Diagnosis: Scleroderma
words by maryann brinley / photographs by pete byron
Alicia Carmine, patient
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ine years ago, Alicia Carmine was 36 years old and a long distance runner when a series of troubling symptoms changed her life forever. She was having difficulty breathing. Her fingers would swell and turn blue even while indoors. She had bouts of indigestion and was gaining weight. “I joined a weight loss program,” she says, remembering her frustrations. What was going on with her body?
After all, she was, or had been, a healthy athlete. Even the spelling of her email address still proudly reflects that “runner” in her psyche though she no longer runs.
Her regular doctor recommended a rheumatologist who sent her to the UMDNJ-Robert Wood Johnson Medical School’s Clinical Research Center (CRC) and Vivien Hsu, MD, director of the Scleroderma Program. “I had classic signs of systemic scleroderma and Raynaud’s though I had never heard of them before,” Carmine explains. Her new team of experts could even hear the crackling of the fibrotic tissue in her lungs.
Hsu, an associate professor of medicine at RWJMS and a 1983 graduate of UMDNJ-New Jersey Medical School, joined the UMDNJ Scleroderma Program in 1996. After spending years in private practice, she says, “Academic medicine offers such a nice balance between teaching, research and patient care. In private practice, there is no time to reflect. And here at the CRC, we do a lot of clinical research for many other subspecialties of medicine and surgery.” More than 50 studies are conducted annually in areas as diverse as gastroenterology, pulmonary hypertension, sleep disorders, cancer, hypertension, dermatology and neuropharmacology. “We have a lab as well as staff here who can do the research and can also take care of the regulatory paperwork, the budgeting and other requirements, because these can change so quickly over time.” The interdisciplinary research effort includes nursing, pharmacy and biostatistics support.
Hsu herself is a rheumatologist by training precisely because the field is so challenging and wide-ranging. “What makes rheumatology so unique is that you have to know a lot about internal medicine, about every organ that is affected by these different rheumatic diseases. Most, like scleroderma, have no cures but we can offer a lot to control the disease.” The term rheumatism commonly describes any painful disorder in the joints, muscles, connective or soft tissues around joints and bones. Rheumatologic diseases run the gamut from arthritis to gout and systemic lupus erythematosus, as well as other complex diseases such as scleroderma, in which the auto-immune and fibrotic pathways are overly active. “Unusual, very different symptoms can send undiagnosed patients bouncing from one doctor to another and wondering what is causing their pain,” according to Hsu. Some people are told that it’s all in their heads. So, many, like Alicia Carmine, are actually relieved when they finally reach Hsu’s clinic doorstep.
Raynaud’s phenomenon, triggered by temperature or stress, turns hands and feet pale and painfully cold, and is associated with a number of rheumatic diseases, especially scleroderma. From the Greek words “sclero” or hard and “derma” or skin, this autoimmune disorder causes a hardening and tightening of the skin and connective tissues. In some forms, skin will be the extent of the abnormal process. In others, according to Hsu, the problem goes deeper, affecting blood vessels and internal organs like the heart, lungs, and kidneys. Some sub-types are very aggressive. “We have learned a lot about the pathways but we still don’t know why this happens. These scary symptoms may also change over time,” she explains. According to the Scleroderma Foundation, approximately 300,000 Americans have this disease and one-third fall into the systemic category where internal organs are affected.
“Through clinical trials, we are learning better ways to measure scleroderma in a scientific manner, to define the disease at a given stage and chart its progression or improvement.” For instance, the modified Rodnan skin score measures skin thickening in 17 different areas, using a scale from 0 (normal ) to 3 (very thickened). This technique has been validated world-wide and is a useful tool in assessing disease activity, predicting course, and ultimately, the patient’s prognosis. “We are still developing better ways to measure lung disease, which is now the principal cause of morbidity and mortality.” Sometimes experts will disagree on measures, such as what defines a digital (finger or toe) ulcer. “But many questions are answered while conducting clinical trials. A few years ago, we weren’t doing any of this.”
Hsu and her colleagues have been studying new biologics, chemotherapies, and pharmaceuticals. (According to the Food and Drug Administration, the simple definition of a biologic would be a product made from a living organism, but biologics include any virus, therapeutic serum, toxin, antitoxin or product to prevent, treat or cure disease.) Hsu would like to see more effective treatments that are safer, easier to take, and compatible with other medications. “Right now, a lot of biologics must be given intravenously.” At the moment, her group is participating in two clinical trials for interstitial lung disease and actively looking for an anti-fibrotic drug for scleroderma. Hsu is proud of their contribution to the successful approval of a topical, nitroglycerin, fast-acting gel, MQX-503, which quickly and safely relieves pain from a Raynaud attack. She remembers the manufacturer, a small San Francisco pharmaceutical firm, MediQuest, “when they first started out.
“Because of this research, I can offer patients treatments to control symptoms, even though there is no cure.” It’s not hard at all to recruit for trials. “Patients come in frightened by a disease making them miserable. They want to feel better, live longer and are hoping to have fewer problems.” Hsu gives them hope. “I establish rapport with them and it’s rewarding for me to see them get better and live longer.” Alicia Carmine knows this personal touch very well. “Oh yes,” she admits, “Dr. Hsu has been there for me when I cry, get frustrated and things are not going well at all. Her personality alone is good medicine. When I see her in the hallway, she gives me a big hug.”
Scleroderma symptoms typically start in the hands but some patients won’t notice changes until the disease has spread to the trunk of the body. Hsu explains that in the lungs, systemic sclerosis will start at the bottom and move to the top.
Vivien Hsu, MD,
associate professor of medicine, UMDNJ-Robert Wood Johnson Medical School
Blood work and other tests quickly confirmed Carmine’s diagnosis. “Unfortunately, my lungs were affected,” she recalls. “As a runner, I took this all pretty hard,” she says. Frightened, she saw the CAT scans herself and thought, “Wow, this is serious.” Facing her incurable disease, Carmine was offered standard treatment or the option to join a clinical trial. “My first thought was ‘No way,’ but I didn’t actually say that.” The idea of not wanting to be a guinea pig in someone’s experiment crossed her mind. “I delayed saying ‘yes’ for three weeks. I was nervous. I’m single and my family was nervous.” Yet, assured that she could stop the trial at any time, that the new medication might make a real difference in her lung inflammation and the fibrosis, and that she would have regular appointments with easy access to a comprehensive, supportive, medical staff, Carmine agreed. All the attention and focused care have made her more than simply comfortable. She feels better. “I can call anytime with even the tiniest problem and not feel like a pain or a bother. Someone gets back to me right away. No matter how busy Dr. Hsu is, I know she’ll be there for me.”
As a result of that first trial, her lungs stabilized. And when it ended about four years later, she moved quickly into a new one to test ulcer medication. Nearly non-stop clinical trials have been part of Carmine’s life for nearly a decade. “I had the best success with that digital ulcer trial medication. Even the trial coordinators were surprised by how well my hands did because beforehand, sometimes they would hurt for days and nights to the point where I couldn’t sleep.”
Always ready to try something new clinically, Carmine continues to work full time as a teaching assistant for children with disabilities. Her last trial with Hsu ended several months ago but she is ready to sign up again. She credits the clinical trials, her faith in God and the prayers of others for her good quality of life now. “I’m excited to be part of this research. When they ask me to be in a study, I say yes.” The scleroderma doesn’t stop her from going places or doing things, even taking a swim or walking on the boardwalk at the beach. “If I run out of breath, I sit down and take a short break.” She may keep a portable oxygen tank handy as well as toe and hand warmers for the shifts in temperature so dangerous to her health but the runner in her is still alive and well.