Prospects for improving outcomes in systemic sclerosis‐related pulmonary hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a leading cause of morbidity and mortality in patients with systemic sclerosis (SSc). Approximately one in 10 will develop PAH during their lifetime. These patients have a worse prognosis than those with PAH due to other causes. The most common clinical feature of SSc‐PAH in the early stages is non‐specific exercise intolerance that can be erroneously attributed to other manifestations of SSc. Screening provides an opportunity for early identification of SSc‐PAH and prompt initiation of therapies with the potential to improve quality of life and survival. International guidelines recommend annual transthoracic Doppler echocardiography (TTE), but TTE has limitations. The tricuspid regurgitant jet required for estimating the systolic pulmonary artery pressure is absent in up to 39% of patients, including a proportion with PAH. This has prompted a move to new screening algorithms that are less dependent on TTE. Not all pulmonary hypertension (PH) in patients with SSc is PAH. Other causes include PH secondary to left heart disease, interstitial lung disease‐related PH, chronic thromboembolic PH and pulmonary veno‐occlusive disease. With the advent of evidence‐based therapies, including newer agents such as macitentan, riociguat and selexipag, the establishment of centres with expertise in PAH and the focus on early detection, there has been considerable improvement in survival. The role of anti‐coagulation for SSc‐PAH has been the subject of a recent meta‐analysis of nine observational studies that suggests it may confer a survival benefit, but to date, there have been no randomised controlled trials to confirm this.

Old and new therapeutic strategies in systemic sclerosis (Review)

“…Although pentoxifylline is an effective vasodilator that can relieve acral lesions, it cannot control the Raynaud's phenomenon. However, pentoxifylline functions as an immunomodulator by blocking TNF production and limits collagen synthesis by stimulating collagenase (17)(18)(19).…”

A Diagnosis at Hand: Pulmonary Arterial Hypertension

“…Our patient's therapy has focused on management of pulmonary arterial hypertension, which relies on drugs that are endothelin receptor antagonists, phosphodiesterase type 5 (PDE5) inhibitors, or prostanoids. 16 In the SUPER-1 trial, treatment with sildenafil, a PDE5 inhibitor, improved results from the 6-minute walk test, WHO functional class, pulmonary artery pressure, and pulmonary vascular resistance in patients with systemic sclerosis complicated by pulmonary arterial hypertension. 17 In another study, similarly afflicted patients receiving treprostinil, a prostanoid, had reduced dyspnea and pulmonary vascular resistance and modestly enhanced performance in the 6-minute walk test.…”

Patient perception of disease burden in diffuse cutaneous systemic sclerosis

“…SSc is classified into two subsets by the degree of skin involvement: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc. 2 Complications of dcSSc include interstitial lung disease, 3 , 4 pulmonary arterial hypertension, 3 , 5 , 6 cardiac involvement, 3 , 7 , 8 renal involvement, 3 , 8 and gastrointestinal (GI) problems. The cause of death in patients with dcSSc is often related to lung and heart complications.…”