Finding new ways to identify and treat patients, rheumatologists and pulmonologists make gains against scleroderma lung disease
“While the most striking physical finding of scleroderma is the skin, because you can see it,” says rheumatologists Fredrick Wigley, M.D., “the thing that’s killing these patients is the hidden problems in the lung.”
Scleroderma, Wigley explains, is a rare autoimmune disease that causes an overproduction of collagen – the principal protein in fibrous connective tissue – in many organ systems in the body, particularly the skin. The disease stiffens the skin on patients’ hands and fingers, causing circulatory problems and infarctions, or “heart attacks of the hands,” a condition known as Raynaud’s phenomenon. Mirroring this disease process in the hands, the lungs stiffen and scar, causing them to shrink and lose their ability to exchange gas. Also, vessels in the lung may constrict severely, blocking blood flow and resulting in pulmonary hypertension, which may shorten life expectancy.
Unfortunately, Wigley stresses, “There’s no drug that’s been proven to cure scleroderma.”
Wigley and pulmonologist Bob
Wise, M.D., however, have been
making some headway in identifying patients at risk for lung disease, allowing
them to treat earlier with new therapies to increase survival. By giving
patients a bronchoalveolar lavage in which fluid is withdrawn from the lungs and
then studied using new cellular and genetic techniques, for example, Wigley and
Wise are able to open a window into the inflammatory state in the lungs. What
they see is not a relentlessly progressive disease, but flare-ups of intense
inflammation over a relatively short period of time – months or a year.
“We can identify those people who are going to be the most susceptible before they have lost significant amounts of lung function,” Wise says. Adds Wigley, “Patients with active lung inflammation can be treated with medication to prevent progression.”
Those treatments include antifibrotic agents to reduce scarring and vasodilators to relieve pulmonary pressures. Prostacyclin, given by intravenous infusion, for example, has been shown to improve pulmonary hypertension.
Wigley and Wise are also testing immunosuppressives, including cyclophosphamide, a powerful anti-inflammatory cancer drug. Lavage of the lungs shows that T cells, the primary cells that orchestrate an immune inflammatory response, are elevated in scerloderma patients. In low doses, cyclophosphamide kills or inactivates these cells and reduces the inflammatory response that causes lung scarring. Preliminary results, Wigley says, “show cyclophosphamide may work by dampening the immune system, shutting off the disease.”
“For a few patients, cyclophosphamide leads to dramatic improvements,” adds Wise. “For most people, it has the potential to stabilize their disease and keep it from progressing.”
Hopkins, a center of excellence in scleroderma, Wigley notes, has been able to develop these therapies because of the number of patients it attracts – 1100 since 1992 with some 100 new patients each year. Scleroderma afflicts only 20 in 1 million individuals each year.