iloprost and Raynaud-Disease

Systemic sclerosis (SSc) is an autoimmune chronic disease characterized by vascular impairment, immune dysfunction and collagen deposition. Raynaud's phenomenon (RP) and digital ulcers (DU) are prominent features of SSc. Intravenous (IV) iloprost (ILO), according to the recently updated EULAR recommendations, is indicated for RP after failure of oral therapy. Moreover, IV ILO could be useful in DU healing. IV ILO is currently available mainly on the European market approved for RP secondary to SSc with 3-5 days infusion cycle. Unfortunately, data published varies regarding regimen (dosage, duration and frequency). Up to now, ILO has been studied in small cohorts of patients and in few randomized controlled trials.. A systematic review of studies on IV ILO in patients with SSc complicated by DU and RP was performed. Insufficient data were available to perform a meta-analysis according to the GRADE system. We performed a three-stage internet-based Delphi consensus exercise.. Three major indications were identified for IV ILO usage in SSc: RP non-responsive to oral therapy, DU healing, and DU prevention. IV ILO should be administered between 0.5 and 2.0ng/kg/min according to patient tolerability with a frequency depending on the indication.. Although these suggestions are supported by this expert group to be used in clinical setting, it will be necessary to formally validate the present suggestions in future clinical trials.

Topics: Consensus; Fingers; Humans; Iloprost; Injections, Intravenous; Raynaud Disease; Scleroderma, Systemic; Skin Ulcer; Vasodilator Agents

Raynaud's Syndrome is a frequent manifestation of digital ischemia which occurs or is aggravated upon exposure to cold temperatures or emotional distress. Primary Raynaud is a benign disease which predominantly affects younger women and is transient without serious sequelae. In contrast, secondary Raynaud is usually one of the manifestations of systemic disease and is, in addition to symptoms of the basic disease, associated with ischemic lesions. The diagnosis of primary Raynaud is mostly based on the clinical presentation. In secondary Raynaud, additional investigating techniques including imaging investigations and laboratory tests for the detection of underline disease are needed. Treatment is based on lifestyle modification, which includes smoking cessation, avoiding low outside temperatures, avoiding the use of vibrating tools and limiting repeated hand actions. Drug treatment consists of calcium-channel blockers, nitroglycerine ointments, prostacyclins and various new drugs such as endothelin receptor antagonists, phosphodiesterase inhibitors and serotonin receptor antagonists. Most of these drugs are effective in less than 50% of treated patients and do not completely abolish vasospastic attacks, but reduce the severity and frequency of attacks. The prostacyclin derivate iloprost is the most promising drug in the management of secondary Raynaud's disease. Other therapeutic procedures including chemical or surgical sympathectomy are obsolete and without any long-term positive effects.

Topics: Calcium Channel Blockers; Epoprostenol; Humans; Iloprost; Ischemia; Life Style; Neglected Diseases; Nitroglycerin; Raynaud Disease; Smoking Cessation; Vasodilator Agents

Raynaud phenomenon (RP) is the hallmark of Systemic Sclerosis (SSc). Visceral RP has also been proposed in SSc patients. Cardiac Raynaud's phenomenon (C-RP) was evaluated in a few clinical studies both as cold-induced transient myocardial ischaemia and as presence of advanced myocardial fibrosis and contraction band necrosis in autopsied patients. Until today numerous techniques, such as scintigraphy and myocardial contrast echocardiography, have been used to evaluate C-RP. In this case report for the first time we have used Cardiac Magnetic Resonance (CMR) after cold test to demonstrate the presence of the C-RP. In addition we have shown that therapy with Iloprost can be used to reduce episodes of C-RP.

Topics: Antibodies, Antinuclear; Female; Fibrosis; Heart; Humans; Iloprost; Ischemic Attack, Transient; Magnetic Resonance Imaging; Middle Aged; Myocardium; Platelet Aggregation Inhibitors; Raynaud Disease; Recovery of Function; Scleroderma, Systemic

Topics: Calcium Channel Blockers; Cold Temperature; Diagnosis, Differential; Hand; Humans; Iloprost; Raynaud Disease; Vasoconstriction; Vasodilator Agents

Patients with systemic sclerosis frequently have Raynaud's phenomenon and digital ischemic ulcers. Iloprost, a synthetic prostacyclin analogue, may be effective in these cases. Searching in Epistemonikos database, which is maintained by screening 20 databases, we identified three systematic reviews including seven randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded iloprost may lead to little or no difference in the frequency or severity of secondary Raynaud, and it is associated to adverse effects and important costs.. Los pacientes con esclerodermia presentan con frecuencia fenómeno de Raynaud asociado y úlceras digitales isquémicas. El iloprost, un análogo sintético de prostaciclina, podría ser efectivo en estos casos. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 20 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen siete estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que iloprost podría disminuir poco o nada la frecuencia y gravedad de los episodios de Raynaud secundario, y se asocia a efectos adversos y costos importantes.

Topics: Databases, Factual; Humans; Iloprost; Randomized Controlled Trials as Topic; Raynaud Disease; Scleroderma, Systemic; Vasodilator Agents

Topics: Antihypertensive Agents; Bosentan; Endothelin Receptor Antagonists; Female; Fingers; Humans; Iloprost; Ischemia; Male; Raynaud Disease; Risk Factors; Scleroderma, Systemic; Skin Ulcer; Sulfonamides; Vasodilator Agents

To present an evidence-based overview of the effectiveness of (non)surgical symptomatic interventions to treat secondary Raynaud's phenomenon (RP).. The Cochrane Library, PubMed, Embase, PEDro, and CINAHL were searched for relevant systematic reviews and randomized controlled trials (RCTs).. Two reviewers independently applied the inclusion criteria to select potential studies.. Two reviewers independently extracted data and assessed the methodologic quality.. If pooling of data was not possible, a best-evidence synthesis was used to summarize the results. Of the 5 reviews and 19 RCTs included, 1 RCT studied acupuncture and another RCT reported on percutaneous radiofrequency thoracic sympathectomy. All others concentrated on the effectiveness of drugs (oral or intravenous [IV]). It appeared that calcium channel blockers significantly reduce the frequency and severity of Raynaud attacks, and are therefore effective in the treatment of secondary RP. Iloprost (oral and IV) was also found to be effective. Limited evidence was found for atorvastatin. For other traditional and more recently discovered interventions, no clear favorable effects were found.. This review shows that there is clear evidence in favor of calcium channel blockers and iloprost (oral and IV) to treat secondary RP. For all other interventions, only limited, conflicting, or no evidence was found. More high-quality, well-designed RCTs are needed in this field, especially for new interventions based on recent knowledge about the pathophysiology of secondary RP.

Topics: Acupuncture Therapy; Calcium Channel Blockers; Humans; Iloprost; Radiofrequency Therapy; Randomized Controlled Trials as Topic; Raynaud Disease; Vasodilator Agents

Raynaud's phenomenon is a common condition characterized by vasospasm of the digital arteries and resulting cyanosis and redness. It often does not require pharmacologic management, but in some cases symptoms are severe and pharmacologic management is necessary. Calcium channel blockers are often used first-line, but in some patients are ineffective. Patients with severe symptoms or intolerance to available therapies have prompted exploration of alternative therapies, including endothelin antagonists, phosphodiesterase-5 inhibitors, antioxidants, newer vasodilators, statins, and botulinum toxin. These newer therapies provide the focus for this review.

Topics: Antioxidants; Bosentan; Botulinum Toxins, Type A; Calcium Channel Blockers; Endothelin Receptor Antagonists; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Iloprost; Phosphodiesterase 5 Inhibitors; Raynaud Disease; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Sulfonamides; Vasodilator Agents

An imbalance between prostacyclin (PGI2) and thromboxane A2 is observed in patients with scleroderma. Iloprost is a stable analogue of PGI2 with a plasma half-life of 20-30 min. Intravenous iloprost is effective in the treatment of Raynaud's phenomenon related to scleroderma, decreasing the frequency and severity of attacks. It also appears useful for the treatment of digital ulcers. Inhaled iloprost is an effective treatment for NYHA class III pulmonary arterial hypertension, either idiopathic primary or associated with a particular condition, such as scleroderma. Intravenous iloprost improves kidney vasospasm in patients with scleroderma. The possible benefits of sequential intravenous iloprost on the natural course of scleroderma require further investigation.

Topics: Humans; Hypertension; Iloprost; Raynaud Disease; Renal Circulation; Scleroderma, Systemic; Vasodilator Agents

The therapy of systemic sclerosis (SSc) remains a challenge for dermatology, rheumatology, internal medicine, and other disciplines. Organ involvement, above all kidney and lungs, is a key therapeutic issue. The current developments in organ-specific therapy are the main topic of the article. Finally, possibilities of disease-modifying drugs and value of HSCT are discussed.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Fibrosis; Fingers; Gastrointestinal Agents; Hematopoietic Stem Cell Transplantation; Humans; Hypertension, Pulmonary; Iloprost; Kidney Transplantation; Piperazines; Purines; PUVA Therapy; Raynaud Disease; Recurrence; Scleroderma, Systemic; Sildenafil Citrate; Skin Ulcer; Sulfones; Ultraviolet Therapy; Vasodilator Agents

Systemic sclerosis is an autoimmune disease of unknown origin affecting multiple organ systems. The management of this disease is challenging. Many therapeutic attempts have only been moderately successful. Iloprost, a stable prostacyclin analogue, with its antifibrotic effect can influence an important step in the pathogenesis of systemic sclerosis. In this review we analyze the published data for the optimal dose and duration of treatment. In three different studies, iloprost given for 5 days in the highest tolerated dose of 1-2 ng/kg/min provided a significant improvement of the disease measured by the number and intensity of Raynaud attacks, healing of digital ulcers, and digital perfusion. This improvement lasted for about one month. When the infusions were repeated once a month, treatment effect could be maintained. Although the effect of this treatment regimen should be proven in further long-term studies, we think that an intermittent continuous therapy with iloprost could result in an improvement or stabilization of systemic sclerosis.

