Nephrogenic fibrosing dermopathy is a very rare and emerging connective tissue disorder associated with the use of gadolinium-based contrast media in patients with renal disease. In addition to the skin, the connective tissue of muscles and internal organs is often affected. The disease can lead to severe mobility restrictions and even death.
What is nephrogenic fibrosing dermopathy?
Nephrogenic fibrosing dermopathy was first discovered in 1997 when a pathological proliferation of the connective tissue of the skin was found in individual patients with renal insufficiency. A connection with the use of gadolinium-based contrast agents in MRI was established fairly quickly. However, the term “nephrogenic fibrosing dermopathy” is already outdated. See phonejust for Meteorism Meaning.
The name was changed to nephrogenic systemic fibrosis (NSF) after it could be shown that the muscles and many internal organs such as the heart, liver or lungs are also often involved. Another term is dialysis-associated systemic fibrosis, although it has recently been questioned that only dialysis patients are affected. Around 315 cases have been observed so far.
The exact formation mechanism of NSF is not yet known. According to previous observations, only patients with renal insufficiency are affected by nephrogenic systemic fibrosis, who, according to recent findings, do not necessarily have to be on dialysis. According to current knowledge, the use of gadolinium-containing contrast agents in patients with healthy kidneys has never led to NSF.
Due to the small number of cases, no general statement on the chances of recovery could be made. While there are individual cases with a very favorable course, no improvement could be achieved in other cases.
Causes
As already mentioned, a prerequisite for the development of nephrogenic systemic fibrosis is renal insufficiency and the use of gadolinium-containing contrast agents in MRI. Gadolinium is a chemical element from the group of rare earths and belongs to the lanthanides. Due to its many unpaired electrons, it is paramagnetic and therefore very well suited for use in magnetic resonance imaging.
For example, contrast media containing gadolinium are used to visualize the brain or other organs during MRI examinations. The toxicity of free gadolinium ions is well known. However, this element is fixed by complex formation, so that it can usually be used without problems. The acute toxicity of free gadolinium ions is based on the fact that they can be exchanged for calcium ions.
In addition, iodine-based contrast media cannot be used in patients with renal insufficiency because they would impair the kidney function even more. However, nephrogenic systemic fibrosis has now been induced in some patients with kidney disease after the use of gadolinium-based contrast agents. The role played by the connection between renal dysfunction and gadolinium is not yet known.
It is assumed that in these patients even a small release of gadolinium ions from the chelate complex induces increased fibrosis of the connective tissue. The onset of nephrogenic systemic fibrosis can range from two days to 18 months after contrast agent administration. It is assumed that the risk of NSF development depends on the degree of gadolinium ion release. Therefore, according to the European Committee for Medicinal Products for Human Use (CHMP), gadolinium-based contrast media are divided into three risk groups: low, medium or high.
Symptoms, Ailments & Signs
Nephrogenic systemic fibrosis affects women and men equally. Red and dark nodules or spots on the hands and feet may initially appear within two days and 18 months after a gadolinium-based contrast agent procedure. As the disease progresses, thickening of the skin develops. The skin hardens and then resembles an orange peel.
These changes often affect the entire trunk, leaving the neck and head mostly bare. Muscles, ligaments and tendons contract. Movement is becoming more and more restricted. Eventually, some patients are only able to get around using a wheelchair. If the heart or lungs are affected, the prognosis is often very unfavorable. Deaths have already been observed.
Diagnosis & course of disease
Nephrogenic systemic fibrosis can be diagnosed by skin and muscle biopsy. However, the changes cannot be verified by specific deviations from laboratory values. A possible scleromyxedema is excluded in the differential diagnosis in the absence of paraproteins. Otherwise, the tissue samples show a significant thickening of the dermis. After an extensive anamnesis, a connection with gadolinium-based contrast agents is established.
Complications
Nephrogenic fibrosing dermopathy is already a very rare complication in patients with severely impaired renal function or in liver transplant recipients who are undergoing MRI scans with gadolinium-based contrast agents. The course of the disease cannot be predicted. In addition to very rare spontaneous healing, a progressive course is usually observed, which causes severe disabilities.
Fatal outcomes can also occur. The gradual thickening of the skin can involve the heart muscle, lungs, diaphragm or skeletal muscles. In addition to restricted mobility, shortness of breath and severe heart problems can also occur. In cases with complete healing, the renal insufficiency was usually successfully treated beforehand.
It is not known whether nephrogenic fibrosing dermopathy always develops when the gadolinium-based contrast agent is used to diagnose severe renal insufficiency. However, since the risk exists, other contrast agents should be used in these patients or dialysis should be followed immediately after contrast agent use with gadolinium.
So far, it has also not been sufficiently clarified whether eliminating gadolinium with the help of intravenous administration of sodium thiosulfate always leads to an improvement in symptoms. Various treatment successes have been achieved here, but there is no guarantee. The same is true for the chances of physical therapy being successful in preventing contractures (shrinkage) of muscles, tendons, ligaments and other parts of the connective tissue that lead to restricted movement.
