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Yale-New Haven Hospital news release
Release date: Feb. 7, 2007
Media contact: (203) 688-2488

Yale-New Haven physicians publish study on newly identified disease

NEW HAVEN — Researchers at Yale-New Haven Hospital and the Yale University School of Medicine have linked a rare and debilitating skin condition to the use of gadolinium, a contrast agent sometimes used in magnetic resonance imaging.

A new disease called nephrogenic systemic fibrosis (NSF) is the subject of a study published in the March edition of the Clinical Journal of the American Society of Nephrology by Shawn E. Cowper, M.D., assistant professor of dermatopathology at Yale University School of Medicine and a skin pathologist at Yale-New Haven Hospital. Dr. Cowper is the foremost expert on the disease, which was first seen in 1997. He and Phillip LeBoit, M.D., identified and named the disease in 2001 at the University of California-San Francisco.

The study indicates that the disease – which occurs only in people with advanced kidney disease on dialysis – is linked with gadolinium, a contrast solution sometimes used with magnetic resonance imaging scans. The study involved 467 patients receiving dialysis in the Bridgeport area over 18 months. Three of those patients developed NSF – and all three had undergone MRI scans within the previous two months. Another 84 patients who received gadolinium did not develop NSF.

NSF is characterized by severe fibrosis of the skin, leading to severe disability and reduced mobility of the joints. Often, the first symptom of NSF is redness of the skin and warmth. Physicians can misdiagnose this as cellulitis – a local skin infection, and prescribe antibiotics. But with NSF, the skin swells, tighten up and turns brown over a period ranging from several days to several weeks or months. The skin becomes almost “woody” with the texture of an orange peel, with feelings of burning, itching or severe sharp pains in the affected areas. Some patients experience skin thickening, which can inhibit the movement of joints, making walking and extending of the arms and legs difficult and painful. Systemic involvement of organs such as the heart, lungs, muscles and esophagus are devastating and are associated with death in some cases.

Contributing authors in this study included Aneet Deo, M.D., of St. Vincent’s Medical Center in Bridgeport; and Mitchell Fogel, M.D., Columbia University College of Physicians and Surgeons in New York.

In a related editorial in the same issue of the journal, Mark A. Perazella, M.D., an attending nephrologist and director of the acute dialysis services Yale-New Haven Hospital, supported the author’s findings in one of the first published editorials on nephrogenic systemic fibrosis (NSF) and its potential link with gadolinium. Dr. Perazella is an associate professor of internal medicine in the section of nephrology and director of the renal fellowship program at the Yale University School of Medicine.

“Despite the absence of irrefutable evidence, the association of gadolinium and NSF in patients with kidney disease is so strong that the FDA has sent out warnings about the use of this contrast agent in this population of patients. The editorial brings to light the belief that all physicians need to be aware of this potential complication of gadolinium contrast during MRIs in patients with kidney disease,” said Dr. Perazella.

While most cases have been noted with the use of gadodiamide, a specific type of gadolinium, all formulations should be considered as potential culprits and be avoided when possible. The continued use of gadolinium in kidney disease patients may increase the number of cases. The editorial cautions against the use of gadolinium, in particular gadodiamide, and gives very important guidelines about using other imaging modalities and providing dialysis in at risk patients after the MR study.

“It is important to remember that gadolinium exposure with an MR does not present a risk for NSF to patients without kidney disease.” stressed Dr. Perazella. “The combined use of gadolinium, with kidney disease creates the complications. The other element that needs to be factored in rests with the dosage used. The higher the dose, the greater potential exists for development of NSF. Unfortunately, there are few alternatives to gadolinium, but using an iodinated radiocontrast CT scan may need to be substituted, despite its attendant nephrotoxic risks.”

Yale-New Haven Hospital is a 944-bed, not-for-profit hospital serving as the primary teaching hospital for the Yale School of Medicine. Yale-New Haven was founded as the fourth voluntary hospital in the U.S. in 1826 and today, the hospital complex includes Yale-New Haven Children's Hospital and Yale-New Haven Psychiatric Hospital, with a combined medical staff of about 2,400 university and community physicians practicing in more than 100 specialties. See www.ynhh.org for additional information.

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Last revised: Jan. 29, 2007 (dh)

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