Nephrogenic systemic fibrosis

Nephrogenic systemic fibrosis (NSF) or Nephrogenic fibrosing dermopathy is a rare and serious syndrome that involves fibrosis of skin, joints, eyes, and internal organs. Its cause is not fully understood, but it seems to be associated with exposure to gadolinium (which is frequently used as a contrast substance for MRIs) in patients with severe kidney failure. It does not have a genetic basis.

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In NSF, patients develop large areas of hardened skin with fibrotic nodules and plaques. Flexion contractures with an accompanying limitation of range of motion can also occur. NSF resembles scleromyxedema at the histologic (microscopic) level; it shows a proliferation of dermal fibroblasts and dendritic cells, thickened collagen bundles, increased elastic fibers, and deposits of mucin. ^[1]

Most patients with NSF have undergone hemodialysis for renal failure, some have never undergone dialysis and others have received only peritoneal dialysis. Many patients have taken immunosuppressive medications and have other diseases, such as hepatitis C. Four of the five FDA-approved gadolinium contrast agents have been principally implicated in NSF, including Omniscan, Multihance, Magnevist, and OptiMARK.

The first cases of NSF were identified in 1997,^[2] but NSF was first described as an independent disease entity in 2000.^[3] While skin involvement is on the foreground, the process may involve any organ and resembles diffuse scleroderma or systemic sclerosis. ^[4] In 2006, the link between NSF and gadolinium-containing contrast agents was made.^[5][6][7] As a result, gadolinium-containing contrast is now considered contraindicated in patients with an estimated glomerular filtration rate (a measure of renal function) under 60 and especially under 30.^[8]

The European Medicines Agency has classified the gadolinium-containing contrast agents in three groups:^[9]

• Least likely (safest) to release free gadolinium ions Gd3+ in the body have a cyclical structure: Dotarem, Gadovist and ProHance
• Intermediate have an ionic linear structure: Magnevist, MultiHance, Primovist and Vasovist
• Most likely to release Gd3+ have a linear non-ionic structure: Omniscan and OptiMARK

It can be noted that this classification was released after another proposition would have left the safest category (ionic cyclical structure) with only one agent (Dotarem, not sold in North America). The intermediate category would have been both ionic linear structure and non-ionic cyclical structure. The third category most at risk was unchanged (linear non-ionic).^[10]

References

1. ^ Scheinfeld, NS; Cowper, S; Kovarik, CL; Butler, DF. "Nephrogenic Fibrosing Dermatopathy." Emedicine. [1]
2. ^ Cowper SE (2003). "Nephrogenic fibrosing dermopathy: the first 6 years". Current Opinion in Rheumatology 15: 785-790.
3. ^ Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE (2000). "Scleromyxoedema-like cutaneous diseases in renal-dialysis patients". Lancet 356 (9234): 1000-1. PMID 11041404.
4. ^ Mendoza FA, Artlett CM, Sandorfi N, Latinis K, Piera-Velazquez S, Jimenez SA (2006). "Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature". Semin. Arthritis Rheum. 35 (4): 238-49. doi:10.1016/j.semarthrit.2005.08.002. PMID 16461069.
5. ^ Grobner T (2006). "Gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?". Nephrol. Dial. Transplant. 21 (4): 1104-8. doi:10.1093/ndt/gfk062. PMID 16431890.
6. ^ Marckmann P, Skov L, Rossen K, et al (2006). "Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging". J. Am. Soc. Nephrol. 17 (9): 2359-62. doi:10.1681/ASN.2006060601. PMID 16885403.
7. ^ (2007) "Nephrogenic fibrosing dermopathy associated with exposure to gadolinium-containing contrast agents--St. Louis, Missouri, 2002-2006". MMWR Morb. Mortal. Wkly. Rep. 56 (7): 137-41. PMID 17318112.
8. ^ Kanal E, Barkovich AJ, Bell C, et al (2007). "ACR guidance document for safe MR practices: 2007". AJR. American journal of roentgenology 188 (6): 1447-74. doi:10.2214/AJR.06.1616. PMID 17515363.
9. ^ Medicines and Healthcare products Regulatory Agency. Drug Safety Update, August 2007 pg 2-4. Link (121 KB)
10. ^ http://www.ismrm.org/special/EMEA2.pdf