Article: Shingles: Hope Through Research


When the itchy red spots of childhood chickenpox disappear and life returns to normal, the battle with the virus that causes chickenpox seems to be won. But for all too many of us this triumph of the body's immune system over the virus that causes chickenpox is only temporary. The virus has not been destroyed, but lays low, ready to strike again later in life. This second eruption of the chickenpox virus is the disease called shingles.

"I was having exams at college and I got a rash in a band around my waist. I first thought it was chickenpox, but I'd had that years before and instead of itching, this time the spots were very painful," recalls a young woman who had shingles in her twenties.

The young woman's memory was correct. She had had chickenpox as a child. You cannot develop shingles unless you have had an earlier bout of chickenpox, and everyone who has had chickenpox is at risk for shingles. The woman had the typical symptoms of this common neurological disorder: more pain compared to chickenpox but less itching. Her age was unusual, however. While young people do develop shingles, the disease most often strikes in later years.

Scientists call the chickenpox/shingles-causing agent varicella-zoster. Varicella is a Latin word meaning "little pox" to distinguish the virus from smallpox, the highly contagious and often fatal scourge that disfigured or killed millions of people, especially during the Middle Ages. Zoster is the Greek word for "girdle"; shingles often produces a girdle of blisters or lesions around the waist. This striking pattern also gives the disease its common name: the word shingles comes from cingulum, the Latin word for belt or girdle.

What is Shingles?

Scientists believe that in the original battle with the chickenpox virus some of the virus particles leave the skin blisters and move into the nervous system. There the viruses settle down in an inactive (latent) form inside specific nerve cells (neurons) that relay information to the brain about what your body is sensing — whether your skin feels hot or cold, whether you've been touched or feel pain. These lie in clusters (ganglia) adjacent to the spinal cord and brain and are one type of sensory neurons.

When the chickenpox virus reactivates, the virus moves down the long nerve fibers that extend from the sensory cell bodies to the skin. The viruses multiply, the telltale rash erupts, and the person now has herpes zoster, or shingles. With shingles, the nervous system is more deeply involved than it was during the bout with chickenpox, and the symptoms are often more complex and severe.

The virus responsible for shingles and chickenpox belongs to a group of viruses called herpesviruses. This group includes the herpes simplex virus that causes cold sores, fever blisters, mononucleosis, genital herpes — a sexually transmitted disease, and Epstein-Barr virus involved in infectious mononucleosis. Like the shingles-causing virus, many other herpesviruses can take refuge in the nervous system after an individual has suffered an initial infection. These viruses may remain latent for years, then travel down nerve cell fibers to cause a renewed infection.

The varicella-zoster virus looks as though it were designed by a mathematician. It is a microscopic sphere encasing a 20-sided geometric figure called an icosahedron. Inside the icosahedron is the genetic material of the virus, deoxyribonucleic acid (DNA). When activated, the virus reproduces inside the nucleus of an infected cell. It acquires its spherical wrapping as it buds through the nuclear membrane.

Who is at Risk?

About 10 percent of normal adults can be expected to get shingles during their lifetimes, usually after age 50. The incidence increases with age so that shingles is 10 times more likely to occur in adults over 60 than in children under 10. Most people who get shingles develop immunity to the virus and will not get the disease again, however, shingles may recur in some individuals. These cases usually involve people with declining or compromised immune systems, such as those infected with HIV or receiving chemotherapy.

A person who is suffering from a disease that damages the immune system, or who is taking anticancer drugs that suppress the immune system, is a prime candidate for an attack of shingles. Even among healthy individuals, temporary depression of the immune system because of stress, a cold, and even sunburn may be associated with an attack of shingles.

Youngsters whose mothers had chickenpox late in pregnancy — 5 to 21 days before giving birth — are also vulnerable to shingles. Sometimes these children are born with chickenpox or develop a typical case within a few days (see section entitled "Do Women Have Special Risks from Shingles" for more information).

What are the Symptoms of Shingles?

