American Journal of Clinical Dermatology

, Volume 7, Issue 4, pp 237–247 | Cite as

Nephrogenic Fibrosing Dermopathy

A Comprehensive Review for the Dermatologist
Review Article

Abstract

Nephrogenic fibrosing dermopathy (NFD) is an acquired, idiopathic, chronic, progressive eruption of the skin sometimes accompanied by systemic fibrosis that occurs in the context of renal failure. The age of patients with NFD ranges from 8 to 87 years at the time of onset, with a mean age of 46.4 years. Most cases have been reported in the US and Europe, but recently cases have also been reported in India. About 175 cases have been noted in a registry established for NFD patients. Even in the setting of renal disease, NFD still occurs rarely and its cause is unknown. Patients present with hard, indurated, sometimes peau d’orange plaques. They often show a distinctive physical appearance, with elbows and knees angled inward, and most patients complain of a loss of range of motion. Histology demonstrates thickened collagen bundles with surrounding clefts, mucin, and a proliferation of fibroblasts and elastic fibers, sometimes with reticular, dermal, large epithelioid or stellate spindle cells. Fibrosis of NFD can affect the internal organs and thus the term nephrogenic systemic fibrosis has been used by some analysts to describe this fibrosing process. The fibrosis of NFD appears to be due to the effects of a cell referred to as the circulating fibrocyte. Rare cases of partial-to-complete spontaneous resolution have been reported in the absence of specific therapy. Treatments yield inconsistent results and include restoration of renal function, extracorporeal photopheresis, photodynamic therapy, high-dose intravenous immunoglobulin, and other immunosuppressive therapies.

Keywords

Systemic Lupus Erythematosus Idiopathic Pulmonary Fibrosis Nephrogenic Systemic Fibrosis Calcipotriol Alport Syndrome 

Notes

Acknowledgments

No sources of funding were used in the preparation of this review. The author has no conflicts of interest that are relevant to the content of this review.

