Mixed connective tissue disease is a term used by some doctors to describe a disorder characterized by features of systemic lupus erythematosus, systemic sclerosis, and polymyositis.
About 80% of people who have this disease are women. Mixed connective tissue disease affects people from ages 5 to 80. Its cause is unknown, but it seems to be an autoimmune disorder.
The typical symptoms are Raynaud's syndrome (in which the fingers suddenly become very pale and tingle or become numb or blue in response to cold or emotional upset—see Peripheral Arterial Disease: Raynaud's Syndrome), joint inflammation (arthritis), swollen hands, muscle weakness, difficulty in swallowing, heartburn, and shortness of breath. Raynaud's 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.
The hands are frequently so swollen that the fingers look like sausages. A purplish butterfly-shaped rash on the cheeks and bridge of the nose, red patches on the knuckles, a violet discoloration of the eyelids, and red spider veins on the face and hands all may appear. Skin changes similar to those in systemic sclerosis also may occur. The hair may thin.
Almost everyone with mixed connective tissue disease has aching joints. About 75% develop the swelling and pain typical of joint inflammation (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.
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.
Occasionally, the heart is weakened, leading to heart failure (see Heart Failure). Symptoms of heart failure may include fluid retention, shortness of breath, and fatigue. The kidneys and nerves are affected in only 10% of people, and the damage is usually mild compared to the damage caused by lupus. Other symptoms may include fever, swollen lymph nodes, abdominal pain, and persistent hoarseness. Sjögren's syndrome may develop. Over time, most people develop symptoms that are more typical of lupus or systemic sclerosis.
Doctors suspect mixed connective tissue disease when some symptoms from lupus, systemic sclerosis, polymyositis, or rheumatoid arthritis overlap.
Blood tests are performed to detect an antibody to ribonucleoprotein, which is present in almost all people who have mixed connective tissue disease. A high level of this antibody without the other antibodies present in lupus is characteristic of mixed connective tissue disease.
Despite treatment, mixed connective tissue disease worsens in about 13% of the people, causing potentially fatal complications in 6 to 12 years. The prognosis is worse for people who have mainly features of systemic sclerosis or polymyositis. Overall, 80% of people survive at least 10 years after the diagnosis is made. Symptom-free periods can last for many years with little or no continuing treatment with a corticosteroid.
The treatment is similar to that of lupus. Corticosteroids are usually effective, especially when the disease is diagnosed early. Mild cases can be treated with aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine or similar drugs, or very low doses of corticosteroids. The more severe the disease, the higher the dose of corticosteroid needed. In severe cases, immunosuppressive drugs (such as azathioprine, methotrexate or cyclophosphamide) may also be needed.
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.
Last full review/revision February 2008 by Rula A. Hajj-ali, MD