Dermatologists Provide Unique Evidence Of Possible Cause Of Rare Skin Condition

Main Category: Dermatology
Also Included In: Urology / Nephrology;  MRI / PET / Ultrasound
Article Date: 17 Nov 2006 - 0:00 PST

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While kidney failure is a serious condition that requires extensive medical intervention, a small subset of these patients are prone to developing another grave condition known as Nephrogenic Systemic Fibrosis or Nephrogenic Fibrosing Dermopathy (NSF/NFD). First recognized as a disease in 1997, NSF/NFD causes discoloration and thickening or tightening of the skin, resulting in pain, muscle weakness and difficulty bending joints. In many cases, NSF/NFD results in scarring of internal organs that inhibit their ability to function properly, which can be fatal.

More than 215 cases of NSF/NFD have been documented in the last decade, but despite ongoing research, the cause of the disease is unknown. Now, results of a pilot study suggest that gadolinium-containing contrasting agents used for Magnetic Resonance Angiography (MRA) in patients with kidney failure may be the culprit.

In the report entitled, "Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis," to be published in an upcoming issue of the Journal of the American Academy of Dermatology, dermatologist Whitney A. High, MD, MEng, Department of Dermatology at the University of Colorado, Denver, Colo., found that gadolinium was detected in tissue samples from four of seven patients with NSF/NFD. The full text of the article can be found at http://download.journals.elsevierhealth.com/pdfs/journals/0190- .

"Although gadolinium-based contrast agents have a long history of safe and effective use in Magnetic Resonance Imaging (MRI), the dose of the agent administered to kidney failure patients undergoing MRA to examine blood vessels is up to three times higher than the amount used in a typical MRI test," explained Dr. High. "Recent publications have suggested an association between exposure to gadolinium and the development of NSF/NFD, and our pilot study was designed to determine whether gadolinium was detected within the skin and soft tissue of patients with the disease who were exposed to this contrast agent."

Dr. High and a team of researchers obtained 13 blocks of paraffin-embedded tissue samples from seven NSF/NFD patients exposed to gadolinium from the national NSF Registry of New Haven, Conn.(1). An additional paraffin-embedded block containing tissue from a routine dermatopathology case served as the negative control. Researchers used a field emission scanning electron microscope equipped with electron dispersion spectroscopy to search the tissue for metals. They also were blinded as to which blocks of tissue were from NSF/NFD cases and which were from negative controls.

The study found that gadolinium was detected in four of 13 tissue specimens from patients with NSF/NFD who were exposed to the contrast agent. As expected, none of the negative controls tested positive for gadolinium.

"While clearly more research needs to be done, we are encouraged by our findings and hope that it provides an important first step in understanding the cause of this elusive disease," said Dr. High. "Until more data becomes available, we urge patients with end-stage kidney disease and their health care providers to be aware of this potentially fatal association between gadolinium and NSF/NDF and make every effort to avoid any unnecessary, excessive dosage of this contrast agent."

The U.S. Food and Drug Administration (FDA) is currently conducting an investigation of whether exposure to gadolinium is linked to the onset of NSF/NDF and advises health care providers to use caution in administering the contrast agent to patients with advanced kidney failure. The FDA's Public Health Advisory issued in June 2006 can be accessed at http://www.fda.gov/cder/drug/advisory/gadolinium_agents.htm . According to the FDA, a second advisory will be issued at the end of this month.

The National Kidney Foundation reports that 20 million Americans -- 1 in 9 U.S. adults -- have chronic kidney disease and another 20 million more are at increased risk.

The American Academy of Dermatology (Academy), founded in 1938, is the largest, most influential, and most representative of all dermatologic associations. With a membership of more than 14,000 physicians worldwide, the Academy is committed to: advancing the diagnosis and medical, surgical and cosmetic treatment of the skin, hair and nails; advocating high standards in clinical practice, education, and research in dermatology; and supporting and enhancing patient care for a lifetime of healthier skin, hair and nails. For more information, contact the Academy at 1-888-462-DERM (3376) or http://www.aad.org.

(1) The national NSF Registry of New Haven, Conn. Is administered by Shawn Cowper, MD, of Yale University Medical Center.

American Academy of Dermatology
http://www.aad.org