Topics: Controlled Clinical Trials as Topic; Forecasting; Humans; Iloprost; Platelet Aggregation Inhibitors; Raynaud Disease; Scleroderma, Systemic; Time Factors; Vasodilator Agents

Topics: Adult; Age Distribution; Calcium Channel Blockers; Female; Humans; Iloprost; Losartan; Male; Middle Aged; Necrosis; Prognosis; Raynaud Disease; Risk Factors; Sex Distribution; Smoking; Vasodilator Agents; Verapamil

Topics: Calcium Channel Blockers; Cold Temperature; Diagnosis, Differential; Female; Humans; Iloprost; Male; Nifedipine; Plasmapheresis; Raynaud Disease; Risk Factors; Sensitivity and Specificity; Sex Factors; Vasodilator Agents

Most patients with systemic sclerosis (SSc) have Raynaud's phenomenon (RP), which is often more severe than idiopathic RP. This study was a meta-analysis to determine the efficacy of calcium-channel blockers for the treatment of RP in SSc. The primary outcome measures were frequency and severity of ischemic attacks, digital skin temperature, patient and physician global assessments, and digital ulcers.. The Cochrane search strategy was used to ascertain all trials in all languages. Primary data sources included Medline, Current Contents, and the Cochrane Controlled Trials Register. Studies that met the inclusion criteria were randomized controlled trials of >2 days' duration with a dropout rate of <35%. Twenty-nine studies were found, of which 8 randomized controlled trials were eligible for inclusion. The total number of patients included was small (n = 109). Most trials included primary and secondary RP, and the main reasons for trial exclusion were inability to extract subset data on SSc patients (18 trials), data published previously (2 trials), and lack of a control group (1 trial). Data were abstracted independently by 2 reviewers, and either a weighted mean difference (WMD) or a standardized mean difference (SMD) was calculated for all continuous outcomes; however, information was not available for all outcomes within trials.. The WMD of all calcium-channel blockers versus placebo (6 trials) and of nifedipine alone versus placebo (5 trials) for the reduction in the frequency of ischemic attacks over a 2-week period was -8.31 (95% confidence interval [95% CI] -15.71, -0.91) and -10.21 (95% CI -20.09, -0.34), respectively. The SMD of all calcium-channel blockers versus placebo (3 trials) and of nifedipine alone versus placebo (2 trials) for the reduction in the severity of ischemic attacks was -0.69 (95% CI -1.21, -0.17) and -0.99 (95% CI -1.74, -0.24), respectively.. Calcium-channel blockers for RP in SSc have been tested in several small clinical trials and appear to lead to significant clinical improvement in both the frequency and the severity of ischemic attacks. Most trials were crossover trials in which order effect was not studied. This could have introduced bias. The results of this study suggest that the efficacy of calcium-channel blockers in reducing the severity and frequency of ischemic attacks in RP secondary to SSc is moderate at best (mean reduction of 8.3 attacks in 2 weeks and 35% less severity), and a further large, randomized controlled trial needs to be conducted.

Topics: Calcium Channel Blockers; Cross-Over Studies; Humans; Iloprost; Injections, Intravenous; Ischemia; Losartan; Randomized Controlled Trials as Topic; Raynaud Disease; Scleroderma, Systemic; Skin Temperature; Skin Ulcer

To assess the effects and toxicity of the following agents:Prostaglandin analogues together with other agents proposed for the treatment of Raynaud's phenomenom (RP) in scleroderma.. We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages.. All randomized controlled trials comparing prostaglandin analogues versus placebo were eligible if they reported clinical outcomes within the start of therapy, and if the dropout rate was less than 35%.. Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous, respectively.. Seven randomized trials and 332 patients were included. Five of the seven trials were of parallel design. Five trials compared I.V. Iloprost and one trial studied p.o. Iloprost and another p.o. Cisaprost. Some trials were dose finding trials so various doses of Iloprost were used. Due to different efficacies of I.V. Iloprost, oral Iloprost and oral Cisaprost, the overall efficacy of these drugs was somewhat diluted. Intravenous Iloprost appears to be effective in the treatment of secondary Raynaud's phenomenon.. Intravenous Iloprost is effective in the treatment of Raynaud's phenomenon secondary to scleroderma at decreasing the frequency and severity of attacks and preventing or healing digital ulcers. The effect seems to be prolonged after the intravenous infusion is given. Oral Iloprost may have less efficacy than intravenous Iloprost. However, Cisaprost has minimal or no efficacy when given orally for the treatment of Raynaud's phenomenon secondary to scleroderma.

Topics: Humans; Iloprost; Raynaud Disease; Scleroderma, Systemic; Vasodilator Agents

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Epoprostenol; Female; Humans; Iloprost; Moxisylyte; Nifedipine; Raynaud Disease

Systemic sclerosis (SSc) is a systemic multi-organ disease. Raynaud's phenomenon (RP) and digital ulcers (DUs) in SSc patients can be resistant to usual treatments. We studied the clinical benefits, capillaroscopy changes, and cost-effectiveness of local injection of botulinum toxin-A (BTX-A) and intravenous prostaglandin analogs (iloprost/alprostadil) in patients with SSc with resistant DUs.. In a clinical trial study, we evaluated 26 patients fulfilling the ACR/EULAR SSc criteria with resistant DUs. Visual analog scale of pain and RP, skin color and type of ulcers, and capillaroscopy were assessed before and 1 month after treatment. In the first group, 20 units of BTX-A was injected at the base of each involved fingers by a dermatologist. In the second group, 20 µg iloprost or 60 µg alprostadil was infused daily. The cost of these treatments was compared.. In 26 patients (43 fingers), there were 16 patients (22 fingers) in the BTX-A and 10 patients (21 fingers) in the prostaglandin group. In 95.5% of the BTX-A and 90.5% of the prostaglandin group, the ulcers were healed. In both groups, a significant decrease in pain was seen (p < 0.0001). Capillaroscopy patterns in both groups were not changed although the microhemorrhages disappeared significantly (p value: BTX-A: 0.03 and prostaglandin: 0.002). The cost was significantly lower in the BTX-A injection group (p < 0.0001).. Both BTX-A and prostaglandins helped in the healing and pain control of DUs. In capillaroscopy, microhemorrhages were significantly decreased in both groups. In the BTX-A group, the cost was significantly lower as an outpatient treatment and was more time-saving.. • BTX-A and prostaglandin analogs both contributed to the healing of digital tip ulcers and improving the pain • In capillaroscopy, microhemorrhages were significantly decreased or disappeared after both treatments • There was no significant side effect in both groups • Comparing both groups, in the BTX-A group, the cost was significantly lower when performed on an outpatient treatment and more time-saving.

Topics: Botulinum Toxins, Type A; Cost-Benefit Analysis; Fingers; Humans; Iloprost; Microscopic Angioscopy; Prostaglandins; Raynaud Disease; Scleroderma, Systemic; Skin Ulcer; Ulcer

Iloprost has been reported to reduce Raynaud`s phenomenon (RP) and to inhibit progression of systemic sclerosis (SSc).. The aim of our study was to compare monthly iloprost infusions with placebo in patients treated long-term.. Seventeen patients, six with RP and 11 with SSc on monthly treatment with iloprost, received either a 3-hour intravenous infusion of iloprost or an equal volume of placebo once per month for 4 months in a monocentric, randomized, placebo-controlled, double-blind study. Raynaud attacks as measured by diary entries, skin temperature, skin sclerosis, fist closure, mouth opening, and digital ulcers were recorded during the observation period.. Whereas mouth opening improved significantly (p = 0.043) in the iloprost-treated group, RS improved in both patient groups. However, no significant differences were found in the outcome measures.. Although iloprost influences the inflammatory cascade in SSc, no statistical differences were seen in our study, indicating that treatment strategies with iloprost should be modified.

Topics: Adult; Aged; Double-Blind Method; Female; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Vasodilator Agents

Topics: Adult; Aged; Capillaries; Female; Humans; Iloprost; Male; Microscopic Angioscopy; Middle Aged; Nails; Pilot Projects; Raynaud Disease; Scleroderma, Systemic; Vasodilator Agents

We compared the efficacy of different dosages of longterm iloprost treatment on Raynaud's phenomenon (RP), ulcer healing, skin thickening, and progression of internal organ sclerosis in patients with systemic sclerosis (SSc).. Fifty patients with SSc were randomized 1:1 for the maximally tolerated dose up to 2 ng/kg body weight per minute or low-dose (0.5 ng/kg bw per min) intravenous iloprost administration, applied for 6 hours daily over 21 days. Effects on RP, ulcer healing, skin thickness, esophageal function, and lung involvement assessed by forced vital capacity (FVC) and DLCO were measured, as well as side effects.. Both regimens yielded 70% reduction of digital ulcers, 40% reduction in frequency of RP, and 30% reduction in duration of RP. One year after therapy, the modified Rodnan skin score appeared to be unchanged. FVC and DLCO-SB were stable in 87% and 74% of the patients, respectively. The effect of iloprost on skin thickness and lung function was sustained in a subgroup of patients receiving several courses of iloprost. As assessed by a patient questionnaire, 12% of all patients did not respond to iloprost therapy, but 78% experienced a longlasting effect. Mild side effects were common in both groups, but did not lead to discontinuation of therapy.. Low-dose iloprost was shown to be equally effective as high-dose iloprost in longterm treatment and was very effective in therapy of digital ulcers. Registered in www.ClinicalTrials.gov (registration no. NCT00622687).

