Nephrogenic Systemic Fibrosis or Nephrogenic Fibrosing Dermopathy (NSF/NFD) is a progressive condition that can develop in those with advanced renal failure. It causes thickening and hardening of the skin, often in the extremities, and in connective tissues throughout the body. NSF/NFD is a rare disease with unknown risk factors although a strong apparent connection to gadolinium-based contrast agents prompted the FDA to issue a warning. Since it was first detected in 1997, hundreds of cases in the U.S. have been reported to the NFD registry.
NSF/NFD usually begins with darkened or reddened papules, patches and plaques that progress rapidly and sometimes lead to joint immobility and the inability to walk. In some cases, the fibrosis spreads to, and patients report pain in the lower abdomen, the diaphragm, and the muscles in the lower thigh. Additional symptoms may include yellow raised spots on the whites of the eyes, deep “bone pain” of the ribs and hips, difficulty breathing, severe secondary illness and death. Approximately five percent of those afflicted experience a rapidly progressive course.
After numerous NSF/NFD patients reported that they had undergone Magnetic Resonance Imaging (MRI) and/or Magnetic Resonance Angiography (MRA) scans with a gadolinium-based contrast agent, a causal link could not be proven, but some research supported a strong enough correlation between these events that the FDA decided to warn health care providers. The FDA warned that “patients with moderate to end-stage kidney disease who receive an MRI or MRA with a gadolinium-based contrast agent may get NSF/NFD which is debilitating and may cause death.”
Gadolinium contrast agents are injected intravenously and accumulate in abnormal tissue, causing the tissue to brighten on images created by MRI and MRA scans. The FDA had approved gadolinium for use with MRA scans as a less toxic and non-radioactive alternative to other contrast agents. The more stable and apparently less toxic substance allowed patients with normal functioning kidneys to excrete it through their urine.
The contrast agent also goes by gadodiamide and gadolinium-DPTA and by various brand names, including Omniscan (made by Nycomed Amersham PLC), Magnevist (Berlex Laboratories, Inc.), OptiMARK (Mallinckrodt), ProHance and MultiHance (both made by Bracco Diagnostics, Inc.).
The FDA may take further action by requiring additional studies, modifying product labeling, and implementing risk management procedures. But until any further action is taken, patients with impaired kidney function who have undergone an MRI or MRA with a gadolinium-containing contrast agent should alert their physician. Physicians should consider a dialysis and report the any cases to the FDA’s MedWatch at http://www.fda.gov/medwatch/.
There is currently no treatment for NSF/NFD that is consistently effective. However, improving renal function may slow the progress of the condition and may even arrest or reverse it.