MCTD vs. UCTD
(Mixed Connective Tissue Disease vs. Undifferentiated Connective Tissue Disease)

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Medical Author: William C. Shiel Jr., MD, FACP, FACR
Medical Editor: Melissa Conrad Stöppler, MD

I note that some viewers have been requesting some clarification of the meaning of the terms "mixed connective tissue disease" (MCTD) and "undifferentiated connective tissue disease" (UCTD).

Connective tissue diseases are a special group of rheumatic diseases (diseases that feature abnormalities of the muscles and/or joints) that can be associated with arthritis. The cause(s) for the connective tissue diseases is (are) unknown. They are characterized as a group by the presence of spontaneous overactivity of the body's immune (defense) system. This overactivity results in the production of unusual antibodies that are found in the blood. The antibodies themselves may or may not cause any problems in patients with connective tissues diseases, but they are commonly found in the blood as a characteristic feature.

The connective tissues are the structural portions of our body that essentially hold the cells of the body together. These tissues form a framework, or matrix, for the body. The connective tissues are composed of two major structural protein molecules, collagen and elastin. There are many different types of collagen protein that vary in amount in each of the body's tissues. Elastin has the capability of stretching and returning to its original length, like a spring or rubber band. Elastin is the major component of ligaments (tissues that attach bone to bone) and skin. In patients with connective tissue diseases, it is common for collagen and elastin to become injured by inflammation. Diseases in which inflammation of collagen tends to occur are also referred to as collagen diseases.

The classic connective-tissue diseases include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, and dermatomyositis. Each of these diseases affects people in a characteristic way and causes typical findings that doctors can recognize during an examination. Each also has characteristic blood-test abnormalities and abnormal antibody patterns. For example, people with systemic lupus erythematosus have dsDNA antibodies, while those with scleroderma have Sc-170 antibodies. Additionally, each of these diseases can evolve either slowly or rapidly from very subtle abnormalities before demonstrating the classic features that help in the diagnosis.

When these conditions have not developed the classic features of a particular disease, doctors will often refer to the condition as "undifferentiated connective tissue disease" or UCTD. This designation implies that the characteristic features that are used to define the classic connective tissue diseases are not present but that some symptoms or signs of a connective tissue disease exist. For example, a person may have a special antibody in the blood, such as antinuclear antibody, along with muscle pains, but no other definable features of a classic connective tissue disease. Individuals with undifferentiated connective tissue disease may never develop a fully definable condition or they may eventually develop a classic connective tissue disease.

Mixed connective tissue disease (MCTD), which was first described in 1972, is "classically" considered as an "overlap," or mix, of three specific connective-tissue diseases: systemic lupus erythematosus, scleroderma, and polymyositis. Patients with this pattern of illness (that is, with MCTD) have features of each of these three diseases. They also typically have very high quantities of antinuclear antibodies (ANAs) and antibodies to ribonucleoprotein (anti-RNP) detectable in their blood. The symptoms of many of these patients eventually evolve to become dominated by features of one of the three component illnesses, most commonly the scleroderma features.

It is now known, however, that overlap syndromes can involve any combination of the connective-tissue diseases. Therefore, for example, patients can have a combination of rheumatoid arthritis and systemic lupus erythematosus (hence, the coined name rhupus). Accordingly, today, true mixed connective tissue disease is diagnosed when patients demonstrate the clinical features (exam findings) of overlap illnesses. These patients also have high amounts of ANA and anti-RNP without having such other antibodies as the dsDNA antibodies of systemic lupus erythematosus and the Sc-l70 antibodies of scleroderma.