Systemic sclerosis

Author: Vanessa Ngan, staff writer, 2003. Updated by A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, December 2015.

What is systemic sclerosis?

Systemic sclerosis (systemic scleroderma) is a multisystem disease that results in fibrosis and vascular abnormalities in association with autoimmune changes. These lead to breakdown of the skin, subcutaneous tissue, muscles and internal organs (e.g. digestive tract, heart, lungs and kidneys). The skin becomes thickened and tightly bound to underlying structures.

Localised scleroderma (also known as morphoea) is an unrelated skin disease and is confined to the skin.

Who gets systemic sclerosis?

Systemic sclerosis is a rare condition that may occur in people of any race, although it is less common in people of Asian descent. It appears to be three to four times more common in women than men and is comparatively rare in children. It usually starts between 30-40 years in women and later in men.

What causes systemic sclerosis?

Systemic sclerosis is classified as an autoimmune disease of an unknown cause. This means the immune system is reacting against one's own tissues. Pathogenesis involves both activated B cells and activated T lymphocytes. Autoantibodies and cytokines injure the cells that line blood vessels (endothelial cells) causing vasoconstriction, and fibroblasts, resulting in excessive production of collagen (fibrosis).

Certain factors have been identified that may trigger the disease. These include injury, drugs (e.g. vitamin K, cocaine, penicillamine, appetite suppressants and some chemotherapeutic agents), and chemicals (e.g. silica, organic solvents, pesticides, aliphatic hydrocarbons and epoxy resin).

What are the clinical features of systemic sclerosis?

Raynaud phenomenon is usually the first symptom of systemic sclerosis. Patients experience episodes of vasospasm , which causes blood vessels in the fingers and toes to constrict. As less blood is reaching these extremities the skin changes colour to white and the fingers and toes may feel cold and numb. As they warm up, they go blue and then red before returning to normal again.

Cutaneous features of systemic sclerosis

Other skin changes include:

Systemic sclerosis affecting other organs

In addition to the skin changes, the disease affects many other organs. Problems that may occur include:

What is the CREST syndrome?

CREST syndrome (also called CRST syndrome) is a limited form of systemic sclerosis in which there is Calcinosis, Raynaud's phenomenon, oEsophageal involvement, Sclerodactyly and Telangiectases. Characteristically, the telangiectases are well-defined and flat (matt).

How is systemic sclerosis diagnosed?

The diagnosis of systemic sclerosis is generally made from the patient's history and the findings on examination of the skin and other organs. Nailfold capillaroscopy typically shows loss of capillaries, haemorrhages and disorganised, enlarged capillaries. A skin biopsy is not usually necessary but characteristically shows excessive ground substance and odd-looking endothelial cells in the dermis, and later, deposits of collagen. The epidermis is usually atrophic (thinned).

Up to 90% of patients with systemic sclerosis have elevated antinuclear antibodies (ANA) but these are less frequent than in the more common connective tissue disease, systemic lupus erythematosus. Thyroid antibodies may occur and result in an under-active thyroid gland

Anticentromere antibodies are characteristic of CREST syndrome and may be present in patients with Raynaud phenomenon before systemic sclerosis appears. Scl-70 is unique to systemic sclerosis and is more likely to be associated with severe systemic sclerosis involving the lungs. Many other less specific antibodies have been reported to be associated with different patterns of disease.

Anaemia, raised sedimentation rate (ESR) and increased gamma globulins (hypergammaglobulinaemia) and varying immune abnormalities are quite common especially positive rheumatoid factors. Blood clotting tests are done in case of coagulopathy associated with lupus anticoagulant and anticardiolipin.

What is the treatment of systemic sclerosis?

There is no cure for systemic sclerosis and treatment is aimed at controlling symptoms and preventing complications. Because the symptoms of systemic sclerosis are so diverse a team of medical specialists is usually necessary.

It is absolutely essential to discontinue smoking. Avoid vasoconstrictive drugs, such as decongestants, amphetamines, ergotamine. Hypertension should be controlled.

The mainstay of treatment is with immune modulating agents, including:

Targeted therapy is being developed against specific cytokines and peptide mediators involved in systemic sclerosis.

  • Topical corticosteroids and emollients for itchy skin
  • Avoid cold temperatures and trauma to the fingers and toes. Wear warm clothing including gloves and socks to prevent Raynaud phenomenon. Medical treatment includes calcium channel blockers (nifedipine, amlodopine), antiplatelet drugs (aspirin, low molecular weight heparin), and the phosphodiesterase inhibitor vasodilating drugs (sildenafil, tadalafil).
  • Iloprost infusions and endothelin inhibitors such as bosentan may be considered in refractory digital ischaemia with tissue damage.
  • Surgery may be necessary to remove infected or necrotic tissue.
  • Calcinosis may be treated with calcium channel blockers, anticoagulants, colchicine and intralesional steroids and possibly excision of deposits
  • Research suggests intensive ultraviolet radiation treatment (phototherapy) with UVA1 (340-400nm) can soften fibrosis.
  • Statins such as atorvastatin may be of benefit because of anti-inflammatory and immunomodulatory properties.
Joint and muscle
  • Nonsteroidal anti-inflammatory agents
  • D-penicillamine
  • Proton pump inhibitor, e.g. omeprazole
  • Cisapride
  • Metoclopramide
  • Surgery for strictures
  • ACE inhibitors
  • Dialysis
  • Vasoldilators such as iloprost, epoprostenol and treprostinil for severe disease
  • Endothelin receptor blockers such as bosentan and ambrisentan

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