Management Of Systemic Sclerosis Research Articles

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.

A rare disease patient-reported outcome measure: revision and validation of the German version of the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) using the Rasch model

BackgroundRare disease patient-reported outcome measures (PROMs) require linguistic adaptation to overcome the challenge of geographically dispersed patient populations. Importantly, PROMs such as health-related quality of life (HRQoL) should accurately capture responses to patient-identified concerns. The Systemic Sclerosis Quality of Life Questionnaire (SScQoL) is a 29-item tool validated in six languages. Previous evaluation of the German version revealed problems with dichotomous responses. This study aimed to revise the German SScQoL, extend the response structure, and evaluate content and construct validity, reliability and unidimensionality.MethodsThe instrument validation study involved revising the German SScQoL response structure, cognitive debriefing with patients and validation using Rasch analysis. The revised SScQoL was completed by Swiss-German-speaking patients with SSc within the Swiss MANagement Of Systemic Sclerosis (MANOSS) study. Rasch analysis was employed to test the validity, reliability and unidimensionality of the revised instrument.ResultsBased on cognitive debriefing with patients (n = 6) dichotomous items were extended to a polytomous 4-point response structure. A total of 78 patients completed the revised SScQoL. Initial analysis of the 29 items suggested the scale lacked fit to the model (χ2 = 51.224, df = 29, p = 0.007). Grouping items into five domains resulted in an adequate fit to the Rasch model (χ2 = 5.343, df = 5, p = 0.376) and unidimensionality (proportion of significant independent t tests: 0.045, 95% CI 0.016–0.114). Overall, the scale was well targeted, had high internal consistency (Person Separation Index, PSI = 0.931) and worked consistently in patients with different demographic and clinical characteristics.ConclusionsThe revised German SScQoL has a 4-point response structure and is a valid, reliable measure. Rasch analysis is useful for validating continuous response structure of quality of life measures. Further evaluation of measurement equivalence with other German-speaking cultures is required for multinational comparisons and data pooling.

An update on recent randomized clinical trials in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by a remarkable clinical heterogeneity and variable disease course. In this multifactorial condition, the interaction of several pathogenic pathways related to inflammation, vasculopathy and fibrosis promote organ damage. The understanding of the pathogenesis of SSc has improved in recent years leading to the identification of relevant therapeutic targets. Over the last few years, insightful clinical trials have been published and great progress has been made in developing effective therapeutic options. The positive results of the Safety and Efficacy of Nintedanib in Systemic SClerosIS (SENSCIS) trial have led to the approval by drug agencies of the first drug for SSc-related interstitial lung disease. However, the majority of clinical trials have focused on immunosuppressive therapy. Although benefit trends have been observed, outstanding results have not been achieved and to date no immunosuppressant has been approved in SSc. Clinical trial design has evolved regarding inclusion criteria with the aim to enrich for progressive patients. Endpoints have also been revised to better cover the fields of patients' feelings and functioning. Finally, background synthetic immunosuppressants have been allowed in some trials evaluating targeted therapies opening the door to combination therapies. Herewith, we provide an overview of the most significant clinical trials developed in recent years for the management of SSc.

Treatment of systemic sclerosis

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by skin and visceral fibrosis, vascular hyperreactivity and obliterative vasculopathy. Some of its complications such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and heart involvement can be life-threatening and are associated with a high mortality and a poor prognosis. Many clinical trials were carried out in order to improve the survival and prognosis of SSc patients. The management of SSc is based on the frequent and regular assessment of the potential organ damage, and if present, the establishment of graduated pharmacological therapeutic strategies, associated with non-pharmacological procedures. Several randomized clinical trials have showed significant positive outcomes regarding some specific involvements. Many advances have been made, especially in the field of targeted therapies and personalized medicine, based on specific characteristics of the patient and the SSc.