Topics: Adult; Aged; Disease Progression; Dose-Response Relationship, Drug; Female; Humans; Iloprost; Lung; Male; Middle Aged; Raynaud Disease; Respiratory Function Tests; Scleroderma, Systemic; Skin; Skin Ulcer; Surveys and Questionnaires; Treatment Outcome; Vasodilator Agents

Oxidative stress is involved in pathogenesis of Raynaud's phenomenon (RP), a hallmark of systemic sclerosis (SSc). Frequent episodes of ischemia-reperfusion may lead to release of free radicals and enhanced lipid peroxidation reflected by elevated levels of malondialdehyde (MDA). The failure of native antioxidants (Catalase [CAT], Superoxide dismutase [SOD], and Ceruloplasmin [CP]) might be crucial in endothelial cells damage in RP. Iloprost (IL) synthetic prostacyclin analogue is currently used in the treatment of SSc patients with RP. The objectives of this study were to compare the serum levels of MDA and CP, CAT and SOD activity in red blood cells hemolysate in SSc patients compared to healthy controls; and to study the effect of 5-days IL infusions on MDA and CP levels, and CAT and SOD activity in SSc patients with RP. Twelve SSc patients were treated with 50 mug IL for 5 days. Blood samples were taken before and after day 1st and after day 5th of IL infusions. Levels of CAT were measured according to the Aebi's method; SOD, according to the Misra and Fridovich method; MDA, according to Slater's method; and CP, according to Ravin's method. Activities of CAT (p < 0.001) and SOD (p < 0.04) were significantly reduced; levels of CP (p < 0.006) and MDA (p < 0.06) were raised in SSc compared to controls. IL infusions caused reduction in MDA (p < 0.0001) levels and enhanced production of SOD (p < 0.006) and CAT (p < 0.003). The levels of CP did not change (p = 0.48). Oxidant status in SSc patients with RP is impaired. Therapy with IL led to normalization of antioxidant activity. We suggest that CAT may be a sensitive and reliable laboratory marker of oxidative stress severity in RP. We found that IL, in addition to its vasoactive properties, has a potential to activate inner antioxidant system. Activation of inner antioxidant activity may explain long-term effect of IL instead of its very short half-life time.

Topics: Adult; Antioxidants; Catalase; Ceruloplasmin; Female; Humans; Iloprost; Malondialdehyde; Middle Aged; Oxidative Stress; Platelet Aggregation Inhibitors; Raynaud Disease; Scleroderma, Systemic; Superoxide Dismutase

To evaluate the clinical efficacy and the effects on the quality of life of iloprost, a prostacyclin analogue, used according to a new protocol in patients with Raynaud's phenomenon secondary to systemic sclerosis.. In this randomized study, we treated 30 patients with iloprost, given by intravenous infusion, at progressively increasing doses (from 0.5 to 2 ng/kg/min) over a period of 6 h each day for 10 days in two consecutive weeks, with repeated cycles at regular intervals of 3 months for 18 months. The results were compared with those obtained in 30 other patients who received the same drug but with different dosing schemes.. The total average daily duration of the attacks, the average duration of a single attack and the average daily frequency of the attacks were reduced significantly in all treatment groups, but the comparison between the groups demonstrated significant differences between patients treated with the new protocol and the others at later times (12 and 18 months). The effects on the quality of life in the group treated with the new protocol, evaluated with the Short Form-36, demonstrated a marked improvement regarding both the scale relating to the physical aspect of the illness and, especially, the scale relating to the mental aspect.. In patients with systemic sclerosis, cyclic intravenous iloprost infusion is efficacious in the treatment of Raynaud's phenomenon. The protocol that we used, compared with others, not only has favourable clinical effects but also leads to a marked improvement in the quality of life.

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Prospective Studies; Quality of Life; Raynaud Disease; Scleroderma, Systemic; Severity of Illness Index; Time Factors; Treatment Outcome; Vasodilator Agents

To evaluate the long term efficacy of treatment with intravenous iloprost for severe Raynaud's phenomenon (RP) and ischemic leg ulcers in patients with autoimmune systemic diseases.. Prospective observational study over 2 years with iloprost (intravenous infusions, 0.5 to 2 ng/kg/min, initial cycle of 5 consecutive days and maintenance infusions during 24 h monthly, lengthened when it was needed) in patients with severe RP and ischemic leg ulcers whithout response to conventional therapy. Treatment was halted in patients with a good response after one year of treatment, with regular clinical controls.. We treated 23 patients. Iloprost reduced significantly the mean number (SD) of monthly episodes of RP (150.38 [102.04] initially and 40.05 [78.06] at the end; p < 0.0005), the mean highest duration of episodes of RP (21.86 [26.96] min initially and 7.14 [9.87] min at the end; p = 0.013), the associated pain (p = 0.005), and the mean number of ischemic digital (4.25 [2.86] initially and 0.63 [2.25] at the end; p = 0.003) and leg ulcers (1.67 [0.52] initially and 0.33 [0.52] at the end; p = 0.01). Articular symptoms and inflammatory markers did not improve. Treatment was stopped in 8 patients (in 5 for a very good evolution and in 3 for other causes), and only 1 of them needed to be treated again. Side effects were seen in all cases but always disappeared after slowing infusion.. Iloprost was effective in the long term treatment of severe RP and ischemic leg ulcers in patients with autoimmune systemic diseases.

Topics: Adult; Autoimmune Diseases; Female; Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Male; Prospective Studies; Raynaud Disease; Severity of Illness Index; Time Factors; Vasodilator Agents

The prostanoids iloprost and alprostadil are widely used to treat ischaemic changes in patients with Raynaud's phenomenon (RP), but the optimal regimen is poorly defined. We evaluated whether there are differences between iloprost and alprostadil, in terms of either clinical efficacy or of laboratory data, with the aim of assisting in the treatment of connective tissue disease (CTD)-associated RP.. Twenty-one women with CTD-associated RP were given intravenous iloprost (11 patients) or alprostadil (10 patients) cyclically (5 consecutive days, followed by 1 day every 30 days). Clinical efficacy (RP symptoms, skin score, digital ulcers) and circulating levels of von Willebrand factor (VWf), tissue plasminogen activator (tPA), thrombomodulin (TM) and Type III procollagen N-terminal propeptide (PIIINP) were evaluated by enzyme-linked immunoassay at different intervals.. The overall benefits of iloprost and alprostadil were similar. RP improved in 45% versus 90% of patients; ulcers in 60% versus 40% of patients (iloprost versus alprostadil). Skin score did not significantly change with either drug. Circulating VWf decreased with either drug (iloprost -6.2%, alprostadil -9.4%), while tPA, TM, and PIIINP remained unchanged. Side effects were only minor and less frequent with alprostadil.. Iloprost and alprostadil were both of benefit in CTD-associated RP, without significant differences in either clinical efficacy or circulating markers. However, ease of handling and the lower price favours alprostadil.

Topics: Adult; Aged; Alprostadil; Biomarkers; Connective Tissue Diseases; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Raynaud Disease; Treatment Outcome; Vasodilator Agents

Iloprost is a chemically stable, pharmacologically highly potent prostacyclin-minietic. The therapeutic efficacy of the intravenous preparation was proven in patients with peripheral arterial occlusive disease or with Raynaud's phenomenon (RP). Recently, a sustained release oral preparation was developed for outpatient therapy. The purpose of the current study was to investigate whether the oral drug has a different pharmacokinetic profile in patients with RP secondary to systemic sclerosis (SSc) in comparison with healthy volunteers. Ten patients with RP secondary to SSc and 10 healthy volunteers (matched for age and sex) participated. Oral iloprost 50 microg was given twice daily for 8 days with dosing intervals of 5 h and plasma levels were taken over 10 h on Day 1 and 8. Plasma levels of iloprost were determined by a validated specific and sensitive radio-immunoassay. Compared with healthy volunteers, patients with SSc exhibited higher AUC values (by mean factors of 2. 1 and 2.0 on Day 1 and 8) and maximum plasma levels (by mean factors of 1.6 and 1.8 on Day 1 and 8). The increased systemic iloprost exposure was observed after both daily doses and on both monitored study days. Mean AUC values did not show accumulation over the 8 days. These findings are in agreement with a reduced total clearance of iloprost given by i.v. route in SSc patients compared to healthy volunteers, although no participant with severe renal impairment was included. A weak but significant correlation was found between individual creatinine clearance and AUC values. In conclusion, RP secondary to SSc is associated with an increased systemic iloprost exposure which is probably caused by changes of the metabolic clearance of iloprost. These effects cannot be explained by changes of renal function alone.

