Overview

Nephrogenic systemic fibrosis is a rare disease that occurs mainly in people with advanced kidney failure with or without dialysis. Nephrogenic systemic fibrosis may resemble skin diseases, such as scleroderma and scleromyxedema, with thickening and darkening developing on large areas of the skin.

Nephrogenic systemic fibrosis can also affect internal organs, such as the heart and lungs, and it can cause a disabling shortening of muscles and tendons in the joints (joint contracture).

For some people with advanced kidney disease, being exposed to older gadolinium-based contrast agents (group 1) during magnetic resonance imaging (MRI) and other imaging studies has been identified as a trigger for development of this disease. Recognition of this link has dramatically reduced the incidence of nephrogenic systemic fibrosis. Newer gadolinium-based contrast agents (group 2) are not associated with an increased risk of systemic nephrogenic fibrosis.

Symptoms

Nephrogenic systemic fibrosis can begin days to months, and even years, after exposure to an older gadolinium-based contrast agent (group 1). Some signs and symptoms of nephrogenic systemic fibrosis may include:

• Swelling and tightening of the skin
• Reddened or darkened patches on the skin
• Thickening and hardening of the skin, typically on the arms and legs and sometimes on the body, but almost never on the face or head
• Skin that may feel "woody" and develop an orange-peel appearance
• Burning, itching or severe sharp pains in areas of involvement
• Skin thickening that inhibits movement, resulting in loss of joint flexibility
• Rarely, blisters or ulcers

In some people, involvement of muscles and body organs may cause:

• Muscle weakness
• Limitation of joint motion caused by muscle tightening (contractures) in arms, hands, legs and feet
• Bone pain, particularly in the hip bones or ribs
• Reduced internal organ function, including heart, lung, diaphragm, gastrointestinal tract or liver
• Yellow plaques on the white surface (sclera) of the eyes

The condition is generally long term (chronic), but some people may improve. In a few people, it can cause severe disability, even death.

Causes

The exact cause of nephrogenic systemic fibrosis isn't fully understood. Fibrous connective tissue forms in the skin and connective tissues, resulting in scarring of tissue throughout the body, most commonly the skin and subcutaneous tissues.

Exposure to older gadolinium-based contrast agents (group 1) during magnetic resonance imaging (MRI) has been identified as a trigger for development of this disease in people with kidney disease. This increased risk is thought to be related to the kidneys' reduced ability to remove the contrast agent from the bloodstream.

The Food and Drug Administration (FDA) recommends avoiding older gadolinium-based contrast agents (group 1) in people with acute kidney injury or chronic kidney disease.

Other conditions may increase the risk of nephrogenic systemic fibrosis when combined with existing kidney disease and exposure to older gadolinium-based contrast agents (group 1), but the link is uncertain. These include:

• Use of high-dose erythropoietin (EPO), a hormone that promotes the production of red blood cells, often used to treat anemia
• Recent vascular surgery
• Blood-clotting problems
• Severe infection

Risk factors

The highest risk of nephrogenic systemic fibrosis after exposure to older gadolinium-based contrast agents (group 1) occurs in people who:

• Have moderate to severe kidney disease
• Have had a kidney transplant but have compromised renal function
• Are receiving hemodialysis or peritoneal dialysis
• Have acute kidney injury

Diagnosis

Diagnosis of nephrogenic systemic fibrosis is made with:

• Physical exam for signs and symptoms of the disease, and evaluation for a possible history of MRI using a gadolinium-based contrast agent when advanced kidney disease is present
• A sample of tissue (biopsy) taken from the skin and muscle
• Other tests as needed that may indicate involvement of muscles and internal organs

Treatment

here is no cure for nephrogenic systemic fibrosis, and no treatment is consistently successful in halting or reversing the progression of the disease. Nephrogenic systemic fibrosis only occurs rarely, making it difficult to conduct large studies.

Certain treatments have shown limited success in some people with nephrogenic systemic fibrosis, but more research is needed to determine if these treatments help:

• Hemodialysis. In people with advanced chronic kidney disease who are receiving hemodialysis, performing hemodialysis immediately after receiving a gadolinium-based contrast agent may decrease the possibility of nephrogenic systemic fibrosis.
• Physical therapy. Physical therapy that helps stretch the involved limbs may help slow the progression of joint contractures and preserve movement.
• Kidney transplant. For people who are appropriate candidates, improvement in renal function because of a kidney transplant may help improve nephrogenic systemic fibrosis over time.
• Extracorporeal photopheresis with ultraviolet A. This treatment involves drawing the blood outside the body and treating the blood with a drug that sensitizes it to ultraviolet light. The blood is then exposed to ultraviolet light and returned to the body. Some people have shown improvement after receiving this therapy.

These medications are experimental, but not currently in use. They have been shown to help some people, but side effects limit their use:

• Imatinib (Gleevec). Although this treatment shows some promise in reducing skin thickening and tightening, more research is needed.
• Pentoxifylline (Pentoxil). There is limited success with this medication, which theoretically decreases the thickness and stickiness (viscosity) of blood, aiding circulation. More research is needed.
• Sodium thiosulfate. Possible benefit has been shown using this medication, but more research is needed.
• High-dose intravenous immune globulin. Possible benefit has been shown using this medication, but more research is needed.