Management Of Systemic Sclerosis Research Articles

Esophagus Dilation and Quality of Life in Adults with Scleroderma and Concomitant Obstructive Sleep Apnea.

(1) Background: Systemic sclerosis (SSc) is a rare systemic disease, which often affects the esophagus, leading to dilation and complications such as dysphagia and reflux. Obstructive sleep apnea (OSA) is a chronic condition with recurrent episodes of upper airway collapsibility and is known to impair quality of life (QoL). The primary aim of this study was to investigate the occurrence of esophagus dilation in patients with SSc and concomitant OSA and, further, to address the impact of these conditions on QoL. (2) Methods: In this cross-sectional cohort study, 62 consecutive patients with SSc underwent chest computer tomography (CT) and home sleep apnea testing. The OSA diagnosis was based on AHI ≥ 15 events/h. The QoL was quantified using the short-form (SF)-36 questionnaire. The patients were dichotomized as high- vs. low-esophageal-diameter groups, based on the median cut-off values. (3) Results: The mean age was 48 ± 11 years; 58 (93.5%) were female; the mean BMI was 26.7 ± 5.0 kg/m2. The median esophageal diameter was 17.47 mm. A larger esophageal diameter was more frequently associated with the diffuse cutaneous subtype of SSc (p = 0.002) and significantly higher Warrick scores (p < 0.001), indicating more severe pulmonary fibrosis. There was a significant linear correlation between the Warrick score and the esophageal diameter (standardized β coefficient 0.544 [%95 confidence interval 0.250-0.609]; p < 0.001). In the subgroup analysis, the patients with both OSA and enlarged esophageal diameter experienced a significant decline in QoL, particularly in the domains of physical functioning, role physical, general health, role emotional, and vitality. (4) Conclusions: While OSA was not directly associated with enlarged esophageal diameter in patients with SSc, those with both OSA and enlarged esophageal diameter exhibited a significant decline in QoL. These findings suggest that the presence of OSA may exacerbate the adverse effects of esophageal dilation on QoL in SSc patients. Our results underline the importance of considering both gastrointestinal and sleep-related aspects in SSc management to enhance patient QoL.

Lifestyle interventions in the management of systemic sclerosis: a systematic review of the literature.

We aimed to investigate the efficacy of lifestyle interventions for the management of SSc. We searched the MEDLINE, Embase, Web of Science and CINAHL databases in June 2021. We included studies conducted on five or more patients with SSc published between 1 January 2000 and the search date evaluating lifestyle interventions, excluding systematic reviews without meta-analyses. Critical appraisal was conducted using critical appraisal tools from the Joanna Briggs Institute. Thirty-six studies were included for full-text evaluation. A total of 17 studies evaluated the effect of physical exercise alone, whereas 14 studies evaluated educational interventions for mental health management, often with physical exercise as a central component. At an aggregated level, these studies support patient education and physical exercise for the improvement of physical function, in particular hand and mouth function. Studies on diet and nutrition were few (n = 5) and pertained to gastrointestinal as well as anthropometric outcomes; these studies were insufficient to support any conclusions. Physical exercise and patient education should be considered for improving physical function in patients with SSc. These interventions can be provided alongside pharmacotherapy, but there is no evidence supporting that they can be a substitute. Further research should aim at assessing the effects of reductions of harmful exposures, including tobacco smoking and alcohol, improving sleep and enhancing social relations, three hitherto underexplored facets of lifestyle in the context of SSc.

