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Nephrogenic Systemic Fibrosis Treatment & Management

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
Updated: Feb 08, 2016

Medical Care

Nephrogenic systemic fibrosis (NSF) is usually a chronic, progressive condition. Rare cases of partial-to-complete spontaneous resolution have been reported in the absence of specific therapy, with the return of renal function. A favorable response to medical intervention is anecdotal. Of all treatments, extracorporeal photopheresis (ECP) seems to provide the best, albeit mild and extremely expensive, treatment modality for nephrogenic systemic fibrosis.

In one patient, ECP resulted in some improvement in skin texture.[58]

In 2011, Elmholdt noted that low-dose oral imatinib mesylate slightly improved skin texture but not joint mobility in patients with nephrogenic systemic fibrosis.[59]

In 2005, Schmook et al[60] reported on successful treatment of nephrogenic systemic fibrosis with photodynamic therapy in a kidney transplant recipient.

In 2004, Kafi et al[61] found that UV-A1 phototherapy improves nephrogenic systemic fibrosis.

Läuchli et al,[62] in 2004, described the case of a 40-year-old woman with renal insufficiency who was treated with hemodialysis and who had undergone kidney transplantation. Two years after transplantation, she developed sclerodermiform brownish plaques on her extremities. The induration improved significantly after 4 cycles of ECP.

Also in 2004, Chung and Chung[63] found that nephrogenic systemic fibrosis responded to high-dose intravenous immunoglobulin.

Wahba et al[64] suggest that UV light therapy has a role in the treatment of nephrogenic systemic fibrosis, based on 2 cases with which they were involved.

Another report noted that patients had no benefit from plasma exchange, intralesional triamcinolone, or intralesional methotrexate.

A trial of localized psoralen plus UV-A treatment in one patient produced no improvement. Oral prednisone (60 mg PO qd) has been effective in several cases, but it has been discontinued in some patients because of its adverse effects.

In 1 of 2 patients, intralesional alpha interferon (3 MU 3 times weekly) improved the skin, although in both patients, it had to be discontinued because of its adverse effects. In another patient, this therapy was associated with a worsening of lesions.

A small series of patients with dual liver/kidney transplants showed marked improvement with plasmapheresis. As renal function had improved posttransplant, the contribution of plasmapheresis to the improvement of cutaneous findings is not clear.

Cyclophosphamide has shown no efficacy in several patients.

Topical calcipotriene (Dovonex) under occlusion has resulted in subjective improvement in 2 patients. Calcipotriene plus betamethasone dipropionate (Taclonex) seemingly might have a role in topical treatment for nephrogenic systemic fibrosis.

Richmond et al[65] noted 8 patients with nephrogenic systemic fibrosis, 5 of whom were treated with ECP for a mean number of 34 treatment sessions over a mean of 8.5 months. Mildly improved skin tightening, range of motion, and/or functional capacity were achieved.

Yerram et al[66] reported on a patient who had nephrogenic systemic fibrosis and had multiple previous exposures to gadolinium (Gd3+)–based MRI studies and experienced a substantial decrease in pain and skin changes after a trial of intravenous sodium thiosulfate.

In 2008, Kreuter et al found limited effects of UV-A1 phototherapy in 3 patients with nephrogenic systemic fibrosis.[67]


Surgical Care

Surgical care has no role in the treatment of this condition. Although surgical care has no direct role in the treatment of nephrogenic systemic fibrosis, patients who have undergone successful kidney transplantation may show resolution of the lesions. Nephrogenic systemic fibrosis is not a contraindication to transplantation; however, because of reports of associated thrombotic events and early graft loss, evaluation for hypercoagulability should be performed.



A dermatologist should assess the patient. The consultation is usually referred by a nephrologist. A dermatopathologist should be requested to review the biopsy material, and the suspicion of nephrogenic systemic fibrosis should be clearly indicated on the accession form.



This disease can result in limited movement. Although the role for physical therapy has not been studied, it would appear intuitive to be useful in patients who are affected.

Contributor Information and Disclosures

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.


