Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis

J Rheumatol. 2001 Apr;28(4):786-94.


Objective: To evaluate the efficacy and safety of prostaglandin (PG) E1alpha-cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc) and its effect on variables of immune activation and endothelial injury in SSc such as tumor necrosis factor-alpha (TNF-alpha), soluble interleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1 (cICAM-1), von Willebrand factor (vWF), and tissue-type plasminogen activator (t-PA).

Methods: We studied 36 women with SSc, 24 of them given three 60 microg intravenous PGE1alpha-cyclodextrin infusions on 5 consecutive days at 6 week intervals during the winter. RP symptoms and healing of digital lesions were evaluated. Twenty age matched healthy women were the controls. TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA were measured after the first and last infusion of PGEE1alpha-cyclodextrin and correlated with clinical features.

Results: RP symptoms improved in 87% of the patients. The benefit of each 5 day cycle lasted 4 or more weeks in 75%. PGE1alpha-cyclodextrin reduced the daily frequency of RP symptoms by 20% (p < 0.05), 41% (p < 0.005), and 53% (p < 0.0005) from baseline after the 1st, 2nd, and 3rd infusions, respectively. The severity of the attacks was reduced to a limited degree. In 12 of the 14 patients with digital lesions, these healed completely. Ten patients had mild side effects during treatment (headache, increased intestinal motility, flushing). TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA plasma concentrations were significantly higher in patients with SSc than controls (p < 0.05, p < 0.001). TNF-alpha, sIL-2R, and cICAM-1 were higher in diffuse SSc and patients with lung involvement. The plasma levels of cICAM-1 and t-PA were significantly reduced after the 1st infusion of PGE1alpha-cyclodextrin (both p < 0.005) and further reduced after the last (p < 0.0005 and p < 0.005).

Conclusion: PGE1alpha-cyclodextrin reduces RP symptoms and plasma levels of the markers of endothelial injury in SSc, suggesting that an improvement of endothelial dysfunction contributes to its prolonged therapeutic effect.

MeSH terms

  • Adult
  • Aged
  • Alprostadil / analogs & derivatives*
  • Alprostadil / therapeutic use*
  • Biomarkers
  • Cyclodextrins / therapeutic use*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / pathology*
  • Female
  • Humans
  • Immune System / drug effects
  • Immune System / physiopathology
  • Injections, Intravenous
  • Middle Aged
  • Raynaud Disease / blood
  • Raynaud Disease / drug therapy*
  • Raynaud Disease / etiology*
  • Raynaud Disease / pathology
  • Reference Values
  • Scleroderma, Localized / blood
  • Scleroderma, Localized / drug therapy
  • Scleroderma, Localized / etiology
  • Scleroderma, Localized / pathology
  • Scleroderma, Systemic / complications*
  • Treatment Outcome
  • alpha-Cyclodextrins*


  • Biomarkers
  • Cyclodextrins
  • alpha-Cyclodextrins
  • prostaglandin E1-alpha-cyclodextrin
  • Alprostadil