Evaluating Skin Involvement in Systemic Sclerosis Using High-Frequency Ultrasound and Virtual Touch Tissue Imaging

ObjectiveThis study aimed to explore the diagnostic significance of high-frequency ultrasound combined with visual touch tissue imaging quantification (VTIQ) in the diagnosis and management of systemic sclerosis (SSc). MethodsPatients diagnosed with SSc and normal volunteers were recruited and divided into an experimental group and a control group, with 30 cases in each group, respectively. The skin thickness at six sites was assessed using high-frequency ultrasound, and the shear wave velocity (SWV) was determined using the VTIQ method. The differences in skin thickness and SWV between the experimental group and the control group were compared and a receiver operating characteristic (ROC) curve was plotted. The value of high-frequency ultrasound, VTIQ, and high-frequency ultrasound combined with VTIQ for evaluating skin involvement in SSc was determined. ResultsThe difference in SWV sum at six sites and the thickness sum was statistically significant (all p = 0.000 < 0.05) from that of the control group, and there was a strong association between the SWV sum, thickness sum, and Rodnan skin score at the six sites in the experimental group (p = 0.000, r = 0.726; p = 0.000, r = 0.679). Based on the ROC curve, the area under the curve (AUC) for high-frequency ultrasound examination was 0.789. The AUC for VTIQ examination was 0.893, while the AUC for high-frequency ultrasound combined with VTIQ examination was 0.923. The combined examination method showed the highest AUC, indicating the best diagnostic performance. ConclusionThe integration of high-frequency ultrasound and VTIQ provides a quantitative approach for assessing the extent of skin involvement in SSc patients, offering valuable insights for clinical diagnosis and treatment purposes.

Impact of the COVID-19 Pandemic on Health Care Access and Diagnosis of Pulmonary Arterial Hypertension Among Patients With Systemic Sclerosis.

Regular clinical assessment for complications of systemic sclerosis (SSc) such as pulmonary arterial hypertension (PAH) is essential for early institution of therapy and improved outcomes. The objective of this study was to determine the impact of COVID-19 pandemic-related restrictions on health care access of patients with SSc, including screening for PAH. South Australian and Victorian patients enrolled in the Australian Scleroderma Cohort Study were surveyed about their perceptions of the impact of the pandemic on mental well-being, access to medications, investigations, and management of SSc. Frequency of annual rheumatology assessments, pulmonary function tests (PFT), and transthoracic echocardiography (TTE) to screen for PAH were compared with rates from before the pandemic. A total of 312 of 810 patients with SSc responded (38.5% response); 273 were female (87.5%), the median age was 64.7 years, 77.2% had limited disease, the median illness duration was 15.6 years, 15.7% were immunosuppressed, 32.1% had interstitial lung disease, and 6.4% had PAH. A total of 65.7% of consultations were by telehealth, of which 81.2% were by telephone. Compared with respondents in South Australia (n=109), Victorian respondents (n=203) experiencing prolonged lockdown, reported reduced access to their rheumatologist (49.3% vs 27.9%; P = 0.004), greater use of consultation by video (17.3% vs 2.1%; P = 0.008), greater health care disruption (49.0% vs 23.2%; P < 0.001), and worse mental health (P = 0.002). Respondents reported reduced access to PFT and TTE (31.7% and 22.5%, respectively). Annual visits, PFT, TTE, and new diagnoses of PAH were reduced in 2020 to 2022 compared with 2011 to 2019. The COVID-19 pandemic-related disruption to health care for patients with SSc was associated with worse mental health and reduced screening and diagnosis of PAH, which may impact long-term outcomes.

Process of Maintaining Self in Individuals Living With Systemic Sclerosis: A Grounded Theory Study of American Women.