Cardiac reserve by 6-minute walk stress echocardiography in systemic sclerosis

ObjectivesThere is a high prevalence of left ventricular diastolic dysfunction (LVDD) in systemic sclerosis (SSc) which is associated with high mortality. Thus, early detection of LVDD could be important in...

A 3-Year Observational Study of Patients with Progressive Systemic Sclerosis Treated with an Intensified B Lymphocyte Depletion Protocol: Clinical and Immunological Response.

Background: B-cells have been suggested to play a role in the pathogenesis of systemic sclerosis (SSc), representing, therefore, a potential therapeutic target. Objectives: We aimed at investigating the 36-month outcomes of 20 SSc patients who underwent an intensified B-depletion therapy (IBCDT) scheme, including both Rituximab (RTX) and cyclophosphamide (CYC). Methods: Data from 20 severe patients (18 females and 2 males, mean age 66.7 ± 11.0 years) with diffuse SSc (anti-topoisomerase I antibody in 95%) patients with multiorgan involvement including interstitial lung disease (ILD) treated with an IBCDT were prospectively collected. IBCDT comprehended: RTX 375 mg/m2 administered for four weekly doses (on days 1, 8, 15, and 22), followed by two additional doses after 30 and 60 days, in addition to two administrations of 10 mg/kg of intravenous CYC plus three methylprednisolone pulses (15 mg/kg) and subsequently followed by oral prednisone rapidly tapered to low minimum dosage of 5 mg daily. In addition, 10 patients with more severe functional respiratory impairment at baseline were also treated with RTX 500 mg every 4 months during the first year and two times a year during the second and the third year. Results: After 36 months of follow-up, we recorded significant amelioration in N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels (mean 385.4 ± 517 pg/mL at baseline to 279 ± 543 after 36 months). In addition, a significant radiological improvement of ILD in 20% of patients (4/20) and a radiological stabilization with no sign of progression of interstitial involvement in 13/20 (65%) were documented. A total of 3 out of 20 (15%) patients experienced a worsening of the ILD. No patient showed further decrease in functional respiratory parameters, including forced vital capacity, forced expiratory volume in one second, and mean values of diffusing capacity for carbon monoxide Moreover, no patient showed any change in the ejection fraction and pulmonary artery pressure when comparing values at baseline and after 24 and 36 months of observation. No severe infection, renal flare, RTX-related side effects were observed. No patient died. Conclusions: Our findings support that the IBCDT was well tolerated and might be a promising therapeutic option for the management of SSc, especially in those subjects with multiorgan involvement that includes ILD.

Hematopoietic stem cell transplantation in systemic sclerosis: Yes!! BUT. . .

Systemic sclerosis is a chronic multisystem, autoimmune disease with high mortality, and to date, has no effective approved therapy. For patients with the most severe forms of systemic sclerosis, autologous hematopoietic stem cell therapy has been proven to be effective, as demonstrated by three randomized controlled clinical trials and at least two registry studies. In the controlled studies, autologous hematopoietic stem cell therapy was shown to improve mortality, skin involvement, quality-of-life, and function compared with patients treated with intravenous cyclophosphamide. There is significant transplant-related mortality associated with autologous hematopoietic stem cell therapy, as well as infectious and noninfectious serious adverse events, including cardiac and renal compromise. Although the results of autologous hematopoietic stem cell therapy clinical trials to date are highly encouraging, a number of important unanswered questions remain. These include the following: What is the optimal transplant regimen; can the spectrum of systemic sclerosis patients who respond to autologous hematopoietic stem cell therapy be expanded; how can disease relapse following autologous hematopoietic stem cell therapy be predicted and managed; can treatment-related toxicity and mortality be mitigated; can response or toxicity be predicted; and finally, is there a place for allogeneic stem cell transplants in systemic sclerosis? Systemic sclerosis is an autoimmune disease with multiple immunological, vascular, and fibrotic abnormalities. Immunosuppressive therapy is frequently used, but to date its efficacy has been generally modest. Stem cell transplantation is the most potent immunosuppressive therapy currently available, and as discussed below, may have an important role in the management of systemic sclerosis.

