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This review examines the role of various imaging techniques in assessing vascular and musculoskeletal manifestations in Systemic Sclerosis (SSc). Imaging modalities, such as thermography, capillaroscopy, ultrasound, optical coherence tomography, laser speckle contrast analysis, radiography, computed tomography, and MRI, offer valuable insights into SSc-related complications. Findings suggest that these techniques aid in diagnosing conditions like Raynaud phenomenon, digital ulcers, calcinosis, acro-osteolysis, and hand contractures. However, each modality has its advantages and limitations, necessitating a multimodal approach for comprehensive evaluation and accurate diagnosis of SSc-related manifestations., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Systemic sclerosis (SSc) is a chronic multisystemic disease characterized by immunological activation, diffuse vasculopathy, and generalized fibrosis exhibiting a variety of symptoms. A recognized precursor of SSc is Raynaud's phenomenon, which is part of the very early disease of systemic sclerosis (VEDOSS) in combination with nailfold videocapillaroscopy (NVC) impairment. The pathophysiology of ocular involvement, alterations in internal organs, and body integumentary system involvement in SSc patients are complicated and poorly understood, with multiple mechanisms presumptively working together. The most prevalent ocular symptoms of SSc are abnormalities of the eyelids and conjunctiva as well as dry eye syndrome, due to fibroblasts' dysfunction and inflammation of the ocular surface. In particular, lagophthalmos, blepharophimosis limitation of eyelid motion, eyelid telangiectasia, and rigidity or tightening of the lids may affect up to two-third of the patients. In addition, reduction in central corneal thickness, iris defects and higher rates of glaucoma were reported. In the first reports based on retinography or fluorescein angiography, about 50% of SSc patients showed signs of vascular disease: peripheral artery occlusion, thinning of retinal pigment epithelium and choroidal capillaries, ischemic areas surrounded by intraretinal extravasation and microaneurysms, and peripheral capillary non-perfusion. Successively, thanks to the advent of optical coherence tomography angiography (OCTA), several studies highlighted significant impairment of either the choriocapillaris and retinal vascular plexuses, also correlating with NVC involvement and skin disease, even in VEDOSS disease. Given the sensitivity of this technique, ocular micro-vasculopathy may act as a tool for early SSc identification and discriminate between disease stages.

Objectives: To evaluate microcirculation abnormalities and their clinical association in patients with BS, especially with vascular manifestations., Methods: A cross-sectional study was carried out using nailfold videocapillaroscopy (NVC) to evaluate the microcirculation in patients with BS., Results: A total of 65 patients were included in the study. Thirty-four (52.3%) were men, and 84.6% were European Caucasian. Vascular involvement was present in 24 (36.9%) patients. Qualitative abnormalities in NVC were observed in 47.7% of patients. The most frequent were tortuous and branched capillaries (21.5%), followed by microhaemorrhage (12.3%), enlarged capillary (7.7%) and giant capillary (3.1%). We found a significant relationship between the presence of tortuous and branched capillaries and previous superficial thrombophlebitis (ST) (p=0.025). The presence of ≥2 qualitative abnormalities in NVC was associated with vascular involvement (p=0.031), mainly with venous thrombotic events (p=0.024) and particularly with ST (p=0.003). No specific Cutolo's pattern was observed. No association was observed between NVC and Raynaud's phenomenon or ANA, although patients with positive ANA presented more frequent non-specific capillaroscopic abnormalities (p=0.003)., Conclusions: The presence of ≥2 qualitative abnormalities in NVC is associated with Vasculo-Behçet. NVC might be a potential tool for early detection of patients at risk of vascular events.

Background: Raynaud's phenomenon is the earliest and most common systemic sclerosis manifestation. Episodes can be triggered by cold exposure and ambient temperature changes. Small studies have found that Raynaud's phenomenon outcomes were associated with season. We aimed to map the degree that differences in ambient temperature are associated with Raynaud's phenomenon outcomes across the temperature spectrum., Methods: People with Raynaud's phenomenon secondary to systemic sclerosis in the Scleroderma Patient-centered Intervention Network Cohort completed past-week Raynaud's phenomenon severity assessments (0-10 numerical rating scale) at enrolment and longitudinally at 3-month intervals. Mean daily temperature and feels like temperature, which incorporates wind chill and humidity, for the week before each assessment were extracted for each participant from a weather site close to the participant's recruiting centre via the Iowa Environmental Mesonet. We used linear mixed models with basis splines to flexibly model non-linear changes in Raynaud's phenomenon severity across the temperature spectrum. People with lived experience of systemic sclerosis contributed to the study design and interpretation., Findings: Between April 15, 2014 and Aug 1, 2023, we included data on 20 233 Raynaud's phenomenon severity assessments from 2243 participants. 1964 (88%) of 2243 participants were women, 279 (12%) were men, and 1813 (82%) were White. Mean age was 54·8 (SD 12·7) years. The maximum predicted Raynaud's phenomenon severity score was 6·8 points (95% CI 5·6-8·1), which occurred at -25°C. Severity scores decreased minimally from -15°C to 5°C (0·05-0·21 points per 5°C difference), then decreased in larger steps between 5°C and 25°C (0·37-0·54 points per 5°C difference). The minimum predicted score was at 25°C (2·6 points [95% CI 2·5-2·7]). Scores increased at temperatures above 25°C to 3·5 points (3·0-4·1) at 35°C and 5·6 points (4·5-6·8) at 40°C. Results were similar for feels like temperature., Interpretation: Raynaud's phenomenon severity is worst at very cold temperatures but also increases with very warm temperatures, presumably due to air conditioning. Clinical management and Raynaud's phenomenon intervention trial designs should consider temperature patterns., Funding: Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University., Competing Interests: Declaration of interests JDP has received speaker honoraria or consultancy fees from Astra Zeneca, Boehringer Ingelheim, IsoMab, Janssen, Permeatus, and Sojournix Pharma. MDM has received research grants or contracts from Prometheus Biosciences, Mitsubishi Tanabe, Boehringer Ingelheim, EICOS, Corbus, and Horizon Pharma; consulting fees from Cabaletta Pharma; an honorarium from GSK Pharma; and was a member of a data safety monitoring board or advisory board with Mitsubishi Tanabe, Boehringer Ingelheim, and EICOS. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: We declare no competing interests.