When should you go to the doctor?
People who are being treated by a doctor for kidney disease and who have been confronted with the use of a contrast agent belong to the risk group of nephrogenic fibrosing dermopathy. You should seek consultation with the attending physician as soon as various complaints arise after a session and the general state of health deteriorates significantly. The first irregularities often appear a few days after the treatment. In some cases, the first signs of an irregularity may only appear after 1 ½ years. Changes in the appearance of the skin and the connective tissue indicate a disorder and should be presented to a doctor.
A doctor is needed if there are restrictions on mobility, a decrease in general muscle strength or problems with locomotion. Patients are often no longer able to move around without outside help. Since the disease can lead to premature death in severe cases, a doctor is needed as soon as the first indications of a discrepancy arise. General functional disorders, a feeling of illness and malaise should be examined. If existing symptoms increase significantly in scope and intensity, a doctor is needed. Medical help is required for pain, sleep disturbances, loss of appetite and irregular heart rhythm.
Treatment & Therapy
The course of nephrogenic systemic fibrosis cannot be predicted. In very rare cases, the symptoms completely regressed. Improvement has been achieved in some patients by restoring kidney function. Spontaneous regression of the skin changes was also observed in some cases after kidney transplants.
It is also suspected that the intravenous injection of sodium thiosulphate contributes to improvement. Sodium thiosulfate forms chelate complexes with gadolinium ions, potentially promoting their elimination from the body. However, there is currently no effective therapy for most patients. Intensive physical therapy is therefore recommended for the symptomatic treatment of skin hardening.
Outlook & Forecast
The prognosis of nephrogenic fibrosing dermopathy must be made according to the individual circumstances. The general course of the disease is unpredictable in this disease. In many cases, the stage of the disease and the existing symptoms are decisive. If organic damage has already occurred, further development is worse. According to the current scientific status, there is no uniform treatment measure that is generally used for this disease. Doctors decide which therapies are necessary based on individual developments.
Spontaneous resolution of existing symptoms can be observed in some patients. However, these do not have to be permanent. The need for a donor organ and lifelong functional disorders are more likely in the further course. It is also to be expected that the affected person may die prematurely. The development of a medical emergency has been documented in some patients. Without treatment, the life expectancy of those affected is reduced. At the same time, a reduction in quality of life can be observed.
With comprehensive medical care, on the other hand, there is a chance of recovery. Cases can be found in the literature in which the disease was successfully cured. They had previously been treated for renal failure. This seems to be a decisive factor for the course of the disease and thus for the prognosis.
Prevention
Gadolinium-based contrast media should be avoided as far as possible in patients with renal insufficiency. However, if this is not possible, preventive measures that prevent the release of gadolinium ions are very important. The Federal Institute for Drugs and Medical Devices (BfArM) already reacted in May 2007.
Because of the incidents, it has withdrawn approval for risky gadolinium-based contrast agents such as Omniscan and Magnevist for patients with severe kidney failure or for liver transplant patients . Low-risk contrast media should be used. These are gadolinium-containing substances with a cyclic structure that are less likely to release gadolinium.
Aftercare
There is no direct follow-up care for nephrogenic fibrosing dermopathy. Since there is no known therapy for the disease, only the symptoms can be observed and treated. The hardening of the connective tissue can be reduced, among other things, by regular treatments with heat and massages. Patients may be prescribed sodium sulfate to slow disease progression.
If a patient has received a kidney transplant, he must regularly take immunosuppressants and go for check-ups. These examinations determine, among other things, whether the kidney functions have improved. At the same time, the doctor checks whether new connective tissue has formed or whether the ability to move limbs has decreased.
As symptoms of nephrogenic fibrosing dermopathy worsen, patients gradually lose mobility. They are then dependent on intensive care. In the follow-up care, the main aim is to alleviate suffering such as breathing difficulties and pain. At this stage, therapeutic approaches that would unnecessarily burden the patient are avoided. Assisted physiotherapy with very little stress is only intended to prevent patients from bed sores. An improvement in mobility is no longer possible.
You can do that yourself
The symptoms of nephrogenic fibrosing dermopathy must be closely observed in order to do something about them in good time. Patients with renal insufficiency in particular should point this out to their doctor in order to avoid breathing or heart problems. Any irregularities can still appear 18 months later.
If there are changes in the complexion and connective tissue, it is important to see a doctor as soon as possible. Other signs of aggravation include reduced mobility, weakening of the muscles and difficulty in moving. Patients should ask for help if they are unable to move properly. A doctor knows what to do against loss of appetite, cardiac arrhythmia, pain and sleep problems. His tips help patients to cope with everyday life and not to be too restricted by the nephrogenic fibrosing dermopathy.
The exact course and the treatment methods cannot always be foreseen. That is why it is so important to observe your own body closely. In addition to the treatment recommended by the doctor, those affected should also find out about physical therapy. With the consistent implementation of these methods, the hardening of the skin and connective tissue can be alleviated.
