cases occur in those under age 15. Children with immune deficiencies are at highest risk. In children with no immune problems, those who have chicken pox before they were one year old are at higher risk for shingles. It is still uncommon, however.

Immunosuppression. People whose immune systems are impaired from diseases such as AIDS or childhood cancer have a risk for herpes zoster that is much, much higher than those with healthy immune systems. Herpes zoster in people who are HIV positive may be a sign of full-blown AIDS. The current drugs used for HIV, called protease inhibitors, may also increase the risk for herpes zoster. But drug-associated herpes does not appear to be as severe as it is in AIDS patients.

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

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

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

These drugs can be used in patients who have undergone organ transplantation, but they are also often 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.

WHAT ARE THE SYMPTOMS OF CHICKENPOX AND SHINGLES?

Symptoms of Chickenpox (Varicella)

The time between exposure to the virus and eruption of symptoms (or incubation 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.

The patient generally begins to feel better 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. They have been described as dewdrops on rose petals. 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 four 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 four to seven days, and the entire disease process lasts between seven and 10 days.

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, which are 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 neuralgi a 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, in fact, that physicians often refer to all syndromes with a single term, zoster-associated pain (ZAP).

Prodrome (Pain) .

Pain is the primary early symptom for shingles. It 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, including fever and muscle aches.

The prodrome stage lasts about two 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% and 60% of cases occur on the trunk. The second most common side 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 endangered.

The active infection is typically marked by the following sequence:

A rash appears, which starts 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 seven to ten 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 up to 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. [ See How Serious Are Chickenpox and Shingle? below].

Postherpetic Neuralgia

Postherpetic neuralgia (PHN) is pain that persists for longer than a month after the onset of herpes zoster. [For detailed information, see Postherpetic Neuralgia under How Serious Are Chickenpox and Shingles? below.] PHN occurs in approximately 10% to 20% of shingles patients.

HOW SERIOUS ARE CHICKENPOX AND SHINGLES?

Complications of Chickenpox (Varicella)

Chickenpox rarely causes complications in healthy children, but it is not always harmless. In fact, one study reported that in the UK chicken pox is responsible for more deaths than measles, mumps, whooping cough and Haemophilus influenzae type B meningitis combined. [ See Box High-Risk Candidates for Complications of Chickenpox, Shingles, or Both.]

About 60% of the 14,000 people who are hospitalized for chicken pox each year are children. Five out of every 1000 children who have the infection require hospitalization, and, in rare cases, chicken pox can be fatal. Adults have the greatest risk for dying from chicken pox, however, with infants having the next highest risk. In all, about 40 of the 100 patients who die each year of the disease are children. Vaccinations could prevent nearly all of these very few deaths. However, according to a 2001 study, emergency room visits due to chicken pox have not declined in one medical center, suggesting that the vaccine is still not being widely administered. [ See How Can Chickenpox and Shingles Be Prevented? below.]

Aside from itching, however, the complications described below are very rare, and parents should not be alarmed at all when their children develop this very common and ordinarily mild disorder. Recurrence of chickenpox is possible, but very rare. One episode of chickenpox almost always means life-long immunity against a second attack.

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

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 How is Chickenpox Treated? below.]

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 spot sites where 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.

Bacterial Superinfection. Bacterial superinfection of the skin caused by group A streptococcus is the most common serious complication of chickenpox. 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). One analysis indicated that streptococcus A is increasing and is a greater problem than previously thought, but it is still very rare.

Symptoms include the following:

A persistent or recurrent high fever.
Redness, pain, and swelling in the skin and in the tissue beneath.
Pneumonia. Pneumonia should be 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, have an even higher risk for pneumonia if they have chickenpox. Oxygen and intravenous acyclovir are key components for treating this condition. One study suggested that corticosteroids might also prove useful for treating varicella pneumonia as well. Pneumonia that is caused by varicella can result in lung scarring, which may impair oxygen exchange over the following weeks, or even months.

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. Again, the incidence of this is extremely rare.

Warning Note
One child given the drug desmopressin (DDAVP, Stimate) for bed-wetting developed neurologic problems two weeks after he had chickenpox. The relationship between the two events is unproven, but parents should be aware of the possible association, and avoid giving desmopressin to children who have recently had chickenpox.

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% and 30%.

