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Objective: Raynaud phenomenon (RP) and digital ulcers (DUs) are the main signs of digital vasculopathy in systemic sclerosis (SSc). Selexipag is an oral prostacyclin agonist approved for SSc-related pulmonary arterial hypertension. Following our previous preliminary short-course report, we herein present long-term data on selexipag safety and efficacy in the treatment of SSc digital vasculopathy., Methods: Selexipag was administered to patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies. Each subject was assessed at baseline and after 3, 6, and 12 months. Clinical outcomes related to RP and DUs were evaluated along with modified Rodnan skin score of the fingers. Digital perfusion was assessed by laser speckle contrast analysis (LASCA). Nailfold videocapillaroscopy (NVC) was also performed., Results: Eight patients with SSc (63% female, mean age 50.1 years) received selexipag. After 12 months of treatment, RP was reported to significantly decrease in the number of daily episodes and mean duration ( P < 0.001 and P = 0.01, respectively). All patients achieved a complete healing of their DUs ( P = 0.03) within 6 months. A progressive reduction of fingers skin score was observed ( P = 0.03). No structural changes of capillaries were noted on NVC. Conversely, LASCA revealed an important increase in total digital perfusion ( P = 0.004) despite seasonal variability. The safety profile was consistent with that reported in the literature., Conclusion: We observed a sustained efficacy of selexipag on SSc digital vasculopathy during 1 year of administration. Our promising results encourage the design of a new randomized controlled trial to evaluate the effect of selexipag on SSc digital vasculopathy., (Copyright © 2024 by the Journal of Rheumatology.)

Background: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc., Methods: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed., Results: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found., Conclusion: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice., (© 2024. The Author(s).)

Objectives: We previously reported that heating of the neck or elbows alleviated Raynaud's phenomenon in patients with systemic sclerosis and upregulated capillary extension factor angiopoietin-1 (Angpt-1) in the fingertips. In this study, we investigated which cases responded better to the effect of heating of the neck or elbows., Methods: The pre- to postheating change in the visual analogue scale (ΔVAS) for Raynaud's phenomenon was examined for correlation with age, disease duration, autoantibodies, disease types, corticosteroid dose, capillaroscopic nailfold capillary damage, fingertip Angpt-1 concentrations at baseline, and increased rate of Angpt-1 concentration., Results: The ΔVAS for elbow heating correlated positively with the baseline Angpt-1 concentration, whereas opposite correlation was observed for neck heating. The other items did not significantly correlate with the ΔVAS; however, the ΔVAS for elbow heating tended to be larger in patients with advanced capillary damage, whereas an opposite trend was observed for neck heating., Conclusions: Elbow and neck heating alleviated Raynaud's phenomenon to a similar extent, but their mechanism was different. Heating of the elbows had a greater effect on patients with advanced capillary damage and lower fingertip Angpt-1 concentrations., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objective: To perform a systematic literature review (SLR) aimed at evaluating the efficacy and safety of pharmacological and non-pharmacological treatments for Raynaud's phenomenon (RP) and digital ulcers (DU) in patients with systemic sclerosis (SSc) and other connective tissue diseases (CTD), in order to inform the Portuguese recommendations for managing RP and DU in these patients., Methods: A SLR was conducted until May 2022 to identify studies assessing the efficacy and safety of pharmacological and non-pharmacological interventions for RP and DU in SSc and other CTD. Eligible study designs included randomized controlled trials (RCTs), controlled clinical trials, and their extensions for assessing efficacy and safety of interventions. Observational studies with a comparator were included for evaluating the efficacy and safety of non-pharmacological interventions and safety of pharmacological interventions. The risk of bias of each study was assessed using standard tools., Results: Out of 71 publications meeting the inclusion criteria, 59 evaluated pharmacological and 12 non-pharmacological interventions. We found moderate quality evidence supporting the efficacy of calcium channel blockers, phosphodiesterase-5 inhibitors, and intravenous prostacyclin analogues in reducing RP frequency, severity, and duration. Intravenous iloprost had a small to moderate effect size in improving DU healing. Phosphodiesterase-5 inhibitors were effective in reducing total DU count, new DU occurrence, and enhancing DU healing. Bosentan effectively prevented new DU in SSc patients. No new safety concerns were associated with these treatments. The studies on non-pharmacological interventions were, in general, of low quality, and had a small sample size. Warming measures decreased frequency and duration of RP attacks; laser therapy improved RP-related outcomes; local oxygen-ozone therapy improved RP outcomes as an add-on therapy; bone marrow mononuclear cell implantation improved DU-associated pain; periarterial sympathectomy and vascular bypass reduced DU number and finger amputation risk., Conclusion: The available evidence supports the efficacy and safety of pharmacological interventions, namely nifedipine, sildenafil, iloprost, and bosentan in treating RP and DU in patients with SSc and other CTD. Scarce and low-quality evidence does support the use of some non-pharmacological interventions but with only a modest effect size. This SLR underscores the limited availability of high-quality evidence for determining the optimal treatment.

