title: Longterm effects of endothelin receptor antagonism on microvascular damage evaluated by nailfold capillaroscopic analysis in systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is characterized by microvascular injury, fibrosis, and hypoxia of involved tissues. The vasoactive peptide endothelin-1 (ET-1) seems to be implicated in these events. Using nailfold videocapillaroscopy (NVC), we evaluated longterm effects of ET-1 antagonist treatment on nailfold microvascular damage in patients with SSc, over a 3-year followup period.
  
  
  METHODS
  Thirty patients with SSc (mean age 64 ± 5 yrs, mean disease duration 8 ± 1 yrs) were recruited during their programmed standard treatment protocols. At baseline (T0), 15 patients with SSc (mean age 63 ± 15 yrs, mean disease duration 7 ± 3 yrs), already receiving cyclic intravenous infusion of iloprost (5 continuous days, average 80 μg/day, every 3 mo), continued the treatment for a further 3 years (ILO group). The remaining 15 patients with SSc (mean age 68 ± 13 yrs, mean disease duration 8 ± 4 yrs), although they continued the same cyclic intravenous iloprost treatment as the previous group, also received bosentan 125 mg twice a day for 3 years (ILO+BOS group). Qualitative analysis (scleroderma patterns) and semiquantitative scoring of the microvascular damage were performed by validated routine NVC methods.
  
  
  RESULTS
  During followup, a statistically significant increase of capillary number was observed in the ILO+BOS group (p < 0.02), with a significant and progressive increase of angiogenesis (p < 0.01). In contrast, the ILO group showed a statistically significant decrease of capillary number (p < 0.05). After 3 years the number of capillaries was significantly higher in the ILO+BOS group than in the ILO group (p < 0.05). The score for giant capillaries decreased significantly in both groups of patients with SSc (p < 0.05).
  
  
  CONCLUSIONS
  In this open study, longterm treatment with ET-1 receptor antagonist in combination with iloprost was found to interfere with progression of nailfold microvascular damage in patients with SSc, as assessed by NVC over a 3-year followup period.
authors.affiliation: Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy. mcutolo@unige.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zampogna
authors.forename: Laura
authors.initials: L
authors.lastname: Vremis
authors.forename: Vanessa
authors.initials: V
authors.lastname: Smith
authors.forename: Carmen
authors.initials: C
authors.lastname: Pizzorni
authors.forename: Alberto
authors.initials: A
authors.lastname: Sulli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077300:Bosentan; D002196:Capillaries / Q000187:drug effects; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016285:Iloprost / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D020678:Microscopic Angioscopy; D055806:Microvessels / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D009262:Nails / Q000098:blood supply / Q000187:drug effects; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D016285:Iloprost; D000077300:Bosentan