Raynaud's phenomenon consists of excessive contraction of the blood vessels in response to various stimuli; although it usually affects the extremities, other locations are less frequently involved. This study focused on describing the characteristics of a series of women with Raynaud's phenomenon of the nipple. Through medical record review and direct communication with patients, data from 12 women diagnosed with Raynaud's phenomenon of the nipple between 2016 and 2023 were collected and analyzed. The following variables were assessed: age, symptoms, triggering factors, treatment, and duration of symptoms. In this case series, Raynaud's phenomenon of the nipple in breastfeeding women was more common among primiparous women around 10 days after delivery; pain was severe and, in most cases, improved with local and/or drug treatment, and did not limit the duration of breastfeeding., (Sociedad Argentina de Pediatría.)

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.)

Hand-arm vibration is a common occupational exposure that causes neurological impairment, myalgia, and vibration-induced Raynaud's phenomena or vibration white fingers (VWF). The pathological mechanism is largely unknown, though several mechanisms have been proposed, involving both immunological vascular damage and defective neural responses. The aim of this study was to test whether the substances interleukin-33 (IL-33), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), endothelin-1 (ET-1), C-C motif chemokine ligand 20 (CCL20), calcitonin, and thromboxane (TXA 2 ) changed before and after occupational hand-arm vibration exposure. 38 full-time shift workers exposed to hand-arm vibration were recruited. All the participants underwent medical examinations regarding symptoms of Raynaud's phenomena. In 29 of the participants, the concentration of IL-33, MDC, IL-10, ET-1, CCL20, calcitonin, and TXA 2 was measured before and after a workday. There was a significant increase in ET-1 and calcitonin concentration and a decrease in the CCL20 concentration after the work shift in all participants. In the group suffering from VWF, but not in the non-VWF group, MDC was statistically significantly lower before the work shift ( p = .023). The VWF group also showed a significant increase in MDC after the work shift. Exposure to occupational hand-arm vibration is associated with changes in ET-1, calcitonin, and MDC concentration in subjects suffering from vibration white fingers, suggesting a role of these biomarkers in the pathophysiology of this condition., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Patients with secondary RP show a wide range of symptoms depending on the condition of vascular structures. If the symptoms are localized to specific fingers and angiography reveals a discrete segment of occlusion of a proper digital artery, we perform proper digital artery reconstruction with an interposition vein graft. The objective of this study was to evaluate the results of the surgery in patients with chronic hand ischaemia., Methods: A retrospective chart review was performed on patients who underwent proper digital artery reconstruction. Each digit that underwent grafting was analysed separately. The results of surgical intervention and recurrence based on patient symptoms were evaluated. Cox proportional hazards regression models were used to identify independent risk factors associated with recurrence, and the Kaplan-Meier method was used to predict the 5-year recurrence-free rate., Results: A total of 79 digits from 57 patients were included in this study. The majority of patients demonstrated resolution of ischaemic pain and ulceration (97.5% and 95.3%, respectively). Recurrence occurred in 16 (20.3%) patients during the follow-up period. In two cases (2.5%) surgery had no effect. In the multivariate Cox regression analysis, smoking and concomitant periarterial sympathectomy were significant factors associated with recurrence. In the Kaplan-Meier analysis, the 5-year recurrence-free rate in the total study population was 69.3%., Conclusions: Digital artery reconstruction using an interposition vein graft is an effective procedure for improving ischaemic pain and ulceration in patients with RP. Smoking and concomitant periarterial sympathectomy were significantly associated with recurrence., (© 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.)