Reye's Syndrome. Reye's syndrome, a disorder that causes sudden and dangerous liver and brain damage, is a very rare 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.

Chickenpox in Pregnancy. 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 in 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 five days before and two days after delivery, their newborns are at risk for life-threatening varicella.

Chickenpox in Infancy. 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. Nevertheless, children under age one who develop chicken pox are at still higher risk for childhood shingles. All infants should have as little exposure to people with chickenpox as possible.

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. Such cases of inflammation are almost always temporary in otherwise healthy patients.

Complications of Shingles (Herpes Zoster)

Risk for Recurrence of Shingles. Shingles can recur, but the risk is low (about 1% to 5% chance). There is some evidence that a first zoster episode boosts the immune system to ward off another attack. To support this, some elderly people with zoster who are exposed to children with chickenpox appear to have extra protection against a second zoster attack. Note: in people with impaired immune systems, such as those with AIDS, such a booster effect does not occur, and these patients are at particular risk for multiple recurrences of shingles. [ See Box High-Risk Candidates for Complications of Chickenpox, Shingles, or Both.]

Postherpetic Neuralgia and Pain. The pain and discomfort of the active herpes zoster infection can be intolerable for some shingles patients. Postherpetic neuralgia (PHN), pain that persists for longer than a month after the onset of herpes, is the most common severe complication of shingles. In most cases it does not affect daily life. Rarely in severe cases, 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.

The pain usually takes one or more of three forms:

Continuous burning or aching pain.
Periodic piercing pain.
Spasm similar to electric shock.
Intense skin sensitivity (a condition called allodynia) that occurs from very little stimulation, such as a light touch of clothing or a cold wind.

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, and some areas have no feeling at all.

Although some studies have reported a risk of PHN ranging from 10% to 70%, a 2000 study indicated that such studies over-reported this complication. The study suggested that PHN occurs very infrequently, particularly in people under 60. On an encouraging note, in the study once a patient was free of zoster pain, it almost never recurred.

Age. PHN affects about 25% of herpes zoster patients over 60 years old. In addition, the older a person is, the longer PHN is likely to last; only 4% of those under 20 have PHN that lasts more than a year compared to 48% of those over 70. Very few children develop PHN.
Gender. Some studies have suggested that women may be at slightly higher risk for PHN than men, although a 2000 study found no difference.
Having 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.
Immune Factors. People with impaired immune systems do not seem to be at any higher risk for persistent PHN than those with normal immune systems.
The herpes zoster virus infection has various effects that may be responsible for PHN:
The 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.

Although PHN usually resolves spontaneously within a year in most patients, it sometimes persists. To date, treatments have not been very effective, and for these patients, the persistent pain and abnormal sensations can be profoundly frustrating and depressing.

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. It should be noted that other viruses (eg, C. jejuni, cytomegalovirus, and Epstein-Barr) are reported to have a stronger association to this syndrome than herpes zoster does. One study, in fact, found no higher incidence of herpes zoster virus in Guillain-Barre patients than in the general population.

Effects on Face and Ears.

Ramsay Hunt syndrome. Ramsay Hunt syndrome occurs when herpes zoster involves facial paralysis and rash on the ear (called herpes zoster oticus ) or mouth. It may cause the severe ear pain and hearing loss, ringing in the ear, loss of taste, nausea, vomiting, and dizziness. It 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.
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 and some patients may not fully recover.

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.

Effects in the Urinary Tract. In rare situations, herpes zoster can infect the urinary tract and cause urinary retention. The condition is treatable.

Infection 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. Herpes zoster can also cause a devastating infection in the retina called imminent acute retinal necrosis syndrome . Prompt treatment with acyclovir can halt its progress. Acyclovir or valacyclovir, a similar agent, may prevent other eye complications, such as conjunctivitis (pink-eye), inflammation of the cornea, and pain. [ See Antiviral Drugs under How Is Shingles Treated? below.]

Disseminated Herpes Zoster. As with disseminated chickenpox, disseminated herpes zoster, which spreads to other organs, can be serious to life-threatening. It may occur in 5% to 25% of immunocompromised patients, and is fatal in 6% to 17% of cases. 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.

Complications of Shingles in Children. Children with impaired immune systems are at high risk for complications from shingles, including widespread rash, facial paralysis (Bells palsy), and meningitis. Although, in general, shingles in children without immune problems tend to be mild, one study suggested complications might be more common in this group than formerly thought. [ See Box High-Risk Candidates for Complications of Chickenpox, Shingles, or Both.]

