Shingles, the painful legacy of childhood chickenpox, is suddenly at the forefront of adult preventive medicine, thanks to a vaccine released in 2006 and the aging of the baby boom population.1 Shingles incidence climbs sharply after age 50, and rates are highest among adults ages 80 years and older.2

Shingles, or herpes zoster, occurs when the virus suddenly reactivates, emerging from nerve cells (dorsal-root ganglia) along the spinal cord where it's been latent, often for many decades. Why it reactivates in some people and not in others isn't well understood, although a weakened immune system is a factor. The usual course of the disease starts with pain, itching, or tingling of the skin followed by a rash of blister-like lesions that lasts from seven to 10 days; complete healing can take from two to four weeks. However, difficult cases can last for years and cause permanent damage, such as blindness if shingles lesions enter the eye.

There's nothing new about varicella-zoster virus (VZV), the virus that causes both chickenpox and shingles. Scientists have traced evidence of it to earliest man. For centuries, the illnesses it caused were confused with life-threatening smallpox because of similarities in the skin lesions the two infections produced. Only in the mid-18th century were the VZV-related rashes recognized as different from smallpox lesions.

By the early 20th century, similarities in the shingles and chickenpox lesions suggested that a single virus might be responsible for both illnesses. In an experiment to test that hypothesis, shocking by today's standards, researchers injected children with fluid from shingles blisters. About half of them came down with chickenpox two weeks later.3

Researchers have established that VZV belongs to the herpes family of viruses; that it enters the human body through the respiratory tract; that it hides in latent form in nerve cells; and as mentioned above, that it can reactivate. Still, the virus remains a wily foe, capable of eluding both natural and vaccine-stimulated immune defenses.

ETIOLOGY

Virtually all people in the United States have VZV in their bodies, either from having chickenpox during childhood or from the chickenpox vaccine, which is made from live virus.3 During the initial chickenpox infection, the virus invades a variety of cells, including nerve, lung, liver, and skin cells. In all but nerve cells, the host cells die over the course of the illness, taking the virus with them. The rash that characterizes chickenpox reflects the death throes of the infected skin cells, progressing from tiny itchy red bumps to blisters oozing the debris of dying cells. As the blisters dry up and crust over, itching subsides and the patient recovers.

It's a different story with nerve cells. Instead of killing them, VZV hunkers down in nerve roots on either side of the spinal column, waiting for an opportunity to reactivate. People vulnerable to shingles include those whose immune systems are weakened by age or who take immunosuppressive drugs to combat cancer or organ transplant rejection or who suffer from diseases that erode the immune system, such as AIDS. Once reactivated, the virus travels along the nerve to surface skin cells, erupting as shingles. Unlike chickenpox, which can spread all over the body, the shingles rash affects only the area associated with the nerve in which the virus reactivated. This explains why shingles appears only on one side of the body, whether on the face, torso, or buttocks. It cannot cross the midline into territory served by nerves from the other side of the spinal column.⁸

TREATMENT AND COMPLICATIONS

Shingles is treated with antiviral medication and painkillers. The antiviral medicines commonly used are acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex). The sooner antivirals are started, the quicker the rash subsides. But diagnosis can be tricky if none of the telltale skin blisters appear. In cases of zoster sine herpete, a form of shingles in which people have acute pain but no rash, the absence of blisters can lead to diagnostic workups and, in some cases, erroneous treatment for pain-producing ailments such as kidney stones or angina. It's also possible to have pain for several days before the first blisters appear.

"The pain is definitely the biggest impact of shingles," says Beth F. Hibbs, MPH, RN, a consultant in the Immunization Safety Office of the Centers for Disease Control and Prevention (CDC). "People tend to feel the pain first, but the virus can present in many ways: pain, tingling, nausea-and all of this without the rash. Other people get the rash first, then the pain."