Primary Raynaud's phenomenon (PRP) is characterised by episodic, reversible, and disabling vasospasms of the peripheral arteries. In the most severe cases, it can lead to ulceration of the fingers and toes. Neuro fascial VascularTraining (NFVT) is a novel therapeutic approach for treating PRP. NFVT aims to enhance peripheral circulation and stimulate the autonomic nervous system (ANS) by engaging multiple physiological mechanisms simultaneously. This integrated approach works to reduce vasospasms and alleviate associated symptoms through neurodynamic and myofascial interventions. A 54-year-old woman, who has experienced pain and hypoesthesia in her hands for 9 years, received a diagnosis of PRP without systemic sclerosis in 2014. The patient reported daily colour changes in her fingers, along with pain and a temporary decrease in tactile sensitivity. The patient engaged in ten 30-minute exercise sessions, and the clinical outcomes were assessed based on several parameters. These included the frequency and duration of vasospastic attacks, evaluated using the Raynaud Condition Score, as well as pain and tingling, measured through the daily Numeric Rating Scale. The Composite Autonomic Symptom Score (COMPASS 31) was utilised to assess dysautonomia, while the frequency of medication use and the Disabilities of the Arm, Shoulder, and Hand questionnaire were also considered. The results indicated a significant improvement in symptoms. NFVT improved symptoms and motor dysfunction in a patient with Raynaud's syndrome, demonstrating how NFVT can increase peripheral blood flow, stimulate the ANS, and improve symptoms in PRP., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

This study aims to analyze the clinical and immunologic features of SLE in Jordan, while also investigating the impact of age and gender on disease presentation. The study included 275 patients diagnosed with SLE. Data were collected through meticulous patient interviews and thorough examination of patient hospital records. The cohort exhibited a mean age of 36.8 ± 12.9 years, with an average disease duration of 7.0 ± 7.8 years. The mean age at diagnosis was 29.9 ± 12.1 years, and the female to male ratio was 7.8:1. The most frequently observed symptoms were arthralgia (90.2%), fatigue (80.7%), hematologic manifestations (62%), photosensitivity (60.7%), Raynaud's phenomenon (53.5%), and malar rash (50.9%). The frequencies of various autoantibodies were as follows: ANA (96.7%), anti-dsDNA (39.6%), anti-SSA/Ro (32.8%), anti-Sm (21.8%), anti-U1-RNP (20.6%), and anti-SSB/La (15.5%). Male patients tended to receive a diagnosis at a younger age and exhibited a higher likelihood of experiencing severe manifestations compared to females. Additionally, juvenile onset patients demonstrated an increased likelihood of fever, photosensitivity, myositis, and anti-dsDNA autoantibodies, while adult onset patients were more predisposed to having anti-Ro, anti-La, and RF autoantibodies. This study reveals that the most prevalent manifestations of SLE in the Jordanian cohort encompassed arthralgia, fatigue, and hematologic manifestations. The prevalence of alopecia and Raynaud's phenomenon exceeded that observed in other published cohorts, while arthritis and discoid rash were less frequently encountered. The study highlights that males are more susceptible to developing severe manifestations of SLE compared to females., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Background: Interstitial lung disease (ILD) is a common pulmonary manifestation of Sjögren's syndrome (SjS) and associated with an increased risk of death. Early detection and treatment of ILDs and knowing the risk factors are very important for prognosis in rheumatic diseases., Aims: This study was performed to determine ILD and associated factors in patients with SjS., Methods: Four hundred three SjS patients were evaluated in this cross-sectional cohort study. Clinical, laboratory, serological, and imaging features were compared of patients with and without pulmonary involvement. Logistic regression analyses were used to identify risk factors for lung involvement and to identify independent risk factors., Results: Thirty-five (8.7%) of SjS patients had ILD and 368 (91.3%) had no ILD. The presence of Raynaud's phenomenon was significantly more common in ILD. The geriatric age group over the age of 65 years (OR 8198; 95% CI 3788-17,742; p < 0.001), Raynaud's phenomenon (OR 17,852; 95% CI 6155-51,779; p < 0.001), and smoking (OR 3598; 95% CI 1495-8657; p = 0.003) were risk factors to be associated for ILD in the multivariable analysis. The most common abnormality was non-specific interstitial pneumonia in 20 patients (57.1%) and usual interstitial pneumonia in 15 (42.9%) patients., Conclusions: The distribution of male patients compared to female patients was higher in patients with lung involvement than in patients without lung involvement. This may be related to older age, higher smoking rate, and longer nicotine consumption in men. Age, smoking, and severity of lung involvement are more important than inflammation status and autoantibodies for prognosis., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objectives: Assessment of construct validity and reliability of a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of RP in SSc., Methods: An international multicentre study validation study of the 27-item Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) and 10-item short-form (ASRAP-SF) questionnaires. The relationship between ASRAP questionnaires and demographics, clinical phenotype and legacy instruments for assessing SSc-RP severity, disability and pain was assessed. Repeatability was evaluated at 1 week. Anchor-based statements of health status facilitated assessment of ASRAP thresholds of meaning., Results: A total of 420 SSc subjects were enrolled. There was good correlation between ASRAP (and ASRAP-SF) with RP visual analogue scale (VAS) and Scleroderma Health Assessment Questionnaire RP VAS (rho range 0.648-0.727, P < 0.001). Correlation with diary-based assessment of SSc-RP attack frequency and duration was lower (rho range 0.258-0.504, P < 0.001). ASRAP questionnaires had good correlation with instruments for assessing disability, hand function, pain and global health assessment (rho range 0.427-0.575, P < 0.001). Significantly higher ASRAP scores were identified in smokers, patients with active digital ulceration (DU), previous history of DU and calcinosis (P < 0.05 for all comparisons). There was excellent repeatability at 1 week among patients with stable SSc-RP symptoms (intra-class coefficients of 0.891 and 0.848, P < 0.001). Patient-acceptable symptom state thresholds for ASRAP and ASRAP-SF were 45.34 and 45.77, respectively. A preliminary Minimally Important Clinical Difference threshold of 4.17 (95% CI 0.53, 7.81, P = 0.029) was estimated., Conclusion: ASRAP and ASRAP-SF questionnaires are valid and reliable novel PRO instruments for assessing the severity and impact of SSc-RP., (© 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.)