High-Risk Candidates for Complications of Chickenpox, Shingles, or Both

Older people. The older the patient the higher the risk for complications from either chicken pox or shingles. Adults who smoke are at higher risk for pneumonia from chicken pox. In England, where chicken pox vaccinations have not been recommended, adults account for 81% of all deaths from chicken pox.
Children. In children, boys have a higher risk for a severe case of chicken pox than girls. 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.
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.
Pregnant women. Chickenpox is harmful for the pregnant woman and her infant, but shingles does not appear to pose a risk for birth defects or infection in the infant. [For more details see Chickenpox in Pregnancy, below.]
Newborns and Infants. Chickenpox can be life threatening in the newborn and pose some risks for infants.

WHAT TESTS ARE USED TO DETECT CHICKENPOX AND SHINGLES?

Both chickenpox (varicella) and shingles (zoster) can usually be diagnosed using symptoms alone. If a diagnosis is still unclear after a physical examination, then 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. Because the early prodrome stage of shingles can cause severe pain on one side of the lower back, chest, or abdomen before the rash appears, herpes zoster may be mistaken for disorders that cause acute pain in internal organs, such as gallstones.

In the active rash stage, shingles may be confused with herpes simplex, particularly in young adults and 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.

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 one and 14 days to detect the virus in the preparation made from the specimen. A culture is usually performed to distinguish between varicella zoster and herpes simplex viruses. 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.

Immunofluorescence

Immunofluorescence is a diagnostic technique used to identify antibodies to a specific disease. 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.

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.

HOW IS CHICKENPOX TREATED?

Home Treatments

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 physician. A child should never be given aspirin or medications containing aspirin, which increase the risk for a dangerous condition called Reye's syndrome. [ See How Serious Are Chickenpox and Shingles? above.]

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 power. 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 it also helps 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

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 chicken pox. 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. [For a more detailed description of acyclovir and similar drugs, see Nucleoside Analogues under How is Shingles Treated? below.]

WHAT ARE THE GENERAL GUIDELINES FOR TREATING SHINGLES?

Therapies have been developed to reduce the effects of the virus, although there is no cure for the disorder.

Treating an Acute Shingles Attack

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

Reduce pain.
Reduce discomfort.
Hasten healing of blisters.
Prevent the disease from spreading (disseminating).

Antiviral agents (acyclovir and others) are sometimes given to older patients and those with severe symptoms, but they must be administered with 72 hours to be effective.

Treating Facial Paralysis (Ramsay Hunt Syndrome or Bell's Palsy)

In Ramsay Hunt syndrome and Bell's palsy, herpes zoster affects the face. Although evidence is weak on treating facial involvement of herpes zoster, some experts recommend oral prednisone (a corticosteroid) and an antiviral agent within seven 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.

Preventing Postherpetic Neuralgia

For prevention of postherpetic neuralgia (PHN) in patients with existing herpes zoster, particularly those over age 55, some experts suggest the following approaches:

Aggressive early treatment of herpes zoster with antiviral medication (such as acyclovir) and analgesics (such as lidocaine). There is no evidence, however, that antiviral treatment entirely prevents PHN. Also, in response to a 2000 study reporting that PHN occurred very rarely in young adults, some experts believe antiviral agents are not warranted in people under age 60. Others believe they are justified in patients over 50 years old with mild symptoms and anyone with severe herpes zoster.
Vaccination against the varicella zoster virus in patents between the ages of 55 and 65.

Treatment Guidelines for Postherpetic Neuralgia

Postherpetic neuralgia is difficult to treat. Once PHN develops, a multidisciplinary approach that involves a pain specialist, psychiatrist, primary care physician, and other health-care providers may provide the best means to relieve the pain and distress associated with this condition. At this time, some experts recommend the following treatment steps:

First, lidocaine skin patch. Effective in many people without producing any known severe side effects.

If that fails:

Low-dose tricyclic antidepressant, typically nortriptyline (Pamelor, Aventyl).

If that fails:

Gabapentin (an antiseizure agent). Starting with a low dose and increasing it until relief or severe side effects occur.

If that fails:

Opioids (potent pain killers).