People with chronic illnesses may struggle to adapt psychologically to the illness experience and have feelings of identity loss, self-diminishment, and biographical disruption. This may limit people's ability to engage in optimal self-management. Systemic sclerosis is a debilitating, stigmatizing, and life-limiting progressive chronic illness with significant disfiguring effects. Little is known about the identity management process in people with disfiguring and debilitating conditions such as systemic sclerosis. The purpose of this study was to generate a grounded theory explicating the process of maintaining a sense of self in people living with systemic sclerosis. Fifteen women with systemic sclerosis were recruited to ensure representation of a range of illness duration and progression. Semi-structured interviews were conducted, transcribed, and analyzed using open, selective, and theoretical coding. A basic social process of "maintaining self" was generated from the data that explained the women's experience of living with systemic sclerosis and how they tried to hold on to their identity. Three core categories were identified. Adapting to changes are the behaviors that participants struggled through to carry on with their everyday lives. Dismantling of self was a distressing internal process where participants lost their sense of self and purpose. Restoring self was a transformative process that allowed participants to rewrite and rebuild their biographies. Findings suggest that the management of identity was important for understanding how people adapt to life with systemic sclerosis. This study can help nurses better understand how to support patients holistically with the management of systemic sclerosis.

Symposium 3

Systemic sclerosis (SSc) remains a refractory condition with poor functional and survival outcomes. This is attributable primarily to the extremely diverse clinical course and distribution of organ involvement. The pathogenesis of SSc includes microangiopathy and chronic inflammation, leading to accumulation of extracellular matrix and resultant irreversible fibrosis resulting in distortion of the normal tissue architecture. This pathogenic process is analogous to that observed in rheumatoid arthritis, in which persistent synovitis leads to articular cartilage and bone destruction, resulting in functional impairment due to joint deformity. Therefore, successful experiences in developing treatment strategies in patients with rheumatoid arthritis can also be applied to SSc. These include early diagnosis and intervention, treat-to-target strategy aiming at achievement of clinical remission or low-disease activity, prediction of disease progression and prognosis, and disease modification by pharmacologic treatment. Immunosuppressants targeting lymphocytes, including mycophenolate mofetil and cyclophosphamide, have been the mainstream of the treatment of SSc, based on treatment evidence showing prevention of decline in forced vital capacity, promotion of improving modified Rodnan skin thickness score, and improved patient-reported outcomes. However, survival benefit has not been shown in long-term follow-up of patients treated with non-specific immunosuppressants. Recently, drugs targeting a variety of molecules involved in the pathologic process of SSc, such as tocilizumab and nintedanib, have been shown to prevent progression of certain organ involvement in clinical trials, resulting in expanding treatment options. Implementation of those potential disease-modifying therapies in management of SSc requires adequate assessment of disease activity and treatment goal setting. In addition, clinical characteristics that predict the progression of organ manifestations, such as skin sclerosis and interstitial lung disease, need to be identified as prognosis factors. Like other rheumatic diseases, early interventions have been shown to be more effective than delayed intervention. This lecture features current standings and challenges of treat-to-target strategy in SSc patients.

The Gut Microbial Metabolite Trimethylamine N-Oxide is Linked to Specific Complications of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease characterized by fibrosis of the skin and internal organs, whose pathogenesis is not fully understood. Recent studies have revealed dysbiosis in patients with systemic sclerosis and have indicated the possible role of the microbiota and its metabolites in the pathogenesis of the disease. Trimethylamine N-oxide (TMAO) is a compound produced by dysbiotic microbiota observed at higher concentrations in several autoimmune diseases. To determine concentrations of the bacteria-derived metabolite TMAO in patients with systemic sclerosis and to assess possible correlation between TMAO and a specific manifestation of the disease. The study included 63 patients with SSc and 47 matched control subjects. The concentration of TMAO was measured with high-performance liquid chromatography. Plasma TMAO level was significantly increased in patients with SSc (283.0 [188.5-367.5] ng/mL versus 205.5 [101.0-318.0] ng/mL; p < 0.01). An increased concentration of TMAO was observed in patients with concomitant interstitial lung disease (ILD) (302.0 ng/mL [212.0-385.5] ng/mL versus 204.0 [135.5-292.0] ng/mL; p < 0.01) and esophageal dysmotility (289.75 [213.75-387.5] ng/mL versus 209.5 ng/mL [141.5-315.0] ng/mL; p < 0.05) compared to patients without these complications. Furthermore, TMAO concentration exhibited significant correlation with markers of heart involvement (left ventricle ejection fraction, NT-proBNP), marker of ILD severity and Scleroderma Clinical Trials Consortium Damage Index. The concentration of TMAO, gut microbiota-associated metabolite, is increased in systemic sclerosis, particularly in patients with advanced organ involvement. This is the first study evaluating plasma TMAO in systemic sclerosis. Bacterial metabolites may be a link between dysbiosis and organ involvement in the course of the disease. Modulation of gut bacterial-derived metabolites may represent a new therapeutic approach in the management of systemic sclerosis.