Topics: Administration, Oral; Delayed-Action Preparations; Female; Humans; Iloprost; Male; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Time Factors; Vasodilator Agents

To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma).. A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary.. Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058).. Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Data Interpretation, Statistical; Double-Blind Method; Female; Headache; Humans; Iloprost; Male; Middle Aged; Nausea; Placebos; Raynaud Disease; Recurrence; Scleroderma, Systemic; Time Factors; Treatment Outcome; Vasodilation; Vasodilator Agents

Topics: Adult; Alprostadil; Connective Tissue Diseases; Female; Fingers; Humans; Iloprost; Male; Middle Aged; Necrosis; Raynaud Disease; Vasodilator Agents

To identify the optimal dose of oral iloprost on the basis of efficacy and tolerability in patients with Raynaud's phenomenon secondary to systemic sclerosis.. Multicentre, randomized, parallel-group comparison of two different doses of oral iloprost and placebo.. European university hospitals.. A total of 103 patients with Raynaud's phenomenon secondary to systemic sclerosis.. Patients received one of three treatments for 6 weeks: placebo, oral iloprost 50 microg or oral iloprost 100 microg. Each treatment was taken twice daily, giving total daily doses of iloprost of 100 and 200 microg.. The frequency, total daily duration and severity of Raynaud's attacks were recorded in a specially designed patient diary; physician's global assessment and adverse events were recorded at visits to the clinic. Analysis was performed on an intention-to-treat population.. A total of 103 patients were recruited, 89 completed the assessments throughout the treatment period and 82 completed an additional 6 weeks of follow-up after treatment. Thirty-five patients received placebo, 33 received iloprost 50 microg and 35 received iloprost 100 microg. The mean percentage reductions in the frequency, total daily duration and severity of Raynaud's attacks were numerically greater in the iloprost groups at the end of treatment and at the end of follow-up. At the end of treatment (6 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.03), but not in the severity (P = 0.07) or the frequency of attacks (P = 0.37). At the end of follow-up (12 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.001) and in the severity of attacks (P = 0.007), but not in the frequency of attacks (P = 0.07). Percentages of patients improved at the end of treatment as assessed by the physician were 44% placebo, 57% iloprost 50 microg and 64% iloprost 100 microg (not significant). Side-effects were reported by 80% of patients on placebo, 85% on oral iloprost 50 microg and 97% on oral iloprost 100 microg. Premature discontinuations of treatment in each group were 9, 30 and 51%, respectively, with 6, 27 and 51% being due to adverse events.. The results on the daily duration of Raynaud's attacks suggest that both 50 and 100 microg oral iloprost twice daily may be effective in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. The 50 microg iloprost dose was better tolerated in this patient group.

Topics: Administration, Oral; Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Iloprost; Male; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Treatment Outcome; Vasodilator Agents

Twelve patients with systemic sclerosis were treated with intravenous infusions of the prostacyclin-stable analogue iloprost 0.5-2.0 ng/kg/min for 6 h from 8 to 13 days. Imminent gangrene was stopped in 2 patients and followed by healing. In 4 of 6 patients iloprost led to complete healing of ischaemic ulcers and in the remaining 2 patients to partial healing. One patient with severe Raynaud's phenomenon discontinued the study after 3 days due to severe headache. The 2 remaining patients with Raynaud's phenomenon as an indication improved, while no improvement was recorded in a patient with vasculitis of the lower leg. Side-effects such as headache, nausea and flushing were the reason that only 5 patients reached the maximum infusion rate. No statistical differences were recorded in digital bloodflow before and after the study or in plasma endothelin in the 9 patients investigated. Three of the 6 patients with healing ulcers, however, showed a pronounced decrease in plasma endothelin. Iloprost appears useful as a treatment of imminent gangrene and ischaemic ulcers in systemic sclerosis. This reparatory capacity could also be of a more general importance in therapy of this disease.

Topics: Adult; Aged; Endothelins; Female; Fingers; Gangrene; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Ulcer; Vasodilator Agents

To compare the efficacy, tolerance and safety of 50-150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud's syndrome.. The study was multicentre (n = 3), double blind and placebo controlled. Sixty three patients who had eight or more vasospastic attacks per week were enrolled. After a one week run-in period, all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days. Diary cards assessed the duration and severity of the vasospastic attacks. Side effects were monitored by direct questioning. A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later.. Patient opinion tended to favour iloprost at the end of the 10 day treatment phase (p = 0.09) and this was significant at day 24 (the follow up visit) (p = 0.011). Although the duration and severity of attacks tended to decrease in the iloprost treated group, these results tended not to reach statistical significance (for severity p = 0.06 at end of treatment, p = 0.09 on day 24).. Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud's syndrome associated with systemic sclerosis, but this route of administration is inconvenient. This study evaluated the use of iloprost administered orally to patients with Raynaud's syndrome. Patient documented improvement was significantly improved by iloprost. Diary card analysis showed a trend in favour of iloprost, but these results did not reach statistical significance.

Topics: Administration, Oral; Adult; Attitude to Health; Double-Blind Method; Female; Humans; Iloprost; Male; Middle Aged; Patients; Raynaud Disease; Scleroderma, Systemic; Time Factors

To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis.. Multicenter, randomized, parallel placebo-controlled, double-blind study.. University medical centers.. 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years.. Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo.. Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing.. Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo.. Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.

Topics: Adult; Aged; Analysis of Variance; Cold Temperature; Double-Blind Method; Drug Administration Schedule; Female; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Severity of Illness Index; Treatment Outcome

Iloprost is a chemically stable analog of prostaglandin I2 showing the same properties as the naturally occurring substance, but with advantages of ease of handling and administration to patients. A double blind within patient comparison of intravenous iloprost and placebo was undertaken in 13 patients with Raynaud's phenomenon severe enough to warrant short term hospitalization for intravenous dilator therapy; thermography was used as one form of assessment. Our results, while showing improvements in frequency of Raynaud's attacks after iloprost compared with placebo, show no significant effects on other variables.

Topics: Adult; Double-Blind Method; Female; Fingers; Humans; Iloprost; Injections, Intravenous; Male; Middle Aged; Raynaud Disease; Thermography

We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis.. Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks.. Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion.. Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear.

Topics: Adult; Aged; Double-Blind Method; Female; Fingers; Hemodynamics; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Middle Aged; Platelet Activation; Raynaud Disease; Scleroderma, Systemic; Skin; Temperature; Ulcer

To compare low (0.5 ng/kg/min) and standard dose (2 ng/kg/min) iloprost (a stable carbacyclin analogue of prostacyclin) in patients with Raynaud's phenomenon secondary to connective tissue disorders.. Double blind, random allocation, three six hour infusions on consecutive days. Follow up period eight weeks.. Rheumatology units, five teaching hospitals.. 55 Patients with Raynaud's phenomenon (greater than seven attacks per week), 32 secondary to well documented classical progressive systemic sclerosis (American Rheumatism Association criteria), 11 CREST syndrome, 5 mixed connective tissue disease, 1 rheumatoid arthritis, 1 Sjögren's syndrome, 1 childhood dermatomyositis, and 4 abnormal nailfold capillaroscopy and antibody profiles but no definite diagnosis.. All other treatment for Raynaud's phenomenon was discontinued two weeks before entry. 28 Patients were randomly allocated to receive the low dose, 27 the standard dose. Differing dilutions allowed infusion rates to be started at 10 ml/h with increments of 10 ml/h every 15 minutes until infusion rates reached 0.5 ng/kg/min and 2 ng/kg/min respectively. MAIN OUTCOME MEASURE(s)--Reduction in frequency, duration, and severity of attacks of Raynaud's phenomenon. Assessment of ulcer and ischaemic lesion healing.. Both dosage regimens were equally effective in reducing severity, frequency, and duration of Raynaud's attacks. Ulcer healing occurred to similar degree in both treatment groups (standard dose 44%, low dose 39%). Low dose was associated with significantly fewer side effects.. Both dosage regimens reduce severity of Raynaud's phenomenon and encourage ulcer healing. Low dose was associated with fewer side effects and was better tolerated by the patients.

Topics: Adult; Aged; Connective Tissue Diseases; Double-Blind Method; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Platelet Count; Raynaud Disease; Wound Healing

To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynaud's phenomenon associated with systemic sclerosis.. Double blind, placebo controlled, randomised group comparison.. Dermatology outpatient clinic.. Twenty three patients with Raynaud's phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy.. Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects.. Reduction in number, duration, and severity of attacks of Raynaud's phenomenon, reduction in number of digital lesions, increase in digital blood flow.. Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynaud's phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine.. Both iloprost and nifedipine are beneficial in the treatment of Raynaud's phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.

Topics: Administration, Oral; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Epoprostenol; Female; Hemodynamics; Humans; Iloprost; Infusions, Intravenous; Male; Nifedipine; Random Allocation; Raynaud Disease; Regional Blood Flow; Scleroderma, Systemic

Iloprost, a stable prostacyclin analogue, was given by intravenous infusion to 29 patients with severe Raynaud's phenomenon, 26 of whom had systemic sclerosis (SS), and compared with placebo infusion in a double blind crossover trial. Iloprost significantly lessened the number and the severity of attacks compared with placebo. Nine patients expressed a preference for effectiveness of treatment, eight of these in favour of Iloprost. Thermography failed to show any long term effect of Iloprost. Side effects of headache, flushing, nausea, and vomiting were common, and the inconvenience of intravenous administration may limit its routine use.