Neutrophil extracellular traps (NETs) are cell-extruded DNA strands coated with neutrophils' nuclear proteins and enzymes from cytotoxic granules, produced by NETosis, a cell death pathway. They perform an important defensive role in innate immunity, but their increased production and/or inefficient degradation expose new antigens, such as DNA or citrullinated histone peptides, triggering autoimmunity. This study aimed to access possible associations between serum NETs levels with epidemiological, clinical, and serological data from a well-characterized SLE Brazilian patients' cohort. NET levels were evaluated in one hundred seventy serum samples of patients with Systemic Lupus Erythematosus (SLE) using an Immunoassay. Univariate and multivariate binary logistic regression used clinical patients' data as independent variables. Parametric and non-parametric tests compared log10 base serum NET levels transformed between patients' groups. SLE patients were also dichotomized into "High serum NET levels" and "Low serum NET levels" groups. All analyses were performed in R language 4.1.2, and p < 0.05 were considered significant. Increased susceptibility for high serum NET levels was observed in SLE patients with Raynaud's phenomenon (OR = 2.30, 95 % CI = 1.06-5.21 and p = 0.039), independently of any other risk factor. Also, SLE patients with Raynaud's phenomenon presented higher mean NET serum levels (mean = -0.13 vs. -0.51, p = 0.01). In addition, higher mean NET serum levels were associated with glomerulonephritis (mean = -0.45 vs. -0.12, p = 0.03). Ultimately, the SLEDAI index scored higher in the high NETs serum levels group (median = 2.0 vs. 0.0, p = 6 × 10 -3 ). The formation of NETs might be implicated in Raynaud's phenomenon, glomerulonephritis, and disease index score in SLE patients. Our results highlight the importance of serum NET levels as a possible therapeutical target to modulate the clinical course of SLE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: To develop evidence-based recommendations for the non-pharmacological and pharmacological management of Raynaud's phenomenon (RP) and digital ulcers (DUs) in patients with systemic sclerosis and other immune-mediated connective tissue diseases (CTDs)., Methods: A task force comprising 21 rheumatologists, two surgeons (vascular and plastic), two nurses, and one patient representative was established. Following a systematic literature review performed to inform the recommendations, statements were formulated and discussed during two meetings (one online and one in-person). Levels of evidence, grades of recommendation (GoR), and level of agreement (LoA) were determined., Results: Five overarching principles and 13 recommendations were developed. GoR ranged from A to D. The mean ± standard difference (SD) LoA with the overarching principles and recommendations ranged from 7.8±2.1 to 9.8±0.4. Briefly, the management of RP and DUs in patients with CTDs should be coordinated by a multidisciplinary team and based on shared decisions with patients. Nifedipine should be used as first-line therapy for RP and/or DUs. Sildenafil, tadalafil, and/or iloprost IV are second-line options for severe and/or refractory patients with RP and/or DUs. Sildenafil, tadalafil and/or Iloprost IV, should be prescribed for healing and prevention (also including bosentan) of DUs. In patients with RP and/or DUs, non-pharmacological interventions might be considered as add-ons, but there is limited quality and quantity of scientific evidence supporting their use., Conclusions: These recommendations will inform rheumatologists, specialist nurses, other healthcare professionals, and patients about a comprehensive and personalized management of RP and DUs. A research agenda was developed to address unmet needs, particularly for non-pharmacologic interventions.

Objective: To explore, from patients' perspectives, the symptoms and impact of Raynaud's phenomenon (RP) on the feet of patients with systemic sclerosis (SSc-RP), and to identify which foot-related domains are important to patients., Methods: Forty participants (34 women) with SSc-RP took part in one of six focus groups held in the United Kingdom or United States. Participants were purposively sampled to ensure diversity in disease type, duration, and ethnicity. The topic guide included questions on RP impact, self-management, and treatment expectations. Qualitative content analysis was employed to identify key concepts in the data relating to foot-specific symptoms and their impact. Themes were organized by corresponding domains of potential importance., Results: Twenty-eight participants (70 %) reported experiencing RP in their feet. Five themes were identified corresponding to domains of potential importance: temperature changes, pain, cramping and stiffness, numbness, and color changes. These issues negatively affected participants' lives, impairing walking, driving, and socializing, and causing issues with footwear and hosiery., Conclusions: This large qualitative study exploring the experiences of patients with SSc-RP in the feet identified several key domains of high importance to patients. SSc-RP is common in the feet, presents in several patterns, and impacts multiple aspects of patients' lives. These findings indicate where future foot-specific interventions for RP could be targeted. Findings from this study improve understanding of what domains are important to patients with SSc-RP affecting the feet and will contribute to the development of a core outcome set for foot and ankle disorders in rheumatic and musculoskeletal diseases., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Raynaud phenomenon (RP) presents with either primary or secondary disease, and both have the potential to negatively impact patient quality of life. First-line management of RP should include lifestyle modifications in all patients. Some patients with primary RP and most with secondary RP require pharmacologic therapies, which may include calcium channel blockers, topical nitrates, phosphodiesterase 5 inhibitors, or endothelin