Patient Assessment Chronic Illness Care (PACIC) and its associations with quality of life among Swiss patients with systemic sclerosis: a mixed methods study

BackgroundThe Chronic Care Model (CCM) is a longstanding and widely adopted model guiding chronic illness management. Little is known about how CCM elements are implemented in rare disease care or how patients’ care experiences relate to health-related quality of life (HRQoL). We engaged patients living with systemic sclerosis (SSc) to assess current care according to the CCM from the patient perspective and their HRQoL.MethodsWe employed an explanatory sequential mixed methods design. First, we conducted a cross-sectional quantitative survey (n = 101) using the Patient Assessment of Chronic Illness Care (PACIC) and Systemic Sclerosis Quality of Life (SScQoL) questionnaires. Next, we used data from individual patient interviews (n = 4) and one patient focus group (n = 4) to further explore care experiences of people living with SSc with a focus on the PACIC dimensions.ResultsThe mean overall PACIC score was 3.0/5.0 (95% CI 2.8–3.2, n = 100), indicating care was ‘never’ to ‘generally not’ aligned with the CCM. Lowest PACIC subscale scores related to ‘goal setting/tailoring’ (mean = 2.5, 95% CI 2.2–2.7) and ‘problem solving/contextual counselling’ (mean = 2.9, 95% CI 2.7–3.2). No significant correlations were identified between the mean PACIC and SScQoL scores. Interviews revealed patients frequently encounter major shortcomings in care including ‘experiencing organized care with limited participation’, ‘not knowing which strategies are effective or harmful’ and ‘feeling left alone with disease and psychosocial consequences’. Patients often responded to challenges by ‘dealing with the illness in tailored measure’, ‘taking over complex coordination of care’ and ‘relying on an accessible and trustworthy team’.ConclusionsThe low PACIC mean overall score is comparable to findings in patients with common chronic diseases. Key elements of the CCM have yet to be systematically implemented in Swiss SSc management. Identified gaps in care related to lack of shared decision-making, goal-setting and individual counselling-aspects that are essential for supporting patient self-management skills. Furthermore, there appears to be a lack of complex care coordination tailored to individual patient needs.

Management of systemic sclerosis: British Society for Rheumatology guideline scope.

This guideline will provide a practical roadmap for management of SSc that builds upon the previous treatment guideline to incorporate advances in evidence-based treatment and increased knowledge about assessment, classification and management. General approaches to management as well as treatment of specific complications will be covered, including lung, cardiac, renal and gastrointestinal tract disease, as well as RP, digital vasculopathy, skin manifestations, calcinosis and impact on quality of life. It will include guidance related to emerging approved therapies for interstitial lung disease and account for National Health Service England prescribing policies and national guidance relevant to SSc. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence accreditation.

