Maksymowych, Walter

Weber, Ulrich

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PERSPECTIVEHow does imaging help the clinician in the evaluationand management of spondyloarthritis?Ulrich Weber & Walter P. MaksymowychPublished online: 29 March 2008# ISS 2008IntroductionClinical practice and research in the field of spondyloarthritis(SpA) have changed dramatically in recent years due to theadvent of magnetic resonance imaging (MRI) and theintroduction of symptomatically highly effective yet expen-sive anti-tumor necrosis factor alpha (TNFα) agents. Whilephysical and laboratory examinations are of limited diagnos-tic value, MRI is regarded as the most sensitive imagingmodality for the detection of early inflammatory lesions inthe axial skeleton before any inflammatory changes can beseen on standard radiography. However, plain radiographycontinues to play a major role in evaluating potential disease-modifying agents in the treatment of SpA.Challenges in clinically suspected earlyspondyloarthritisDiagnosing SpA at an early disease stage remains achallenge in routine practice, because physical examinationhas limited sensitivity, while laboratory investigation haslimited specificity for this disorder. A combination ofhistorical features has been proposed as diagnostic criteria[1], although elicitation of these historical items requiresstandardization and validation is necessary in primary carecohorts.The modified New York classification criteria publishedin 1984 [2] are still widely used in clinical practice formaking a diagnosis of ankylosing spondylitis (AS). Theseclassification criteria rely primarily on plain radiographicfeatures of sacroiliitis, which include erosions and sclerosisthat have high disease specificity, as required for classifi-cation criteria. However, plain radiography is not helpful inmost patients with clinically suspected early AS becauseonly about 50% of patients with inflammatory back painhave developed definite radiographic features of sacroiliitisby 10 years of follow-up [3]. Hence, these criteria are notideal for making an early diagnosis in an individual patient.Furthermore, defining reliable morphologic criteria thatdistinguish equivocal (stage 1) from definite (stage 2)sacroiliitis is notably difficult and is primarily quantitative.Radiographic stage 2 sacroiliitis had only modest sensitivityand specificity for AS, whether films were read byrheumatologists or radiologists, and training did notimprove this [4]. Standard radiography serves primarily toconfirm late-stage disease and is not suitable for earlydiagnosis.In 2004, a literature review reported specificity, sensi-tivity, and likelihood ratios for various clinical features,laboratory findings and skeletal imaging techniques used inclinical practice for diagnosing pre-radiographic AS [5].When clinical features of inflammatory back pain andpositive HLA B27 status are present the probability of ASis estimated at 59%. The presence of inflammatory lesionson MRI is estimated to increase the probability of AS to80–95%. The MRI studies on which these estimates werebased recruited small numbers of patients with inflamma-tory and mechanical causes of back pain and so must beSkeletal Radiol (2008) 37:487–490DOI 10.1007/s00256-008-0477-9U. Weber (*)Department of Rheumatology, Balgrist University Hospital,Forchstrasse 340,8008 Zurich, Switzerlande-mail: ulrich.weber@balgrist.chW. P. MaksymowychDepartment of Rheumatology, University of Alberta,562 Heritage Medical Research Building,Edmonton, AL T6G 2S2, Canadae-mail: walter.maksymowych@ualberta.caregarded as preliminary. MR evaluation consisted largely ofdynamic imaging of the sacroiliac (SI) joints with gadolin-ium augmentation, which is costly and therefore unlikely tobe feasible in routine practice. Moreover, these estimatesdepend greatly on the clinical criteria used to select patientsfor further examination by MRI. In a cohort of 68 patientswith inflammatory back pain of less than 2 years’ duration,assessment of structural changes by standard radiographs,together with evaluation of inflammatory lesions on STIRsequences, was optimal for the detection of sacroiliitis [6].However, the frequency of abnormalities detected by MRIwas higher in patients meeting three sets (58%) as opposedto only one set (7%) of clinical classification criteria forSpA [7]. MRI is therefore most appropriately used in pre-radiographic disease where there is a reasonable pre-testprobability based on clinical evaluation together with apositive test for HLA B27.The second most frequent region (after the SI joints)affected by inflammation in SpA is the thoracic spine [8].With conventional MRI the spine is imaged in the sagittalorientation in two halves, a