Objectives: Measurement of digital perfusion, sometimes coupled with a cold challenge, has been widely used as an objective outcome in trials evaluating drug therapies in RP, in addition to patient-reported outcomes or to establish the proof-of-concept in preliminary studies. However, whether digital perfusion is a valid surrogate for clinical outcomes in RP trials has never been explored. The principal aim of this study was to evaluate the potential surrogacy of digital perfusion, by combining individual-level and trial-level data., Methods: We used individual data from a series of n-of-1 trials, and trial data from a network meta-analysis. We estimated individual-level surrogacy through coefficients of determination between digital perfusion and clinical outcomes (R2ind). We further calculated the coefficients of determination between treatment effect on the clinical outcomes and on digital perfusion, at the individual level (R2TEind) and at the trial level (R2trial), using non-weighted linear regression, with their 95% CI calculated through bootstrapping., Results: Results from 33 patients and 24 trials were included in the final analysis. At the individual level, there was no correlation between digital perfusion and clinical outcomes at rest and in response to various cooling tests (the highest R2ind was 0.03 [-0.07, 0.09]), and R2TEind was also very low 0.07 (0, 0.29). At the trial level, the highest value of R2trial was 0.1 (0, 0.477)., Conclusions: Digital perfusion, at rest or in response to a cold challenge, and whatever the method used, does not fulfil the criteria of a valid surrogate for existing patient-reported outcomes in RP trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Juvenile systemic sclerosis (SSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed, but clearly defining appropriate outcomes is necessary if successful therapies are to be developed. Our objective here was to propose such outcomes., Methods: This proposal is the result of 4 face-to-face consensus meetings with a 27-member multidisciplinary team of pediatric rheumatologists, adult rheumatologists, dermatologists, pediatric cardiologists, pulmonologists, gastroenterologists, a statistician, and patients. Throughout the process, we reviewed the existing adult data in this field, the more limited pediatric literature for juvenile SSc outcomes, and data from 2 juvenile SSc patient cohorts to assist in making informed, data-driven decisions. The use of items for each domain as an outcome measure in an open label 12-month clinical trial of juvenile SSc was voted and agreed upon using a nominal group technique., Results: After voting, the domains agreed on were global disease activity, skin, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, and gastrointestinal involvement, and quality of life. Fourteen outcome measures had 100% agreement, 1 item had 91% agreement, and 1 item had 86% agreement. The domains of biomarkers and growth/development were moved to the research agenda., Conclusion: We reached consensus on multiple domains and items that should be assessed in an open label, 12-month clinical juvenile SSc trial as well as a research agenda for future development., (© 2023 American College of Rheumatology.)

We evaluated the predictive value of dynamic blood flow scintigraphy with 99m Tc-HDP (hydroxymethylene diphosphonate) for therapeutic response in patients with Raynaud's phenomenon (RP). Eighty patients who underwent dynamic blood flow scintigraphy using the one-hand chilling method were enrolled. We analyzed the quantitative variables as the ratio of chilled fingers to ambient fingers (CA finger ), that of the chilled hand to ambient hand (CA hand ), and that of chilled fingers to ambient palm (FPR) (CA FPR ) at 15 and 30 s after 99m Tc-HDP bolus injection. Total cumulative radioactivity counts for 180 s were obtained. We evaluated the clinical utility of these quantitative parameters with other clinical variables, including RP severity, therapeutic compliance, types of RP, and scintigraphic interpretation of findings in patients with RP. Fifty-two patients showed poor therapeutic response. There were significant differences between good- and poor-therapeutic responder groups in RP intensity (p = 0.003), CA finger15s (p = 0.008), CA finger30s (p = 0.002), CA finger180s (p = 0.011), CA hand15s (p = 0.008), CA hand30s (p = 0.007), CA hand180s (p = 0.017), CA FPR30s (p = 0.004), and CA FPR180s (p = 0.002). After multivariate logistic regression analysis, only CA finger30s (p = 0.002) had an independent predictive value of the therapeutic response. 99m Tc-HDP dynamic blood flow scintigraphy could be helpful in predicting the therapeutic response in patients with RP., (© 2023. The Author(s).)

Objective: Systemic sclerosis (SSc) is burdened by Raynaud phenomenon (RP) and digital ulcers (DUs), and sometimes standard vasoactive therapies are ineffective or contraindicated. Selexipag is an oral selective IP prostacyclin receptor agonist approved for the treatment of SSc-related pulmonary arterial hypertension. We aimed to evaluate the clinical and instrumental efficacy of selexipag in SSc digital vasculopathy., Methods: Patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies were administered selexipag. RP- and DU-related clinical outcomes were evaluated, and digital perfusion was assessed by laser speckle contrast analysis (LASCA), all at baseline and after 3 months., Results: Selexipag was administered to 9 patients with SSc (66.6% female, mean age 52.3 [SD 16.6] yrs). One patient had to stop the drug because of adverse effects. After 3 months of selexipag administration, there was a significant reduction in RP daily episodes ( P = 0.01) and RP mean duration ( P = 0.04). The number of DUs decreased from 10 to 4 without reaching statistical significance. A significant improvement in mean perfusion of the fingers ( P = 0.02) was observed with LASCA., Conclusion: Selexipag showed good potential for the treatment of SSc digital vasculopathy. Our results are certainly preliminary, yet quite encouraging. New trials for the evaluation of selexipag efficacy in SSc digital vasculopathy are needed., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: Botulinum toxin (Btx) therapy has emerged as a potential treatment for patients with Raynaud phenomenon (RP) in recent years. This study aimed to investigate the efficacy and safety of Btx treatment for RP., Methods: Databases of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception up to August 2022. Studies that reported Btx use for the treatment of RP were included. A meta-analysis was conducted for the Shortened version of the Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score and visual analog scale pain score using a random-effects model., Results: Thirteen full-text studies were included. The pooled standard mean changes for the visual analog scale pain score and QuickDASH score were -3.82 (95% confidence interval, -6.62 to -1.02) and 0.83 (95% confidence interval, -1.47 to -0.19), respectively. The 2 most common complications were injection site pain and intrinsic hand weakness., Conclusions: The effect of Btx treatment on RP is promising based on current evidence. Nevertheless, more studies and randomized clinical trials with larger sample sizes are needed to confirm the current results., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Raynaud's phenomenon describes symptoms caused by digital vascular spasm and is classically induced by cold exposure. Severe cases can result in ulceration, necrosis, and digital autoamputation. When standard and adjunctive medical therapies fail or are contraindicated, botulinum toxin A (BTX-A) is an effective treatment option that can be added to existing regimens and should be considered before utilizing rescue therapies associated with higher risk and often higher cost. This report describes our technique, highlights considerations relevant to pediatric patients, and provides photos and videos of the procedure performed on a 16-year-old girl., (© 2023 Wiley Periodicals LLC.)

