What is Systemic Scleroderma (Systemic Sclerosis)

Scleroderma is a disorder with an unknown cause. It is characterized by thickening of the skin due to extra tissue being deposited within it. The excess tissue is called connective tissue, connective tissue is the framework which keeps much of the body together. Scleroderma is a group of conditions that are linked by the changes in the skin, however there are many other effects of the disease, and as a result it is classified into a variety of distinct conditions depending on the pattern of disease.

Classification of Scleroderma

Scleroderma is classified broadly into two categories in both the childhood and adult forms of the condition:

  • Localised Scleroderma: This condition is confined to the skin, it does not progress to systemic sclerosis.
  • Systemic Sclerosis: In this condition there is skin and/or organ involvement that is more severe and widespread than the localized form.

Localised scleroderma is classified into the following categories:

  • Morphea
    • Plaque morphea
    • Generalised mophea
    • Bullous morphea
    • Deep morphea
  • Linear scleroderma

Systemic sclerosis is classified as follows:

  • Limited cutaneous scleroderma (CREST syndrome)
  • Diffuse cutaneous scleroderma
  • Sine scleroderma
  • Environmentally induced scleroderma
  • Overlap syndromes
  • Pre-scleroderma

Statistics on Systemic Scleroderma (Systemic Sclerosis)

Scleroderma is found throughout the world and affects all races. The incidence of scleroderma increases with age and is most common between the ages of 30 and 50.

Scleroderma occurs most commonly in women, and women are at three times greater risk of getting this disease than men, this risk further increases in women during the mid to late childbearing years. In Australia the annual incidence (the number of new cases of the disease) of systemic sclerosis is 16 per 1 000 000 with a prevalence (number of people who have the condition at a point in time) of 233 per 1 000 000. The female to male ratio of the condition is 4 : 1 respectively.

Juvenile (childhood) Systemic Sclerosis:

It is thought that approximately 10% of systemic sclerosis occurs before the age of 20. As in the adult form of systemic sclerosis there is a higher proportion of females affected as compared to males, however this only occurs above the age of 8. In the juvenile form the female: male ratio is 3:1 respectively. In younger children the incidence is similar in both genders.

Risk Factors for Systemic Scleroderma (Systemic Sclerosis)

  • Females are three times more likely to be affected than males, and up to eight times more likely in childbearing years.
  • Indigenous Australians, African Americans, Hispanics and Native Americans are more likely to be affected.

Genetic susceptibility:

  • Scleroderma in a first degree relative.
  • Presence of anti-nuclear antibodies (immune proteins) in a first degree relative.
  • Other autoimmune diseases (diseases where the person’s immune system attacks its own body) in first degree relatives.

Exposure to infections

Environmental exposure – Scleroderma is found to be more common in:

  • Gold and coal miners
  • Exposure to polyvinyl chloride
  • Exposure to certain hydrocarbons such as benzene, toluene and trichloroethylene
  • Exposure to drugs such as pentazocine and bleomycin.

Progression of Systemic Scleroderma (Systemic Sclerosis)

Pathogenesis

Systemic sclerosis is a condition that is of unknown cause. However some things are known about the mechanism by which the disease occurs. The disease occurs due to abnormal activation of cells called fibroblasts, these cells are responsible for making connective tissue in the body. The activation of these fibroblasts can occur by abnormalities in the cells of the immune system, as well as damage to endothelial cells (the cells that line blood vessels). The end result is constriction of blood vessels and excess connective tissue in the body.

Clinical Features of Systemic Sclerosis Skin Involvement:

The fingers, hands and face are usually the earliest areas that are affected by the condition. The pattern of skin involvement and the involvement of the internal organs determines how this condition is classified. The differing patterns of skin involvement include:

  • Limited cutaneous systemic sclerosis (CREST syndrome): usually have their skin sclerosis confined to their hands. Less commonly the skin of the face and neck become involved. In the CREST syndrome the following changes occur: Calcinosis (calcium deposition in the joints), Raynaud’s Phenomenon (where fingers turn white, blue then red due to lack of blood supply), Oesophageal Dysfunction, Sclerodactyly (condition causing skin tightening and thickening on the hands), Telangietasia (Red spots on the skin) (CREST is an acronym for these changes).
  • Diffuse cutaneous systemic sclerosis: skin lesions on the chest, abdomen, upper arms or shoulders is characteristic. Patients with this form of systemic sclerosis are more likely to experience internal organ disease than those with the limited cutaneous form.
  • Systemic sclerosis sine scleroderma: patients with this form of the disease do not all have skin manifestations.

Vascular Disease:

Raynaud’s phenomenon is the most common symptom that is caused by blood vessel disease. This is precipitated by cold, stress or a change in temperature. Initially the fingers turn ‘white’ due to narrowing of the blood vessels then the fingers become ‘blue’ as the blood loses oxygen, and when blood flows through the fingers again they turn ‘red’. Raynaud’s phenomenon usually occurs early in the disease process, apart from in diffuse cutaneous systemic sclerosis where it may coincide with other symptoms. Raynaud’s phenomenon is not specific to systemic sclerosis and is found in many other conditions.

