Shingles is an infection of the central nervous system, in particular, the dorsal root ganglia of the spine, which migrates through sensory nerves to the skin. There it manifests (usually on the upper trunk) as painful, bumpy, fluid-filled eruptions or vesicles. Shingles may also cause nerve pain (neuralgia). The affected areas of skin are those supplied by sensory nerves radiating from the infected dorsal root ganglia. Sensory nerves from these ganglia serve non-overlapping, sharply bounded strips or areas of the skin called dermatomes. Because the left and right sides of the body are divided into separate sets of dermatomes, shingles lesions do not cross the midline of the body.
The virus that causes shingles is usually contracted in childhood. It is the same virus that causes chicken pox, which is primarily a disease of childhood because it is highly contagious; that is, few individuals live to adulthood without contracting chicken pox. (This statement applies to the temperate zones of the world. For unknown reasons, chicken pox and shingles are less prevalent in tropical regions.) The virus that causes both chicken pox and shingles can, however, be contracted by an individual for the first time in adulthood. First infection, at whatever age it occurs, is called primary infection. Primary infection does not cause shingles; shingles arises from reactivation of virus introduced to the body by an earlier, primary infection.
Shingles arises in individuals who have already had chicken pox, and especially in people with weakened immune systems, such as the elderly or people receiving chemotherapy or bone marrow transplantation. Persons with AIDS are also vulnerable to shingles. Shingles incidence increases steadily with age. Among 10–19 year olds, the rate per 1,000 persons per year is only 1.38. In the 30–49 age range, it rises to 2.29 cases of shingles per 1,000 persons per year. By age 60–79, almost seven cases occur per 1,000 people per year, and this increases to 10 in the 80–89 age group.
Causes and symptoms
Shingles is caused by the varicella-zoster virus (VZV), also known as HHV-3. VZV is genetically similar to the herpes simplex viruses, the type of viruses that
Following primary infection, VZV remains as a symptomless infection in the dorsal root ganglia of the spinal cord. It may or may not become active again, that is, begin reproducing, later in life. Reactivation occurs more often in older people, probably as a result of decreased immune response with age. Reactivation may be symptomless, but usually causes shingles. Repeat episodes of shingles are rare (occurring in less than 4% of patients) because the immune system's response to VZV is boosted by a first shingles episode.
Chills, fever, malaise, gastrointestinal problems, and pain in the affected skin areas may precede appearance of skin eruptions by several days. Viral particles travel away from the spinal cord along the sensory nerves toward the skin, causing inflammation of those nerves, which may be painful. On the fourth or fifth day, skin vesicles begin to appear. The affected area is usually hypersensitive, and disabling pain (described as sharp, stabbing, or burning) may occur in the affected area. About the fifth day after appearing, the vesicles begin to crust or scab and the disease resolves within the next two weeks. There may be no visible aftereffects, although slight scarring from the vesicles may occur.
Especially in elderly patients, pain may persist for months or years after shingles has otherwise resolved. This pain, postherpetic neuralgia, is caused by damage to the dorsal root ganglia that renders them either spontaneously active (perceived as chronic pain) or hypersensitive to slight stimuli such as light touch.
VZV can become active in the cranial nerves as well as in the spinal ganglia. Involvement of branches of the trigeminal nerve (fifth cranial nerve) is most common. When the ophthalmic branch of the trigeminal nerve is involved, this condition is called herpes zoster ophthalmicus. It can cause swelling of the eyelid, pain, and other complications involving the eye. Herpes zoster ophthalmicus can also lead to weakness or partial paralysis (hemiparesis) on the opposite side of the body from the nerve affected, possibly by inducing irritation of the blood vessels in the brain. Infection of cranial nerves by reactivated VZV can also affect the hearing. When this occurs, it is usually associated with facial palsy and is known as Ramsay-Hunt syndrome.
Large amounts of free virus (i.e., virus not held inside cells) is present in the fluid-filled vesicles or bumps that erupt on the skin during shingles. Thus, people who are not resistant to VZV are easily infected by contact with persons having an outbreak of shingles. A particular strain of VZV can remain latent for decades and then reappear as a new epidemic.
