Raynaud Condition Score Research Articles

A phase 2 trial investigating the efficacy and safety of the mPGES-1 inhibitor vipoglanstat in systemic sclerosis-related Raynaud's.

Our objective was to test the hypothesis, in a double-blind, placebo-controlled study that vipoglanstat, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) which decreases prostaglandin E2 (PGE2) and increases prostacyclin biosynthesis, improves RP. Patients with systemic sclerosis (SSc) and ≥7 RP attacks during the last screening week prior to a baseline visit were randomised to four weeks treatment with vipoglanstat 120 mg or placebo. A daily electronic diary captured RP attacks (duration and pain) and Raynaud's Condition Score, with change in RP attacks/week as primary end point. Cold challenge assessments were performed at baseline and end of treatment. Exploratory endpoints included patients' and physicians' global impression of change, Assessment of Scleroderma-associated Raynaud's Phenomenon questionnaire, mPGES-1 activity, and urinary excretion of arachidonic acid metabolites. Sixty-nine subjects received vipoglanstat (n = 33) or placebo (n = 36). Mean weekly number of RP attacks (baseline; vipoglanstat 14.4[SD 6.7], placebo 18.2[12.6]) decreased by 3.4[95% CI -5.8;-1.0] and 4.2[-6.5;-2.0] attacks per week (p= 0.628) respectively. All patient reported outcomes improved, with no difference between the groups. Mean change in recovery of peripheral blood flow after cold challenge did not differ between the study groups. Vipoglanstat fully inhibited mPGES-1, resulting in 57% reduction of PGE2 and 50% increase of prostacyclin metabolites in urine. Vipoglanstat was safe and well tolerated. Although vipoglanstat was safe, and well tolerated in a dose achieving full inhibition of mPGES-1, it was ineffective in SSc-related RP. Further development and evaluation of vipoglanstat will therefore be in other diseases where mPGES-1 plays a pathogenetic role.

Medium- and Long-Term Outcomes of Autologous Fat Grafting to Hands and Feet for Patients With Raynaud Phenomenon.

Autologous fat grafting (AFG) has emerged as a promising treatment option for Raynaud phenomenon. However, existing studies are limited by short follow-up, and there is little evidence regarding predictive factors for successful outcomes. A retrospective chart review and standardized phone interviews were performed for all patients (n = 17, 65% response rate) treated with AFG to the hands or feet at our institution for primary or secondary Raynaud from 2010 to 2021. Each occurrence of AFG was defined as a separate surgery (n = 23), with an average follow-up of 3.7 years. At follow-up, patients reported a 31% reduction in cold attack frequency, a 45% reduction in the intensity of individual attacks, a 29% reduction in the duration of attacks, and a 40% improvement in overall Raynaud Condition Score (P < 0.01). Although initial AFG to an extremity significantly improved symptoms, subsequent attempts were not shown to statistically improve outcomes. Digital ulcers were present in 65% of cases, and AFG resulted in ulcer healing in 87% of those cases. Median duration of maximum symptom relief was 1 year postoperatively, with 74% of patients reporting diminishing symptom relief by 4 years postoperatively. Those with a BMI ≥25, with primary Raynaud phenomenon or without preoperative ulcers experienced significantly longer symptom relief (P < 0.05). Average patient satisfaction was 7.7 of 10, and 91% would recommend the procedure to others. Autologous fat grafting is an effective, albeit sometimes temporary, treatment for Raynaud and digital ulcers. Certain patients may be more likely to experience lasting symptom relief beyond 1 year.

Copeptin as a Biomarker of Microcirculation Alterations in Systemic Sclerosis.

