Pulmonary hypertension (PH) and the more severe pulmonary arterial hypertension (PAH) refer to high blood pressure in the blood vessels of the lungs. The lungs’ narrowing arteries lead to an increase in vascular resistance, which raise pressure on the right side of the heart. This compromises the heart’s ability to pump blood into the lungs efficiently and provide the required oxygen. If left untreated, PAH can lead to heart failure. 

PAH and scleroderma

PAH is a late complication in around 10 percent of scleroderma cases. People with limited cutaneous scleroderma are at greater risk of developing PAH than those with diffused cutaneous scleroderma.

In both types, endothelial cells in the inner lining of the blood vessels are injured, and the connective tissue is laid down inside the walls of these blood vessels. These tissues outgrow and constrict the walls of the lungs’ blood vessels, hampering blood flow.

Patients with hepatic scleroderma have scarred lung tissues which reduce blood flow and consequently the oxygen levels. That, in turn, reflexively increases pressure in the arteries of the lungs.

PAH develops in scleroderma patients five to 10 years after the onset of scleroderma symptoms. In many cases, people who develop scleroderma at a later stage are affected with more severe PAH.

Prognosis and assessment

Shortness of breath, chest pain and dyspnea are the common symptoms of PAH with scleroderma. However, the symptoms are generic and non-specific, and may result from any heart and lung complication, including pulmonary veno-occlusive disease. Early intervention is vital to decrease the chances of PAH progressing, making differential and systematic diagnosis crucial.

Mortality rates associated with scleroderma with PAH are higher compared to idiopathic PAH, because of the difference in severity of the two conditions and associated comorbidities with the former.

Diagnosis

Lung function tests that measure the lungs’ diffusing capacity — or oxygen’s ability to move through the lungs and the walls of blood vessels, and diffuse into the bloodstream — can be a vital indicator of PAH. Values of 50 percent or less indicate the need for further examination and possible right-heart catheterization.

Imaging techniques like pulmonary echocardiograms, chest X-rays and non-invasive tomography scans are accessory techniques that could help in zeroing in on PAH. Meanwhile, research is underway to determine a fixed and systematic approach to a step-wise assessment of PAH, by eliminating other similar complications.

Selective biomarkers are also being assessed for a possible diagnosis. The new knowledge may help detect PAH at earlier stages. One such biomarker is CXCL4, which is secreted by the plasmacytoid dendritic cells (pDCs) circulating in the blood stream of scleroderma patients. A study published in the New England Journal of Medicine showed that the blood of scleroderma patients with PAH had higher levels of CXCL4.

Treatment

There are currently no treatments specific to scleroderma-associated PAH. Therefore the condition is often treated with medication that is approved by the U.S. Food and Drug Administration (FDA) for the treatment of PAH. These include drugs that dilate the blood vessels such as prostacyclin analogs like epoprostenol, iloprost, and treprostinilphosphodiesterase 5 inhibitors like Revatio (sildenafil), endothelin receptor antagonists like Tracleer (bosentan), Opsumit (macitentan), and Letairis (ambrisentan), and guanylate cyclase stimulators such as Adempas (riociguat). These therapies have led to increased median survival rate by as much as 70 to 80 percent.

Further research into screening for biomarkers could help in better diagnosis and treatment options at the early stage of the disease.

Clinical trials

Clinical trials testing approaches specifically to treat scleroderma-associated PAH are also ongoing. For example, a Phase 2 clinical trial (NCT01086540) testing rituximab for the treatment of scleroderma-associated PAH is currently recruiting participants.

Another clinical trial (NCT02682511) is assessing the effect of oral ifetroban to treat scleroderma-associated PAH and is also currently recruiting participants.

Note: Pulmonary Hypertension News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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