This review of the literature highlights the results of the recent randomized controlled trials about the management of systemic sclerosis (SSc) and its complications. The latest randomized studies have failed to demonstrate the utility against placebo of the injections of botulinum toxin A to achieve a better control of Raynaud's phenomenon and the efficacy of the adipose-derived cell transplantation for the treatment of hand dysfunction. Rituximab allows a significant improvement of cutaneous induration. The injections of mesenchymal stromal cells are well tolerated and should encourage future randomized trials to evaluate their efficacy. Finally, nintedanib and tocilizumab allow a reduction in the rate of decline of lung function, as well as a possible stabilization with tocilizumab., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: To determine whether a single session of botulinum toxin type A (BTA) injections into both hands more effectively decreases the frequency of systemic sclerosis-associated Raynaud's phenomenon (SSc-RP) episodes than placebo., Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III trial in patients with SSc-RP assessed the effect of 50-unit BTA or placebo injections into the palms of both hands around each neurovascular bundle during 1 session in winter. The primary end point was the between-group difference in the median change in the number of RP episodes from baseline (day 0) to 4 weeks postinjection. Values between the groups were compared with the Wilcoxon rank-sum test., Results: The intent-to-treat analysis included 46 BTA-treated patients and 44 placebo recipients. At 4 weeks after assigned treatment injections, the median number of daily RP episodes decreased comparably in the BTA and placebo groups (median change -1 episode/day [interquartile range (IQR) -1.5, 0 episodes/day] and -1 episode/day [IQR -2.5, 0 episodes/day], respectively) (P = 0.77 versus placebo). Moreover, change in Raynaud's Condition Score, quality of life assessed by Health Assessment Questionnaire disability index, and hand function assessed by shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Cochin Hand Function Scale from baseline to follow-up weeks 4, 12, and 24 did not differ significantly between groups. The BTA group experienced transient hand muscle weakness significantly more frequently (P = 0.003)., Conclusion: Neither the primary nor secondary end points were reached, and our results do not support any beneficial effect of palmar BTA injections to treat SSc-RP., (© 2022 American College of Rheumatology.)

Background: Substantial placebo response has been observed in trials assessing treatments in Raynaud's Phenomenon (RP), which makes any treatment effect difficult to detect. However, whether this response is due to a real placebo effect or to other nonspecific effects, such as regression towards the mean (RTM), has not been explored. Our objectives were to explore and quantify placebo response in RP, and to evaluate the magnitude of RTM contribution., Methods: We combined trial-level and individual-level data from a series of n-of-1 trials and a network meta-analysis, respectively. Main outcomes were the daily frequency and the mean duration of RP attacks, as well as the Raynaud's Condition Score (RCS). We estimated the placebo response by the mean difference between the placebo period (or arm) and the baseline. RTM was estimated by the relationship between placebo response and baseline, and with Galton squeeze plots. Finally, we simulated the effect of the threshold used for inclusion in clinical trials on RTM., Findings: We observed a large and significant placebo response from both individual and trial data for RCS [-1.20 (-1.63, -0.77) and -0.65 (-0.89, -0.41)] and the daily frequency of RP [-0.61 (-0.85, -0.37) and -0.75 (-0.95, -0.54)]. Outcome at baseline was significantly associated with placebo response, suggesting the presence of RTM. The latter was confirmed on individual data, through Galton squeeze plots., Interpretation: Placebo response is large in RP trials, and likely due to regression towards the mean rather than 'true' placebo effect. This should be carefully considered when designing future trials., Funding: This work has been partially supported by MIAI @ Grenoble Alpes (ANR-19-P3IA-0003)., Competing Interests: Declaration of Competing Interest The authors declare no competing interest for this work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The management of systemic sclerosis (SSc) is complex, evolving, and requires a multidisciplinary approach. At diagnosis and throughout the disease course, clinical assessment and monitoring of skin involvement is vital using the modified Rodnan Skin Score, patient-reported outcomes, and new global composite scores (such as the Combined Response Index for Systemic Sclerosis, which also considers lung function). Immunomodulation is the mainstay of skin fibrosis treatment, with mycophenolate mofetil considered first line. Meanwhile vasculopathy-related manifestations (Raynaud's phenomenon, digital ulcers) and calcinosis, require general measures combined with specific pharmacologic (calcium-channel blockers, phosphodiesterase type 5 inhibitors, and prostanoids), nonpharmacologic (digital sympathectomy and botulinum toxin injections), and often multifaceted, management approaches. Patients should be screened at the time of diagnosis specifically for systemic manifestations and then regularly thereafter, with appropriate treatment. Numerous targeted therapeutic options for SSc, including skin fibrosis, are emerging and include B-cell depletion, anti-interleukin 6, Janus kinase, and transforming growth factor β inhibition. This second article in the continuing medical education series discusses these key aspects of SSc assessment and treatment, with particular focus on skin involvement. It is vital that dermatologists play a key role in the multidisciplinary approach to SSc management., Competing Interests: Conflicts of interest Dr Nikpour has received research grant support from Actelion, BMS, GSK, Janssen, and UCB and honoraria from Actelion, Boehringer Ingelheim, Janssen, Eli Lilly, Pfizer, and UCB. Dr Krieg has received speaking fees from Actelion. Dr Denton reports personal fees or research grants to his institution from GlaxoSmithKline, Galapagos, Boehringer Ingelheim, Roche, CSL Behring, Corbus, Horizon, and Arxx Therapeutics outside the submitted work. Dr Saracino has received speaking fees from UCB. Dr Jerjen has no conflict of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest There are no competing interests for any author. All the authors gave substantial contributions to the conception or design of the work, acquisition, analysis or interpretation of data, drafting the work or revising it critically for important intellectual content and final approval of the version published., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Follow-up of patients with treatment-resistant Raynaud's phenomenon (RP) one-year after single-port thoracoscopic sympathicotomy (SPTS)., Methods: Eight patients (six males, two females, median age of 45 years) with treatment-resistant RP underwent left-sided SPTS at the third rib (R3), unilaterally. Questionnaires were taken, and number and duration of RP attacks were reported over a 2-week period. Perfusion was assessed with a cooling and recovery procedure at baseline and one year after SPTS. Furthermore, laser speckle contrast analysis, pulse wave velocity, heart rate variability and nailfold capillary microscopy were performed., Results: One year after SPTS the duration of the attacks of was reduced with 1.9 h in the left hand versus 0.3 h in the right hand. Furthermore, three aspects of the questionnaire showed a significant improvement (role limitations due to physical health (p = 0.017), pain (p = 0.027) and physical functioning (p = 0.025)). The total area under the curve of the total cooling and recovery procedure of the left hand was larger one year after surgery (101 (75-140) at baseline versus 118 (95-190) one year post-operatively, p = 0.012), implying a better perfusion in the fingers. This was mainly due to the improvement during the recovery phase (21 (1-41) at baseline versus 38 (24-43) one year post-operatively, p = 0.028)., Conclusion: One year after unilateral R3 SPTS the benefit with regard to the majority of outcome variables persisted, though some effects seem to attenuate. Long-term effects and long-term follow-up results will be investigated in an on-going study., Clinical Trial Registration Number: NCT02680509., Competing Interests: Declaration of Competing Interest The authors have declared no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

