Iloprost Infusion Research Articles

Thromboangiitis Obliterans (Buerger's Disease): A Young Woman's Rare Case and Current Knowledge

AbstractIn this paper, we described the clinical features and the typical vascular imaging picture of a rare case of thromboangiitis obliterans (TAO) in a 47-year-old, young, Caucasian woman without relevant medical records except for smoking habits and admitted to our Department of Internal Medicine with a necrotic lesion of the first and third toes of the right foot. After a rapid clinical and instrumental evaluation, necrotic tissue debridement was performed and the patient was treated with Iloprost infusion and antibiotics (for overlapping infection) with clinical improvement. Moreover, we summarized the current knowledge about the disease making an update and critical examination of the literature. TAO, also known as Buerger's disease, is a rare disease. In recent decades, the incidence of TAO has decreased in Europe and the United States in men but several studies have reported an increase in the prevalence of disease in women. TAO is a segmental nonatherosclerotic inflammatory disorder that involves primarily small and medium arteries, veins, and nerves of the extremities with limb ischemia, pain, claudication, ulcers, and necrosis that can lead to amputation. Smoking is considered the main risk factor, but despite that, more than 100 years have passed since the first description of the disease by Leo Buerger, and knowledge on pathogenesis, precipitating factors, and therapy remain still unclear.

Iloprost and Organ Dysfunction in Adults With Septic Shock and Endotheliopathy

Soluble thrombomodulin is a marker of endotheliopathy, and iloprost may improve endothelial function. In patients with septic shock, high plasma levels of soluble thrombomodulin (>10 ng/mL) have been associated with worse organ dysfunction and mortality. To assess the effects of treatment with iloprost vs placebo on the severity of organ failure in patients with septic shock and plasma levels of soluble thrombomodulin higher than 10 ng/mL. This investigator-initiated, adaptive, parallel group, stratified, double-blind randomized clinical trial was conducted between November 1, 2019, and July 5, 2022, at 6 hospitals in Denmark. The trial had a maximum sample size of 380, with an interim analysis for futility only at 200 patients with 90 days of follow-up. In total, 279 adults in the intensive care unit (ICU) with septic shock and endotheliopathy were included. Patients were randomized 1:1 to masked intravenous infusion of iloprost, 1 ng/kg/min (n = 142), or placebo (n = 137) for 72 hours. The primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score in the ICU adjusted for trial site and baseline SOFA score for the per-protocol population. SOFA scores for each of the 5 organ systems ranged from 0 to 4, with higher scores indicating more severe dysfunction (maximum score, 20). The secondary outcomes included serious adverse reactions and serious adverse events at 7 days and mortality at 90 days. Of 279 randomized patients, data from 278 were analyzed (median [IQR] age, 69 [58-77] years; 171 (62%) male), 142 in the iloprost group and 136 in the placebo group. The trial was stopped for futility at the planned interim analysis. The mean [IQR] daily SOFA score was 10.6 (6.4-14.8) in the iloprost group and 10.5 (5.9-15.5) in the placebo group (adjusted mean difference, 0.2 [95% CI, -0.8 to 1.2]; P = .70). Mortality at 90 days in the iloprost group was 57% (81 of 142) vs 51% (70 of 136) in the placebo group (adjusted relative risk, 1.12 [95% CI, 0.91-1.40]; P = .33). Serious adverse events occurred in 26 of 142 patients (18%) for the iloprost group vs 20 of 136 patients (15%) for the placebo group (adjusted relative risk, 1.25 [95% CI, 0.73-2.15]; P = .52). Only 1 serious adverse reaction was observed. In this randomized clinical trial of adults in the ICU with septic shock and severe endotheliopathy, infusion of iloprost, 1 ng/kg/min, for 72 hours did not reduce mean daily SOFA scores compared with placebo. In a clinical context, administration of iloprost will be unlikely to improve outcome in these patients. ClinicalTrials.gov Identifier: NCT04123444.

Evaluation of changes in cardiac longitudinal strain rate in patients with systemic sclerosis undergoing iloprost treatment: an observational study.