Shawn Cowper, MD Director, NSF Registry Project, Associate Professor, Departments of Dermatology and Pathology, Yale University School of Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bracco pharmaceuticals; Ecron-Acunova.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Carrie L Kovarik, MD Assistant Professor of Dermatology, Dermatopathology, and Infectious Diseases, University of Pennsylvania School of Medicine

Carrie L Kovarik, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

  1. Wahba IM, Simpson EL, White K. Gadolinium is not the only trigger for nephrogenic systemic fibrosis: insights from two cases and review of the recent literature. Am J Transplant. 2007 Oct. 7(10):2425-32. [Medline].

  2. Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol. 2006 Sep. 17(9):2359-62. [Medline].

  3. Ross C, De Rosa N, Marshman G, Astill D. Nephrogenic systemic fibrosis in a gadolinium-naïve patient: successful treatment with oral sirolimus. Australas J Dermatol. 2015 Aug. 56 (3):e59-62. [Medline].

  4. Larson KN, Gagnon AL, Darling MD, Patterson JW, Cropley TG. Nephrogenic Systemic Fibrosis Manifesting a Decade After Exposure to Gadolinium. JAMA Dermatol. 2015 Oct. 151 (10):1117-20. [Medline].

  5. Idée JM, Fretellier N, Robic C, Corot C. The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update. Crit Rev Toxicol. 2014 Nov. 44(10):895-913. [Medline].

  6. Cowper SE, Kuo PH, Bucala R. Nephrogenic systemic fibrosis and gadolinium exposure: association and lessons for idiopathic fibrosing disorders. Arthritis Rheum. 2007 Oct. 56(10):3173-5. [Medline].

  7. Yokoyama Y, Takeuchi Y, Monma F, Suzuki T, Ishikawa O Motegi S, Okada E, et al. Role of endothelin-1/endothelin receptor signaling in fibrosis and calcification in nephrogenic systemic fibrosis. Exp Dermatol. 2014 Sep. 23(9):664-9. [Medline].

  8. Wermuth PJ, Jimenez SA. Gadolinium Compounds Signaling through TLR 4 and TLR 7 in Normal Human Macrophages: Establishment of a Proinflammatory Phenotype and Implications for the Pathogenesis of Nephrogenic Systemic Fibrosis. J Immunol. 2012 Jul 1. 189:318-27. [Medline].

  9. Thomsen HS, Marckmann P, Logager VB. Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents. Cancer Imaging. 2007 Sep 24. 7:130-7. [Medline].

  10. Bongartz G, Kucharczyk W. Nephrogenic systemic fibrosis: Summary of the special symposium. J Magn Reson Imaging. 2007. 26:1179-81.

  11. Thomsen HS, Morcos SK, Almén T, Bellin MF, Bertolotto M, Bongartz G, et al. Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines. Eur Radiol. 2013 Feb. 23:307-18. [Medline].

  12. Taupitz M, Stolzenburg N, Ebert M, Schnorr J, Hauptmann R, Kratz H, et al. Gadolinium-containing magnetic resonance contrast media: investigation on the possible transchelation of Gd(3+) to the glycosaminoglycan heparin. Contrast Media Mol Imaging. 2013. 8:108-16. [Medline].

  13. Goveia M, Chan BP, Patel PR. Evaluating the role of recombinant erythropoietin in nephrogenic systemic fibrosis. J Am Acad Dermatol. 2007 Oct. 57(4):725-7. [Medline].

  14. Saab G. Epoetin and nephrogenic systemic fibrosis. J Am Acad Dermatol. 2008 Jan. 58(1):174-5. [Medline].

  15. Gibson SE, Farver CF, Prayson RA. Multiorgan involvement in nephrogenic fibrosing dermopathy: an autopsy case and review of the literature. Arch Pathol Lab Med. 2006 Feb. 130(2):209-12. [Medline].

  16. Brown H. Gadodiamide, NSF: Direct Link Identified. Skin and Allergy News. 2007 Dec.

  17. Parsons AC, Yosipovitch G, Sheehan DJ, Sangueza OP, Greenberg CS, Sane DC. Transglutaminases: the missing link in nephrogenic systemic fibrosis. Am J Dermatopathol. 2007 Oct. 29(5):433-6. [Medline].

  18. Edward M, Fitzgerald L, Thind C, Leman J, Burden AD. Cutaneous mucinosis associated with dermatomyositis and nephrogenic fibrosing dermopathy: fibroblast hyaluronan synthesis and the effect of patient serum. Br J Dermatol. 2007 Mar. 156(3):473-9. [Medline].

