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Features of Nephrogenic Systemic Fibrosis on Radiology Exam

Features of Nephrogenic Systemic Fibrosis on Radiology Exam

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Radiological findings on patients with a confirmed diagnosis of nephrogenic systemic fibrosis.
Radiological findings on patients with a confirmed diagnosis of nephrogenic systemic fibrosis.

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Published by: gasfgd on Apr 15, 2012
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AJR:193, July 2009 61
gen bundles seen in the dermis, and otenincreased dermal deposits o mucin.These criteria have been expanded in a re-cent review [32].Because NSF primarily involves the skin,little attention has been paid to its imagingcharacteristics [33]. We have seen the imag-ing studies o 26 biopsy-conrmed cases o NSF at our institution. This article illustratesthe spectrum o imaging ndings in theseNSF patients with photographic and histo-pathologic correlation.
Deep punch biopsy specimens o NSF le-sions show, in varying proportions, spindlecell prolieration, thickened collagen bun-dles, and mucin deposition (Fig. 1) in a pro-cess believed to be mediated by circulatingbrocytes inappropriately stimulated by gad-olinium [34]. Although NSF primarily a-ects the skin, involvement o skeletal mus-cle, heart, and lungs has also been reported[23, 32, 35]. The histologic eatures o NSFcan be very similar in appearance to otherdermatologic conditions, including sclero-myxedema, scleroderma and deep morphea,lipodermatosclerosis, eosinophilic asciitis(Shulman syndrome), and chronic grat-ver-sus-host disease [32]. Thus, diagnosing NSFrequires a combination o characteristic his-tologic and clinical ndings.
Clinical Manifestations
All NSF patients have signicant renalimpairment, with an estimated GFR o < 30
Features of Nephrogenic SystemicFibrosis on Radiology Examinations
Michael F. Morris
Yang ZhangHonglei ZhangJoan C. ProwdaDavid N. SilversRashid A. FawwazMartin R. Prince
Morris MF, Zhang Y, Zhang H, et al.
All authors: Department o Radiology and Departmento Dermatology and Dermatopathology at Columbia andCornell Universities, 416 E 55th St., New York, NY 10022.Address correspondence to M. R. Prince(map2008@med.cornell.edu).
Gastrointestinal Imaging • Pictorial Essay
2009; 193:61–690361–803X/09/1931–61© American Roentgen Ray Society
ephrogenic systemic brosis (NSF)is a rare disease seen in patientswith severe renal impairment thathas garnered increased interestamong radiologists because o reports o its as-sociation with gadolinium-based contrast agents(GBCAs) [1–20]. Many case series have report-ed that high doses o GBCA and possibly o lin-ear nonionic GBCA contribute to an increasedrisk o NSF [16, 17, 21–25]. These ndingshave led to recommendations or radiologiststo avoid the use o GBCA or reduce the doseo GBCA in patients with an estimated glom-erular ltration rate (GFR) o less than 30 mL/ min [26]. It is also recommended that dialysispatients undergo dialysis immediately aterGBCA injection to urther minimize the risk o NSF when GBCA is essential [27].NSF was originally reported by Cow-per et al. [28] to have rst occurred in 1997.NSF aects male and emale patients equal-ly and has been reported to occur in patientso all ages including children as young as 8years old [29]. Although the cause o NSF re-mains unknown, most patients have a historyo gadolinium exposure and gadolinium hasbeen detected in NSF skin lesions, as report-ed by several authors [9, 30].Cowper [31] has established the ollowingdiagnostic criteria or NSF:…large areas o hardened skin withslightly raised plaques, papules, or con-fuent papules; with or without pigmen-tary alteration and/or with biopsies show-ing increased numbers o broblasts,alteration o the normal pattern o colla-
CT, gadolinium, mammography, MRI,nephrogenic systemic brosis, PET, scintigraphy,ultrasoundDOI:10.2214/AJR.08.1352Received June 5, 2008; accepted ater revisionDecember 25, 2008.M. R. Prince has patent agreements with the ollowingcompanies, which manuacture gadolinium-basedcontrast agents: GE Healthcare, Bayer HealthCare,Mallinckrodt Imaging, Bracco Laboratories, and Epix.