Systemic Sclerosis (SSc) is characterized by widespread microangiopathy and fibrosis of skin and visceral organs. Left ventricle involvement is usually subclinical, characterized by systolic and/or diastolic dysfunction. The global longitudinal strain (GLS), a validated and reliable technique for the measurement of ventricular longitudinal deformation by means of echocardiography, may detect subclinical systolic dysfunction of SSc myocardium. The improvement of myocardial perfusion by means of intravenous Iloprost administration could ameliorate the contractility of SSc heart. Therefore, we aimed to evaluate GLS in a series of SSc patients prior and after Iloprost infusion. Fifteen consecutive SSc patients (age: 54 ± 11 years; 12 females) treated with Iloprost because of the presence/history of digital ulcers underwent echocardiography, including GLS technique. This evaluation was conducted immediately before Iloprost administration and at the end of the 6-h infusion session. Significant improvement in the mean GLS was observed after Iloprost administration (from -13.5 ± 2.5 to -15 ± 3.3; p= 0.011). The echocardiographic data obtained from the four-chamber view showed the best quality for GLS analysis and showed a highly significant improvement of the strain after Iloprost administration (from -13.4 ± 2.2 to -15.6 ± 3; p= 0.001). The degree of GLS improvement did not correlate with any SSc parameters. Iloprost administration improved GLS, suggesting that the increase of myocardial perfusion allowed, at least in part, a correction of left ventricular systolic dysfunction. Further studies are needed to confirm these findings, further exploring the mid/long-term effects of Iloprost on myocardial contraction.

#2421 Kidney injury in scleroderma: serum level of fibroblast growth factor-23, klotho and neutrophil gelatinase-associated lipocalin after iloprost infusion

Abstract Background and Aims Systemic sclerosis (SSc) is characterized by progressive derangement of the microcirculation leading to a state of chronic tissue hypoxia with release of several inflammatory cytokines such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Renal scleroderma associated-vasculopathy is characterized by vascular damage with normal renal function and increased intrarenal stiffness, assessed by renal resistive index (RRI) Aim of this study was to evaluate at baseline serum levels of FGF-23, Klotho and NGAL in SSc patients and healthy controls (HC) and to correlate the serum levels of these markers with microvascular damage of skin and kidney. Secondary aim was to evaluate the serum levels of FGF-23, Klotho and NGAL after Iloprost infusion. Method Twenty-one SSc patients and 20 HC were enrolled. All patients had a 2-months wash-out of Iloprost infusion before of clinical, laboratory and instrumental assessment. Peripheral venous blood was collected at three different time points for SSc patients: t0 immediately before the first Iloprost infusion (after 2-months wash-out period), t1 immediately after the first Iloprost infusion and t2 the day of the next Iloprost infusion (about 14 days from the last infusion). Results SSc patients had higher serum level of FGF-23 [18.7 pg/mL (± 6.4) vs 3.6 pg/mL (± 2.2), p < 0.001], Klotho [5.1 pg/mL (±0.8) vs 2.3 pg/mL (±0.6), p < 0.001] and NGAL [20.9 pg/mL (±2.6) vs 14.5 pg/mL (±1.7), p < 0.001] compared to HC. The one-way repeated-measures ANOVA showed that mean FGF-23 [F (2,40) = 71.255, p < 0.001], Klotho [F (1.405, 28.103) = 195.095, p < 0.001] and NGAL [F (2,40) = 48.024, p < 0.001] differed significantly between time points. Conclusion SSc patients had higher FGF-23, Klotho and NGAL than HC. Our present data demonstrate that microvascular damage is associated to chronic hypoperfusion with increased circulating markers such as FGF-23, Klotho and NGAL. For the first time, we demonstrated that Iloprost infusion reduces significantly serum level of FGF-23, Klotho and NGAL and it has showed to be a key role in renal vasculopathy in SSc patients. In literature, there are no data about the modification of these serum markers before and after vasoactive treatment, especially of Iloprost infusion.

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

IntroductionSystemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost.MethodsTwenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2).ResultsSSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC.Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2.ConclusionsSSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL.

Long peripheral catheters for intravenous infusions of iloprost or alprostadil therapy in rheumatologic outpatients.