The first sign of shingles is often burning or tingling pain, or sometimes numbness, in or under the skin. The individual may also feel ill with fever, chills, headache, or stomach upset. After several days, a rash of small fluid-filled blisters, reminiscent of chickenpox, appears on reddened skin. The pain associated with shingles can be intense and is often described as "unrelenting." People with lesions on the torso may feel spasms of pain at the gentlest touch or breeze. The blisters are usually limited to a band, called dermatomes, spanning one side of the trunk, around the waistline, or clustered on one side of the face.

The distribution of the shingles spots is a telltale clue to where the chickenpox virus has been hiding since the initial infection. Scientists now know that the shingles lesions correspond to the dermatome supplied by a specific sensory nerve that exits from the brain or spinal cord.

For the majority of healthy individuals, this second bout with the chickenpox virus is almost always a second triumph of the body's immune system. The shingles attack may last longer than chickenpox, and the patient may need medication for pain, but in most cases the body has the inner resources to fight back. The lesions heal, the pain subsides within 3 to 5 weeks, and for most patients the blisters leave no scars.

How is it Treated?

The severity and duration of an attack of shingles can be significantly reduced by immediate treatment with antiviral drugs, which include acyclovir, valacyclovir, or famcyclovir. Antiviral drugs may also help stave off the painful aftereffects of shingles known as postherpetic neuralgia (see section entitled "What are the Complications of Shingles?). Doctors now recommend starting antiviral drugs within 72 hours of the first sign of the shingles rash. Early treatment is believed to reduce the risk of postherpetic neuralgia and may speed up the healing process. Other treatments for post-herpetic neuralgia include steroids, antidepressants, anticonvulsants, and topical agents. Scientists continue to work toward developing newer antiviral agents and more effective pain killers.

Is Shingles Contagious?

As early as 1909 a German scientist suspected that the viruses causing chickenpox and shingles were one and the same. In the 1920's and 1930's the case was strengthened. In an experiment, children were inoculated with fluid from the lesions of patients with shingles. Within 2 weeks about half the children came down with chickenpox. Finally in 1958 detailed analyses of the viruses taken from patients with either chickenpox or shingles confirmed that the viruses were identical.

This study also proved that a person with shingles can pass the virus to individuals who have never had chickenpox, but these individuals will develop chickenpox not shingles. A person with chickenpox cannot communicate shingles to someone else. In order for people to develop shingles they must already harbor the virus in their nervous system, and for those who do harbor the virus, having contact with someone with chickenpox will not trigger shingles. Additionally, a person with shingles cannot communicate shingles to another individual.

What are the Complications?

People with "optical" shingles (where the virus has invaded an ophthalmic nerve) may suffer painful eye inflammations that leave them temporarily blind or impair their vision. Individuals with this type of shingles should see an ophthalmologist immediately. If shingles appears on the face and affects the auditory nerves, it can also lead to complications in hearing. Infections of facial nerves can lead to temporary paralysis.

Postherpetic Neuralgia

Sometimes, particularly in older people, symptoms of shingles persist long after the rash is healed. In these cases, facial paralysis, headache, and persistent pain can be the aftermath. Possibly because the nerve cells conveying pain sensations are hardest hit, or are exquisitely sensitized by the virus attack, pain is the principal persistent complication of shingles. This pain, called postherpetic neuralgia, is among the most devastating known to mankind — the kind of pain that leads to insomnia, weight loss, depression, and that total preoccupation with unrelenting torment that characterizes the chronic pain sufferer.

Although it can be extraordinarily painful, postherpetic neuralgia is not life-threatening. Doctors treating the pain currently employ a variety of medications. Powerful narcotic pain relievers can offer relief but, because they can have serious side effects, doctors often prescribe newer nonaddictive but potent painkillers. Ointments containing capsaicin, the heat-producing ingredient found in hot chili peppers, are effective in relieving pain from postherpetic neuralgia, as well as pain from other disorders such as arthritis. Such ointments are currently available by prescription. Although these creams contain less than 1 percent capsaicin, new research suggests that patients may be able to tolerate creams containing 5 to 10 percent of this active ingredient if used in combination with other pain killers. More research is needed before these higher dose ointments will be available to patients with postherpetic neuralgia (see section entitled "What Research is Being Done?").

