ObjectivesThe Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint (SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation.MethodsThe literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC).ResultsNo revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97).ConclusionThe ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.

The new SPARCC MRI SSS method can detect structural changes in the SIJ with acceptable reliability over a 1-2-year timeframe, and should be further validated in patients with SpA.

Objective. Fat metaplasia in bone marrow on T1-weighted magnetic resonance imaging (MRI) scans may develop after resolution of inflammation in patients with ankylosing spondylitis (AS) and may predict new bone formation in the spine. Similar tissue, termed backfill, may also fill areas of excavated bone in the sacroiliac (SI) joints and may reflect resolution of inflammation and tissue repair at sites of erosions. The purpose of this study was to test our hypothesis that SI joint ankylosis develops following repair of erosions and that tissue characterized by fat metaplasia is a key intermediary step in this pathway.Methods. We used the Spondyloarthritis Research Consortium of Canada (SPARCC) SI structural lesion score (SSS) method to assess fat metaplasia, erosions, backfill, and ankylosis on MRIs of the SI joints in 147 patients with AS monitored for 2 years. Univariate and multivariate regression analyses focused first on identifying significant MRI predictors of new backfill and fat metaplasia. We then assessed the role of backfill and fat metaplasia in the development of new ankylosis. All analyses were adjusted for demographic features, treatment, and baseline and 2-year change in SSS values for parameters of inflammation and MRI structural lesions.Results. Resolution of inflammation and reduction of erosions were each independently associated with the development of new backfill and fat metaplasia at 2 years on multivariate analyses. Multivariate regression analysis that included demographic features, baseline and 2-year change in parameters of inflammation and MRI structural lesion showed that reduction in erosions (P ‫؍‬ 0.0005) and increase in fat metaplasia (P ‫؍‬ 0.002) at 2 years was each independently associated with the development of new ankylosis.Conclusion. Our data support a disease model whereby ankylosis develops following repair of erosions, and fat metaplasia and backfill are key intermediary steps in this pathway.Spondyloarthritis (SpA) is an inflammatory disorder primarily of the axial spine that typically begins with sacroiliitis. The first sign of disease on radiography is the appearance of erosion of the subchondral bone of the ilium, which is seen as a blurred cortical outline. Progression results in more extensive erosion involving the sacral bone and the appearance of pseudowidening. Subsequent features include bone sclerosis and, finally, ankylosis across the joint. Magnetic resonance imaging (MRI) constitutes a major advance in the field through its ability to demonstrate active inflammation on fatsuppressed sequences, such as short tau inversion recovery (STIR), and structural lesions, such as fat metaplasia, erosions, and ankylosis, on T1-weighed sequences (1).

BackgroundStudies have shown that structural lesions may be present in patients with non-radiographic axial spondyloarthritis (nr-axSpA). However, the relevance of structural lesions in these patients is unclear, particularly without signs of inflammation on magnetic resonance imaging (MRI). We assessed the presence of structural lesions at baseline on MRI in the sacroiliac joints (SIJ) of patients with nr-axSpA with and without SIJ inflammation on MRI.MethodsBone marrow edema (BME) was assessed on short tau inversion recovery (STIR) scans from 185 patients with nr-axSpA, by two independent readers at baseline using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Structural lesions were evaluated on T1 weighted spin echo scans, with readers blinded to STIR scans, using the SPARCC MRI SIJ structural score. Disease characteristics and structural lesions were compared in patients with SIJ BME (score ≥2) and without SIJ BME (score <2).ResultsBoth SIJ BME and structural lesions scores were available for 183 patients; 128/183 (69.9%) patients had SIJ BME scores ≥2 and 55/183 (30.1%) had scores <2. Frequencies of MRI structural lesions in patients with vs without SIJ BME were: erosions (45.3% vs 10.9%, P < 0.001), backfill (20.3% vs 0%, P < 0.001), fat metaplasia (10.9% vs 1.8%, P = 0.04), and ankylosis (2.3% vs 1.8%, P = ns). Significantly more patients with both SIJ BME and structural lesions were male and/or HLA-B27 positive than patients with only SIJ BME. Mean (SD) spinal scores (23 discovertebral units) were significantly higher in patients with SIJ structural lesions than without: 6.5 (11.5) vs 3.3 (5.1), respectively, P = 0.01.ConclusionsIn patients with nr-axSpA, SIJ structural lesions, particularly erosions, may be present on MRI when radiographs are normal or inconclusive, even in patients negative for MRI SIJ inflammation. They may reflect more severe disease with greater spinal inflammation.Trial RegistrationClinicalTrials.gov, NCT01258738. Registered on 9 December 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1342-9) contains supplementary material, which is available to authorized users.

Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS). Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural protein of cartilage and type III collagen of connective tissues, and obvious targets for the collagenalytic, which increase during tissue inflammation. The objective of the study was to investigate the diagnostic and prognostic utility of cartilage, C2M, and synovial, C3M, turnover biomarkers in AS. Serum samples were retrieved from patients suffering from AS (n = 103), RA (n = 47) and healthy controls (n = 56). AS progressors were defined as having new vertebral syndesmophytes or more that 3 unit change in mSASSS over a two-year period. Type II collagen degradation markers in serum were measured by the C2M ELISA, and type III collagen degradation by the C3M ELISA. Logistic regression and dichotomized decision tree were used to analyze the prognostic value of the markers individually or in combination. Both C2M and C3M levels were significantly higher in RA patients than in healthy controls (p<0.0001). Diagnostic utility was analyzed by ROC and areas under the curve (AUCs) were 72% and 89% for C2M and C3M, respectively. Both C2M and C3M, were significantly higher in serum samples from AS patient than from healthy controls (p<0.0001). The AUCs of C2M and C3M, respectively, were 70% and 81% for AS. A combination of C2M and C3M, dichotomized according to best cut-offs for individual markers, could correctly identify 80% of the progressors and 61% of the non-progressors. The present study is the first to show that specific biomarkers of cartilage and connective tissue degradation facilitate both diagnosis and prediction of progression of RA and AS.

Objective. Ankylosing spondylitis (AS) has been considered a seronegative rheumatic disease based on absent or low levels of antibodies against citrullinated proteins. The present study was undertaken to evaluate whether a citrullinated and matrix metalloproteinasedegraded fragment of vimentin (VICM) could be a prognostic biomarker in AS.Methods. VICM was measured in serum samples from healthy controls (n ‫؍‬ 35), control patients with rheumatoid arthritis (RA) (n ‫؍‬ 47), and patients with AS (n ‫؍‬ 201). The optimal cutoff for diagnostic sensitivity and specificity was determined by receiver operating characteristic curve analysis. Baseline and 2-year spine radiographs were available from 118 AS patients, and were scored using the modified Stoke AS Spine Score (mSASSS). We assessed correlations with patient demographic characteristics (age, disease duration), disease activity (Bath AS Disease Activity Index [BASDAI], C-reactive protein level), and disease severity (mSASSS) using Spearman's rho. The independent association of VICM with 2-year radiographic progression, defined as a change of >0 in the mSASSS or the development of a new syndesmophyte, was analyzed by multivariate regression.Results. Levels of degraded VICM were significantly higher in both RA patients and AS patients than in healthy controls (both P < 0.001). AS patients with the highest levels of VICM had the largest burden of disease (P < 0.01), i.e., highest mSASSS score and BASDAI. VICM levels were significantly and independently associated with radiographic progression after 2 years (␤ ‫؍‬ 0.69, P ‫؍‬ 0.0005). Patients with both a high VICM level and a high baseline mSASSS had the highest risk of radiographic progression (odds ratio 13 for mSASSS change, 32 for new syndesmophytes), with progression occurring in 67% of these patients.Conclusion. The present findings show that serum VICM may be of prognostic value in AS. The data also suggest that citrullination may be relevant in AS pathogenesis.

Objectives To determine quantitative sacroiliac joint (SIJ) MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial spondyloarthritis (axSpA) and that predict clinical diagnosis. Methods The ASAS MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises: A. 169 cases and 7 central readers; B. 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SIJ quadrants or slices with bone marrow edema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with ≥95% specificity were analyzed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPV/NPV) and selecting cut-offs with PPV≥95%. Results Active or structural lesions typical of axSpA on MRI had PPV≥95% for clinical diagnosis of axSpA. Cut-offs that best reflect definite active lesion typical of axSpA were either ≥4 SIJ quadrants with BME at any location or at the same location in ≥ 3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of ≥ 3 SIJ quadrants with erosion or ≥ 5 with fat lesion, erosion at the same location for ≥2 consecutive slices, fat lesion at the same location for ≥3 consecutive slices, or presence of a ‘deep’ (&gt;1cm) fat lesion. Conclusion We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPV for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research.

ObjectiveWe tested the hypothesis that fat metaplasia on MRI of the sacroiliac joints (SIJ) increases the propensity for new bone formation in the spine of patients with spondyloarthritis.MethodsWe assessed baseline T1-weighted and short τ inversion recovery SIJ MRIs from patients in the Follow Up Research Cohort in Ankylosing Spondylitis (FORCAST). Radiographic progression was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Structural and inflammatory lesions were scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ structural and SPARCC SIJ inflammation scores, respectively. Radiographic progression was compared in cases with and without definite MRI lesions (score ≥2 or <2) and the extent of MRI lesions at baseline was compared in patients with and without radiographic progression. The predictive capacity of MRI SIJ lesions for radiographic progression in the spine was assessed in univariate and multivariate regression analyses.ResultsThe extent of MRI structural lesions in the SIJ at baseline was significantly greater in those patients who had spinal radiographic progression on follow-up (p=0.003, 0.02, 0.003 for fat metaplasia, backfill and ankylosis, respectively). Also, radiographic progression was significantly greater in cases with definite baseline SIJ ankylosis (p=0.008). In multivariate regression that included all types of MRI lesions and was adjusted for age, sex, symptom duration, duration of follow-up, CRP, baseline mSASSS and treatment, the extent of SIJ fat metaplasia and ankylosis at baseline were independently associated with radiographic progression.ConclusionsSIJ ankylosis and fat metaplasia but not inflammatory lesions increase the propensity for radiographic progression in the spine.