Long peripheral catheters (LPCs) role in Difficult IntraVenous Access (DIVA) patients admitted to the emergency department has already been studied, resulting in a rapid, safe, and cost-effective procedure. Although their use in outpatient settings is established, there is a lack of studies assessing their benefits. In particular, rheumatologic outpatients affected by scleroderma, especially those affected by digital ulcers, are often treated with intravenous infusions of prostaglandin I2 (PGI2) analog (IV-PGI2A). From 1 October 2021 to 31 March 2024, we conducted a prospective study enrolling DIVA outpatients affected by systemic sclerosis or undifferentiated connective tissue disease who needed IV-PGI2A therapy at L. Sacco Hospital in Milan (Italy). Each treatment cycle consisted of four consecutive days of infusion of iloprost or alprostadil. The primary aim was to assess the efficacy and potential complications associated with LPCs for IV-PGI2A. Twenty-six patients were enrolled 23 were females (88.5%), and the median age was 72 years (IQR 56-78.7). In total, 97 LPCs were inserted, with a mean number of insertions per patient/year of 2.3. An increase in LPCs insertion during the 30 months of the enrollment period was observed. Eighteen patients required more than one LPC placement, and in 61% of them, the second venipuncture was executed at a different site. No procedural complications were registered (accidental puncture of the brachial artery, accidental median nerve puncture, bleeding) nor late complications (Catheter-Related Thrombosis, Catheter-Related Bloodstream Infections, Accidental Removal). Our experience shows that LPCs could be valuable and safe for rheumatologic outpatients. The increased number of insertions and new and total patients enrolled each year defines the satisfaction of patients and health care professionals.

Prevention of Delayed Graft Function in Kidney Transplant Recipients through a Continuous Infusion of the Prostaglandin Analogue Iloprost: A Single-Center Prospective Study.

Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. This prospective, randomized (1:1), placebo-controlled study enrolled all consecutive patients who received a kidney transplant from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin analogue iloprost at 0.27 μg/min through an elastomeric pump (treatment group) or with a placebo (control group). A total of 476 patients were included: DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that the donor's age > 70 years (OR 2.50, 95% confidence interval (CI): 1.40-3.05, p < 0.001), cold ischemia time > 24 h (OR 2.60, 95% CI: 1.50-4.51, p < 0.001), the donor's acute kidney injury (OR 2.71, 95% CI: 1.61-4.52, p = 0.021) and, above all, the recipient's arterial hypotension (OR 5.06, 95% CI: 2.52-10.1, p < 0.0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p < 0.001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.5 ± 8.3 vs. 13.4 ± 6.7, days, p = 0.016). This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased-donor kidneys, allowing a better graft functionality as well as a better graft survival.

EFFICACY AND SAFETY OF INTRAVENOUS ILOPROST IN THE TREATMENT OF RAYNAUD’S PHENOMENON AND DIGITAL ULCERS IN PATIENT WITH SYSTEMIC SCLERODERMA

Objectives: To evaluate the efficacy and safety of intravenous iloprost in the treatment of Raynaud’s phenomenon and digital ulcers in patients with SSc (systemic scleroderma).Methods: 31 patients with SSc were treated with intravenous iloprost in NHDV from April, 2017 to March, 2020. Evaluation was done after 2 weeks and included: width of ulcer, depth of ulcer, Raynaud phenomenon, laboratory tests, drug side effects.Results: VAS of Raynaud’s syndrome decreased markedly after iloprost infusion, from 71.5 points to 36.9 points. (p &lt; 0.001). The depth of ulcer improved markedly after 2 weeks of treatment, the rate of deep ulcers decreased from 20.6% to 1% (p &lt; 0.001). The ulcer width improved significantly after 2 weeks of treatment, the rate of grade 3 ulcers decreased from 35.1% to 13.4% (p &lt; 0.001). Side effects were found in 38.7% of patients, mainly headache (25.7%), flushing (9.7%); nausea/vomiting (6.5%); reaction at the site of infusion (6.5%). All side effects disappear when the infusion rate reduced. The majority of patients tolerated the drug at the maximum infusion rate (level 4), accounted for 61.3%.Conclusion: Intravenous iloprost is an effective and safe drug in the treatment of Raynaud’s phenomenon and digital ulcers in patients with SSc. The infusion process should be monitored according to the instructions.