Systemic sclerosis is a connective tissue disease characterized by vasculopathy and progressive fibrosis, leading to multiorgan dysfunction. Given the complex and not fully elucidated pathogenesis, biomarkers of rapid disease progression and therapeutic response are lacking. Copeptin, which reflects vasopressin activity in serum, is used in diagnosing or prognosing different cardiometabolic conditions. The aim of study was to investigate the concentration of copeptin in patients with systemic sclerosis and correlate it with specific clinical symptoms. Serum copeptin was measured in patients with systemic sclerosis (34 women and 3 men; mean age 57.6 years) and in healthy individuals (n=30) using commercially available ELISA kits. According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). The median duration of the disease was 10 [4-14] years. We found significantly higher copeptin concentration in patients with systemic sclerosis (4.21 pmol/L [3.04-5.42]) in comparison to control group (3.40 pmol/L [2.38-3.76], p<0.01). Copeptin significantly correlated with Raynaud's condition score (r=0.801, p<0.05). Patients with "late" capillaroscopic patterns had higher copeptin concentrations (5.37 pmol/L [4.29-8.06]) than patients with "early" (2.43 pmol/L [2.25-3.20], p<0.05) and "active" patterns (3.93 pmol/L [2.92-5.16], p<0.05]). Copeptin was found to be significantly higher in SSc patients with DUs (5.71 pmol/L [IQR 4.85-8.06]) when compared to SSc patients without DUs (3.31 pmol/L, [2.28-4.30], p<0.05). Additionally, copeptin concentration had good diagnostic accuracy in discriminating between patients with and without digital ulcers (AUC=0.863). Alprostadil decreased copeptin concentration from 4.96 [4.02-6.01] to 3.86 pmol/L [3.17-4.63] (p<0.01) after 4-6 cycles of administration. Our findings suggest that copeptin may be a promising biomarker of microcirculation alterations in systemic sclerosis.

Qualitative Interviews to Assess the Content Validity and Usability of the Electronic Raynaud Diary in Patients with Systemic Sclerosis.

To better understand the symptoms and impacts of Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc) and to evaluate the content validity and usability of a new electronic patient-reported outcome (PRO) measure for RP: the Raynaud Diary. The Raynaud Diary was developed as a daily eDiary for assessing the number and duration of symptomatic Raynaud attacks; worst pain, numbness, tingling, and discomfort in the fingers; and overall disease severity, captured using the Raynaud's Condition Score. The Raynaud Diary was debriefed in two waves of qualitative interviews with adults with self-reported RP secondary to SSc. All interviews included open-ended questions about participants' experiences of RP. Participants (N=39) had a mean age of 55.1 years, and 87% were female. Frequently reported RP symptoms were color change (reported by all participants), numbness (90%), tingling (82%), pain (77%), and discomfort (72%). Common attack triggers included temperature-related factors and stress. Participants reported being unable to be outside or do outdoor activities and had problems gripping objects. All participants demonstrated understanding of the Raynaud Diary instructions. Most participants indicated that they would be able to use the Raynaud Diary to record the worst severity of individual RP symptoms in the previous 24 hours. Patients with RP secondary to SSc bear a heavy symptom burden. The Raynaud Diary is a content valid PRO measure that captures the most frequent symptoms of RP in patients with SSc.