Unfortunately, these treatments often fail to provide complete pain relief. Other therapies are needed. Of promise are treatments using injections of a combination of a corticosteroid (methylprednisolone) given with lidocaine, an anesthetic.

WHAT ARE THE OVER-THE-COUNTER REMEDIES FOR TREATING SHINGLES?

Applied Cold

Cold compresses soaked in Burrow's solution and cool baths may help relieve the blisters. It is important not to break blisters, which 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, including the following:

Children should take acetaminophen.
Adults may take aspirin or other nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil). Such remedies, however, are not very effective for postherpetic neuralgia.
Capsaicin (Zostrix) is an ointment prepared from the active ingredient in hot chili peppers. Although it is approved for postherpetic neuralgia, its benefits are limited. In one study, it reduced pain by 21% compared to 6% in those who were given a placebo. This substance should not be used until the blisters have completely dried out and are falling off the skin. Capsaicin 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 six weeks for the patient to experience its full effect, however, and about a third cannot tolerate the burning sensation. Many find no benefit.

Psychologic Methods

Stress Reduction Techniques. A panel of experts concluded that a number of relaxation and stress-reduction techniques were helpful in 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 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 only one negative and, to a degree, a manageable experience among many positive ones. Cognitive therapy may be expensive and is often not covered by insurance. The skill of the therapist is also very important to its success.

Alternative Treatments

Many people with chronic pain, such as those with PHN, turn to alternative treatments for relief. It should be noted that few have been rigorously tested and some can be harmful [see Warning Box.] Among those tried for PHN include the following:

Hypnosis. There are some reports that hypnosis may be useful for alleviating pain.
Topical use of diluted apple cider vinegar. (No proof that this is effective at all.)
Acupuncture. Although acupuncture is becoming increasingly popular for a number of painful conditions, one study reported that it offered no benefits for postherpetic neuralgia.
Colostrum, a pre-milk fluid produced by mammals. This fluid contains transfer factor, a substance that carries immune factors and which is being studied for viral disease [ see Antiviral Drugs below ].
Pantothenic acid (Vitamin B5). (No proof of effectiveness.)

Warnings on Alternative and So-Called Natural Remedies

It should be strongly noted that alternative or natural remedies are not regulated and their quality is not publicly controlled. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. In addition, some so-called natural remedies were found to contain standard prescription medication. Most problems reported occur in herbal remedies imported from Asia. Even if studies report positive benefits, most, to date, are very small. In addition, the substances used in such studies are, in most cases, not what are being marketed to the public.

The following website is building a database of natural remedy brands that it tests and rates. Not all are available yet. http://www.ConsumerLab.com/

The Food and Drug Administration has a program called MEDWATCH for people to report adverse reactions to untested substances, such as herbal remedies and vitamins (call 800-332-1088).

WHAT ARE THE MEDICATIONS USED FOR SHINGLES AND POSTHERPETIC NEURALGIA?

The primary goal in the treatment of shingles is the reduction of pain. Antiviral agents are used for shingles attacks. A number of other medications are available for treating postherpetic neuralgia. In addition psychologic therapies aimed at coping and reducing the effects of pain may be useful.

Antiviral Drugs

The best class of drugs developed against varicella-zoster are those known as nucleoside, or guanosine, analogues, which are able to block viral reproduction. Because herpes zoster tends to resolve fairly quickly in young adults, these drugs are generally used in severe cases of patients who are susceptible to complications. These include elderly people and those whose eyes are endangered by the infection. It is not clear if any of the antiviral agents have any effect in preventing PHN, although a major analysis suggests that they might if given early enough.

Approved Anti-Viral Agents. Acyclovir (Zovirax), famciclovir (Famvir), and valaciclovir (Valtrex) are approved for shingles. Acyclovir is the oldest most studied of these drugs. It is available orally or intravenously. (Intravenous administration is usually limited to patients who are immunosuppressed, such as those with AIDS.) Famciclovir (Famvir) and valaciclovir (Valtrex) are both metabolized by the body into acyclovir. They have the advantage of requiring fewer daily doses (typically three) than the five doses needed with acyclovir.

