Nephrogenic Systemic Fibrosis (NSF): 10 High-Yield Facts 1.) Patients with NSF may present to the Emergency Department: NSF was first seen in 1997 and first reported in 2000.1-3 The current generation of medicine infrequently witnesses the development of an entirely new disease, but this is one example. 2.) NSF patients have thickened and hardened skin of the extremities and trunk, with brawny hyperpigmentation; the fibrosis may occur in other areas of skin, and in deeper tissues (subcutaneous tissue, fascia, muscle, liver, lung, and other tissues).4 3.) NSF has only occurred in patients with renal insufficiency; in this group, the risk of NSF within days to months after gadolinium exposure is roughly 3%-5% higher doses tend to be most associated with disease occurrence.1 4.) Though treatment with plasmapheresis, photopheresis, and thalidomide have been attempted, there is no cure for NSF; it is a progressive, disabling, and possibly fatal condition that can occur at any age, mostly seen in middle-age patients.1 5.) These patients need a deep incisional biopsy or punch biopsy to provide an adequate pathology sample; light microscopy will demonstrate expansion of the dermis with fibrosis in the setting of CD34+ fibrocytes – special stains show increased collagen, mucin, and elastic fiber deposition, and occasionally gadolinium deposits.4, 5 Pathogenesis might involve inappropriate activation of tissue-injury response, or increased production and recruitment of fibrocytes.4 6.) Other names used for this condition include Nephrogenic Fibrosing Dermopathy (NFD)2, scleromyxoedema-like cutaneous disease3, and Hemodialysis-Associated Systemic Fibrosis (HASF, considered a distracting term and not generally used).6 7.) So far, only association with, and not causation by, gadolinium, has been demonstrated. Many gadolinium-containing contrast agents exist: Omniscan has been associated most of the cases of NSF, while ProHance and MultiHance have been associated with none and one case, respectively. (The MultiHance patient also received Omniscan 5 days afterward).1, 7, 8 8.) Hemodialysis after gadolinium administration is the fastest way to remove the chemical from blood, but has not yet been demonstrated to decrease the incidence or severity of NSF. Though gadolinium is nephrotoxic, generally used doses are low so this is negligible; metformin usually does not need to be discontinued.4, 9-12 9.) Experts4 recommend GFR to stratify risk for NSF: a. GFR >30: Generally do not need hemodialysis after the scan; only 2 reported cases of NSF in this GFR range, confounded by acute renal injury (inaccurate GFR evaluations in this setting)4 b. GFR 15-29: Consider hemodialysis, risk may not outweigh benefit. c. GFR <15 (FDA’s definition of “chronic severe renal failure” as of 2007) or hepatorenal syndrome, or perioperative patients for hepatic transplant: Hemodialyze these patients after scan. 10.) There is an official registry to contribute patient cases of NSF for national and international research efforts: http://www.icnfdr.org. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Kanal E, Barkovich AJ, Bell C, Borgstede JP, Bradley WG Jr, Froelich JW, Gilk T, Gimbel JR, Gosbee J, Kuhni-Kaminski E, Lester JW Jr, Nyenhuis J, Parag Y, Schaefer DJ, Sebek-Scoumis EA, Weinreb J, Zaremba LA, Wilcox P, Lucey L, Sass N, ACR Blue Ribbon Panel on MR Safety. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol. 2007 Jun;188(6):1447-74. Cowper SE, Su LD, Bhawan J, Robin HS, LeBoit PE. Nephrogenic fibrosing dermopathy. Am J Dermatopathol 2001;23:383-93. Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S., LeBoit PE. Scleromyxoedema-like cutaneous disease in renal-dialysis patients. Lancet 2000;356:1000-1. UpToDate. Galan A, Cowper SE, Bucala R. Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy). Curr Opin Rheumatol. 2006 Nov;18(6):614-7. Cowper SE; Bucala R; Leboit PE, Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis-setting the record straight. Semin Arthritis Rheum. 2006 Feb;35(4):208-10. Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, Thomsen HS. 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. Grobner T. Gadolinium–a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006; 21:1104–1108. Widmark JM. Imaging-related medications: a class overview. Proc (Bayl Univ Med Cent). 2007 Oct;20(4):408-17. Saitoh T, Hayasaka K, Tanaka Y, Kuno T, Nagura Y. Dialyzability of gadodiamide in hemodialysis patients.Radiat Med. 2006 Jul;24(6):445-51. Okada S, Katagiri K, Kumazaki T. Yokoyama H Safety of gadolinium contrast agent in hemodialysis patients. Acta Radiol. 2001 May;42(3):339-41. Joffe P; Thomsen HS. Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Meusel M Acad Radiol. 1998 Jul;5(7):491-502.