Publications
APS Bulletin • Volume 10, Number 1, January/February 2000
Patient Advocacy Groups
Myra Glajchen, DSW, Department Editor
VZV: The Virus That Strikes Twice
Richard T. Perkin
Ten years ago, I thought I knew everything I needed to know about shingles. On the one hand, there were the shingles on a roof. On the other hand, there was the bothersome, itchy rash of which older people complained. I never gave either one a second thought until my elderly mother contracted shingles. Because of her plight, I became intent upon seeking any and all information available on this virus, and went on to consult with numerous specialists in this and other areas of medicine. I soon realized that there were no black and white answers where shingles was concerned.
The founding of VZVRF
In the course of my inquiries, I came to know some of the top specialists in the field of varicella-zoster virus (VZV) research. It soon became clear that the VZV field was in desperate need of funding, organization, and attention.
Funding. VZV researchers find it difficult to compete for funding with headliner diseases such as AIDS, heart disease, and cancer.
Organization. Although VZV scientists here and around the world have made important strides in the field, they are not unified in their efforts. A focused endeavor is required to generate more interdisciplinary research, unravel the reasons for the virus’ reemergence, and develop more effective therapeutic and preventive measures for shingles and postherpetic neuralgia (PHN).
Attention. Health professionals and the general public have to know more about shingles and its signs and the urgent need to diagnose and treat the disease early. Antiviral intervention is most effective within 24 to 72 hours of the onset of the rash.
Armed with this information and the knowledge that there was no organization in the world dedicated to VZV research and education, I founded the VZV Research Foundation (VZVRF) in 1991. I did not do it alone. Chief among my mentors was our scientific advisory board chair, Dr. Anne Gershon, professor of pediatrics and director of the division of pediatric infectious diseases at Columbia University in New York. Dr. Gershon is an internationally renowned scientist in the VZV field, best known for her work on the chicken pox vaccine, which the Food and Drug Administration (FDA) approved in 1995.
Dr. Gershon went quickly to work to compile a list of potential scientific advisory board members and organize our first meeting. Meanwhile, I formed a board of directors, established our not-for-profit status, and began the fund-raising process. We decided to call our organization the VZV Research Foundation because (a) we wanted to cover the gamut of VZV disease; not only shingles, but also chicken pox and PHN, and (b) we wanted to be primarily research based.
The foundation’s key objectives remain constant: to foster scientific research on VZV and to educate the public and healthcare professionals about VZV infections.
The three faces of VZV: Varicella, zoster, and PHN
VZV first strikes as chicken pox or varicella, a highly infectious disease that affects more than 90% of Americans by the age of 15 (Straus, 1993), or an estimated 4 million people annually. According to the Centers for Disease Control and Prevention (CDC), this number is steadily declining, due to the availability (since mid-1995) of the varicella vaccine.
Although it is commonly believed that varicella is a harmless illness, in fact, it is a potentially serious infection. Varicella can result in complications ranging from bacterial skin infections to encephalitis and pneumonia, although such complications are rare in otherwise healthy people. The CDC reports that complications from chicken pox result in 10,000 hospitalizations and nearly 100 deaths in the United States each year. Most of the deaths and hospitalizations occur among healthy children and adults, with 55% of the deaths occurring in people over the age of 20 (Centers for Disease Control and Prevention, 1997).
In May 1999, the CDC recommended that all states require chicken pox vaccinations for all children entering day care or elementary school. Beginning this year, chicken pox vaccinations will be required by law in Colorado, Florida, Maryland, Massachusetts, Michigan, Oklahoma, Oregon, Rhode Island, Tennessee, Texas, Virginia, and Washington, DC (Centers for Disease Control and Prevention, 1999).
