Connective tissue disease

What is connective tissue disease?

Connective tissue disease is an umbrella term for a large group of conditions, over 200 in total, that affect the tissues holding your body together, including your skin, bones, cartilage, tendons and ligaments. These conditions can be inherited, caused by your immune system attacking your own tissues, or, more rarely, a type of cancer.

Symptoms of connective tissue disease

Because connective tissue is found throughout your body, symptoms can affect almost any part of it and vary widely depending on which condition you have. Common symptoms across many connective tissue diseases include:

• pain, weakness or stiffness in your muscles and joints
• fatigue
• skin changes, such as thickening, tightening, rashes, or unusual stretchiness
• swelling, puffiness or colour changes in your fingers, sometimes with numbness or a loss of colour in cold weather, called Raynaud's phenomenon
• breathing difficulties, a cough, or chest pain, since many connective tissue diseases affect your lungs
• changes in blood pressure or heart rhythm

Some genetic connective tissue conditions also cause differences in height, such as being unusually tall with long limbs, or unusually brittle bones. Symptoms of different connective tissue diseases can develop gradually over time rather than appearing all at once, so it's worth mentioning any new or unusual symptoms to your doctor, even if they seem unrelated to each other.

Causes and who is at risk

Connective tissue disease happens when something goes wrong in how your body makes or maintains these tissues. There are three broad causes:

• Autoimmune: your immune system mistakenly attacks your own healthy tissue, causing ongoing inflammation
• Genetic: a gene change you're born with affects how your connective tissue develops, usually involving collagen or elastin, the two main building blocks of connective tissue
• Cancer (sarcoma): cells in your connective tissue divide uncontrollably. This is much less common than the other two causes

For most people, scientists don't fully understand why these problems develop. Possible contributing factors for the autoimmune types include:

• exposure to toxic chemicals, such as those in air pollution or cigarette smoke
• poor nutrition, particularly a lack of vitamins D and C
• infections
• too much ultraviolet light
• severe infections or illness that puts stress on your immune system

Autoimmune connective tissue diseases are diagnosed more often in women than men. Genetic types are inherited from a parent, though the risk of passing them on, and how severely they affect a child, varies depending on the specific condition.

Are there different types of connective tissue disease?

Yes, there are more than 200 known connective tissue disorders, generally grouped into three categories.

Autoimmune connective tissue diseases

These are what most people think of when they hear 'connective tissue disease'. Your immune system causes ongoing inflammation in parts of your body. Examples include:

• rheumatoid arthritis: causes joint inflammation, which can lead to joint damage and deformity over time
• lupus: can cause inflammation in your skin, joints and organs, including your heart, lungs and kidneys
• scleroderma: causes your body to overproduce collagen, thickening and hardening your skin and sometimes your organs
• Sjögren's syndrome: damages your moisture-producing glands, causing dryness in your eyes, mouth and elsewhere
• polymyositis and dermatomyositis: cause inflammation and weakness in your muscles, and sometimes a skin rash
• vasculitis: a group of conditions causing inflammation in your blood vessels.

If you have overlapping features of several of these conditions, it's called mixed connective tissue disease. If you have some symptoms of an autoimmune connective tissue disease, but not enough to meet the criteria for any specific one, it's called undifferentiated connective tissue disease.

Genetic (inherited) connective tissue diseases

These result from a gene change passed down from a parent, affecting how your collagen or elastin develops. Examples include:

• Ehlers-Danlos syndrome: weakens collagen throughout your body, making your skin and joints overly stretchy, fragile and unstable
• Marfan syndrome: affects elastin, causing overly loose tissues, unusually long limbs, and sometimes heart and blood vessel problems
• osteogenesis imperfecta: causes a lack of a particular type of collagen, leading to brittle bones and teeth and loose joints
• epidermolysis bullosa: makes your skin fragile, so it blisters or tears easily

Cancers of the connective tissue (sarcomas)

Sarcomas are cancers that start in your bones, cartilage, fat, muscles, ligaments or tendons. Examples include osteosarcoma (the most common type of primary bone cancer) and chondrosarcoma (bone cancer starting in cartilage). This is a rarer category than the other two.

How is connective tissue disease diagnosed?

Diagnosing a connective tissue disease usually starts with your doctor asking about your symptoms, your medical history, and your family's medical history, followed by a physical examination. Depending on what's suspected, further tests may include:

• blood and urine tests
• imaging, such as X-rays or an MRI scan
• blood tests for markers of inflammation, such as CRP or ESR (erythrocyte sedimentation rate)
• tests for specific antibodies, particularly for autoimmune conditions
• tests for dry eyes or a dry mouth
• a tissue biopsy, taking a small sample for examination in a laboratory

Some conditions, particularly overlap conditions like mixed connective tissue disease, can take years to diagnose accurately, since the different features involved often develop one after another rather than all at once. You'll usually be referred to a specialist, such as a rheumatologist, if an autoimmune connective tissue disease is suspected.

How is connective tissue disease treated?

Non-surgical treatment

Most connective tissue diseases are long-term conditions, and treatment focuses on controlling symptoms and complications rather than curing the underlying disease. What's recommended depends heavily on which condition you have. For autoimmune connective tissue diseases, treatment usually aims to control inflammation and may include:

• non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, for mild pain and inflammation
• corticosteroids, to reduce inflammation and calm an overactive immune system
• disease-modifying anti-rheumatic drugs (DMARDs), such as antimalarial medicines or methotrexate
• other immunosuppressant medicines, for more severe disease or when major organs are affected
• calcium channel blockers, to help with Raynaud's phenomenon (poor blood flow to the fingers)
• medicines for high blood pressure in the lungs (pulmonary hypertension), a serious complication of some connective tissue diseases.

Regular low-impact exercise or physical therapy is often recommended alongside medicines to help with musculoskeletal pain. Self-care steps such as keeping your hands warm in cold weather, not smoking, and managing stress can also help with symptoms like Raynaud's phenomenon. For genetic connective tissue diseases, there's currently no way to treat the underlying gene change. Instead, your healthcare team treats each symptom and complication individually and monitors you throughout your life.

Surgical treatment

Surgery plays a role for some connective tissue diseases:

• for inherited conditions such as Ehlers-Danlos syndrome or Marfan syndrome, surgery to repair an enlarged or at-risk section of the aorta (the body's main artery) can be lifesaving, and works best when done before it ruptures
• for sarcomas (cancers of the connective tissue), treatment usually includes surgery, alongside chemotherapy or radiotherapy as needed.

Most connective tissue diseases don't require surgery for the condition itself, though you may need surgery to manage specific complications as they arise.

When should I see a doctor?

See your doctor if you develop symptoms of a connective tissue disease, especially if they're affecting your daily life. This might include new or unexplained muscle or joint pain, puffy or numb fingers, unusual skin changes, or persistent fatigue.

It's worth mentioning all your symptoms, even ones that seem unrelated to each other, since different symptoms can be connected effects of the same underlying condition. Getting a diagnosis and starting treatment sooner generally puts you in a better position to manage your condition, so don't ignore symptoms or wait for them to resolve on their own. If you already have a diagnosis, contact your doctor if your symptoms get worse or you develop new ones.