The current conservative and surgical treatments are not fully effective and have complications for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). Botulinum toxin A (BTX-A) can be used to manage RP, but the literature mostly includes case reports and case series. Thus, we performed a randomized controlled trial to explore the efficacy of BTX-A in the treatment of RP secondary to SSc. Sixteen patients with RP secondary to SSc were recruited. One hand was randomly included in the BTX-A group and the other as control. Both hands were tested before treatment and 4 weeks later using qualitative and quantitative dermatoscopic assessments and the cold water test. Reynolds score (from 6.7 ± 4.0 to 2.9 ± 3.7, p < 0.001), T base (from 25.8 ± 3.0°C to 27.9 ± 2.1°C, p = 0.031) and T change (from 2.1 ± 1.2°C to 4.5 ± 2.1°C, p < 0.001) in the experimental group were improved, while there were no improvements in T base and T change in the control group. In the experimental group, the sum of the six dermoscopic parameters was improved after treatment (from 4.00 (3.00, 5.75) to 3.00 (2.00, 5.00), p = 0.002); the nailfold capillary pattern staging was also improved (from 2.00 (2.00, 3.00) to 2.00 (1.00, 3.00), p = 0.004). There were no improvements in the dermoscopic assessment in the control group. None of the patients reported adverse reactions such as infection, hematoma, hand muscle weakness, allergic reaction and nerve injury. In conclusion, local injection BTX-A to treat RP secondary to SSc might be safe and effective., (© 2022 Wiley Periodicals LLC.)

The normal biological wound healing process consists of three precisely and highly programmed phases that require optimal conditions including internal and external factors. Any negative factors that disrupt the sequence or time frame of the healing mechanism can result in a non-healing wound or chronic ulcers. Botulinum neurotoxin A (BoNT-A) which is generally known as anti-contraction of muscles has been reported as a successful treatment in various types of chronic ulcers. The aim of this study is to review the outcome of treatment with BoNT-A for chronic skin ulcers. The results demonstrated some positive effects of BoNT-A on chronic ulcers. Ischemic ulcers secondary to Raynaud's phenomenon seem to be the most promising type of ulcers that have benefited from BoNT-A. The rationale behind using BoNT-A to fasten the wound healing process is also discussed. Further clinical trial studies should be conducted to affirm the efficacy of wound healing using BoNT-A administration.