Hyperspectral imaging in systemic sclerosis-associated Raynaud phenomenon

Background/purposeLack of robust, feasible, and quantitative outcomes impedes Raynaud phenomenon (RP) clinical trials in systemic sclerosis (SSc) patients. Hyperspectral imaging (HSI) non-invasively measures oxygenated and deoxygenated hemoglobin (oxyHb and deoxyHb) concentrations and oxygen saturation (O2 sat) in the skin and depicts data as oxygenation heatmaps. This study explored the potential role of HSI in quantifying SSc-RP disease severity and activity.MethodsPatients with SSc-RP (n = 13) and healthy control participants (HC; n = 12) were prospectively recruited in the clinic setting. Using a hand-held camera, bilateral hand HSI (HyperMed™, Waltham, MA) was performed in a temperature-controlled room (22 °C). OxyHb, deoxyHb, and O2 sat values were calculated for 78-mm2 regions of interest for the ventral fingertips and palm (for normalization). Subjects underwent a cold provocation challenge (gloved hand submersion in 15 °C water bath for 1 min), and repeated HSI was performed at 0, 10, and 20 min. Patients completed two patient-reported outcome (PRO) instruments: the Raynaud Condition Score (RCS) and the Cochin Hand Function Scale (CHFS) for symptom burden assessment. Statistical analyses were performed using the Mann-Whitney U test and a mixed effects model (Stata, College Station, TX).ResultsNinety-two percent of participants were women in their 40s. For SSc-RP patients, 69% had limited cutaneous SSc, the mean ± SD SSc duration was 11 ± 5 years, and 38% had prior digital ulcers—none currently. Baseline deoxyHb was higher, and O2 sat was lower, in SSc patients versus HC (p < 0.05). SSc patients had a greater decline in oxyHb and O2 sat from baseline to time 0 (after cold challenge) with distinct rewarming oxyHb, O2 sat, and deoxyHb trajectories versus HCs (p < 0.01). There were no significant correlations between oxyHb, deoxyHb, and O2 sat level changes following cold challenge and RCS or CHFS scores.ConclusionHyperspectral imaging is a feasible approach for SSc-RP quantification in the clinic setting. The RCS and CHFS values did not correlate with HSI parameters. Our data suggest that HSI technology for the assessment of SSc-RP at baseline and in response to cold provocation is a potential quantitative measure for SSc-RP severity and activity, though longitudinal studies that assess sensitivity to change are needed.

Long Term Outcomes of Autologous Fat Grafting to Hands and Feet for Patients with Raynaud’s

PURPOSE: Autologous fat grafting (AFG) has emerged as a promising treatment option for primary and secondary Raynaud’s, both with and without digital ulcers. However, prospective and retrospective studies of the procedure are limited by short follow-up, and there is scant data regarding factors that can impact the likelihood of successful long-term outcomes. The aims of this study were to (1) characterize the long-term outcomes and patient satisfaction for AFG used to treat Raynaud’s and digital ulcers, and (2) identify factors that affected the longevity and magnitude of symptom relief. METHOD: A retrospective chart review was performed of all patients (n=17) treated with AFG to the hands or feet at our institution for primary or secondary Raynaud’s over an 11-year period between 2010 and 2021. Standardized phone interview follow ups were conducted with all patients, with a 65% response rate (n=11 patients). AFG to each extremity was defined as a separate surgery, and results were measured per surgery (n=23). Demographics, medical information, operative notes, and post-operative clinic notes were collected from chart review. A phone survey was used to assess pre- and post-operative symptoms based on the validated Raynaud Condition Score (RCS), initial response to AFG, long-term symptom relief, and satisfaction. RESULTS: Digital ulcers were present prior to AFG in 65% of surgeries, the average RCS was 5.8 (scored 0-10), and patients experienced an average of 3.5 cold attacks per day that lasted for 19.2 mins with an intensity of 2.0 (scored 0-3). At peak response level 83% of surgeries improved Raynaud’s symptoms and 87% of those with ulcers reported healing. Diminished symptom relief following peak response was reported in 70% of surgeries, but in 81% of those cases symptoms at follow-up were still better than before AFG. At follow-up (defined as time of survey or time of presentation for subsequent AFG), the average RCS was 3.5 (delta -2.3, p<0.01), frequency of cold attacks was 2.4 per day (delta -1.1, p<0.01), duration was 13.7 mins (delta -5.4, p<0.01), and intensity was 1.1 (delta of -0.9, p<0.01). Younger age and primary Raynaud’s correlated with larger improvements in RCS (p<0.05). Average follow-up was 2.9 years from AFG; 2.5 for surgeries with eventually diminishing symptom relief and 3.9 for those without. Diminishing symptom relief with symptom recurrence at 0.5, 1, and 2 years was observed in 30%, 52%, and 64% of surgeries. Median duration of maximum symptom relief was 10.5 months post-operatively. Patients with no ulcers prior to AFG (OR 0.43), higher BMI (26.2 vs. 22.6), and non-White race (OR 0.40) were less likely to experience diminishing symptom relief (p<0.05). In addition, patients with primary Raynaud’s were less likely to experience diminishing symptom relief than those with CREST or systemic scleroderma (33% vs. 50% vs. 91%, p<0.10). Average patient satisfaction with AFG was 7.2/10, and 91% would recommend AFG to others. CONCLUSION: AFG is an effective, albeit sometimes temporary, treatment for Raynaud’s and digital ulcers. Certain subsets of patients may be more likely to experience lasting symptom relief beyond 1 year.