Each of these drugs is usually taken for seven days. If taken within 72 hours of the onset of infection, they can significantly reduce symptoms, although none can actually destroy the virus and cure the disease. Most of these drugs appear to have little or no harmful effect on healthy cells and can penetrate most body tissues, including cerebrospinal fluid. Possible side effects and complications of all nucleoside analogues include:

Rash.
Headache.
Fatigue.
Tremor.
Nausea and vomiting.
Seizures (very rarely).
Complications of intravenous administration, which is used for AIDS and other immunocompromised patients, include an increased risk for kidney damage and blood clots at the injection site.

As with antibiotics, physicians are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS).

Brivudin. Brivudin (Helpin) is another anti-viral agent of note that only needs to be taken once a day and is proving to be very effective. It is not yet available in the US. Two large 2001 studies reported that it had similar side effects and was as effective as famciclovir and more effective than acyclovir. It is also only needs to be taken once a day, which improves compliance.

Other Nucleoside Analogues. Other drugs under investigation include trifluridine, fialuridine, netivudine, and lobucavir. Further research is needed to compare the effectiveness of these medications.

Foscarnet. Foscarnet (Foscavir) is a powerful antiviral agent known as a pyrophophate 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.

Tricyclic Antidepressants and Postherpetic Neuralgia

Tricyclic antidepressants help relieve several symptoms that affect herpes zoster sufferers with postherpetic neuralgia, including depression and pain. Tricyclic antidepressants are currently the standard treatments for PHN, and relieve pain in up to two-thirds of patients.

Nortriptyline (Pamelor, Aventyl) is the preferred tricyclic for herpes zoster. Amitriptyline (Elavil, Endep) and desipramine (Norpramin) are other standard agents. Desipramine and nortriptyline have fewer side effects than amitriptyline, however, and are preferred for older patients. Other tricyclics being investigated for PRN include maprotiline, doxepin (Sinequan), imipramine (Tofranil), and amoxapine (Asendin).

It may take several weeks for the drugs to become fully effective, however, and they can have significant side effects. Side effects include:

Dry mouth.
Blurred vision.
Constipation.
Dizziness.
Difficulty in urinating.
Disturbances in heart rhythm.
An abrupt drop in blood pressure when standing up.

Elderly people are at higher risk for side effects of the tricyclics and so these agents should be used with caution in this group.

Topical Substances for Postherpetic Neuralgia

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

Anesthetic Patches. A patch that contains the anesthetic lidocaine (Lidoderm) is approved specifically for postherpetic neuralgia (PHN). In one 1999 study the lidocaine patch brought significant relief for PHN compared to a "dummy" patch. And no serious effects are associated with the lidocaine patch. One to three patches can be applied for 12 hours a day. Another patch (EMLA) containing lidocaine also includes prilocaine,, a second anesthetic. These patches are expensive. The most common side effects are skin redness or rash.

Topical Aspirin. Topical combinations of aspirin (chemically known as acetylsalicylic acid, or ASA) dissolved in ether may bring relief. It may even have antiviral properties. There is some concern about this preparation because it is flammable.

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.

Injected and Intravenous Treatments to Block Nerves.

Injected agents that block the nerves causing pain are being investigated. Although studies suggest they may be useful, their use is still controversial.

Epidural Blocks. Epidural blocks are injections of local anesthetics or steroids outside the tough membrane surrounding the spinal cord (the dura matter ). The injected substances block the nerves and offer relief from acute herpes zoster pain for some people. Some studies, but not all, have indicated that if they are administered early enough (within two months), they may prevent nerve damage that leads to postherpetic neuralgia. Combinations of anesthetics with steroids in the epidural blockade may be particularly beneficial.

Intrathecal Corticosteroid Injections. Steroid injections administered within the dura mater (called intrathecal) may relieve persistent PHN. According to a 2000 study, they are particularly beneficial in combination with the anesthetic lidocaine. In the study, more than 90% of PHN patients reported good to excellent pain relief for up to two years. Extreme sensitivity to touch (allodynia) was reduced by more than 70%. There were no severe adverse effects. And another study suggested that an epidural block using an anesthetic combined with an antiviral agent (acyclovir) might also be effective. These procedures are very invasive, however,. and pose a risk for complications.

Anti-Epileptic Drugs

Anti-epileptic drugs help PHN patients who have episodes of searing or tearing pain. Gabapentin (Neurontin). Gabapentin is the most effective to date. Unlike older anti-seizure medications, they may even reduce persistent pain as well as improve sleep, mood, and quality of life. Studies are reporting significant relief in patients with PHN, including, according to one survey, relief from throbbing, shooting, cramping, and burning pain. Some experts now recommend gabapentin as a first-line drug against PHN. Others used for PHN include carbamazepine (Tegretol), valproic acid (Depakene, Depakote), and phenytoin (Dilantin), although they are not as beneficial as gabapentin.