Introduction: Vasculopathy is a crucial feature of systemic sclerosis (SSc). It occurs in almost every patient with SSc, with Raynaud's phenomenon (RP) and digital ulcers (DU) having a great impact on the quality of patients' lives. Intravenous (IV) iloprost, a synthetic analogue of prostacyclin, is broadly used to treat RP and DU secondary to SSc. Currently, there is no standard protocol defined for the iloprost treatment of SSc-associated RP and DU, and, consequently, the management of this treatment is largely based on each centre's experience., Objective: The objective of this study is to evaluate the safety profile of a particular scheme of IV iloprost used in our centre as the standard treatment of SSc-related vascular complications., Methods: We retrospectively evaluated the clinical records of SSc patients, classified according to the 2013 European Alliance of Associations for Rheumatology (EULAR) criteria (31) with SSc-related DU and/or severe RP not responsive to CCB, receiving or who have received IV iloprost infusions from January 1st 2011 to March 31st 2021 Results: Within this time frame, 60 patients (n=44 for DU; n=16 for severe RP) were treated with a monthly 10-hour IV iloprost perfusion with a dosing regimen adapted to individual tolerance. Forty-nine of these 60 patients (81.7%) were on iloprost for more than one year. Within 12 months of therapy, 40 patients have healed the DUs (90.9%), with only 4 patients maintaining active DUs. A significant clinical improvement in RP at 12 months was observed in 87.5% (n=14/16) of SSc patients with severe RP. Eleven AE implying treatment dose/frequency adjustments or suspension were recorded (18.3% of patients): severe headache (n=5), hypotension (n=3), tachycardia (n=1), flushing (n=1) and generalised erythroderma (n=1). In all patients, the perfusion rate was reduced in the following treatment sessions with good tolerance, with the exception of the patient with the generalised erythroderma reaction, who suspended the perfusion and was later switched to bosentan. After a mean follow-up time of 6.9 (+/-) 4.0 years of treatment (range 0.06-22), 24 patients (40%) stopped the therapy, 14 (58.3%) of whom due to clinical improvement. The overall 5-, and 10-year survival rates of IV iloprost were 68.2% and 55.6%, respectively., Conclusion: SSc patients who received this flexible IV iloprost regimen achieved clinical improvement, reflected in the high persistence rate of the drug, with a good tolerability profile. In addition, most side effects were mild and easily managed.

Introduction: 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., Method: 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., Result: 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)., Conclusion: 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., Key Messages: • 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., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background/aims: Raynaud's phenomenon by episodically reversible constriction of the arteries in the fingers and toes causes pain, numbness, sores, and gangrene. However, the treatment of Raynaud's phenomenon is one of the clinical issues. Recent studies have shown that botulinum toxin is considered a potential and effective therapeutic option for improving finger blood circulation in patients with Raynaud's syndrome. In this study, we sought to investigate the therapeutic effect of botulinum toxin type A on exacerbated Raynaud's phenomenon in patients with scleroderma., Methods: In this prospective study, 11 patients with systemic scleroderma who were referred due to aggravated Raynaud's were included. For all patients, questionnaires were filled up, and physical examination was performed separately for both treatment and control hands, and then similar volumes of botulinum toxin type A (Botox) and normal saline were randomly injected., Results: The results showed that there was a significant difference in Raynaud's score (P = 0.001), Quick-Dash score (P = 0.01), Mc-Cabe cold score (P = 0.003), the mean frequency of recurrences arracks (P = 0.01), pain (0.005) (P = 0), skin color (P = 0.01), and duration of Raynaud's phenomenon (P = 0.006) between the intervention and control groups after two months., Conclusion: Following Botox injection, a significant improvement in terms of various Raynaud's parameters as well as the clinical manifestations was observed in the intervention group. Together, botulinum toxin type A could retrieve the hand function, the cold sensitivity, and the painful feeling caused by Raynaud's syndrome., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The association between central nervous (CNS) stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon (RP) has received little attention to date. Our aim was to map the existing literature on aetiopathogenesis, clinical presentation and management of peripheral vasculopathy, with a focus on RP, secondary to drug therapy for ADHD. We searched the PubMed® database (01/11/1951 to 01/08/2020) and included articles written in English, which focussed on CNS stimulants used to treat ADHD and RP. The search identified 150 articles 9 of which were eligible for inclusion (70 patients). The majority of studies (n = 6) related to children or adolescents; however, adult cases were also identified. Peripheral vascular manifestations included attacks of RP (new and worsening) and cold sensitivity (acrocyanosis and perniosis). Irreversible ischaemic complications including digital autoamputation and lower limb critical digital ischaemia have also been reported. The implicated causative CNS stimulants were Methylphenidate (n = 5), Dextroamphetamine (n = 4), Atomoxetine (n = 2), and Lisdexamphetamine (n = 2). Complete resolution of RP symptoms was observed in half (n = 5) of studies upon drug cessation. Other therapeutic strategies have included dose reduction and switching to an alternative drug therapy. A potential autoimmune association has also been postulated including drug-induced autoimmunity and new cases of systemic sclerosis which have been potentially attributed to treatment. Future research is required to understand the association between CNS stimulant drug therapies for ADHD and peripheral vascular manifestations, including RP., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To explore patient priorities and ranking of factors influencing patient decision-making concerning treatment escalation in the management of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc)., Methods: Patients with SSc were invited to participate in an online survey disseminated through patient-led organizations and social media platforms., Results: Responses from 747 individuals with self-reported SSc-RP were evaluable with broad international representation. The mean ± SD age (54.7 ± 12.1 years), clinical phenotype, and disease subsets distribution (limited cutaneous SSc [402 of 747, 53.8%], diffuse cutaneous SSc [260 of 747, 34.8%], and overlap disease [85 of 747, 11.4%]) were consistent with expected demographic information. Around one-half (56.3%) of patients reported that their SSc-RP symptoms were adequately controlled. The 5 highest ranked factors (of 13) that would prompt treatment escalation for SSc-RP were as follows: 1) inability to use the fingers properly; 2) emergence of new digital ulcer on ≥1 fingers; 3) worsening pain or discomfort from RP; 4) more severe attacks; and 5) if it may help with internal problems. Despite symptoms not being adequately controlled, 47.1% were concerned about potential treatment side effects and were more likely to accept mild (~20-40%) versus severe (2%) side effects. Patients were open to different management strategies for uncontrolled RP that included adding new treatment in combination with existing treatment (52.8%), drug substitution (40.9%), increasing the current dose (28.8%), or focusing on nonpharmacologic approaches (29.7%)., Conclusion: We have identified the relative importance of different factors influencing patient preferences for treatment decision-making regarding SSc-RP. Side-effect profiles influence acceptability of drug treatments, and many patients report a preference for nonpharmacologic management of SSc-RP., (© 2021, American College of Rheumatology.)

