Nephrogenic Fibrosing Dermopathy

Abstract

This report details the histopathologic findings in a unique fibrosing disorder that recently emerged among patients with renal disease. The affected patients were initially identified among recipients of renal transplants at a single institution, but later cases at other centers were identified, and included patients receiving renal dialysis for a variety of different kidney diseases. The cutaneous changes consisted largely of indurated plaques and papules on the extremities and trunk. Systemic findings seen in scleromyxedema, which the condition resembles in some respects, were absent. By routine microscopy, the findings range from a very subtle proliferation of dermal fibroblasts in early lesions, to a florid proliferation of fibroblasts and dendritic cells in fully developed cases. Thick collagen bundles with surrounding clefts are a prominent finding, and a variable increase in dermal mucin and elastic fibers was usually evident with special stains. CD-34 positive dermal dendrocytes were floridly abundant, with dendritic processes aligned with elastic fibers and around collagen bundles in a dense network. Factor XIIIa and CD-68 positive mono-and multinucleated cells are also present in increased numbers. Electron microscopy highlighted increased elastic fibers closely apposed to dendritic cell processes. The entire dermis was commonly involved, with increased spindle cells, collagen, mucin, and elastic fibers extending through the subcutis along the septa of fatty lobules. In some instances, the process resembled a sarcoma on histopathologic examination. The recent emergence of this condition and the apparent clustering of cases in specific dialysis centers initially suggested a possible infectious and/or toxic agent. To date, however, no such agent has been identified. We propose the term "nephrogenic fibrosing dermopathy (NFD)" until a specific cause can be identified.

Mechanism of NSF: New evidence challenging the prevailing theory

“…Histopathologically, NSF is characterized in the early stages by the presence of dermal collagen interspersed with fluid edema, mucin, and elastin (15). Fibrocytes or ''spindle'' cells are abundant and very closely associated with the developing fibrosis (1).…”

“…Although both CD34 and procollagen I are key markers of fibrocytes, collagen and procollagen I positivity are low in the early stages (1). As disease develops, extracellular collagen deposition appears to correlate with increases in the procollagen I positivity of fibrocytes (15).…”

Good MRI images: to Gad or not to Gad?

“…On 7 February 2007, the medical community was informed that gadodiamide (Omniscan) is now not only contraindicated in patients with end-stage renal disease (ESRD), but also in pre-or postoperative liver transplantation patients and, due to their renal-organ immaturity, in newborns and infants up to 1 year old. This change in policy was motivated by recent reports of a possible link between the use of gadodiamide and the development of so-called "nephrogenic systemic fibrosis" (NSF) [1][2][3][4] in patients with renal failure. This discovery came as quite a surprise to the nephrology and radiology communities.…”

“…A glimpse into medical literature reveals approximately 200 cases of NSF, previously known as nephrogenic fibrosing dermopathy (NFD) [1][2][3][4][5][6]. One pediatric case is published in this issue [7].…”

“…The diagnosis of NSF is confirmed by skin biopsy. Characteristically, histopathologic features such as thickened collagen bundles with surround-ing clefts, mucin deposition, and proliferation of fibroblasts and elastic fibers are present, whereas signs of inflammation are absent, which makes this disorder a distinct entity [2,8]. Grobner [8] was the first to report that five of nine gadodiamide-exposed hemodialysis patients developed NSF within 2-4 weeks after contrast-dye exposure.…”