After a bout of varicella, VZV remains dormant in the sensory ganglia, usually for decades. However, in an estimated one out of seven people over the course of an 85-year lifetime, the virus reemerges, causing zoster or shingles (VZV Research Foundation, 1996). This reactivation is a result of the decline in cellular immunity to VZV (VZV Research Foundation, 1997). The VZVRF estimates that nearly 1 million people are afflicted by shingles each year in the United States alone. It is most common among people over the age of 50, as well as among those who have conditions, or are undergoing medical treatments, that weaken their immune systems. These include HIV infection, chemotherapy or radiation therapy, corticosteroids, and transplant operations. The incidence of zoster is expected to rise dramatically because of sharp increases projected in both the elderly and immunocompromised populations.
Whereas itching is the key symptom of the rash of varicella, pain that can be severe and persistent is the overriding characteristic of zoster. In the prodromal stage, on average 48 to 72 hours before the appearance of a rash, diagnosis can be difficult.
Typical symptoms can include localized numbness; localized tingling, burning, or shooting pain that may be constant or intermittent; localized itching; and fever, headache, chills, and nausea (VZV Research Foundation, 1997).
The eruptive stage is characterized by a painful rash of blistered skin that typically is limited to a band on one side of the body, often localized to the trunk, face, or forehead. Thus the names are zoster, which is Greek for belt, and shingles, which comes from the Latin cingulum, meaning girdle or belt. The skin lesions of zoster resemble those of varicella (the lesions of which progress to vesicles, pustules, and scabs), but, unlike varicella lesions, zoster lesions usually are painful and not disseminated widely (VZV Research Foundation, 1997). When the eye is affected, as was the case with my mother, ophthalmic zoster results. The cornea can become infected, and unilateral blindness can result (Pavan-Langston, 1995).
New lesions may appear for up to 5 days. In immunocompetent patients, healing is usually complete within 2 to 4 weeks. Individuals who are immunocompromised are most susceptible to more prolonged and even repeat bouts of zoster (National Institute of Neurological Disorders and Stroke, 1996).
PHN is the name given to the pain that persists 1 to 3 months or longer after the shingles rash has healed (Nurmikko, 1995). The risk of developing PHN is directly related to the patient’s age when zoster first appears, and patients with ophthalmic zoster may be at increased risk. PHN is one of the most severe and intractable types of chronic pain; it can persist for months or years after the disappearance of zoster blisters (Kost & Straus, 1996).
The pain of PHN may be sharp, piercing, throbbing, or stabbing. It is the result of injury to the peripheral nerves and resultant changes in the signal processing of the central nervous system. The pain may extend beyond the margins of the original zoster eruption (Kost & Straus, 1996). The skin may be unusually sensitive to even the lightest touch (as from clothing), the smallest breeze, and changes in temperature (either hot or cold).
The severity and duration of pain appears to increase with age (VZV Research Foundation, 1997). The devastating effect of PHN on quality of life cannot be underestimated. In fact, PHN sufferers often write to the foundation to relate their ordeal.
A 71-year-old man wrote that the “ice pick pains” of PHN were the most severe pains he had ever endured. “I wanted to float away and leave my burning left leg behind.”
A woman in her seventies noted that 5 years before PHN struck, she had been an “active, happy person.” She added, “Today, I’m a recluse!” She could not stand to touch her side and back, where the nerves had been destroyed, and her activities were restricted. She had tried every method of pain relief her doctor recommended, but nothing relieved her constant discomfort.
An 88-year-old woman stated, “I am almost out of my mind with pain and itch. I can’t sleep at night and my body feels worn out. I would be very happy if God would take me so that I could be out of my misery.”
Shingles cannot be prevented. However, in 1998, a 37,000-subject shingles prevention study was launched to determine whether immunization with live attenuated Oka/Merck varicella-zoster vaccine could significantly reduce the burden of illness caused by shingles in older adults. A secondary goal of the Shingles Prevention Study is to determine whether vaccination will protect against PHN (VZV Research Foundation, 1999).
Antiviral drugs can lessen the duration of shingles and lower the risk for PHN if they are taken within 24 to 72 hours after the rash first appears. PHN is treated (although not always successfully) by a variety of pain-relieving approaches, including nonster- oidal anti-inflammatory drugs, opioids, specific medications for nerve injury-related pain (e.g., antidepressants), and a lidocaine patch recently approved by the FDA.