In 1999, the Food and Drug Administration approved a new method of treating the pain of postherpetic neuralgia. The product is an adhesive patch containing lidocaine, a commonly used local anesthetic. The patch allows lidocaine to be released into the top layers of the skin, reducing pain from the damaged nerves. Because it delivers the drug via the skin, it does not produce any significant levels of the drug in the blood and, therefore, does not cause serious systemic side effects if used appropriately.

Studies have also shown that some anticonvulsant drugs used to treat epilepsy, such as carbamazepine, are sometimes effective in relieving the pain of postherpetic neuralgia. Antidepressants can help also. In addition to their effects on mood, the antidepressants appear to relieve pain. Some doctors report that patients occasionally benefit from alternative treatments for pain, such as acupuncture and electrical stimulation of nerve endings.

It is important to realize that individuals with postherpetic neuralgia no longer have shingles: their infection is over. Instead, they are suffering from damage to the nervous system. Scientists believe that the virus attack has led to scarring or other lesions affecting the cells in sensory ganglia and associated nerves. Even in such severe cases, however, the paralysis, headaches, and pain generally subside, although it may take time.

Is Shingles Life-Threatening?

Shingles is a serious threat to life in immunosuppressed individuals — for example, those with HIV infection or patients with cancer who are receiving treatments that can weaken their immune systems. These treatments destroy cancerous tissue but unfortunately they also have the potential to damage cells of the immune system that normally fight invading organisms. Patients who receive organ transplants (for kidney disease, for example) are also vulnerable to shingles. To prevent the body from rejecting the foreign tissue of the transplant, these patients are given drugs that suppress the immune system. Should any of these patients contract shingles, there is a possibility that the zoster virus will spread throughout the body, reaching vital organs like the lungs. If unchecked, such disseminated zoster can lead to death from viral pneumonia or secondary bacterial infection.

Do Women Have Special Risks from Shingles?

Many mothers-to-be are concerned about any infection contracted during pregnancy, and rightly so. It is well known that certain viruses can be transmitted across the mother's bloodstream to the fetus, or can be acquired by the baby during the birth process.

Maternal chickenpox poses some risk to the unborn child, depending upon the stage of pregnancy during which the mother contracts the disease. During the first 30 weeks, maternal chickenpox may, in some cases, lead to congenital malformations. Such cases are rare and experts differ in their opinions on how great the risk is.

If the mother gets chickenpox from 21 to 5 days before giving birth, the newborn may have chickenpox at birth or develop it within a few days, as noted earlier. But the time lapse between the start of the mother's illness and the birth of the baby generally allows the mother's immune system to react and produce antibodies to fight the virus. These antibodies can be transmitted to the unborn child and thus help fight the infection. Still, a third of the babies exposed to chickenpox in the 21 to 5 days before birth develop shingles in the first 5 years of life because the virus must also be fought by immune cells.

What if the mother contracts chickenpox at precisely the time of birth? In that case the mother's immune system has not had a chance to mobilize its forces. And although some of the mother's antibodies will be transmitted to the newborn via the placenta, the newborn will have precious little ability to fight off the attack because the immune system is immature. For these babies chickenpox can be fatal. They must be given "zoster immune globulin," a preparation made from the antibody-rich blood of adults who have recently recovered from chickenpox or shingles.

What Research is Being Done?

Because of the nervous system involvement, the chickenpox/shingles virus is of great interest to the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health (NIH) and the principal Federal agency supporting research on the nervous system. The disease is of equal interest to another branch of the NIH — the National Institute of Allergy and Infectious Diseases (NIAID). In addition, the National Cancer Institute (NCI) and the National Institute on Aging (NIA) support research on shingles: NCI's interest in the disorder relates to the high incidence of shingles in patients receiving immunosuppressant treatments for cancer, and NIA conducts studies because of the prevalence and severity of the disease among elderly adults.