Topics: Clinical Trials as Topic; Double-Blind Method; Epoprostenol; Female; Humans; Iloprost; Injections, Intravenous; Male; Raynaud Disease; Scleroderma, Systemic

Twelve female patients with severe secondary Raynaud's phenomenon were treated in a randomized order with both placebo and Iloprost infusions. Infusions were for 5 hours on 3 consecutive days and Iloprost was administered at variable dosage from 1.0 to 3.0 ng/kg/min. A 6-week follow-up period was used between the two sets of infusions. A significant number of patients reported Iloprost had improved Raynaud's symptomatology compared with placebo and this effect lasted for up to 6 weeks. The number of attacks of Raynaud's as recorded by patients in diary books was similarly reduced after Iloprost. Digital and nail-bed blood flows measured by laser-Doppler methods were increased for up to 6 weeks after Iloprost, but not after placebo infusions. Iloprost may be a useful therapeutic agent in the treatment of severe secondary Raynaud's syndrome.

Topics: Aged; Body Temperature; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Epoprostenol; Female; Fingers; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Platelet Aggregation; Random Allocation; Raynaud Disease; Regional Blood Flow; Time Factors

Topics: Humans; Iloprost; Raynaud Disease; Scleroderma, Systemic

Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used.. A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion. Severity, and frequency of RP, new DUs onset or aggravation of those pre-existing were reported. Last available capillaroscopic images were also evaluated.. The analysis includes 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (p = 0.007). Only 8 patients of them also complained of an increased frequency (p = 0.07). None of the patients experienced digital ulcers for the first-time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrence of DUs. Overall, 17 patients (34.0 %) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Reduced capillary density was associated with RP worsening, in particular, each unit increase of capillary density corresponds to an average 44 % decrease in the odds of RP worsening (OR 0.56, CI 95 % 0.36-0.97, p = 0.037). As for RP worsening, the aggravation of DU was associated with a lower capillary density.. Low capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients.

Topics: COVID-19; Humans; Iloprost; Pandemics; Raynaud Disease; Scleroderma, Systemic; Skin Ulcer; Ulcer

Paroxysmal vascular acrosyndromes are related to a peripheral vasomotor disorder and presented as paroxysmal color changes of the fingers. They include primary Raynaud's phenomenon (RP), which is the most common, secondary RP and erythermalgia. They are to be distinguished from non-paroxysmal acrosyndromes such as acrocyanosis and chilblains, which are very frequent and often associated with RP, digital ischemia and necrosis, spontaneous digital hematoma and acrocholosis. The challenge of a consultation for a vascular acrosyndrome is to make positive diagnosis through history and clinical examination, and to specify its nature, to prescribe complementary exams. In any patient consulting for RP, assessment includes at least an antinuclear antibody test and capillaroscopy. For erythermalgia, a blood count and even a search for JAK2 mutation are required. A thryoid-stimulating hormon assay, a test for antinuclear antibodies, and a search for small fiber neuropathy are also performed. The treatment of RP is essentially documented for secondary RP where calcium channel blockers are indicated in first line, and iloprost in severe cases. The treatment of primitive erythermalgia is based on sodium channel blockers such as mexiletine or lidocaine infusions, and on drugs effective on neuropathic pain, such as gabapentin or amitryptiline, in case of erythermalgia associated with small fiber neuropathy. The treatment of erythermalgia associated with myeloproliferative syndromes is based on etiological treatment and aspirin.

Topics: Antibodies, Antinuclear; Aspirin; Calcium Channel Blockers; Erythromelalgia; Gabapentin; Humans; Iloprost; Lidocaine; Mexiletine; Raynaud Disease; Small Fiber Neuropathy; Sodium Channel Blockers

This study aims at evaluating the disease progression, specifically in terms of cardiopulmonary function, in a group of consecutively enrolled systemic sclerosis (SSc) patients treated with the approved iloprost regimen.. A retrospective observational study was performed on 68 SSc patients treated with 5-6 infusions of iloprost per month for 6 hours per day at a dosage of 0.5-2.0 ng/kg/min through a portable syringe pump. All patients were evaluated for modified Rodnan skin score, systolic pulmonary arterial pressure, tricuspid annular plane systolic excursion, diffusing capacity of the lungs for carbon monoxide, forced vital capacity, alveolar volume, diffusing capacity of the lungs for carbon monoxide/alveolar volume, pro-brain natriuretic peptide (pBNP), New York Heart Association class, and the presence or absence of digital ulcers (DUs).. After a follow-up period of 9.9±2.9 years, all patients improved in frequency and severity of the Raynaud phenomenon and showed a stabilization or improvement of cardiopulmonary parameters. The pulmonary arterial pressure and pBNP improved significantly from baseline (30.91±6.4 mmHg vs. 27.36±7.1 mmHg, and 97.20±69.3 pg/ml vs. 66.65±44.3 pg/ml, respectively; p<0.0001 for both). A significant improvement was observed in the modified Rodnan skin score in 57 patients who continued the treatment during the entire follow-up (5.09±5.7 vs. 3.30±4.2, p<0.0001).. Despite the retrospective design and the lack of a control group, the regular and continued administration of iloprost maintained the stability of the cardiopulmonary and cutaneous parameters in SSc. It significantly reduced pBNP levels, a prognostic cardiac biomarker of SSc. Future research should be addressed to demonstrate a stronger causality of this effect.

Topics: Carbon Monoxide; Humans; Iloprost; Raynaud Disease; Retrospective Studies; Scleroderma, Systemic

Intravenous iloprost improves Raynaud's phenomenon (RP) and promotes healing of digital ulcers in systemic sclerosis (SSc; scleroderma). Despite a short half-life, its clinical efficacy lasts weeks. Endothelial adherens junctions, which are formed by VE-cadherin clustering between endothelial cells (ECs), regulate endothelial properties including barrier function, endothelial-to-mesenchymal transition (EndoMT), and angiogenesis. We undertook this study to investigate the hypothesis that junctional disruption contributes to vascular dysfunction in SSc, and that the protective effect of iloprost is mediated by strengthening of those junctions.. Dermal ECs from SSc patients and healthy controls were isolated. The effect of iloprost on ECs was examined using immunofluorescence, permeability assays, Matrigel tube formation, and quantitative polymerase chain reaction.. Adherens junctions in SSc were disrupted compared to normal ECs, as indicated by reduced levels of VE-cadherin and increased permeability in SSc ECs (P < 0.05). Iloprost increased VE-cadherin clustering at junctions and restored junctional levels of VE-cadherin in SSc ECs (mean ± SD 37.3 ± 4.3 fluorescence units) compared to normal ECs (mean ± SD 29.7 ± 3.4 fluorescence units; P < 0.05), after 2 hours of iloprost incubation. In addition, iloprost reduced permeability of monolayers, increased tubulogenesis, and blocked EndoMT in both normal and SSc ECs (n ≥ 3; P < 0.05). The effects in normal ECs were inhibited by a function-blocking antibody that prevents junctional clustering of VE-cadherin.. Our data suggest that the long-lasting effects of iloprost reflect its ability to stabilize adherens junctions, resulting in increased tubulogenesis and barrier function and reduced EndoMT. These findings provide a mechanistic basis for the use of iloprost in treating SSc patients with RP and digital ulcers.

Topics: Adherens Junctions; Antigens, CD; Cadherins; Capillary Permeability; Case-Control Studies; Cells, Cultured; Endothelial Cells; Epithelial-Mesenchymal Transition; Female; Humans; Iloprost; Male; Middle Aged; Neovascularization, Physiologic; Raynaud Disease; Scleroderma, Diffuse; Vasodilator Agents

Iloprost (ILO) is employed intravenously for the treatment of severe Raynaud phenomenon (RP) and digital ulcers (DU) in systemic sclerosis (SSc). The aim of this study was to evaluate the safety and tolerability of the intravenous treatment with ILO in different phases of SSc. Eighty-one consecutive non-selected SSc patients, all on nifedipine, with moderate RP, treated with ILO infusion, were retrospectively evaluated. Patients were sub classified according to the edematous or fibrotic/atrophic cutaneous phase of the disease. ILO was infused with a progressive increase of the dosage up to the achievement of patient's tolerance, 1 day/week. In cases of slower infusion regimen due to adverse events (AE) at the beginning of the administration, patients received a lower dose of the drug (not possible to quantify precisely the final cumulative dosage). 16/81 SSc patients presented digital edema, 5 developed diarrhea, and 9 developed transient hypotension during the infusion at 20 ml/h that ameliorated when the drug was withdrawn. Moreover, 10/16 edematous patients experienced significant and painful digital swelling, unlike patients in the fibrotic group (p < 0.0001); 11/16 patients reported flushing and 7/16 headache, always controlled with dose tapering below 10 ml/h. In the atrophic/fibrotic phase patients (65/81), 10 developed diarrhea and 24 hypotension at infusion rate of 20 ml/h that led to temporary withdrawal of the drug. When ILO was restarted and kept below 10 ml/h, no side effects were experienced. 23/65 patients experienced flushing and 8/65 headache, all controlled with infusion reduction below 10 ml/h. In these patients, adverse events were significantly less frequent than in the edematous group (p = 0.023 and p = 0.008, respectively). Our data suggest that calcium channel blockers should be transitorily stopped while using ILO and that a pre-treatment approach might reduce or control adverse events. In patients with digital edema, ILO infusion should be carefully employed after the evaluation of patient's drug tolerance.

