Scleroderma, or systemic sclerosis (SSc), and pulmonary arterial hypertension (PAH) are two separate diseases that often coexist, making treatment and disease management for patients more complicated. Below is an overview of both scleroderma and PAH, and why one disease can lead to the other.
It is estimated that around 300,000 Americans live with scleroderma. The disease is difficult to diagnose but manifests in an overgrowth of connective tissue in the skin and/or internal organs. The collagen protein produced by the cells of the connective tissue is overproduced and leads to thickened tissue. Internal organs most commonly affected by scleroderma include those of the gastrointestinal tract, the heart, and the lungs.
It is also common for the tissue surrounding blood vessels to become thickened, causing narrowing of the blood vessels. When this happens in the hands, patients experience symptoms of Raynaud’s disease, one of the most common comorbidities — the presence of several conditions at the same time — of scleroderma.
Pulmonary arterial hypertension (PAH)
PAH is considered a rare disease, meaning it affects fewer than 200,000 people at any given time in the United States. The disease is often difficult to diagnose because its symptoms are similar to other heart and lung conditions.
After a physical exam and tests that may include an echocardiogram and a six-minute walk test, your doctor will confirm a diagnosis for PAH with a right heart catheterization, where the blood pressure in the right ventricle of the heart is measured.
A mean pulmonary arterial pressure (mPAP) of more than 25 mmHg at rest is classified as PAH (the normal range is between 8 and 20 mmHg). Patients are classified into one of four groups according to the World Health Organization (WHO) classification system, with group 1 showing the fewest and least severe complications, and group 4 showing the most.
In patients with PAH, an increase in blood pressure in the arteries of the lungs can lead to shortness of breath, fatigue, light-headedness and swelling.
Link between scleroderma and PAH
PAH can be caused by connective tissue diseases such as scleroderma, and patients with scleroderma are at a higher risk of developing PAH (around 10 percent of scleroderma patients develop PAH) due to the thickening of connective tissue around blood vessels.
When blood vessels are blocked or narrowed, the right ventricle of the heart must work harder to pump blood to the lungs. This can eventually lead to heart failure and death. It is recommended that scleroderma patients are screened for PAH once a year to diagnose early onset of PAH and begin treating the disease. If left untreated, PAH can be fatal.
Treatment of scleroderma-associated PAH
To treat scleroderma-associated PAH, doctors usually prescribe medications that are approved by the U.S. Food and Drug Administration (FDA) for patients with PAH. While prognosis from scleroderma-associated-PAH patients is generally poorer than patients with PAH alone, improvements in medication and better screening techniques to allow earlier diagnosis have improved this.
Medications for PAH used to treat scleroderma-associated PAH include prostacyclin analogs such as epoprostenol, iloprost, and treprostinil; endothelin receptor antagonists such as Tracleer (bosentan), Opsumit (macitentan), and Letairis (ambrisentan); phosphodiesterase-5 inhibitors such as Revatio (sildenafil); and guanylate cyclase stimulators such as Adempas (riociguat).
Pharmaceutical and biotech companies are working to develop new treatments for scleroderma-associated PAH.
Oral Vasculan (ifetroban), a thomboxane A2/prostaglandin H2 receptor antagonist from Cumberland Pharmaceuticals, is an investigative treatment that may help alleviate blood vessel contraction causing high blood pressure. Vasculan is currently in Phase 2 clinical trials (NCT02682511).
Another potential treatment is rituximab, a monoclonal antibody against a protein called CD20 found on the surface of B-cells, a type of immune cell. It is thought that rituximab may slow the progression of fibrosis in the lungs and is currently being tested for this indication in a Phase 2 clinical trial (NCT01086540).
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