Shingles poses two immediate challenges to medical research. The first is to develop drugs to fight the disease and to prevent complications. The second challenge is to understand the disease well enough to prevent it, especially in people known to be at high risk. To protect susceptible patients from a shingles attack scientists need to know much more about the varicella-zoster virus, especially how it remains latent in the body for so long and what induces it to become active again. NIA-supported scientists are studying the biology of the varicella-zoster virus in an effort to gain a better understanding of the molecular basis of viral latency and reactivation.

Although the virus is presumed to hide in the nervous system between bouts of chickenpox and shingles, it has never been recovered from nerve cells at autopsies unless the patient had shingles at the time of death. In contrast, herpes simplex, which causes recurrent infections of cold sores and fever blisters, has been identified in spinal nerve cells during its latent periods.

If the whole varicella-zoster virus does not remain intact in nerve cells, perhaps its core genetic material — the DNA — survives. Scientists suspect that the viral DNA may be inserted into one of the chromosomes of the nerve cell — the larger units that house the cell's own genetic material.

What keeps the varicella-zoster virus quiet during its long latency? Probably the immune system. A healthy immune system protects against all kinds of diseases, but people with depressed immunity are vulnerable to many illnesses, and have a high incidence of shingles. Antibodies, one of the immune system's major defense mechanisms against infection, are not very helpful against shingles. Studies have shown that patients with shingles produce varicella-zoster antibodies but they don't halt the infection. Similarly, injections of antibody-rich blood serum do not prevent the dissemination of shingles in cancer patients or others whose immune systems are depressed. (This is in contrast to the protection conferred by the immunoglobulin given to newborns with chickenpox.)

The components of the immune system that do appear to combat shingles are two types of white blood cells: the T lymphocytes and scavenger cells called macrophages. Scientists are trying to find ways of boosting the activity of these cells — especially in patients at high risk for severe or disseminated shingles (a rare condition in which the virus spreads to other areas of the body, sometimes vital areas such as the blood or the lungs).

Current research is aimed at finding new methods for treating shingles and its complications. In one NINDS-supported study, investigators are studying the effectiveness of a long-acting preparation of morphine (a type of analgesic used to manage pain) as a possible treatment for postherpetic neuralgia. Research from this study could lead to improved treatment for this condition, which complicates many cases of shingles.

Capsaicin ointment (containing less than 1 percent of the active ingredient) is a currently available treatment for the pain of shingles, especially postherpetic neuralgia. In 1998 a group of scientists tested a higher dose capsaicin cream (5 to 10 percent) in a small group of patients suffering from pain caused by a number of different conditions, including diabetes, arthritis, and HIV infection. Seven of ten patients reported a 50 percent reduction in pain after using these higher dose creams. Further studies, using larger groups of patients, will be conducted to establish the safety and effectiveness of this promising treatment, which could bring relief to patients suffering from postherpetic neuralgia.

The development of preventive measures and treatments for shingles has long been hindered by scientists' difficulty in working with the varicella-zoster virus in the laboratory. The virus grows very poorly in laboratory cells and does not infect animals other than man. Recently, however, the Department of Veteran Affairs (VA) launched a nationwide trial — the Shingles Prevention Study — to study an experimental shingles vaccine (see the Information Resources card in the back pocket of this brochure for information on the VA trial). In the study, which is a cooperative Federal government effort involving the VA and NIAID, investigators will test a more potent version of the vaccine currently used to immunize children against chickenpox. The purpose of the trial is to find out if the vaccine is safe and how well it works to prevent shingles. Successful results would represent a big step toward eradicating shingles.

Although shingles will continue to afflict people in the years to come, there is now hope that scientists are close to creating a vaccine capable of preventing this painful condition. In the course of this work on vaccines, scientists expect to uncover important information to use against other diseases, to learn more about the body's immune system, and ultimately to outwit the clever viruses that evade that system.

On Catching Chickenpox . . . but not Catching Shingles

Chickenpox and shingles are caused by the same virus — varicella-zoster. When a person, usually a child, is first exposed to the varicella-zoster virus, he or she develops chickenpox, a highly contagious disease. Most of us catch it during childhood because the virus can be spread through air as well as through contact with the rash. The infection begins in the upper respiratory tract where the virus reproduces over a period of 15 days or more (the incubation period). The virus then spreads to the bloodstream and migrates to the skin, giving rise to the familiar rash.

