Journal of Scleroderma and Related Disorders最新文献

Objective: People with systemic sclerosis (SSc or scleroderma), a rare chronic autoimmune disease, often face significant physical and emotional challenges. Peer mentoring, where someone with similar lived experiences offers guidance and support, shows promise in enhancing the well-being of recipients and may benefit individuals with systemic sclerosis. This study aims to evaluate the feasibility and potential health effects of peer mentoring through a digital platform for people with systemic sclerosis.

Methods: We conducted a one-group study to evaluate a 16-week peer mentoring program for people with systemic sclerosis. Mentors and mentees were matched by demographics and systemic sclerosis characteristics. Feasibility was evaluated using Orsmond and Cohn criteria: recruitment, data collection, acceptability, available resources, and participant responses to the program. Perceptions and usability of the peer mentoring program through a digital platform were assessed at week 16 (post-program). The health effects of peer mentoring were measured at baseline, week 8, and week 16.

Results: Five trained mentors and 15 mentees were enrolled. Each mentor was paired with 2-4 mentees. We found that peer mentoring through a digital platform was feasible, acceptable, and had good usability for both mentors and mentees. Mentees reported significantly less anxiety at week 16 (p < 0.001). Other improvements in fatigue, pain interference, depressed mood, and resilience were observed, but did not reach statistical significance.

Conclusion: The peer mentoring program through a digital platform was well-received. Results provided preliminary support for the feasibility and potential health benefits of peer mentoring to enhance well-being in people with systemic sclerosis. Findings lay the groundwork for future peer mentoring research in systemic sclerosis.

Introduction: In several rheumatic diseases, the skin is involved and therefore it is an organ of interest which may be investigated by the rheumatologist. Ultrasound imaging has been proposed for assessing multiple skin conditions providing qualitative and quantitative information about different parameters in distinct skin layers. Our aim was to describe with a pictorial essay the main challenges that the ultrasound imaging may encounter when investigating the healthy skin in different body areas.

Subjects and methods: Fourteen healthy subjects were submitted to skin ultrasound. The body areas that were investigated were decided following the 17 modified Rodnan skin score anatomical areas used in systemic sclerosis. Skin ultrasound was performed with a GE Logiq 10 with two probes (20 and 24 MHz). For an optimal quantification of the skin layers, the dermis interfaces either with the epidermis and hypodermis were investigated.

Results: The results of the ultrasound analysis are described and summarized in a pictorial essay which shows that some main factors may significantly influence the quality of the images of the skin layers. Specifically, age, scanning position, probe frequency, and the optimal positioning of some anatomical areas, in particular the hands and digits, emerged as factors that may have a relevance in influencing the quality of the imaging of the skin layers. Moreover, some technical suggestions are proposed to help optimizing and standardizing the performance of skin ultrasound assessment in healthy population.

Conclusion: The pictorial essay we performed shows that the performance of skin ultrasound in healthy subjects still presents several issues that need to be addressed. The definition of the interface in different body areas is the first step which should be standardized before any measurement of the thickness of the skin layers is performed in rheumatic diseases.

Objective: Juvenile-onset systemic sclerosis (jSSc) is a rare and life-threatening disease with no formal studies evaluating the indications for, access to, or benefits of autologous stem cell transplantation (ASCT). As a first step toward understanding pediatric jSSc specialist thoughts and experiences with ASCT, we conducted a multinational survey.

Methods: An electronic survey was developed and distributed in November 2023 to members of the Pediatric Rheumatology European Society (PRES) and/or Childhood Arthritis and Rheumatology Research Alliance (CARRA) pediatric scleroderma workgroups.

Results: Twenty-nine (69%) jSSc specialists completed the survey. All participants have considered or would consider ASCT referral for a jSSc patient. Nearly all respondents indicated disease-modifying anti-rheumatic drugs (DMARDs) should be trialed prior to ASCT referral, with most indicating two to four DMARDs. The most common reasons selected for referral were rapidly progressive disease (despite DMARD) (90%), followed by severe disease status (83%), and significant impact on quality of life (83%). All respondents selected pulmonary disease as an indication for referral, followed by cardiac (93%), gastrointestinal (72%), and skin disease (66%). While pulmonary and cardiac involvement were considered individually sufficient for referral for ASCT, only a minority considered musculoskeletal involvement (28%) sufficient on its own.

