Many patients with symptoms and signs of a connective tissue disease have features of more than one type of rheumatic disease. Special attention has been drawn to a subset of antinuclear antibody–positive patients who have high titers of RNP autoantibodies and overlapping features of SLE, systemic sclerosis, rheumatoid arthritis, and inflammatory myositis. Swollen or puffy hands are a common early feature of this disease, referred to as mixed connective tissue disease. Raynaud phenomenon, arthralgias, and myalgias are common. Unlike patients with SLE, renal or CNS disease is uncommon. A key reason to identify this subset of patients is that pulmonary hypertension and interstitial lung disease are major causes of mortality, and regular screening for these manifestations is required. Some patients have features of more than one connective tissue disease (eg, rheumatoid arthritis and SLE, SLE and systemic sclerosis) in the absence of high-titer anti-RNP antibodies and are called having an “overlap syndrome;” others have only a few features of autoimmunity and cannot yet be classified (“undifferentiated connective tissue disease”). Treatments are guided more by the distribution and severity of patients’ organ system involvement than by therapies specific to these overlap syndromes.
et al. Progression and mortality of interstitial lung disease in mixed connective tissue disease: a long-term observational nationwide cohort study. Rheumatology (Oxford). 2018;57:255.
et al. Differentiating between UCTD and early-stage SLE: from definitions to clinical approach. Nat Rev Rheumatol. 2022;18:9.