References

  1. 1.
    Cowper SE, Robin HS, Steinberg SM, et al. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet. 2000; 356: 1000–1PubMedCrossRefGoogle Scholar
  2. 2.
    Cowper SE. The International Center for Nephrogenic Fibrosing Dermopathy Research (ICNFDR). Nephrogenic fibrosing dermopathy [NFD/NSF website], 2001–2006. [online]. Available from URL: http://www.icnfdr.org/ [Accessed 2006 Jul 13]Google Scholar
  3. 3.
    Scheinfeld N, Cowper SE. Nephrogenic fibrosing dermopathy. Emedicine dermatology chapter [online]. Available from URL: http://www.emedicine.com/derm/topic934.htm [Accessed 2005 Sep 1]Google Scholar
  4. 4.
    Neudecker BA, Stern R, Mark LA, et al. Scleromyxedema-like lesions of patients in renal failure contain hyalmonan: a possible pathophysiological mechanism. J Cutan Pathol. 2005; 32: 612–5PubMedCrossRefGoogle Scholar
  5. 5.
    Mackay-Wiggan JM, Cohen DJ, Hardy MA, et al. Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease). J Am Acad Dermalot. 2003; 48: 55–60CrossRefGoogle Scholar
  6. 6.
    Cowper SE. Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol. 2003; 15: 785–90PubMedCrossRefGoogle Scholar
  7. 7.
    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: 754–9PubMedCrossRefGoogle Scholar
  8. 8.
    Leboit PE. What nephrogenic fibrosing dermopathy might be. Arch Dermatol. 2003; 139: 928–30PubMedCrossRefGoogle Scholar
  9. 9.
    McNeill AM, Barr RJ. Scleromyxedema-like fibromucinosis in a patient undergoing hemodialysis. Int J Dermatol. 2002; 41: 364–7PubMedCrossRefGoogle Scholar
  10. 10.
    Cowper SE, Su LD, Bhawan J, et al. Nephrogenic fibrosing dermopathy. Am J Dermatopathol. 2001; 23: 38–93Google Scholar
  11. 11.
    Quan TE, Cowper S, Wu SP, et al. Circulating fibrocytes: collagen-secreting cells of the peripheral blood. Int J Biochem Cell Biol. 2004; 36: 598–606PubMedCrossRefGoogle Scholar
  12. 12.
    Yang L, Scott PG, Giuffre J, et al. Peripheral blood fibrocytes from burn patients: identification and quantification of fibrocytes in adherent cells cultured from peripheral blood mononuclear cells. Lab Invest. 2002; 82: 1183–92PubMedGoogle Scholar
  13. 13.
    Cowper SE, Bucala R. Nephrogenic fibrosing dermopathy: suspect identified, motive unclear [letter]. Am J Dermatopathol. 2003; 25: 358PubMedCrossRefGoogle Scholar
  14. 14.
    Jimenez SA, Artlett CM, Sandorfi N, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor betal expression in affected skin. Arthritis Rheum. 2004; 50: 2660–6PubMedCrossRefGoogle Scholar
  15. 15.
    Ortonne N, Lipsker D, Chantrel F, et al. Presence of CD45RO+ CD34+ cells with collagen synthesis activity in nephrogenic fibrosing dermopathy: a new pathogenic hypothesis. Br J Dermatol. 2004; 150: 1050–2PubMedCrossRefGoogle Scholar
  16. 16.
    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: 563–72PubMedCrossRefGoogle Scholar
  17. 17.
    Fazeli A, Lio PA, Liu V. Nephrogenic fibrosing dermopathy: are ACE inhibitors the missing link? [letter]. Arch Dermatol. 2004; 140: 1401PubMedCrossRefGoogle Scholar
  18. 18.
    Department of Dermatology, Wayne State University School of Medicine. Case 4 — nephrogenic fibrosing dermopathy [online]. Available from URL: http://www.med.wayne.edu/dermatology/MichDerm%200nline%202002/4NEPHROGENIC%20FIBROSING%20DERMOPATHY.htm [Accessed 2006 May 30]Google Scholar
  19. 19.
    Jan F, Segal JM, Dyer J, et al. Nephrogenic fibrosing dermopathy: two pediatric cases. J Pediatr. 2003; 143: 678–81PubMedCrossRefGoogle Scholar
  20. 20.
    Jain SM, Wesson S, Hassanein A, et al. Nephrogenic fibrosing dermopathy in pediatric patients. Pediatr Nephrol. 2004; 19: 467–70PubMedCrossRefGoogle Scholar
  21. 21.
    Engelen JW, Kooistra MP, Canninga-van Dijk MR, et al. Nephrogenic fibrosing dermopathy. Ned Tijdschr Geneeskd. 2003; 147: 2435–8PubMedGoogle Scholar
