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      Intermetatarsal Bursitis, a Novel Feature of Juxtaarticular Inflammation in Early Rheumatoid Arthritis Related to Clinical Signs: Results of a Longitudinal Magnetic Resonance Imaging Study

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          Abstract

          <div class="section"> <a class="named-anchor" id="acr24640-sec-0001"> <!-- named anchor --> </a> <h5 class="section-title" id="d24630500e240">Objective</h5> <p id="d24630500e242">Intermetatarsal bursae in the forefeet possess a synovial lining similar to joints and tendon sheaths. Inflammation of these bursae (intermetatarsal bursitis [IMB]) was recently identified as specific for early rheumatoid arthritis (RA). The present study was undertaken to determine if IMB is indeed an RA feature by assessing the following: 1) the association with other local inflammatory measures (synovitis, tenosynovitis, and osteitis), 2) the association with clinical signs, and 3) whether it responds to disease‐modifying antirheumatic drug (DMARD) therapy similarly to other local inflammatory measures. </p> </div><div class="section"> <a class="named-anchor" id="acr24640-sec-0002"> <!-- named anchor --> </a> <h5 class="section-title" id="d24630500e245">Methods</h5> <p id="d24630500e247">One hundred fifty‐seven consecutive early RA patients underwent unilateral contrast‐enhanced 1.5T forefoot magnetic resonance imaging (MRI) at diagnosis. MRIs were evaluated for IMB presence and for synovitis, tenosynovitis, and osteitis in line with the RA MRI Scoring (RAMRIS) system (summed as RAMRIS inflammation). MRIs at 4, 12, and 24 months were evaluated for IMB presence and size in patients who had IMB at baseline and received early DMARD therapy. Logistic regression and generalized estimating equations were used. Anti–citrullinated protein antibody (ACPA) stratification was performed. </p> </div><div class="section"> <a class="named-anchor" id="acr24640-sec-0003"> <!-- named anchor --> </a> <h5 class="section-title" id="d24630500e250">Results</h5> <p id="d24630500e252">Sixty‐nine percent of RA patients had ≥1 IMB. In multivariable analysis on bursa level, presence of IMB was independently associated with local presence of synovitis and tenosynovitis, with odds ratios (OR) of 1.69 (95% confidence interval [95% CI] 1.12, 2.57) and 2.83 (95% CI 1.80, 4.44), respectively, but not osteitis. On the patient level, IMB presence was most strongly associated with tenosynovitis (OR 2.92 [95% CI 1.62, 5.24]). IMB presence was associated with local joint swelling (OR 2.7 [95% CI 1.3, 5.3]) and tenderness (OR 1.7 [95% CI 1.04, 2.9]) independent of RAMRIS inflammation. During treatment, IMB size decreased between 0 and 12 months. This decrease associated with decrease in RAMRIS inflammation, which was driven by synovitis decrease. Within ACPA‐positive and ACPA‐negative RA, similar results were obtained. </p> </div><div class="section"> <a class="named-anchor" id="acr24640-sec-0004"> <!-- named anchor --> </a> <h5 class="section-title" id="d24630500e255">Conclusion</h5> <p id="d24630500e257">IMB particularly accompanies inflammation of the synovial lining of joints and tendon sheaths, showed a similar treatment response after DMARD initiation, and associates with typical clinical signs. These findings suggest that IMB represents a frequently present novel RA feature of juxtaarticular synovial inflammation. </p> </div>

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          2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

          The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."
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            EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

            To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.
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              Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score.

              An investigation of clinical and laboratory variables which might form the basis for judging disease activity in clinical practice was made by six rheumatologists in a prospective study of up to three years' duration of 113 patients with early rheumatoid arthritis. Decisions to start treatment with slow acting antirheumatic drugs were equated with moments of high disease activity. If treatment with slow acting antirheumatic drugs was not started or if the slow acting antirheumatic drug remained unchanged for at least one year or if treatment was stopped because of disease remission, this was equated with periods of low disease activity. Two groups, one with high and one with low disease activity according to the above criteria, were formed. Factor analysis was performed to enable easy handling of the large number of clinical and laboratory variables without loss of information; this resulted in five factors. Next, discriminant analysis was done to determine to what extent each factor contributed to discrimination between the two groups of differing disease activity. Finally, a multiple regression analysis was carried out to determine which laboratory and clinical variables underlie the factors of the discriminant function, resulting in a 'disease activity score'. This score consisted of the following variables: Ritchie index, swollen joints, erythrocyte sedimentation rate, and general health, in declining importance. The rheumatologists' decisions to prescribe slow acting antirheumatic drugs, or not, were mainly based on articular symptoms.
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                Author and article information

                Contributors
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                Journal
                Arthritis Care & Research
                Arthritis Care & Research
                Wiley
                2151-464X
                2151-4658
                July 16 2022
                Affiliations
                [1 ]Leiden University Medical Centre Leiden The Netherlands
                [2 ]Erasmus Medical Center Rotterdam The Netherlands
                Article
                10.1002/acr.24640
                8dce57b6-a09d-4301-8e20-d5da66615870
                © 2022

                http://creativecommons.org/licenses/by-nc/4.0/

                http://doi.wiley.com/10.1002/tdm_license_1.1

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