Diseases of connective tissue include a large number of different disorders that can affect skin, fat, muscle, joints, tendons, ligaments, bone, cartilage, and even the eye, blood, and blood vessels. Connective tissue holds the cells of our body together. It allows for tissue stretching followed by a return to its original tension (like a rubber band). It’s made up of proteins, such as collagen and elastin. Blood elements, such as white blood cells and mast cells, are also included in its makeup.
There are several types of connective tissue disease. It’s useful to think of two major categories. The first category includes those that are inherited, usually due to a single-gene defect called a mutation. The second category includes those where the connective tissue is the target of antibodies directed against it. This condition causes redness, swelling, and pain (also known as inflammation).
Connective tissue diseases due to single-gene defects
Connective tissue diseases due to single-gene defects cause a problem in the structure and strength of the connective tissue. Examples of these conditions include:
- Ehlers-Danlos syndrome (EDS)
- Epidermolysis bullosa (EB)
- Marfan syndrome
- Osteogenesis imperfecta
Connective tissue diseases characterized by inflammation of tissues
Connective tissue diseases characterized by inflammation of tissues are caused by antibodies (called autoantibodies) that the body incorrectly makes against its own tissues. These conditions are called autoimmune diseases. Included in this category are the following conditions, which are often handled by a medical specialist called a rheumatologist:
- Rheumatoid arthritis (RA)
- Sjogren’s syndrome
- Systemic lupus erythematosis
People with diseases of connective tissue may have symptoms of more than one autoimmune disease. In these cases, doctors often refer to the diagnosis as mixed connective tissue disease.
The causes and symptoms of connective tissue disease caused by single-gene defects vary as a result of what protein is abnormally produced by that defective gene.
Ehlers-Danlos syndrome (EDS) is caused by a collagen formation problem. EDS is actually a group of over 10 disorders, all characterized by stretchy skin, abnormal growth of scar tissue, and over-flexible joints. Depending on the particular type of EDS, people may also have weak blood vessels, a curved spine, bleeding gums or problems with the heart valves, lungs, or digestion. Symptoms range from mild to extremely severe.
More than one type of epidermolysis bullosa (EB) occurs. Connective tissue proteins such as keratin, laminin, and collagen can be abnormal. EB is characterized by exceptionally fragile skin. The skin of people with EB often blisters or tears at even the slightest bump or sometimes even just from clothing rubbing against it. Some types of EB affect the respiratory tract, the digestive tract, the bladder, or the muscles.
Marfan syndrome is caused by a defect in the connective tissue protein fibrillin. It affects the ligaments, bones, eyes, blood vessels, and heart. People with Marfan syndrome are often unusually tall and slender, have very long bones and thin fingers and toes. Abraham Lincoln may have had it. Sometimes people with Marfan syndrome have an enlarged segment of their aorta (aortic aneurysm) which can lead to fatal bursting (rupture).
People with different single-gene problems placed under this heading all have collagen abnormalities along with typically low muscle mass, brittle bones, and relaxed ligaments and joints. Other symptoms of osteogenesis imperfecta are dependent upon the specific strain of osteogenesis imperfecta they have. These may include thin skin, a curved spine, hearing loss, breathing problems, teeth that break easily, and a bluish gray tint to the whites of the eyes.
Connective tissue diseases due to an autoimmune condition are more common in people who have a combination of genes that increase the chance that they come down with the disease (usually as adults). They also occur more often in women than men.
Polymyositis and dermatomyositis
These two diseases are related. Polymyositis causes inflammation of the muscles. Dermatomyositis causes inflammation of the skin. The symptoms of both diseases are similar and may include fatigue, muscle weakness, shortness of breath, difficulty swallowing, weight loss, and fever. Cancer can be an associated condition in some of these patients.
In rheumatoid arthritis (RA), the immune system attacks the thin membrane that lines the joints. This causes stiffness, pain, warmth, swelling, and inflammation throughout the body. Other symptoms may include anemia, fatigue, loss of appetite, and fever. RA can permanently damage the joints and lead to deformity. There are adult and less-common childhood forms of this condition.
Scleroderma causes tight, thick skin, a buildup of scar tissue, and organ damage. The types of this condition fall into two groups: localized or systemic scleroderma. In localized cases, the condition is confined to the skin. Systemic cases also involve the major organs and blood vessels.
The main symptoms of Sjogren’s syndrome are dry mouth and eyes. People with this condition can also experience extreme fatigue and pain in the joints. The condition increases the risk of lymphoma and can affect the lungs, kidneys, blood vessels, digestive system, and nervous system.
Systemic lupus erythematosus (SLE or lupus)
Lupus causes inflammation of the skin, joints, and organs. Other symptoms may include a rash on the cheeks and nose, mouth ulcers, sensitivity to sunlight, fluid on the heart and lungs, hair loss, kidney problems, anemia, memory problems, and mental illness.
Vasculitis is another group of conditions that affect the blood vessels in any area of the body. Common symptoms include loss of appetite, weight loss, pain, fever, and fatigue. Stroke can occur if blood vessels of the brain become inflamed.
There is currently no cure for any of the connective tissue diseases. Breakthroughs in genetic therapies, where certain problem genes are silenced, hold promise for the single-gene diseases of connective tissue.
For autoimmune diseases of connective tissue, treatment is aimed at helping to reduce the symptoms. Newer therapies for conditions such as psoriasis and arthritis can suppress the immune disorder that causes the inflammation.
Commonly used medications used in the treatment of autoimmune connective tissue diseases are:
- Corticosteroids. These medications help prevent the immune system from attacking your cells and prevent inflammation.
- Immunomodulators. These medications benefit the immune system.
- Antimalarial drugs. Antimalarials can help when symptoms are mild, they can also prevent flare-ups.
- Calcium channel blockers. These medications help to relax the muscles in the walls of the blood vessels.
- Methotrexate. This medication helps control symptoms of rheumatoid arthritis.
- Pulmonary hypertension medications. These medications open the blood vessels in the lungs affected by autoimmune inflammation, allowing blood to flow more easily.
Surgically, an operation on an aortic aneurysm for a patient with Ehlers Danlos or Marfan’s syndromes can be lifesaving. These surgeries are particularly successful if performed prior to rupture.
Infections can often complicate autoimmune diseases.
Those with Marfan syndrome can have a burst or ruptured aortic aneurysm.
Osteogenesis Imperfecta patients can develop difficulty breathing due to spine and rib cage problems.
Patients with lupus often have fluid accumulation around the heart which can be fatal. Such patients can also have seizures due to vasculitis or lupus inflammation.
Kidney failure is a common complication of lupus and scleroderma. Both these disorders and other autoimmune connective tissue diseases can lead to complications with the lungs. This can lead to shortness of breath, coughing, difficulty breathing, and extreme fatigue. In severe cases, the pulmonary complications of a connective tissue disease can be fatal.
There is a wide variability in how patients with single-gene or autoimmune connective tissue disease do in the long run. Even with treatment, connective tissue diseases often get worse. However, some people with mild forms of Ehlers Danlos syndrome or Marfan syndrome need no treatment and can live into old age.
Thanks to newer immune treatments for autoimmune diseases, people can enjoy many years of minimal disease activity and can benefit when the inflammation “burns out” with advancing age.
Overall, the majority of people with connective tissue diseases will survive for at least 10 years after their diagnosis. But any individual connective tissue disease, whether single-gene or autoimmune-related, can have a far worse prognosis.