antagonists. Additional approaches to treatment for those with signs of critical ischemia or those who fail pharmacologic therapy include botulinum toxin injection and digital sympathectomy. Herein, we describe in detail the treatment options for patients with RP as well as provide treatment algorithms for each RP subtype., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Vibration white finger is a form of secondary Raynaud's phenomenon (RP) caused by the use of handheld vibrating tools. RP usually appears on the extremities of the fingers, and its borders are well recognised. No reports have been published on 'mottled' RP in continuous observation from the onset to the disappearance of RP. A man in his 60s who had been using vibrating tools such as jackhammers and tampers for 30 years presented with sensations of coldness, burning and numbness. Whole-body cold exposure was performed outdoors in winter, and RP was photographed continuously. 'Mottled' RP can be defined as triphasic colour changes: white, blue and red. The patient was taken off work, kept warm and medicated. His symptoms improved slightly after 10 years of follow-up, but the RP did not disappear. 'Mottled' RP is rare and refractory and should be recognised as a form of RP., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose of Review: To describe the clinical significance of and the diagnostic approach to Raynaud phenomenon (RP) in the peripheral extremities and the heart., Recent Findings: Nailfold capillaroscopy has recently been standardized in an expert consensus paper. Abnormal capillaroscopy in combination with specific autoantibody profiles and clinical signs are highly predictive of progression of RP to systemic sclerosis (SSc). Magnetic resonance imaging (MRI) can also perform tissue characterization of both the extremities and the heart. Microvascular wall abnormalities detected using nailfold capillaroscopy in patients with SSc may lead to deposition of erythrocyte-derived iron, due to microhemorrhages, which may predispose to fibrosis. MRI can assess the presence of iron using T2∗ measurements., Summary: RP is a hallmark of the microvasculopathy in SSc and can affect both the peripheral extremities and the heart. Nailfold capillaroscopy is the current gold standard for the evaluation of the peripheral microvasculature. Other imaging modalities include thermography, laser Doppler-derived methods, 99m Tc-pertechnetate hand perfusion scintigraphy, power Doppler ultrasonography, dynamic optical coherence tomography, MRI, and photoacoustic imaging, but these are currently not widely used. Cardiac RP can be investigated with positron emission tomography or cardiovascular magnetic resonance, with the latter offering the additional possibility of tissue characterization and iron content quantification secondary to microhemorrhages., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Raynaud's phenomenon is an exaggerated response to cold stimuli that may be primary or secondary. The diagnosis relies on patient history and physical examination to distinguish RP from other vasomotor dysfunction (e.g. acrocyanosis, pernio, small fiber neuropathy with vasomotor symptoms, and complex regional pain syndrome). Achenbach syndrome, or spontaneous venous hemorrhage, may also be mistaken for RP but is a self-limiting phenomenon. Laboratory evaluation and vascular diagnostic testing may identify SRP causes. Regardless of etiology, treatment includes warming with trigger avoidance, and consideration of vasodilators (eg. calcium channel, alpha-1 blockers). SRP with digital ulceration may require PDE5i, endothelin-1 receptor blockers, and prostanoids. Refractory cases may require pneumatic arterial pumps, botulinum toxin administration, or surgical sympathectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: 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., Methods: 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., Results: 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., Conclusions: Heating of the upper arm near the elbow is effective in alleviating Raynaud's phenomenon in SSc., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

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: To develop, refine, and score a novel patient-reported outcome instrument to assess the severity and impact of Raynaud's phenomenon (RP) in systemic sclerosis (SSc)., Methods: The Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) questionnaire items were developed with patient insight partner support and grounded in the lived patient experience of SSc-RP. ASRAP items underwent formal qualitative assessment and linguistic testing. An international multicenter study was undertaken to field test the preliminary ASRAP questionnaire., Results: A preliminary 37-item ASRAP questionnaire was supplemented with 2 additional items following expert review to enhance content coverage before undergoing formal linguistic testing to optimize readability. Patient cognitive debriefing interviews were undertaken to enhance comprehension, ambiguity, cognitive difficulty, relevance, and content coverage of both the ASRAP items and instructions. We enrolled 420 SSc patients from scleroderma centers in the UK and US over 2 consecutive winters. Factor analysis with item response theory was undertaken to remove redundant and poorly fitting items. The retained 27-item long-form ASRAP questionnaire was calibrated and scored using the graded response model. A fixed 10-item short-form ASRAP questionnaire was developed using computerized adaptive testing simulations., Conclusion: The ASRAP questionnaire has been developed with extensive SSc patient input, with items grounded in the lived experience of SSc-RP to ensure strong content validity, with a focus on how patients feel and function. An advanced psychometric approach with expert input has removed redundant and/or poorly fitting items without eroding content validity. Long- and short-form ASRAP questionnaires have been calibrated and scored to permit formal validation., (© 2022 American College of Rheumatology.)

