{ "abstract": "Objectives\n\nTo characterize clinical manifestations, major organ involvement, real-world treatment patterns and factors associated with severity classification in Japanese patients with mixed connective tissue disease (MCTD), aiming to clarify its heterogeneous clinical spectrum.Methods\n\nThis nationwide retrospective multicentre study analyzed clinical data from 249 patients who strictly fulfilled the 2019 Japanese Ministry of Health, Labour and Welfare diagnostic criteria for MCTD, derived from an initial real-world registry of 311 clinically diagnosed patients. Clinical features, autoantibodies and therapeutic regimens were summarized and compared between patients with severe vs nonsevere disease.Results\n\nThe cohort was 93.1% female (median onset age 40.6 years). Common findings, specifically Raynaud's phenomenon and/or swelling of the fingers or dorsum of the hands, were present in 100%. Phenotypically, an overlap of systemic lupus erythematosus (SLE)-like and systemic sclerosis (SSc)-like features was most frequent (56.0%), while 32.0% had manifestations across all three phenotypic domains (SLE-, SSc- and IIM-like). Major organ involvement occurred in 32.9% of patients, including pulmonary arterial hypertension in 12.8%. Approximately 28.7% of evaluable patients were classified as severe. Off-scale-high anti-U1-RNP antibody status was not associated with severity classification (P = 0.492) or with broad phenotypic categories. Glucocorticoids and immunosuppressive agents were used in 66.7% and 56.5% of the patients, respectively.Conclusions\n\nMixed connective tissue disease exhibits marked clinical heterogeneity. Severity classification was not associated with off-scale-high anti-U1-RNP antibody status or broad phenotypic categories. These findings support rigorous cardiopulmonary screening and management tailored to the dominant clinical phenotype.", "abstract_shown": true, "affiliations": [ "The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.", "Division of Rheumatology, Toho University, Tokyo, Japan.", "Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.", "Department of Pediatrics, Nippon Medical School, Tokyo, Japan.", "Department of Rheumatology and Clinical Immunology, Wakayama Medical University, Wakayama, Japan.", "Department of Allergy and Rheumatology, The University of Tokyo, Tokyo, Japan.", "Department of Dermatology, Fujita Health University, Toyoake, Japan.", "Division of Rheumatology, Department of Internal Medicine, Fujita Health University, Toyoake, Japan.", "Department of Rheumatology, Kobe City Medical Center General Hospital, Kobe, Japan.", "Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.", "Office of Global Affairs, Institute of Science Tokyo, Tokyo, Japan.", "Department of Clinical Immunology and Rheumatology, Hiroshima University, Hiroshima, Japan.", "Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.", "Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.", "Department of Molecular Targeted Therapeutics, University of Occupational and Environmental Health, Kitakyushu, Japan." ], "article_type": "research article", "arxiv": null, "author_total": 25, "authors": [ { "affs": [ 0 ], "name": "Satoshi Kubo", "orcid": "0000-0001-9693-9263" }, { "affs": [ 0 ], "name": "Yurie Kanda" }, { "affs": [ 1 ], "name": "Hideto Kameda", "orcid": "0000-0002-4330-5782" }, { "affs": [ 2 ], "name": "Masataka Kuwana", "orcid": "0000-0001-8352-6136" }, { "affs": [ 3 ], "name": "Hidehiko Narazaki", "orcid": "0000-0002-7182-3800" }, { "affs": [ 4 ], "name": "Takao Fujii", "orcid": "0000-0002-1789-1984" }, { "affs": [ 5 ], "name": "Keishi Fujio", "orcid": "0000-0001-7276-5254" }, { "affs": [ 6 ], "name": "Yoshinao Muro", "orcid": "0000-0003-2329-8375" }, { "affs": [ 7 ], "name": "Konomi Akamatsu" }, { "affs": [ 8 ], "name": "Koichiro Ohmura", "orcid": "0000-0003-2927-9159" }, { "affs": [ 1 ], "name": "Takehisa Ogura", "orcid": "0000-0003-4173-0651" }, { "affs": [ 2 ], "name": "Yuichiro Shirai", "orcid": "0000-0002-6864-8941" }, { "affs": [ 3 ], "name": "Yujiro Tanabe", "orcid": "0009-0003-0628-8535" }, { "affs": [ 9 ], "name": "Ran Nakashima", "orcid": "0000-0001-6247-0647" }, { "affs": [ 5 ], "name": "Yumi Tsuchida" }, { "affs": [ 0 ], "name": "Shingo Nakayamada", "orcid": "0000-0002-2209-8454" }, { "affs": [ 10 ], "name": "Hisanori Hasegawa" }, { "affs": [ 11 ], "name": "Shintaro Hirata", "orcid": "0000-0002-2474-9943" }, { "affs": [ 7 ], "name": "Shusaku Fukaya" }, { "affs": [ 4 ], "name": "Takashi Kato" }, { "affs": [ 7 ], "name": "Hidekata Yasuoka" }, { "affs": [ 12 ], "name": "Yuta Yamashita" }, { "affs": [ 13 ], "name": "Michihito Kono", "orcid": "0000-0002-7663-534X" }, { "affs": [ 13 ], "name": "Tatsuya Atsumi", "orcid": "0000-0001-5657-962X" }, { "affs": [ 0, 14 ], "name": "Yoshiya Tanaka", "orcid": "0000-0002-0807-7139" } ], "bibtex": "https://research.draconitic.com/paper/73vmxh0e68yd8.bib", "cited_by": 0, "doi": "10.1093/rheumatology/keag577", "fulltext_url": "https://europepmc.org/articles/PMC13693593", "id": "73vmxh0e68yd8", "issns": [ "1462-0324", "1462-0332" ], "landing_url": "https://europepmc.org/article/MED/42879733", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2734|Systemic Sclerosis and Related Diseases" ] ], "openalex": "W7222050863", "pdf_url": "https://europepmc.org/articles/PMC13693593?pdf=render", "pmcid": "PMC13693593", "pmid": "42879733", "published": "2026-10-01", "publisher": null, "ris": "https://research.draconitic.com/paper/73vmxh0e68yd8.ris", "sources": [ { "first_seen": "2026-10-30T12:19:00Z", "native_id": "MED:42879733", "source": "europepmc", "url": "https://europepmc.org/article/MED/42879733" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2734|Systemic Sclerosis and Related Diseases", "subfield": "general" } ], "title": "Clinical characteristics and severity classification in mixed connective tissue disease: a nationwide retrospective study.", "title_text": "Clinical characteristics and severity classification in mixed connective tissue disease: a nationwide retrospective study.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:19:00Z", "url": "https://research.draconitic.com/paper/73vmxh0e68yd8", "venue": "Rheumatology (Oxford, England)", "versions": [] }