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Nephrogenic systemic fibrosis and its association with gadolinium exposure during MRI

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ABSTRACTNephrogenic systemic fibrosis (NSF) is a newly recognized systemic disorder characterized by widespread tissue fibrosis in patients with impaired renal function. Recent reports suggest that NSF is associated with exposure to gadolinium-based contrast agents used in magnetic resonance imaging. NSF can be very debilitating and can lead to serious complications and death. Health care providers should exercise caution when considering the use of gadolinium-based imaging studies in patients with renal dysfunction.

KEY POINTS

  • NSF seems to arise in roughly 3% of patients with renal insufficiency who receive gadolinium, although the data are somewhat sketchy and the true incidence might be higher if the NSF is specifically looked for.
  • Manufacturers of all available gadolinium contrast agents now must include a boxed warning about the risk of NSF in patients with acute or chronic severe renal insufficiency (glomerular filtration rate < 30 mL/minute/1.73 m2) and in patients with acute renal insufficiency of any severity due to hepatorenal syndrome or in the perioperative liver transplantation period.
  • As yet, we have no effective treatment for NSF. If the patient is already on hemodialysis, it may be reasonable to perform hemodialysis immediately after exposure to gadolinium and again the next day.


 

References

The use of gadolinium as a contrast agent in magnetic resonance imaging (MRI) in patients with impaired kidney function has come under scrutiny because of recent reports of a potential association between its use and nephrogenic systemic fibrosis (NSF).

See related editorial

This entity was first identified in the United States in 1997. Cowper et al 1 in 2000 described 15 hemodialysis patients who developed thickening and hardening of the skin with brawny hyperpigmentation, papules, and subcutaneous nodules on the extremities.

This “new disease” was initially called “nephrogenic fibrosing dermopathy,” as it was exclusively seen in patients with renal impairment and was thought to affect only the skin and subcutaneous tissue. With growing evidence of the extent and pathogenicity of the fibrosis in visceral organs, the nomenclature was changed to NSF, to better reflect the systemic nature of the disease.

PRESENTATION: MILD TO DEVASTATING

NSF has thus far been reported only in patients with renal impairment, most of whom were dialysis-dependent. It does not seem to be more common in one sex or the other, in any age range, or in any ethnic group. It can range in severity from mild to a devastating scleroderma-like systemic fibrosing disorder.

Figure 1. Typical skin lesions of nephrogenic systemic fibrosis (indurated erythematous plaques) affecting the lower extremities.

Cutaneous changes are the most predominant and impressive manifestations. NSF typically causes dermal hardening with tethering to deep dermal tissues, giving the skin the appearance of textured plaques, papules, or nodules with irregular edges and a brawny wooden texture to palpation ( Figure 1 ). The lesions can be erythematous or brown-pigmented and can be painful and pruritic. NSF typically presents between the ankles and the thighs in a symmetric fashion and progresses proximally and distally to involve the entire lower extremities. Upper extremity involvement occurs frequently, but usually with lower extremity disease. 2 The trunk is involved less commonly than the legs and arms, and usually late in extensive disease. The face is typically spared ( Figure 2 ).

Figure 2. The pattern of involvement is usually symmetric. The lesions most often affect the lower extremities, followed by the upper and lower extremities and then the trunk and upper and lower extemities. The face is usually spared.

NSF can cause loss of motion and contractures in multiple joints, leading to almost total loss of function and devastating debility within a short time—days to a few weeks. 2 These contractures are attributed to periarticular fibrosis of the overlying skin and subcutaneous tissue rather than to erosive joint disease. About 5% of patients develop a fulminant form of NSF 3; these patients may become wheelchair-dependent.

The heart, lungs, skeletal muscle, and diaphragm can also be involved, sometimes leading to serious complications and death. 4–6

The disease is usually progressive and unremitting. Mendoza et al, 7 in a review of 12 cases of NSF, reported that the disease had a progressive course in 6 patients, of whom 3 died within 2 years and 3 were ultimately confined to a wheelchair. More severe findings and rapid progression of the skin disease are associated with a poor prognosis.

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