What Is Nephrogenic Fibrosing Dermopathy?
A rare condition known as nephrogenic systemic fibrosis or nephrogenic fibrosing dermopathy primarily affects individuals with advanced kidney failure and those receiving dialysis. Nephrogenic fibrosing dermopathy may resemble conditions that cause thickness and darkening of vast areas of skin, such as scleroderma (chronic autoimmune disease affecting connective tissues of the body) and scleromyxedema (chronic skin disorder). This condition can shorten muscles and tendons in the joints and impact internal organs, including the heart, lungs, and kidneys.
It has been determined that exposure to older gadolinium-based contrast agents during magnetic resonance imaging (MRI) and other imaging investigations in patients with the development of advanced renal disease has triggered the development of this disease. The prevalence of nephrogenic fibrosing dermopathy has significantly decreased since this connection was discovered. However, modern gadolinium-based contrast agents have shown a reduced risk of developing nephrogenic fibrosing dermopathy.
What Causes Nephrogenic Fibrosing Dermopathy?
The exact cause of nephrogenic fibrosing dermopathy is not entirely clear, but it involves the formation of fibrous connective tissue and scarring in tissues throughout the body, particularly in the skin and subcutaneous tissues. Older gadolinium-based contrast agents used during magnetic resonance imaging (MRI) have been identified as a trigger for developing the disease in individuals with kidney disease. The risk is thought to be linked to kidneys' decreased ability to eliminate the contrast agent from the bloodstream. The Food and Drug Administration (FDA) advises against using older gadolinium-based contrast agents (group 1) in people with acute kidney injury or chronic kidney disease.
The association between other medical conditions and an increased risk of nephrogenic systemic fibrosis in individuals with existing kidney disease and exposure to older gadolinium-based contrast agents is uncertain. These conditions may include the use of high-dose erythropoietin (EPO) to treat anemia, recent vascular surgery, blood-clotting disorders, and severe infections.
The association of end-stage renal disease (ESRD) with calciphylaxis and soft tissue calcification has been well-established. In addition, a newly recognized syndrome called nephrogenic fibrosing dermopathy (NFD) has been observed in ESRD patients, which is characterized by sclerotic plaques with histological features similar to scleromyxedema. Initially reported as a scleromyxedema-like cutaneous disease, this disorder was later renamed nephrogenic fibrosing dermopathy by Cowper and colleagues.
What Are the Symptoms of Nephrogenic Fibrosing Dermopathy?
The symptoms of nephrogenic fibrosing dermopathy can develop anytime after exposure to an older type of gadolinium-based contrast agent. Symptoms of the condition may include:
-
Swelling and tightening of the skin.
-
Dark or red patches on the skin.
-
Skin hardening or thickening, particularly on the arms and legs, but rarely on the face or head.
-
Affected skin may feel "woody". The skin can have an orange-peel appearance, accompanied by burning, itching, or sharp pains.
-
In some cases, thickened skin can restrict movement and lead to joint flexibility loss, while blisters or ulcers can rarely occur.
-
The involvement of muscles and organs may cause muscle weakness, joint limitations, bone pain, reduced organ function, and yellow plaques on the sclera.
-
Nephrogenic fibrosing dermopathy is generally a chronic condition, but some individuals may improve. Severe cases can cause a disability or sometimes death.
How Is Nephrogenic Fibrosing Dermopathy Diagnosed?
-
Physical Examination - To diagnose nephrogenic fibrosing dermopathy, a physical examination is conducted to look for signs and symptoms of the condition and review individual's medical history, including any prior MRI using gadolinium-based contrast agents when the advanced kidney disease is present.
-
Skin and Muscle Biopsy - A skin and muscle biopsy sample may be obtained to confirm the diagnosis.
How Is Nephrogenic Fibrosing Dermopathy Treated?
Currently, there is no treatment for nephrogenic fibrosing dermopathy. Treatments that can reverse or stop the disease progression have not been established yet. The condition is so rare that it makes it difficult to conduct large-scale studies. However, some treatments have shown limited success in some people with nephrogenic fibrosing dermopathy, although further research is necessary to determine their effectiveness. These treatments include:
-
Hemodialysis: People with advanced chronic kidney disease who are receiving hemodialysis may be treated immediately after receiving a gadolinium-based contrast agent to decrease the likelihood of nephrogenic systemic fibrosis.
-
Physical Therapy: Physical therapy that helps stretch the affected limbs can help slow the progression of joint contractures and maintain movement.
-
Kidney Transplant: A kidney transplant can improve renal function, which may, in turn, help improve nephrogenic systemic fibrosis over time.
-
Extracorporeal Photopheresis With Ultraviolet A: This therapy involves treating the blood outside the body by exposing it to the light-sensitive drug and returning it to the body. Some people have shown improvement after receiving this treatment.
The following treatments have shown some potential in treating nephrogenic systemic fibrosis, but more research is needed to determine their efficacy:
-
Imatinib : This drug can reduce skin thickening and tightening.
-
Pentoxifylline: This medication theoretically aids circulation by decreasing the thickness and stickiness (viscosity) of blood, but its success in treating nephrogenic systemic fibrosis is limited, and more research is needed.
-
Sodium Thiosulfate: This medication has shown possible benefits, but further research to determine its effectiveness is required.
-
High-Dose Intravenous Immunoglobulin: This treatment has shown promising , but need for further research is to confirm its efficacy is felt.
What Are the Risk Factors for Nephrogenic Fibrosing Dermopathy?
The most significant risk for developing nephrogenic systemic fibrosis after being exposed to older gadolinium-based contrast agents is present in people who:
-
Have moderate-to-severe kidney disease.
-
Have impaired renal function even after a kidney transplant surgery.
-
Have been undergoing hemodialysis or peritoneal dialysis.
-
Are dealing with acute kidney injury.
The prevention of nephrogenic fibrosing dermopathy is centered on avoiding the use of older gadolinium-based contrast agents (group 1), as newer contrast agents (group 2) are considered safer and do not have increased risk.
Conclusion
Nephrogenic systemic fibrosis (NSF) is a condition characterized by skin fibrosis and internal organs. While it shares some similarities with scleroderma and scleromyxedema, it is a distinct disease. NSF is primarily caused by exposure to gadolinium, a contrast agent used in imaging studies such as magnetic resonance angiography. The condition almost exclusively affects individuals with renal insufficiency. Gadolinium has been found in tissue samples of NSF, and researchers are currently exploring alternative contrast agents to reduce the risk of developing the condition.
