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Connective tissue disease

Dr. Suvansh Raj NirulaMBBS

December 07, 2020

December 07, 2020

Connective tissue disease
Connective tissue disease

Connective tissues join two or more parts of the body. Types of connective tissue in the body include flexible tissue like cartilage, dense tissue like fascia, specialised tissues like our bones and fluid tissues like blood.

Either due to genetically determined defects in the protein components of these tissues or due to inflammation produced by autoantibodies erroneously targeted towards the body's own connective tissues, connective tissue diseases arise.

Genetically inherited connective diseases, such as Marfan's syndrome, are rare syndromes. Whereas connective diseases like rheumatoid arthritis are more commonly occurring autoimmune diseases. The presentation (symptoms) of these diseases varies based on the site of inflammation of connective tissues.

Largely the management of these diseases consists of two components: symptomatic treatment and longer-term disease-modifying therapy. Rheumatologists (specialists dealing with autoimmune diseases) can effectively control the disease with the help of disease-modifying antirheumatic drugs (DMARDs), but relapses and remissions are expected and natural. The aim of the treatment remains to keep the disease in tight check to prevent irreversible deformities.

What are connective tissue diseases?

Connective tissue is the biological tissue of the body that, as the name suggests, connects two or more parts of the body.

All connective tissues share a common composition: an extracellular matrix—composed mainly of two structural proteins, elastin and collagen—with tissue-specific cells embedded in it. Elastin is a stretchy protein with elastic recoiling properties. Various kinds of collagen are present in different parts of the body. Examples of connective tissues include bone, cartilage, tendon, ligaments, skin and fat.

Sometimes, certain diseases cause the inflammation and weakening of these tissues by faulty immune system mechanisms that misread the body's own tissue and target them. This phenomenon is called autoimmunity and such diseases, like rheumatoid arthritis, that manifest by it, are called autoimmune connective tissue diseases.

However, not all connective tissue diseases are autoimmune. Some diseases, like Ehlers-Danlos syndrome and Marfan's syndrome, are heritable (passed from parent to child) and run in the family.

Types of connective tissue diseases

Depending on the cause, connective tissue disorders can be of different types:

  • Inherited connective tissue diseases: These are rare disorders of connective tissues. They arise because of the presence and expression of disease-specific genes that are passed on from one or both parents to the child. Some examples include:
    • Ehlers-Danlos syndromes: There are 13 types of Ehlers-Danlos syndromes of which hypermobile Ehlers-Danlos is the most common. It is characterised by hypermobile joints and stretchy skin that bruises easily.
    • Marfan's syndrome: This condition is caused by a genetic problem where the body can't make fibrillin-1 protein properly, resulting in long thin “spider-like” fingers and toes, eye problems (like dislocation of the lens of the eye) and heart problems (like mitral valve prolapse).
    • Epidermolysis bullosa: This condition might be apparent at birth. Due to anomalies in several structural proteins, the skin is extremely thin and delicate. It blisters on the slightest of bumps or impact.
    • Osteogenesis imperfecta (also known as the brittle bone disease): Type I collagen, an important component of bones, is either defective or deficient, leading to brittle bones and low muscle mass. Other associated problems in this condition are blue sclera (white portion of the eyeball appears bluish), teeth break easily, thin skin and curved spine.
  • Autoimmune connective tissue diseases: For reasons that aren't completely understood, the body's immune system can—by mistake—start seeing certain normal factors of connective tissues as foreign. When this happens, the immune system attacks this tissue and inflammation of connective tissues arises. Human leukocyte antigens (HLA), encoded by chromosome 6, are responsible for the recognition of antigens (proteins that are foreign and potentially harmful to the body) by T-lymphocytes (T-cells) in order to ensure correct inflammatory response against undesirable targets. However, certain variations of HLA confer autoimmunity and are linked to specific autoimmune diseases. Examples of common autoimmune connective tissue diseases are:
    • Rheumatoid arthritis: A chronic, progressive autoimmune disease that causes joint inflammation and later deformities—primarily of the small joints like the fingers—rheumatoid arthritis more commonly affects the small joints of the hand (wrist and fingers) than the foot (ankle and toes). Acute attacks are managed with common anti-inflammatory drugs, but the condition requires longer-term disease-modifying therapy with special oral medicines or injectable biological drugs.
    • Systemic lupus erythematosus (SLE): Systemic lupus erythematosus (SLE) is another autoimmune disease. The characteristic sign is a red butterfly-shaped facial rash across the two cheekbones. The condition causes widespread inflammation in connective tissues of different parts of the body, including the joints, skin, brain, kidney, blood vessels, etc.
    • Scleroderma: Due to exaggerated and excessive production of collagen protein in scleroderma, the skin gets thickened, tightened and stretched across the face. The face appears encased in a mask, the mouth looks shrunken and at times the nose might break as well. The kidneys and lungs, too, get scarred with deposits of extra collagen. CREST syndrome, marked by blueing of fingertips, nail changes and feeding problems can occur with scleroderma. (Read more: SCL-70 antibodies test)
    • Psoriasis (and psoriatic arthritis): Psoriasis is an autoimmune condition primarily affecting the skin. It presents with red flaky patches and can at times be accompanied by inflammation of the joints (psoriatic arthritis).
    • Vasculitis: Various kinds of vasculitides, or inflammation of blood vessels (vasculitis), are caused by autoantibodies that target connective tissue components in the blood vessels. These diseases are classified based on the size of the vessels they affect—small, medium and large. Examples include Behçet’s disease, polyarteritis nodosa and giant cell arteritis.

