Connective Tissue Disorder

Connective tissue disorders are a group of over 200 conditions that affect the tissues holding your body together. These disorders can range from inherited genetic conditions to autoimmune diseases where the body attacks its own tissues, causing inflammation and damage throughout the body.

Table of contents

• What is Connective Tissue Disorder
• Types of Connective Tissue Disorders
• Symptoms
• Causes and Risk Factors
• Diagnosis
• Treatment
• Complications
• Living with Connective Tissue Disorder

What is Connective Tissue Disorder

Connective tissue disorder is an umbrella term for a wide range of diseases that affect your body’s connective tissues. These are the tissues that connect and support your organs and body structure^[1]. Connective tissues hold your muscle fibers together and cover and protect your nerves. They also include body fat, bones, cartilage, fascia (layers of tissue surrounding muscles), ligaments, skin, and tendons^[1].

These tissues are made up of two different proteins: collagen (found in tendons, ligaments, skin, cartilage, bone, and blood vessels) and elastin (found in ligaments and skin)^[5]. Because connective tissues are in almost every part of your body, connective tissue diseases can affect you all over. They might affect one or two types of tissues throughout your body or many, and they can also affect many organs^[1].

There are more than 200 disorders that affect connective tissue, and each disorder has its own symptoms and needs different treatment^[3].

• Body fat
• Bones
• Cartilage
• Fascia
• Ligaments
• Skin
• Tendons
• Blood vessels
• Muscles
• Joints
• Eyes
• Heart
• Lungs
• Kidneys
• Digestive system

Types of Connective Tissue Disorders

Connective tissue disorders fall into three main categories: autoimmune diseases, genetic disorders, and cancers^[1]. It’s useful to think of two major categories: those that are inherited, usually due to a faulty gene or gene mutation, and those where the connective tissue is the target of antibodies directed against it, causing inflammation^[9].

Autoimmune Connective Tissue Disorders

Autoimmune diseases are what many people think of when they think of connective tissue disease. In these conditions, your immune system generates chronic inflammation (long-lasting swelling and irritation) in some parts of your body. Chronic inflammation causes pain, swelling, and eventually permanent damage to your tissues^[1].

Some examples of autoimmune connective tissue disorders include:

• Rheumatoid arthritis: This causes joint inflammation, sometimes leading to joint destruction and deformity. In some cases, the inflammation may spread to blood vessels or other organs^[1].
• Systemic lupus erythematosus (lupus): This condition can cause inflammation in any of your connective tissues, and sometimes all of them. Systemic lupus may affect your skin, joints, and vital organs like your heart, lungs, and kidneys^[1].
• Scleroderma (also called systemic sclerosis): This condition causes your body to overproduce collagen, which can cause thickening and hardening of your skin and organs, including your digestive system, kidneys, heart, and lungs^[1].
• Sjögren’s syndrome: This inflames and damages your moisture-producing glands, causing dryness throughout your body, including your eyes, mouth, digestive system, and respiratory system^[1].
• Myositis: This causes inflammation and degeneration of your muscles, making them feel weak. There are different types of myositis that can affect both the muscles and/or skin, causing rashes^[1].
• Relapsing polychondritis: This causes inflammation and degeneration of the cartilage in your ears, nose, and throat, which can affect your hearing and breathing. Sometimes, it affects your eyes^[1].

If you have overlapping features of several autoimmune connective tissue disorders, it’s called mixed connective tissue disease^[1]. Mixed connective tissue disease has features of three other connective tissue diseases: systemic lupus erythematosus, scleroderma, and polymyositis^[16]. About 25% of people with a connective tissue disease develop another connective tissue disease over the course of several years, which is why mixed connective tissue disease is known as an “overlap syndrome”^[16].

If you have some symptoms of autoimmune diseases but they don’t meet the criteria for any specific disorder, it’s called undifferentiated connective tissue disease^[1]. This term describes a condition in people who have symptoms and lab test results that suggest a systemic autoimmune disorder or connective tissue disease but which are not extensive or specific enough to meet usual criteria for a diagnosis of a defined connective tissue disease^[17].