In contrast, you can't catch shingles. You must already have had a case of chickenpox and harbor the virus in your nervous system to develop shingles. When reactivated — most often because the immune system is weakened, allowing the virus to break out of its dormant state — the virus travels down nerves to the skin causing the painful shingles rash. In shingles, the virus does not normally spread to the bloodstream or lungs, so the virus is not shed in air. Because the shingles rash contains active virus particles however, a person who has never had chickenpox can contract chickenpox by exposure to the shingles rash.

Shingles Prevention Study

The Department of Veterans Affairs (VA) is conducting a nationwide, multicenter trial to study an experimental shingles vaccine. The Shingles Prevention Study represents a scientific collaboration between the VA, the National Institute of Allergy and Infectious Diseases, and Merck & Co., Inc. — the company that produces the vaccine.

The study will test a more potent version of the vaccine currently used to immunize children against the chickenpox virus. The purpose of the trial is to find out if the vaccine is safe and how effective it is in preventing shingles.

In the 5-year, double-blind study, participants will receive either the vaccine or a placebo — neither the doctors nor the study participants will know which injection was given until the end of the study. The study will involve approximately 20 medical centers and 37,000 volunteers across the country.

A successful vaccine could lead to improved quality of life for older individuals. In addition to a possible vaccine, the study will also yield new information on the incidence and natural history of shingles and its complications.

For more information about this study, residents of the Metropolitan Washington, D.C., area should call 1-800-411-1222. Residents of other areas should call 1-877-841-6251.

This pamphlet was written and published by the National Institute of Neurological Disorders and Stroke (NINDS), the United States' leading supporter of research on disorders of the brain and nerves, including shingles. NINDS, one of the U.S. Government's 18 National Institutes of Health in Bethesda, Maryland, is part of the Public Health Service within the U.S. Department of Health and Human Services.


acyclovir - one of a group of antiviral drugs that may reduced the severity and duration of a shingles attack if given soon after the onset of symptoms.

capsaicin - an active ingredient in hot chili peppers that is used in topical ointments to relieve nerve pain. It appears to work by reducing a chemical substance found at nerve endings and involved in transmitting pain signals to the brain.

carbamazapine - a drug that works both as an anticonvulsant and a pain reliever.

chickenpox - an acute contagious disease usually occurring in children and caused by the varicella-zoster virus.

famcyclovir - an antiviral drug. See acyclovir.

herpes zoster - the medical term for shingles; an infection caused by the varicella-zoster virus (one of the herpesviruses).

herpes simplex - the medical term for a common and usually mild viral disease that causes eruptions of the skin or mucous membrane.

herpesviruses - a large family of viruses that cause a number of related conditions including, but not limited to, oral and genital herpes simplex, varicella (chickenpox), and varicella-zoster (shingles).

immunosuppressed - having a weakened immune system.

latent - hidden, dormant, inactive. The virus that causes chickenpox remains hidden in the body after the initial attack of chickenpox is over. When it becomes reactivated, usually many years later, the virus causes shingles.

lidocaine patch - a new method for treating postherpetic neuralgia in which an adhesive patch containing lidocaine is placed on the skin allowing the drug to be released into the top layers of the skin, reducing pain from the damaged nerves.

neuron—the primary functional cell of the brain and nervous system.

postherpetic neuralgia - a condition characterized by unrelenting pain, caused by damage to the nervous system.

valacyclovir - an antiviral drug. See acyclovir.

varicella-zoster - a virus that causes two distinct diseases, chickenpox and shingles. It is a member of the herpesvirus family. Varicella is Latin for "little pox"; zoster is the Greek word for girdle. Medically, zoster is sometimes used as a synonym for shingles.

"Shingles: Hope Through Research", NINDS. Publication date July 2001.

NIH Publication No. 00-307

Source: National Institute of Neurological Disorders and Stroke
Cache Date: December 16, 2004