What is Mixed Connective Tissue Disease (MCTD)?

From the Guidelines

Mixed Connective Tissue Disease (MCTD) should be treated with mycophenolate as the preferred first-line therapy for interstitial lung disease (ILD), according to the 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline 1. MCTD is a rare autoimmune disorder characterized by overlapping features of several connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and rheumatoid arthritis. The hallmark of MCTD is the presence of high levels of anti-U1-RNP antibodies in the blood. Symptoms typically include:

• Raynaud's phenomenon (fingers turning white then blue in cold temperatures)
• Swollen hands
• Joint pain and swelling
• Muscle inflammation
• Lung involvement
• Esophageal dysfunction The disease affects predominantly women, with onset usually occurring between ages 15 and 25. Diagnosis requires clinical evaluation, blood tests for specific antibodies, and sometimes imaging or tissue biopsies.

Treatment depends on symptom severity and organ involvement, and mycophenolate is conditionally recommended over other listed therapies for ILD treatment in MCTD patients 1. Other treatment options may include:

• NSAIDs for mild symptoms
• Corticosteroids like prednisone, but with caution in patients with an SSc phenotype who may be at increased risk of renal crisis 1
• Immunosuppressants such as hydroxychloroquine, methotrexate, or rituximab for more severe manifestations
• Patients with pulmonary hypertension may require specific treatments like sildenafil or bosentan Regular monitoring for organ involvement is essential, as the disease course varies widely among patients. The use of glucocorticoids as first-line ILD treatment is strongly recommended against, particularly in patients with SSc-ILD, due to the risk of renal crisis 1. While there is no cure for MCTD, proper treatment can effectively manage symptoms and prevent complications, allowing many patients to maintain good quality of life. It is also important to note that nintedanib is not recommended as a first-line ILD treatment option for MCTD-ILD patients, according to the 2023 ACR/CHEST guideline 1.

From the Research

Definition and Characteristics of MCTD

• Mixed connective tissue disease (MCTD) is a rare autoimmune condition that shares features of other autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myopathy, rheumatoid arthritis, and Sjogren's syndrome 2.
• MCTD is characterized by the combination of clinical manifestations of SLE, cutaneous systemic sclerosis (SSc), and polymyositis-dermatomyositis, in the presence of elevated titers of anti-U1-RNP antibodies 3.
• The disease is defined by a serologic test, with antibodies to RNAse sensitive extractable nuclear antigen, specifically polypeptides on the U1 ribonuclear protein component of the splicesosome (U1RNP) 4.

Clinical Features of MCTD

• Clinical features of MCTD include a high frequency of Raynaud's syndrome, swollen hands, sclerodactyly, arthritis, polymyositis, and interstitial lung disease 4.
• Other symptoms may include polyarthritis, hand oedema, myositis, and oesophageal hypomobility 3.
• Severe myositis is a rare presentation of MCTD, but it can occur, especially in cases with high titers of anti-U1RNP antibodies 5.

Diagnosis and Management of MCTD

• Diagnosis of MCTD is based on the presence of anti-U1-RNP antibodies and distinct clinical features, such as Raynaud's phenomenon, "puffy hands," arthritis, myositis, and interstitial lung disease 6.
• Management of MCTD requires specific follow-up exams and treatment, although there are currently no formal recommendations for treatment 2.
• Treatment may include pulse corticosteroid therapy and methotrexate, especially in cases with severe myositis and elevated muscle enzyme levels 5.

Epidemiology and Etiology of MCTD

• The point prevalence of adult-onset MCTD is estimated to be 3.8 per 100,000, and the mean annual incidence is 2.1 per million per year, making it the least common connective tissue disease 6.
• Little is known about the etiology of MCTD, but recent genetic studies have confirmed that MCTD is a strongly HLA-linked disease, with distinct HLA profiles compared to other connective tissue diseases 6.