  19. Reimer P, Vosshenrich R. Contrast agents in radiology : Current agents approved, recommendations, and safety aspects. Radiologe. 2013 Jan 24. [Medline].

  20. Bose C, Megyesi JK, Shah SV, Hiatt KM, Hall KA, Karaduta O, et al. Evidence Suggesting a Role of Iron in a Mouse Model of Nephrogenic Systemic Fibrosis. PLoS One. 2015. 10 (8):e0136563. [Medline].

  21. Mackay-Wiggan JM, Cohen DJ, Hardy MA, Knobler EH, Grossman ME. Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease). J Am Acad Dermatol. 2003 Jan. 48(1):55-60. [Medline].

  22. McNeill AM, Barr RJ. Scleromyxedema-like fibromucinosis in a patient undergoing hemodialysis. Int J Dermatol. 2002 Jun. 41(6):364-7. [Medline].

  23. Jimenez SA, Artlett CM, Sandorfi N, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum. 2004 Aug. 50(8):2660-6. [Medline].

  24. Ortonne N, Lipsker D, Chantrel F, Boehm N, Grosshans E, Cribier B. Presence of CD45RO+ CD34+ cells with collagen synthesis activity in nephrogenic fibrosing dermopathy: a new pathogenic hypothesis. Br J Dermatol. 2004 May. 150(5):1050-2. [Medline].

  25. Kucher C, Xu X, Pasha T, Elenitsas R. Histopathologic comparison of nephrogenic fibrosing dermopathy and scleromyxedema. J Cutan Pathol. 2005 Aug. 32(7):484-90. [Medline].

  26. Deo A, Fogel M, Cowper SE. Nephrogenic systemic fibrosis: a population study examining the relationship of disease development to gadolinium exposure. Clin J Am Soc Nephrol. 2007 Mar. 2(2):264-7. [Medline].

  27. Todd DJ, Kagan A, Chibnik LB, Kay J. Cutaneous changes of nephrogenic systemic fibrosis: predictor of early mortality and association with gadolinium exposure. Arthritis Rheum. 2007 Oct. 56(10):3433-41. [Medline].

  28. Hubbard V, Davenport A, Jarmulowicz M, Rustin M. Scleromyxoedema-like changes in four renal dialysis patients. Br J Dermatol. 2003 Mar. 148(3):563-8. [Medline].

  29. Khor LK, Tan KB, Loi HY, Lu SJ. Nephrogenic Systemic Fibrosis in a Patient With Renal Failure Demonstrating a "Reverse Superscan" on Bone Scintigraphy. Clin Nucl Med. 2013 Jan 24.:[Medline].

  30. Elmholdt TR, Olesen AB, Jørgensen B, Kvist S, Skov L, Thomsen HS, et al. Nephrogenic systemic fibrosis in denmark- a nationwide investigation. PLoS One. 2013 Dec 9. 8(12):e82037. [Medline].

  31. Amet S, Launay-Vacher V, Clément O, Frances C, Tricotel A, Stengel B, et al. Incidence of nephrogenic systemic fibrosis in patients undergoing dialysis after contrast-enhanced magnetic resonance imaging with gadolinium-based contrast agents: the prospective fibrose nephrogenique systémique study. Invest Radiol. 2014 Feb. 49(2):109-15. [Medline].

  32. Cowper SE, Su LD, Bhawan J, Robin HS, LeBoit PE. Nephrogenic fibrosing dermopathy. Am J Dermatopathol. 2001 Oct. 23(5):383-93. [Medline].

  33. Jan F, Segal JM, Dyer J, LeBoit P, Siegfried E, Frieden IJ. Nephrogenic fibrosing dermopathy: two pediatric cases. J Pediatr. 2003 Nov. 143(5):678-81. [Medline].

  34. Weller A, Barber JL, Olsen OE. Gadolinium and nephrogenic systemic fibrosis: an update. Pediatr Nephrol. 2013 Oct 22.

  35. Hancox JG, Mengesha YM, Sangueza OP, Yosipovitch G. Nephrogenic fibrosing dermopathy after five days of hemodialysis. J Drugs Dermatol. 2003 Oct. 2(5):550-3. [Medline].

