Clinical characteristics and severity classification in Mixed Connective Tissue Disease: a nationwide retrospective study

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.