Topics: Adult; Diarrhea; Female; Fingers; Humans; Iloprost; Male; Microscopic Angioscopy; Middle Aged; Raynaud Disease; Retrospective Studies; Scleroderma, Systemic; Skin Ulcer; Treatment Outcome

Laser speckle contrast analysis (LASCA) is a good tool to evaluate the variation in peripheral blood perfusion during long-term follow-up and is able to safely monitor digital ulcer evolution in scleroderma patients. It evaluates blood perfusion in different areas within the skin lesions and surrounding them during standard treatment.

Topics: Bosentan; Female; Fingers; Humans; Iloprost; Lasers; Methotrexate; Microcirculation; Microscopic Angioscopy; Middle Aged; para-Aminobenzoates; Raynaud Disease; Scattering, Radiation; Scleroderma, Systemic; Skin Ulcer; Sulfonamides; Tramadol; Treatment Outcome

Vascular involvement plays a decisive role in systemic sclerosis (SSc) pathogenesis; it is responsible for some important clinical manifestations of the disease such as Raynaud's phenomenon and digital ulcers (DU). Bosentan, a dual receptor endothelin antagonist, and iloprost, often in combination therapy, seems to be able to interfere with the scleroderma microangiopathy.. Aim of the study was to evaluate the effect of bosentan and iloprost on scleroderma microangiopathy, analyzed by means of capillaroscopic skin ulcer risk index (CSURI), in SSc patients treated for the prevention of DU.. Nailfold videocapillaroscopy (NVC) was performed in 95 SSc patients, treated with iloprost alone (group 1) or combination therapy with iloprost and bosentan (group 2), at baseline and after one year. In all patients CSURI was calculated according to the formula "diameter × number of megacapillaries/(total number of capillaries). After 12 months, we observed a reduction of the number of giant capillaries in both groups, while an increase of ramified capillaries was recorded only in group 2. CSURI improved slightly in group 2 without statistical significance; on the contrary, in group 1 a significant worsening was recorded (p ≤ 0.001).. Our study confirms the effectiveness of bosentan, in combination with iloprost, in SSc microangiopathy observed to NVC. Moreover, the observed findings further support the role of CSURI in the evaluation and monitoring of SSc microangiopathy.

Topics: Adult; Aged; Antihypertensive Agents; Bosentan; Capillaries; Drug Therapy, Combination; Female; Humans; Iloprost; Male; Microscopic Angioscopy; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Sulfonamides; Treatment Outcome

Intravenous iloprost is a first-line option for the treatment of scleroderma-related digital vasculopathy, and some studies have suggested its favourable role on disease progression. The aim of our study is to evaluate the disease progression, specifically in terms of cardiopulmonary function, in a group of consecutive patients chronically treated with intravenous iloprost. Our retrospective study enrolled 68 scleroderma patients (68 F, 54.4 ± 12.3 years) treated with iloprost for 7.1 ± 2.9 years, with a schedule of 5-6 consecutive daily infusions per month (6 h/day, 0.5-2.0 ng/kg/min). In all patients, modified Rodnan skin score (4.7 ± 5.3 vs. 3.7 ± 5.3, p < 0.0001), systolic pulmonary arterial pressure (sPAP) (30.9 ± 6.4 vs. 24.0 ± 3.2 mmHg, p < 0.0001), tricuspid annular plane systolic excursion (22.1 ± 2.4 vs. 23.8 ± 3.5 mm, p = 0.0001), pro-brain natriuretic peptide (97.2 ± 69.3 vs. 65.8 ± 31.7 pg/ml, p = 0.0005) showed statistically significant improvement from baseline. In the subgroup of patients with baseline sPAP ≥36 mmHg (n = 17), a significant sPAP reduction was observed (from 39.5 ± 3.8 to 25.1 ± 4.5 mmHg, p < 0.0001) after 7.6 ± 2.5 years of follow-up. The number of patients with digital ulcers (DUs) at follow-up was reduced from baseline (42.6 vs. 11.8%, p < 0.001), and none of the free-DU patients at baseline presented DUs at follow-up. An intensive and chronic regimen of IV iloprost administration seems to stabilize and potentially improve the long-term development of disease in SSc patients, as suggested by stabilization or significant improvement of cardiopulmonary parameters and vasculopathy.

Topics: Adult; Aged; Disease Progression; Female; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Skin Ulcer; Treatment Outcome; Vasodilator Agents

Topics: Administration, Intravenous; Connective Tissue Diseases; Disease Management; Humans; Iloprost; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Raynaud Disease; Scleroderma, Systemic

Topics: Adolescent; Age of Onset; Antiphospholipid Syndrome; Child; Female; Foot; Foot Ulcer; Humans; Iloprost; Ischemia; Raynaud Disease; Regional Blood Flow; Treatment Outcome; Vasoconstriction; Vasodilator Agents; Wound Healing

The aim of this study was to visualize soft tissue inflammation using FOI on patients with Systemic Sclerosis (SSc) characterized by SSc-related Raynaud's phenomenon and to detect the therapeutic response to treatment with iloprost or alprostadil.. Twenty-one patients with SSc and Raynaud's phenomenon and twenty-six healthy controls were prospectively included. The SSc patients were intravenously treated with iloprost or alprostadil over seven days. FOI was performed at baseline and after seven days using an intravenous application of indocyanine green (ICG). The hands were divided into nineteen segments per hand. All segments were quantitatively evaluated to determine changes in ICG.. The sensitivity and specificity of FOI in the detection of ICG enhancement in patients with SSc were 95% versus 96%. At baseline, 31.5% hand segments showed ICG enhancement. After seven days of either iloprost or alprostadil therapy a significant reduction in the ICG was observed which ranged from 40.9% to 24.7%.. The study demonstrates that the FOI technique is able to visualize soft-tissue inflammation with both high sensitivity and specificity. The anti-inflammatory therapeutic effects of iloprost were slightly stronger than alprostadil. FOI offers promising benefits in the diagnosis and therapy of patients with SSc-associated Raynaud's phenomenon.

Topics: Adult; Alprostadil; Case-Control Studies; Female; Fluorescence; Humans; Iloprost; Indocyanine Green; Inflammation; Male; Optical Imaging; Prospective Studies; Raynaud Disease; Scleroderma, Systemic; Sensitivity and Specificity; Vasodilator Agents; Young Adult

Topics: Amputation, Surgical; Antibodies, Antinuclear; Female; Fingers; Humans; Iloprost; Middle Aged; Necrosis; Platelet Aggregation Inhibitors; Prednisolone; Raynaud Disease; Severity of Illness Index; Syndrome; Toes; Treatment Failure

Aim of the study was to assess whether Iloprost treatment summer suspension modifies systemic cytokines levels, cutaneous thermal properties and functional response to a cold-induced stress in patients affected by systemic sclerosis (SSc).. Twenty-eight patients fulfilling the American College of Rheumatology (ACR) criteria for SSc were included in the study. Patients recorded number, duration and pain-severity of Raynaud phenomenon (RP). Pain-severity was determined by a visual analog scale. Cytokines expression and production in peripheral blood mononuclear cells and serum were evaluated by RT-PCR and ELISA assay. Basal finger temperature (Tb), distal-dorsal difference temperature (DTdd) and thermal recovery time (tr) from cold stress were measured by means of functional infrared imaging (fIR). Measurements were performed in late spring, during routine Iloprost therapy (1-3 days infusion of 0.5-2 ng/kg every month), and in late summer after a therapy-withdrawal period.. Deterioration of SSc patients' skin thermal properties was observed in the period of therapy withdrawal (Tb reduction and tr enhancement; no DTdd differences) despite the improvement in symptoms of RP. A reduction in IL-12/23p40 gene expression was recorded after therapy withdrawal and a direct correlation between IL-12/23p40 and IL-23p19 gene expression was observed, stronger after therapy suspension.. Our data suggest that Iloprost treatment summer suspension may induce the loss of the therapy beneficial effect on microcirculation despite the objective reduction of RP, thus favouring a continuous use of Iloprost in absence of severe side effects. Iloprost showed to modulate only IL-23 expression corroborating the idea that this cytokine is crucial for SSc development and progression.

Topics: Adjuvants, Immunologic; Aged; Biomarkers; Cold Temperature; Cytokines; Female; Humans; Iloprost; Interleukin-12; Interleukin-23; Male; Middle Aged; Pain Measurement; Raynaud Disease; Scleroderma, Systemic; Seasons; Time Factors; Transforming Growth Factor beta; Treatment Outcome; Tumor Necrosis Factor-alpha; Vasodilator Agents; Withholding Treatment

Raynaud's phenomena is a common disorder which may be primary or secondary to some connective tissue disorders such as systemic sclerosis and systemic lupus erythematosus. Jellyfish sting is a rare but life-threatening cause of Raynaud's phenomena. Digital gangrene is reported in 3% of children with secondary Raynaud's phenomena but does not occur in children with primary Raynaud's phenomena. We report a case of a 4-year-old boy who initially presented with episodes of pain and bluish to blackish discolouration and necrosis affecting the fingers on both hands after a jellyfish sting without any sign of connective tissue disorder.