Side effects include skin rashes, increased risk for infection, headache, sleepiness, 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 the tricyclics for this group.

Opioids

Powerful pain-killing opioid drugs may be needed in patients with severe pain that does not respond to tricyclic antidepressants. Oxycodone is most often tried first. Methadone (Dolophine) may also be helpful. Although there is some concern that drug dependency may develop, studies indicate that if these narcotics are carefully monitored, they remain effective and the risk for addiction is very low. Side effects include nausea, sleepiness, and constipation.

Oral Corticosteroids

Oral corticosteroids, including prednisolone or prednisone, are powerful anti-inflammatory medications, and experts believed they would reduce the nerve inflammation that causes zoster pain. They have some benefit for reducing pain in acute attacks, and may be helpful for improving symptoms of Bell's palsy and Ramsay Hunt syndrome. They do not appear prevent a further attack or reduce the risk for PHN. Side effects of corticosteroids can be severe and oral steroids should be taken 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.) [ See Injected and Intravenous Treatments, above.]

Mexiletine

Mexiletine (Mexitil) is an agent that dampens the peripheral nerves (those that connect the nerves in the skin, muscles, and organs to the central nervous system.). It is normally used for heart rhythm disorders but is being used in some cases for PHN.

WHAT ARE NON-DRUG TREATMENTS FOR SHINGLES?

Transcutaneous Electrical Nerve Stimulation

Transcutaneous electrical nerve stimulation (TENS) uses low-level electrical pulses to suppress pain in specific areas. The standard approach is to give 80 to 100 pulses per second for 45 minutes three times a day. Patients are barely aware of the sensation. In small studies, this technique provided partial to complete relief for some PHN patients.

Iontophoresis. Iontophoresis is an interesting method that applies ions of medication through the skin using a direct electrical current. One study reported that patients who were given iontophoresis using ions of lidocaine, and a corticosteroid, reported no increase or reduction in pain over a four-year period. Although about 40% still need some treatment, over 90% of the patients were able to take care of themselves.

Surgical Techniques

Certain surgical techniques in the brain or spinal cord have been used to block pain centers contributing to 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.

Laser Therapy

A small study suggests that repeated irradiation with a low-power laser is effective and safe for the relief of pain in postherpetic neuralgia.

WHAT IS THE VACCINATION USED FOR CHICKENPOX AND SHINGLES?

A live-virus vaccine (Varivax) produces persistent immunity against chicken pox. Data show that the vaccine can prevent chicken pox or reduce the severity of the illness even if it is used within three days, and possibly up to five days, after exposure to the infection. The vaccine is protective in about 85% of cases, and even if a vaccinated person becomes infected, the disease is almost always mild. In spite of some concerns, studies are also finding that protection is long lasting.

Recommendations for the Vaccine in Children

Recommendations for the Vaccine in Children. The vaccine is now recommended for all children between the ages of 18 months and adolescence who have not yet had chicken pox. Immunization rates are now between 50% and 70%. Some physicians are reluctant to vaccinate children because it is not yet known how long the effects last and if they contract the infection as adults, the consequences are much more severe. In one 2001 study on day care centers, about 60% of the children had been vaccinated. Interestingly, the incidence of chickenpox was much lower than normal in the unvaccinated group. Although good news in the short term, these children then are neither immunized by the vaccination or by chickenpox itself, suggesting that they may be at risk for a more severe case as they get older. The vaccine is now recommended for all children between the ages of 18 months and adolescence who have not yet had chicken pox. (In spite of these recommendations, the vaccine is still not being as widely administered as other vaccinations.)

Recommendations for the Vaccine in Adults

Some experts suggest that every healthy adult without a known history of chicken pox be vaccinated. In general, however, the following adults should consider vaccinations:

Older people without a history of chicken pox and who are at high risk of exposure or serious complications.
People who live or work in environments in which viral transmission is likely.
Nonpregnant women of childbearing age.
Adolescents and adults living in households with children.
International travelers.
As with other live-virus vaccines, the chicken pox vaccine is not recommended for the following:
Pregnant women.
People whose immune systems are compromised by disease or drugs. The vaccine is being studied, however, for its safety in some of these patients, particularly children with cancer or other high-risk conditions. Experts report that it is safe in children with acute lymphoblastic leukemia (ALL), who should receive two doses. Certain children who are HIV positive may be candidates for the vaccine.

