{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T13:11:33Z","timestamp":1767791493589,"version":"3.49.0"},"reference-count":63,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,9,15]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mixed connective tissue disease (MCTD) has long been debated as an early nonspecific phase\/symptom of differentiated connective tissue diseases (dCTD), similarly to interstitial pneumonia with autoimmune features (IPAF) and very early diagnosis of systemic sclerosis (SSc) (VEDOSS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to evaluate the predictive value of IPAF, VEDOSS and dCTD classification criteria variables in MCTD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an observational study within the French MCTD cohort. IPAF, VEDOSS and current dCTD classification criteria were used to classify patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three hundred and twenty-four MCTD patients were included and followed for 8 (3.3\u201313) years. Among them, 111 (34.3%) progressed into a dCTD, that is, 50 (15.4%) SSc, 40 (12.3%) systemic lupus erythematosus (SLE) and 11 (3.4%) Sj\u00f6gren\u2019s disease. At diagnosis, 38 (11.7%) patients fulfilled IPAF criteria, among which 15 (39.5%) progressed into a dCTD (vs 75 (26.2%) in patients who did not fulfil IPAF criteria; p=0.09). At diagnosis, 293 (90.4%) patients fulfilled VEDOSS criteria but did not progress significantly more frequently to SSc than MCTD patients without VEDOSS criteria (46 (15.7%) vs 4 (12.9%); p=0.8). At baseline, SSc classification criteria did not predict evolution toward SSc, whereas antiphospholipid antibodies and low C3 and\/or C4 were predictive of an evolution toward SLE (p=0.01\u2009and p=0.04, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>At MCTD diagnosis, fulfilment of IPAF and\/or VEDOSS criteria was not predictive of evolution toward SSc, whereas antiphospholipid antibodies and low C3 and\/or C4 were predictive of an evolution toward SLE. This suggests that MCTD patients should be excluded from IPAF and VEDOSS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-006145","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:15:13Z","timestamp":1761214513000},"page":"e006145","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Unravelling IPAF, VEDOSS and connective tissue diseases classifications through the mixed connective tissue disease spectrum"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7823-1827","authenticated-orcid":false,"given":"Kevin","family":"Chevalier","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Centre de R\u00e9f\u00e9rence Maladies Auto-Immunes et Syst\u00e9miques Rares d\u2019Ile de France, AP-HP.Centre, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Thoreau","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, CHRU de Tours, Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, H\u00f4pital Henri Mondor, Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertrand","family":"Godeau","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, H\u00f4pital Henri Mondor, Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Agard","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne, Centre Hospitalier Universitaire de Nantes, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Papo","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat Claude-Bernard, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6544-234X","authenticated-orcid":false,"given":"Karim","family":"Sacre","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat Claude-Bernard, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Bader-Meunier","sequence":"additional","affiliation":[{"name":"Pediatric Hematology-Immunology and Rheumatology, Hopital universitaire Necker-Enfants malades, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5523-1856","authenticated-orcid":false,"given":"Raphaele","family":"Seror","sequence":"additional","affiliation":[{"name":"Rheumatology, Hopital Bicetre, Le Kremlin-Bic\u00eatre, 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Diagnostic criteria for classification of MCTD. Mixed connective tissue disease and antinuclear antibodies. Amsterdam: Elsevier, 1987:23\u201332."},{"key":"2026010700551802000_11.4.e006145.16","unstructured":"Alarcon-Segovia D , Villarreal M . Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R , Sharp GC , eds. Mixed connective tissue disease and anti-nuclear antibodies. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division), 1987: 33\u201340."},{"key":"2026010700551802000_11.4.e006145.17","unstructured":"Kahn MF , Appelboom T . Syndrome de sharp. In: Kahn MF , Peltier AP , Mayer O , eds. Les maladies syst\u00e9miques. Paris: Flammarion, 1991: 545\u201356."},{"key":"2026010700551802000_11.4.e006145.18","unstructured":"Kasukawa R , Tojo T , Miyawaki S , et al . Preliminary diagnostic criteria for classification of mixed connective tissue disease. In: Kasukawa R , Sharp GC , eds. 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