Undifferentiated mixed connective tissue disease

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit

Information, in part, from the American College of Rheumatology

There is a tremendous amount of confusion when the topic of connective tissue diseases is raised. Connective tissue diseases are a special group of rheumatic diseases (diseases that affect the muscles and/or joints) that can be associated with arthritis.

The cause for the connective tissue diseases is unknown. These diseases are characterized by the presence of over-activity of the body's immune system. This over-activity results in the production of antibodies found in the blood.

The connective tissues form a framework 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. Elastin has the capability of stretching and returning to its original length. 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 both 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. Each also has characteristic blood test abnormalities and abnormal antibody patterns. As an example, systemic lupus erythematosus has double-stranded or dsDNA antibodies, while scleroderma has Sc170 antibodies.

When these conditions have not evolved into 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 and muscle pains, but no other definite features of a classic connective tissue disease. Individuals with undifferentiated connective tissue disease may never develop a fully definable condition or they may go on to develop a classic connective tissue disease.

UCTD is distinct from mixed connective tissue disease or MCTD. Mixed connective tissue disease, which was first described in 1972, is "classically" considered 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 that overlap syndromes can involve any combination of the connective tissue diseases. For example, patients can have a combination of rheumatoid arthritis and systemic lupus erythematosus (hence, the coined name "rhupus"). Accordingly, true mixed connective tissue disease is diagnosed when patients demonstrate the clinical features 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 Scl70 antibodies of scleroderma.

Yes... I know it is confusing but it's like the old joke..."Neurologists diagnose the untreatable... rhumatologists treat the undiagnosable"

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