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AB0802 Endothelin1 receptor-antagonism (bosentan) reduces the progression of microvascular damage as assessed by nailfold capillaroscopy in systemic sclerosis patients: A 2 year survey
  1. M. Cutolo,
  2. L. Vremis,
  3. G. Zampogna,
  4. C. Pizzorni,
  5. C. Ferrone,
  6. F. Ravera,
  7. M.A. Cimmino,
  8. E. Alessandri,
  9. B. Seriolo,
  10. A. Sulli
  1. Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genova, Italy

Abstract

Background Systemic sclerosis (SSc) is characterized by microvascular injury, fibrosis and hypoxia of involved tissues causing progressive organ damage (i.e.digital ulcers-DU). The endothelin1 receptor antagonism (bosentan-BOS) is actually used to prevent DU in SSc patients. Nailfold videocapillaroscopy (NVC) allows to characterize (SSc patterns), quantify and monitor the nailfold microvascular damage progression in SSc.

Objectives To evaluate by NVC the effects of BOS treatment on nailfold microvascular damage evolution in SSc patients already under symptomatic treatment with prostacyclin (iloprost-ILO).

Methods 26 SSc patients (pts- mean age 64±5 yrs, disease duration 7.4±1yrs) according to the LeRoy and Medsger’s criteria, entered an open study after informed consent and Etical Committee approval. Subsequently, 13 SSc pts of them (mean age 61±16, disease duration 6.6±2.8) already receiving ILO from an average of 5.5±1.4 yrs, continued their treatment for at least 2 yrs (cycles of 5 day ILO iv-infusion-24 hours, 80 microgr/day every 4 months); the remaining 13 SSc pts (mean age 68±14, disease duration 8.1±3.8) were under treatment with ILO from an average of 7.3±2.8 yrs and at the first appearance of DU combined treatment with ILO+BOS (125mg twice a day). All SSc pts were followed for at least 2 yrs. NVC was yearly performed from basal analysis, in order to detect the SSc patterns and to score the markers of damage (namely number of normal and giant capillaries, microhaemorrhages and angiogenesis). Statistical analysis was carried out by non-parametric tests.

Results At baseline, no statistically significant differences were present between the two groups concerning NVC SSc patterns. Interestingly, at 2 yrs, NVC showed a statistically significant increase of capillary number limited to the ILO+BOS SSc group (p=0.05). At the same time, both giant capillaries and microhaemorrhage scores significantly decreased only in ILO+BOS SSc pts (p=0.05 and p=0.02, respectively). On the contrary, the microangiopathy score (MES), evaluating the capillary markers of microvascular damage progression, significantly increased only in ILO-treated pts at 2 yrs (p=0.05). No side effects and appearance of further DU was observed during the survey in all SSc pts.

Conclusions In SSc patients affected by DU, bosentan addiction significantly reduces the progression of the microvascuar damage as assessed by NVC over a period of 2 years. In particular, the number of normal capillaries significantly increases, whereas the number of giant capillaries and related microhaemorrhages significantly decreases, in comparison to SSc pts treated only with ILO. For the first time the microvascular effects induced by the long term endothelin1 receptor antagonism in SSc are detected by NVC.

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  2. Sulli A, et al. Arthritis Rheum 2011;29. doi: 10.1002/art.33463.

  3. Smith V et al. Ann Rheum Dis. 2010;69:1092-6.

  4. Cutolo, M. et al. Nature Rev Rheumatol 2010;6:578–587.

  5. LeRoy EC et al.J Rheumatol 2001;28:1573-6.

Disclosure of Interest None Declared

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