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MRI Can Lead to Incurable Disease Part IV

Tuesday, 4th November 2008

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Gadolinium injection used to get a better MRI image can cause a rare disease known as nephrogenic fibrosing dermopathy (NFD) or  nephrogenic systemic fibrosis (NSF) in people with kidney problems.

NFD/NSF: What Are The Treatment options?

While there is no consistently successful treatment for NSF, improving renal function (due to any modality) seems to slow or arrest NSF (and in many cases allows for gradual reversal of the process over time).

Critical assessment of the effects of any investigational therapy requires careful attention *and reporting* of the patient’s renal function during therapy. Investigational therapies that show objective improvement in the setting of worsening or stable chronic renal failure should be targeted for further investigation. Therapies that show improvement of NSF while renal function is improving may or may not be contributing to the observed improvement. Given the recent association of NSF with gadolinium administration, any reports of investigational therapies should also clearly indicate whether gadolinium was administered during the therapeutic evaluation, and whether there was an identifiable clinical change in the patient’s disease.

Treatments that have been tried and continue to be investigated include:

Oral steroids (prednisone):  Patients with concurrent diabetes should be aware of the risks of hyperglycemia while taking this medication. All patients should be aware of the possibility of gastrointestinal ulceration while taking prednisone. In addition, osteoporosis is often accelerated while taking this medication.

Topical Dovonex (Dovonex is an ointment approved by the FDA for treating psoriasis) : So far, responses have been anecdotal and largely subjective. Some patients report improvement in localized disease.

Extracorporeal photopheresis (ECP): (Note: the patient is given certain drugs which are sensitive to the influence of light then the patients blood is run through a device outside the body [extracorporeal] during which the blood is subjected to ultraviolet rays.)  A recent article describes three patients in Europe who  responded with softening of plaques after several courses of ECP. Each of these patients had no improvement in renal function during the treatment. All three of these patients had had NSF for less than one year.  Experience at Yale suggests that patients with longstanding NSF (arbitrarily set at one year) may not respond to this modality. This treatment is currently under investigation, although no formal trials are yet offered. Some insurance carriers are receptive to covering a trial of therapy, but in the event coverage cannot be secured, be advised that therapy is exceedingly expensive. Many patients and providers have reported that Medicare has provided coverage for ECP in recent cases.

Plasmapheresis: (this is a blood purification procedure which removes antibodies from the blood) As with photopheresis this treatment method is extracorporeal meaning the blood is routed out of the body, treated, and then routed back to the body.  One study from Loma Linda University (ref 12) reported improvement in three patients with liver/kidney transplant. Two of these patients were noted to have concurrent improving renal function. It is unclear what contribution improving renal function may have had in the overall clinical improvement. Nevertheless, anecdotally, some persons have reported slight improvement following plasmapheresis. Several others have been reported who noted no improvement at all.

Cytoxan: (this drug is normally used in chemotherapy to treat cancer) Anecdotally, this medication has shown no improvement in a number of NSF patients.

Thalidomide: (Thalidomide was first marketed in the 1950s and a sleeping pill and as a treatment for morning sickeness.  It is now believed to cause birth defects and so is not approved for sale in the U.S. but the FDA allows its usage in certain studied. )  There are no formal reports on the success of this medication in NSF. However, some patients have reported subjective improvement. Long term tolerance of the drug may be an issue, however. .

Ultraviolet therapy: Some anecdotal use but no reports of success.

Physical therapy (PT): Some patients have reported that physical therapy, in particular, swimming, may be helpful in slowing the progression of joint contractures.  (Contractures are joints that are bent but unmovable from scar tissue formation.)  There is no contraindication to PT, and the definite potential up-side suggests that PT should be pursued whenever possible. Deep massage has been reported to be of benefit.

Pentoxifylline (PXF): ( This medication which is also known as Trental decreases the “stickiness” (viscosity) of blood and thereby improves its flow. This increased blood flow helps patients with peripheral arterial disease to obtain better circulation and oxygen delivery to vital tissues. It is used to treat a condition of painful legs that develop with exercise because of inadequate circulation to the legs and feet)   A recent report describes two NSF patients who received 1200 mg per day of oral pentoxifylline . Both patients stabilized, and the one with less severe disease improved somewhat. As thrombosis (blood clotting)  seems to be an inciting event for many NSF patients, this mechanism could also be partially responsible for the improvements noted clinically. Many more patients will need to be treated to further evaluate the efficacy of this drug.

High Dose Intravenous Ig (Immunoglobulin) Therapy: (Immunoglobulins are antibodies found in the human body) One patient showed objective improvements with one cycle of therapy with this medication. Further improvement with additional cycles was not observed. No comment was made regarding the renal status of the patient while receiving this therapy.   There is anecdotal information suggesting this therapy has been helpful in one other patient with NSF. Additional anecdotal data have been less promising.

Kidney transplant: Several patients have improved significantly with a return to normal kidney function (either as a result of transplantation or medical therapy). In other cases, kidney transplant has resulted in no obvious improvement of the lesions, even with a fully functioning, successfully transplanted organ.

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