Conclusion: This survey is the first explore thoughts and experience with ASCT for jSSc. Results indicate pediatric rheumatologists were aware of and would consider ASCT for their patients. Our results indicate there is likely some variability in clinical practice regarding who is referred for ASCT, and further research is needed to guide development of evidence-based clinical care guidelines.

Introduction: Systemic sclerosis is a rare autoimmune connective tissue disease characterised by (1) microvasculopathy; (2) immune dysregulation; and (3) progressive fibrosis of the skin and internal organs. Soluble guanylate cyclase plays an important role in maintaining vascular and immunological homeostasis and preventing organ fibrosis. Pharmacological modulation of soluble guanylate cyclase with soluble guanylate cyclase stimulators has shown anti-inflammatory and antifibrotic effects in animal models of systemic sclerosis, with a trend towards clinical efficacy in a Phase II study (RISE-SSc). However, the efficacy of soluble guanylate cyclase stimulators may be reduced under conditions of hypoxia and oxidative stress. Soluble guanylate cyclase activators have the potential to overcome this limitation. This paper describes the study design of VITALISScE™, a Phase II clinical trial assessing the efficacy, safety and tolerability of avenciguat, a novel soluble guanylate cyclase activator in patients with active systemic sclerosis at risk of progression.

Methods: The VITALISScE™ study (NCT05559580) is evaluating the action of avenciguat on all three aspects of systemic sclerosis pathophysiology. The primary endpoint is the rate of decline in forced vital capacity (mL) over 48 weeks. Secondary endpoints include absolute change from baseline at Week 48 in modified Rodnan skin score, Health Assessment Questionnaire Disability Index score and the proportion of responders based on the revised Composite Response Index in Systemic Sclerosis. Additional endpoints include a composite assessment of Raynaud's phenomenon, digital ulcer burden, functional outcomes and quality of life, safety, pharmacokinetics, and biomarkers associated with systemic sclerosis and the mechanism of action of avenciguat.

Results: VITALISScE™ is an ongoing, multicentre (180 sites; 38 countries), placebo-controlled, double-blind, parallel-group, Phase II clinical study. Recruitment is currently ongoing.

Conclusions: The VITALISScE™ study is assessing the efficacy, safety and tolerability of avenciguat in patients with active systemic sclerosis at risk of progression. Results will inform further development of avenciguat.

Trial registration: VITALISScE™; EU CT No. 2022-500332-11-00; Clinicaltrials.gov: NCT05559580 (https://www.clinicaltrials.gov/study/NCT05559580).

Objective: Safe, effective therapies are urgently needed for patients with systemic sclerosis. However, clinical trial recruitment is challenging given the limited number of people with systemic sclerosis and further restrictions imposed by eligibility criteria. Innovative approaches are needed to accelerate development of new therapies. This article describes the rationale and trial design for CONQUEST (NCT06195072), a novel platform clinical trial sponsored by the Scleroderma Research Foundation, a not-for-profit organization.

Methods: CONQUEST is a multicentre, double-blind, randomized, placebo-controlled, Phase 2b platform trial evaluating the efficacy, safety and pharmacodynamics of multiple investigational products to treat early active systemic sclerosis with interstitial lung disease versus placebo. The primary objective is to evaluate change from baseline to Week 52 in forced vital capacity (mL). Secondary objectives include evaluating changes from baseline to Week 52 in high-resolution computed-tomography-assessed lung involvement and dyspnoea, and overall treatment response (measured using the revised composite response index in diffuse systemic sclerosis score in participants with diffuse cutaneous systemic sclerosis).

Results: Patients will be enrolled across more than 150 centres in over 25 countries. Recruitment started on 15 April 2024.