  36. Ruiz-Genao DP, Pascual-Lopez MP, Fraga S, Aragues M, Garcia-Diez A. Osseous metaplasia in the setting of nephrogenic fibrosing dermopathy. J Cutan Pathol. 2005 Feb. 32(2):172-5. [Medline].

  37. Obermoser G, Emberger M, Wieser M, Zelger B. Nephrogenic fibrosing dermopathy in two patients with systemic lupus erythematosus. Lupus. 2004. 13(8):609-12. [Medline].

  38. Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve. 2004 Nov. 30(5):569-77. [Medline].

  39. Hauser C, Kaya G, Chizzolini C. Nephrogenic fibrosing dermopathy in a renal transplant recipient with tubulointerstitial nephritis and uveitis. Dermatology. 2004. 209(1):50-2. [Medline].

  40. Glaich AS, Martinelli PT, Markus RF, Hsu S. Generalized elastolysis following nephrogenic fibrosing dermopathy. J Am Acad Dermatol. 2005 Jul. 53(1):174-6. [Medline].

  41. Kucher C, Steere J, Elenitsas R, Siegel DL, Xu X. Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis with diaphragmatic involvement in a patient with respiratory failure. J Am Acad Dermatol. 2006 Feb. 54(2 Suppl):S31-4. [Medline].

  42. Edward M, Fitzgerald L, Thind C, Leman J, Burden AD. Cutaneous mucinosis associated with dermatomyositis and nephrogenic fibrosing dermopathy: fibroblast hyaluronan synthesis and the effect of patient serum. Br J Dermatol. 2007 Mar. 156(3):473-9. [Medline].

  43. Saenz A, Mandal R, Kradin R, Hedley-Whyte ET. Nephrogenic fibrosing dermopathy with involvement of the dura mater. Virchows Arch. 2006 Sep. 449(3):389-91. [Medline].

  44. Naylor E, Hu S, Robinson-Bostom L. Nephrogenic systemic fibrosis with septal panniculitis mimicking erythema nodosum. J Am Acad Dermatol. 2008 Jan. 58(1):149-50. [Medline].

  45. Keyrouz S, Rudnicki SA. Neuromuscular involvement in nephrogenic systemic fibrosis. J Clin Neuromuscul Dis. 2007 Dec. 9(2):297-302. [Medline].

  46. Sanchez-Ross M, Snyder R, Colome-Grimmer MI, Blumberg M, Huttenbach Y, Raimer S. Nephrogenic fibrosing dermopathy in a patient with systemic lupus erythematosus and acute lupus nephritis. Pediatr Dermatol. 2007 Sep-Oct. 24(5):E36-9. [Medline].

  47. Goddard DS, Magee CC, Lazar AJ, Miller DM. Nephrogenic fibrosing dermopathy with recurrence after allograft failure. J Am Acad Dermatol. 2007 May. 56(5 Suppl):S109-11. [Medline].

  48. High WA, Ayers RA, Cowper SE. Gadolinium is quantifiable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol. 2007 Apr. 56(4):710-2. [Medline].

  49. Gathings RM, Reddy R, Santa Cruz D, Brodell RT. Gadolinium-Associated Plaques: A New, Distinctive Clinical Entity. JAMA Dermatol. 2014 Nov 12. [Medline].

  50. Ross C, De Rosa N, Marshman G, Astill D. Nephrogenic systemic fibrosis in a gadolinium-naïve patient: Successful treatment with oral sirolimus. Australas J Dermatol. 2014 Oct 21. [Medline].

  51. Smorodinsky E, Ansdell DS, Foster ZW, Mazhar SM, Cruite I, Wolfson T, et al. Risk of nephrogenic systemic fibrosis is low in patients with chronic liver disease exposed to gadolinium-based contrast agents. J Magn Reson Imaging. 2014 May 9. [Medline].

  52. Nguyen CV, Boyle AM, Lee RA. Perforating osteoma cutis in the setting of longstanding nephrogenic systemic fibrosis. Int J Dermatol. 2014 Jun 25. [Medline].

  53. Solomon GJ, Wu E, Rosen PP. Nephrogenic systemic fibrosis mimicking inflammatory breast carcinoma. Arch Pathol Lab Med. 2007 Jan. 131(1):145-8. [Medline].

  54. Saab G, Cheng S. Nephrogenic systemic fibrosis: a nephrologist's perspective. Hemodial Int. 2007 Oct. 11 Suppl 3:S2-6. [Medline].