P027 Immune checkpoint inhibitor associated vasculitis: a limitation to cancer therapy

Abstract Background/Aims The increasing use of immune checkpoint inhibitors (ICIs) underlies the importance of close monitoring and recognition of associated adverse events. We report a rare case of nivolumab-related peripheral vasculitis with digital gangrene and auto-amputation in a patient treated for mesothelioma. Methods A 69-year-old male with T4M0N0 pulmonary sarcoid mesothelioma was commenced on second-line Nivolumab therapy. 11 days later, he presented with worsening dyspnoea and dry cough. CTPA demonstrated new bilateral lower zone and peripheral predominant ground glass patchy consolidation consistent with acute pneumonitis. He sustained a significant clinical benefit from IV methylprednisolone and cessation of Nivolumab. 20 days after the pneumonitis episode, the patient re-presented with extremely tender, blue-black discoloration of the 2nd, 3rd and 4th fingers bilaterally, accompanied by localised sensory loss. Petechiae were also seen distributed across the digital pulp and nailbeds. Although bilateral, the left side was notably worse, with clear evidence of digital ischaemia and dry gangrene. Urine dipstix was bland. Immunology revealed normal C3/C4, ANCA and dsDNA serology, but mildly raised ANA (1.5). An echocardiogram excluded infective emboli. High dose IV methylprednisolone and iloprost infusion was commenced to treat ICI-associated peripheral vasculitis. Concurrently, dalteparin was required for a non-occlusive right subclavian venous thrombus. Nevertheless, his digital ischaemia progressed proximally to the left middle distal phalanx. MDT decision was made to avoid Cyclophosphamide given the infection risk. Sildenafil was introduced alongside a reduction regime of oral prednisolone. Unfortunately, the patient was subsequently hospitalised for acute PCP infection requiring high flow oxygen and intravenous antimicrobials. Following this stormy course, a slow but consistent and substantial clinical improvement was noted with respect to his digital ischaemia with minimal tissue loss. 7 months on, the patient’s digits remain free from ischaemia, infection and pain with good functional ability on Sildenafil treatment. Results Reports of PD-1 blockade-associated vasculitides mention ANCA-vasculitis, IgA vasculitis, leukocytoclastic vasculitis, eGPA and granulomatous vasculitis; however, drug-induced digit necrosis and auto-amputation is not widely reported. In this rare presentation of digital gangrene, immediate discontinuation of nivolumab treatment with initiation of high dose steroids and sildenafil, allowed eventual recovery of digits with limited auto-amputation and minimal sequelae. Management of nivolumab-associated vasculitis and pneumonitis required a multidisciplinary approach involving oncology, rheumatology, plastics and respiratory medicine. In the context of nivolumab discontinuation, the patient remains only on symptomatic treatment and follow up with no active cancer therapy meaning that prognosis is poor, in keeping with other reports of vasculitic reactions to nivolumab in cancer patients. Conclusion ICIs have revolutionised the management and outcomes across a range of malignancies. However, their mechanism can inadvertently induce undesired toxicity, the awareness of which is paramount. Disclosure M. Au: None. A. Faher: None. E. Htut: None.

E082 A review of the development of gangrene in patients with systemic lupus erythematosus: a 44-year follow-up study