  22. 22.
    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: 469–73PubMedCrossRefGoogle Scholar
  23. 23.
    Scleromxoedema-like changes in four renal dialysis patients. Br J Dermatol 2003; 148: 563–8Google Scholar
  24. 24.
    Panda S, Bandyopadhyay D, Tarafder A. Nephrogenic fibrosing dermopathy: a series in a non-Western population. J Am Acad Dermatol. 2006; 54: 155–9PubMedCrossRefGoogle Scholar
  25. 25.
    Markus JS, James AJ, Nunez-Gussman JK, et al. Nephrogenic fibrosing dermopathy. J Am Acad Dermatol. 2005; 52: 166–7PubMedCrossRefGoogle Scholar
  26. 26.
    Hancox JG, Mengesha YM, Sangueza OP, et al. Nephrogenic fibrosing dermopathy after five days of hemodialysis. J Drugs Dermatol. 2003; 2: 550–3PubMedGoogle Scholar
  27. 27.
    Taylor EN, Henderson JM, Rennke HG, et al. Traumatic calcinosis cutis in a dialysis patient. Am J Kidney Dis. 2004; 44: e18–21PubMedCrossRefGoogle Scholar
  28. 28.
    Ruiz-Genao DP, Pascual-Lopez MP, Fraga S, et al. Osseous metaplasia in the setting of nephrogenic fibrosing dermopathy. J Cutan Pathol. 2005; 32: 172–5PubMedCrossRefGoogle Scholar
  29. 29.
    Hershko K, Hull C, Ettefagh L, et al. A variant of nephrogenic fibrosing dermopathy with osteoclast-like giant cells: a syndrome of dysregulated matrix remodeling?. J Cutan Pathol. 2004; 31: 262–5PubMedCrossRefGoogle Scholar
  30. 30.
    Edsall LC, English III JC, Teague MW, et al. Calciphylaxis and metastatic calcification associated with nephrogenic fibrosing dermopathy [published erratum appears in J Cutan Pathol 2004; 31: 518]. J Cutan Pathol. 2004; 31: 247–53PubMedCrossRefGoogle Scholar
  31. 31.
    Glaich AS, Martinelli PT, Markus RF, et al. Generalized elastolysis following nephrogenic fibrosing dermopathy. J Am Acad Dermatol. 2005; 53: 174–6PubMedCrossRefGoogle Scholar
  32. 32.
    Chin H, Wells G, Carag H, et al. Nephrogenic fibrosing dermopathy: a rare entity in patients awaiting liver transplantation. Liver Transpl. 2004; 10: 465–6CrossRefGoogle Scholar
  33. 33.
    Baron PW, Cantos K, Hillebrand DJ, et al. Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis. Am J Dermatopathol. 2003; 25: 204–9PubMedCrossRefGoogle Scholar
  34. 34.
    Gremmels JM, Kirk GA. Two patients with abnormal skeletal muscle uptake of Tc-99m hydroxymethylene diphosphonate following liver transplant: nephrogenic fibrosing dermopathy and graft vs host disease. Clin Nucl Med. 2004; 29: 694–7PubMedCrossRefGoogle Scholar
  35. 35.
    Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve. 2004; 30: 569–77PubMedCrossRefGoogle Scholar
  36. 36.
    Bardin T. Musculoskeletal manifestations of chronic renal failure. Curr Opin Rheumatol. 2003; 15: 48–54PubMedCrossRefGoogle Scholar
  37. 37.
    Hauser C, Kaya G, Chizzolini C. Nephrogenic fibrosing dermopathy in a renal transplant recipient with tubulointerstitial nephritis and uveitis. Dermatology. 2004; 209: 50–2PubMedCrossRefGoogle Scholar
  38. 38.
    Obermoser G, Emberger M, Wieser M, et al. Nephrogenic fibrosing dermopathy in two patients with systemic lupus erythematosus. Lupus. 2004; 13: 609–12PubMedCrossRefGoogle Scholar
  39. 39.
    Streams BN, Liu V, Liegeois N, et al. Clinical and pathologic features of nephrogenic fibrosing dermopathy: a report of two cases. J Am Acad Dermatol. 2003; 48: 42–7PubMedCrossRefGoogle Scholar
  40. 40.
    Perazella MA, Ishibe S, Perazella MA, et al. Nephrogenic fibrosing dermopathy: an unusual skin condition associated with kidney disease. Semin Dial. 2003; 16: 276–80PubMedCrossRefGoogle Scholar
  41. 41.
    Gambichler T, Paech V, Kreuter A, et al. Nephrogenic fibrosing dermopathy. Clin Exp Dermatol. 2004; 29: 258–60PubMedCrossRefGoogle Scholar
  42. 42.
