Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: MONDAY, January 18, 1993 TAG: 9301180043
SECTION: VIRGINIA PAGE: A3 EDITION: METRO
SOURCE: CAROLYN CLICK STAFF WRITER
DATELINE: LENGTH: Long
STUDY AIMS TO EASE SHINGLES' PAIN
MEN AND WOMEN have been plagued by painful shingles since ancient times. But researchers are just now testing drugs they believe can alleviate the misery of this viral disease. Now, they need volunteers to help.James has survived two wars, two open-heart surgeries and persistent arthritis in his right shoulder.
But nothing quite prepared the retired Marine for the pain that seared his left shoulder after a day of deer hunting in mid-November.
By the next morning, the pain had traveled around the veteran's side and into his breastbone, alarming him enough to take two nitroglycerine pills.
As the pain grew in intensity over the next few days, he sought help in the emergency room of the Veterans Affairs Medical Center in Salem. Doctors there were as baffled as he was. The likely source of the pain, they surmised, was his recurring arthritis.
Two days later, the pain had not subsided, so he returned to the VA emergency room. Doctors sent him downstairs to his regular physician, who "knew as soon as I pulled my shirt off."
A rash now accompanied the pain and there was no question he had herpes zoster, commonly known as shingles.
"I had never had such pain in my life," the 67-year-old Roanoke man said. "It was like your bones were broken and all mashed together."
James' description of this sometimes misunderstood disease parallels that of other patients who, without warning, find themselves virtually immobilized by pain and itching. For many, putting anything more binding than a cotton T-shirt over the rash is excruciating.
Each stage brings a new level of discomfort, as the rash blisters, ulcerates and then crusts.
Victims do not lack for words when describing their misery. Some say the sensation is akin to having hundreds of bees stinging all at once; others describe it as having a burning cigarette ground into their skin. Generally, an outbreak of shingles is a one-time event, but residual pain continues long after the rash has disappeared.
"The natural history of this disease is that seven or eight days into the disease the virus has done the damage," said Dr. Charles Schleupner, chief of medical services at the Salem VA Medical Center and a professor at the University of Virginia Medical School.
But Schleupner says there are many questions surrounding the disease, which is triggered by the same virus, varicella-zoster, that causes chicken pox. Doctors cannot exactly predict who is susceptible to the viral strain, what triggers an outbreak, and why it generally strikes older people.
Because the virus enters a peripheral nerve and isolates itself in the ganglion, or nucleus, of the nerve, outbreaks have been linked to stress. But again no studies have absolutely proved any connection.
"Shingles will start out with a vague sensation, then 24 hours later, you see red papules," or pimples, Schleupner said. For months after an attack, patients feel residual pain, called post-herpetic neuralgia.
In rare cases, a person who has never been exposed to the varicella-zoster virus can contract chicken pox by being exposed to a person who has shingles.
Schleupner and his colleagues at the VA hospital and UVa are joining researchers around the country in unlocking some of the mysteries behind shingles. The physicians are participating in two companion studies in hopes of targeting drugs that can alleviate some of the pain associated with the disease.
The studies, funded by the National Institutes of Health and drug companies, are coordinated by the University of Alabama at Birmingham. There are 35 study sites around the country.
For both studies, the hospital needs volunteers, veterans and nonveterans, although there are different requirements for participation in each study.
The first study involves the use of an experimental anti-viral drug with the chemical name of bromo-vinyl-arabinosyl-uracil, or BVAU. It is manufactured by Bristol-Myers Squibb.
Because the drug has not been licensed for general use, volunteers must already be high-risk, suffering from diseases such as cancer, AIDS or lupus that already have wreaked havoc on the patient's immune system.
"The FDA says you have to use it [the experimental drug] on the highest-risk group," Schleupner said. "Once we establish safety, we can use it in a similar study" on patients who do not have abnormal immune systems.
In the study, patients will either receive BVAU or acyclovir, a drug often prescribed to deal with the pain associated with shingles.
Although acyclovir is highly effective in treating herpes simplex, or cold sores, doctors have been disappointed with the results of acyclovir in shingles treatment, Schleupner said.
Patients must take four times the normal dose used in treating cold sores to obtain any measure of relief for shingles' sufferers.
"There isn't any other standard treatment besides acyclovir" for shingles, Schleupner said, even though the benefits are known to be limited.
For the second study, Schleupner is seeking volunteers ages 50 and over who, like James, have healthy immune systems. They will participate in a study to determine the combined effectiveness of acyclovir and the steroid prednizone in alleviating shingles' pain and speeding the healing process.
Because the study is "double-blind" - neither the participants nor the doctors know who is receiving what medicine - James still does not know if he is getting a combination of acyclovir with steroids, steroids without acyclovir, acyclovir without steroids or a placebo. The study is set up in that fashion to avoid any unintentional bias.
"What we are hoping to see is that those who had prednizone with acyclovir had benefits; that is, they had less pain," Schleupner said.
To participate in either study, volunteers should contact the VA center within 72 hours of the initial outbreak of lesions. They will then be screened, fully apprised of how the study will be conducted, and asked to sign a consent form if they agree to participate.
The studies' coordinator, registered nurse Mary Lou Barritt, monitors each patient's progress on a daily basis during the 28 days after the rash appears, measuring the size of the lesions, how long the lesions continue to contain the virus, when the sores crust and how long it takes for the body to heal.
After the rash clears up, researchers plan to track the subjects regularly for the following 12 months to monitor the level of pain each person experiences.
"The skin will totally clear, but they will have continued pain," Schleupner said. "This is pretty painful stuff. You are talking about evolution of pain over a period of up to years."
James knows about that evolution of pain all too well. Although he readily consented to become a part of the study in November, a month later he wasn't so sure.
In late December, nearly two weeks after his rash had all but disappeared but his pain lingered, he developed an allergic reaction to a separate pain medication. That reaction created even more discomfort than he had experienced with the shingles.
Once Schleupner pinpointed the problem and changed the medicine, the retired Marine decided to remain as a volunteer in the study.
The fact that doctors may have to prescribe additional narcotic pain medications to James and other study subjects will all be factored in as scientists begin to analyze the data from subjects across the country.
"Just the fact that they need additional medication for pain tells us to a degree whether the acyclovir is lessening pain," Barritt said. In the case of James, "every medication that he is on is reported; that is all part of the study. We are very seldom going to find a patient who is not on medication."
Schleupner believes the two studies will contribute to greater understanding - and better treatment - for shingles sufferers.
Eventually, he said, scientists will be measuring the effectiveness of BVAU on healthy patients, perhaps unlocking the key that will end the prolonged suffering of patients like James.
"If it [BVAU] pans out, I would predict it would be licensed in a couple of years," he said. `I think we are fortunate to have it locally."
For now, nearly two months after that initial, heart-stopping stab of pain, the retired Marine is feeling a little better.
"I still have the burning and pinching under my arm," James said. And, at times, it still feels "like something has a pair of pliers yanking" on his nerves.
"I'm a lot better than when I started," he said, chuckling. "But that isn't saying a whole lot."
If you have a new outbreak of shingles and would be interested in participating in the study, contact Dr. Charles Schleupner at (703) 982-2463, Ext. 2201.