Arm heating to relieve Raynaud's phenomenon in systemic sclerosis: A single-arm multicentre prospective clinical trial.

Raynaud's phenomenon, one of the major symptoms of systemic sclerosis (SSc), is difficult to treat. Although it is empirically considered that warming is a beneficial technique, there is no supportive evidence. We conducted a multicentre study to evaluate whether continuous heating of the arm alleviates Raynaud's phenomenon in SSc. A pair of disposable warmers was applied to the upper arm near the elbow of patients with SSc. Two weeks of non-warmer application were followed by 2 weeks of warmer application, which was repeated twice. The Raynaud Condition Score (RCS), number of episodes, and duration of Raynaud's phenomenon were recorded. The differences in the mean RCS, frequency, and duration of Raynaud's phenomenon between the warmer application and non-application periods were analysed. Twenty-eight patients were included in the analysis. The average RCS was 1.98 and 2.66 during the warmer application and non-application periods, respectively. The change between the two periods was statistically significant by paired t-test. In addition, the frequency and total duration of Raynaud's phenomenon in the warmer application period were significantly lower than those in the non-application period. Heating of the upper arm near the elbow is effective in alleviating Raynaud's phenomenon in SSc.

Placebo response in Raynaud's Phenomenon clinical trials: The prominent role of regression towards the mean: Placebo response in Raynaud's Phenomenon

BackgroundSubstantial 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. MethodsWe 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. FindingsWe 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. InterpretationPlacebo 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. FundingThis work has been partially supported by MIAI @ Grenoble Alpes (ANR-19-P3IA-0003).

Evaluation of sweating responses in patients with systemic connective tissue disorders using the quantitative sudomotor axon reflex test

AbstractBackgroundIn systemic connective tissue disorders, eccrine sweat glands are frequently attacked by immune cells, as evidenced by pathological observations.AimsSweating affects vascular activity through the autonomic nervous system, while few studies have reported sweating ability in systemic connective tissue disorders or the relationship between sweating ability and Raynaud's phenomenon caused by sympathetic hyperreactivity.Materials &amp; methodsWe performed the quantitative sudomotor axon reflex test on 85 patients diagnosed with systemic sclerosis, mixed connective tissue disease, systemic lupus erythematosus, Sjogren's syndrome, and dermatomyositis. Evaluations were performed once in summer and once in winter. We investigated the relationship between the axon reflex sweat volume or the reaction time and Raynaud's phenomenon assessed by a Raynaud's condition score, skin symptoms such as nailfold capillary changes, skin sclerosis severity, digital ulcers, chilblains, subcutaneous calcifications, and telangiectasia, and patient background.ResultsMost patients did not show a decrease in sweating compared to healthy participants, but patients with systemic sclerosis who were positive for anti‐RNA polymerase III antibodies showed little or no sweating. One in three patients showed less sweating in summer than in winter, which is the opposite of the normal seasonal variation. Although no relationship was observed between the sweat volume and the total Raynaud's condition scores, patients with pain had more sweating than those without pain.ConclusionThis is the first exploratory observational study of sweating ability in patients with systemic connective tissue disorders, revealing several clinical factors associated with acetylcholine‐induced sweating.

The effect of silver fibre gloves on Raynaud's phenomenon in patients with systemic sclerosis: a double-blind randomized crossover trial.