Conclusion: As the first platform clinical trial in the rheumatology field, CONQUEST aims to meaningfully accelerate the development of new therapies for early active systemic sclerosis. Depending on regimen-specific results, trial data could be used to plan and design a Phase 3 trial or may be used alone or together with another registrational trial to establish substantial evidence of effectiveness and safety. The first molecules to be studied, amlitelimab and nerandomilast, both have a strong scientific rationale to modify underlying disease processes in systemic sclerosis.

Clinicaltrialsgov: Platform Clinical Study for Conquering Scleroderma (CONQUEST); NCT06195072; https://www.clinicaltrials.gov/study/NCT06195072.

Objective: Assessment of gastrointestinal and autonomic symptoms in patients with systemic sclerosis, and possible associations with gastric emptying rate.

Methods: Participant and patient disease-related characteristics were collected. Gastrointestinal and autonomic symptoms were assessed by the UCLA-SCTC GIT 2.0 and COMPASS-31 questionnaires, respectively. Potentially confounding gastrointestinal medications were discontinued where possible. Gastric emptying was assessed using a non-radioactive ¹³C sodium acetate isotope, end-expiratory breath samples collected at baseline and then serial timepoints up to 120 min.

Results: In total, 49 participants were studied: 17 with systemic sclerosis with variable gastrointestinal involvement, and healthy matched (n = 17) and non-matched controls (n = 15), the last to control for the impact of age rather than disease on gastric emptying and autonomic function. The total mean (range) UCLA GIT 2.0 questionnaire for patients with systemic sclerosis was 0.63 (0.0-1.5) and for both healthy matched and non-matched controls was 0.04 (0.0-0.2), and was higher in patients with systemic sclerosis across all domains. The total mean (range) COMPASS-31 score for patients with systemic sclerosis patients was 32.2 (0.0-54.9) and for healthy matched- and non-matched controls: 7.45 (0.0-24.9) and 4.25 (0.0-2.1), respectively, again higher for patients with systemic sclerosis across all domains. No association was observed between patients' UCLA GIT 2.0 total score (s = -0.039, p = 0.38), total COMPASS 31 score (s = -0.108, p = 0.68), or COMPASS-31 GI domain (s = -0.051, p = 0.85) and gastric emptying rates.

Conclusion: Gastrointestinal and autonomic symptoms are overrepresented in patients with systemic sclerosis but did not associate with gastric emptying rates.

Objectives: The aim of this review was to summarize existing data on the contribution of Vitamin D level and/or deficiency/insufficiency to systemic sclerosis susceptibility and its clinical features.

Methods: An electronic literature search for eligible studies among all papers published prior to 30 June 2024 was conducted through PubMed, EMBASE, Web of science, and Scopus databases. Meta-analyses estimating pooled raw mean differences, odds ratios, and Pearson r together with subgroup analyses and meta-regressions were performed for the association of Vitamin D with susceptibility to systemic sclerosis and disease presentation.

Results: Combined analysis revealed a significant decrease in Vitamin D level in systemic sclerosis patients comparatively to healthy controls, with raw mean differences 95% CI = -11.68 [-15.43 to -7.92] ng/mL, p < 1 E-10. Likewise, Vitamin D insufficiency (Vitamin D < 30 ng/mL) and deficiency (<10 ng/mL) were significantly associated with systemic sclerosis; odds ratios 95% CI = 3.58 [2.59-4.95], p < 1 E-10 and odds ratios 95% CI = 7.67 [3.97-14.83], p < 1 E-10, respectively. Moreover, decreased Vitamin D level was significantly associated with interstitial lung disease occurrence (raw mean differences 95% CI = -3.61 [-6.93 to -0.3], p = 0.003), while Vitamin D deficiency was associated with increased systolic pulmonary arterial pressure, raw mean differences (95% CI = 4.17 [1.44-6.89], p = 0.003). Besides, Vitamin D level was negatively correlated with the modified Rodnan skin score, r (95% CI = -0.26 [-0.44 to -0.08], p = 0.004). Conversely, Vitamin D level was significantly increased in systemic sclerosis patients with cutaneous calcinosis, raw mean differences (95% CI = 4.18 [1.07-7.28], p = 0.008).

