Nephrogenic fibrosing dermopathy (NFD), also known as nephrogenic systemic fibrosis (NSF), is a rare condition that primarily affects the skin. First described in patients with kidney disease in 1997, this progressive disorder involves the thickening and hardening of various body tissues. Understanding NFD is important for individuals with compromised kidney function.
Understanding the Condition
NFD is characterized by the proliferation of fibroblast-like cells and increased collagen deposition, leading to skin hardening and thickening, which can give it an “orange-peel” texture. Although most visible on the skin, NFD is a systemic disorder, with fibrotic changes potentially affecting underlying tissues like skeletal muscle and internal organs such as the heart, lungs, and liver.
Identifying the Causes and Risk Factors
The development of NFD is strongly linked to exposure to certain gadolinium-based contrast agents (GBCAs), which are dyes used in magnetic resonance imaging (MRI). This association primarily occurs in individuals with pre-existing kidney disease. The kidneys are responsible for clearing GBCAs from the body, and when kidney function is impaired, the contrast agent remains in the bloodstream for a longer duration. This prolonged presence is thought to increase the risk of free gadolinium ions being released from the contrast agent, which can then deposit in tissues and trigger the fibrotic process.
Patients with moderate to severe kidney disease, including those on dialysis or who have undergone kidney transplantation with compromised renal function, face the highest risk. The risk is particularly elevated with older, less stable Group 1 GBCAs. While the connection to gadolinium and kidney impairment is well-established, other factors may also contribute to the risk. These include conditions that promote inflammation, such as recent surgery, infection, or blood-clotting problems, though their exact role is less confirmed.
Recognizing Symptoms and Diagnosis
The primary symptoms of NFD involve changes to the skin. Individuals typically experience thickening and hardening of the skin, often beginning on the extremities and potentially spreading to the trunk. The affected skin may develop a firm, “woody” texture or an orange peel appearance (peau d’orange). Other skin manifestations can include red or darkened patches, itchiness, burning sensations, and a shiny appearance.
Beyond skin changes, NFD can lead to functional limitations. The hardening of skin around joints may cause stiffness, pain, and restricted movement, potentially leading to joint contractures. Diagnosis involves a comprehensive evaluation, including patient history focusing on GBCA exposure and kidney function, and a physical examination. The definitive diagnostic tool is a skin biopsy, which reveals a proliferation of fibroblast-like cells and increased deposition of collagen and other fibrous tissue within the dermis.
Current Approaches to Management
There is currently no cure for NFD, and management primarily focuses on supportive care to alleviate symptoms and prevent disease progression. Improving kidney function is an objective, as this can sometimes stabilize or even improve the condition. This may involve optimizing dialysis treatments or, in suitable cases, considering a kidney transplant. Physical therapy plays a role in maintaining mobility and reducing the severity of joint contractures caused by skin tightening.
Various experimental therapies have been explored. These approaches include phototherapy and immunomodulators. Other treatments investigated include medications like imatinib, pentoxifylline, and sodium thiosulfate, as well as procedures like extracorporeal photopheresis.
The prognosis for NFD can vary. The disease may stabilize or improve, particularly with kidney function recovery, but it can also be progressive and debilitating. Early diagnosis and strict avoidance of high-risk GBCAs in susceptible patients are important in preventing the condition or limiting its severity.