Nephrogenic systemic fibrosis associated with stromal and vascular calcification, report of two cases

Abstract

Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disorder characterized by the development of large indurated plaques on the skin, primarily in patients with end-stage renal disease (ESRD). Skin biopsy reveals an increased frequency of CD34(+) and Factor XIIa+ cells. Microscopic calcification has been reported in the skin biopsies of rare cases of NSF. The etiology and significance of this calcification is not clear. We present two cases of typical NSF, for which marked stromal and vascular calcification was identified on skin biopsy. In both cases, the calcification was within typical NSF lesions and was intimately associated with aggregates of CD34(+), Factor XIIIa+ spindle and stellate cells. This particular pattern of calcification strongly argues against either nonspecific dystrophic calcification or coincidental metastatic calcification. These findings suggest that calcification may be intrinsic to the pathophysiology of NSF, at least in a subset of NSF patients. In addition, the vascular calcification involving small arteries and arterioles in these two cases morphologically resembled calciphylaxis, which is another poorly understood complication of ESRD. This resemblance raises the possibility that NSF may predispose to or develop in the vicinity of indolent lesions of early-stage calciphylaxis. We propose that skin biopsies performed as part of a diagnostic workup for suspected NSF should preferably include the deep dermis and subcutis, in order to assess possible vascular calcification.

Cutaneous Manifestations of ESRD

“…Renal transplant for patients with NSF does not guarantee disease improvement, but the majority of cases has had successful outcomes, with skin softening and increased joint mobility (94,97,105,106). Treatments with limited benefit include oral corticosteroids, ultraviolet A phototherapy, plasmapheresis, sirolimus, high-dose intravenous Ig, methotrexate, and pentoxifylline (97,100,104,107). Several case reports of extracorporeal photopheresis have shown moderate clinical improvement (100,108,109).…”

“…Proliferation of dermal spindle cells, increased stromal mucin, and minimal inflammatory infiltrate are common. The epidermis is usually unaffected (98,99), and patients may have abnormal calcification in the dermis and subcutaneous tissue (99,104). The entire dermis may be involved, with the fibrocytes extending through the subcutaneous tissue.…”

Kutane Kalziphylaxie

“…Faktor-XIIIa-positive spindelige und sternförmige Zellen treten ebenfalls auf. Eine mikroskopische Kalzifizierung wurde in Einzelfällen beobachtet [53] . 7 Natriumthiosulfat ist ein Kationenchelator und Antioxidans und bildet hochlösliche Kalziumthiosulfat-Komplexe.…”

New insights into the mechanism of abnormal calcification in nephrogenic systemic fibrosis – gadolinium promotes calcium deposition of mesenchymal stem cells and dermal fibroblasts

“…Recently, it has been reported that a spectrum of abnormal calcifications, such as dystrophic calcinosis cutis, benign nodular calcifications, metastatic calcinosis cutis, and osseous metaplasia, develop in NSF patients [10][11][12][13][14][15][16][17][18]. Although many NSF patients have been diagnosed, there is no consensus on the etiology or significance of abnormal calcification in NSF.…”