Raynaud&rsquo;s phenomenon (RP), a common presenting symptom of systemic sclerosis (SSc), is a painful and debilitating condition of the digits caused by increased vascular reactivity.1,2.

Raynaud's phenomenon (RP) is common in rheumatic diseases. In the setting of systemic sclerosis (SSc), it can be complicated by digital ischemia that includes ulceration and gangrene. Systemic adverse effects may preclude the use of oral or topical vasodilators for the treatment of RP and its complications. In this article, we review effectiveness/efficacy of botulinum toxin injection in primary and secondary RP. We discuss botulinum toxin formulations, dosage, sites of administration, and adverse effects. The evidence for botulinum toxin in the treatment of primary and SSc-associated RP is promising. Consistency across patient populations, treatment options (botulinum serotype, dose, and injection site), and outcome measures will be essential for further research., Competing Interests: Declaration of competing interest Dr. Johnson has been a site investigator for trials supported by Bayer, Boehringer Ingelheim, Corbus, GSK, Roche, Merck and served in advisory boards sponsored by Boehringer Ingelheim and Ikaria., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: The Dang-Gui-Si-Ni (DGSN) decoction as a classic prescription has been widely used for thousands of years in the clinical practice of traditional Chinese medicine (TCM). Especially in recent years, the potential efficacy of TCM for the treatment of Raynaud's syndrome has attracted great attention as there are still no specific remedies for this disease. However, the active constituents and underlying mechanisms responsible for the therapeutic benefits are not well understood, which makes it difficult to ensure quality control or to design research and drug development strategies. To identify the potential pharmacodynamic ingredients (PPIs) of TCM will help to achieve suitable process control procedures for industrial production and large-scale manufacturing., Aim of the Study: In the present study, we propose a multi-dimensional qualitative analysis method combining water-decoction spectra, in-vitro intestinal absorption spectra, in-vivo plasma spectra, and molecular docking of components to quickly identify the PPIs for the DGSN decoction of TCM., Materials and Methods: Water-based decoctions of DGSN were prepared in accordance with the clinical use registered in ancient books. Ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS) coupled with computerized modelling activity screening was used to quickly identify the PPIs of the DGSN decoction. Bioactive compounds absorbed in vitro were identified using the everted intestinal sac model from rats and compounds absorbed in vivo were confirmed in portal vein blood samples obtained following oral administration in rats. Molecular docking validation experiments were adopted to predict the binding activity to coagulation factors I, II, VII, X, and IX. The active components were further confirmed by pharmacodynamics analysis. The anticoagulant activity of the DGSN decoction was verified using rat models., Results: Thirty-one compounds were identified in the DGSN decoction. According to the in vivo experiments, 22 compounds that could be absorbed in vivo were detected by the everted intestinal sac model in rats. This model greatly reduces the scope of PPIs and is easy to perform. Ten compounds were detected in the portal vein blood in rats. The compounds detected in plasma provide stronger evidence supporting the PPIs. Molecular docking in vitro experiments indicated that 7 compounds exhibited better binding activity with coagulation factors I, II, VII, X, and IX. The animal experiments confirmed that the DGSN decoction could improve the microcirculation, providing indirect proof of anticoagulant activity suggested by the molecular docking studies. Finally, based on the multi-dimensional methods, 9 potential compounds present in the DGSN decoction were identified as PPIs (i.e., ferulic acid, paeoniflorin, albiflorin, chlorogenic acid, cryptochlorogenic acid, liquiritin, liquiritin apioside, cinnamaldehyde and glycyrrhizic acid)., Conclusion: Overall, this study combined the water-decoction spectra, intestinal absorption spectra in vitro, plasma spectra in vivo, and molecular docking studies to establish a multi-dimensional qualitative analysis method of the DGSN decoction. Meanwhile, 9 compounds in DGSN decoction were identified as PPIs using this method, and are proposed for application as quality standards for complex TCM prescriptions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Raynaud's phenomenon (RP) is a disorder of the microvasculature which causes poor blood flow to the digits. This disorder is common in young females and may be associated with several underlying connective tissue diseases including systemic sclerosis. Although RP may have a tremendous impact on quality of life, treatment options are limited. Conventional medical treatment mainly consists of vasodilatory drugs, which are not effective in all patients and may induce undesired side effects. The current clinical lesson describes three patients with severe RP who all underwent a novel, minimally invasive, single-port thoracoscopic sympathicotomy (SPTS). Although this procedure seems promising in patients with treatment-resistant RP, as shown with patients A and B, future research has yet to show what the long-term effects are.