Background: Raynaud phenomenon (RP) is a vasospastic condition of the digits that can be primary or secondary to systemic disease. Symptoms are triggered by cold or stress and can cause pain and skin color changes. The chronic ischemia may lead to necrosis, ulceration, and amputation. There are no Food and Drug Administration-approved treatments and cases refractory to pharmacologic and surgical treatments are difficult to control. Local botulinum toxin injections have been increasingly used in the treatment of Raynaud disease and have shown promising results., Aim of the Study: To examine the outcomes, techniques, and complications of botulinum toxin use for the treatment of Raynaud disease., Methods: The PubMed database was queried using "botulinum toxin" AND "Raynaud phenomenon" as title key words. Preferred reporting items for systematic reviews and meta-analysis criteria were used. Additional articles were selected while reviewing the references of the articles from PubMed. No time restrictions were followed. Articles of all languages were included. Articles were analyzed for study type, demographics, diagnosis/inclusion criteria, treatment methods, outcome measures, length of follow-up, results, and complications. A positive outcome was defined as subjective improvement in symptoms and/or improvement in the outcome measures. A poor outcome was defined as harm done to the patient by the injection that would not have occurred otherwise., Results: Forty-two clinical studies describing the use of botulinum toxin for Raynaud's phenomenon were found. A total of 425 patients with primary or secondary Raynaud's were treated, with ages ranging from 14 to 91 years. There were 342 women and 81 men, with a female-to-male ratio of 38:9. Outcomes were positive in 96.2% of patients. There were 14.2% of the studies that reported 3.5% of all patients showing no subjective improvement. A single study reported a poor outcome for 1 patient. There were 40.5% of the studies that reported complications, affecting 20.2% of all patients. The most frequently reported complication was transient hand weakness, affecting 44.2% of patients with complications and 8.9% of total patients. Weakness resolved in hours to months after injection. Pain at the injection site lasting minutes to days was reported in 40.7% of patients with complications, and 8.2% of total patients., Conclusions: Botulinum toxin treatment for RP is effective. Complications are minor and self-limiting., Competing Interests: Conflicts of interest and sources of funding: None declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The objective of the study was to establish the repeatability of baseline diagnostic images of the dorsum of the hands acquired using a high-resolution laser Doppler imager in patients with Raynaud's phenomenon secondary to systemic sclerosis (SSc)., Methods: The dorsal side of the hands of 22 patients (8 male 14 female), age range 29-73, median 62, with SSc and secondary Raynaud's phenomenon were imaged over two consecutive days at approximately the same time using a Moor Instruments' high-resolution laser Doppler imaging unit. The images were analysed by taking regions of interest at discrete locations in the images to calculate dimensionless values of flux (PU). Repeatability of the diagnostic investigation was assessed using methods described by Bland and Altman and by also plotting the results from visit 1 against visit 2 and calculating the line of best fit., Results and Conclusions: Based on the criteria that 95% of all measurement differences should be within a factor of 1.96 of the standard deviations of the mean values, then high-resolution laser Doppler imaging technique is probably repeatable when acquiring and analysing baseline images of patients with Raynaud's phenomenon secondary to SSc. However, a larger study with more patients is required to prove this conclusively-as only data from 19 patients were analysed (3 patients were not included due to technical issues)-and was therefore susceptible to marked clinical variations in patients presenting on different days for the investigations., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 characterise associations between individual nailfold capillary aberrations with autoantibodies in a cross-sectional study on children and adults with Raynaud's phenomenon (RP)., Methods: Consecutive children and adults with RP and without previously known connective tissue disease (CTD) systemically underwent nailfold capillaroscopy and laboratory tests for the presence of antinuclear antibodies (ANA). The prevalence of individual nailfold capillary aberrations and ANA was assessed, and the associations between individual nailfold capillary aberrations and ANA were analysed separately in children and adolescents., Results: In total, 113 children (median age 15 years) and 2858 adults (median age 48 years) with RP and without previously known CTD were assessed. At least one nailfold capillary aberration was detected in 72 (64%) of included children and in 2154 (75%) of included adults with RP (children vs adults p<0.05). An ANA titre ≥1:80, ≥1:160 or≥1:320 was observed in 29%, 21% or 16% of included children, and in 37%, 27% or 24% of screened adults, respectively. While the occurrence of individual nailfold capillary aberrations was related to the presence of an ANA titre of ≥1:80 in adults (reduced capillary density, avascular fields, haemorrhages, oedema, ramifications, dilations and giant capillaries: each p<0.001), no comparable association between nailfold capillary aberrations and ANA was observed in children with RP without previously known CTD., Conclusion: In contrast to adults, the association between nailfold capillary aberrations and ANA might be less pronounced in children. Further studies are warranted to validate these observations in children with RP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Objective: Our main aim was to investigate the effect of a single oral dose of C21, a selective angiotensin II type 2 receptor agonist, on cold-induced vasoconstriction in SSc-related RP., Methods: This was a phase IIa, randomized, double-blind, cross-over, single-dose, placebo-controlled, single-centre study. Twelve female patients with SSc (median age 58.5 years, median duration of RP 19.0 years) attended on four occasions: screening, treatment visits 1 and 2 (separated by 3-7 days) and follow-up. At the first treatment visit, patients were randomized to receive either a single oral dose of C21 (200 mg) or placebo, then the opposite treatment on the second visit. Forty min after each treatment, each patient underwent a standard hand cold challenge. The primary end point was the area under the curve (AUC) for rewarming for each finger (eight fingers) over 15 min. Secondary end points included the maximum finger temperature after rewarming (MAX). Statistical analyses were performed by multiplicative ANCOVA models., Results: For all eight fingers combined, mean AUC for rewarming was higher after treatment with C21 than after placebo (geometric mean 20 046°C*s vs 19 558°C*s), but not significantly (P = 0.380) and MAX (at 15 min) was also higher (geometric mean 23.5°C vs 22.5°C; P = 0.036). C21 was well tolerated., Conclusion: Despite the small trial size, a signal emerged suggesting that even in patients with established SSc, C21 may confer benefit for RP and deserves further investigation., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04388176., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Raynaud's phenomenon is a symptom complex manifested as intermittent fingertip ischemia caused by cold or other sympathetic drivers. Secondary Raynaud's phenomenon is often more severe and could even lead to finger ulceration, making it particularly complicated to treat. We describe a case of severe Raynaud's phenomenon secondary to subclinical hypothyroidism lasting for more than 6 hours in a 65-year-old woman. The patient was also diagnosed with hypothyroidism, epilepsy, and secondary soft tissue infection of the right middle and ring fingers. After careful multidisciplinary consultation and discussion, the patient received vasodilation, anticoagulation, thyroxine supplementation, stellate ganglion block, hyperbaric oxygen therapy and debridement. The patient responded well to the medication, avoiding amputation or obviously dysfunction. Multidisciplinary team gathering the doctors from different departments proposes appropriate strategies for patients with severe Raynaud's phenomenon and could improve the prognosis and satisfaction of patient effectively.

