Diagnosing and Treating Systemic Sclerosis With PAH Remains Challenging

While diagnostic algorithms have evolved in the last decade, there remains an urgent need for innovative therapeutic options to treat systemic sclerosis with pulmonary arterial hypertension.

Given the challenge of diagnosing systemic sclerosis with pulmonary arterial hypertension (SSc-PAH), referral to an expert PAH center is crucial. While diagnostic algorithms have evolved in the last decade, there remains an urgent need for innovative therapeutic options to treat this severe condition, according to a paper published in La Presse Médicale.

Patients with SSc-PAH tend to be asymptomatic early on and PAH symptoms can often be attributed to SSC global impairment issues, the authors explained. PAH is a leading cause of morbidity and mortality in SSc.

“Despite advances and progresses in PAH therapy, prognosis of SSc-PAH is worse than other forms of the disease with a 1-year mortality reaching up to 30%,” the authors wrote.

Patients diagnosed with SSc need to be regularly assessed for cardiovascular involvement and Doppler transthoracic echocardiography is recommended if PAH is suspected. An annual screening is recommended because of the high prevalence of PAH in SSc.

The only validated screening strategies for PAH are for patients who have SSc, the authors noted. The DETECT algorithm screens for SSc-PAH in patients with a disease duration of longer than 3 years and a diffusion capacity for carbon monoxide less than 60% of predicted.

Treatment continues to be a challenge. Basic therapy includes diuretics in certain cases. High-dose calcium channel blocker therapy is not recommended based on the lack of long-term favorable response. Corticosteroids and immunosuppressants are not efficacious in SSc-PAH. And because of an increased risk of bleeding, the long-term risk-benefit ratio of oral anticoagulation is not favorable.

The currently approved drugs for PAH target 3 pathways: nitric oxide pathway, endothelin pathway, and prostacyclin pathway. The 2015 European Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines recommend that “treatment of patients with SSc-PAH should follow the same algorithm as in idiopathic PAH,” the authors wrote.

Patients with low or intermedia risk should start on initial monotherapy or oral combination, while patients with high-risk SSc-PAH should be treated with a parenteral prostacyclin. All patients should be regularly assessed for risk/functional class to evaluate their response to treatment. Manifestation of other vasculopathy may be impact the choice of therapy in SSc-PAH.

While the current PAH therapies improve symptoms and survival by targeting endothelial dysfunction, there are no treatments that reverse abnormal pulmonary vascular proliferation and remodelling. Given the roles of autoimmunity and inflammation in SSc and PAH, clinical trials are currently exploring the impact of anti-inflammatory agents, such as rituximab and tocilizumab.

“We urgently need innovative therapeutic options for this very severe condition,” the authors concluded. “Some preclinical and clinical studies are currently underway and could pave the way for potent tailored therapies for SSc-PAH patients.”


Lechartier B, Humbert M. Pulmonary arterial hypertension in systemic sclerosis. Presse Med. Published online February 3, 2021. doi:10.1016/j.lpm.2021.104062