Silver fibre gloves transport heat from the palm to the fingers, possibly reducing the burden of RP in SSc patients. We aim to evaluate the clinical efficiency of this intervention. A multicentre, double-blind, randomized trial was performed, accounting for interindividual differences and external factors using a crossover design. Patients were randomized in two groups: group 1 wore 8% silver fibre gloves in period 1 and normal gloves in period 2 and group 2 vice versa. Each period lasted 6 weeks. The primary outcome was the Raynaud Condition Score (RCS) over time (minimal clinical important difference 1.4), assessed three times per week using an online questionnaire. Secondary outcomes included vascular complications and Scleroderma-Health Assessment Questionnaire (SHAQ). Outcomes were evaluated before unblinding using linear mixed models. A total of 85 SSc patients were included, with 76 completing the study. The mean RCS during 2 weeks before the study (i.e. without gloves) was 6.4 (s.d. 1.6). Both with silver fibre gloves and normal gloves the mean RCS decreased to 3.9 (s.d. 2.3) with a similar course over time. There was no difference in mean RCS over time between the type of gloves [β = 0.067 (95% CI -0.006, 0.19)]. Of secondary outcomes, total SHAQ [β = 0.036 (95% CI 0.026, 0.046)] was slightly higher with silver fibre gloves, which is clinically irrelevant. Three patients developed new digital ulcers with normal gloves vs one patient with silver fibre gloves [odds ratio 3.2 (95% CI 0.32, 31.1)]. Wearing gloves in SSc patients clearly decreases the RP burden. Our results do not support the hypothesis that increased heat transport of 8% silver fibre gloves is associated with less disease burden as measured in this study by the RCS compared with normal gloves. Netherlands Trial register (https://www.trialregister.nl/) NL7904.

Study Protocol: A Randomized Controlled Prospective Single-Center Feasibility Study of Rheopheresis for Raynaud's Syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT Study).

IntroductionRaynaud’s phenomenon (RP) and digital ulcers (DU) are frequent manifestations of Systemic Sclerosis (SSc). Despite being very common in SSc patients, both conditions have proven to be notoriously difficult to study. There are very few available approved drugs with varying efficacy. It has been shown that the presence of DU is associated with increased whole blood viscosity (WBV). Rheopheresis (RheoP) is an extracorporeal apheresis technique used to treat microcirculatory disorders by improving blood viscosity. Improved blood flow and wound healing after RheoP treatments have been reported in single case reports.Methods and AnalysisWe report the clinical trial protocol of “A randomized controlled prospective single-center feasibility study of Rheopheresis for Raynaud’s syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT).” RHEACT aims to investigate the efficacy of RheoP on the Raynaud Condition Score (RCS) as the primary efficacy outcome measure after 16 weeks from baseline. Thirty patients will be randomized in a 1:1:1 ratio to one of two RheoP treatment groups or assigned to the standard of care (SoC) control group (intravenous iloprost). Secondary endpoints include changes in DU, changes in nailfold video capillaroscopy and patient-reported-outcomes (Scleroderma Health Assessment Questionnaire, FACIT-Fatigue, and the Disability of Arm, Shoulder, and Hand, quick version).DiscussionApheresis techniques have been investigated in SSc but mainly in observational, retrospective studies, or single case reports. RheoP is a pathophysiologically driven potential new therapy for heavily burdened patients with SSc-associated secondary RP with or without DU.Ethics and DisseminationThe study was registered at clinicaltrials.gov (Identifier: NCT05204784). Furthermore, the study is made publicly available on the website of the German network of Systemic Sclerosis “Deutsches Netzwerk Systemische Sklerodermie (DNSS).”

Efficacy and safety of mesenchymal stem cells in the treatment of systemic sclerosis: a systematic review and meta-analysis

