From the Guidelines
Mixed connective tissue disease (MCTD) is characterized by the presence of high-titer antibodies against U1-ribonucleoprotein (U1-RNP), which is the hallmark laboratory finding, and is typically detected through enzyme-linked immunosorbent assay (ELISA) or immunoblot testing, as reported in the most recent study 1. The diagnosis of MCTD relies on a combination of laboratory findings and clinical features that overlap multiple connective tissue diseases. Some key laboratory and diagnostic features of MCTD include:
- High-titer antibodies against U1-RNP
- Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
- Mild to moderate anemia, leukopenia, thrombocytopenia, and hypergammaglobulinemia
- Presence of additional autoantibodies such as anti-Ro (SSA), anti-La (SSB), rheumatoid factor, and occasionally low titers of anti-DNA or anti-Smith antibodies
- Normal or slightly decreased complement levels
- Diagnostic imaging such as high-resolution CT scans to reveal interstitial lung disease or pulmonary hypertension
- Echocardiography to show cardiac involvement
- Nailfold capillaroscopy to demonstrate capillary abnormalities similar to those seen in scleroderma
- Elevated muscle enzymes like creatine kinase in patients with myositis features. According to the most recent study 1, interstitial lung disease (ILD) is estimated to be present in 40% to 80% of patients with MCTD, and treatment during the acute inflammatory phase is associated with a good prognosis. The study also reports that signs of fibrosis on high-resolution computed tomography (HRCT) are associated with increased mortality, with a mortality rate of 20.8% in patients with severe pulmonary fibrosis compared with just 3.3% in those with a normal HRCT scan. Therefore, early detection and monitoring of ILD in patients with MCTD are crucial for informed treatment decisions and prognosis, as emphasized in the recent joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society 1.
From the Research
Laboratory Features
- The presence of anti-Ribonucleoprotein antibodies directed against the U1 complex (anti-U1RNP) is a key laboratory feature of Mixed Connective Tissue Disease (MCTD) 2, 3, 4.
- Anti-U1RNP antibodies are necessary for the diagnosis of MCTD, but they are also prevalent in other connective tissue diseases, especially Systemic Lupus Erythematosus (SLE) 4.
- Antinuclear Antibody (ANA) positivity with a coarse speckled pattern is almost always associated with anti-U1RNP 3.
Diagnostic Features
- MCTD is characterized by a combination of clinical, serological, and instrumental evaluations 3.
- The disease shares clinical characteristics with Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Systemic Sclerosis 2, 3, 5.
- Diagnosis is challenging due to the lack of validated classification criteria and heterogeneous clinical presentation 3, 5.
- The presence of scleroderma features, such as swollen hands, sclerodactyly, and esophageal reflux, is significantly associated with the diagnosis of MCTD 4.
Clinical Features
- Common clinical manifestations of MCTD include Raynaud's phenomenon, arthralgias, swollen joints, esophageal dysfunction, muscle weakness, and fingers with a sausage-like appearance 2, 3, 6.
- Organ involvement can be extensive, with potential development of pulmonary, kidney, cardiovascular, gastrointestinal, and central nervous system manifestations 6.
- Pulmonary hypertension and interstitial lung disease are significant causes of mortality in MCTD 2, 3.