Re: [occ-env-med-l] MMWR/07-02-23, Nephrogenic Fibrosing Dermopathy from Gd-med-contrast (fwd)

February 26, 2007

well, I'm about talked out of haveing this done

MRI of the head

http://www.webmd.com/brain/Magnetic-Resonance-Imaging-MRI-of-the-Head?

page=4

>

> Nephrogenic Fibrosing Dermopathy from Gd-med-contrast

>

> February 23, 2007 / 56(07);137-141

>

> http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5607a1.htm?

s_cid=mm5607a1_e%0A

>

> Nephrogenic Fibrosing Dermopathy Associated with Exposure to

> Gadolinium-Containing Contrast Agents --- St. Louis, Missouri,

> 2002--2006

>

> Nephrogenic fibrosing dermopathy (NFD) causes thickening and

hardening

> of the skin, often in the extremities, and occurs in patients with

> underlying renal disease. The skin lesions can progress rapidly,

> sometimes leading to joint immobility and the inability to walk (1).

> In May 2006, nephrologists at hospital A in St. Louis, Missouri,

> reported to CDC and the Missouri Department of Health and Senior

> Services (MoDHSS) a cluster of NFD among patients treated in their

> dialysis units. CDC and MoDHSS conducted an investigation to

determine

> the number of affected patients and identify risk factors for NFD.

> Thirty-three patients with NFD were identified in St. Louis, 28 of

> whom had been treated at hospital A. A matched case-control study

was

> conducted at the hospital. This report summarizes the preliminary

> results of that study, which indicated that exposure to

> gadolinium-containing contrast agents during magnetic resonance

> imaging (MRI) studies was independently associated with NFD.

> Clinicians should be aware of the potential for NFD, and when

> possible, should avoid use of gadolinium-containing contrast agents

in

> patients with advanced renal disease.

>

> A confirmed case was defined as clinical findings (i.e., skin

> thickening or hardening) and skin biopsy findings consistent with

NFD

> in a person with renal disease in St. Louis during January

> 2000--August 2006. Suspected cases met either the clinical or the

> biopsy criteria but not both. Hospital A staff members manually

> searched a logbook of dermatology biopsies to identify diagnoses

> consistent with NFD from January 2000 onward. Study investigators

> searched the hospital pathology database for diagnoses of NFD and

> potentially related diagnoses from the same period. Investigators

> searched for additional cases that would not have been identified at

> hospital A by contacting eight pathology referral centers in St.

Louis

> and requesting information on all patients who had NFD diagnosed

since

> January 2000.

>

> Demographics, comorbid conditions, and medication data for

> case-patients and controls were collected from hospital A inpatient

> and outpatient medical records, which included information from

> hospital A admissions (including emergency department visits),

> outpatient dialysis and other clinic visits, and laboratory and

> radiology studies performed in the hospital A system. The maximum

> erythropoietin (epoetin alfa) dose received during the preceding 6

> months and the dose received at the time of disease detection (for

> case-patients) or match date (for controls) were classified as high

or

> low relative to the median weekly dose received by all patients in

the

> study. Continuous variables were compared using the Wilcoxon rank-

sum

> test, and categorical variables were compared using a chi-square

test

> or Fisher's exact test. Matched univariate odds ratios (ORs) were

> calculated. After adjusting for clinically relevant variables

> determined to be associated within the univariate analysis,

> multivariable ORs were calculated using a conditional logistic

> regression model.

>

> The case-control study included confirmed cases from hospital A.

Three

> controls per case-patient were selected randomly from a group of

> patients who were treated in the same hospital A dialysis clinic or

> treatment center on the same day that a case was diagnosed. These

> matched controls were required to have received dialysis for at

least

> 4 weeks or to have had renal insufficiency (serum creatinine >2.5

> mg/dL) for at least 6 months preceding their match date. Only

> case-patients and controls with medical record information available

> for at least 3 of the 6 months preceding the match date were

included.

>

> Twenty-eight cases were identified at hospital A during December

> 2002--August 2006, including 25 confirmed and three suspected cases

> (Figure). Five additional patients from St. Louis with NFD outside

of

> hospital A were identified during the study period; however, minimal

> information was available for these patients, and they were

excluded.

