{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:57:23Z","timestamp":1792612643233,"version":"4.5.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["714312"],"award-info":[{"award-number":["714312"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Introduction<\/jats:title>\n<jats:p>Arthralgia and MRI-detected subclinical inflammation can precede the development of clinically evident rheumatoid arthritis (RA). However, part of the patients presenting with clinically suspect arthralgia (CSA) do not progress to RA. In these \u2018non-progressors\u2019, we aimed to study the frequencies of spontaneous improvement of arthralgia and its relation with the course of subclinical inflammation.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Between April 2012 and April 2015, 241 patients were considered at risk for RA based on the clinical presentation and included in the CSA cohort. One hundred fifty-two patients with complete data on clinical follow-up did not develop clinical arthritis, of which 98 underwent serial 1.5T MRI scans (wrist, MCP2\u20135, and MTP1\u20135 joints) at baseline and after 2\u00a0years. MRI scans were scored for synovitis, tenosynovitis, and bone marrow oedema (summed: MRI inflammation score). MRI scores were compared to scores of symptom-free persons.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>After a 2-year follow-up, 33% of the \u2018non-progressors\u2019 had complete resolution of symptoms; 67% had no symptom resolution and were diagnosed as persistent CSA (44%), osteoarthritis (10%), and tendinomuscular complaints (13%). With symptom-free controls as a reference, patients without resolution did not have increased MRI scores at any time point. However, patients achieving resolution of symptoms had increased MRI inflammation scores at baseline (4.0 vs. 2.6, <jats:italic>p<\/jats:italic>\u2009=\u20090.037), but not after 2\u00a0years (3.0 vs. 2.6; <jats:italic>p<\/jats:italic>\u2009=\u20090.57), and during follow-up, their MRI inflammation score decreased significantly (<jats:italic>p<\/jats:italic>\u2009=\u20090.036).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>A subgroup of CSA patients that did not progress to RA had spontaneous improvement of symptoms and resolution of subclinical joint inflammation. This time relationship suggests that symptoms and inflammation were causally related in these patients. Further research is needed to identify the mechanisms underlying the resolution of inflammation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13075-020-2102-9","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T17:03:13Z","timestamp":1579194193000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Improvement of symptoms in clinically suspect arthralgia and resolution of subclinical joint inflammation: a longitudinal study in patients that did not progress to clinical arthritis"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6128-6888","authenticated-orcid":false,"given":"Robin M.","family":"ten Brinck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie M.","family":"Boeters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna W.","family":"van Steenbergen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette H. M.","family":"van der Helm-van Mil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"key":"2102_CR1","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1136\/annrheumdis-2015-208138","volume":"75","author":"HW van Steenbergen","year":"2016","unstructured":"van Steenbergen HW, Mangnus L, Reijnierse M, et al. Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflammation in relation to progression from clinically suspect arthralgia to arthritis. Ann Rheum Dis. 2016;75:1824\u201330. https:\/\/doi.org\/10.1136\/annrheumdis-2015-208138.","journal-title":"Ann Rheum Dis"},{"key":"2102_CR2","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1136\/annrheumdis-2015-207871","volume":"75","author":"JL Nam","year":"2016","unstructured":"Nam JL, Hunt L, Hensor EMA, et al. Enriching case selection for imminent RA: the use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms \u2013 a cohort study. Ann Rheum Dis. 2016;75:1452\u20136. https:\/\/doi.org\/10.1136\/annrheumdis-2015-207871.","journal-title":"Ann Rheum Dis"},{"key":"2102_CR3","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nrrheum.2011.78","volume":"7","author":"JMW Hazes","year":"2011","unstructured":"Hazes JMW, Luime JJ. The epidemiology of early inflammatory arthritis. Nat Rev Rheumatol. 