Raynaud syndrome, joint pains, various skin abnormalities, muscle weakness, and problems with internal organs can develop.
The diagnosis is based on symptoms and the results of blood tests to detect levels of characteristic antibodies.
Treatment varies depending on the severity of symptoms and may include nonsteroidal anti-inflammatory drugs, hydroxychloroquine, corticosteroids, immunosuppressive drugs, or a combination.
Mixed connective tissue disease is more common among women than men. Mixed connective tissue disease occurs worldwide and affects people of all ages, often peaking in incidence during adolescence and the 20s. The cause of mixed connective tissue disease is unknown, but it is an autoimmune disease.
The typical symptoms of mixed connective tissue disease are Raynaud syndrome (in which the fingers suddenly become very pale and tingle or become numb or blue in response to cold or emotional upset), joint inflammation (arthritis), swollen hands, muscle weakness, difficulty swallowing, heartburn, and shortness of breath. Raynaud syndrome may precede other symptoms by many years. Regardless of how mixed connective tissue disease starts, it tends to worsen, and symptoms spread to several parts of the body.
Lupus-like rashes may develop. Skin changes similar to those of systemic sclerosis also may occur, such as tightening of the finger skin. The hair may thin.
Almost everyone with mixed connective tissue disease has aching joints. About 75% of people develop the swelling and pain typical of arthritis. Mixed connective tissue disease damages the muscle fibers, so the muscles may feel weak and sore, especially in the shoulders and hips. Tasks such as lifting the arms above the shoulders, climbing stairs, and getting out of a chair can become very difficult.
The lungs are affected in up to 75% of people with mixed connective tissue disease. Fluid may collect in or around the lungs. In some people, abnormal lung function is the most serious problem, causing shortness of breath during exertion. Interstitial lung diseases, which affect the tissue around the air sacs of the lungs (alveoli), are the most common lung problems. Pulmonary hypertension, a condition in which blood pressure in the arteries of the lungs (the pulmonary arteries) is abnormally high, is a major cause of death.
Occasionally, the heart is weakened, leading to heart failure. Symptoms of heart failure may include fluid retention, shortness of breath, and fatigue. The kidneys are affected in about 25% of people, and the damage is usually mild compared to the damage caused by lupus. Other symptoms may include fever, swollen lymph nodes, and abdominal pain.
Doctors suspect mixed connective tissue disease when symptoms of lupus, systemic sclerosis, and polymyositis overlap.
Blood tests are done to detect levels of antinuclear antibodies (ANA) and an antibody to ribonucleoprotein (RNP), which are present in most people who have mixed connective tissue disease. People who have a high level of these antibodies but who do not have other antibodies present in similar disorders are most likely to have the disease. Although blood test results can help doctors diagnose the disease, they alone cannot confirm a definite diagnosis of mixed connective tissue disease because sometimes the abnormalities they detect are present in healthy people or in people who have other disorders. The diagnosis of mixed connective tissue disease is based on all of the information doctors gather, including symptoms, physical examination results, and all test results.
To determine whether people have pulmonary hypertension, doctors do pulmonary function testing to assess the lungs and echocardiography to assess the heart. If doctors suspect other organs are affected, they may do other tests, such as magnetic resonance imaging (MRI) or a muscle biopsy (removal of a piece of muscle tissue for examination and testing), to detect problems.
Overall, the 10-year survival rate is about 80%, but the prognosis depends largely on a person's symptoms. For example, the prognosis is worse for people who have mainly symptoms of systemic sclerosis and polymyositis. Causes of death include pulmonary hypertension (mainly), kidney failure, and heart disease.
The treatment of mixed connective tissue disease is similar to that of lupus, systemic sclerosis, and autoimmune myositis. Corticosteroids are usually effective, especially when the disease is diagnosed early. Mild cases can be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarial drugs (such as hydroxychloroquine or chloroquine), or very low doses of corticosteroids. The more severe the disease, the higher the dose of corticosteroid needed. In moderate to severe cases, immunosuppressive drugs (such as azathioprine, methotrexate, or mycophenolate mofetil) may also be needed. People whose major organs are severely affected usually require higher doses of corticosteroids and additional immunosuppressive drugs.
In general, the more advanced the disease and the greater the organ damage, the less effective the treatment. Systemic sclerosis–like damage to the skin and esophagus is least likely to respond to treatment.
People who develop myositis or systemic sclerosis are treated based on their symptoms. People who have Raynaud syndrome are treated based on their symptoms and may be given a calcium channel blocker (such as nifedipine) and drugs that increase blood flow (such as sildenafil or tadalafil).
People who take corticosteroids are at risk of fractures related to osteoporosis. To prevent osteoporosis, these people are given the drugs used to treat osteoporosis, such as bisphosphonates and supplemental vitamin D and calcium. People who are receiving immunosuppressants are also given drugs to prevent infections such as by the fungus Pneumocystis jirovecii (see prevention of pneumonia in immunocompromised people).
People who have mixed connective tissue disease are at increased risk of atherosclerosis, are closely monitored by doctors, and are treated for specific symptoms and complications of atherosclerosis as they occur.