> Among the 19 confirmed case-patients at hospital A who met criteria

> for inclusion in the case-control study, the median age was 50 years

> (range: 21--67), and 10 (53%) were male. The median number of months

> on dialysis was 30 (range: 0.1--192 months). The primary type of

> dialysis received in the 6 months preceding disease detection was

> hemodialysis for 11 (58%) of the 19 case-patients and peritoneal

> dialysis for six (32%) case-patients. Two of the 19 case-patients

had

> acute renal failure and received dialysis only for a brief time (4

> days for one patient, 45 days for the other) during the 6 months

> preceding disease diagnosis. The clinical sites at which NFD was

first

> detected were hospital A during inpatient hospitalization for 13

(68%)

> case-patients, an outpatient peritoneal dialysis clinic affilitated

> with hospital A for four (21%) case-patients, and an outpatient

> hemodialysis unit affiliated with hospital A for two (11%)

> case-patients.

>

> No significant differences were detected between case-patients (n =

> 19) and matched controls (n = 57) regarding sex, number of months

> since first dialysis, primary type of dialysis received, inpatient

> hospitalization days in the preceding year, and presence of diabetes

> mellitus (Table 1). Significant differences were detected in median

> age, history of deep venous thrombosis (DVT), history of

> hypothyroidism, and presence of dependent edema. In univariate-

matched

> analysis, exposure to gadolinium-containing contrast agents during

the

> preceding 6 months or preceding year was more common among

> case-patients than controls (Table 2). The presence of dependent

> edema, history of DVT, and history of hypothyroidism also were

> associated with NFD. Although the associations were not

statistically

> significant, case-patients were more likely than controls to have

> received a high dose (>18,000 U/week) of erythropoietin at the time

of

> disease detection and a high maximum dose (>30,000 U/week) of

> erythropoietin in the preceding 6 months. After adjusting for age,

> presence of dependent edema, history of DVT, and history of

> hypothyroidism, only exposure to gadolinium-containing contrast

agents

> during the preceding 6 months or preceding year remained

statistically

> significant.

>

> Five case-patients had no identified gadolinium exposure within 1

year

> preceding NFD diagnosis. However, of these, four had gadolinium

> exposure from 16 to 68 months preceding diagnosis; the fifth patient

> had no evidence of gadolinium exposure. Among case-patients (n = 14)

> and controls (n = 14) with gadolinium-containing contrast exposure

in

> the preceding year, case-patients were more likely to have received

> peritoneal dialysis as their primary type of dialysis in the

preceding

> 6 months (36% versus 0%) and had a longer median time on dialysis

(27

> months versus 10 months). Thirteen patients (nine case-patients,

four

> controls) had multiple gadolinium-containing contrast exposures

during

> the preceding year. The NFD attack rate estimated for persons

> undergoing outpatient chronic dialysis in the hospital A system for

> the 4 years in which cases were identified was 4.6 cases per 100

> peritoneal dialysis patients and 0.61 cases per 100 hemodialysis

> patients.

>

> Reported by: S Cheng, MD, L Abramova, MD, Washington Univ School of

> Medicine, St. Louis; G Saab, MD, Univ of Missouri School of

Medicine,

> Columbia; G Turabelidze, MD, Missouri Dept of Health and Senior

Svcs.

> P Patel, MD, M Arduino, DrPH, T Hess, Div of Healthcare Quality

> Promotion, National Center for Preparedness, Detection, and Control

of

> Infectious Diseases (proposed); A Kallen, MD, M Jhung, MD, EIS

> officers, CDC.

>

> Editorial Note:

>

> NFD was first identified in 1997 as a fibrotic disorder of the skin

in

> patients with renal failure (1). Since then, systemic involvement

has

> been described in some patients with NFD, resulting in use of the

term

> nephrogenic systemic fibrosis (NSF); NFD and NSF have been used to

> describe the same condition (3). No clear etiology has been

> established for NFD, and little is known about its pathogenesis or

> natural history. This report describes the largest geographic

cluster

> of NFD that has been identified and provides evidence that exposure

to

> a gadolinium-containing contrast agent is a risk factor for the

> development of the disease.

>

> Although risk factors for NFD have not been studied extensively,

> possible correlations with severity of renal failure, thrombotic

> episodes, edema, and vascular procedures have been reported (2,4).

> Recently, medication exposures such as erythropoietin and

> gadolinium-containing contrast agents have been identified as

> potential risk factors for NFD (5,6). In May 2006, the Danish

> Medicines Agency reported 25 cases of NFD diagnosed in Europe among

> patients with recent exposure to gadolinium-containing contrast. In

> response, the Food and Drug Administration (FDA) issued a public

> health advisory in June 2006 regarding the use of these contrast

> agents in patients with renal failure (7). As of December 25, 2006,

> the FDA MedWatch system had received 90 reports of NFD possibly

> related to gadolinium-containing contrast agents.