A woman in her mid-60s presented to transient ischaemic attack (TIA) clinic with a 3-year history of intermittent sensory changes and white discolouration affecting the left side of her tongue. Following extensive investigation, a provisional diagnosis of posterior circulation TIA was made, and the patient was commenced on clopidogrel therapy. Despite anti-platelet treatment, she continued to have identical episodic symptoms. She was referred to the rheumatology team for assessment of possible underlying autoimmune pathology. On rheumatology assessment, the patient reported colour changes on the tongue, associated with numbness, followed by paraesthesia of the affected area. A comprehensive assessment excluded secondary causes and a diagnosis of primary Raynaud's phenomenon of the tongue was made. The diagnosis of TIA was revoked. This case illustrates a rare presentation of a common condition and highlights the sensory symptoms which are associated with Raynaud's phenomenon., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: The early heterogenous presentation of systemic sclerosis (SSc), in particular without skin involvement, has been a confounding factor delaying early diagnosis. In fact, early signs of SSc as Raynaud's phenomenon and puffy fingers, are also typical of other connective tissue diseases (CTDs) such as mixed CTD and undifferentiated CTD. In the last decade, a significant effort has been dedicated in defining molecular characteristics that could be used as early SSc biomarkers. In this narrative review, we address the present situation where several clinical scenarios are in search of a correct positioning into the prescleroderma (pre-SSc) phase as well as in the very early phase of SSc., Recent Findings: Literature data showed that a part of patients classified as sine scleroderma SSc (ssSSc), mixed CTD and undifferentiated CTD may already belong to the very early phase of SSc, thus having a different pattern of progression to SSc. Recently, the very early diagnosis of systemic sclerosis (VEDOSS) criteria has been validated., Summary: while the area of pre-SSc still remains fuzzy, the VEDOSS study has shown that a 'window of opportunity' does exist also for SSc. In the very next future, this may allow to start the treatment to prevent the disease progression to a more advanced fibrotic stage., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Epidemiology, clinical presentation, and outcomes for digital gangrene in connective tissue disorders (CTD) remain underreported from tropical countries like India. In this series, we aimed to explore the clinical profile and outcomes of patients who presented with digital gangrene and a diagnosis of CTD. Hospital-based longitudinal observational study. Patients with digital gangrene and underlying diagnosis of CTD presenting to our tertiary-care centre in Jodhpur, India between1 st January 2018 and 31 st June 2021 were included. Clinical outcomes including mortality, limb outcomes, functional status and other systemic involvement were assessed. Of the 312 patients registered in the rheumatology clinic during this period, 22 (7%) patients were found to satisfy the inclusion criteria. Mean age was 46 years and 90% were females. The most common underlying diagnosis was Mixed connective tissue disorder (MCTD). Digital gangrene was the presenting symptom in 13 (60%) patients. Half of the patients received only corticosteroids as immunosuppression. Two died due to systemic complications. Complete resolution occurred in 17 (85%), autoamputation in 3, and infection requiring surgical drainage in one patient. All surviving patients reported good functional limb outcome on 6 months follow-up. MCTD is an important cause of digital gangrene in rheumatology practice. In patients presenting with digital gangrene, an active search for an underlying CTD is imperative, as this could result in timely initiation of appropriate limb-saving therapy. Corticosteroids alone with rapid tapering may be an appropriate option to consider in the initial management of digital gangrene in CTD. Key Points • Mixed connective tissue disorder is an important cause of digital gangrene in rheumatology practice in western India. • In patients presenting with digital gangrene, an active search for an underlying connective tissue disorder is imperative, as this could result in timely initiation of appropriate therapy and can prove limb saving. • Corticosteroids alone with rapid tapering may be an appropriate option to consider in the initial management of digital gangrene in connective tissue disorders., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Raynaud's phenomenon (RP) is a vasospastic condition of the extremities in response to cold or stress, affecting approximately 3% to 5% of the population. While most patients have primary RP, the condition can also occur secondary to a variety of underlying medical conditions. RP may be the presenting symptom of connective tissue diseases, especially systemic sclerosis, and RS may therefore provide an opportunity for early diagnosis and treatment. This review addresses the causes, clinical features, diagnostic workup, and treatment possibilities of RS.