Autologous hematopoietic stem cell transplantation improves long-term survival—data from a national registry

BackgroundCurrent recommendations on the management of systemic sclerosis (SSc) suggest that autologous hematopoietic stem cell therapy (HSCT) can be a rescue therapy for patients with rapidly progressive SSc.ObjectivesTo assess the safety and efficacy of HSCT for patients with SSc and to compare these with non-HSCT patients in a control cohort with adjusted risk factors.MethodsA retrospective analysis of data from the multicentric German network for systemic scleroderma (DNSS) with 5000 patients with SSc. Control groups consisted of all patients with diffuse cutaneous (dc)-SSc (group A) and an adjusted high-risk cohort of male patients with Scl70-positive dc-SSc (group B).ResultsEighty SSc patients received an HSCT 4.1 ± 4.8 years after SSc diagnosis. Among them, 86.3% had dc-SSc, 43.5% were males, and 71.3% were positive for Scl70 antibodies. The control group A (n=1513) showed a significant underrepresentation of these risk factors for mortality. When the survival of the control group B (n=240) was compared with the HSCT group, a lower mortality of the latter was observed instead. Within 5 years after HSCT, we observed an improvement of the mRSS from 17.6 ± 11.5 to 11.0 ± 8.5 (p=0.001) and a stabilization of the DLCO. We did not see differences in transplant-related mortality between patients who received HSCT within 3 years after SSc diagnosis or later.ConclusionOur analysis of real-life data show that the distribution of risk factors for mortality is critical when HSCT cohorts are compared with non-HSCT control groups.

Vitamin D in Systemic Sclerosis: A Review.

(1) Background: In the present paper we aimed to review the evidence about the potential implication of vitamin D in the pathogenesis and management of systemic sclerosis (SSc); (2) Methods: we performed a review of the literature looking for studies evaluating the potential role of vitamin D and its analogs in SSc. We searched the PubMed, Medline, Embase, and Cochrane libraries using the following strings: (vitamin D OR cholecalciferol) AND (systemic sclerosis OR scleroderma). We included cohort studies, case-control studies, randomized controlled trials, and observational studies. (3) Results: we identified nine pre-clinical and 21 clinical studies. Pre-clinical data suggest that vitamin D and its analogs may suppress fibrogenesis. Clinical data are concordant in reporting a high prevalence of hypovitaminosis D and osteoporosis in SSc patients; data about the association with clinical manifestations and phenotypes of SSc are, conversely, far less consistent; (4) Conclusions: in vitro data suggest that vitamin D may play an antifibrotic role in SSc, but clinical data confirming this finding are currently lacking. Hypovitaminosis D is common among SSc patients and should be treated to reduce the risk of osteoporosis.

Scleroderma autoantibodies in guiding monitoring and treatment decisions.

One of the key clinical challenges of systemic sclerosis (SSc) is diversity in clinical presentation, organ involvement and disease progression. Antinuclear autoantibodies (ANA) are central to the diagnosis of SSc. ANA specificities associated with distinct clinical patterns of organ and skin involvement. Understanding of the molecular differences and pathogenesis of scleroderma has helped further inform clinical acumen. Here, we provide an update on ANA on clinical profiling, management and future direction of SSc. There has been further development in delineating clinical patterns in ANA, genetic susceptibility and antigen triggers predisposing to ANA subtypes. Sub-group analysis of recent clinical trials shows differing treatment responses to novel therapeutics. ANA subtyping is likely to be firmly embedded into future classification systems. Beyond informing current management and monitoring of scleroderma patients, ANA subsets have implication on future research and clinical trial design.

The Preventive Role of Physical Activity in Systemic Sclerosis: A Cross-Sectional Study on the Correlation with Clinical Parameters and Disease Progression.