Organ involvement:

Many organs are involved in systemic sclerosis, examples of which include:

  • Gastrointestinal involvement: Any part of the gastrointestinal system can be involved causing the following symptoms: difficulty swallowing, heartburn, choking, cough after swallowing, bloating, alternating diarrhoea and constipation as well as malabsorption.
  • Lung disease: Pulmonary fibrosis (deposition of connective tissue in the lungs) and pulmonary hypertension (high blood pressure in the lung blood vessels) can occur. These can cause shortness of breath on exertion and a non-productive cough.
  • Kidney disease: This is life threatening with the risk of kidney failure.
  • Cardiac disease: There is a poor prognosis if this occurs. People can get chest pain and palpitations due to this.
  • Musculoskeletal disease: This can be responsible for the joint pain, muscle pain, weakness and swelling that can occur in these patients.

Cancer risk

The most important cancer risk associated with scleroderma is lung cancer. Other cancers that patient may be at increased risk of include: hepatic cancers, skin cancers, blood cancers.

Juvenile Systemic Sclerosis

Diffuse Cutaneous Systemic Sclerosis:

This has a slow onset and people can experience periods of active and inactive disease. The symptoms experienced can be:

  • Skin problems

The condition is most active during the first 3 – 5 years since onset. In this period of time the main symptoms are fatigue, weight loss as well as rapid skin thickening and tightening, joint pain, and muscle pain. After this first five years the symptoms mentioned previously can disappear, the skin symptoms stabilize, however the major organ involvement may still progress.

Limited Cutaneous Systemic Sclerosis :

This is not common in children. It still remains unclear whether this condition is a variant of diffuse cutaneous systemic sclerosis. In adults this syndrome is commonly known as CREST syndrome. During the first 10 years of this condition the involvement of internal organs rarely occurs. However in this period the Raynaud’s phenomenon, pitting, digital ulceration (ulcers forming on the fingers due to poor blood supply), calcinosis and telangiectasias worsen.

Symptoms of Systemic Scleroderma (Systemic Sclerosis)

The doctor will ask about the following things:

  • Raynaud’s phenomenon, and anything that precipitates it.
  • Itching and tightness of the skin.
  • Dysphagia, heartburn, choking, cough after swallowing, bloating, alternating diarrhoea and constipation as well as malabsorption.
  • Shortness of breath on exertion and a non-productive cough.
  • Chest pain, shortness of breath when lying flat, waking up from sleep with shortness of breath, palpitations, fainting.
  • Swelling of the hands, joint and muscle pain.
  • Dry eyes

Medications the person might be using e.g. bleomycin. Family history of scleroderma, as well as the person’s occupation.

Clinical Examination of Systemic Scleroderma (Systemic Sclerosis)

The doctor will examine the patient’s skin, joints, face, chest and abdomen to determine if any abnormalities are present. The doctor will also check your blood pressure, temperature and urine.

How is Systemic Scleroderma (Systemic Sclerosis) Diagnosed?

The doctor will generally perform the following tests routinely:

  • Full blood count.
  • Urea and Electrolytes: to assess kidney function.
  • Autoantibodies.
  • Urine Microscopy (to look for signs of damage to the kidneys) and 24 hour collection for protein and creatinine clearance (to assess kidney function).
  • Imaging: High resolution CT (for lung disease), Echocardiography (To look at the pressures in the vessels supplying the lungs).
  • Lung function tests.

The doctor may perform many other test, but these will differ from patient to patient depending on what the doctor is looking for, and what organ he/she is assessing.

Prognosis of Systemic Scleroderma (Systemic Sclerosis)

People with this condition experience have a reduced life expectancy. The degree of skin disease as well as involvement of other organs is associated with a worse prognosis.

How is Systemic Scleroderma (Systemic Sclerosis) Treated?

The treatment of systemic sclerosis depends on the severity of the disease and where it occurs. A summary of treatment is as follows :

  • Drugs against the immune system and against fibrosis: however it hasn’t been proven that these drugs cause more benefit than harm but are used in some circumstances.
  • Skin disease: antihistamines for itching, calcium channel blockers for calcinosis, laser therapy for telangiectasias that are severe.
  • Blood vessel disease: avoidance of triggers for Raynaud’s phenomenon such as cold, stress, nicotine, caffeine, and decongestants.
  • Kidney disease: treatment with blood pressure lowering medication.
  • Gastrointestinal disease: drugs for reflux, and drugs that stimulate gut movement.
  • Lung disease: treatment with drugs that dilate the lung blood vessels reducing the pressure in them e.g. bosentan and sildenafil.
  • Musculoskeletal disease: pain killers such as paracetamol and aspirin.
  • Heart disease: pain killers for chest pain and steroids if heart failure occurs.

Juvenille Systemic Sclerosis:

The management strategies should include the following:

  • Encouragement of the child to stay as active as possible, with physiotherapy used to maximize the childs ability to function.
  • The use of splints should be used to prevent and treat deformities.
  • Skin care with the regular application of moisturizers to the skin, and avoidance of substances which can dry out the skin.
  • Avoidance of the cold, heat, the sun and trauma is needed to avoid exacerbation of skin symptoms.
  • Drug therapy.

Systemic Scleroderma (Systemic Sclerosis) References

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