Background: Numerous agents have been suggested for the symptomatic treatment of primary Raynaud's phenomenon. Apart from calcium channel blockers, which are considered to be the drugs of choice, evidence of the effects of alternative pharmacological treatments is limited. This is an update of a review first published in 2008., Objectives: To assess the effects of drugs with vasodilator effects on primary Raynaud's phenomenon as determined by frequency, severity, and duration of vasospastic attacks; quality of life; adverse events; and Raynauds Condition Score., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trial register to November 16, 2020., Selection Criteria: We included randomized controlled trials evaluating effects of oral, intravenous, and topical formulations of any drug with vasodilator effects on subjective symptoms, severity scores, and radiological outcomes in primary Raynaud's phenomenon. Treatment with calcium channel blockers was not assessed in this review, nor were these agents compared., Data Collection and Analysis: Two review authors independently selected studies for inclusion, assessed studies using the Cochrane "Risk of bias" tool, and extracted study data. Outcomes of interest included frequency, severity, and duration of attacks; quality of life (QoL); adverse events (AEs); and the Raynaud Condition Score (RCS). We assessed the certainty of the evidence using GRADE., Main Results: We identified seven new studies for this update. In total, we included 15 studies involving 635 participants. These studies compared different vasodilators to placebo. Individual studies used different methods and measures to report different outcomes. Angiotensin-converting enzyme (ACE) inhibitors Combining data from three studies revealed a possible small increase in the frequency of attacks per week after treatment (captopril or enalapril) compared to placebo (mean difference [MD] 0.79, 95% confidence interval [CI] 0.43 to 1.17; low-certainty evidence). There was no evidence of a difference between groups in severity of attacks (MD -0.17, 95% CI -4.66 to 4.31; 34 participants, 2 studies; low-certainty evidence); duration of attacks (MD 0.54, 95% CI -2.42 to 1.34; 14 participants, 1 study; low-certainty evidence); or AEs (risk ratio [RR] 1.35, 95% CI 0.67 to 2.73; 46 participants, 3 studies; low-certainty evidence). QoL and RCS were not reported. Alpha blockers Two studies used alpha blockers (buflomedil or moxisylyte). We were unable to combine data due to the way results were presented. Buflomedil probably reduced the frequency of attacks compared to placebo (MD -8.82, 95% CI -11.04 to -6.60; 31 participants, 1 study; moderate-certainty evidence) and may improve severity scores (MD -0.41, 95% CI -0.62 to -0.30; moderate-certainty evidence). With moxisylyte, investigators reported fewer attacks (P < 0.02), less severe symptoms (P < 0.01), and shorter duration of attacks, but the clinical relevance of these results is unclear. No evidence of a difference in AEs between buflomedil and placebo groups was noted (RR 1.41, 95% CI 0.27 to 7.28; 31 participants, 1 study; moderate-certainty evidence). More AEs were observed in participants in the moxisylyte group than in the placebo group. Prostaglandin/prostacyclin analogues One study compared beraprost versus placebo. There was no evidence of benefit for frequency (MD 2.00, 95% CI -0.35 to 4.35; 118 participants, low-certainty evidence) or severity (MD -0.06, 95% CI -0.34 to 0.22; 118 participants, low-certainty evidence) of attacks. Overall, more AEs were noted in the beraprost group (RR 1.59, 95% CI 1.05 to 2.42; 125 participants; low-certainty evidence). This study did not report on duration of attacks, QoL, or RCS. Thromboxane synthase inhibitors One study compared a thromboxane synthase inhibitor (dazoxiben) versus placebo. There was no evidence of benefit for frequency of attacks (MD 0.8, 95% CI -1.81 to 3.41; 6 participants; very low-certainty evidence). Adverse events were not reported in subgroup analyses of participants with primary Raynaud's phenomenon, and the study did not report on duration of attacks, severity of symptoms, QoL, or RCS. Selective serotonin reuptake inhibitors One study compared ketanserin with placebo. There may be a slight reduction in the number of attacks per week with ketanserin compared to placebo (MD -14.0, 95% CI -27.72 to -0.28; 41 participants; very low-certainty evidence) and reduced severity score (MD -133.00, 95% CI -162.40 to -103.60; 41 participants; very low-certainty evidence). There was no evidence that ketanserin reduced the duration of attacks (MD -4.00, 95% CI -14.82 to 6.82; 41 participants; very low-certainty evidence), or that AEs were increased in either group (RR 1.54, 95% CI 0.89 to 2.65; 41 participants; very low-certainty evidence). This study did not report on QoL or RCS. Nitrate/nitrate derivatives Four studies compared topical treatments of nitroglycerin or glyceryl trinitrate versus placebo, each reporting on limited outcomes. Meta-analysis demonstrated no evidence of effect on frequency of attacks per week (MD -1.57, 95% CI -4.31 to 1.17; 86 participants, 2 studies; very low-certainty evidence). We were unable to pool any data for the remaining outcomes. Phosphodiesterase inhibitors Three studies compared phosphodiesterase inhibitors (vardenafil, cilostazol or PF-00489791) to an equivalent placebo. Results showed no evidence of a difference in frequency of attacks (standardized MD [SMD] -0.05, 95% CI -6.71 to 6.61; 111 participants, 2 studies; low-certainty evidence), severity of attacks (MD -0.03, 95% CI -1.04 to 0.97; 111 participants, 2 studies; very low-certainty evidence), duration of attacks (MD -1.60, 95% CI -7.51 to 4.31; 73 participants, 1 study; low-certainty evidence), or RCS (SMD -0.8, 95% CI -1.74 to 0.13; 79 participants, 2 studies; low-certainty evidence). Study authors reported that 35% of participants on cilostazol complained of headaches, which were not reported in the placebo group. PF-00489791 caused 34 of 54 participants to experience AEs versus 43 of 102 participants receiving placebo (RR 1.49). Headache was most common, affecting 14 participants (PF-00489791) versus nine participants (placebo)., Authors' Conclusions: The included studies investigated several different vasodilators (topical and oral) for treatment of primary Raynaud's phenomenon. Small sample sizes, limited data, and variability in outcome reporting yielded evidence of very low to moderate certainty. Evidence is insufficient to support the use of vasodilators and suggests that vasodilator use may even worsen disease., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Raynaud's phenomenon is a vasospastic condition affecting hands and feet which may lead to rest pain, ischemic ulcers and gangrene. Botulinum toxin A has been shown to improve peripheral circulation and relieve vasospastic symptoms. Our aim was to assess our treatment outcomes following Botulinum toxin A injections in patients with Raynaud's phenomenon and to explore the importance of toxin concentration and injection sites. Retrospective chart review of patients with primary and secondary Raynaud's syndrome treated with Botulinum toxin A injections and a literature review was conducted. The toxin dose, injection sites, symptom relief, healing of ulcers and complications were assessed. A total of 30 treatment episodes over a 7½ year period were included. All patients had failed medical management. Botulinum toxin A injection was injected primarily in the vicinity of the palmar digital neurovascular bundle. The average total Botulinum toxin A dose injected was 156 U and the concentration was 50 U/ml. All patients reported an improvement in symptoms and healing of digital ulcers. One patient reported a temporary muscle weakness. Six patients had a single treatment episode with long term benefit. Systemic sclerosis patients had an average of 6-month interval between treatment episodes. Higher doses of Botulinum toxin A has been well tolerated with no long term adverse effects. Our study shows that targeted low volume higher concentration Botulinum toxin A injections are effective in treating Raynaud's phenomenon.