BackgroundSystemic sclerosis (SSc) is an autoimmune disease with high morbidity and mortality characterized by fibrosis of the skin and internal organs. Some studies have investigated the use of stem cells to treat SSc. Herein, a systematic review and meta-analysis was conducted to determine the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of SSc.MethodsPubMed, Embase, Cochrane Library, Web of Science, OVID, China National Knowledge Infrastructure and Wanfang databases were searched up to February 1, 2021. Literature screening, data extraction and quality assessment were conducted independently by two researchers in according to the inclusion and exclusion criteria. The discrepancies were resolved by a third researcher.ResultsA total of 9 studies encompassing 133 SSc patients were included in the study. Compared to the baseline after treatment with MSCs: 1. The modified Rodnan skin score (mRSS) was significantly reduced in patients with SSc (P < 0.00001). 2. MSCs decreased the number of digital ulcer, mouth handicap scale, and visual analog scale of hand pain in SSc patients (P = 0.0007 and P = 0.03, respectively). 3. No statistical differences were detected in Raynaud's condition score and Cochin hand function scale score at 6 months of MSCs therapy (P = 0.5 and P = 0.62). 4. After 12 months of follow-up, MSCs improve carbon monoxide diffusing capacity and forced vital capacity of SSc patients (P < 0.05). 5. Overall, MSCs application was safe; a few cases exhibited swelling at the injection site, diarrhea and arthralgia, which had self-recovery, and no severe adverse events occurred in the included trials.ConclusionsMSC therapy improves the degree of skin thickening, lung function, and mouth opening and relieves finger ulcers and pain in patients with SSc without severe adverse events. Thus, MSCs or MSCs combined with plasma and traditional medicine might be an effective and promising treatment of SSc patients.PROSPERO registration number: CRD42020200350

Bosentan versus nifedipine in the treatment of vasculopathy in systemic sclerosis patients: A randomized control trial.

Bosentan is effective agent in scleroderma vasculopathy. However, there are no studies evaluating effectiveness of bosentan in Vietnamese patients, where nifedipine is still the common treatment. To compare the efficacy of bosentan versus nifedipine in scleroderma vasculopathy in Vietnamese patients. We randomly assigned 70 patients in a 2:1 ratio to receive oral bosentan or oral nifedipine for 16 weeks, respectively. The primary outcomes were the change in Raynaud's Condition Score (RCS), appearance of new digital ulcers (DUs) and change in World Health Organization (WHO) functional class. Secondary outcomes were the change in the nailfold capillaries disease stage and systolic pulmonary arterial pressure (sPAP) value. At week 16, patients in bosentan group had no RCS imprvement, the mean difference was 0.8 ± 0.2 (95% CI, 0.4 to 1.1, p < 0.001) and improved WHO functional class, a mean treatment effect of 35.6% in favor of bosentan (95% CI, 13.4 to 57.7%, p < 0.05). Bosentan treatment was associated with a 58% reduction in the number of new DUs compared with nifedipine (mean ± standard error: 0.22 ± 0.42 vs 0.52 ± 0.59 new DUs, p < 0.05). sPAP was decreased by 4.1 ± 3.8 mmHg (95% CI, 3.0 to 5.3, p < 0.001) in bosentan group, versus 1.0 ± 2.9 mmHg (95% CI, -0.2 to 2.1, p > 0.05) in nifedipine group. Headache was the most common adverse event in both groups. Bosentan significantly limited the occurrence of new DUs, reduced symptoms of pulmonary arterial hypertension and sPAP value and all were better than nifedipine.

Vasodilators for primary Raynaud's phenomenon.

Vasodilators for primary Raynaud's phenomenon.

O15 Using a smartphone app to characterise and quantify skin colour changes in Raynaud's attacks