Shingles complications can be dire. One of these is postherpetic neuralgia, a debilitating and difficult-to-treat condition in which pain persists for months or even years after the rash subsides.4 Scientists believe this is due to nerve scarring caused by migration of the reactivated virus that tricks the nerve into sending pain signals to the brain, even though the skin has healed. In patients with severe neuralgia appearing after an outbreak of shingles on the face, for example, the slightest breeze can cause lancing pain, reducing formerly active people to shut-ins. Shingles of the eye, caused when reactivated virus travels up a branch of the trigeminal nerve, can lead to permanent vision damage and other ophthalmic problems.

About one million new cases of shingles occur each year in the United States.2 Age also affects complication rates: in older patients, rates are higher and complications are more severe. A person's lifetime risk of contracting shingles is estimated to be 32%.5

Shingles is not contagious; the illness is caused solely by reactivation of the virus in one's own nerve cells. But people with shingles can spread VZV infection to those who've never been exposed to the virus. In the United States, unvaccinated children (or infants under 12 months of age who are too young to be vaccinated) are most likely to be vulnerable to VZV infection from someone with shingles. But the infection would produce chickenpox, not shingles.

THE SHINGLES VACCINE: ZOSTAVAX

A vaccine to prevent VZV reactivation, Zostavax, has been available since 2006. It's licensed by the Food and Drug Administration for use in people 60 years of age and older who have healthy immune systems.1 Lowering the suggested vaccination age to 50, the age when shingles incidence begins to rise, is under investigation.

The vaccine is made from the same laboratory-produced strain of live VZV virus as the chickenpox vaccine, only it's more potent. Adverse effects are minimal, mostly soreness or itching at the injection site. In one clinical trial, vaccination cut the overall risk of developing shingles roughly in half and reduced the incidence of postherpetic neuralgia by 67%.4 But efficacy varies greatly, especially according to age. In that clinical trial, the vaccine worked best in younger patients, reducing the incidence of shingles by 64% in those 60 to 69 years of age but by significantly less in those 70 to 79 years of age and even less in those 80 years of age and older.1, 4

"This is considered a relatively safe vaccine," says Hibbs. "But it's important to note that not everyone who receives it will be protected. As we age, vaccines become less protective in general because our immune systems don't respond as well."

CDC RECOMMENDS ROUTINE USE

In June 2008 the CDC recommended routine shingles vaccination in all eligible patients, noting that surveys showed Zostavax to be greatly underused.5 An estimated 50.6 million people in the United States are eligible for the vaccine, but the vaccine's manufacturer, Merck, reports that only about four million doses have been distributed. The slow rollout has been attributed to a number of factors, including limited awareness among physicians, nurses, and other clinicians, and minimal public demand.

Vaccine storage and administration are also somewhat complicated. "The vaccine, which is administered subcutaneously, must be stored in the freezer, then reconstituted with a room temperature or refrigerated diluent," explains Hibbs. "Once reconstituted, it must be given within 30 minutes." Detailed information from the CDC on vaccine handling is available at http://www.cdc.gov%2fvaccines%2fvpd-vac%2fshingles%2fdefault.htm.

Also contributing to low rates of vaccination is a nationwide Zostavax shortage that has discouraged providers trying to order supplies for their offices. Merck ran low on VZV bulk, which serves as the base for the manufacture of both the chickenpox and shingles vaccines. Amy Rose, a Merck spokeswoman, said the company opted to give priority to chickenpox vaccine because it's mandatory in schoolchildren.

Finally, cost can be a deterrent. Merck sells the vaccine to health care providers at $161.50 per dose, but physician administration fees and other charges can boost the cost to consumers as high as $300. This is hefty, compared with the price of two common vaccines for older adults, influenza ($11 to $15) and pneumococcus ($24).

Despite the CDC recommendation, not all private insurers cover shingles vaccination. Medicare coverage also varies, depending on the type of plan. Also Zostavax isn't covered under Medicare Part B, as influenza and pneumococcus vaccines are, but under Part D, the so-called prescription drug plan.1 This makes it complicated for both providers and patients, adding steps to receive reimbursement. In 2008 administration costs for Zostavax became eligible for payment under Part D.

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