cervicothoracic and a thora-columbar portion. It is important to scan and evaluate thelateral portions of the thoracic spine, which include thecostovertebral and costotransverse joints since one studyhas shown that inflammation is more common in the lateralthan in the central sagittal slices [9].The histopathological basis of bone marrow signalabnormalities seen on STIR and gadolinium-augmentedsequences in SpA remains to be determined. One studydemonstrated a direct correlation between the severity ofhistopathological abnormalities observed on CT-guidedbiopsies of the SI joints and the degree of gadoliniumaugmentation observed with dynamic MRI [10]. A recentstudy in 8 patients with long-standing disease undergoingspinal extension surgery showed moderate correlationbetween bone marrow inflammatory lesions on STIRsequences and histopathological findings of interstitialmononuclear cell infiltrates in zygapophyseal joints [11].An MRI–histological correlation study of normal SI jointsfound that the synovial part of this joint is confined to thedistal cartilaginous portion at the iliac side [12]. Thisfinding may explain why early inflammatory signs on MRIof patients with clinically suspected SpA are often seen inthe inferior iliac portion of the SI joints [13].Whole body MRI is a recently introduced modificationof conventional MRI that allows simultaneous assessmentof the entire spine, the SI joints, the shoulder, the pelvicgirdle, and the anterior chest wall in SpA [14]. Acquisitionof T1-weighted spin-echo and STIR images in the coronaland sagittal planes takes 30 min to perform, which iscomparable to conventional imaging. Spatial resolution issimilar to that of standard MR examination. With its morecomprehensive assessment of inflammation in the entireaxial skeleton, whole body MRI is a promising tool for thediagnostic work-up of patients with suspected early SpA,and it may serve as an objective and quantitative measureof inflammation.In suspected pre-radiographic SpA, computed tomography(CT) of the SI joints is no longer recommended for routinediagnostic evaluation due to the increased exposure toradiation, which is relevant to the younger SpA population.In particular, the earliest features of SpA include synovitis andcapsulitis in the posterocaudal portion of the SI joints withadjacent bone marrow edema and these features are notcaptured on CT.Limited studies that have compared imaging modalitieshave shown that bone scintigraphy of the SI joints is lesssensitive than MRI in the diagnostic evaluation of inflam-matory back pain [15, 16]. Its limited specificity ishighlighted by the observation of increased isotope uptakein the SI joints after hopping on one leg [17]. Recentsystematic literature research concluded that scintigraphy ofthe SI joints is of limited diagnostic value for clinicallysuspected early SpA [18].The importance of MRI as the imaging method of choicefor early detection of inflammation of the axial skeleton isreinforced by its inclusion in the Assessment in AnkylosingSpondylitis (ASAS) International Working Group recom-mendations for the management of AS [19]. However, thereare still many issues that have to be clarified. We needstandardized morphologic definitions for acute and chronicinflammatory lesions seen on MRI and an evaluation oftheir specificity and sensitivity, particularly in comparisonto patients with mechanical back disorders. One of the mostrelevant questions for clinical practice is whether theapparently inflammatory lesions seen on MRI are indeedpredictive of future structural changes visible as radio-graphic sacroiliitis and syndesmophyte formation. Theseclinically highly relevant issues have to be addressed beforethe radiographic sacroiliitis included in the modified NewYork classification criteria may be supplanted by MRI informulating diagnostic criteria for early SpA.Imaging in the assessment of a patient with establishedspondyloarthritis unresponsive to standard treatmentClinical and laboratory evaluation are limited in their abilityto discriminate between inflammatory and mechanicalsources of back pain. Consequently, MRI provides addi-tional information regarding disease activity in a patientwith established AS who has failed conventional treatment.This may be particularly useful before initiating therapywith anti-TNFα agents and it may even be considereddesirable to obtain a baseline MRI before committing apatient to long-term therapy with these agents.488 Skeletal Radiol (2008) 37:487–490Transdiscal fractures in an ankylosed spine (transversefractures through intervertebral syndesmophytes, the formerdisk and the posterior elements of the spinal column) andtransvertebral fractures may occur after minor trauma, andrepresent