title: Effects of Longterm Treatment with Bosentan and Iloprost on Nailfold Absolute Capillary Number, Fingertip Blood Perfusion, and Clinical Status in Systemic Sclerosis.
abstract: To quantify in patients with systemic sclerosis (SSc) the absolute nailfold capillary number/mm (the absolute number of capillaries, observable in the first row, in 1 mm per field) and fingertip blood perfusion (FBP) during longterm therapy with the endothelin receptor antagonist bosentan (BOSE) and the synthetic analog of prostacyclin PGI2iloprost (ILO) by multiple diagnostic tools. Observed values were correlated with clinical outcomes.
  
  
  
  Thirty patients with SSc already receiving intravenous ILO (80 μg/day) for 5 continuous days (every 3 mos) were recruited in the clinic. Fifteen patients continued such treatment (ILO group), while in 15 patients BOSE (125 mg twice/day) was added (ILO + BOSE group) because of the onset of pulmonary arterial hypertension or digital ulcers (DU). The followup period was 4 years (T0-T4). Every year the following were evaluated: absolute nailfold capillary number/mm by nailfold videocapillaroscopy, FBP by laser Doppler flowmetry, DU incidence, DLCO, systolic pulmonary arterial pressure (sPAP), renal arterial resistive index, and other biomarkers. From T2 to T4, laser speckled contrast analysis was added. Nonparametric tests were used for statistical analysis.
  
  
  
  Limited to the ILO + BOSE group, absolute capillary number/mm and FBP showed a progressive increase independently from other variables. In addition, during followup there was a significant reduction (80%) in the incidence of new DU, whereas DLCO and sPAP did not worsen.
  
  
  
  The study shows in patients with SSc with up to 4 years of combined therapy a progressive significant recovery in structure and function of microvasculature linked to improved clinical outcomes, independent of disease severity.
authors.affiliation: From the Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium.|A.C. Trombetta, MD, PhD, Trainee in Clinical and Experimental Immunology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; C. Pizzorni, MD, PhD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; B. Ruaro, MD, Trainee in Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; S. Paolino, MD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; A. Sulli, MD, Associate Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; V. Smith, MD, PhD, Associate Professor of Rheumatology, Head of Clinics in Rheumatology, Ghent University Hospital, Ghent University; M. Cutolo, MD, Full Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa.
authors.forename: Amelia Chiara
authors.initials: AC
authors.lastname: Trombetta
authors.affiliation: From the Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium.|A.C. Trombetta, MD, PhD, Trainee in Clinical and Experimental Immunology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; C. Pizzorni, MD, PhD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; B. Ruaro, MD, Trainee in Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; S. Paolino, MD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; A. Sulli, MD, Associate Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; V. Smith, MD, PhD, Associate Professor of Rheumatology, Head of Clinics in Rheumatology, Ghent University Hospital, Ghent University; M. Cutolo, MD, Full Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pizzorni
authors.affiliation: From the Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium.|A.C. Trombetta, MD, PhD, Trainee in Clinical and Experimental Immunology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; C. Pizzorni, MD, PhD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; B. Ruaro, MD, Trainee in Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; S. Paolino, MD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; A. Sulli, MD, Associate Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; V. Smith, MD, PhD, Associate Professor of Rheumatology, Head of Clinics in Rheumatology, Ghent University Hospital, Ghent University; M. Cutolo, MD, Full Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruaro
authors.affiliation: From the Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium.|A.C. Trombetta, MD, PhD, Trainee in Clinical and Experimental Immunology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; C. Pizzorni, MD, PhD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; B. Ruaro, MD, Trainee in Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; S. Paolino, MD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; A. Sulli, MD, Associate Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; V. Smith, MD, PhD, Associate Professor of Rheumatology, Head of Clinics in Rheumatology, Ghent University Hospital, Ghent University; M. Cutolo, MD, Full Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Paolino
authors.affiliation: From the Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium.|A.C. Trombetta, MD, PhD, Trainee in Clinical and Experimental Immunology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; C. Pizzorni, MD, PhD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; B. Ruaro, MD, Trainee in Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; S. Paolino, MD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; A. Sulli, MD, Associate Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; V. Smith, MD, PhD, Associate Professor of Rheumatology, Head of Clinics in Rheumatology, Ghent University Hospital, Ghent University; M. Cutolo, MD, Full Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sulli
authors.affiliation: From the Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium.|A.C. Trombetta, MD, PhD, Trainee in Clinical and Experimental Immunology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; C. Pizzorni, MD, PhD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; B. Ruaro, MD, Trainee in Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; S. Paolino, MD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; A. Sulli, MD, Associate Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; V. Smith, MD, PhD, Associate Professor of Rheumatology, Head of Clinics in Rheumatology, Ghent University Hospital, Ghent University; M. Cutolo, MD, Full Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Smith
authors.affiliation: From the Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium. mcutolo@unige.it.|A.C. Trombetta, MD, PhD, Trainee in Clinical and Experimental Immunology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; C. Pizzorni, MD, PhD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; B. Ruaro, MD, Trainee in Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; S. Paolino, MD, Assistant Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; A. Sulli, MD, Associate Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa; V. Smith, MD, PhD, Associate Professor of Rheumatology, Head of Clinics in Rheumatology, Ghent University Hospital, Ghent University; M. Cutolo, MD, Full Professor of Rheumatology, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa. mcutolo@unige.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077300:Bosentan; D002196:Capillaries / Q000187:drug effects* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D005385:Fingers / Q000098:blood supply*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020678:Microscopic Angioscopy; D008875:Middle Aged; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000187:drug effects; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D014665:Vasodilator Agents; D016285:Iloprost; D000077300:Bosentan
keywords: BLOOD FLOW; BOSENTAN; ILOPROST; LASER SPECKLED CONTRAST ANALYSIS; NAILFOLD VIDEOCAPILLAROSCOPY; SYSTEMIC SCLEROSIS