title: Current therapies for the treatment of systemic sclerosis-related pulmonary arterial hypertension: efficacy and safety.
abstract: BACKGROUND
  Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. Patients with limited SSc typically develop pulmonary arterial hypertension (PAH). TNF-α, VEGF, platelet-derived growth factor and endothelin-1 play a key role in the development of PAH.
  
  
  METHODS
  This paper addresses the efficacy and safety of current drugs used for the treatment of PAH.
  
  
  CONCLUSIONS
  Bosentan, ambrisentan, sildenafil, tadalafil, iloprost, epoprostenol and treprostinil were associated with hemodynamic improvements in PAH patients. Ambrisentan has a better safety profile compared with bosentan, regarding the risk of increase in hepatic transaminases. Flushing, dyspepsia and diarrhea were the most frequent adverse events in patients treated with sildenafil, while headache, myalgia and flushing were the adverse events in those receiving tadalafil. Inhaled iloprost is also effective, but it requires multiple daily nebulizations up to 15 min each and may induce cough, flushing, jaw pain and headache. Epoprostenol is considered the most effective approved therapy for severe PAH in WHO functional class III and class IV. TNF-α inhibitors reduce the systemic inflammation in patients with chronic immune-mediated diseases and improve the endothelial function, decreasing the risk of PAH progression.
authors.affiliation: University of Genova, Department of Internal Medicine, Clinical Immunology Unit , Viale Benedetto XV, n. 6, 16132 Genova , Italy +39 0103537924 ; +39 0105556950 ; Giuseppe.Murdaca@unige.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Murdaca
authors.forename: Francesca
authors.initials: F
authors.lastname: Spanò
authors.forename: Francesco
authors.initials: F
authors.lastname: Puppo
mesh_terms: D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology*; D012595:Scleroderma, Systemic / Q000150:complications*
chemical_list: D000959:Antihypertensive Agents