Treatment of Nephrogenic Systemic Fibrosis

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): Has had some efficacy in doses of 1 mg/kg po qd. 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, sometimes creating a rapid calcium-wasting state. It is not clear whether the prednisone is affecting the cutaneous disease, or the renal disease, but it does seem to work in a subset of patients.
Topical Dovonex (under occlusion): So far, responses have been anecdotal and largely subjective. Some patients report improvement in localized disease. The combination of occluded dovonex and clobetasol with vascular compression stockings has reportedly been of benefit.
Extracorporeal photopheresis (ECP): 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. This report corroborates other anecdotal reports in the US that photopheresis is helpful in a subset of patients. 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: 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: Anecdotally, this medication has shown no improvement in a number of NSF patients.
Thalidomide: 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. There have been two reports among Registry patients of development of NSF in patients already taking thalidomide for other medical problems.

Ultraviolet therapy: I am aware of anecdotal use of PUVA, but have heard no reports of success. Article 38 discusses the use of UVA-1, evidently beneficial in the single case in this report. PUVA in combination with Soriatane and prednisone has been anecdotally helpful in two patients.
Physical therapy (PT): Some patients have reported that physical therapy, in particular, swimming, may be helpful in slowing the progression of joint contractures. 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): A recent report describes two NSF patients who received 1200 mg per day of oral pentoxifylline (ref 57). Both patients stabilized, and the one with less severe disease improved somewhat. The use of PXF is theoretically justified as it has known antifibrotic activity (thought to be at least partially related to TNF alpha antagonism). In addition, PXF is known to improve red blood cell flexibility, and therefore to improve circulation. As thrombosis 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 Therapy: Reference number 25 describes a patient who 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. I have heard anecdotal information suggesting this therapy has been helpful in one other patient with NSF. Additional anecdotal data have been less promising.