Antisynthetase syndrome (AS) is a rare disease that affects patients with inflammatory myopathies such as polymyositis (PM) and dermatomyositis (DM). In patients with AS, up to 95% of patients develop antisynthetase syndrome-associated interstitial lung disease (AS-ILD). Although AS-ILD commonly occurs in patients with a well-established diagnosis of AS, it can be the first or only manifestation of an occult AS. The frequency of interstitial lung disease (ILD), myopathy, and skin involvement are often dependent on the type of myositis-specific antibodies present. AS-ILD patients who are positive for both anti-Jo-1 and anti-SSA/RO-52 autoantibodies often present with a severe degree of lung restriction on pulmonary function tests and radiologic imaging with an inadequate response toward immunosuppressive therapies. We describe a 65-year-old woman who presents with chronic dyspnea. She was initially diagnosed with corticosteroid-resistant cryptogenic organizing pneumonia based on the radiological findings on her CT chest. Her symptoms did not improve, and she suffered from intolerable corticosteroid-related side effects. Reviews of systems were positive for arthritis and Raynaud's phenomenon. She was found to have elevated inflammatory markers and autoantibodies such as anti-Jo-1, anti-RO-52, and anti-SSA. A diagnosis of AS-ILD resistant to corticosteroid therapy was made. Her lung function improved with combination therapy of mycophenolate and rituximab. Our case highlights that a detailed history and physical exam, compatible radiologic imaging, and autoantibodies are essential for the diagnosis of AS-ILD., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2020, American College of Rheumatology.)

Introduction: Pharmaceutical prescription in systemic sclerosis is guided by national and international recommendations. This study's primary objective was to describe and analyze these prescriptions among patients of our cohort. We also aimed to assess drug compliance among our patients., Methods: This is a monocentric observational study on two cohorts of patients with systemic sclerosis; a primary cohort comprising ambulatory patients, who were prospectively included, with exhaustive prescription's data collection; and a secondary cohort included patients asked to fill in a self-questionnaire on treatment compliance., Results: The main cohort included 157 patients, including 31 cases of diffuse systemic sclerosis. A vasodilator drug for Raynaud's phenomenon was prescribed in 75 patients (47.9%) and a specific treatment for pulmonary arterial hypertension in 10 patients (6.4%). Immuno-modulators/immunosuppressants was prescribed in 62 patients (39.5%), who received prednisone (n=37, 23.6%), mycophenolate mofetil (n=14, 8.9%), hydroxychloroquine (n=12, 7.6%) and colchicine (n=22, 14%). Treatment for "gastro-intestinal tract involvement" was prescribed for 106 patients (67.5%) and treatment of a scleroderma renal crisis with an angiotensin-converting enzyme inhibitor for 6 patients (3.8%). Among the 42 patients in the secondary cohort, 21.4% reported a good compliance, mostly older patients (P=0.045) or those who had not experienced adverse events (P=0.009)., Conclusion: This study provides original real-life data illustrating the heterogeneity of prescription habits in systemic sclerosis. As previously reported, treatment compliance was insufficient., (Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Raynaud 's Phenomenon (RP) results from exaggerated cold-induced vasoconstriction. RP patients suffer from vasospastic attacks and compromised digital blood perfusion leading to a triple color change at the level the fingers. Severe RP may cause ulcers and threaten tissue viability. Many drugs have been used to alleviate the symptoms of RP. These include calcium-channel blockers, cGMP-specific phosphodiesterase type 5 inhibitors, prostacyclin analogs, and angiotensin receptor blockers. Despite their variety, these drugs do not treat RP but rather alleviate its symptoms. To date, no drug for RP has been yet approved by the U.S Food and Drugs Administration. Cilostazol is a selective inhibitor of phosphodiesterase-III, originally prescribed to treat intermittent claudication. Owing to its antiplatelet and vasodilating properties, cilostazol is being repurposed as a potential drug for RP. This review focuses on the different lines of action of cilostazol serving to enhance blood perfusion in RP patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Raynaud phenomenon (RP) is a condition causing vasospasm in the fingers and toes of patients that can have a significant negative impact on quality of life. This can lead to pain, ulceration, and possible loss of digits. Several pharmacological options are available for treatment. However, RP can often be refractory to traditional modalities, leaving surgery or injections as the next available options. This article provides a review and update on the use of botulinum toxin as an effective therapy for the treatment of RP refractory to medical management., (Copyright © 2021 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)