Satoshi Kubo, Yurie Kanda, Hideto Kameda, Masataka Kuwana, Hidehiko Narazaki, Takao Fujii, Keishi Fujio, Yoshinao Muro, Konomi Akamatsu, Koichiro Ohmura, Takehisa Ogura, Yuichiro Shirai, Yujiro Tanabe, Ran Nakashima, Yumi Tsuchida, Shingo Nakayamada, Hisanori Hasegawa, Shintaro Hirata, Shusaku Fukaya, Takashi Kato, Hidekata Yasuoka, Yuta Yamashita, Michihito Kono, Tatsuya Atsumi, Yoshiya Tanaka
University of Occupational and Environmental Health, Japan. Toho University. Nippon Medical School. Wakayama Medical University. University of Tokyo. Fujita Medical University. Fujita Health University. Kobe City Medical Center General Hospital. Kyoto University Graduate School of Medicine. Institute of Science Tokyo. Hiroshima University. Nagoya University Graduate School of Medicine. Hokkaido University.
Japan
Rheumatology
Rheumatology 2026;
DOI: 10.1093/rheumatology/keag577
Abstract
Objectives: To 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: This nationwide retrospective multicenter 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 versus non-severe disease.
Results: The 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: Mixed 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.
Category
Class I. Pulmonary Hypertension Associated with Connective Tissue Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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