15. Nephrogenic Systemic Fibrosis

Definition

A progressive disease in patients with advanced kidney dysfunction caused by gadolinium contrast used in MRI, leading to dramatic, painful skin thickening due to proliferation of fibrocytes and collagen deposition. Fibrosis of lung, skeletal muscle, liver, testes and myocardium has also been reported. 

Etiology

NSF is thought to result from gadolinium toxicity after administration and prolonged excretion of gadolinium-based contrast agents (GBCAs) with less-stable gadolinium ions. There are two primary risk factors:

Exposure to gadolinium-based contrast:

  • Gadolinium exposure is thought to be necessary in development of NSF.
  • Certain GBCAs are recognized as high risk, which is thought to result from decreased stability of the gadolinium ion contained in the contrast molecule. Cases are exceedingly rare with low-risk GBCAs.
  • NSF most commonly occurs after exposure to high doses of gadolinium-based contrast or multiple doses over months to years.
  • High risk GBCAs: gadodiamide (Omniscan (R)), gadopentetate dimeglumine (Magnevist (R)), Gadoversetamide (OptiMARK (R)).

Kidney dysfunction:

  • Most cases of have occurred in persons with eGFR <15 or those requiring maintenance dialysis.
  • NSF has also been described in persons with less advanced CKD and those with normal kidney function after receiving a gadolinium-enhanced MRI during AKI.

Clinical Presentation & Evaluation

  • Mean time from gadolinium exposure to onset of symptoms is 25 days.
  • Early symptoms: skin discoloration, swelling and pain, primarily in the distal lower extremities. 
  • Later symptoms: distal swelling of the extremities, then thickening and induration due to collagen deposition. In advanced stages, the fibrosis extends to the trunk. At this stage, joint movement is limited by the thickened skin and IV access becomes difficult. The face is invariably spared. Diagnosis should be confirmed by full thickness skin biopsy and scoring against clinical and histological criteria.

Management

  • There is currently no treatment.
  • Avoidance of gadolinium exposure in at-risk patients is the only effective strategy.
    • In patients with ESRD, the gadolinium study should be coordinated with the patient’s hemodialysis schedule (e.g., MRI in AM, HD in PM). Consider immediate post-gadolinium HD (i.e., within a couple hours) and/or increased frequency of dialysis (i.e., daily dialysis for 3 days post-gadolinium), though this is rarely done since there have not been trials to show benefit.
  • Kidney transplantation has been reported to partially reverse the disease.

 

Daftari B, Aran S, Shaqdan K et al. Current status of nephrogenic systemic fibrosis. Clinc Radiol. 2014;69(7):661-8

Girardi et al. Nephrogenic systemic fibrosis: Clinicopathological definition and workup recommendations. J Am Acad Dermatol. 2011 Dec;65(6):1095-1106.e7.

Kaewlai R, Abujudeh H. Nephrogenic systemic fibrosis. Am J Roentgenl. 2012;199(1):W17-23.

Thomsen HS, Morcos SK, Almen T, et al. Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines. Eur Radiol. 2013;23(2):307-18.

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