Paroxysmal vascular acrosyndromes are related to a peripheral vasomotor disorder and presented as paroxysmal color changes of the fingers. They include primary Raynaud's phenomenon (RP), which is the most common, secondary RP and erythermalgia. They are to be distinguished from non-paroxysmal acrosyndromes such as acrocyanosis and chilblains, which are very frequent and often associated with RP, digital ischemia and necrosis, spontaneous digital hematoma and acrocholosis. The challenge of a consultation for a vascular acrosyndrome is to make positive diagnosis through history and clinical examination, and to specify its nature, to prescribe complementary exams. In any patient consulting for RP, assessment includes at least an antinuclear antibody test and capillaroscopy. For erythermalgia, a blood count and even a search for JAK2 mutation are required. A thryoid-stimulating hormon assay, a test for antinuclear antibodies, and a search for small fiber neuropathy are also performed. The treatment of RP is essentially documented for secondary RP where calcium channel blockers are indicated in first line, and iloprost in severe cases. The treatment of primitive erythermalgia is based on sodium channel blockers such as mexiletine or lidocaine infusions, and on drugs effective on neuropathic pain, such as gabapentin or amitryptiline, in case of erythermalgia associated with small fiber neuropathy. The treatment of erythermalgia associated with myeloproliferative syndromes is based on etiological treatment and aspirin., (Copyright © 2022 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Raynaud's phenomenon (RP) is a cardinal feature of systemic sclerosis (SSc) and manifests with pain, digital colour change, sensory symptoms, and impaired function. SSc-RP is exacerbated by cold exposure (RP 'attacks') but many patients report persistent symptoms of background digital ischaemia. The aim of our study was to examine the significance of RP with digital colour change with or without symptoms, and persistent colour change in between attacks. Patients with SSc responses were obtained from the Patient Survey of experiences of Raynaud's Phenomenon (PASRAP). We enquired about symptoms associated with Raynaud's attacks, and persistent symptoms in between attacks. Data were analysed as descriptive statistics with appropriate parametric/non-parametric testing. Relevant PASRAP survey question data from 747 evaluable SSc patients from across three continents were analysed. Isolated colour change was rare (29/484, 6%). Digital ulcers were more common in SSc-RP associated with other sensory symptoms (42.1% vs. 24.1%, P=0.057) and more readily treated with phosphodiesterase-type 5 inhibitors (22.5% vs. 10.3%%, P=0.124). Over one-third of patients (n=92/239, 38%) reported persistent colour change in between Raynaud's attacks. Patients with persistent colour change were more likely to have pulmonary arterial hypertension (15.2% vs. 7.5%, P=0.057) and be treated with calcium channel blockers (54.3% vs. 39.0%, P=0.021). SSc-RP with colour change and other symptoms and/or or persistent decolourisation in between attacks were more likely to have vascular complications of SSc and be treated with vascular therapies. Future research should explore the judicious use of vascular therapies as a potential form of disease modification in SSc. Key Points • Isolated colour change without other symptoms is rare in SSc patients. • SSc patients often identify persistent symptoms in between attacks of RP. • SSc-RP with colour change and other symptoms, or persistent decolourisation, may have greater disease severity and be treated with vascular therapies., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Nailfold videocapillaroscopy (NVC) non-specific abnormalities may be present in subjects with isolated Raynaud's phenomenon (RP) before the potential transition to systemic sclerosis (SSc) specific microvascular alterations ('scleroderma pattern'). This study aims to investigate NVC non-specific abnormalities, notably capillary dilations, in RP patients, as possible forerunners of the 'scleroderma pattern'., Methods: A 10-year retrospective NVC-based investigation evaluated 55 RP patients sorted into 3 sex-matched and age-matched groups according to clinical evolution: 18 later developing SSc (cases), 19 later developing other connective tissue disease and 18 maintaining primary RP at long-term follow-up (controls). All patients had a basal NVC showing non-specific abnormalities, namely non-specific &gt;30 µm dilated capillaries (30-50 μm diameter). Sequential NVCs were longitudinally evaluated using current standardised approach. Statistical analysis assessed the risk for developing a 'scleroderma pattern'., Results: Significantly larger capillary diameters were observed in cases versus controls both at basal NVC and during follow-up NVC (p=&lt;0.05 to &lt;0.001). Interestingly, controls showed stable NVC non-specific abnormalities over the study follow-up. The number of &gt;30 µm dilated capillaries/mm at basal NVC was the strongest single predictor of 'scleroderma pattern' evolution with 24% increased risk per each dilated capillary (OR 1.24, 95% CI 1.17,1.32). Additionally, a tree-based analysis suggested the efferent (venous) diameter of the most dilated capillary on basal NVCas a variable of interest to identify patients maintaining primary RP., Conclusion: This is the first study to describe an NVC 'prescleroderma signature' to potentially identify RP patients later developing a 'scleroderma pattern'., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)