    Kucher C, Xu X, P asha T, et al. Histopathologic comparison of nephrogenic fibrosing dermopathy and scleromyxedema. J Cutan Pathol. 2005; 32: 484–90PubMedCrossRefGoogle Scholar
  43. 43.
    Gilliet M, Cozzio A, Burg G, et al. Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis. Br J Dermatol. 2005; 152: 531–6PubMedCrossRefGoogle Scholar
  44. 44.
    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: 220–2PubMedCrossRefGoogle Scholar
  45. 45.
    Chung HJ, Chung KY. Nephrogenic fibrosing dermopathy: response to high-dose intravenous immunoglobulin. Br J Dermatol. 2004; 150: 596–7PubMedCrossRefGoogle Scholar
  46. 46.
    Kafi R, Fisher GJ, Quan T, et al. UV-Al phototherapy improves nephrogenic fibrosing dermopathy. Arch Dermatol. 2004; 140: 1322–4PubMedCrossRefGoogle Scholar
  47. 47.
    Lauchli S, Zortea-Caflisch C, Nestle FO, et al. Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis. Dermatology. 2004; 208: 278–80PubMedCrossRefGoogle Scholar
  48. 48.
    Tan AW, Tan SH, Lian TY, et al. A case of nephrogenic fibrosing dermopathy. Ann Acad Med Singapore. 2004; 33: 527–9PubMedGoogle Scholar
  49. 49.
    Caldwell-Brown D, Stern RS, Lin AN, et al. Lack of efficacy of phenytoin in recessive dystrophic epidermolysis bullosa. Epidermolysis Bullosa Study Group. N Engl J Med. 1992; 327: 163–7PubMedCrossRefGoogle Scholar
  50. 50.
    Mesa RA, Elliott MA, Schroeder G, et al. Durable responses to thalidomide-based drug therapy for myelofibrosis with myeloid metaplasia. Mayo Clin Proc. 2004; 79: 883–9PubMedCrossRefGoogle Scholar
  51. 51.
    Moschella SL, Kay J, Mackool BT, et al. 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: 2219–27PubMedCrossRefGoogle Scholar
  52. 52.
    Alopecia neoplastica responsive to tamoxifen. J R Soc Med 1990; 83: 647–8Google Scholar
  53. 53.
    Taylor RA, Levine JM, Jimenez SA. Case 35-2004: nephrogenic fibrosing dermopathy [letter]. N Engl J Med. 2005; 352: 1723PubMedCrossRefGoogle Scholar
  54. 54.
    Cowper SE, Bucala R, LeBoit PE. Case 35-2004: nephrogenic fibrosing dermopathy [letter]. N Engl J Med. 2005; 352: 1723PubMedCrossRefGoogle Scholar
  55. 55.
    Cowper SE. Nephrogenic systemic fibrosis: the nosological and conceptual evolution of nephrogenic fibrosing dermopathy. Am J Kidney Dis. 2005; 46: 763–5PubMedCrossRefGoogle Scholar
  56. 56.
    Dundova I, Treska V, Simanek V, et al. Nephrogenic fibrosing dermopathy: a case study. Transplant Proc. 2005; 37: 4187–90PubMedCrossRefGoogle Scholar
  57. 57.
    Dawn G, Holmes SC. Scleromyxoedema-like eruption following haemodialysis or nephrogenic fibrosing dermopathy?. Br J Dermatol. 2004; 150: 167–8PubMedCrossRefGoogle Scholar
  58. 58.
    Brisch M, Schneider T, Requena L, et al. Nephrogenic fibrosing dermopathy. J Dtsch Dermatol Ges. 2003; 1: 464–7PubMedCrossRefGoogle Scholar
  59. 59.
    Dupont A, Majithia V, Ahmad S, et al. Nephrogenic fibrosing dermopathy, a new mimicker of systemic sclerosis. Am J Med Sci. 2005; 330: 192–4PubMedCrossRefGoogle Scholar
  60. 60.
    Silver RM. Pathophysiology of the eosinophilia-myalgia syndrome. J Rheumatol Suppl. 1996; 46: 26–36PubMedGoogle Scholar
  61. 61.
    Matsuzaki Y, Nakano A, Jiang QJ, et al. Tissue-specific expression of the ABCC6 gene. J Invest Dermatol. 2005; 125: 900–5PubMedGoogle Scholar
  62. 62.
    Sapadin AN, Lebwohl MG, Teich SA, et al. Periumbilical pseudoxanthoma elasticum associated with chronic renal failure and angioid streaks: apparent regression with hemodialysis. J Am Acad Dermatol. 1998; 39: 338–44PubMedCrossRefGoogle Scholar
  63. 63.
    Abe R, Donnelly SC, Peng T, et al. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol. 2001; 166: 7556–62PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Department of DermatologySt Lukes-Roosevelt Hospital CenterNew YorkNew YorkUSA

Personalised recommendations