Mesenchymal stem cells in systemic sclerosis therapy.

Systemic sclerosis (SSc) is a rare autoimmune disorder with a high mortality rate. There are still many unknowns concerning the pathophysiology of this disease, due to its clinical heterogeneity. Since there is still no curative treatment, researchers focus on finding novel methods to help the patients. One of the valid options is cellular therapy, and mesenchymal stem cells (MSCs)-based therapy yields great expectations. These cells possess especially valuable attributes regarding key points of SSc. Nevertheless, the effectiveness and safety of this therapy must undergo a rigorous process of verification.In preclinical trials, animal models proved to be a valuable source of scientific knowledge regarding SSc. Because of that, it has been possible to test autologous or allogeneic MSCs from various sources in many clinical trials. A lot of aspects still have to be determined to assess their potential in the management of SSc, probably in association with other therapies.

Interstitial pneumonia with autoimmune features.

Interstitial lung disease (ILD) is an umbrella term for lung disease characterised by inflammation and fibrosis of the interstitium. ILD can be idiopathic or secondary to connective tissue disorders, drugs or environmental exposures. Before labelling it as idiopathic we have to rule out secondary causes. ILD is one of the most common extra-articular manifestations of connective tissue diseases (CTDs), causing significant morbidity and mortality. Patients with pre-existing CTD can develop ILD; some patients develop ILD against the background of either one or two clinical features of a CTD or isolated auto-antibody positivity. The current terminology for such an entity is interstitial pneumonia with autoimmune features (IPAF). The current criterion is based on three domains: clinical, serologic and morphologic. To satisfy the IPAF classification criteria, one needs to satisfy the mandatory criterion with one feature from two of the three domains. Classifying patients with this criterion helps in early initiation of immunosuppression and in monitoring them closely for development of features of a well defined CTD. There are a few limitations like the clinical domain being more skewed towards systemic sclerosis and in˜flammatory myositis, exclusion of antineutrophilic cytoplasmic antibody (ANCA) and cytoplasmic pattern in antinuclear antibody (ANA). There are no clear protocols for treatment of IPAF and most of the data has been extrapolated from the management of systemic sclerosis (SSc) ILD and idiopathic non-specific c interstitial pneumonia (NSIP). Progressive disease in spite of treatment demands stronger immunosuppressive agents. Studies on the role of antifibrotics in IPAF are underway, with few small studies showing positive outcomes. There are con˜flicting reports on the survival and outcome of the IPAF cohort. Certain studies suggest that they have better survival compared with idiopathic pulmonary fibrosis (IPF) though other studies contradict this statement.

FRI0228 TOFACITINIB IN THE TREATMENT OF SKIN AND MUSCULOSKELETAL INVOLVEMENT IN ADULT PATIENTS WITH EARLY SYSTEMIC SCLEROSIS, EVALUATED BY ULTRASOUND

