Pulmonary arterial hypertension (PAH) and systemic sclerosis (SSc) are two separate diseases that are often comorbidities (coexisting) of each other — which makes treatment and disease management for patients more complicated. Below is an overview of both systemic sclerosis and pulmonary arterial hypertension, and why one disease can lead to the other.
Systemic Sclerosis (SSc)
An estimated 300,000 Americans have SSc. The disease is difficult to diagnose but manifests in an overgrowth of connective tissue in the skin and, or internal organs. Protein collagen, produced by cells in connective tissue, is overproduced and leads to thickened tissue. Internal organs most commonly affected by SSc include those of the gastrointestinal tract, the heart, and the lungs. It is common for the tissue surrounding blood vessels to become thickened, causing narrowing of the blood vessels, and when it happens in the hands, patients can experience symptoms of Raynaud’s phenomenon, one of the most common comorbidities of SSc.
Pulmonary Arterial Hypertension (PAH)
PAH is considered a rare disease; fewer than 200,000 new cases are diagnosed each year in America. Diagnosis for PAH is achieved through right heart catheterization, where the blood pressure in the right ventricle is measured. A mean pulmonary arterial pressure (mPAP) of more than 25 mmHg at rest is classified as PAH (normal is considered 8-20 mmHg). Patients are categorized into World Health Organization Groups 1-4, with Group 1 showing the fewest and least severe complications and Group 4 showing the most.
Connection Between SSc and PAH
PAH can be caused by connective tissue diseases such as SSc. Patients with SSc are at a higher risk (8-30 percent of SSc patients will develop PAH) due to the thickening of connective tissue around blood vessels. When blood vessels are narrowed in the lungs, the right ventricle must work harder to pump blood to the lungs. This can eventually lead to left heart failure and death. It is recommended that SSc patients are screened for PAH once a year in order to catch an early onset of PAH and begin to treat the disease.
To treat SSc-PAH, doctors usually prescribe medications intended for patients with idiopathic pulmonary hypertension. Unfortunately, studies suggest there is no survival advantage for SSc patients taking currently available PAH treatments relative to those who are not treated with medication. The three-year survival rate of SSc-PAH remains at approximately 50%. A wealth of clinical trials have been conducted with SSc-PAH patients to develop new PAH therapies, but there are currently no cures for SSc-PAH.
Pharmaceutical and biotech companies are working to develop treatments for SSc-PAH. Oral Ifetroban, a thomboxane A2/prostaglandin H2 receptor antagonist from Cumberland Pharmaceuticals, may help alleviate vascular contraction causing high blood pressure. Rituximab, a monoclonal antibody against CD20 proteins on B-cells, may slow the progression of fibrosis in the lungs. Ambrisentan, a potent type-A selective endothelin receptor antagonist, may prevent vasoconstriction in the lungs and lower the amount of stress on the heart. Rosuvastatin, a statin commonly used to treat high cholesterol, may reduce endothelial dysfunction in SSc, improving blood flow to the lungs. Reata Pharmaceuticals is testing its experimental therapy Bardoxolone Methyl in PAH patients with Scleroderma as well. These drug therapies are at various stages of investigation for SSc-PAH, ranging from trials that have not yet begun recruiting to those with completed results.
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