Get the facts on mixed connective tissue disease
- Connective tissues are the framework of the cells of the body.
- Mixed connective tissue disease is considered an "overlap" of three connective tissue diseases, systemic lupus erythematosus, scleroderma, and polymyositis.
- Diagnosis of mixed connective tissue disease is supported by detecting abnormal antibodies in the blood.
- Treatment of mixed connective tissue disease is directed at suppressing immune-related inflammation of tissues.
What are connective tissues?
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 molecules, collagen and elastin. There are many different collagen proteins that vary in amount in each tissue of the body. Elastin is another protein that has the capability of stretching and returning to original length like a spring. Elastin is the major component of ligaments (tissues which attach bone to bone).
Connective tissue diseases are disorders featuring abnormalities involving the collagen and elastin. Connective tissue diseases are often characterized by a variety of immune abnormalities that are common for each particular type of illness.
What diseases characteristically affect connective tissue?
Diseases of connective tissue that are strictly inheritable (due to genetic inheritance) include Marfan syndrome (can have tissue abnormalities in the heart, aorta, lungs, eyes, and skeleton) and Ehlers-Danlos syndrome (may have loose, fragile skin or loose [hyperextensible] joints). Pseudoxanthoma elasticum is an inherited disorder of elastin.
Other diseases of connective tissue do not have specific gene abnormalities as their sole cause. These connective tissue diseases occur for unknown reasons. They are characterized as a group by the presence of spontaneous overactivity of the immune system, which results in the production of unusual antibodies in the blood.
The classic immune-related connective tissue diseases include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, and dermatomyositis. Each of these diseases has a characteristic presentation with typical clinical findings that doctors can recognize during an examination. Each also has characteristic blood test abnormalities and abnormal antibody patterns. However, each of these diseases can evolve 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." This implies that the characteristic features that are used to define the classic connective tissue disease are not present, but some symptoms or signs of connective disease exist. Individuals with undifferentiated connective tissue disease may never develop a fully definable condition or they may eventually develop a classic connective tissue disease.
MCTD vs. UCTD (Mixed Connective Tissue Disease vs. Undifferentiated 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.
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.
What is mixed connective tissue disease?
Mixed connective tissue disease, as first described in 1972, is "classically" considered an "overlap" of three diseases, systemic lupus erythematosus, scleroderma, and polymyositis. Patients with this pattern illness 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 three component illnesses, most commonly scleroderma. Mixed connective tissue disease is often abbreviated MCTD.
It is now known that overlap syndromes can occur that 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").
What are causes and risk factors for mixed connective tissue disease?
The most significant causes and risk factors for developing mixed connective tissue disease are certain gene patterns that are inherited from ancestors. There is no known environmental toxin that has been shown to cause mixed connective tissue disease.
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What are signs and symptoms of mixed connective tissue disease?
The signs and symptoms of mixed connective tissue disease vary greatly from one individual affected to another. If polymyositis is the dominant feature, muscle weakness is prominent. If systemic lupus erythematosus prevails, there may be chest pain with breathing, kidney disease, and/or arthritis of the joints. If scleroderma symptoms dominate, there can be diffuse swelling and thickening of the fingers and feet with bluish discoloration of the fingers after cold exposure (Raynaud's phenomenon).
What types of doctors treat mixed connective tissue disease?
Doctors who treat patients with mixed connective tissue disease include primary-care providers such as general practitioners, internists, and family medicine doctors. Other specialists who can be involved in the care for these patients include neurologists, cardiologists, pulmonologists, and nephrologists. Specialists with a particular interest in mixed connective tissue disease are rheumatologists.
How do doctors diagnose mixed connective tissue disease?
Today, true mixed connective tissue disease is diagnosed when patients demonstrate the clinical features (exam findings) of overlap illnesses (as described above) and have high amounts of the antibodies ANA and anti-RNP in their blood. Mixed connective tissue disease patients do not typically have antibodies such as dsDNA and Scl70, which are particularly common in systemic lupus erythematosus and scleroderma respectively.
What are treatment options for mixed connective tissue disease?
The treatment of mixed connective tissue disease is based on which features are causing symptoms and signs. The prognosis (outlook) varies accordingly. Therapies must be targeted for each of the organ systems affected. In general, treatment is often directed at suppressing the inflammation present in the tissues by using anti-inflammatory and immunosuppressive medications. These medications include nonsteroidal anti-inflammatory drugs (NSAIDs), cortisone drugs/steroids (such as prednisone), antimalarial drugs (hydroxychloroquine), and cytotoxic drugs (such as methotrexate, azathioprine, and cyclophosphamide). Organ damage, such as in the kidneys, can require additional treatments directed at high blood pressure, etc.
For the joint and muscle pains of mixed connective tissue disease, treatment options including NSAIDs, low-dose prednisone, hydroxychloroquine, and methotrexate can be helpful. Sometimes TNF blockers infliximab (Remicade), etanercept (Enbrel), or adalimumab (Humira) are considered for inflammatory arthritis. Physical therapy for certain joints is sometimes helpful. For pulmonary hypertension, medications that tend to open the arteries to the lungs are used along with blood-thinning drugs and even supplemental oxygen. For interstitial lung disease, prednisone and cyclophosphamide are considered. Angiotensin-converting enzyme inhibitors, such as captopril (Capoten) and enalapril (Vasotec), are used to prevent damage to the kidneys, especially if blood pressure is elevated. Esophagus irritation and heartburn can be prevented by elevating the head of the bed and can be relieved with omeprazole (Prilosec) or lansoprazole (Prevacid). Antacids can also be helpful. Constipation, cramping, and diarrhea are sometimes caused by bacteria that can be treated with tetracycline or erythromycin.
For Raynaud's phenomenon, patients are recommended to use hand- and body-warming techniques while protecting the fingers from injury. Nifedipine (Procardia), losartan (Cozaar, Hyzaar), and nitroglycerin cream are used to dilate the constricted blood vessels. Severe RP can lead to gangrene and the loss of digits. In rare cases of severe disease, nerve surgery called "sympathectomy" is sometimes considered. In order to prevent blood vessel constriction, the nerves that stimulate the constriction of the vessels (sympathetic nerves) are surgically interrupted. Usually, this is performed during an operation that is localized to the sides of the base of the fingers at the hand. Through small incisions the tiny nerves around the blood vessels are stripped away. This procedure is referred to as a digital sympathectomy.
What are home remedies for mixed connective tissue disease?
Gastroesophageal reflux disease in mixed connective tissue disease can be helped by elevation of the head of the bed and taking stomach acid-blocking medications. Raynaud's phenomenon can be helped by general body warming and wearing gloves to prevent chilling.
The term arthritis refers to stiffness in the joints.
What is the prognosis of mixed connective tissue disease?
The outlook for mixed connective tissue disease very much depends on the location and intensity of the organs affected. Those who are treated and monitored early tend to have better outcomes.
Is it possible to prevent mixed connective tissue disease?
No. There is no prevention for mixed connective tissue disease.
Are there support groups for mixed connective tissue disease?
See the local chapter of the Arthritis Foundation for information about support groups.
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Medically Reviewed on 10/2/2020
Firestein, Gary S., et al. Kelley's Textbook of Rheumatology, 9th Edition. Philadelphia, PA: Saunders, 2013.