Background:The whole management of systemic sclerosis (SSc) remains to be defined while trials mainly focus on the treatment of different organ involvement and disease-modifying treatments are still not available.Objectives:To assess the safety and efficacy of tofacitinib (TOF) treatment on skin and musculoskeletal involvement as compared to methotrexate (MTX) treatment in patients with early SSc.Methods:In this 52-week, prospective, investigator-initiated, open-label, single-centre study, 66 patients with SSc were enrolled. Thirty-three patients received 5mg of oral TOF twice a day; and thirty-three received 7.5-10 mg of MTX weekly. The primary outcome measures were: skin fibrosis improvement at week 26, assessed by the reduction in skin thickness - evaluated by the modified Rodnan skin score (mRSS) and the ultrasound (US) measured skin thickness; improvement in the musculoskeletal involvement, assessed by the reduction in the joint and tendon score (US10SSc score); and adverse events from baseline to week 26. The dynamics in the outcome measures within each group were examined through Wilcoxon tests and between-group comparisons were performed through Mann-Whitney U and Chi-square tests.Results:At baseline, both groups of patients had similar median scores with no significant differences on all measures: mRSS (p = 0.589), US measured skin thickness (p = 0.822), and US10SSc score (p = 0.918). At week 26, significant differences were observed between the two treatment groups as the TOF treated patients showed a greater reduction in mRSS and musculoskeletal manifestations. In the TOF group, the median mRSS score decreased by 50% from 24 to 12 (IQR = 7.50) versus a smaller decrease of 8.70% in the MTX group, from 23 to 21 (IQR = 8.00), p < 0.001. The median US measured skin thickness in the TOF treated patients decreased by 12.87% from 1.71 to 1.49 (IQR =0.31) versus a decrease of 4.73%, from 1.69 to 1.61 (IQR =0.52) in the MTX group, p = 0.040. The US10SSc median score in the TOF group decreased by 56.25% from 16 to 7 (IQR = 6.50) versus a decrease of 12.5% in MTX group from 16 to 14 (IQR =10.50), p < 0.001. There was no significant difference between the groups in the number of adverse events from baseline to week 26. No cases of herpes zoster and deep vein thrombosis were observed in the TOF group.Conclusion:The data show that in early SSc TOF may lead to a significant improvement of skin thickness, measured with the mRSS and US, and of the musculoskeletal involvement, measured by the US10SSc score. TOF has also shown a satisfactory safety profile.

Management of systemic sclerosis: the first five years.

This review provides a risk-stratified and evidence-based management for subsets of systemic sclerosis (SSc) patients in the first five years from disease onset. Cardiopulmonary disease remains the primary cause of mortality in SSc patients. Morbidity and mortality in SSc-associated pulmonary arterial hypertension have improved with combination treatment, in either an upfront or sequential treatment pattern. Traditional therapies for interstitial lung disease (SSc-ILD) have targeted those with clinically significant and progressive ILD with immunosuppression. New data suggest a possible paradigm shift, introducing immunosuppressive therapy to patients before they develop clinically significant or progressive ILD. The year 2019 saw the approval of the first FDA-approved therapy for SSc-associated interstitial lung disease, using an antifibrotic agent previously approved for idiopathic pulmonary fibrosis. To date, only autologous hematopoietic stem cell transplant has demonstrated a mortality benefit for SSc-ILD, albeit in a narrow spectrum of SSc-ILD patients. SSc is a highly heterogeneous autoimmune disease typified by varying clinical trajectories. Its management may be stratified within the first five years by subclassifying patients based on factors that have important prognostic significance: skin distribution and autoantibody status.

Treatment modalities and drug survival in a systemic sclerosis real-life patient cohort

BackgroundEuropean data indicate that systemic sclerosis (SSc)-related death rates are increasing, thus raising concerns about SSc’s optimal management. Herein, we describe current treatment modalities and drug survival in a real-life SSc cohort.MethodsDetails on immunosuppressive/antiproliferative (methotrexate, mycophenolate, cyclophosphamide, azathioprine, rituximab, tocilizumab) and vasoactive agent [(endothelin receptor antagonists (ERAs), sildenafil, iloprost, and calcium channel blockers (CCB)] administration during the disease course (11.8 ± 8.4 years, mean + SD) of 497 consecutive patients examined between 2016 and 2018 were retrospectively recorded. Drug survival was assessed by Kaplan–Meier analysis.ResultsMethotrexate was the most frequently administered immunosuppressive/antiproliferative agent (53% of patients), followed by cyclophosphamide (26%), mycophenolate (12%), and azathioprine (11%). Regarding vasoactive agents, CCB had been ever administered in 68%, ERAs in 38%, iloprost in 7%, and sildenafil in 7% of patients; 23% of patients with pulmonary fibrosis had never received immunosuppressive/antiproliferative agents, 33% of those with digital ulcers had never received ERAs, iloprost, or sildenafil, whereas 19% of all patients had never received either immunosuppressive/antiproliferative or other than CCB vasoactive agents. Survival rates of methotrexate, cyclophosphamide, and mycophenolate differed significantly, being 84/75%, 59/43%, and 74/63% at 12/24 months, respectively, with inefficacy being the most frequent discontinuation cause. Conversely, CCB, ERAs, and sildenafil had high and comparable retention rates of 97/91%, 88/86%, and 80/80%, respectively.ConclusionsExisting therapeutic limitations indicate that more evidence-based treatment is warranted for successful management of SSc. Vasculopathy seems to be managed more rigorously, but the low retention rates of immunosuppressive/antiproliferative drugs suggest that effective and targeted disease-modifying agents are warranted.