>

> Intravenously administered contrast agents are used routinely for

MRI

> studies; the contrast agents contain gadolinium (a paramagnetic

heavy

> metal), which is bound to a chelating agent. The mechanism for

> possible gadolinium-associated NFD is unknown; however, one

hypothesis

> is that the gadolinium ions might dissociate from the chelate and

> result in a fibrotic reaction (5). Five gadolinium-based contrast

> agents are available in the United States; the first was approved

for

> use in 1988 (7). Adverse events associated with these agents

typically

> are minor (e.g., nausea); severe effects such as allergic reactions

or

> tissue necrosis as a result of extravasation are rare. In addition,

> gadolinium-containing contrast agents are believed to be less

> nephrotoxic than iodinated contrast agents used for computed

> tomography (CT) imaging (8). Excretion of gadolinium-containing

> contrast agents primarily occurs renally; the amount of contrast

> eliminated from the body after dialysis has not been well-evaluated.

> Two studies suggest that 65%--78% of gadolinium-containing contrast

> might be cleared after one hemodialysis session and 98% after three

> sessions (9,10). Peritoneal dialysis might achieve less effective

> gadolinium-contrast clearance than hemodialysis. In one study, 69%

of

> total gadolinium-containing contrast was excreted after 22 days in

> patients undergoing continuous ambulatory peritoneal dialysis (9).

> Delayed clearance might prolong the duration of gadolinium-

containing

> contrast exposure among patients undergoing peritoneal dialysis.

> However, patients undergoing peritoneal dialysis have not been

> previously reported to be at higher risk for NFD than patients

> undergoing hemodialysis. The chronic peritoneal dialysis outpatients

> in this investigation had higher estimated NFD attack rates than

> chronic hemodialysis outpatients. No controls who had

> gadolinium-containing contrast exposure underwent primarily

peritoneal

> dialysis.

>

> The number of cases identified at hospital A decreased during the

> second and third quarters of 2006 (Figure), and the reason for this

> decrease is unclear. Because NFD was not recognized at hospital A

> until late 2002, initially identified cases likely represented both

> incident (new) and prevalent (existing) cases; the decline might

> represent the subsequently smaller number of remaining prevalent

cases

> that had not been identified. Although hospital A instituted changes

> such as limiting the use of gadolinium-containing contrast agents in

> patients with renal failure, these changes were initiated shortly

> before the investigation began and are unlikely to account

completely

> for the decline.

>

> The findings in this report are subject to at least two limitations.

> First, NFD is a rare condition. Even though the data in this report

> represent the largest cluster of NFD cases identified to date, the

> small sample size of the case-control study might have limited the

> power to demonstrate statistically significant associations for

> variables other than exposure to gadolinium-containing contrast

> agents. Second, the date of disease diagnosis was used instead of

date

> of disease onset; the actual date of disease onset is unknown. To

> identify exposures that preceded the actual date of disease onset,

> exposures as early as 1 year before the date of diagnosis were

> included. This might have resulted in the inclusion of gadolinium

> exposures that were not related to the development of NFD.

>

> When possible, use of gadolinium-containing contrast agents should

be

> avoided in patients with advanced renal failure, particularly in

> patients who are undergoing peritoneal dialysis. Depending on the

> indication for imaging, other radiologic modalities (e.g.,

ultrasound

> and CT) might be acceptable substitutes in certain situations. If

> gadolinium-containing contrast is medically necessary, prompt

> hemodialysis after contrast administration to facilitate clearance

of

> the contrast might be reasonable for patients who have established

> hemodialysis access; however, the effectiveness of this strategy in

> reducing the risk for NFD development or progression is unknown.

Among

> patients with no other indication for chronic or acute hemodialysis,

> the risks of establishing hemodialysis access should be weighed

> against theoretical benefits of hemodialysis after

> gadolinium-containing contrast administration. CDC and FDA are

> collaborating to assess potential differences among

> gadolinium-containing contrast agents, including the associated risk

> for NFD and possible related factors. Additional studies are needed

to

> assess the ability of peritoneal dialysis and hemodialysis to clear

> gadolinium-containing contrast agents and to clarify the mechanism

by

> which use of gadolinium or chelating agents might result in NFD.

