Medicine – Mixed Connective Tissue Disease

Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder characterised by an overlap of clinical features from several connective tissue diseases, particularly polymyositis, systemic sclerosis, and systemic lupus erythematosus (SLE). Rather than displaying the typical manifestations of only one autoimmune condition, patients develop a combination of features from these different disorders. The disease is strongly associated with high titres of antibodies against U1-ribonucleoprotein (anti-U1-RNP).

1. Features of Polymyositis

Patients with mixed connective tissue disease may develop manifestations resembling polymyositis, an inflammatory disorder affecting skeletal muscles. The most characteristic manifestation is symmetrical proximal muscle weakness, particularly involving the muscles around the shoulders and hips. Patients may therefore have difficulty climbing stairs, rising from a chair, lifting objects, or raising their arms above their head. Laboratory investigations may demonstrate elevated muscle enzymes when active inflammatory myositis is present.

2. Features of Systemic Sclerosis

MCTD can also produce clinical manifestations resembling systemic sclerosis (scleroderma). Raynaud phenomenon is particularly common and may occur early in the course of the disease. Patients may also develop swollen or puffy fingers, followed in some cases by sclerodactyly and tightening of the skin. Oesophageal dysmotility and other gastrointestinal manifestations may occur. Pulmonary involvement is especially important because interstitial lung disease and pulmonary hypertension can contribute substantially to morbidity.

3. Features of Systemic Lupus Erythematosus

Features resembling systemic lupus erythematosus (SLE) may also occur. These can include inflammatory joint pain or arthritis, skin manifestations, constitutional symptoms, and haematological abnormalities. However, the pattern of organ involvement varies considerably between patients, and the combination of manifestations may evolve over time.

4. Anti-RNP Antibodies

The characteristic serological finding in mixed connective tissue disease is a high titre of antibodies against U1-ribonucleoprotein (anti-U1-RNP). These antibodies are an important marker supporting the diagnosis when the appropriate overlapping clinical features are present. Anti-RNP antibodies can also occur in other autoimmune diseases, particularly SLE, so their presence alone is not sufficient to establish the diagnosis. In MCTD, they are typically found at high titres together with characteristic clinical features of overlapping connective tissue diseases.

Key Concept

Mixed connective tissue disease can therefore be remembered as an overlap syndrome combining features of polymyositis, systemic sclerosis, and SLE, associated with high-titre anti-U1-RNP antibodies.