Genetic Connective Tissue Disorders

Genetic disorders of the connective tissue result from a gene mutation that you inherit at birth. The mutation affects how your connective tissues develop. It usually affects one of the two primary building blocks in all connective tissues: collagen or elastin. This causes various defects in your tissues^[1].

Examples of hereditary connective tissue diseases include:

• Marfan syndrome: This syndrome affects the elastin fibers that give your tissues elasticity, making your tissues too loose. It causes elongated limbs and can also cause issues in your cardiovascular system^[1]. People with Marfan syndrome tend to be tall, have extremely long bones, and thin “spider-like” fingers and toes. Other problems may include eye problems due to abnormal placement of the eye lens and enlargement of the aorta (the largest artery in the body), which can lead to a fatal rupture^[2].
• Ehlers-Danlos syndrome: This condition weakens the collagen throughout your body^[1]. It is a group of more than 10 disorders characterized by overflexible joints, stretchy skin, and abnormal growth of scar tissue. Symptoms can range from mild to disabling^[2].
• Epidermolysis bullosa: People with this condition have fragile skin that can easily tear or blister as a result of a minor bump, stumble, or even friction from clothing. Some forms may involve the digestive tract, respiratory tract, muscles, or bladder^[2].
• Osteogenesis imperfecta: This is a condition of brittle bones, low muscle mass, and lax joints and ligaments. There are several types of this condition. Specific symptoms depend on the type and may include a blue or gray tint to the whites of the eyes, thin skin, curved spine, breathing problems, hearing loss, and teeth that break easily^[2].

Symptoms

Since there are so many connective tissue diseases, your symptoms will depend on the disease you have^[2]. Different types of connective tissue disease have different symptoms. In general, symptoms may affect your bones, joints, skin, heart and blood vessels, lungs, head and face, height, muscles, and fingers^[2].

Common symptoms across various connective tissue disorders include:

• Joint pain or weakness^[2]
• Muscle weakness^[2]
• Fatigue and feeling generally unwell^[8]
• Low-grade fever^[8]
• Skin changes or rashes^[2]
• Swelling and color changes to your fingers and fingertips^[2]

More serious symptoms related to inflammation around the lungs may include difficulty breathing, shortness of breath, breathlessness, fatigue, a cough with bloody phlegm, chest discomfort or pain, and respiratory failure^[5].

Raynaud’s phenomenon is a common symptom in several connective tissue disorders. This condition causes reduced blood flow to your fingers, toes, ears, and nose, causing sensitivity, numbness, and loss of color in these areas. The fingers might get puffy and the fingertips become white and numb, often in response to being cold or stress. Fingers or toes might turn white and then blue or gray, and after warming, they turn red^[8].

Early symptoms of mixed connective tissue disease can include a feeling of not being well (including tiredness and mild fever), cold and numb fingers or toes (Raynaud’s disease), swollen fingers or hands, muscle and joint pain, and rash. Red or brown patches can appear over the knuckles^[8].

Causes and Risk Factors

The cause of connective tissue disorders is not always known^[5]. Some are caused by a genetic component, while others can be caused by injury. Others seem to appear without any known cause^[5].

Autoimmune Connective Tissue Diseases

Researchers don’t know what triggers autoimmune connective tissue diseases. The actual cause, like that of many rheumatic diseases, is not well understood. One theory is that some people have a genetic predisposition or risk of developing connective tissue disease and then experience an environmental trigger, such as an infection. This then leads the immune system to incorrectly target the body itself as if it is a “foreign invader”^[17].

You might get an autoimmune connective tissue disease because of:

• Toxic chemicals found in things such as air pollution and cigarette smoke^[2]
• Poor nutrition, mostly a lack of vitamins D and C^[2]
• Infection^[2]
• Too much ultraviolet light^[2]

For mixed connective tissue disease, it’s not directly inherited, although some research shows that the disease may occur more often in people with a biological family history of connective tissue diseases. Exposure to certain viruses, chemicals, or materials like polyvinyl chloride and silica are other possible causes^[16].