> Clinicians who treat patients with renal disease should be aware of

> the risk for NFD and consider the diagnosis in patients with

> characteristic skin lesions. Suspected adverse drug events should be

> reported to FDA via the MedWatch program by phone (1-800-FDA-1088),

by

> fax (1-800-FDA-0178), or online

> (http://www.fda.gov/medwatch/index.html).

>

> Acknowledgments

>

> The findings in this report are based, in part, on contributions by

S

> Cowper, MD, Yale Univ School of Medicine, New Haven, Connecticut; C

> Kwoh, MD, D Berk, MD, Washington Univ School of Medicine, St. Louis,

> Missouri; DG Kleinbaum, PhD, Dept of Epidemiology, Rollins School of

> Public Health at Emory Univ, Atlanta; R Wang, DO, S Pappas, PhD, J

> Jarrett, MS, Div of Laboratory Sciences, National Center for

> Environmental Health, and J Guarner, MD, Div of Viral and

Rickettsial

> Diseases, National Center for Zoonotic, Vector-Borne, and Enteric

> Diseases (proposed), CDC.

>

> References

>

> 1. Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE.

> Scleromyxoedema-like cutaneous diseases in renal-dialysis patients.

> Lancet 2000;356:1000--1.

>

> 2. Cowper SE. Nephrogenic fibrosing dermopathy: the first 6 years.

> Curr Opin Rheumatol 2003;15:785--90.

>

> 3. Ting WW, Stone MS, Madison KC, Kurtz K. Nephrogenic fibrosing

> dermopathy with systemic involvement. Arch Dermatol 2003;139: 903--

6.

>

> 4. Jan F, Segal JM, Dyer J, LeBoit P, Siegfried E, Frieden IJ.

> Nephrogenic fibrosing dermopathy: two pediatric cases. J Pediatr

> 2003;143: 678--81.

>

> 5. Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic

> fibrosis: suspected causative role of gadodiamide used for

> contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol

> 2006;17:2359--62.

>

> 6. Swaminathan S, Ahmed I, McCarthy JT, et al. Nephrogenic fibrosing

> dermopathy and high-dose erythropoietin therapy. Ann Intern Med

> 2006;145:234--5.

>

> 7. Food and Drug Administration. Public health advisory:

> gadolinium-containing contrast agents for magnetic resonance imaging

> (MRI): Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance.

> Available at

http://www.fda.gov/cder/drug/advisory/gadolinium_agents.htm.

>

> 8. Runge VM. Safety of approved MR contrast media for intravenous

> injection. J Magn Reson Imaging 2000;12:205--13.

>

> 9. Joffe P, Thomsen HS, Meusel M. Pharmacokinetics of gadodiamide

> injection in patients with severe renal insufficiency and patients

> undergoing hemodialysis or continuous ambulatory peritoneal

dialysis.

> Acad Radiol 1998;5:491--502.

>

> 10. Okada S, Katagiri K, Kumazaki T, Yokoyama H. Safety of

gadolinium

> contrast agent in hemodialysis patients. Acta Radiologica 2001;42:

> 339--41.

>

> TABLE 1. Characteristics of nephrogenic fibrosing dermopathy

> case-patients and matched controls* from hospital A — St. Louis,

> Missouri, December 2002–August 2006

> http://www.cdc.gov/mmwr/preview/mmwrhtml/figures/m607a1t1.gif

>

> TABLE 2. Odds ratios (ORs) for selected characteristics among

> nephrogenic fibrosing dermopathy case-patients and matched controls*

> from hospital A — St. Louis, Missouri, December 2002–August 2006

> http://www.cdc.gov/mmwr/preview/mmwrhtml/figures/m607a1t2.gif

>

> FIGURE. Number of confirmed and suspected cases of nephrogenic

> fibrosing dermopathy at hospital A, by date of disease detection —

St.

> Louis, Missouri, December 2002– August 2006

> http://www.cdc.gov/mmwr/preview/mmwrhtml/figures/m607a1f.gif

>

February 27, 2007

I'VE HAD SOOOOOOOOOOOO MANY MRI'S OF MY CNS (HEAD & SPINAL CORD) WITH NO

PROBLEMS. I ALMOST OWN MY OWN MRI SCANNER BY NOW, LOL!! :>(

VICTORIA

[] Re: [occ-env-med-l] MMWR/07-02-23, Nephrogenic

Fibrosing Dermopathy from Gd-med-contrast (fwd)