Gadolinium Exposure Independently Linked to Nephrogenic Fibrosing Dermopathy

Yael Waknine

February 23, 2007 — Exposure to gadolinium-containing contrast agents during magnetic resonance imaging (MRI) studies has been independently linked to nephrogenic fibrosing dermopathy (NFD), according study results from the Centers for Disease Control and Prevention (CDC) in the February 23 issue of the Morbidity and Mortality Weekly Report.
NFD was first identified in 1997 as a fibrotic disorder of the skin in patients with renal failure; since then, systemic involvement has led to interchangeable use of the term nephrogenic systemic fibrosis (NSF). Although it is not well understood, potential risk factors for the condition have included renal failure severity, thrombotic episodes, edema, and vascular procedures.
The impetus for the study was generated by a report from the Danish Medicines Agency regarding 25 cases of NFD in patients recently exposed to a gadolinium-containing contrast agent for magnetic resonance angiography (MRA) at doses higher than that recommended for MRI.
As of December 21, 2006, the US Food and Drug Administration had received 90 reports of patients with moderate to end-stage renal disease who developed NFD within 2 days to 18 months of gadolinium exposure during MRI or MRA.
The current study was undertaken in response to a cluster of NFD cases reported from the dialysis unit of a hospital in St. Louis, Missouri, in May 2006 and involved an analysis of data from 19 case patients and 57 matched control patients.
After adjusting for other significant factors such as age, dependent edema, history of deep vein thrombosis, and history of hypothyroidism, results showed that exposure to gadolinium remained a significant factor.
NFD patients were significantly more likely than controls to have been exposed to gadolinium-containing contrast agents during the 6 months (odds ratio [OR], 6.11; 95% confidence interval [CI], 1.92 - 19.52) or year (OR, 7.99; 95% CI, 2.22 - 28.77) preceding diagnosis. Although 5 case patients had no identified gadolinium exposure within this time frame, 4 had been exposed from 16 to 68 months prior to diagnosis.
In addition, comparison of 14 case patients with a similar number of gadolinium-exposed control patients showed that the former were more likely to have primarily received peritoneal dialysis in the preceding 6 months (36% vs 0%), required dialysis for a longer period of time (median, 27 vs 10 months), and received multiple exposures.
Healthcare professionals are therefore advised to refrain from using gadolinium-containing contrast agents in patients with advanced renal failure, particularly those undergoing peritoneal dialysis, according to the CDC. Consideration should be given to using other radiologic modalities such as ultrasound and computed tomography (CT) if possible.
If alternatives to gadolinium-enhanced procedures are not feasible, prompt hemodialysis should be considered after the procedure to facilitate clearance; however, its utility for reducing NFD development or progression remains unknown. For patients with no other hemodialysis indication, the risks associated with establishing access should be weighed against these theoretical benefits.
Patients at risk for NFD should be closely observed after gadolinium exposure and instructed to contact a healthcare professionals regarding potential symptoms such as skin burning, itching, reddened/darkened patches and/or inflammation, hardening, and/or tightening; yellow raised spots on the sclera; and joint stiffness, limited range of peripheral movement, deep hip/rib pain, and/or muscle weakness.
Five gadolinium products are currently approved by the US Food and Drug Administration (FDA) for use in MRI: Omniscan (Amersham Health, GE Healthcare), OptiMARK (Mallinckrodt, Inc), Magnevist (Berlex Laboratories, Inc), ProHance (Bracco Diagnostics, Inc), and MultiHance (Bracco Diagnostics, Inc).
Healthcare professionals are encouraged to report cases of NFD potentially associated with exposure to gadolinium-containing contrast agents to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.
MMWR. 2007;56(7):137-141.