Genetic Connective Tissue Disorders

Some connective tissue diseases, often called heritable disorders of connective tissue, result from changes in certain genes. A mutation in genes responsible for proteins essential to the structure of bones, skin, and other tissues causes these disorders^[2].

Risk Factors

Certain conditions may show an increased rate of occurrence in certain groups, but they can affect both men and women of all ages^[5]. Mixed connective tissue disease occurs most often in females in their 20s and 30s, but people of all ages, including children, can develop the disease^[16].

Tell your doctor if you have a family history of a connective tissue disorder or if you have a relative who died suddenly at a young age. That information can help with a diagnosis^[4].

Diagnosis

Diagnosis begins with the physician taking a medical history and performing a neurological examination^[5]. Because connective tissue disorders can have symptoms similar to other conditions, diagnostic tests will help rule out other causes and confirm a diagnosis^[5].

Connective tissue disorders can be difficult for healthcare providers to diagnose because symptoms of different conditions usually don’t happen at all once. Because they occur one after the other over a long period of time, it may take several years before a provider can make an accurate diagnosis. You’ll likely work with a specialist called a rheumatologist in the diagnosis^[16].

Blood Tests

Blood tests are commonly used to diagnose connective tissue disorders. A complete blood count checks for anemia (low red blood cell count) and overall health. Blood tests can measure the degree of inflammation in the body^[12].

A blood test can check for antibodies that are linked with connective tissue diseases. These include antinuclear antibodies (ANAs), which must be present for the diagnosis of certain conditions^[12]. For mixed connective tissue disease, high concentrations of antiribonucleoprotein antibodies (anti-RNP antibodies) are a diagnostic marker^[16].

Imaging Tests

These tests may include a magnetic resonance imaging (MRI) scan of the brain and spinal cord^[5]. Chest x-rays may be ordered to see if signs of inflammation are present in the lungs^[5].

Other Tests

Other tests may include an electromyogram to record the signals between muscles and nerves, and nerve or muscle biopsy of the affected area to confirm the diagnosis^[5]. Urine tests can help show whether the kidneys are affected and how badly^[12]. A lumbar puncture (also known as a spinal tap) may also be performed^[5].

Some common tests that look for connective disorders include imaging tests or genetic testing. Genetic testing on its own isn’t enough to rule out some conditions because the test doesn’t detect all possible genetic factors that can lead to the condition^[4].

Treatment

There’s no cure for most connective tissue diseases. Treatment varies depending on the type of connective tissue disorder diagnosis the patient receives^[5]. The type of medicine you take depends on how bad your condition is and what organs it affects^[12].

Medications

Nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarials (such as hydroxychloroquine), and corticosteroids (medicines that reduce inflammation) are the mainstay of therapy^[15]. Immunosuppressive drugs are generally reserved for treating specific clinical manifestations and for patients with major organ involvement^[15].

Medicines may include:

• Corticosteroids: Medicines such as prednisone can help keep the immune system from attacking healthy cells and ease swelling and irritation. Corticosteroids may be used to reduce inflammation for a short period or indefinitely^[5]. Long-term use can lead to serious side effects including mood swings, weight gain, high blood sugar, increased blood pressure, higher risk of infection, weakened bones, and cataracts^[12].
• Medicines that treat malaria: Hydroxychloroquine can treat mild connective tissue disease and might prevent flares of the condition^[12].
• Calcium channel blockers: These medicines, including nifedipine and amlodipine, help relax the muscles in the walls of blood vessels and can help treat Raynaud’s phenomenon^[12].
• Immunosuppressant agents: Other medicines to keep the immune system in check may be prescribed^[12].

Approximately 20 years have passed since the approval of infliximab for rheumatoid arthritis in 2003. Since then, several biological therapeutics have been marketed and adapted for many connective tissue diseases. Although conventional treatment for patients with these diseases is rarely used because of their poor prognosis, these cases may benefit from biological therapeutics^[14].

