Systemic sclerosis (SSc) is a chronic disease where the immune system, which normally protects the body from infections and disease, starts to attack the body’s own cells, causing tissue destruction. In the case of SSc it is the connective tissue, that provides the structure and support for the body (for example bones, ligaments, cartilage, tendons), which is affected.

SSc occurs when there is an over production of collagen in the skin and internal organs, such as the gastrointestinal tract, kidney, heart, and lungs. Collagen is a protein that primarily makes up fibrous connective tissue found in tendons and ligaments, in the skin and in some other organs. Symptoms result when the collagen build-up in the blood vessels of the affected organs causes inflammation, blood vessel dysfunction and scarring, making the vessels stiffer or thicker (progressive fibrosis) all of which causes the small vessels within the circulatory system to become blocked.

As a result of the damage caused to these blood vessels, complications such as pulmonary arterial hypertension (PAH) and digital ulcers (DU) can occur.

Around 40%-50% of systemic sclerosis patients suffer from digital ulcers, necrotic lesions located at distal digits, at least once and in 66% of cases the DUs will recur. Digital ulcers are very painful difficult-to-heal open sores on the fingers and toes. They leave deep scars and affect the patient’s ability to perform work and daily activities effectively, particularly those associated with fingertip functions. In very severe cases, infection can become a complication, leading to bone inflammation and gangrene, for which surgery and sometimes even amputation may be required.

Endothelin (ET),  a protein that regulates blood flow by restricting blood vessels is also implicated in fibrotic process which stiffen blood vessels and tissues. The resulting accumulation of connective tissue plays a key role in the underlying blood vessel damage or disease (vasculopathy), of DUs. The way in which vasculopathy occurs in DUs is similar to that of PAH, involving excessive tightening or narrowing of the vessels (vasoconstriction) and subsequently leads to the blood vessels changing shape or remodeling, often becoming smaller and more restrictive than previously.  DUs are visible evidence of blood vessel damage or disease in a patient that has SSc.

HOW IS DU DIAGNOSED?

SSc patients with DUs will have dead tissue around the bony, prominent parts of the fingers. Insufficient oxygen supply to the fingertips caused by ongoing blockage of the blood vessels results in dead tissue and substantial tissue loss. The open sores (ulcerations) can be extremely painful, unsightly and incapacitating for the patient, and in most cases are very slow to heal.

HOW CAN DU BE TREATED?

There are not many medicinal treatments for DUs and surgical amputation is considered only for severe gangrenous cases. A treatment that prevents new ulcers is therefore addressing a real unmet patient need.

Treatment of DUs includes frequent local wound care, dressing changes and pain management. DUs are prone to infection and often require prolonged courses of intravenous antibiotics (administered directly into the bloodstream via a catheter). A delay in treating the infection may lead to bone shortening and deformity.

Until recently, the evidence for medicinal treatment of DUs has been limited. However, the similarities in the way in which the blood vessel disease and damage occur in both PAH and DUs has led to a dual ET receptor antagonist (drugs that block the receptors of the protein, which regulates blood flow), used for the treatment of PAH patients to be studied in patients with DUs as a consequence of SSc.

Results from two large studies support the use of a dual ET receptor antagonist in DUs, where an effect was shown to reduce the number of new ulcers in either patients with existing ulcerations or in patients with a history of DU disease.

Other drug therapies which are routinely used for DUs, but with very limited evidence to support their efficacy are:

  • Prostanoid therapy, in particular intravenous iloprost which is a drug that opens-up (dilates) the blood vessels
  • Calcium channel blockers used to help relax the muscles in blood vessel walls

For further information about treatment for digital ulcers please speak with your doctor.

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