Although exercise is associated with improved health in many medical conditions, little is known about the possible influences of physical activity (PA) habits pre- and post- a diagnosis of systemic sclerosis (SSc) on disease activity and progression. This cross-sectional study assessed, for the first time, self-reported pre- and post-diagnostic PA levels with the aim to verify if changes in these levels were correlated with demographic/anthropometric data (e.g., weight, height, gender, age, BMI), disease duration, diagnostic/clinical parameters (e.g., skin involvement, pulmonary hemodynamic/echocardiographic data, disease activity) related to disease activity and progression, and quality of life in a population-based sample of patients with SSc. Adult participants (n = 34, age 56.6 ± 13.3 years) with SSc (limited cutaneous SSc, lcSSc, n = 20; diffuse cutaneous SSc, dcSSc, n = 9; sine scleroderma SSc, n = 5) were enrolled at the Division of Rheumatology and Clinical Immunology of the Humanitas Research Hospital. All medical data were recorded during periodic clinical visits by a rheumatologist. Moreover, all subjects included in this study completed extensive questionnaires to evaluate their health-related quality of life (HRQOL), and others related to health-related physical activity performed before (PRE) and after (POST) the diagnosis of disease. The linear regression analysis has shown that either a high Sport_index or Leisure_index in the PRE-diagnostic period was correlated with lower disease duration in dcSSc patients. Physical load during sport activity and leisure time accounted for ~61.1% and ~52.6% of the individual variation in disease duration, respectively. In lcSSc patients, a high PRE value related to physical load during sporting activities was correlated with a low pulmonary artery systolic pressure (sPAP) and the POST value of the Work_index was positively correlated with the left ventricular ejection fraction (LVEF), and negatively with creatine kinase levels (CK). Interestingly, the univariate analysis showed that Work_index accounts for ~29.4% of the variance in LVEF. Our analysis clearly reinforces the concept that high levels of physical load may play a role in primary prevention—delaying the onset of the disease in those subjects with a family history of SSc—as well as in secondary prevention, improving SSc management through a positive impact on different clinical parameters of the disease. However, it remains a priority to identify a customized physical load in order to minimize the possible negative effects of PA.

Recent advances in elucidating the genetic basis of systemic sclerosis.

Systemic sclerosis (SSc) is a complex autoimmune disorder that affects the connective tissue and causes severe vascular damage and fibrosis of the skin and internal organs. There are recent advances in the field that apply novel methods to high throughput genotype information of thousands of patients with SSc and provide promising results towards the use of genomic data to help SSc diagnosis and clinical care. This review addresses the development of the first SSc genomic risk score, which can contribute to differentiating SSc patients from healthy controls and other immune-mediated diseases. Moreover, we explore the implementation of data mining strategies on the results of genome-wide association studies to highlight subtype-specific HLA class II associations and a strong association of the HLA class I locus with SSc for the first time. Finally, the combination of genomic data with transcriptomics informed drug repurposing and genetic association studies in well characterized SSc patient cohorts identified markers of severe complications of the disease. Early diagnosis and clinical management of SSc and SSc-related complications are still challenging for rheumatologists. The development of predictive models and tools using genotype data may help to finally deliver personalized clinical care and treatment for patients with SSc in the near future.

The impact of systemic sclerosis on oral health

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by a wide range of manifestations, including oral changes. The pathogenesis of SSc is complex and remains incompletely understood. In the development of SSc following mechanisms are involved: immune activation, vascular alterations, and increased accumulation of extracellular collagen matrix. Genetics plays an important role in SSc development. Oral manifestations of SSc include microstomia, xerostomia, telangiectasia, periodontitis, increased width of the periodontal ligament, and alveolar bone resorption. These manifestations are a significant cause of comorbidities and a decreased quality of life in SSc patients. Education on oral hygiene and home-based orofacial physiotherapy may improve the oral status of these patients. A multidisciplinary team should be involved in the management of SSc.

P117 Nailfold capillaroscopy: a survey of current UK practice and ‘next steps’ to facilitate generalised uptake