Digital ulcer debridement in systemic sclerosis: a systematic literature review.

Optimal wound care is an essential component in the management of systemic sclerosis (SSc) digital ulcers (DUs). DU debridement has been suggested to reduce ulcer-related pain and improve tissue healing. However, only a minority of rheumatologists perform DU debridement, and there is no standard of care/protocol. Our objectives were to (i) evaluate the current evidence for the use of debridement in DU management and (ii) assess whether there are any specific protocols. A systematic literature review was performed searching the PubMed database (between 01/01/1950-01/03/2019) in accordance with PRISMA guidelines. Two independent reviewers screened and extracted the abstracts/full manuscripts. Articles in English, which focussed on SSc-DU debridement/curettage, were included. Exclusion criteria included studies of juvenile/paediatric patients and basic/non-clinical research. Our search identified 1497 studies of which 4 studies were included in our final analysis. Three studies used scalpel debridement, and one study used this in combination with autolytic debridement. No studies specifically reported the effect on DU healing from debridement. Autolytic debridement with hyaluronate-based products was associated with significant ulcer pain and inflammation. Local anaesthetic significantly reduces pain both during and after debridement. Combined local and oral analgesia is often required for more severe or infected DUs. DU (scalpel and autolytic) debridement is being used by some clinicians in rheumatology; however, there are no standardised protocols. To improve wound care for SSc-DUs, future research should focus on developing a standardised protocol for SSc-DU debridement, with a view to facilitate randomised controlled trials to demonstrate safety and treatment efficacy.Key Points• Optimal wound care is an essential component in the management of systemic sclerosis-digital ulcers.• 'Sharp' debridement uses a scalpel, whereas 'autolytic' debridement uses dressings to optimize endogenous tissue lysis.• There is significant variation in the use of digital ulcer debridement in systemic sclerosis.• A standardized protocol and randomized controlled trials are needed to demonstrate debridement the safety and efficacy of digital ulcer debridement in systemic sclerosis.

Nailfold Capillaroscopy and Retinal Findings in Patients with Systemic Sclerosis: Is There An Association?

Introduction:Systemic sclerosis (SSc) is characterized by fibrosis and intimal proliferation of cutaneous and visceral small vessels. These architectural abnormalities can be visualized with nailfold capillaroscopy (NFC); the changes being quite characteristic. At the same time, morphological alterations in retinal vascular bed are expected but sparsely described.Aim:We aimed to characterize the frequency and type of retinal microvascular changes in patients with SSc and to analyze any association with NFC changes.Patients and Methods:With institutional ethical committee approval, we recruited 45 consecutive patients with SSc (diagnosed based on American College of Rheumatology and European League against Rheumatism [ACR/EULAR-2013] criteria). NFC was done for all of them with a Universal Serial Bus (USB) dermatoscope; additionally, fundoscopy, fundus photography, and optical coherence tomography (OCT) were analyzed. Disease characteristics in patients with and without retinal disease were compared.Results:Among the 45 SSc patients, 12 (26.67%) had limited cutaneous SSc (lSSc) while 33 (73.33%) had diffuse cutaneous disease (dSSc). Retinal microvascular changes seen as mild arteriolar alteration and arteriovenous crossing changes were recorded in 13 patients (28.89%); mostly in those with dSSc (12/13). The NFC architectural changes were more severe in patients with retinal disease, though the difference was not statistically significant.Conclusion:Patients with SSc can often have retinal microvascular abnormalities commensurate with the vascular changes characteristic of SSc. The severity of retinal changes correlates with changes in NFC. NFC, which is now an essential tool for the management of SSc, could be a surrogate marker for retinal involvement in these patients.

