Nephrogenic Systemic Fibrosis and Other Scleroderma Mimickers

Abstract

Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disorder that mimics systemic sclerosis (scle-roderma) and is strongly associated with exposure to gadolinium in the setting of renal insufficiency. In addition to the skin, fibrotic changes can occur in the lungs, diaphragm, muscles, heart, and esophagus. Both clinical and histopathological findings are required to confirm the diagnosis of NSF. No cases of NSF have been described in patients with normal kidney function or mild underlying renal disease. The more severe the kidney dysfunction and the higher the dose of gadolinium, the greater is the risk of NSF. NSF develops subacutely in most cases. It usually becomes apparent first in the lower extremities with symmetrical edema that may involve the upper extremities. The edema may be associated with erythema, blisters, and bullae. Upon resolution of the edema, the indurated skin is nonpitting and “unpinchable.” NSF tends to spare the skin of the face, in contrast to both scleroderma and scleromyxedema. Yellow scleral plaques are described in many cases of NSF. The histopathological features of NSF are consistent with a dermal reaction to injury: fibrocyte-like cells, histiocytes, dermal dendritic cells, scar-like fibrosis, mucin, edema, calcification, and ossification. Scleroderma mimickers such as morphea, scleromyxe-dema, and eosinophilic fasciitis are generally distinguished from scleroderma by their absence of extracutaneous disease, Raynaud's phenomenon, and antinuclear antibodies.