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Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced renal failure

Authors
Dana Miskulin, MD
Michael R Rudnick, MD
Section Editor
Thomas A Golper, MD
Deputy Editor
Alice M Sheridan, MD

TERMINOLOGY

Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder seen only in patients with kidney failure. It is characterized by two primary features [1,2]:

Thickening and hardening of the skin overlying the extremities and trunk

Marked expansion and fibrosis of the dermis in association with CD34-positive fibrocytes

NSF was originally named nephrogenic fibrosing dermopathy (NFD) because of the characteristic skin findings. However, subsequent studies showed that some patients had fibrosis of deeper structures, including muscle, fascia, lungs, and heart [1]. Because of the systemic findings, nephrogenic systemic fibrosis is preferred to nephrogenic fibrosing dermopathy [3]. (See 'Systemic involvement' below.)

NSF has also been called dialysis-associated systemic fibrosis [4,5]. However, this term is too narrow since the disease is not limited to patients on dialysis [3].

                                 

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Literature review current through: Nov 2016. | This topic last updated: Wed Feb 19 00:00:00 GMT+00:00 2014.
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References
Top
  1. Galan A, Cowper SE, Bucala R. Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy). Curr Opin Rheumatol 2006; 18:614.
  2. Kuo PH, Kanal E, Abu-Alfa AK, Cowper SE. Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. Radiology 2007; 242:647.
  3. Cowper SE, Bucala R, Leboit PE. Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis--setting the record straight. Semin Arthritis Rheum 2006; 35:208.
  4. Jiménez 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; 50:2660.
  5. Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve 2004; 30:569.
  6. Centers for Disease Control and Prevention (CDC). Fibrosing skin condition among patients with renal disease--United States and Europe, 1997-2002. MMWR Morb Mortal Wkly Rep 2002; 51:25.
  7. Cowper SE, Robin HS, Steinberg SM, et al. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000; 356:1000.
  8. Hubbard V, Davenport A, Jarmulowicz M, Rustin M. Scleromyxoedema-like changes in four renal dialysis patients. Br J Dermatol 2003; 148:563.
  9. LeBoit PE. What nephrogenic fibrosing dermopathy might be. Arch Dermatol 2003; 139:928.
  10. Mendoza FA, Artlett CM, Sandorfi N, et al. Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature. Semin Arthritis Rheum 2006; 35:238.
  11. Swartz RD, Crofford LJ, Phan SH, et al. Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure. Am J Med 2003; 114:563.
  12. Cassis TB, Jackson JM, Sonnier GB, Callen JP. Nephrogenic fibrosing dermopathy in a patient with acute renal failure never requiring dialysis. Int J Dermatol 2006; 45:56.
  13. 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; 17:2359.
  14. Dundová I, Treska V, Simanek V, Michal M. Nephrogenic fibrosing dermopathy: a case study. Transplant Proc 2005; 37:4187.
  15. Schmook T, Budde K, Ulrich C, et al. Successful treatment of nephrogenic fibrosing dermopathy in a kidney transplant recipient with photodynamic therapy. Nephrol Dial Transplant 2005; 20:220.
  16. Gilliet M, Cozzio A, Burg G, Nestle FO. Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis. Br J Dermatol 2005; 152:531.
  17. Sadowski EA, Bennett LK, Chan MR, et al. Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 2007; 243:148.
  18. Igreja AC, Mesquita Kde C, Cowper SE, Costa IM. Nephrogenic systemic fibrosis: concepts and perspectives. An Bras Dermatol 2012; 87:597.
  19. The International Center for Nephrogenic Fibrosing Dermopathy Research http://www.icnfdr.org (Accessed on October 10, 2008).
  20. Auron A, Shao L, Warady BA. Nephrogenic fibrosing dermopathy in children. Pediatr Nephrol 2006; 21:1307.
  21. Krefting, Ira, FDA, 2012, personal communication. Presented at: 5th Annual Scientific Symposium on Nephrogenic Systemic Fibrosis and Allied Fibrotic Disorders. May 20, 2011 at the Yale University School of Medicine, New Haven, CT.
  22. Moschella SL, Kay J, Mackool BT, Liu V. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 35-2004. A 68-year-old man with end-stage renal disease and thickening of the skin. N Engl J Med 2004; 351:2219.
  23. Daram SR, Cortese CM, Bastani B. Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis: report of a new case with literature review. Am J Kidney Dis 2005; 46:754.