Conclusion: This meta-analysis showed that decreased Vitamin D level was associated with susceptibility to systemic sclerosis, interstitial lung disease occurrence, increased systolic pulmonary arterial pressure, and higher modified Rodnan skin score. Conversely, calcinosis was found to be associated with increased Vitamin D level.

Registration: This review has been registered on PROSPERO: CRD42024565045, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565045.

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis and vascular abnormalities, often leading to the development of digital ulcers (DUs). DUs are painful and debilitating, significantly impacting patients' quality of life. Effective pain management during debridement is crucial, yet there is no consensus on the optimal approach. This study evaluates the efficacy and safety of digital nerve block (DNB) using lidocaine and mepivacaine for pain control during sharp debridement of DUs in SSc patients.

Methods: This prospective observational study was conducted from September 2023 to May 2024 at the Rheumatology Operating Unit, University of Verona. Patients were randomized to receive either 1 mL of 2% lidocaine or 2% mepivacaine for DNB. Pain levels were assessed using a categorical grading scale during the injection and debridement. The outcomes were pain control and performance of lidocaine versus mepivacaine.

Results: The cohort developed 46 ulcers. The pain was abolished in almost all patients. Lidocaine achieved faster anaesthesia (127.92 ± 34.32 s) compared with mepivacaine (252.65 ± 49.89 s, p < 0.001). Mepivacaine resulted in less pain during injection (p = 0.006). No significant difference in pain levels during debridement was observed between the two anaesthetics. Three mild adverse effects (Raynaud's phenomenon) were reported. All procedures were completed successfully, and 35 ulcers healed with a mean time of 6.1 ± 7.77 weeks.

Conclusions: DNB with mepivacaine provides effective pain control during DU debridement in SSc patients, with lower injection site pain and comparable efficacy to lidocaine. The procedure is safe, well-tolerated and facilitates successful ulcer healing. Further studies with larger cohorts are warranted to confirm these findings.

Systemic sclerosis is a progressive fibrotic autoimmune disease which mainly affects young women causing fibrosis of the skin and internal organs. In systemic sclerosis patients, facial and hand alterations are significant as these may have an impact on body image. In fact, systemic sclerosis could cause disfigurement of the most visible parts of the body, hindering self-confidence and quality of life. Therefore, the assessment of body image in systemic sclerosis is crucial in order to optimize a tailored care of the patient. In the near future, the creation of a pathway involving dedicated specialists (psychologists, physiotherapists, dermatologists, and plastic surgeons) should become an integral part of the disease management.

Objective: To optimise the organisation of care and encourage the adoption of good clinical practices, the RarERN Path^© methodology was designed within ERN ReCONNET. The aim of our work was to report the application of RarERN Path^© on systemic sclerosis within the ERN ReCONNET centres, providing a feasible and flexible organisational reference model for optimising the systemic sclerosis care pathway in different countries.

Methods: RarERN Path^© is a six-phase methodology which enables the creation of a reference organisational model co-designed on the basis of the expertise of different stakeholders. It foresees six phases, ranging from the map of existing patients' care pathways and patients' stories, to the consensus on a common organisational patient care pathways, and its key performance indicators definition.

Results: The agreed reference model highlights the importance of having an organisational flow for referrals that foresees how patients may access directly the specialised unit from the different referrals. Specific specialised visits were considered as mandatory to be organised and they included cardiologist, pneumologist, gastroenterologist, psychologist, nephrologist, dermatologist, wound care specialist/nurses and other healthcare professionals (such as nurses, social workers and nutritional counselling). Moreover, specific services related to therapy were highlighted as strongly recommended to be organised, mainly represented by infusion therapy and wound care, as well as occupation therapy and physiotherapy.

Conclusion: The organisational model emerged from our investigation emphasises that the organisation of specific services for systemic sclerosis treatment should be organised as a solid support for implementing the existing recommendations on systemic sclerosis management in real life.