2011;7:381\u201390. https:\/\/doi.org\/10.1038\/nrrheum.2011.78.","journal-title":"Nat Rev Rheumatol"},{"key":"2102_CR4","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1136\/ard.2009.122473","volume":"69","author":"KP Machold","year":"2010","unstructured":"Machold KP, Landewe R, Smolen JS, et al. The Stop Arthritis Very Early (SAVE) trial, an international multicentre, randomised, double-blind, placebo-controlled trial on glucocorticoids in very early arthritis. Ann Rheum Dis. 2010;69:495\u2013502. https:\/\/doi.org\/10.1136\/ard.2009.122473.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"2102_CR5","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1093\/rheumatology\/key220","volume":"58","author":"Leonie E Burgers","year":"2018","unstructured":"Burgers LE, ten Brinck RM, Van der Helm-van Mil AH. Is joint pain in patients with arthralgia suspicious for progression to rheumatoid arthritis explained by subclinical inflammation? A cross-sectional MRI study. Rheumatology. https:\/\/doi.org\/10.1093\/rheumatology\/key220.","journal-title":"Rheumatology"},{"key":"2102_CR6","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1136\/annrheumdis-2014-205522","volume":"74","author":"HW van Steenbergen","year":"2015","unstructured":"van Steenbergen HW, van Nies JAB, Huizinga TWJ, et al. Characterising arthralgia in the preclinical phase of rheumatoid arthritis using MRI. Ann Rheum Dis. 2015;74:1225\u201332. https:\/\/doi.org\/10.1136\/annrheumdis-2014-205522.","journal-title":"Ann Rheum Dis"},{"key":"2102_CR7","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1002\/art.30200","volume":"63","author":"MPM van der Linden","year":"2011","unstructured":"van der Linden MPM, Batstra MR, Bakker-Jonges LE, et al. Toward a data-driven evaluation of the 2010 American College of Rheumatology\/European League Against Rheumatism criteria for rheumatoid arthritis: is it sensible to look at levels of rheumatoid factor? Arthritis Rheum. 2011;63:1190\u20139. https:\/\/doi.org\/10.1002\/art.30200.","journal-title":"Arthritis Rheum"},{"key":"2102_CR8","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1002\/art.39749","volume":"68","author":"L Mangnus","year":"2016","unstructured":"Mangnus L, van Steenbergen HW, Reijnierse M, et al. Magnetic resonance imaging-detected features of inflammation and erosions in symptom-free persons from the general population. Arthritis Rheumatol. 2016;68:2593\u2013602. https:\/\/doi.org\/10.1002\/art.39749.","journal-title":"Arthritis Rheumatol"},{"key":"2102_CR9","doi-asserted-by":"publisher","unstructured":"Mangnus L, van Steenbergen HW, Lindqvist E, et al. Studies on ageing and the severity of radiographic joint damage in rheumatoid arthritis. 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Ann Rheum Dis. 2005;64:i3\u20137. https:\/\/doi.org\/10.1136\/ard.2004.031773.","journal-title":"Ann Rheum Dis"},{"key":"2102_CR12","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1136\/ard.2006.068361","volume":"66","author":"EA Haavardsholm","year":"2007","unstructured":"Haavardsholm EA, \u00d8stergaard M, Ejbjerg BJ, et al. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Ann Rheum Dis. 2007;66:1216\u201320. https:\/\/doi.org\/10.1136\/ard.2006.068361.","journal-title":"Ann Rheum Dis"},{"key":"2102_CR13","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1136\/annrheumdis-2016-209846","volume":"76","author":"HW van Steenbergen","year":"2017","unstructured":"van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJJ, et al. EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. 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Rheumatology. 2017;56:2145\u201353. https:\/\/doi.org\/10.1093\/rheumatology\/kex340.","journal-title":"Rheumatology"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-2102-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-020-2102-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-2102-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:32:08Z","timestamp":1610670728000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-020-2102-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,16]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2102"],"URL":"https:\/\/doi.org\/10.1186\/s13075-020-2102-9","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,16]]},"assertion":[{"value":"9 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the medical ethics committee of the Leiden University Medical Centre, which is named Commissie Medische Ethiek (CME), under Ethics Approval Number NL38832.058.11. All patients signed an informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors consented to the publication of the manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11"}}