An Update on Scleroderma-Related PAH

While it is commonly accepted that patients with scleroderma are at a higher risk for contracting pulmonary hypertension, the field has progressed immensely since the first hypothesis was tested in the laboratory. “Recent Advances in Scleroderma-associated Pulmonary Hypertension,” published in Current Opinion in Rheumatology by Dr. Kristin Highland at the Respiratory Institute in the Cleveland Clinic Foundation, concisely reviewed the wealth of knowledge gained over the years relating to scleroderma and pulmonary hypertension.

“…Pulmonary hypertension, a debilitating and progressive condition that can lead to right-sided heart failure and death [is a] well known and deadly complication of scleroderma…” noted Dr. Highland. In fact, pulmonary hypertension has been given equal recognition as other complications of scleroderma by the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR).

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Between 8% and 30% of scleroderma patients are estimated to have elevated pressure that qualifies as pulmonary arterial hypertension. Most commonly, patients with scleroderma who develop pulmonary hypertension contract Group I pulmonary arterial hypertension, which is characterized by pulmonary vascular remodeling in the precapillary pulmonary arteries due to inflammation and fibrosis. WHO Group 1, 2, and 3 pulmonary hypertension are also subgroups that appear in scleroderma patients, but WHO Group 4 pulmonary hypertension (CTEPH) is very rare in scleroderma patients.

No matter the classification, there are a wealth of risk factors associated between scleroderma and pulmonary hypertension diagnoses. Antibodies against certain proteins, poor lung function, and increases in right ventricular systolic pressure by more than 2 mmHg per year have shown a significant association with pulmonary hypertension development.

After development, a patient’s pulmonary hypertension can be identified by a variety of pathologies. Inflammatory cell infiltration of the pulmonary arteries, vessel remodeling, and elevated levels of Type I, II, and III interferon levels have all been demonstrated during studies of scerloderma-pulmonary hypertension progression.

Clinicians may become suspicious of pulmonary hypertension pathogenesis if their scleroderma patients show signs of unexplained breathlessness (dyspnoea) during times of low exertion or have unexplained loss of consciousness (syncope). Suspicions can be confirmed by conducting echocardiography, right heart catheterization, chest computed tomography, biomarker screens, and other forms of testing.

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To prevent morbidity and mortality in patients with a confirmed diagnosis, therapies used to treat idiopathic pulmonary arterial hypertension patients have been used, largely due to the lack of studies on treating patients with scleroderma-pulmonary arterial hypertension. “No therapy has ever demonstrated a survival advantage in SSc-PAH,” asserted Dr. Highland, however, one study that administered epoprostenol intravenously did improve exercise capacity and hemodynamics in afflicted patients.

Unfortunately, a lack of effective treatments and sometimes missed diagnoses lead to morbidity and mortality. There is a more than three-fold increased risk of mortality for scleroderma patients with pulmonary arterial hypertension than those without. It has been suggested that prostanoid treatment may alleviate some of these deaths, but more studies need to be conducted.

The overall theme is just that: more studies need to focus on the connection between scleroderma and pulmonary arterial hypertension. This topic is somewhat obscure in the field of research, but a portion of the population would greatly benefit from new advances in obtaining earlier diagnosis and treatment.