Mixed connective tissue disease (MTCD) is a rare connective tissue disorder. MCTD is used to describe what may be an overlapping group of connective tissue disorders that cannot be diagnosed in more specific terms. These disorders include systemic lupus erythematosus, polymyositis, and scleroderma. Individuals with MCTD have symptoms of each of these disorders including arthritic, cardiac, pulmonary and skin manifestations; kidney disease; muscle weakness, and dysfunction of the esophagus. The exact cause of mixed connective tissue disease is unknown.
Individuals with mixed connective tissue disease have symptoms that are similar to or directly overlap with those of several different connective tissue diseases. These diseases include systemic lupus erythematosus, polymyositis, scleroderma, and rheumatoid arthritis. (For more information on these disorders, see the Related Disorders section of this report.)
A condition known as Raynaud’s phenomenon may precede the development of additional symptoms of MCTD by months or years. Raynaud’s phenomenon is characterized by painfully cold fingers and toes caused by widening (dilation) or narrowing (constriction) of small blood vessels in the hands and feet in response to cold. It occurs in approximately 85 percent of individuals with MCTD.
Pain in multiple joints (polyarthralgia) or inflammation of joints (arthritis) similar to rheumatoid arthritis also occurs in most affected individuals. Muscle weakness due to inflammation (myopathy) of various muscles with or without tenderness is also common. Additional frequent symptoms include fevers of unknown origins and fatigue.
Affected individuals may have abnormal accumulation of fluid in the tissue of the hands that may result in puffiness and swelling (edema). Increased collagen content in the skin (found in two-thirds of individuals with MCTD) may also be present. Additional frequent skin findings include lupus-like rashes (including reddish brown patches), reddish (erythematous) patches over the knuckles, violet discoloration of the eyelids, non-scarring loss of hair (alopecia), and dilation of small blood vessels around the fingernails (periungual telangiectasia).
Dysfunction of the esophagus (hypomotility) may be found in 80 percent of individuals with MCTD, including many who show no other symptoms. The esophagus is the tube that carries food from the mouth to the stomach. Abnormalities in lung function have been found in 80 percent of individuals with MCTD. In some affected individuals, lung involvement may lead to breathing (respiratory) difficulties. In some cases, affected individuals have high blood pressure of blood vessels of the lung (pulmonary hypertension).
Heart (cardiac) involvement appears to be less common in MCTD than lung problems. However, two-thirds of children in one pediatric study had evidence of pericarditis, myocarditis and aortic insufficiency.
Kidney (renal) disease occurs in 10 percent of individuals with MCTD and is often mild. On occasion, however, it can become a major complication.
Neurologic abnormalities are noted in approximately 10 percent of individuals with MCTD. These findings may include a functional disturbance of facial sensation due to involvement of the fifth cranial nerve (trigeminal sensory neuropathy), a cognitive disorder caused by or associated with impaired brain tissue function (organic mental syndrome), blood vessel narrowing (constriction) causing “vascular” headaches, a mild form of meningitis (aseptic meningitis), seizures, blockage of a cerebral vessel (cerebral thrombosis) or hemorrhage, and various sensory disturbances in multiple areas of the body (multiple peripheral neuropathies).
Low levels of circulating red blood cells (anemia) and a reduction in the white blood cell count (leukopenia) occur in 30 to 40 percent of cases. Disease of the lymph nodes (lymphadenopathy), enlargement of the spleen (splenomegaly), enlargement of the liver (hepatomegaly), and intestinal involvement may also occur in some cases.
The exact cause of mixed connective tissue disease is unknown, although certain findings suggest that a dysfunction of the immune system may be involved, or in some cases it may be genetic.
MCTD appears to be an autoimmune disorder. Autoimmune syndromes are caused by the body’s natural defenses (antibodies) against invading organisms that, for unknown reasons, begin to attack healthy tissue. Individuals with MCTD have high amounts of antinuclear antibodies (ANAs) and antibodies that affect ribonucleoprotein (anti-RNP).
Onset of mixed connective tissue disease can occur anytime from early childhood to elderly adulthood, but the average age of onset is 37 years. Approximately 80 percent of individuals are female.
Debate exists in the medical literature as to whether mixed connective tissue disease is a distinct syndrome or a random association of symptoms most commonly found with various connective tissue diseases.
Mixed connective tissue disease may be diagnosed based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings, and specialized tests such as blood tests that reveal abnormally high levels of antinuclear antibodies and antibodies that affect ribonucleoprotein (anti-RNP).
The treatment of mixed connective tissue disease is based upon the specific symptoms present in each case. Although no controlled studies have been performed, many of the manifestations of MCTD appear to respond to therapy with corticosteroids such as prednisone. Mild forms of the disease appear to be controlled by nonsteroidal anti-inflammatory drugs (NSAIDs) or low doses of corticosteroids. When more severe involvement of major organs occurs, larger doses of corticosteroids may be of benefit. This drug treatment also seems to improve skin symptoms and functioning of the esophagus and lungs.
In some cases, drugs that suppress the immune system (immunosuppressive drugs) have been used to treat individuals with mixed connective tissue disease.
Research into connective tissue diseases is ongoing. The primary goal at this time is to understand the cause. Discovery of the mechanisms that cause this group of diseases would be a major step forward in discovering better treatment or a cure.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
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