Abstract Background/Aims Gangrene is a well-recognised complication of diabetes, peripheral arterial disease, frostbite and meningococcal disease amongst other conditions but is rare in patients with systemic lupus erythematosus [SLE]. Most reports describe individual patients and the prevalence in cohorts is very scarce. In 2008, our group reported five patients who had developed digital gangrene and two patients with “near gangrene”. We reviewed all the SLE patients seen in our lupus clinic between January 1978 and June 2022.The main goal was to address the prevalence and identify the possible trigger factors, aiming to find common clinical and serological features. We have also reviewed the acute and long-term management of gangrene in these patients as well as their long-term outcome. Methods We reviewed 820 patients with SLE attending the SLE Clinic in our UK tertiary referral center, followed up over 44 years, assessing demographics, clinical and serological features, treatment in the acute phase, outcome and long-term management. Results Eight out of 820 patients (0.97%) have developed gangrene. The age of onset of disease ranged from 12 to 26 years (mean 17.5 years, SD 4.609). The first episode of gangrene ranged from between presentation to 27 years after SLE onset, with a mean duration of SLE at the onset of the gangrene of 15.5 years (SD 11.711). All had active SLE at the time of critical peripheral ischaemia and anti-phospholipid (PL) antibodies were present in five out of the eight reported patients. The acute treatment was intravenous (IV) iloprost infusions with antiphospholipid-positive patients being anti-coagulated, most staying on long term anticoagulation therapy. The possible identified triggers (such as infection and cancer) were treated accordingly. Two patients did not respond to the initial treatment and needed further immunosuppression. All of these patients suffered digit loss. Conclusion Gangrene is a rare complication of SLE in patients with active disease but potentially able to cause severe damage. Anti-phospholipid antibodies are overrepresented in these patients but infection and cancer are other possible contributors. Anticoagulation therapy, steroids and iloprost are the first line therapy but in non-responders further immunosuppression may be needed to stop the evolution of gangrene. Disclosure J. Rua: None. D. Isenberg: Honoraria; Servier, Anges, Astrazeneca, UCB, Eli Lilly.

E004 Inpatient admission pathway for patients with rheumatological disorders

Abstract Background/Aims Rheumatology is a complex specialty covering many conditions of varying severity, from muscle pain through inflammatory arthritis such as Rheumatoid arthritis (RA) and connective tissue diseases. Most of the conditions can be managed in an outpatient/day case setting. However, acutely ill patients require safe and prompt inpatient management including specific intravenous infusions. This need to be done urgently and cannot wait to be accommodated through the Infusion unit at our hospital. Historically Medicine Acute Admission Unit has been the route to bring in these patients. However, operational bed pressures faced challenges leading to instances of delayed treatment with complications including fatality. This led to creating a direct inpatient admission pathway to the specialist ward. Methods Ward Matron designed the following robust pathway for direct patient admission to our specialist Rheumatology ward, Jevington ward. This was implemented in February 2022 after discussion and agreement with Clinical Lead consultant, pharmacist, clinical site managers and other colleagues. Rheumatology team and nurses covered the ward during working hours and by the on-call team out of hours. The overall responsibility remained with the rheumatology team. The referrals accepted only after completing appropriate paperwork. Patients carried out Lateral Flow Test (LFT) at home prior to admission. We ensured negative results and followed the Trust COVID 19 screening protocols. Subsequent screenings were done according to the updated guidelines. The planned assessment and treatments were carried out by the ward team complying with BSR/EULAR Guidelines, infusion protocols such as standard and continuous Iloprost Infusion Protocols of the Trust. Results We assessed the delay in patient's admission, length of stay, patient outcome and experience after implementing the pathway. The significant change has been in the time to admit; from two weeks in 2018 &amp; 19 to two days this year. This is reflected in the patient feedback. All our acutely ill patients were assessed, treated and discharged promptly on this specialist ward. Conclusion This pathway allowed safe and prompt treatment, prognosis and excellent experience for acutely ill patients with rheumatological disorders. This additionally enabled reduced length of stay supporting financial sustainability of the Trust. Disclosure S. Panthakalam: None.

A new digital health tool for the telemonitoring of patients with scleroderma during iloprost administration: a feasibility and acceptability study.

To assess the feasibility of a new device for telemonitoring vital parameters during iloprost infusion. In a pilot study, patients with systemic sclerosis received iloprost infusion while being telemonitored with Umana T1 Heart Monitor, within the hospital, under the supervision of family/community nurses and rheumatologists. Patients were administered a questionnaire to obtain information on satisfaction, practicability, and compliance with the new monitoring device. Data recorded by the device for blood pressure, heart rate, and oximetry were concordant with those registered directly by nurses. Most patients found the device useful and thought it could be used at home, even while working. Umana Heart Monitor T1 could be a valuable aid in at-home iloprost therapy in patients with systemic sclerosis.

