Headlines
As reported by The Hartford Courant, March 16, 2005.
Disease Turns Skin Hard as Wood
Scientists Are Gaining Greater Understanding of Scleroderma
By William Hathaway
Cheryl Argiros of Coventry has already participated in four clinical trials of experimental treatments for scleroderma, a disease that turns skin to the consistency of mahogany. It has scarred her lungs and turned her hands into claws.
Researchers say the prospects for developing new therapies to treat the connective-tissue disease have never been better. About a dozen new treatments - including vaccines, stem cell transplants and specialized antibodies - are being tested in patients.
But the mother of two adult daughters does not know if medical help will arrive soon enough to lift the death sentence she has been living under for nine years.
"When I first got it, I thought I was a goner," says Argiros, 46. "Maybe in my lifetime there will be something that might save me. There is still hope, but time is running out."
History is not on her side. Scleroderma, which literally means hard skin, has had a long history of mystifying medical scientists. West Hartford resident Mary Mannillo, who runs the Connecticut, New York and New Jersey chapter of the Scleroderma Foundation, says that when she was diagnosed with the disease in 1959, "you couldn't find `scleroderma' in the dictionary."
Even today, no one knows why Mannillo or Argiros or an estimated 300,000 other Americans have developed scleroderma. Three out of four scleroderma patients are women, and the disease usually - but not always - strikes in middle age. The outlook remains bleak for the approximately 100,000 patients like Argiros who develop diffuse or systemic scleroderma, which affects multiple areas of the body.
About half the people with this diagnosis die within five years, a mortality rate equivalent to some cancers, says Dr. Daniel Furst, a rheumatologist at the University of California at Los Angeles and an expert on the disease.
The high mortality rate and lack of knowledge about the underlying pathology of the disease has meant that clinicians have emptied out the medicine cabinet in a desperate attempt to find effective treatments.
"It has been said that no pharmaceutical company deemed a drug completely worthless until it was tried on scleroderma," says Furst. "What happened was we didn't understand the disease. But a lot has changed in the past five years."
Furst says scientists now have a pretty good understanding about what occurs when the body's immune system sets off a chain reaction of events that creates excess amounts of collagen, a ubiquitous protein that serves as a sort of glue that holds together much of the body. In most scleroderma cases, excess collagen tends to harden the skin, particularly the hands. In more serious cases, the disease can turn the tissue of organs such as the heart, kidney, lungs and stomach to the consistency of wood.
Medical science also understands the course of the disease better, which makes it easier to assess the benefits of new treatments. While the course of scleroderma is different in each patient, Argiros' experience is not unusual for someone with the systemic disease.
Argiros was 36 and healthy when she noticed that, in cold weather, her fingers drained of blood and turned blue. Medical tests revealed a thyroid problem and signs of limited scleroderma, in which the disease usually is confined to the hands or face. Within months, however, her doctors told her that she had systemic scleroderma. Argiros read in a medical book that the average life expectancy of someone with her condition was seven years.
Within a few years, her skin had become so taut that it pulled her fingers down to her palm. The skin on her arms, legs and chest became hard. Her face also took on the consistency of stone and now has an unnaturally smooth sheen.
"Believe me, I would love to have wrinkles," she says.
In winter, ulcers develop on her knuckles and fingertips. The disease has damaged her esophagus, which causes severe heartburn. She also suffers from anemia and anxiety and is constantly fatigued.
Her lungs present the most dangerous problem. While patients with limited scleroderma often develop dangerous pulmonary hypertension, others like Argiros develop fibrous tissue on their lungs. It is the loss of lung function that Argiros fears will kill her.
Last year, Argiros was pulled from a clinical trial of the cancer drug Cytotoxin, which doctors hoped would help her damaged lungs, because she developed a painful case of shingles.
She twice participated in trials of the hormone relaxin, which is produced during childbirth and helps widen the birth canal. She says that on both occasions she felt the disease's hard grip on her skin subside.
However, relaxin failed its last clinical trial because the hormone showed no more benefit than a placebo, says Dr. Naomi Rothfield, Argiros' doctor and founder of the rheumatology section at the University of Connecticut Health Center in Farmington, where she is currently a professor of medicine.
"We were very disappointed by the results," Rothfield said.
However, patients such as Argiros have many more options than a few years ago, she said.
For instance, a trial of a collagen vaccine that researchers hope will prevent the body from overproducing the protein is finishing up, Rothfield said.
Biotech companies also are developing antibodies designed to attack the specific proteins that produce fibrous tissue. Researchers also are investigating whether a new generation of immune suppressants will halt the disease. For severe cases, bone marrow transplants similar to those being used in leukemia patients are being tried.
"The market is small, but the need is great," Furst said.
When Argiros was diagnosed, she was afraid she wouldn't live long enough to see her daughters, Renee and Jeanine, then 12 and 15, become adults. Now she has a 4-year-old grandson, Cody, and would like to see him grow up as well.
So each day she manages to get herself to work at the U.S. Postal Service offices in Windsor.
"My doctor is amazed by me. She calls me her hero," Argiros said. "You always have hope."
A version of this story first ran on Nov. 23.