    F    O    C    U    S    O    N   :
The objective o this article is to illustrate the spectrum o imaging nd-ings with photographic and histopathologic correlation in patients with biopsy-proven neph-rogenic systemic brosis (NSF).
Features o NSF may be evident on the patient’s skin as well as on rou-tine imaging studies, although these imaging ndings are nonspecic and are more likely tooccur with other diseases.
Morris et al.Imaging Features o NSFGastrointestinal ImagingPictorial Essay
62 AJR:193, July 2009
Morris et al.
mL/min (stage IV or V kidney disease), dial-ysis-dependent end-stage renal disease, oracute renal ailure. Patients oten initiallypresent with nonspecic complaints—includ-ing joint pain, extremity swelling, and sti-ness—that in turn may lead to multiple imag-ing procedures. On physical examination, thecutaneous maniestations o NSF commonlyinvolve the extremities and trunk beginningdistally and spreading proximally while spar-ing the ace. Patients with mild disease canpresent with a variety o nonspecic ndingsranging rom erythema, papules, and plaques(Fig. 2) to skin dimpling and peau d’orange(Fig. 3). Patients may develop contracturesthat reduce mobility (Fig. 4). Although mostcases o NSF are sel-limiting and some re-gress spontaneously, an estimated 5% have arapidly progressive ulminate course [23].Unlike allergic reactions that happen with-in minutes o injection and are independento contrast agent dose, the skin changes o NSF typically are delayed, occurring rom 2weeks to 2 months ater high-dose GBCA in- jection. NSF is rare with standard 0.1 mmol/ kg doses o gadolinium [27]. There may bean initial prodrome o muscle pain, ever,weakness, swelling, redness, pruritus, or painin the limbs sometimes with muscle weak-ness, edema, or erythema and occasionallywith palpable warmth o the involved extrem-ities; there may be forid scleral telangiec-tasia resembling conjunctivitis [36]. Clinicalseverity is related to both the extent o thebrosing dermopathy and the degree o sys-temic involvement. Muscle involvement tendsto be underlying the cutaneous lesions withbrotic bands in the subcutaneous tissuestethering the skin to the underlying ascia. Insome patients the NSF lesions resolve withrestoration o normal renal unction ater re-nal transplantation or resolution o acute re-nal ailure. In many cases the lesions persist,although a recent report shows promising re-sults or treating patients with NSF usingimatinib mesylate [37].
The conventional radiographic ndings o NSF are nonspecic, and abnormalities onradiographs are rare and usually are second-ary to the sequelae o joint contracture andimmobility. Flexion deormities and disuseosteopenia rom contractures occur mostcommonly in the eet (Fig. 4), knees, hands,and elbows. In 140 NSF patients described indetail in case reports, limited range o mo-tion or joint contractions were noted clinical-ly in 106 (58%) [38]. We saw joint contrac-tures on radiographs in two o our 26 patients,but the contractures in one patient were dueto juvenile rheumatoid arthritis and had beenpresent beore NSF developed. Note that thedierential diagnosis or joint contracturesincludes arthritides and immobilization (e.g.,due to trauma, burns, nerve injury, or stroke);the likelihood that a joint contracture signi-es NSF is negligible.Although microscopic dermal calcica-tions are common in NSF specimens andCowper and colleagues have described skincalcications on radiographs, these calcica-tions are rare in NSF cases [39]. We oundcutaneous calcications on an imaging studyin only one o our 26 biopsy-positive NSF pa-tients. In that patient, skin calcications onabdominopelvic CT were thought to be morelikely related to the patient’s other diseasesincluding juvenile rheumatoid arthritis, dial-ysis-dependent end-stage renal ailure, andsystemic lupus erythematosus. Vascular cal-cications visible on radiographs are usuallyrelated to diabetes or renal ailure.
