|55 Kenosia Avenue
Danbury, CT 06810
Toll Free: 1.800.999.6673
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
Copyright 1987, 1989, 1996, 2001, 2007
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.
Symptoms of the following disorders can be similar to those of mixed connective tissue disease. Comparisons may be useful for a differential diagnosis:
Systemic lupus erythematosus (lupus) is a chronic, inflammatory autoimmune disorder affecting the connective tissue. In autoimmune disorders, the body's own immune system attacks healthy cells and tissues causing inflammation and malfunction of various organ systems. In lupus, the organ systems most often involved include the skin, kidneys, blood and joints. Many different symptoms are associated with lupus, and most affected individuals do not experience all of the symptoms. In some cases, lupus may be a mild disorder affecting only a few organ systems. In other cases, it may result in serious complications. (For more information on this disorder, choose "lupus" as your search term in the Rare Disease Database.)
Scleroderma is a rare connective tissue disorder characterized by abnormally increased production and accumulation of collagen, the body's major structural protein, in skin and other organs of the body. There are systemic and localized forms of scleroderma. Systemic scleroderma is characterized by hardening (induration) and thickening of the skin and abnormal degenerative changes and formation of fibrous tissue (fibrosis) in certain organs of the body including the lungs, heart, kidneys, and gastrointestinal tract. Associated symptoms, which may vary widely from case to case, may include abnormal discoloration of and pain affecting the skin of the hands and feet upon exposure to cold temperatures (Raynaud's phenomenon), abnormal tightness, thickening, "waxiness", and loss of elasticity of the skin; shortness of breath; difficulty swallowing; muscle weakness; joint pain; heart abnormalities including irregular heart beats (palpitations), kidney (renal) abnormalities, and/or other symptoms and findings. In individuals with localized scleroderma, involvement is restricted to the skin, tissue under the skin (subcutaneous tissue), and, in some cases, underlying muscle and bone. Although the exact cause of scleroderma is unknown, some researchers suggest that the disorder represents an abnormal autoimmune response in which the immune system reacts against part of the affected individual's own body. (For more information on this disorder, choose "scleroderma" as your search term in the Rare Disease Database.)
Polymyositis is a rare connective tissue disease. The cause is unknown. Polymyositis is characterized by inflammatory degenerative changes in the muscle fibers and the supportive collagen of connective tissue. The major early symptom of this disorder is muscle weakness, usually in the neck, trunk and shoulders. Eventually, it may become difficult to rise from a sitting position, climb stairs, lift objects and/or reach overhead. Occasionally, joint pain and tenderness also occur. Additional symptoms may also include inflammation of the lungs (interstitial pneumonitis), difficulty breathing, coughing, extreme sensitivity to cold that is most often felt in the fingers caused by narrowing of blood vessels in the fingers (Raynaud's phenomenon), digestive problems, and/or heart irregularities. (For more information on this disorder, choose "Polymyositis" as your search term in the Rare Disease Database.)
Rheumatoid arthritis (RA) is a chronic progressive form of arthritis that eventually leads to the destruction of the bone joints causing pain and physical deformity. Rheumatoid Arthritis is characterized by inflammation of the joints (arthritis) on both sides of the body (symmetrical) leading to swelling, pain, and decreased mobility. The symptoms of this disease usually appear during middle age and it is most common in females. The course of the disease is highly variable and may include episodes of remission.
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:
(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at email@example.com.)
Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:1447.
Hoffman RW, et al. Mixed connective tissue disease. Curr Opin Rheumatol. 2000;12:386-90.
Maddison PJ. Mixed connective tissue disease: overlap syndromes. Baillieres Best Pract Res Clin Rheumatol. 2000;14:111-24.
Yang YH, et al. Childhood mixed connective tissue disease. J Formos Med Assoc. 2000;99:158-61.
Zdrojewicz Z, et al. Mixed connective tissue disease, etiology, pathogenesis, clinical significance, treatment. Postepy Hig Med Dosw. 1999;53:751-66.
Shen N, et al. Mixed connective tissue disease: a disease entity? Chin Med J (Engl). 1998;111:214-17.
Burdt MA, et al. Long-term outcome in mixed connective tissue disease: longitudinal clinical and serological findings. Arthritis Rheum. 1999;42:899-909.
Kallenberg CG, et al. Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions. Curr Opin Rheumatol. 1995;7:568-73.
Report last updated: 2007/10/12 00:00:00 GMT+0