Abstract Background/Aims The lack of objective outcome measures for Raynaud's phenomenon (RP) has been a major limiting factor in development of effective treatments. At present, the Raynaud's Condition Score (RCS) is the only validated outcome measure, and is highly subjective. Mobile phone technology could provide a way forward. We have developed a smartphone app for RP monitoring that guides the patient through the process of capturing images of their hands during RP episodes, as well as capturing other data through post-attack and daily questionnaires. One of the objectives of our research programme (reported here) was to compare digital image (photographic) parameters to the RCS. Methods 40 patients with RP (8 with primary RP, 32 with RP secondary to systemic sclerosis) were recruited (40 female, median age (range): 57 years (25-74), median (range) duration of RP symptoms: 17 (0-53) years). Patients were given a smartphone handset with a pre-installed Raynaud’s Monitoring app and were trained on how to use it/take usable photographs. They were then asked to take photographs of RP attacks over a 14 day period and also to record the RCS for each episode. The app specifically prompts the patient to take a picture of their hand every minute during an attack, until confirmation is given that the attack is complete. At a 2nd visit, the handsets, images, and data were collected for analysis. The mean colour change during each RP attack was quantified (semi-automated method) by the Bhattacharyya distance (BD) in colour space between a region of interest (e.g. a section of a digit) and a control region (dorsal hand). BD was then compared to the RCS using ANOVA, after controlling for patient variability in the range of RCS values used by each patient. Results A total of 3,030 images were collected, describing 229 RP attacks. The median RCS reported was 6 (inter-quartile range [IQR]: 4), while the median for BD was 5.6 (IQR 3.2). ANOVA showed that measured values of the mean image BD were significantly different when different values of RCS were recorded by the patient (p &amp;lt; 0.001), i.e. attacks where patients selected different values of RCS had significantly different values of BD. Across all attacks/patients the F-value from ANOVA for RCS was 76.2, suggesting that the variation in BD for different values of RCS is much greater than the variation in BD for any one value of RCS. Conclusion Patients successfully used a smartphone app to collect photographs and data during episodes of RP. A strong association was found between skin colour change (via BD) and the gold-standard RCS. Mobile phone-documented colour change therefore has potential as an objective measure of RP. Further validation work is now required, as well as studies examining sensitivity to change. Disclosure G. Dinsdale: None. J. Manning: None. A. Herrick: None. M. Dickinson: None. C. Taylor: None.

Evolving Symptom Characteristics of Raynaud's Phenomenon in Systemic Sclerosis and Their Association With Physician and Patient-Reported Assessments of Disease Severity.

Assessment of Raynaud's phenomenon (RP) in systemic sclerosis (SSc) is reliant on self-report. The Raynaud's Condition Score (RCS) diary assumes discrete episodic RP attacks, although not all SSc patients identify with this paradigm. We investigated the clinical associations of SSc-RP symptom characteristics and the evolution of SSc-RP symptoms with disease progression. A cross-sectional study at UK and US sites captured digital color changes of SSc-RP and patients' ability to identify with diagrammatic representations (and descriptive stems) of 4 distinct theoretical SSc-RP patterns (progressing severity A through D) reflecting progressively severe SSc-RP experiences. SSc-RP self-management and symptom evolution were explored. Patient demographics, the clinical phenotype, the Scleroderma Health Assessment Questionnaire (SHAQ), the 2-week RCS diary, and patient and physician global assessments were collected. We enrolled 107 patients with SSc (with questionnaires returned by 94). A higher number of self-reported digital color changes of SSc-RP were associated with increased SSc-RP symptom severity but not with the SSc clinical phenotype. Patients could identify with distinct patterns of SSc-RP. These patterns were associated with disease duration, global disease severity, and conceptually linked physician and patient assessments of peripheral vascular severity (e.g., SHAQ RP subscale and RCS diary parameters), but not with conceptually unrelated outcomes (e.g., SHAQ breathing subscale). SSc-RP characteristics and symptom severity evolve during the disease course. Patients identify with distinct patterns of SSc-RP that may relate to progression of the obliterative microangiopathy of SSc. Difficulty distinguishing discrete SSc-RP attacks from persistent digital ischemia in patients with advanced SSc could influence diary-based approaches to assessing SSc-RP, with implications for future clinical trials.

Sexual Dysfunction in Female Scleroderma Patients and Its Correlation with Vascular Involvement

Objectives: Investigating the sexual dysfunction in scleroderma patients and its relation to their vascular involvements. Method: A case control study was done on 80 married female scleroderma patients with age between 20-60 years old. Eighty normal individuals adjusted for age, place of living and socioeconomic status were also recruited. Sexual performance in both groups was assessed using FSFI standardized questionnaire, which evaluated it in 6 domains of desire, arousal, lubrication, orgasm, satisfaction, and pain. Micro and macro-vascular involvements of the patients were also determined using Raynaud Condition Score, Echocardiography, physical exam for assessing their digital ulcers and reviewing their medical records for past or present history of renal crisis and thromboembolic events. Results: The total score of FSFI in the case group was significantly lower compared to control one (16.68 ± 6.35, 19.69 ± 6.01, P-value