Supportive Therapies

Some conditions can affect a patient’s daily life, so physical and occupational therapy may be used to manage symptoms and help patients adjust to living and working situations. Physical aids such as braces or a cane may also be needed. For some patients, pain management may be needed^[5].

Physical therapy techniques for connective tissue disorders include joint protection strategies, customized exercise plans, and hydrotherapy (water-based exercises that reduce pressure on joints while providing resistance)^[22]. Occupational therapists can provide adaptive equipment, energy conservation strategies, and workplace modifications^[22].

Regular, appropriate exercise is crucial for managing connective tissue diseases. The right activities can reduce stiffness, improve strength, and enhance overall well-being. Low-impact cardiovascular exercise such as swimming helps maintain heart health and stamina without stressing vulnerable joints^[22].

Lifestyle Medicine

Incorporating lifestyle medicine into the management of connective tissue diseases offers a patient-centered approach that complements pharmacologic treatments. By addressing modifiable risk factors, healthcare providers can empower patients to improve quality of life, reduce reliance on medications, and potentially slow disease progression^[23].

Key lifestyle factors include nutrition, physical activity, sleep, stress management, avoidance of harmful substances, and social connections. Specifically, ultra-processed foods and other lifestyle factors could impact the risk of systemic lupus erythematosus. In contrast, the Mediterranean diet is particularly beneficial for rheumatoid arthritis, offering anti-inflammatory properties and potential improvements in symptoms. Smoking and alcohol consumption were identified as modifiable risk factors that exacerbate disease progression^[23].

Restorative sleep and effective stress management are critical in mitigating disease activity, as poor sleep and high stress are associated with worsened outcomes^[23].

Complications

Mixed connective tissue disease and other connective tissue disorders can lead to severe complications. These may include:

• High blood pressure in your lungs (pulmonary hypertension)^[16]
• Interstitial lung disease (scarring of lung tissue)^[16]
• Heart disease^[16]
• Kidney damage^[16]
• Digestive tract damage^[16]
• Anemia^[16]
• Tissue death (necrosis)^[16]
• Hearing loss^[16]
• Nerve damage^[16]

Damage to connective tissue can cause serious health issues. The effects of these conditions can range from mild to severe^[4]. One condition, Marfan syndrome, can lead to balloon-like bulges called aneurysms in blood vessels. These bulges are especially dangerous when they occur in the body’s largest blood vessel, the aorta, which carries blood to the heart. If it bursts, it can cause sudden death^[4].

Living with Connective Tissue Disorder

Living with a connective tissue disease doesn’t mean accepting limitations as inevitable. With proper medical care, targeted treatments, and lifestyle adjustments, you can effectively manage symptoms and maintain an active, fulfilling life^[22].

Patients with connective tissue disorders are typically monitored for progression of specific manifestations, evolution to a defined disease, and safety and efficacy of treatment. The frequency of monitoring that is necessary depends on the severity of disease. During the first 5 years after diagnosis, the frequency of follow-up visits may be greater, given the propensity for the disease to evolve early in the disease course^[15].

In general, activities are not restricted in the absence of specific functional limitations. Patients with photosensitivity should minimize prolonged exposure to sunlight and should use protective clothing and sunblock lotions/creams to protect against ultraviolet light. Patients with severe Raynaud phenomenon should avoid prolonged exposure to severe cold temperatures to avoid digital vasospasm. Layered clothing, hats, and gloves help to maintain a warm core body temperature and decreased vasospastic symptoms. Tobacco use should be avoided^[15].

Many patients have found that maintaining a positive attitude helps. “Don’t wait for life. You live it,” as one patient with mixed connective tissue disease advised^[24]. Another patient shared: “I have learned a lot about the disease and about myself. I have learned to be grateful for what I have and not to mourn what I have lost”^[25].

Family and friends are often a good support. Daily walks and moderate strength training help keep patients moving and provide mental balance^[25]. Although symptoms like chronic pain and chronic fatigue are often missed or dismissed, it’s important to talk with your doctor about any symptoms you have^[4].