Background/AimsNailfold capillaroscopy has a key role in the assessment of patients with Raynaud’s phenomenon (RP) providing a window of opportunity for the early diagnosis of systemic sclerosis (SSc). Anecdotal evidence indicates that this opportunity is not being fully realised across UK rheumatology centres. Reasons for apparent discrepancies in use of capillaroscopy may relate to a lack of expertise, confidence or equipment. Exploratory work has demonstrated the potential for an internet-based standardised system for clinical reporting of nailfold capillaroscopy images to mitigate current inequities in care provision. The overall aim of this study was to understand current practices in the diagnosis of SSc in UK rheumatology centres with specific reference to identifying barriers to the use of nailfold capillaroscopy. A secondary aim was to understand rheumatologists’ views on a standardised system to facilitate the timely diagnosis of SSc.MethodsAn online survey comprising closed and free-text questions was developed using expert (n = 7) opinion from clinicians, scientists and health service researchers. The survey was piloted (n = 5) and sent to UK-based rheumatologists using established electronic mailing lists between 2nd October 2020 and 8th March 2021. Respondents were asked to describe workloads and practices typically seen before the COVID-19 pandemic. Data were analysed using descriptive statistics and thematic analysis.ResultsSurvey responses were received from 104 rheumatologists representing centres across the UK. Wide variation in terms of workloads and practices were described (See Table 1). Only 41% (n = 43) of respondents reported using nailfold capillaroscopy provided at their centres. Key barriers were access to equipment and a lack of expertise in terms of acquiring and analysing images. Respondents indicated that a centralised internet-based system for storing images and sharing diagnoses would provide access to expertise and the possibility of timely diagnoses. P117 Table 1:Use of nailfold capillaroscopy (NFC) across UK centresNumber (n = 104)%Do you use nailfold capillaroscopy at your site?No6159Yes4341Total104100In what context are nailfold capillaroscopy images taken?At the general clinic appointment2251At a separate hospital appointment1637Other12Either general clinic or separate hospital appointment25Missing/unclear25Is there a dedicated room where imaging is done?No2354Yes1842Unclear/missing25What type of equipment do you use for NFC?Video microscope921Stereomicroscope12USB microscope1228Dermatoscope1330Ophthalmoscope12Stereomicroscope & dermatoscope12Don't know614Who usually does NFC imaging in your centre?I do it myself2047Another consultant or SpR921Nurse/AHP37Technician/medical physics614Medical photography49Clinical scientist12Who usually interprets the NFC imaging in your centre?I do it myself2558Another consultant or SpR819Nurse/AHP25Technician/medical physics512other12Clinical scientist12Technician & consultant/SpR12From how many RP patients do you obtain NFC images?0381 to 5386 to 1092311 to 2061521 to 30410more than 30923Not sure513How many of those patients imaged were diagnosed with SSc?04101 to 516416 to 1082111 to 203821 to 3025more than 3025Not sure410How are results of NFC reported to the patients?Face-to-face at imaging session1126Face-to-face at clinic appointment1433Letter / as part of treatment plan1330No specific nailfold capillaroscopy reporting25Other25Letter / face-to-face12Do you (also) refer patients to other centres for NFC?No6260Yes4240How many patients per year do you refer to other centres?1 to 526636 to 10112711 to 201221 to 3025more than 3012*participants asked to base answers on the situation in 2019 before the COVID-19 pandemicConclusionSubstantial variation in approaches to the diagnosis of SSc across the UK was identified. Potential benefits of a standardised system were described by respondents including the improved diagnosis and management of SSc, realising potential patient benefits and reducing current health inequalities. Survey findings provide evidence to help develop future studies to develop and evaluate the proposed new system.Disclosure M. Eden: None. S. Wilkinson: None. A. Murray: None. P. Gurunath Bharathi: None. C. Taylor: None. K. Payne: None. A.L. Herrick: None.

Emerging Evidence and Treatment Perspectives from Randomized Clinical Trials in Systemic Sclerosis: Focus on Interstitial Lung Disease.