At present, most patients who cannot be vaccinated but are exposed to chicken pox are given immune globulin antibodies against varicella virus. This helps prevent complications of the disease if they become infected. [See Varicella-Zoster Immune Globulin below.]

Side Effects of the Varicella (Chicken Pox) Vaccine

Discomfort at the Injection Site. About 20% of vaccine recipients have pain, swelling, or redness at the injection site.
Risk of Transmission. The vaccine may also produce a mild rash within about a month of the vaccination, which has been known to transmit chicken pox to others. Individuals who have recently been vaccinated should avoid close contact with anyone who might be susceptible to severe complications from chicken pox until the risk for a rash has passed.
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 have fewer complications than naturally acquired chicken pox.
Severe Side Effects. Between 1995 and 1998 there were about 6,580 adverse effects out of 9.7 million doses. Of those, 263 cases (one in 33,000 doses) were serious. Such events included seizures, pneumonia, anaphylactic reaction, encephalitis, Stevens-Johnsons syndrome, neuropathy, herpes zoster, and blood abnormalities. There were 14 deaths reported, although many of these were clearly not related to the vaccination. Any risk for serious effects appears to be higher if the vaccination is given at the same time as the MMR vaccination (for measles, mumps, and rubella). National experts have called for a halt to simultaneous administration of these vaccinations.

Need for Booster

Some physicians are concerned that because the initial vaccination series wears off, children who do not have a booster shot later on will be at risk for catching chickenpox in adulthood when it is more severe. They are also worried about unvaccinated adults contracting chickenpox from vaccinated children. But experience with other childhood live-virus vaccines indicates that there will be an overall reduction in incidence of chickenpox both in children and adults. The vaccine is completely protective in between 70% and 95% cases, and even if a vaccinated person becomes infected, the disease is mild 95% of the time. Studies are also finding that protection is long lasting. [For more information, see Report #90, Immunizations.]

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 four 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 chicken pox.

WHERE ELSE CAN HELP BE FOUND FOR SHINGLES?

Centers for Disease Control and Prevention, 1600 Clifton Road, NE, Atlanta, GA 30333 Call (404) 639-2709 or (800) 311-3435 or on the Internet (http://www.cdc.gov/)

VZV Research Foundation, 40 East 72 #4B., New York, NY 10021 Call (212) 472-3181 or on the Internet (http://www.vzvfoundation.org)

American Chronic Pain Association, P.O. Box 850, Rocklin, CA 95677 Call (916) 632-0922 or on the Internet (http://www.theacpa.org)

National Chronic Pain Outreach Association, 7979 Old Georgetown Road, Suite 100, Bethesda, MD 20814-2429, Call (301) 652-4948, or on the Internet (http://neurosurgery.mgh.harvard.edu/ncpainoa.htm)

Neuropathy Association, 60 E 42 Street, Suite 942, New York, NY 10165. Call (212-692-0662) or on the Internet (http://www.neuropathy.org)

American Pain Society, 4700 W. Lake Avenue, Glenview, IL 60025 Call (847) 375-4715 or on the Internet (http://www.ampainsoc.org)

International Association for the Study of Pain, 909 NE 43rd St., Suite 306, Seattle, WA 98105-6020 Call (206) 547-6409 or on the Internet (http://dasnet02.dokkyomed.ac.jp/IASPM/IASP.html)

National Institute of Neurological Disorders and Stroke, Office of Communications and Public Liaison, P.O. Box 5801, Bethesda, MD 20824. On the Internet (http://www.ninds.nih.gov)

Immunization Action Coalition, 1573 Selby Avenue, Ste. 234, St. Paul MN 55104 Call (612) 647-9009 or on the Internet (http://www.immunize.org)

American Academy of Neurology, 1080 Montreal Avenue, St. Paul, Minnesota 55116 Call (651) 695-1940 or on the Internet (http://www.aan.com)

On the Internet:

International Herpes Management Forum (http://www.ihmf.org/)

Australian Herpes Management Forum (http://herpes.on.net)