Diseases of Connective Tissue, from Genetic to Autoimmune

There are several types of connective tissue diseases. It’s useful to think of two major categories.

The first category includes those that are inherited, usually due to a faulty gene or gene mutation.

The second category includes those where the connective tissue is the target of antibodies directed against it. This causes redness, swelling, and pain (also known as inflammation).

Connective tissue diseases due to gene defects

Connective tissue diseases due to 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

Connective tissue diseases characterized by inflammation are caused by antibodies called autoantibodies that the body incorrectly makes to attack 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:

• polymyositis
• dermatomyositis
• rheumatoid arthritis (RA)
• scleroderma
• Sjogren’s syndrome
• systemic lupus erythematosus
• vasculitis

People living with connective tissue diseases 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 diseases are caused by gene defects vary as a result of what protein is abnormally produced by that defective gene.

Ehlers-Danlos syndrome

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
• overly 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.

Epidermolysis bullosa

Epidermolysis bullosa (EB) is caused by a gene mutation that makes skin more fragile. The skin of people with EB often blisters or tears at even the slightest bump or sometimes even just from clothing rubbing against it.

More than one type of EB can occur. Depending on the type, the genetic mutation affects how different proteins in your skin, such as keratin, laminin, or collagen, are made.

Some types of EB can affect the respiratory tract, the digestive tract, the bladder, or the muscles.

Marfan syndrome

Marfan syndrome is caused by a defect in the connective tissue protein fibrillin. It affects the:

• bones
• ligaments
• tendons
• cartilage
• eyes
• blood vessels and heart
• lungs
• skin

People with Marfan syndrome are often unusually tall and slender, have very long bones, and have thin fingers and toes. Sometimes people with Marfan syndrome have an enlarged segment of their aorta (aortic aneurysm), which can lead to fatal bursting (rupture).

Osteogenesis imperfecta

Osteogenesis imperfecta is caused by gene mutations that affect the body’s ability to produce collagen. People with different gene defects that fall under this heading typically have:

• collagen abnormalities
• low muscle mass
• brittle bones
• relaxed ligaments and joints

Other symptoms of osteogenesis imperfecta are dependent upon the specific subtype. 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.

The causes and symptoms of connective tissue diseases that are caused by an autoimmune disease vary from condition to condition. Most tend to occur more often in women than men.

Polymyositis and dermatomyositis

These two diseases of unknown cause are related.

Polymyositis leads to inflammation of the muscles. Dermatomyositis results in inflammation of the skin. The symptoms of both diseases are similar and may include:

• fatigue
• muscle weakness
• shortness of breath
• difficulty swallowing
• weight loss
• fever

Cancer can also be an associated with polymyositis and dermatomyositis.

Rheumatoid arthritis

In rheumatoid arthritis (RA), the immune system mistakenly attacks the thin membrane that lines the joints. This commonly leads to symptoms of the joints, such as:

• pain
• inflammation
• stiffness
• swelling
• warmth

Left untreated, RA can permanently damage the joints and lead to deformities. There are forms of RA specific to adults and less common childhood forms of this condition.

Scleroderma

Scleroderma occurs when the immune system mistakenly attacks connective tissue under the skin and around the internal organs and blood vessels. This leads to symptoms like:

• tight, thick skin
• scar tissue buildup
• organ damage

Types of scleroderma fall into two groups: localized scleroderma and systemic scleroderma. In localized cases, the condition is confined to the skin. Systemic cases also involve major organs and blood vessels.

Sjogren’s syndrome

Sjögren’s syndrome occurs when the immune system attacks areas of the body that produce fluids, such as the salivary and tear-secreting glands. As a result, the main symptoms are dry mouth and eyes. However, people with this condition can also experience extreme fatigue and pain in the joints.

Sjogren’s syndrome increases the risk of lymphoma and can also 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 health conditions.

While there’s no one known cause for lupus, it may be related to a combination of things, such as genetic, environmental, and hormonal factors.

Vasculitis

Vasculitis is another group of conditions that occurs when the immune system mistakenly attacks blood vessels in any area of the body. Common symptoms of vasculitis include:

• shortness of breath
• cough
• numbness and weakness in the hands or feet
• red spots on the skin (purpura)
• skin lumps (nodules)
• sores (ulcers)

Vasculitis can also lead to nonspecific symptoms, such as loss of appetite, weight loss, pain, fever, and fatigue. Stroke can occur if blood vessels of the brain become inflamed.

There’s currently no cure for any of the connective tissue diseases. Each type of disorder has its own treatment options.

Treatment for genetic connective tissue diseases

Breakthroughs in genetic therapies, where certain problem genes are silenced, hold promise for genetic connective tissue diseases.

For someone living with Ehlers-Danlos syndrome or Marfan syndrome, surgery on an aortic aneurysm can be lifesaving. These operations are particularly successful if performed prior to rupture.

Treatment for autoimmune connective tissue diseases

For autoimmune connective tissue diseases, treatment is aimed at helping to control inflammation and reduce symptoms. Autoimmune connective tissue diseases are commonly treated with:

• Nonsteroidal anti-inflammatory drugs (NSAIDs): These drugs can help relieve pain and inflammation.
• Corticosteroids: These medications help stop the immune system from attacking your cells and prevent inflammation.
• Disease-modifying anti-rheumatic drugs (DMARDs): Options like antimalarial drugs and methotrexate can be used to suppress the underlying overactive immune response to help manage symptoms and prevent worsening of the disease.
• Immunosuppressants: These medications also work to suppress an overactive immune system and manage symptoms.
• Calcium channel blockers: These medications help relax the muscles in the walls of blood vessels.
• Pulmonary hypertension medications: These medications open the blood vessels in the lungs affected by autoimmune inflammation, allowing blood to flow more easily.

Work with your doctor to develop the right treatment plan based on your diagnosis and needs.

A number of health complications are thought to be related to various connective tissue diseases. For example:

• Autoimmune diseases and their treatments often come with an increased risk of infections, and infections can worsen certain autoimmune conditions.
• Marfan syndrome can lead to a burst or ruptured aortic aneurysm.
• Osteogenesis imperfecta can lead to difficulty breathing due to spine and rib cage problems.
• Lupus can lead to fluid accumulation around the heart, which can be fatal. People with lupus may also have seizures due to vasculitis or lupus inflammation.

Kidney failure is a common complication of both lupus and scleroderma. Both these disorders and other autoimmune connective tissue diseases can also lead to complications with the lungs. This can lead to:

• shortness of breath
• coughing
• difficulty breathing
• extreme fatigue

In severe cases, the pulmonary complications of a connective tissue disease can be fatal.

There is a wide variability in the outlook for people living with connective tissue disease.

Though treatments are available, connective tissue diseases often worsen over time.

However, some people with mild forms of Ehlers-Danlos syndrome or Marfan syndrome may not need treatment and live long lives. And thanks to newer treatments for autoimmune diseases, many people can achieve minimal disease activity.