  55. Gadolinium-based Contrast Agents: Class Labeling Change - Risk of Nephrogenic Systemic Fibrosis. US Food and Drug Administration. September 9, 2010. Available at

  56. Thakral C, Abraham JL. Automated scanning electron microscopy and x-ray microanalysis for in situ quantification of gadolinium deposits in skin. J Electron Microsc (Tokyo). 2007 Oct. 56(5):181-7. [Medline].

  57. Christensen KN, Lee CU, Hanley MM, Leung N, Moyer TP, Pittelkow MR. Quantification of gadolinium in fresh skin and serum samples from patients with nephrogenic systemic fibrosis. J Am Acad Dermatol. 2011 Jan. 64(1):91-6. [Medline].

  58. Kintossou R, D'Incan M, Chauveau D, et al. [Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis: role of gadolinium?]. Ann Dermatol Venereol. 2007 Aug-Sep. 134(8-9):667-71. [Medline].

  59. Elmholdt TR, Buus NH, Ramsing M, Olesen AB. Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: an open-label non-randomized, uncontrolled clinical trial. J Eur Acad Dermatol Venereol. 2011 Dec 20. [Medline].

  60. Schmook T, Budde K, Ulrich C, Neumayer HH, Fritsche L, Stockfleth E. Successful treatment of nephrogenic fibrosing dermopathy in a kidney transplant recipient with photodynamic therapy. Nephrol Dial Transplant. 2005 Jan. 20(1):220-2. [Medline].

  61. Kafi R, Fisher GJ, Quan T, et al. UV-A1 phototherapy improves nephrogenic fibrosing dermopathy. Arch Dermatol. 2004 Nov. 140(11):1322-4. [Medline].

  62. Lauchli S, Zortea-Caflisch C, Nestle FO, Burg G, Kempf W. Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis. Dermatology. 2004. 208(3):278-80. [Medline].

  63. Chung HJ, Chung KY. Nephrogenic fibrosing dermopathy: response to high-dose intravenous immunoglobulin. Br J Dermatol. 2004 Mar. 150(3):596-7. [Medline].

  64. Wahba IM, White K, Meyer M, Simpson EL. The case for ultraviolet light therapy in nephrogenic fibrosing dermopathy--report of two cases and review of the literature. Nephrol Dial Transplant. 2007 Feb. 22(2):631-6. [Medline].

  65. Richmond H, Zwerner J, Kim Y, Fiorentino D. Nephrogenic systemic fibrosis: relationship to gadolinium and response to photopheresis. Arch Dermatol. 2007 Aug. 143(8):1025-30. [Medline].

  66. Yerram P, Saab G, Karuparthi PR, Hayden MR, Khanna R. Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure--role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate. Clin J Am Soc Nephrol. 2007 Mar. 2(2):258-63. [Medline].

  67. Kreuter A, Gambichler T, Weiner SM, Schieren G. Limited effects of UV-A1 phototherapy in 3 patients with nephrogenic systemic fibrosis. Arch Dermatol. 2008 Nov. 144(11):1527-9. [Medline].

  68. Marckmann P, Nielsen AH, Sloth JJ. Possibly enhanced Gd excretion in dialysate, but no major clinical benefit of 3-5 months of treatment with sodium thiosulfate in late stages of nephrogenic systemic fibrosis. Nephrol Dial Transplant. 2008 Oct. 23(10):3280-2. [Medline].

  69. Zou Z, Zhang HL, Roditi GH, Leiner T, Kucharczyk W, Prince MR. Nephrogenic systemic fibrosis: review of 370 biopsy-confirmed cases. JACC Cardiovasc Imaging. 2011 Nov. 4:1206-16. [Medline].

  70. Scheinfeld N. Nephrogenic fibrosing dermopathy: a comprehensive review for the dermatologist. Am J Clin Dermatol. 2006. 7(4):237-47. [Medline].

Nephrogenic fibrosing dermopathy on the abdomen, demonstrating a peau d'orange appearance.
Nephrogenic systemic fibrosis on the abdomen, demonstrating a peau d'orange appearance. A keloid from a previous surgery is present.
Nephrogenic systemic fibrosis on the leg, demonstrating a bound-down and sclerotic appearance and texture.
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