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After 10 years of research, a rare skin disease is traced to a chemical used in MRIs

Yale Medicine Magazine, 2007 - Spring


In 1997 investigators in California came across a mysterious skin disease. It often started with redness of the skin and warmth, but as it progressed, the skin swelled, tightened and turned brown, becoming almost “woody.” The unnamed disease led to disability, reduced mobility of the joints and could be fatal.

After almost 10 years of research, Shawn E. Cowper, M.D., assistant professor of dermatology and pathology, has provided additional evidence that the disorder affects a small number of patients with kidney disease who undergo magnetic resonance imaging (MRI) scans with contrast. The disease that he identified in 2001, with Philip LeBoit, M.D., of the University of California, San Francisco, is now called nephrogenic systemic fibrosis (NSF). Cowper started a registry of the disease that now numbers about 235 cases.

At first Cowper thought the disorder affected only the skin. It turns out that it is mediated by a cell involved in wound healing that was originally identified in 1992 by Richard Bucala, M.D., Ph.D., professor of medicine (rheumatology), pathology and epidemiology (microbial diseases).

While pondering its causes, Cowper noticed that most of the patients in his registry had undergone vascular imaging. Working with investigators in Bridgeport, Conn., he examined the records of 467 patients receiving dialysis. Three developed NSF following MRI, and all three had received the contrast agent gadolinium. Another 84 patients received gadolinium but did not develop the disease. In March, Cowper published a study in the Clinical Journal of the American Society of Nephrology, linking gadolinium to NSF, which occurs only in patients with advanced kidney disease.

Based on Cowper’s work and a Danish study, the Food and Drug Administration issued a public health advisory last year warning of the dangers to kidney patients who receive a contrast-enhanced MRI. “What’s really key now, and what everybody is excited about finding, is what makes these 3 percent different than the other 97 percent who have renal failure and have been exposed to gadolinium without developing NSF,” said Cowper.

Understanding the mechanism behind NSF may explain why it occurs. In contrast agents, gadolinium is bound to a chelate, a molecule that keeps it from interacting with the body and allows it to be quickly eliminated by the kidneys. But patients with advanced kidney disease can’t efficiently rid themselves of such toxins as gadolinium, which may build up, dissociate from the chelate and do damage.

Unfortunately, all contrast agents used for routine MRIs in the United States contain gadolinium. Kidney patients who must undergo an MRI with contrast are advised to undergo dialysis immediately afterward, but no one is certain that this will decrease the chances of developing NSF. “There are a lot of questions that need to be answered before anyone declares this disease gone, or even this technique safe,” said Cowper.