M. Gardinali et al., Treatment of Raynaud's phenomenon with intravenous prostaglandin E-1 alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis, J RHEUMATOL, 28(4), 2001, pp. 786-794
Objective. To evaluate the efficacy and safety of prostaglandin (PG) E(1)al
pha -cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic scler
osis (SSc) and its effect on variables of immune activation and endothelial
injury in SSc such as tumor necrosis factor-alpha (TNF-alpha), soluble int
erleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1
(cICAM-1), von Willebrand factor (VWF). and tissue-type plasminogen activa
tor (t-PA).
Methods. We studied 36 wommen with SSc, 24 of them given three 60 mug intra
venous PGE(1)alpha -cyclodextrin infusions on 5 consecutive days at 6 week
intervals during the winter. RP symptoms and healing of digital lesions wer
e 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 infus
ion of PGE(1)alpha -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%. PGE(1)alpha -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, resp
ectively. The severity of the attacks was reduced to a limited degree. In 1
2 of the 14 patients with digital lesions, these healed completely. Ten pat
ients had mild side effects during treatment (headache, increased intestina
l motility. flushing). TNF-<alpha>. sIL-2R, cICAM-1, vWF and t-PA plasma co
ncentrations 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 PGE(1)alpha -cyclo
dextrin (both p < 0.005) and further reduced after the last (p < 0.0005 and
p < 0.005).
Conclusion. PGE(1)<alpha>-cyclodextrin reduces RP symptoms and plasma level
s of the markers of endothelial injury in SSc, suggesting that an improveme
nt of endothelial dysfunction contributes to its prolonged therapeutic effe
ct.