Nephrogenic Systemic Fibrosis (NSF) or Nephrogenic Fibrosing Dermopathy (NSD)
First reported in this article about Gadolinium Contrast Agents
The decision to conduct a magnetic resonance imaging (MRI) or magnetic resonance angiography (MRA) examination, two commonly performed diagnostic tests, often is very simple. The patient goes to the doctor with complaints of internal problems that may escape detection with traditional x-ray machines, so an MRI or MRA scan is ordered. Until now, the contraindications for having an MRI or MRA have been very limited: patients with cardiac pacemakers, insulin pumps, cochlear implants or other electronically, mechanically or magnetically activated implanted devices, should not have MRI or MRA scans or must proceed very cautiously. Information coming to light now and backed by the FDA, indicates that for people with renal failure or kidney transplants, the very diagnostic test used to cure, may result in devastating injuries or death. The risk may encompass more than this group as additional information surfaces.
Gadolinium is a rare metal found in the earth. Gadolinium is atomic number 64 on the periodic table; which many of us studied in high school or college chemistry. It is a silvery metal that is “ferromagnetic” or strongly attracted by a magnetic, which makes it an ideal product to enhance MRI and MRA images. Gadolinium is a stable compound in dry air, but when exposed to moist air, it will tarnish and forms a loose “film” which falls off and exposes more of the surface area to oxidation. The gadolinium also reacts to water and will dissolve in dilute acid.
Besides being used as a contrast agent for MRI and MRA images, Gadolinium has a number of other uses. Gadolinium is used to make a component of our microwave ovens, it is used in a compound that makes phosphors for color television tubes and it is also used to make computer memory and compact discs. Gadolinium is also used in nuclear marine propulsion as a burnable poison. Gadolinium also has other unique metallurgic properties so that a very small amount of gadolinium can improve the workability and resistance of iron, chromium and other related alloys to oxidation and high temperatures. Today, the medical profession uses gadolinium regularly as an intravenous agent to enhance the images taken by MRI and MRA studies.
Because gadolinium is a highly toxic, when it is used as a medical contrast agent it is attached to another chemical called a “chelate.” A chelate is a compound that “holds” the gadolinium so that it is not toxic and the body can process the gadolinium and dispose of it through our natural waste filtration system, the kidneys. Under most circumstances, the gadolinium is simply passed out of the body through the kidneys in urine. However, in some individuals who have compromised kidney function, the kidneys cannot work efficiently to remove it and some of the gadolinium remains in the body causing potentially serious gadolinium side effects. The longer the gadolinium stays in the bloodstream, the more chelates lose their hold on the gadolinium and break off, allowing more of the toxic gadolinium to contaminate the bloodstream. As the blood circulates throughout the body, the gadolinium is deposited in the skin, tissue and numerous organs. Once the gadolinium has taken up residence in human tissue, there is no proven way to remove it.
Over the past years, physicians saw patients with renal failure who received toxic gadolinium develop a deadly disease, and now gadolinium has been linked with a serious disease called Nephrogenic Systemic Fibrosis (NSF) or Nephrogenic Fibrosing Dermopathy (NFD).
NSF and NFD affect the skin, joints, eyes and internal organs. As the terms “fibrosis” and “fibrosing” imply, NSF and NFD result it the formation of excess, abnormal fibrous connective tissue. Patients with NSF or NFD develop large areas of hardened skin that takes on a shiny, darkened or brownish, metallic sheen. As the skin tightens it can cause contractures of the joints which restrict flexibility and movement. NSF or NFD can also cause yellow colored plaques in the eyes. Symptoms also include painful joints and hips. It can severely damage the lungs, heart and internal organs, resulting in death.
Patients with NSF or NFD are often misdiagnosed with scleroderma, because testing for NFS and NFD is still fairly uncommon. Reports of NSF or a skin biopsy is used to confirm the diagnosis of NSF or NSD. The biopsy needs to be at least five millimeters or more in width and needs to go down to and include the subcutaneous tissue but not the muscle. A dermatologist can perform the biopsy and a pathologist or dermato-pathologist will read the slides.
There are a number of different brands of gadolinium-based contrast dyes known as GBCAs on the market today which are commonly used when patients undergo an MRI. Five gadolinium-based contrast agents have been approved for use in the United States and most of them have been associated with NSF or NFD:
Magnevist – gadopentetate dimeglumine – Approved June 2, 1988
Ominiscan – gadodiamide – Approved January 8, 1993
OptiMARK – gadoversetamide – Approved December 8, 1999
MultiHance – gadobenate dimeglumine – Approved November 23, 1994
Prohance – gadoteridol – Approved November 16, 1992
In May 2007, the Federal Drug Administration issued a request that the manufacturers of the gadolinium dye included a new boxed warning on the product labels. The new warning would state that patients with severely compromised kidney function who received a gadolinium based contrast dye are at risk for developing a debilitating and possibly fatal disease known as NSF. The warning also stated that patients with chronic liver disease or those people just before or after a liver transplant, were also at risk of developing NSF is they had any kidney compromise. The FDA recommended that patients receive kidney function screening prior to have a MRI or MRA with contrast.
Reports have identified the development of NSF following single and multiple administrations of the gadolinium-based contrast agents. The reports have not always identified a specific agent. When a single product was used, and NSF developed in the patient, General Electric’s product, Omniscan, was the most commonly reported gadolinium based agent. Magnevist and OptiMARK followed as the second and third most reported agents associated with a report of NSF.
If you or someone you know has compromised kidney function and has had at least one MRI or MRA, the following symptoms may be a sign of NSF or NFD: hip pain; changes of the skin including hardening, tightening and dark patches; contractures of the arms, legs and feet which make them difficult to straighten; joint pain and stiffness; muscle pain and weakness; and yellow patches in the eyes. If you have any of these symptoms, you should see your doctor for testing and diagnosis.
Beth Klein is a Denver-based personal injury lawyer. Learn more about Gadolinium / NSF on her website.