Topics: Animals; Bites and Stings; Child, Preschool; Fingers; Gangrene; Humans; Iloprost; Male; Raynaud Disease; Scyphozoa; Vasodilator Agents

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Fingers; Hodgkin Disease; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Multimodal Imaging; Necrosis; Positron-Emission Tomography; Raynaud Disease; Remission Induction; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome; Vasodilator Agents; Vinblastine

Topics: Bosentan; Botulinum Toxins, Type A; Calcium Channel Blockers; Education, Medical, Continuing; Endothelin Receptor Antagonists; Evidence-Based Medicine; Female; Fingers; Humans; Iloprost; Ischemia; Life Style; Middle Aged; Orthopedics; Phosphodiesterase 5 Inhibitors; Prostaglandins; Randomized Controlled Trials as Topic; Raynaud Disease; Scleroderma, Systemic; Sulfonamides; Vascular Resistance; Vasodilator Agents

To report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement.. In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5-1 ng/kg/min (6 hours per day, for 5 days every 6-8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased.. Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient.. This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.

Topics: Adult; Humans; Iloprost; Male; Raynaud Disease; Scleroderma, Diffuse; Vasodilator Agents

To investigate possible correlations between fingertip blood perfusion (FBP) status, assessed by laser Doppler flowmetry (LDF), and morphological microvascular abnormalities, detected by nailfold videocapillaroscopy (NVC), in patients with systemic sclerosis (SSc). The effects on FBP of intravenous (IV) treatment with the prostacyclin analog iloprost were also investigated.. Thirty-four consecutive patients with SSc and 16 healthy subjects were evaluated. LDF was performed by analyzing blood perfusion at the fingertips in both hands. Patients with SSc were distributed into the appropriate NVC pattern of microangiopathy (early, active, and late). Iloprost was administered to inpatients with SSc by 24-hour IV infusion for 7 consecutive days (4 microg/h).. FBP was significantly lower in patients with SSc (p < 0.05) compared to controls. Heating of the LDF probe at 36 degrees C induced a significant increase of FBP in all subjects (p < 0.001), but the slope of variation was significantly lower in patients with SSc compared to controls (p < 0.05). Patients with SSc showing the late NVC pattern of microangiopathy had significantly lower FBP than patients with the active and early NVC patterns (p < 0.05). A negative correlation was observed between FBP and NVC rating of the microvascular damage (p < 0.05). After iloprost treatment, a significant increase of FBP was observed in patients with SSc (p < 0.05).. Patients with SSc show a decreased FBP partially reversible by local skin heating. The FBP correlated negatively with the extent of nailfold microvascular damage, and IV iloprost treatment increased the FBP.

Topics: Capillaries; Female; Humans; Hyperthermia, Induced; Iloprost; Injections, Intravenous; Laser-Doppler Flowmetry; Microcirculation; Microscopic Angioscopy; Middle Aged; Nails; Raynaud Disease; Scleroderma, Systemic; Vasodilation; Vasodilator Agents

In patients with systemic sclerosis or mixed connective tissue disease (MCTD) acral ulcers are considered as frequent manifestations that may lead to amputation and loss of function, respectively, as a result of secondary Raynaud's phenomenon. Thus it is necessary to take advantage of all available medical and supportive measures. Adjuvant treatments such as hyperbaric oxygenation and regional sympathetic block represent interdisciplinary treatment options to improve oxygenation of critical ischemia and analgesia and should be subject of further investigation.

Topics: Adult; Amides; Analgesia, Patient-Controlled; Angiography, Digital Subtraction; Autonomic Nerve Block; Azathioprine; Combined Modality Therapy; Drug Therapy, Combination; Female; Fingers; Humans; Hyperbaric Oxygenation; Iloprost; Infusions, Intravenous; Mixed Connective Tissue Disease; Nifedipine; Prednisolone; Raynaud Disease; Ropivacaine; Skin Ulcer; Vasodilator Agents

A single series of patients affected by systemic sclerosis (SSc) and cyclically treated with iloprost was reviewed in order to evaluate the incidence of digital ulcers (DUs) and to compare the characteristics between the patients with and without this painful and disabling vascular complication. The record charts of 85 SSc patients were revised. Ischemic DUs and scleroderma contracture ulcers were separately considered. Twenty-nine subjects developed ischemic DUs during the course of the disease; whereas, scleroderma contracture ulcers occurred in six subjects. Ischemic DUs were associated with younger age at scleroderma onset, a longer disease duration, a longer time delay from scleroderma diagnosis to iloprost therapy, a bigger skin involvement, the presence of joint contractures, a videocapillaroscopic late pattern, a history of smoking, and of corticosteroids therapy. After the exclusion of four subjects with concomitant peripheral arterial disease, a forward-stepwise logistic regression analysis showed that only four variables, i.e., age at scleroderma onset, delay in beginning iloprost therapy, history of smoking, and presence of joint contractures remained significantly associated with ischemic DUs. In a score reflecting the sum of these four risk factors, the prevalence of ischemic DUs increased progressively from the lowest to the highest value of the score. The predictivity of this model was evaluated by the receiver-operating characteristics curve, with an estimated area under the curve of 0.836 with 95% confidence interval from 0.736 to 0.937. All the patients with scleroderma contracture ulcers were characterized by both diffuse pattern of disease and positivity for anti-Scl70 antibody. In this retrospective study, scleroderma patients with ischemic DUs are characterized by early disease onset, delay in beginning iloprost therapy, smoking habit, and presence of joint contraction. A score reflecting the sum of these factors may be useful to predict the risk of developing ischemic DUs.

Topics: Female; Fingers; Humans; Iloprost; Ischemia; Male; Middle Aged; Raynaud Disease; Risk Factors; ROC Curve; Scleroderma, Systemic; Skin; Ulcer; Vasodilator Agents

We report a patient who developed sudden, bilateral, sensorineural hearing loss during therapeutic use of iloprost for Raynaud's phenomenon. The sudden hearing loss was attributed to iloprost use and completely reversed in eight days with conservative therapy. Iloprost may be a potentially ototoxic drug, causing sudden hearing loss.

Topics: Adult; Hearing Loss, Bilateral; Hearing Tests; Humans; Iloprost; Male; Raynaud Disease; Tinnitus; Vasodilator Agents

Topics: Adult; Capillaries; Female; Hemorrhage; Humans; Iloprost; Nails; Neovascularization, Pathologic; Raynaud Disease; Treatment Outcome; Vasodilator Agents

Topics: Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Iloprost; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Skin Ulcer; Vasodilator Agents

Topics: Aged; Humans; Iloprost; Infusions, Intravenous; Male; Raynaud Disease; Scleroderma, Systemic; Vasodilator Agents

Iloprost is useful in the short-term treatment of severe Raynaud's phenomenon and ischaemic ulcers in patients with systemic sclerosis (SSc), but its long-term effects are largely unknown. The aim of this study was to report long-term outcome (median follow-up 36 months) in a prospective observational study of a cohort of 30 consecutive patients with SSc who received iloprost therapy with maintenance infusions every 3 weeks after an initial cycle of 5 consecutive days. At the end of the observation, compared to the pretreatment point, we observed complete healing of digital ulcers in 19/21 patients (90%), a decrease of the Raynaud's phenomenon visual analogue score from 10/10 (25th-75th percentile 7-10) to 5/10 (4-6.75) ( P <0.001) and, in patients with diffuse cutaneous involvement, of the modified Rodnan skin thickness score from 25.5 (16.5-31.5) to 16 (13.5-20) ( P = 0.02), minimal improvement of the Health Assessment Questionnaire from 0.87 (0.68-1.37) to 0.75 (0.62-1.25), which was neither statistically nor clinically significant. The forced vital capacity was not significantly changed, but the diffusion capacity corrected for the alveolar volume decreased from 71% (54-76.7) of the expected value to 62% (51.5-71) ( P = 0.02). In one patient with limited SSc a positive effect on pulmonary hypertension was observed. Six patients, after a median of 25 months of treatment and healing of digital ulcers, discontinued the therapy; after a median of 10 months ulcers did not recur in five of these six. Other reasons for discontinuation were: tolerability (1), disease progression (normotensive renal crisis: 1), and death due to intracranial haemorrhage (1). This same patient had previously suffered a central retinal vein thrombosis. In conclusion, long-term therapy with iloprost in patients with SSc has a durable effectiveness on ischaemic ulcers and Raynaud's phenomenon, but it is not possible to conclude that the natural history of the disease was modified.

Topics: Adult; Aged; Cohort Studies; Female; Fingers; Humans; Hypertension, Pulmonary; Iloprost; Ischemia; Longitudinal Studies; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Raynaud Disease; Respiratory Function Tests; Scleroderma, Systemic; Skin; Ulcer; Vasodilator Agents

A 37-year-old man with ischaemic finger necrosis and recent-onset Raynaud's phenomenon associated with cocaine abuse is reported. Initial therapy with systemic vasodilators, low-molecular-weight heparin and aspirin failed. Resolution of the ischaemia and ulcer healing was rapidly achieved with intravenous infusions of the prostacyclin analogue iloprost. The mechanism of vascular ischaemic injury and the development of secondary Raynaud's phenomenon due to cocaine use is discussed.

