22-34: Nephrogenic Systemic Fibrosis

Nephrogenic systemic fibrosis is a multisystem disorder seen exclusively in patients with advanced CKD (primarily with an eGFR less than 15 mL/minute/1.73 m², but rarely 15–29 mL/minute/1.73 m²), AKI, and after kidney transplantation. Histopathologically, there is an increase in dermal spindle cells positive for CD34 and procollagen I. Collagen bundles with mucin and elastic fibers are also noted.

Nephrogenic systemic fibrosis was first recognized in hemodialysis patients in 1997 and has been strongly linked to use of select contrast agents containing gadolinium. Incidence following exposure to historical (“group I”) gadolinium agents is approximately 1–4% in the highest risk (ESKD) population and lower in patients with less severe kidney disease. This incidence has decreased over time due to limiting use of gadolinium in patients with CKD and AKI, and the development of safer gadolinium preparations with different molecular structures that have not been associated with NSF (“group II” agents). There is an FDA warning regarding avoidance of group I gadolinium agents for patients with an eGFR less than 30 mL/minute/1.73 m².

CLINICAL FINDINGS

Nephrogenic systemic fibrosis affects several organ systems, including the skin, muscles, lungs, and cardiovascular system. The most common manifestation is a debilitating fibrosing skin disorder that can range from skin-colored to erythematous papules, which coalesce to brawny patches. The skin can be thick and woody in areas and is painful out of proportion to findings on examination.

TREATMENT

No treatment has proven definitively effective; a preventive approach of avoiding group I gadolinium exposure in high-risk patients is paramount. Case reports and series describe potential benefit of corticosteroids, photopheresis, plasmapheresis, and sodium thiosulfate, but their true efficacy is unknown. CT is preferred to MRI with gadolinium when similar diagnostic information can be gleaned. If gadolinium absolutely must be used in patients on dialysis, practice guidelines recommend using a group II agent at no more than the standard dose. Hemodialysis immediately after exposure to gadolinium previously was advised but is not considered necessary for group II agents.