Three o the six emale NSF patients whounderwent mammography at our hospital hadskin thickening and increased subcutaneouslinear markings (Fig. 5) corresponding toNSF lesions. Although the breast skin thick-ening in these patients was readily identiedas part o the NSF process occurring overthe legs, arms, and chest, skin thickening onmammography is much more likely to be re-lated to infammatory breast cancer, cellulitis,scarring, or venous or lymphatic obstruction.
Duplex ultrasound may be perormed toassess or extremity deep venous thrombo-sis (DVT) in patients with NSF because o the common complaints o extremity painand swelling. Breast ultrasound may be per-ormed in emale patients with NSF whohave mammographic abnormalities, and itmay show skin thickening and subcutane-ous edemalike infammatory changes. Notethat these ndings are nonspecic; are muchmore likely to result rom DVT, infamma-tion, or cellulitis; and would not be expectedto elicit the diagnosis o NSF.
The most common CT study perormedin patients with NSF is o the abdomen andpelvis; however, occasionally CT o an ex-tremity is perormed during a workup or ex-tremity pain. Depending on the severity o disease, CT may show varying degrees o skin thickening and inltration o the subcu-taneous and sot tissues (Figs. 6 and 7). Re-ormations in coronal and sagittal planes andalong the axis o the bones may acilitate as-sessment o dermal inltration. In particu-lar, bands o collagen in the subcutaneous attether the skin to underlying sot tissues [40].Systemic involvement o the internal organsis dicult to identiy on CT and thus hasbeen reported only at autopsy or on surgicaland biopsy specimens. The dierential diag-nosis or skin thickening and inltration o the subcutaneous at on CT includes edema,cellulitis, ascitis and panniculitis, sclero-derma and sclerodermalike conditions (e.g.,morphea), cutaneous T-cell lymphoma, andMerkel cell carcinoma.
The spectrum o abnormal MRI ndingsin patients with NSF can be similar to thatseen on CT. Subtle areas o edema are seen onSTIR or T2-weighted at-saturated images inpatients with mild clinical maniestations o NSF, whereas patients with more severe in-volvement show skin thickening and diuseinfammatory changes throughout the sottissues (Figs. 8–10). Although gadolinium iscontraindicated in patients with severe renalimpairment, enhancement o the subcutane-ous tissues and skeletal muscle may be seenon T1-weighted at-saturated images whenGBCA is administered [24]. These nonspe-cic ndings are seen in many infammato-ry, neoplastic, and traumatic conditions andshould not raise suspicion or NSF.
Nuclear Medicine
Extraosseous accumulation o 
Tc-hy-droxydiphosphonate (HDP) can be seenin NSF patients undergoing bone scintig-raphy (Fig. 11) and was previously report-ed [32, 41, 42]. The dierential diagnosisor diuse extremity sot-tissue uptake onbone scans includes myositis ossicans andheterotopic calcications; dermatomyositis;rhabdomyolysis; polymyositis; metastaticcalcications; and technical actors, includ-ing contamination and tourniquet eects.There is a case report describing FDG up-take in NSF [41]. We ound only one NSFpatient with FDG uptake on PET and that pa-tient had cutaneous T-cell lymphoma, whichwas more likely to be the reason or FDG ac-tivity in the skin.
AJR:193, July 2009 63
Imaging Features of NSFConclusion
NSF has a variable appearance on routineimaging studies. Oten there are no abnor-mal imaging ndings. However, convention-al radiographs can show joint contractures,skin thickening, and possibly cutaneous cal-cinosis; ultrasound may show thickening andedema o the cutis, particularly in the breast;CT may show skin thickening and inltra-tion o subcutaneous tissues; MRI may showincreased signal on fuid-sensitive sequenc-es in the skin, subcutaneous tissues, and ex-tremity musculature; and bone scintigraphymay show diuse sot-tissue uptake in theextremities. Studies o the head and anteri-or neck ail to show changes related to NSFbecause the disease spares that region. Allthese imaging ndings are nonspecic andcannot be used to diagnose NSF using thecurrently accepted diagnostic criteria.
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