a serious complication with the risk of spinal cordinjury. If the diagnosis is initially missed, these transversespinal fractures may result in a painful intervertebralpseudarthrosis, which may be mistaken for spinal inflam-matory disease activity. These fractures may be difficult tolocate by standard radiography. The imaging methods ofchoice are CT with high resolution multiplanar reconstruc-tion and MRI; the combination of both imaging modalitiesyields the highest sensitivity for detection of transversespinal fractures [20, 21].Osteoporosis is a common complication, not only inadvanced SpA with spinal ankylosis, but may also occurearly in the disease course. Loss of bone mineral density(BMD) correlates with the degree of inflammatory diseaseactivity and improves following treatment with anti-TNFαagents [22]. Insufficiency fractures of vertebral endplatesafter minor trauma may be a reason for prolonged back pain.Low BMD at the femoral neck is associated with increasedvertebral fracture risk in AS patients [23]. Dual energy X-rayabsorptiometry screening should be considered not only inpatients with spinal fusion, but also in relatively shortduration disease (<10 years) if it has been marked bypersistently high inflammatory activity.Imaging in the evaluation of response to therapeuticinterventionMagnetic resonance imaging is rapidly gaining importanceas an objective measure of inflammation in the spine and SIjoints in AS and in complementing clinical and laboratoryevaluation of disease activity, particularly because theprimary validated measures of efficacy are patient self-reports. Scoring indices based on MRI have been developedthat allow quantification of inflammation and are increas-ingly used to assess treatment response in clinical trialswith the TNFα inhibitors etanercept, infliximab, andadalimumab [24–26]. An international multireader exerciseevaluated three different MRI scoring methods for spinalinflammation in AS [27]. All three methods are based onthe assessment of STIR sequences of the spine imaged inthe sagittal plane. Two of the methods (Berlin score; ASspinal MRI activity [ASspiMRIa] score) score inflammato-ry lesions in a single sagittal slice, while the third method(Spondyloarthritis Research Consortium of Canada[SPARCC]) scores lesions in consecutive sagittal slicespermitting three-dimensional assessment of the extent ofthe lesion. Feasibility and discriminatory capacity werecomparable for all three scoring systems, but greaterreliability was observed with the SPARCC method. TheSPARCC group has also developed a scoring index forquantification of inflammation in the SI joints. A recentlypublished randomized controlled trial of adalimumab inactive AS used MRI to assess disease activity both in thespine and in the SI joints with the SPARCC methodology.The SPARCC indices were shown to be reliable and highlydiscriminatory between treatment groups, reinforcing theirvalue in the clinical trial assessment of new treatmentapproaches [26].At present, the suspicion of early axial SpA is mainlybased on clinical grounds. There is increasing evidence thatthe recent advances in MRI will become essential in routinecare for patients with suspected SpA to enable an earlierdiagnosis of this potentially disabling disorder. In routineclinical practice STIR and T1-weighted spin-echo se-quences are sufficient. Contrast-enhanced images are costlyand have not been shown to offer any advantages. Imagingof the spine should be included in diagnostic protocols forSpA to ensure the evaluation of the costovertebral joints.MRI is also valuable in clinical care of patients withestablished SpA unresponsive to standard treatment, be-cause it may not be possible to distinguish differingpathologies on clinical grounds alone. Monitoring theresponse to treatment in SpA by MRI is a focus of interestin clinical research because most efficacy measures arebased on patient self-reports.Acknowledgements Dr. Maksymowych is a senior scholar at theAlberta Heritage Foundation for Medical Research. The project wholebody magnetic resonance imaging in AS is supported by the Walter L.and Johanna Wolf Foundation, Zurich, Switzerland and the Foundationfor scientific research at the University of Zurich, Switzerland.Competing interests The authors have no competing interests inrelation to this article.References1. Rudwaleit M, Khan MA, Sieper J. 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How does imaging help the clinician in the evaluation and management of spondyloarthritis?

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How does imaging help the clinician in the evaluation and management of spondyloarthritis?

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