Diagnosis is based on history and symptoms. The person must have initially had chicken pox in order to have shingles. Definite diagnosis is difficult before eruption of the characteristic vesicles or bumps on the skin. Often persons with early shingles mistake the reddened, painful area as an accidental burn. Once vesicles appear, however, they are hard to mistake because of their dermatome-bounded distribution on the body. In children, shingles (VZV reactivation) must be differentiated from chicken pox (primary VZV infection). This is normally not difficult, as chicken pox vesicles occur widespread on the body and shingles lesions are usually limited to one area on the person's midsection. Herpes simplex virus can also produce vesicle eruptions similar to those of shingles. If there is doubt about which virus is present, virus from the patient can be cultured.
Treatment for shingles is primarily with antiviral drugs, traditionally acyclovir but, more recently, famcyclovir and valacyclovir. Additionally, a live attenuated-virus vaccine for chicken pox has been licensed since
The pain associated with shingles, and with the postherpetic neuralgia that may linger (especially in older patients, after the condition has otherwise resolved), is best treated using combination therapy based on antivirals, antidepressants, corticosteroids, opioids (morphine), and topical agents (applied directly to the skin). The inexpensive amino acid lysine has also been reported to ease the symptoms of both herpes simplex infections and shingles.
Recovery and rehabilitation
As of mid 2004, several clinical trials related to shingles are recruiting patients. One is sponsored by the National Center for Research Resources, University of Texas, and titled "Randomized Study of Two Doses of Oral Valacyclovir in Immunocompromised Patients with Uncomplicated Herpes Zoster." The study seeks to investigate the efficacy of higher-than-standard doses of valacyclovir by assessing quality of life, pain level, and utilization of medical resources of patients treated with a higher-than-standard dose of valacylovir as compared to a control group treated with the standard dose. Contact information is University of Texas Medical Branch, Galveston, Texas, 77555-0209; Stephen K. Tyring is the recruiter, telephone: (281) 333-2288.
Another trial recruiting patients as of 2004 is sponsored by the Baylor College of Medicine, Texas Children's Hospital, and titled "Valacyclovir in Immunocompromised Children." The study seeks to learn how the body handles valacyclovir, its efficacy in treating immunocompromised children with shingles, and the side effects of such treatment. The recruiting inquiries in Pennsylvania is Children's Hospital of Philadelphia, Pennsylvania, 19104; Donna Sylvester, RN, phone: (215) 590-3284. The recruiting inquiries in Texas is Texas Children's Hospital, Houston, Texas, 77030; Susan Blaney, MD, phone: (832) 822-4215, e-mail: firstname.lastname@example.org, or Lisa R Bomgaars, MD, phone: (832) 824-4688, e-mail: email@example.com.
A third study ongoing in 2004 is sponsored by the drug maker NeurogesX and titled "Controlled Study of NGX-4010 for the Treatment of Postherpetic Neuralgia." NGX-4010 consists of a capsaicin dermal (skin) patch. Capsaicin is the active substance in chili peppers, and is used, paradoxically, both as an irritant and for pain relief. The purpose of this clinical trial is to evaluate the efficacy of a capsaicin patch for relief of postherpetic neuralgia. Contact information varies by state but can viewed at the National Institutes of Health Web site at <http://www.clinicaltrials.gov/ct/show/NCT00068081?order=3>.
Generally, the prognosis for persons with shingles is good. Shingles is almost never a life-threatening disease in otherwise healthy patients, and usually resolves without treatment in a few weeks. However, postherpetic neuralgia, which occurs more often in elderly patients, can be disabling and difficult to treat.
Persons who have an impaired immune system, such as those deficient in cytotoxic T lymphocytes, persons undergoing immune suppression (e.g., for organ transplant), and persons who have AIDS or leukemia may suffer more serious effects from shingles, as the reactivated virus sometimes disseminates from the dorsal root ganglia to other parts of the body. In these cases, complications can resemble those for primary infection of adults with VZV, namely, viral pneumonia, male sterility, acute liver failure, and (in pregnant women) birth defects.
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Larry Gilman, PhD