French translation and linguistic validation of the Raynaud's condition score

The Raynaud's condition score is a 11-point scale severity score used in Raynaud's phenomenon clinical trials since 1998. The Raynaud's condition score diary has been recommended for use in clinical trials assessing efficacy of interventions on scleroderma related Raynaud's phenomenon. However, this score has never been formally validated in French. We thus performed a translation and a linguistic validation of the Raynaud's condition score through a forward/backward translations process followed by an expert review and cognitive patient interviews. The translations led to a French version of the Raynaud's condition score that was linguistically valid, and conceptually equivalent to the original English version. This "Score de Raynaud" will be usable to perform and harmonize clinical trials in French-speaking patients with secondary Raynaud's phenomenon.

Factors Influencing Raynaud Condition Score Diary Outcomes in Systemic Sclerosis.

Raynaud phenomenon (RP) in systemic sclerosis (SSc) could be influenced by clinical phenotype, environmental factors (e.g., season), and personal factors (e.g., coping strategies and ill-health perceptions). We studied the relative influence of a range of putative factors affecting patient-reported assessment of SSc-RP severity. SSc patients were enrolled at UK and US sites. Participants completed the 2-week Raynaud Condition Score (RCS) diary alongside collection of patient demographics, clinical phenotype, the Coping Strategies Questionnaire, Pain Catastrophizing Scale, Scleroderma Health Assessment Questionnaire (SHAQ), and both patient/physician visual analog scale (VAS) assessments for RP, digital ulcer disease, and global disease. Environmental temperature data were obtained at each site. A second RCS diary was completed 6 months after enrollment. We enrolled 107 patients (baseline questionnaires returned by 94). There were significant associations between RCS diary variables and both catastrophizing and coping strategies. There were significant associations between RCS diary outcomes and both environmental temperature and season of enrollment. Age, disease duration, sex, disease subtype, smoking, and vasodilator use were not associated with RCS diary outcomes. The best-fitting multivariate model identified the patient RP VAS, SHAQ pain VAS, and SHAQ gastrointestinal VAS subscales as the strongest independent predictors of the RCS. Patient-reported assessment of SSc-RP severity is associated with a number of factors including pain, catastrophizing, and coping strategies. The effects of seasonal variation in environmental temperature on SSc-RP burden has implications for clinical trial design. Treatments targeting SSc-RP pain and the development of behavioral interventions enhancing coping strategies may reduce the burden of SSc-RP.

Patient-reported outcome instruments for assessing Raynaud's phenomenon in systemic sclerosis: A SCTC Vascular Working Group Report.

The episodic nature of Raynaud's phenomenon (RP) in systemic sclerosis (SSc) has led to a reliance on patient-reported outcome (PRO) instruments such as the Raynaud's Condition Score (RCS) diary. Little is known about the utilisation in routine clinical practice and health professional attitudes towards existing PRO instruments for assessing SSc-RP. Members of the Scleroderma Clinical Trials Consortium Vascular Working Group (SCTC-VWG, n=28) were invited to participate in a survey gauging attitudes towards the RCS diary and the perceived need for novel PRO instruments for assessing SSc-RP. Nineteen SCTC-VWG members (68% response rate) from academic units based in North America (n=9), Europe (n=8), South America (n=1) and Australasia (n=1) took part in the survey. There was broad consensus that RCS diary returns could be influenced by factors including seasonal variation in weather, efforts made by patients to avoid or ameliorate attacks of RP, habituation to RP symptoms, evolution of RP symptom characteristics with progressive obliterative microangiopathy, patient coping strategies, respondent burden and placebo effect. There was consensus that limitations of the RCS diary might be a barrier to drug development (79% of respondents agree/strongly agree) and that a novel PRO instrument for assessing SSc-RP should be developed with the input of both clinicians and patients (84% agree/strongly agree). Perceived potential limitations of the RCS diary have been identified along with concerns that such factors might impede drug development programs for SSc-RP. There is support within the systemic sclerosis community for the development of a novel PRO instrument for assessing SSc-RP.