Pulmonary arterial hypertension (PAH) is a severe vascular complication of connective tissue diseases. In the context of systemic sclerosis (SSc), PAH is a devastating disease with a dramatic impact on prognosis and survival. Despite advances in early diagnosis and the development of new targeted treatments, SSc-related pulmonary arterial hypertension (SScPAH) represents the leading cause of death in SSc patients with reported poorer response in therapy and worse prognosis compared with idiopathic PAH. Recent findings indicate that factors accounting for these differences may include cardiac involvement, pronounced autoimmune and inflammatory response and pulmonary venous vasculature remodeling. Deeper understanding of the underlying pathogenic mechanisms of pulmonary vascular disorders in SScPAH may lead to novel therapeutic strategies which are currently under investigation and may improve the outcome of these patients, for whom our therapeutic armamentarium is not effective enough. In this article we attempt to critically analyze the factors contributing to the unique phenotype of SScPAH focusing on future challenges for the design of novel targeted treatments which may alter the natural history of the disease.
Keywords: Systemic sclerosis, pulmonary hypertension, drug treatments, vasodilators, antineoplastic drugs, connective tissue diseases, pulmonary vascular resistance, inflammatory infiltration, pulmonary interstitial fibrosis, neurohormones