Systemic sclerosis (SSc) is a complex rare autoimmune disease with heterogeneous clinical manifestations. Currently, interstitial lung disease (ILD) and cardiac involvement (including pulmonary arterial hypertension) are recognized as the leading causes of SSc-associated mortality. New molecular targets have been discovered and phase II and phase III clinical trials published in the last 5 years on SSc-ILD will be discussed in this review. Details on the study design; the drug tested and its dose; the inclusion and exclusion criteria of the study; the concomitant immunosuppression; the outcomes and the duration of the study were reviewed. The two most common drugs used for the treatment of SSc-ILD are cyclophosphamide and mycophenolate mofetil, both supported by randomized controlled trials. Additional drugs, such as nintedanib and tocilizumab, have been approved to slow pulmonary function decline in SSc-ILD. In this review, we discuss the therapeutic alternatives for SSc management, offering the option to customize the design of future studies to stratify SSc patients and provide a patient-specific treatment according to the new emerging pathogenic features of SSc-ILD.

Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches.

Systemic sclerosis (SSc) is a systemic, immune-mediated chronic disorder characterized by small vessel alterations and progressive fibrosis of the skin and internal organs. The combination of a predisposing genetic background and triggering factors that causes a persistent activation of immune system at microvascular and tissue level is thought to be the pathogenetic driver of SSc. Endothelial alterations with subsequent myofibroblast activation, excessive extracellular matrix (ECM) deposition, and unrestrained tissue fibrosis are the pathogenetic steps responsible for the clinical manifestations of this disease, which can be highly heterogeneous according to the different entity of each pathogenic step in individual subjects. Although substantial progress has been made in the management of SSc in recent years, disease-modifying therapies are still lacking. Several molecular pathways involved in SSc pathogenesis are currently under evaluation as possible therapeutic targets in clinical trials. These include drugs targeting fibrotic and metabolic pathways (e.g., TGF-β, autotaxin/LPA, melanocortin, and mTOR), as well as molecules and cells involved in the persistent activation of the immune system (e.g., IL4/IL13, IL23, JAK/STAT, B cells, and plasma cells). In this review, we provide an overview of the most promising therapeutic targets that could improve the future clinical management of SSc.

Combining systemic and locally applied cellular therapies for the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by a functional and structural alteration of the microvascular network associated with cutaneous and visceral fibrosis lesions. Conventional therapies are based on the use of immunomodulatory molecules and symptomatic management but often prove to be insufficient, particularly for patients suffering from severe and rapidly progressive forms of the disease. In this context, cellular therapy approaches could represent a credible solution with the goal to act on the different components of the disease: the immune system, the vascular system and the extracellular matrix. The purpose of this review is to provide an overview of the cellular therapies available for the management of SSc. The first part will focus on systemically injected therapies, whose primary effect is based on immunomodulatory properties and immune system resetting, including autologous hematopoietic stem cell transplantation and intravenous injection of mesenchymal stem cells. The second part will discuss locally administered regenerative cell therapies, mainly derived from adipose tissue, developed for the management of local complications as hand and face disabilities.

Raynaud's phenomenon and digital ulcers: advances in evaluation and management.

The aim of this review is to give an update on advances in evaluation and management of systemic sclerosis (SSc)-related Raynaud's phenomenon and digital ulceration, focusing on reports from the last 18 months. The increasing recognition of the huge impact of Raynaud's phenomenon and of digital ulceration on the everyday lives of patients with SSc has sparked enthusiasm internationally to develop better outcome measures and better treatments, and so a review is timely. There have been recent advances in the development of patient reported outcome instruments [e.g. the Hand Disability in Systemic Sclerosis-Digital Ulcers (HDISS-DU) instrument] and also in noninvasive imaging techniques, including thermography and laser Doppler methods. Improved outcome measures will facilitate future clinical trials, both early phase proof-of-concept and later phase trials. New insights have been gained into mechanisms of action and methods of administration of 'conventional' therapies, for example phosphodiesterase inhibitors and intravenous prostanoids. New treatment approaches are being investigated, including topical and procedural therapies. Clinicians can look forward to seeing these advances translating into clinical benefit over the next 5 years. To help ensure this, they should strive whenever possible to recruit patients with SSc-related digital vasculopathy into observational studies and clinical trials.