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Rheumatologists are specialized doctors who diagnose and treat a wide variety of conditions, such as musculoskeletal disease and systemic autoimmune conditions, that fall under the umbrella of rheumatic disease. Arthritis and other rheumatic diseases often involve significant inflammation, changes in the joints and surrounding structures, and involvement of internal organs and/or connective tissues of the body.

Some forms of rheumatic diseases are caused primarily by normal aging, such as osteoarthritis, but others are systemic autoimmune diseases, such as RA, lupus, or scleroderma, that can affect people of any age. Patients can develop one or more of these conditions and experience symptoms that overlap. Some diseases that combine common overlap conditions may become their own unique disease, such as in mixed connective tissue disease which is called an overlap syndrome.

What is mixed connective tissue disorder (MCTD)?

Mixed connective tissue disease is a rheumatic disease that combines clinical features of lupus, scleroderma, polymyositis or dermatomyositis, and/or rheumatoid arthritis.  While symptoms may be systemic, they may not be as severe or widespread when compared to those experienced by patients who develop only one of these diseases in isolation. In some cases, however, MCTD may progressively get worse and evolve into classic systemic sclerosis (scleroderma) or lupus. MCTD is more common in women than men (approximately 10:1 ratio) and onset usually occurs between 15 and 35 years of age.

Symptoms of MCTD

Common clinical signs of MCTD include Raynaud’s phenomenon (which may occur years before other symptoms emerge), pain and/or inflammation of multiple joints, swollen hands/puffy fingers, and myositis (muscle inflammation). Muscle weakness, fevers, and fatigue are also common. 

MCTD may cause skin changes such as lupus-like rashes, reddish patches over the knuckles, violet coloring of the eyelids, loss of hair (alopecia), and dilation of small blood vessels around the fingernails or on the face.

Nearly 80% of people with MCTD develop abnormalities in lung function which may lead to breathing difficulties and/or pulmonary hypertension. Potential heart involvement includes pericarditis, myocarditis, and aortic insufficiency. 

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Patients may also develop problems swallowing, gastrointestinal difficulties, kidney disease, or enlargement of the spleen or liver. Anemia and leukopenia develop in 30-40% of cases.

Neurological abnormalities may include sensory disturbances in various areas of the body (such as trigeminal neuralgia that affects the face and jaw, and peripheral neuropathy that can affect hands and feet), seizures, vascular headaches, cerebral thrombosis, or cognitive dysfunction.

Diagnosis and Treatment

The cause of MCTD is unknown and currently there is no cure. When MCTD is suspected, your rheumatologist may order blood tests to measure for anti-U1-RNP and anti-U1-70 kd antibodies and rheumatoid factor, an electromyogram (EMG) to measure how well nerves and muscles are communicating, and/or muscle biopsy to test for damage to muscle fibers.

MCTD is a chronic and usually mild disease which can be treated symptomatically with nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarial drugs, glucocorticoids, or other immunosuppressant medications if the severity of disease justifies it. Proton pump inhibitors can control esophageal reflux symptoms and calcium channel blocking agents may help patients with Raynaud phenomenon. Patients with mild disease may experience long periods of time when symptoms disappear (remission) and do not require treatment.

Flare-ups and complications may require stronger therapy including higher doses of steroids or long term immunosuppressant therapy. The 10-year survival rate of MCTD is approximately 80%. Pulmonary hypertension is recognized as the most frequent disease-associated cause of death and may be treated with phosphodiesterase inhibitors, endothelin receptor antagonists, or prostacyclins.

What is the difference between MCTD and Undifferentiated Connective Tissue Disease (UCTD)?

With undifferentiated connective tissue disease (UCTD), patients have symptoms and blood test results that point to a systemic autoimmune disorder, but do not have enough features to meet the diagnostic criteria of a well-defined connective tissue disorder (such as RA, lupus, scleroderma).  Because they have features from several known diseases but cannot be accurately classified, they are said to be “undifferentiated” which simply means that there just isn’t enough evidence yet to diagnose you with any one of the 100s of rheumatic diseases.

UCTD is not an overlap syndrome, as is MCTD, in which patients meet the diagnostic criteria of more than one connective tissue disorder. However, in order to be diagnosed with UCTD, patients must have had the disease for at last 3 years with lab test results detecting antinuclear antibodies on 2 different occasions. More common symptoms include Raynaud’s phenomenon, joint pain and swelling, skin changes such as photosensitivity, malar rash, alopecia (hair loss), and oral ulcers, low-grade fever, dry eyes or mouth, and CNS symptoms.

UCTD may evolve into a defined connective tissue disease in 20-40% of patients, while 50-60% remain undifferentiated and 10-20% experience a complete remission of symptoms. UCTD is most likely to evolve to a defined disease during the first 3-5 years. The clinical course of UCTD tends to be mild as compared to other defined diseases, with notable exceptions involving life-threatening complications. It is believed that as many as 25% of patients seen by rheumatologists have UCTD.

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