NSF is caused by exposure to gadolinium in gadolinium-based MRI contrast agents (GBCAs) in patients with impaired kidney function.

[6] Joint contractures of the fingers, elbows and knees can develop secondary to skin involvement and can severely impair physical function.

The etiology or duration of renal failure seems not to be relevant, but NSF risk greatly depends on the residual kidney function.

[16] It is also supported by subchronic rodent toxicity experiments, which demonstrate a set of gross and microscopic findings similar to those known to be caused by Zn2+ deficiency.

[16] Under the transmetallation hypothesis, we can expect that subtle changes in formulation can affect the intrinsic safety of gadolinium complexes, which is indeed observed.

[7] At the microscopic level, NSF shows a proliferation of dermal fibroblasts and dendritic cells, thickened collagen bundles, increased elastic fibers, and deposits of mucin.

[17] More recent case reports have described the presence of sclerotic bodies (also known as elastocollagenous balls) in skin biopsies from NSF patients.

While not universally present, this finding is believed to be unique to patients exposed to gadolinium, although not necessarily limited to areas involved by NSF.

[6][7] NSF affects males and females in approximately equal numbers and has been reported in patients of different ethnic and geographic regions.