Radial arterial thrombosis in COVID-19: A case report

Thrombosis due to hypercoagulable state is an important cause of morbidity and mortality in coronavirus disease 2019 (COVID-19). . Increased D-dimer levels are an important marker of the presence and risk of thrombosis. In this report, we present that a 59-yearold male patient developed thrombosis in the distal radial arteries despite normal D-dimer level. The patient was treated with enoxaparin, iloprost infusion, and cilostazol. This

Radial arterial thrombosis in COVID-19: A case report

Thrombosis due to hypercoagulable state is an important cause of morbidity and mortality in coronavirus disease 2019 (COVID-19).&#x0D; Increased D-dimer levels are an important marker of the presence and risk of thrombosis. In this report, we present that a 59-yearold&#x0D; male patient developed thrombosis in the distal radial arteries despite normal D-dimer level. The patient was treated with&#x0D; enoxaparin, iloprost infusion, and cilostazol. This case should lead us to be very careful that people diagnosed with COVID-19 with&#x0D; normal D-dimer levels may also have thrombosis.

OA04 Paediatric APS - children are not just small adults

OA04 Paediatric APS - children are not just small adults

OA17 An evolving case of Anti PM/Scl Anti body associated Aggressive Systemic Sclerosis

OA17 An evolving case of Anti PM/Scl Anti body associated Aggressive Systemic Sclerosis

Effectiveness of intravenous prostaglandin to reduce digital amputations from frostbite: an observational study

We assessed the effectiveness and safety of a 5-day intravenous prostaglandin (iloprost) protocol at reducing digital amputation for patients with severe frostbite injuries at urban emergency departments. This retrospective study examines consecutive patients who presented to Calgary emergency departments from April 2017 to April 2020 with Grade 2-4 frostbite injuries. Patients from February 2019 onward were managed using a 5-day iloprost infusion protocol, whereas patients prior to this time were managed with standard care (local best practice without iloprost as a therapeutic option). The primary effectiveness outcome was rate of affected digits amputated, stratified by frostbite severity. The secondary safety outcome was the incidence of serious adverse events associated with iloprost (allergic reactions or symptomatic hypotension requiring treatment or discontinuation of the infusion). 90 patients were included, 26 were treated with iloprost, compared to 64 patients who received usual care. Both the treatment and usual care groups experienced substantial rates of homelessness and substance use. No digital amputations were required for patients with Grade 2 injuries in either group, but significantly lower digital amputation rates were observed for patients with more severe frostbite injuries treated with iloprost versus usual care: Grade 3 (18% vs 44%, p < 0.001), Grade 4 (46% vs 95%, p < 0.001). No serious adverse events were associated with iloprost. In this unselected socially complex urban population, administration of iloprost for patients with frostbite was shown to be safe and was associated with lower digital amputation rates, particularly for those with more severe injuries.

Sudden winter iloprost withdrawal in scleroderma patients during COVID-19 pandemic.

IntroductionIntravenous 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.MethodsA 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.ResultsThe 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.ConclusionsLow capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients.

Iloprost Duration for Digital Ulcers in Systemic Sclerosis: French Retrospective Study at Two Centers and Literature Review.

ObjectiveIschemic digital ulcers (DUs) are frequent and severe complications of systemic sclerosis (SSc). Treatment options for SSc-related digital vasculopathy are based on aggressive vasodilation, with the objective to improve blood flow in ischemic areas. Intravenous prostanoids are recommended to treat active DUs. However, the level of evidence for the duration of 5 days is low. Therefore, the aim of this study was to determine whether prolonging the infusion beyond 5 days increases the rate of healing of active DUs in SSc.MethodsThis is an observational longitudinal retrospective bicenter study from 2000 to 2017. The objective was to compare the healing rate and time (defined by a healing of at least 50% of DUs) between two durations of iloprost administration: 5 days or less, or more than 5 days.ResultsForty-one patients, with a mean age of 47 ± 15 years at diagnosis and 32 (78%) females have been included. Systemic sclerosis was diffuse in 10 (24%) cases and 13 (32%) had an interstitial lung disease. A total of 243 iloprost infusions for DUs were performed: 140 infusions for 5 days or less, and 103 infusions for more than 5 days (prolonged duration). Patients with active DUs which received >5 days of iloprost had higher modified Rodnan skin scale at the time of iloprost infusion (median 33 vs. 15; p < 0.05), more interstitial lung disease (44 vs. 27%; p < 0.05), more anti-topoisomerase I antibody positivity (59 vs. 44%; p < 0.05), and received more previous cyclophosphamide therapy (48 vs. 19%; p < 0.05). While the number of active DUs before iloprost infusion was not significantly different among those who received ≤5 days and >5 days of iloprost, the time to healing after iloprost infusion significantly decreased in SSc patients who received >5 days iloprost infusion: 48 [7–392] vs. 91 [9–365] days (p < 0.05). The proportion of SSc patients with healed DUs tended to increase in patients with >5 days iloprost infusion (log rank = 0.06). The number of patients with complete DU healing at day 90 was significantly increased in SSc who received >5 days of iloprost: 53 (51%) vs. 52 (37%) (p < 0.05). In addition, the time to healing was not significantly associated with the use of calcium channel blockers, endothelin receptor antagonists or a combination of PDE-5 inhibitors.ConclusionProlonging duration of iloprost >5 days could improve the healing rate and the time to healing of SSc-related DUs. Prospective randomized studies are needed to confirm these data and define the optimal duration of iloprost therapy.