Connective tissue disease symptoms

Connective tissues are present throughout the body and the signs and symptoms of connective tissue disease depend on the site of inflammation. Here are the signs and symptoms a few connective tissue diseases:

Inherited connective tissue diseases

Marfan syndrome

  • Arms that are too long for the body
  • Legs that are too long for the body
  • Tall and thin body
  • Heart murmur
  • A sunken or protruding breastbone (sternum)
  • The palate or roof of the mouth is high and curved. The teeth are crowded (very close together or on top of each other) and misaligned.
  • Flat feet
  • Nearsightedness

Autoimmune connective tissue diseases

Rheumatoid arthritis

  • Inflammation of the joints which results in joint pain, joint stiffness and swelling of the joints. The pain and stiffness are worse in the morning after getting up and persist throughout the day. Rheumatoid arthritis commonly affects small joints (like fingers, wrists, feet and ankles) and rarely large joints (like knees or hips). The joints are usually symmetrically affected, that is both sides are affected. For example, if the right index finger is affected so is the left index finger.
  • Deformities: Untreated joint inflammation causes some deformities peculiar to rheumatoid arthritis. Examples include:
    • Ulnar deviation: The fingers of the palm point away from the body (out towards the little finger) and the wrist points towards it
    • Swan neck deformity of the fingers: The joint closest to the fingertip is bent towards the palm and the joint farthest is bent away
    • Boutonnière deformity of fingers: Inverse of the swan neck deformity
    • Baker’s cyst—fluid-filled bulge at the back of the knee which pains on activity— among other kinds of deformity
  • Rheumatoid nodules: Small painless lumps appear around the elbow in some patients.
  • Anaemia
  • Inflammation of tendons (connective tissue joining muscle to bone) can accompany arthritis (joint pain and swelling) in rheumatoid arthritis
  • Osteoporosis: The bones become porous due to prolonged inflammation and steroid therapy
  • Pleural effusion: Sometimes fluid may accumulate in the pleural cavity (space surrounding the lung)
  • Fever
  • Weight loss
  • Inflammation of other organs like eyes, blood vessels, heart, etc., can occur rarely

Systemic Lupus Erythematosus

Psoriasis: It is a condition in which skin cells grow too fast and there is inflammation of the skin. Symptoms include:

  • Generalised redness of the skin (most of the skin of the body is affected)
  • Scaling of the skin: These scales are coarse and silvery
  • Sometimes, the scales can be fine and flaky
  • Pain in the affected areas
  • Itching in the affected areas

Connective tissue disease causes

Although many connective tissue diseases arise due to the body’s inherent autoimmune mechanism (improper attack on the body’s connective tissue by the body's own immune system) and some are inherited, many may be caused by secondary factors such as:

  • Exposure to toxins like air pollution and cigarette smoke: Examples include pulmonary fibrosis or scarring/toughening of the lung fibres due to excessive collagen deposition.
  • Exposure to ultraviolet light
  • Nutritional deficiencies, especially vitamin C deficiency (scurvy). Vitamin C plays an important role in the correct structure formation of collagen—the most abundant protein in the body, collagen gives structure and elasticity to many parts of the body.
  • Certain infections

Connective tissue disorders precautions and lifestyle modifications

Though you can't prevent connective tissue diseases, you can manage them better by taking the following precautions:

  • Reduce stress: Some of the symptoms observed in patients of connective tissue diseases are due to stress. Relaxation techniques might be beneficial in controlling your stress levels and help you avoid some of the issues that connective tissue diseases present with.
  • Stop smoking: The blood vessels of smokers become very narrow, thus causing the symptoms of connective tissue disorders to worse. So it is important that patients stop smoking to avoid common complications of these diseases.
  • Protective gear: Wearing gloves while going out in the cold may help prevent Raynaud’s phenomenon in which the blood vessels in the extremities spasm due to the temperature change and disrupt blood supply.