  24. Cowper SE. Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 2003; 15:785.
  25. Cowper SE, Bucala R, LeBoit PE. Case 35-2004: nephrogenic fibrosing dermopathy. N Engl J Med 2005; 352:1723.
  26. Centers for Disease Control and Prevention (CDC). Nephrogenic fibrosing dermopathy associated with exposure to gadolinium-containing contrast agents--St. Louis, Missouri, 2002-2006. MMWR Morb Mortal Wkly Rep 2007; 56:137.
  27. Perazella MA, Rodby RA. Gadolinium use in patients with kidney disease: a cause for concern. Semin Dial 2007; 20:179.
  28. Reilly RF. Risk for nephrogenic systemic fibrosis with gadoteridol (ProHance) in patients who are on long-term hemodialysis. Clin J Am Soc Nephrol 2008; 3:747.
  29. Joffe P, Thomsen HS, Meusel M. Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Acad Radiol 1998; 5:491.
  30. Schuhmann-Giampieri G, Krestin G. Pharmacokinetics of Gd-DTPA in patients with chronic renal failure. Invest Radiol 1991; 26:975.
  31. Saitoh T, Hayasaka K, Tanaka Y, et al. Dialyzability of gadodiamide in hemodialysis patients. Radiat Med 2006; 24:445.
  32. High WA, Ayers RA, Chandler J, et al. Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 2007; 56:21.
  33. Boyd AS, Zic JA, Abraham JL. Gadolinium deposition in nephrogenic fibrosing dermopathy. J Am Acad Dermatol 2007; 56:27.
  34. High WA, Ayers RA, Cowper SE. Gadolinium is quantifiable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 2007; 56:710.
  35. Schroeder JA, Weingart C, Coras B, et al. Ultrastructural evidence of dermal gadolinium deposits in a patient with nephrogenic systemic fibrosis and end-stage renal disease. Clin J Am Soc Nephrol 2008; 3:968.
  36. Grobner T. Gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006; 21:1104.
  37. http://www.fda.gov/cder/drug/advisory/gadolinium_agents_20061222.htm (Accessed on January 08, 2008).
  38. Elmholdt TR, Pedersen M, Jørgensen B, et al. Nephrogenic systemic fibrosis is found only among gadolinium-exposed patients with renal insufficiency: a case-control study from Denmark. Br J Dermatol 2011; 165:828.
  39. http://www.fda.gov/cder/drug/infoSheets/HCP/gcca_200705.htm (Accessed on October 10, 2008).
  40. Perazella MA. How should nephrologists approach gadolinium-based contrast imaging in patients with kidney disease? Clin J Am Soc Nephrol 2008; 3:649.
  41. 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; 2:264.
  42. Stenver DI. Investigation of the safety of MRI contrast medium Omniscan. Danish Medicines Agency, 29 May 2006. http://www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=8931 (Accessed on March 07, 2007).
  43. Shabana WM, Cohan RH, Ellis JH, et al. Nephrogenic systemic fibrosis: a report of 29 cases. AJR Am J Roentgenol 2008; 190:736.
  44. Broome DR, Girguis MS, Baron PW, et al. Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol 2007; 188:586.
  45. Penfield JG, Reilly RF. Gadolinium and nephrogenic systemic fibrosis: have we overreacted? Semin Dial 2011; 24:480.
  46. Perez-Rodriguez J, Lai S, Ehst BD, et al. Nephrogenic systemic fibrosis: incidence, associations, and effect of risk factor assessment--report of 33 cases. Radiology 2009; 250:371.
  47. Wang Y, Alkasab TK, Narin O, et al. Incidence of nephrogenic systemic fibrosis after adoption of restrictive gadolinium-based contrast agent guidelines. Radiology 2011; 260:105.
  48. Hägele J, Simon M. [Nephrogenic systemic fibrosis (NSF): Effects of stricter guidelines on the use of contrast media containing gadolinium]. Radiologe 2011; 51:831.
  49. Hope TA, High WA, Leboit PE, et al. Nephrogenic systemic fibrosis in rats treated with erythropoietin and intravenous iron. Radiology 2009; 253:390.
  50. Swaminathan S, Ahmed I, McCarthy JT, et al. Nephrogenic fibrosing dermopathy and high-dose erythropoietin therapy. Ann Intern Med 2006; 145:234.
  51. Golding LP, Provenzale JM. Nephrogenic systemic fibrosis: possible association with a predisposing infection. AJR Am J Roentgenol 2008; 190:1069.
  52. Maloo M, Abt P, Kashyap R, et al. Nephrogenic systemic fibrosis among liver transplant recipients: a single institution experience and topic update. Am J Transplant 2006; 6:2212.
  53. Baron PW, Cantos K, Hillebrand DJ, et al. Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis. Am J Dermatopathol 2003; 25:204.
  54. Chow DS, Bahrami S, Raman SS, et al. Risk of nephrogenic systemic fibrosis in liver transplantation patients. AJR Am J Roentgenol 2011; 197:658.
  55. Fazeli A, Lio PA, Liu V. Nephrogenic fibrosing dermopathy: are ACE inhibitors the missing link? Arch Dermatol 2004; 140:1401.
  56. 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; 7:2425.
