iloprost and Scleroderma--Localized

Digital ulcers are a serious complication in 50% of patients with scleroderma. These ulcers have the potential to resist conventional therapies. There have been several reviews of scleroderma care over the last 5 years, but there are new developments in this field that advance clinician knowledge. This review provides an overview of previous digital ulcer management and a concise summary of new peer-reviewed literature on the topic since 2015 to provide guidance to practitioners and researchers seeking well-supported and novel/off-label therapies to consider.

Topics: Female; Fingers; Humans; Iloprost; Male; Prognosis; Risk Assessment; Scleroderma, Localized; Skin Ulcer; Treatment Outcome; Vasodilator Agents; Wound Healing

Patients with scleroderma receiving Iloprost as a treatment for severe Raynaud's phenomenon report a reduction in skin tightness, suggesting that this drug inhibits skin fibrosis. Connective tissue growth factor (CTGF), a recently described profibrotic cytokine, acts downstream and in concert with TGF-beta to stimulate the fibrotic process and is involved in the fibrosis seen in scleroderma. Here we show that Iloprost, acting by elevation of cAMP, blocks the induction of CTGF and the increase in collagen synthesis in fibroblasts exposed to TGF-beta. The potency of Iloprost with respect to suppression of CTGF far exceeds that of other prostanoid receptor agonists, suggesting that its effect is mediated by the prostacyclin receptor IP. By sampling dermal interstitial fluid using a suction blister device, we show that CTGF levels are greatly elevated in the dermis of scleroderma patients compared with healthy controls and that Iloprost infusion causes a marked decrease in dermal CTGF levels. These studies suggest that Iloprost could be reducing the level of a key profibrotic cytokine in scleroderma patients and that endogenous production of eicosanoids may limit the fibrotic response to TGF-beta.

Topics: Cells, Cultured; Collagen; Connective Tissue Growth Factor; Cyclic AMP; Down-Regulation; Drug Administration Schedule; Fibroblasts; Growth Substances; Humans; Iloprost; Immediate-Early Proteins; Infusions, Intravenous; Intercellular Signaling Peptides and Proteins; Prostaglandins; Receptors, Prostaglandin; RNA, Messenger; Scleroderma, Localized; Scleroderma, Systemic; Skin; Transforming Growth Factor beta

To evaluate the safety and efficacy of cyclic intravenous iloprost therapy in diffuse or limited scleroderma.. Twenty patients, 14 women and 6 men with a mean age of 47.8 +/- 8.2 years, were given iloprost infusions for six hours a day during five consecutive days, at a rate of 0.5 to 2 ng/kg/min. The course was repeated every three months for one year. Efficacy was evaluated based on a scleroderma skin lesion score, an ischemic lesion score, a well-being self-assessment score, and lung function tests including measurement of the diffusing capacity of the lung for carbon monoxide. Safety was assessed based on adverse event collection.. The scleroderma skin lesion and ischemic lesion scores decreased significantly over the one-year treatment period, from 37.1 +/- 16.5 to 10.2 +/- 6.9 (P < 0.001) and from 31.8 +/- 19.1 to 2.2 +/- 2.0 (P < 0.05), respectively. The well-being self-assessment score also showed a significant improvement, from 71.4 +/- 16.5 to 15.0 +/- 6.6 (P < 0.001). The diffusing capacity for carbon monoxide was decreased in 11 patients at baseline and showed a slight, non significant increase in these patients after the treatment period. No serious or persistent side effects were recorded.. Cyclic intravenous iloprost therapy was associated with improvements in skin changes and in general health, as well as with a slight increase in the diffusing capacity of the lung for carbon monoxide. Our data suggest that iloprost may act on some of the pathogenetic mechanisms of scleroderma in a way that improves the course of the disease.

Topics: Female; Fingers; Humans; Iloprost; Infusions, Intravenous; Lung; Male; Microcirculation; Middle Aged; Pilot Projects; Prospective Studies; Respiratory Function Tests; Safety; Scleroderma, Localized; Scleroderma, Systemic; Skin; Toes; Treatment Outcome

The guidelines for digital ulcers (DUs) management in systemic sclerosis (SSc) indicate the use of iloprost to induce wound healing and bosentan to prevent the onset of new DU. The aim of our study was to evaluate whether the combination treatment may surmount the effect of the single drug.. We analyzed data regarding 34 patients with SSc and at least one active DU persisting despite 6 months of iloprost therapy, and treated for other 6 months with a combination therapy, i.e. iloprost plus bosentan.. Overall, patients initially presented 69 DUs (58 on the fingers and 11 on the legs). At the end of the study 34 (49.3%) DUs were completely healed (responding, R), 18 (26.1%) started the healing process (partially responding, PR), and 17 (24.6%) did not respond (NR) to therapy. No new DU was recorded and the ulcers localized on the legs did not respond to the combination therapy. Finally, data have been analyzed by dividing the patients in two groups according to the fibrosis level on the finger. In the group with mild fibrosis, 83.4% of DUs resulted with showing complete healing while, in the group with severe fibrosis, only 18% of DUs were healed (P = 0.024).. The treatment with iloprost plus bosentan is effective in determining healing of DUs in SSc patients with mild digital skin fibrosis. Conversely, the severity of skin fibrosis strongly influences the healing process of DUs. The study confirmed the efficacy of bosentan to prevent onset of new DUs.

Topics: Adult; Bosentan; Female; Fingers; Humans; Iloprost; Leg; Male; Middle Aged; Retrospective Studies; Scleroderma, Localized; Scleroderma, Systemic; Skin Ulcer; Sulfonamides; Treatment Outcome; Wound Healing

Topics: Aged; Humans; Iloprost; Middle Aged; Scleroderma, Localized; Scleroderma, Systemic