Topics: Adult; Cocaine-Related Disorders; Fingers; Follow-Up Studies; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Necrosis; Raynaud Disease; Risk Assessment

A 25-year-old woman with progressive Raynaud's phenomenon and digital necrosis is presented. Systemic sclerosis and other connective tissue disorders as well as atherosclerosis and arterial emboli were excluded with appropriate laboratory examinations. Arteriography revealed multiple palmar and digital occlusions with corkscrew-shaped vessels. Based on these characteristic arteriographic and clinical findings, the diagnosis of thromboangiitis obliterans was finally retained. With intravenous perfusion of the prostacyclin analogue iloprost (2 ng/kg/min, 6 h daily during 21 days), a complete healing of Raynaud's phenomenon and of the digital necrosis was observed. There was no recurrence during the 1-year follow-up. This observation demonstrates that thromboangiitis obliterans is a potential reversible cause of severe Raynaud's phenomenon in young women even in the absence of lower limb involvement. Early recognition is important to avoid irreversible complications such as loss of digits.

Topics: Adult; Female; Fingers; Humans; Iloprost; Raynaud Disease; Skin Diseases, Vascular; Thromboangiitis Obliterans

Currently available drug therapies for patients suffering severe ischaemia with rest pain and trophic lesions of the limbs remain unsatisfactory. Also vascular reopening procedures are suitable in only about half of the patients. In atherosclerotic disease when the vascular endothelium is damaged prostacyclin synthesis is decreased and thromboxane A2 production increases. Prompted by this knowledge of the importance of prostacyclin in pathogenesis of atherosclerotic disease an attempt was made to employ PGI2 clinically--for treatment of advanced forms of peripheral arterial atherosclerotic disease. Favourable effects of the stable analogue of prostacyclin (Iloprost), were reported in various studies, which included patients with peripheral atherosclerotic arterial disease, thromboangiitis obliterans and Raynaud's phenomenon. The use of Iloprost resulted in a significantly superior response than other drugs and placebo in terms of alleviation of rest pain, ulcer healing and decrease of amputation rate of ischaemic limbs. Therefore prostacyclin provides a therapeutic option in patients with advanced forms of arterial disease--including critical ischaemia.

Topics: Arteriosclerosis; Epoprostenol; Extremities; Humans; Iloprost; Ischemia; Raynaud Disease; Thromboangiitis Obliterans

Topics: Adjuvants, Immunologic; Adult; Anticoagulants; Antidepressive Agents, Second-Generation; Depressive Disorder; Drug Therapy, Combination; Female; Fluoxetine; Heparin; Humans; Iloprost; Interferon beta-1a; Interferon-beta; Multiple Sclerosis, Relapsing-Remitting; Raynaud Disease; Vasodilator Agents

Topics: Aged; CREST Syndrome; Female; Humans; Iloprost; Masseter Muscle; Pain; Platelet Aggregation Inhibitors; Raynaud Disease; Scleroderma, Systemic; Vasodilator Agents

Topics: Aged; Female; Fingers; Follow-Up Studies; Gangrene; Humans; Iloprost; Raynaud Disease; Treatment Outcome; Vasodilator Agents

Topics: Alprostadil; Angiotensin-Converting Enzyme Inhibitors; Cold Temperature; Humans; Iloprost; Microcirculation; Microscopic Angioscopy; Outcome Assessment, Health Care; Raynaud Disease; Regional Blood Flow; Scleroderma, Systemic; Vasodilator Agents

Topics: Adult; Aged; Calcium Channel Blockers; Diagnosis, Differential; Female; Humans; Iloprost; Male; Middle Aged; Nifedipine; Raynaud Disease; Sympathectomy; Vasodilator Agents

Topics: Administration, Oral; Drug Approval; Humans; Iloprost; Infusions, Intravenous; Raynaud Disease; United States

The authors have evaluated the effects of long-term treatment of digital vasculitis secondary to various types of connective tissue disease, Systemic Lupus Erythematosus (SLE), Progressive Systemic Sclerosis (PSS), Sjögren's Syndrome (SS), using iloprost. The drug has proven to be effective both in reducing pain and clinical symptoms induced by vasospastic phenomena, as well as in promoting the healing of serious acral ischemic lesions. In the patient with LES, clinical modifications of the local vasculitic phenomena have been associated with a contemporaneous remission of the disease. The persistence of the drug's clinical effects even after suspension of treatment, instrumental and biohumoral changes and concomitant systemic effects on the disease lead to the conclusion that the drug's effect, is not merely due its vasodilating action and its ability to interfere with the coagulative process, but rather must be sought within the context of a morpho-structural repair of the microcirculation.

Topics: Adult; Aged; Connective Tissue Diseases; Drug Tolerance; Female; Fingers; Humans; Iloprost; Middle Aged; Raynaud Disease; Vasculitis

One of the most appealing current pathogenetic concepts is that progressive systemic sclerosis (PSS) is a reaction to repeated episodes of endothelial cell injury. Injury of small arteries and capillary endothelium initiates reactions which involve increased permeability of the vessels, platelet adherence, myointimal cell proliferation, luminal narrowing and heightened sensitivity of the vessel wall. Clinical evidence of the vessel damage is Raynaud's phenomenon, involving both skin and viscera. The Authors evaluated the effects of iloprost on Raynaud's phenomenon in patients with PSS. This drug provides prolonged vasodilation, reduces platelet aggregation and promotes endothelial lining function repair. This last pattern is of primary importance because it may stop the vicious circle: endothelial injury-platelet hyperaggregation-microangiospasm. Five females were recruited, aged 41-66 years, suffering from well-documented (ARA criteria) PSS, associated with typical Raynaud's phenomenon. The trial provided for intravenous infusion of iloprost at a rate of 1-2 ng/kg/min. First treatment consisted of six-hour infusions on six successive days. After this first treatment, weekly infusions during the winter months were carried on. Drug effectiveness was considered through subjective and objective parameters. All patients showed prominent reduction of number, duration and severity of attacks of Raynaud's phenomenon, improvement of prehensile strength, healing of finger ulcerations and improvement or normalization of digital photoplethysmography. So far, the treatment has been prolonged for years in our patients and still goes on. The side effects of iloprost (headache, flushing, nausea) have been very poor. Therefore, iloprost proved to be a valid drug in the management of Raynaud's phenomenon in patients with PSS, but the inconvenience of intravenous administration may limit its routine use.

Topics: Adult; Aged; Female; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Photoplethysmography; Raynaud Disease; Scleroderma, Systemic; Time Factors

One hundred and twenty seven patients who had Raynaud's attacks secondary to connective tissue disease received intravenous infusions of iloprost in controlled clinical trials. Results of previous treatments for Raynaud's attacks had been recorded by clinicians in 84 of these cases, allowing a comparison to be made with the response to iloprost treatment. Iloprost was reported by the patients as beneficial in 49 (58%) of 84 cases, whereas only 36 (43%) of the 84 patients had previously found any other treatment to be useful. Twenty four of 48 (50%) patients who had not responded to any previous treatment found iloprost to be of benefit. Success or failure of treatment with iloprost was not accurately predicted by the result of treatment with any other drug, except prostacyclin. This survey suggests that iloprost is a useful treatment for patients with severe secondary Raynaud's phenomenon and can be effective in patients unresponsive to other treatments.

Topics: Connective Tissue Diseases; Humans; Iloprost; Infusions, Intravenous; Nifedipine; Raynaud Disease; Retrospective Studies

Topics: Cardiovascular Agents; Epoprostenol; Extremities; Humans; Iloprost; Ischemia; Raynaud Disease

Thirteen patients with Raynaud's phenomenon secondary to systemic sclerosis received three 8-hour infusions of a synthetic prostacyclin analogue (Iloprost) on consecutive days and were followed-up over a period of 10 weeks during the winter of 1985/86. Six weeks after infusion, digital peripheral vascular resistance had fallen (P less than 0.05) and dicrotic notch proportion of pulse amplitude increased (P less than 0.05). Digital blood flow and pulse amplitude (measured by photoplethymography) were also increased but did not reach statistical significance. The trend of improvement in these blood flow parameters was still evident after 10 weeks. The number of cutaneous lesions (digital ulcers, etc) fell from 26 lesions before infusion to only 7 lesions by the end of the study, confirming the subjective improvement reported by the patients.

Topics: Adult; Cardiovascular Agents; Epoprostenol; Female; Fingers; Humans; Iloprost; Infusions, Intravenous; Male; Microcirculation; Middle Aged; Raynaud Disease; Regional Blood Flow; Scleroderma, Systemic; Vascular Resistance

Vascular prostacyclin (PGI2) regulates platelet function and blood flow. In systemic sclerosis (SS) there is increased platelet aggregation (PA) but no information is available on the platelet/PGI2 relationship. We evaluated platelet sensitivity to a PGI2 analogue ZK36374 in 17 SS patients and 18 controls. The percentage (%) inhibition of PA was measured at two doses of ZK36374 with saline giving the 100% baseline. In the SS group 2 ng ZK36374 produced a percentage inhibition of 19 + 14 compared to a control value of 60 + 21, and 3 ng a percentage inhibition of 47 + 21 in the SS group and 82 + 20 in the controls. In 11 SS patients treated with either prostaglandin E or nifedipine the sensitivity approached normal. These data suggest that SS platelets are less sensitive to the inhibitory effect of PGI2 on PA. This may contribute to the vascular lesions of SS. Other cells are resistant to the effects of PGI2 and our findings support this picture of cellular resistance.

Topics: Adult; Dinoprostone; Dose-Response Relationship, Drug; Epoprostenol; Humans; Iloprost; Middle Aged; Nifedipine; Platelet Aggregation; Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Raynaud Disease; Scleroderma, Systemic