  57. Cowper SE, Su LD, Bhawan J, et al. Nephrogenic fibrosing dermopathy. Am J Dermatopathol 2001; 23:383.
  58. Wermuth PJ, Del Galdo F, Jiménez SA. Induction of the expression of profibrotic cytokines and growth factors in normal human peripheral blood monocytes by gadolinium contrast agents. Arthritis Rheum 2009; 60:1508.
  59. Swaminathan S, Horn TD, Pellowski D, et al. Nephrogenic systemic fibrosis, gadolinium, and iron mobilization. N Engl J Med 2007; 357:720.
  60. Bellin MF. MR contrast agents, the old and the new. Eur J Radiol 2006; 60:314.
  61. Edsall LC, English JC 3rd, Teague MW, Patterson JW. Calciphylaxis and metastatic calcification associated with nephrogenic fibrosing dermopathy. J Cutan Pathol 2004; 31:247.
  62. Evenepoel P, Zeegers M, Segaert S, et al. Nephrogenic fibrosing dermopathy: a novel, disabling disorder in patients with renal failure. Nephrol Dial Transplant 2004; 19:469.
  63. Kafi R, Fisher GJ, Quan T, et al. UV-A1 phototherapy improves nephrogenic fibrosing dermopathy. Arch Dermatol 2004; 140:1322.
  64. Bangsgaard N, Marckmann P, Rossen K, Skov L. Nephrogenic systemic fibrosis: late skin manifestations. Arch Dermatol 2009; 145:183.
  65. Ting WW, Stone MS, Madison KC, Kurtz K. Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 2003; 139:903.
  66. Kucher C, Steere J, Elenitsas R, et al. Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis with diaphragmatic involvement in a patient with respiratory failure. J Am Acad Dermatol 2006; 54:S31.
  67. 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; 130:209.
  68. Mackay-Wiggan JM, Cohen DJ, Hardy MA, et al. Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease). J Am Acad Dermatol 2003; 48:55.
  69. Girardi M, Kay J, Elston DM, et al. Nephrogenic systemic fibrosis: clinicopathological definition and workup recommendations. J Am Acad Dermatol 2011; 65:1095.
  70. Kucher C, Xu X, Pasha T, Elenitsas R. Histopathologic comparison of nephrogenic fibrosing dermopathy and scleromyxedema. J Cutan Pathol 2005; 32:484.
  71. Cowper SE, Bucala R. Nephrogenic fibrosing dermopathy: suspect identified, motive unclear. Am J Dermatopathol 2003; 25:358.
  72. 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; 56:3433.
  73. The International Center for Nephrogenic Fibrosing Dermopathy Research http://www.icnfdr.org (Accessed on February 19, 2014).
  74. Chrysochou C, Power A, Shurrab AE, et al. Low risk for nephrogenic systemic fibrosis in nondialysis patients who have chronic kidney disease and are investigated with gadolinium-enhanced magnetic resonance imaging. Clin J Am Soc Nephrol 2010; 5:484.
  75. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 2013; 3:5.
  76. Okada S, Katagiri K, Kumazaki T, Yokoyama H. Safety of gadolinium contrast agent in hemodialysis patients. Acta Radiol 2001; 42:339.
  77. Murashima M, Drott HR, Carlow D, et al. Removal of gadolinium by peritoneal dialysis. Clin Nephrol 2008; 69:368.
  78. Ramaizel L, Sliwa JA. Rehabilitation in nephrogenic systemic fibrosis. PM R 2009; 1:684.
  79. Taylor RA, Levine JM, Jimenez SA. Case 35-2004: nephrogenic fibrosing dermopathy. N Engl J Med 2005; 352:1723.
  80. Cuffy MC, Singh M, Formica R, et al. Renal transplantation for nephrogenic systemic fibrosis: a case report and review of the literature. Nephrol Dial Transplant 2011; 26:1099.
  81. Cowper SE. Nephrogenic systemic fibrosis: the nosological and conceptual evolution of nephrogenic fibrosing dermopathy. Am J Kidney Dis 2005; 46:763.
  82. Läuchli S, Zortea-Caflisch C, Nestle FO, et al. Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis. Dermatology 2004; 208:278.
  83. Fisher GJ, Datta S, Wang Z, et al. c-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid. J Clin Invest 2000; 106:663.
  84. Kay J, High WA. Imatinib mesylate treatment of nephrogenic systemic fibrosis. Arthritis Rheum 2008; 58:2543.
  85. Chandran S, Petersen J, Jacobs C, et al. Imatinib in the treatment of nephrogenic systemic fibrosis. Am J Kidney Dis 2009; 53:129.
  86. Robinson MR, Routhouska SB, Paspulati RM, Korman NJ. Alefacept therapy for nephrogenic systemic fibrosis: a case series. J Drugs Dermatol 2011; 10:922.
  87. Yerram P, Saab G, Karuparthi PR, et al. 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; 2:258.
  88. Kadiyala D, Roer DA, Perazella MA. Nephrogenic systemic fibrosis associated with gadoversetamide exposure: treatment with sodium thiosulfate. Am J Kidney Dis 2009; 53:133.
  89. Chung HJ, Chung KY. Nephrogenic fibrosing dermopathy: response to high-dose intravenous immunoglobulin. Br J Dermatol 2004; 150:596.