Connective tissue disease tests and diagnosis

The diagnosis could vary, depending on which connective tissue condition the doctor suspects. The following tests and examinations may be used:

Marfan syndrome: This condition is diagnosed based on symptoms, family history of the disease and certain tests such as:

  • An echocardiogram to check for damage to the aorta or heart
  • Eye tests like the slit lamp test
  • Genetic testing

Rheumatoid arthritis: The diagnosis of rheumatoid arthritis is made based on clinical evidence (the characteristic presentation of arthritis) supported by some blood tests.

Systemic Lupus Erythematosus: Lupus is diagnosed on the basis of typical symptoms and high-levels of certain autoantibodies in the blood. A diagnosis of lupus is made on the basis of:

  • Clinical presentation
  • Blood tests: While various autoantibodies are associated with systemic lupus erythematosus (SLE), two are most useful. The antinuclear antibody (ANA) test is the best screening test for SLE. However, it can be present in other conditions as well. The anti-dsDNA antibody test is the most specific for SLE, that is to say that if anti-dsDNA is found in the blood, SLE is diagnosed.
  • Follow up tests: blood and urine tests to monitor kidney function and imaging studies for heart and lung function are done. A blood test to measure a factor called complement informs about disease activity.

Psoriasis: It is diagnosed clinically based on how the rash appears. Sometimes, the doctor might perform a biopsy (sample of the affected area is taken) and view the tissue under a microscope to look for the classical findings in patients suffering from psoriasis.

Connective tissue disorders treatment

The treatment can vary, depending on the cause:

Marfan's syndrome: There's no cure for this condition. Having said that, timely treatment can help to avoid the complications of this syndrome.

  • The first and foremost thing is to avoid damage to the aorta, the main artery taking blood from the heart to the body. Doctors may do this with blood pressure medication to reduce pressure and, therefore, wear and tear to the aorta. Surgical options to repair the aorta could be explored in more severe cases.
  • Corrective glasses and eye surgery may be advised in case of eye problems like a torn retina.
  • In the case of scoliosis, or abnormal curvature of the spine, surgery may be recommended.

Rheumatoid arthritis

  • Ensure adequate rest, physiotherapy and splinting of affected joints as required.
  • Medical treatment consists of two parts. First, the administration of pain relief with an anti-inflammatory agent (NSAID like ibuprofen). Steroid injections may be given to inflamed joints. Second, the initiation of disease-modifying antirheumatic drugs (DMARDs). Usually, oral once-weekly methotrexate is started along with folic acid (to reduce the side effects of methotrexate) the next day.
  • If methotrexate is ineffective, other DMARDs can be added in combination.
  • If adequate response is still not generated biologicals (injectables) are introduced. The two common options are biweekly subcutaneous injections of etanercept and intravenously administered infliximab given every few weeks.
  • Immunosuppressants might be needed to block out harmful immune response.

Systemic Lupus Erythematosus

  • Symptomatic relief during relapses with anti-inflammatory medicines like NSAIDs (for mild aches) and steroids (for severe symptoms).
  • Hydroxychloroquine for skin lesions
  • Immunosuppressants: as last resort in severe disease with kidney dysfunction

Psoriasis

There is no definitive cure for psoriasis. In case of flare ups, your doctor might prescribe steroids. Most of the time, patients are prescribed emollients and creams. The ultimate goal of this form of treatment is to clear the rash. The treatment regimen may vary from one patient to another.



References

  1. Charles J., Britt H., Pan Y. Rheumatoid arthritis. Australian Family Physician, November 2013; 42(11): 765. PMID: 24217093.
  2. Gordon C., Amissah-Arthur M.B. and Gayed M., et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology (Oxford), 1 January 2018; 57(1): e1-e45. doi: 10.1093/rheumatology/kex286.
  3. Langley R.G., Krueger G.G. and Griffiths C.E. Psoriasis: epidemiology, clinical features, and quality of life. Annals of the Rheumatic Diseases, March 2005. 64 Suppl 2(Suppl 2):ii18-23; discussion ii24-5. PMID: 15708928 doi: 10.1136/ard.2004.033217
  4. Rosenbach M., Hsu S., Korman N.J., et al. Treatment of erythrodermic psoriasis: from the medical board of the National Psoriasis Foundation. Journal of the American Academy of Dermatology, April 2010; 62(4): 655-62. Epub 8 August 2009. PMID: 19665821 doi: 10.1016/j.jaad.2009.05.048

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