TH17 cells\xa0expressing CD146 are significantly increased in patients with Systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation. CD146 is an adhesion molecule essentially expressed in the vascular system, but also on TH17 lymphocytes. In view of the recently described role of CD146 in SSc, we hypothesized an involvement of CD146 positive TH17 cells in this disease. Compared to healthy controls, we showed that both soluble form of CD146 (sCD146), and IL17A levels were increased in patients with SSc with a positive correlation between both factors. A significant increase in TH17 cells attested by an increase of RORγT, IL17A mRNA and CD4+ IL17A+ cell was observed in patients with SSc. Interestingly, the percentage of TH17 cells expressing CD146 was higher in patients with SSc and inversely correlated with pulmonary fibrosis. In vitro experiments showed an augmentation of the percentage of TH17 cells expressing CD146 after cell treatment with sCD146, suggesting that, in patients the increase of this sub-population could be the consequence of the sCD146 increase in serum. In conclusion, TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc.

Developing a rare disease chronic care model: Management of systemic sclerosis (MANOSS) study protocol.

The aim of the management of systemic sclerosis (MANOSS) study described in this protocol is to develop a chronic care model, based on a contextual analysis and stakeholder involvement, for patients living with the rare disease systemic sclerosis (SSc) in Switzerland. Applying an implementation science approach, this study starts with an explanatory sequential mixed method study for contextual analysis, followed by broad stakeholder involvement for model development and a Delphi study to reach consensus. First, a quantitative cross-sectional survey with patients and healthcare professionals (HPs) will be conducted to identify current practice patterns of chronic illness management and technology readiness. Second, qualitative interviews with patients, family members and HPs will be performed to gain a deeper understanding of care needs identified in the quantitative survey. Third, a model of care will be co-created with input from patients, HPs and other experts. The eHealth enhanced Chronic Care Model will serve as a guiding framework. The new model and corresponding outcome parameters will be refined using a Delphi-study approach to reach consensus on a testable model of care for persons living with SSc. The protocol has received research ethics committee approval in September 2018 by the Swiss Ethics Committee. The MANOSS study's participatory approach is essential for contextual fit of the model for patients with SSc in this setting. Subsequent feasibility testing and implementation are planned to evaluate the model's value in relation to health disparities faced by this patient population. Patients living with this rare disease lack access to coordinated, specialized care and self-management support from qualified HPs. Reengineering of current care, with consideration for technological opportunities, is warranted to meet patients' and families' needs.

Management of systemic sclerosis: A dermatologist's approach

Systemic sclerosis (SSc) is an autoimmune connective tissue disease affecting the blood vessels, skin, and internal organs. The main pathogenic mechanisms are vascular dysregulation, tissue fibrosis due to collagen and extracellular protein deposition, and autoantibody production due to immune dysfunction. The treatment also targets these mechanisms. Various criteria including the American College of Rheumatology and the European League against Rheumatism are laid down for the clinical diagnosis of scleroderma, and treatment is tailored to the systems involved. In the initial stages of the SSc, immunosuppressants are more useful, whereas in the later stages, antifibrotic therapies are important. Vasospasm and endothelial dysfunction are seen in all stages of the disease, and hence, vascular therapies are needed throughout the course of the disease. Special care should be taken to rule out gastrointestinal, pulmonary, and renal system involvement if the primary treatment is by a dermatologist.