Leading the fight against VZV infections
Since its inception, the VZVRF has served as an information resource for thousands of VZV sufferers and their families and for the scientific and medical communities. To date, its primary activities have included
- Sponsorship of four international scientific meetings, in addition to scientific symposia and roundtables around the world, and the publication of the proceedings of these meetings in prestigious journals
- Provision of ten 2-year research fellowships totaling more than $1 million to Investigate the reasons for the virus’ reemergence; develop new vaccines to prevent chicken pox and shingles in immunocompromised patients and seek out new treatments for PHN pain.
- Develop educational materials for scientists and physicians, including continuing medical education courses.
- Creation of educational materials and programs for the general public, including brochures; a Web site (www.vzvfoundation.org), a toll-free VZV information line (800/472-VIRUS), a radio public service campaign, and public health forums
- Establishment of the VZVRF Scientific Achievement Award honoring those who have made significant contributions to the study of VZV
Looking forward
It has been 8 years since VZVRF first opened its doors. In that time, there have been many significant advances in the field of VZV, including the development of new antiviral drugs to combat zoster, the approval of the varicella vaccine, the launch of the shingles prevention study, and the growing focus on new PHN pain therapies. Through it all, the VZVRF has worked tirelessly to raise funds for VZV research and to raise awareness of VZV infections. Yet, more remains to be done.
We have to better understand the VZV virus, which presents many challenges, because it is difficult to study. For example, what causes latency, and, for that matter, reactivation? Can we develop a better, safer vaccine for immunocompromised patients? How do we put an end to PHN pain? VZV scientists, including the foundation’s own research fellows, are working on these issues today.
On the educational side of the VZV spectrum, the virus is perceived to be relatively benign and its high and ever-increasing incidence is not common knowledge. In addition, there is intense competition for the ever-shrinking number of government research grants and donations from a citizenry bombarded with fund-raising appeals.
Nevertheless, we believe the future holds much promise. Therefore, with sustained financial support and encouragement from individuals, foundations, and corporations, we will continue the fight against VZV infections in the new millennium.
References
Centers for Disease Control and Prevention (1997). Varicella-related deaths among adults: United States, 1997. Morbidity and Mortality Weekly Report, 46(19), 409-412.
Centers for Disease Control and Prevention
(1999, May 28). Prevention of varicella: Updated recommendations of the advisory committee on immunization practices (ACIP). Morbidity and Mortality Weekly Report, 48(06), 1-5.
Kost, R., & Straus, S. (1996). Postherpetic neuralgia: Pathogenesis, treatment and prevention. New England Journal of Medicine, 335, 32.
National Institute of Neurological Disorders and Stroke (1996). Shingles [Online]. Available: Shingles
Nurmikko, T. (1995). Clinical features and pathophysiologic mechanisms of postherpetic neuralgia. Neurology, 45(12) (Suppl. 8), S54.
Pavan-Langston, D. (1995). Herpes zoster ophthalmicus. Neurology, 45(12) (Suppl. 8), S50-S51.
Straus, S. (1993). Shingles: Sorrows, salves and solutions. Journal of the American Medical Association, 269, 1836.
VZV Research Foundation (1996). The chickenpox vaccine: Answers to parents’ questions. New York: Author.
VZV Research Foundation (1997). It could be shingles: Diagnosing and managing shingles & PHN. New York: Author
VZV Research Foundation (1999). Landmark shingles prevention study underway. VZV Focus, VI, 1.
Note: The VZVRF does not practice medicine and nothing in this article should be considered medical advice. For more information on VZV infections or the work of the VZVRF, please contact VZVRF, 40 East 72nd Street, New York, NY 10021, 212/ 472-3181 (fax 212/861-7033; e-mail rtp@vzvfoundation.org), or visit the VVRF Web site at http://www.vzvfoundation.org/
Richard T. Perkin is chairman and founder of the VZV Research Foundation in New York.