Higher body mass index is associated with a lower iloprost infusion rate tolerance and higher iloprost-related adverse events in patients with systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasospasm and microvascular involvement. Iloprost (ILO), a prostaglandin analogous, is used for the treatment of SSc-related Raynaud's phenomenon and digital ulcers. The suggested dose is 0.5-2 ng/kg/min for 6-8 h, and the maximum dose is decided upon the patient's tolerance. This study aims to analyze ILO infusion tolerance and possible predictive factors in patients with SSc. This is a retrospective observational study. We evaluated 113 patients with SSc beginning ILO intravenous (IV) infusion treatment between 2004 and 2021. We assessed the maximum tolerated ILO IV infusion rate, the incidence of adverse events (AEs), and the need for symptomatic therapy during the dose-finding sessions. We collected relevant demographic and medical and employed generalized linear models to assess possible predictors of maximum tolerated ILO infusion rate and AEs and logistic regression to assess predictors of AEs. The median ILO infusion rate at the end of the dose-finding process was 0.88 ng/kg/min [interquartile range (IQR) = 0.37]. We found a significant inverse correlation between ILO infusion rate and body mass index (BMI) at the beginning of treatment. BMI was negatively associated with ILO infusion rate (β = -0.21, p = 0.02) after correction for relevant confounding factors. Overweight patients (BMI >26) presented a 13-fold increased risk of developing AEs during ILO titration [adjusted odds ratio = 13.979, 95% confidence interval (CI) = 2.359-82.845]. AEs during ILO titration occurred in 47.8% of patients, of whom 22.2% presented hypotension. Other AEs were headache, nausea, vomiting, diarrhea, and edema. Symptomatic therapy was needed in half of the patients at least once. This study showed that higher BMI was statistically associated with lower ILO infusion rate tolerance and higher AEs rate, underlying a possible BMI-dependent endothelial dysfunction. Individual ILO regimens still need to be tailored to the patient. Introduction: Systemic sclerosis is a rare a rheumatic disease characterized by skin thickening, vasospasm, and digital ulcers (DUs), as well as other organs involvement. Iloprost, which is administered as intravenous infusion, is one of the main treatments for this disease, and it is effective in reducing vasospasm and the frequency of DUs. Even if there is a suggested dose range, the exact dose must be tailored on each patient, because the tolerance to the drug is variable. Tolerance is limited by dose-dependent unwanted effects, as headache, low blood pressure, dizziness, and sickness. This study aimed to identify possible predictors of such tolerance.Materials and Methods: We collected data from our patients with systemic sclerosis beginning the treatment with iloprost between January 2004 and November 2021 at our hospital facility in Verona, Italy, and analyzed different factors that could be associated with a better tolerance, as age, sex, disease duration, smoking habit, body mass index (a measure of body fatness), blood pressure, concomitant medications, and different patterns of the disease.Results: We found that a higher body mass index was associated with lower iloprost tolerance and higher adverse events rate in patients with systemic sclerosis, while we did not find a correlation with other factors. We believe overweight and obese patients (who have a higher body mass index) have a defect in the vasodilatation mechanism and can therefore be more susceptible to the effect of this medication.Conclusions: While preliminary, our results could provide a good starting point to develop a predictive tool to limit adverse events during this therapy.