Gastrointestinal tract microbiota modifications in systemic sclerosis.

Systemic sclerosis (SSc) is a complex autoimmune disease of unknown etiology. Genetic factors are thought to collude with various environmental triggers to induce SSc and subsequently manifest various SSc disease phenotypes. Emerging evidence suggests that the microbiota of the gastrointestinal tract (GIT) may represent a key pathogenic participant in this disease state. Recent studies have demonstrated specific alterations in the GIT microbial composition in SSc patients, and this article reviews studies that have investigated the GIT microbiota in SSc patients. The focus of this article is to highlight the modifications in the GIT microbiota observed in SSc patients belonging to different cohorts and to demonstrate how these alterations may be associated with specific SSc features. This article presents the results of these SSc microbiota studies in the context of findings from microbiotic studies in other autoimmune states to explore similarities and differences across disease states affecting the immune system. Finally, this article provides insights into potential SSc therapies that target the GIT microbiota. Given the complexity and variability of the SSc disease state, any treatment aimed at modulating GIT microbiota will likely need to be coupled with additional interventions that target other SSc disease components

Gastrointestinal involvement in systemic sclerosis: Effects on morbidity and mortality and new therapeutic approaches.

The majority of research studies in systemic sclerosis focus largely on addressing skin and cardiopulmonary manifestations. Fewer studies assess the pathogenesis and treatment of gastrointestinal tract involvement in systemic sclerosis, despite the fact that the majority of patients with systemic sclerosis have gastrointestinal manifestations and these manifestations are a leading cause of death in systemic sclerosis. The present review provides a comprehensive update on morbidity and mortality outcomes related to gastrointestinal involvement in systemic sclerosis. This review also describes conventional and emerging approaches to managing gastrointestinal symptoms in systemic sclerosis. Recent developments in systemic sclerosis-gastrointestinal research efforts have revealed promising treatment targets, including specific auto-antibodies and microbiota alterations. This review will conclude with an overview of future research directions that may improve our understanding of systemic sclerosis-gastrointestinal involvement and ultimately help to alleviate suffering from this devastating dimension of systemic sclerosis

Education and the capabilities approach: Life skills education as a bridge to human capabilitie

International audienc

Scleroderma Skin: How Is Treatment Best Guided by Data and Implemented in Clinical Practice?

As skin involvement is the hall mark of systemic sclerosis (SSc) and changes of skin involvement have shown to correlate with internal organ involvement, assessing the extend of skin involvement is key. Although the modified Rodnan skin score is a validated tool used to evaluate the skin in SSc, it has its drawbacks. Novel imagine methods are promising but should be further evaluated. As for molecule markers for skin progression there are conflicting data on the predictive significance of baseline SSc skin gene expression profiles, but immune cell type signature in SSc skin correlates with progression

Gastrointestinal involvement in systemic sclerosis: Effects on morbidity and mortality and new therapeutic approaches

The majority of research studies in systemic sclerosis focus largely on addressing skin and cardiopulmonary manifestations. Fewer studies assess the pathogenesis and treatment of gastrointestinal tract involvement in systemic sclerosis, despite the fact that the majority of patients with systemic sclerosis have gastrointestinal manifestations and these manifestations are a leading cause of death in systemic sclerosis. The present review provides a comprehensive update on morbidity and mortality outcomes related to gastrointestinal involvement in systemic sclerosis. This review also describes conventional and emerging approaches to managing gastrointestinal symptoms in systemic sclerosis. Recent developments in systemic sclerosis–gastrointestinal research efforts have revealed promising treatment targets, including specific auto-antibodies and microbiota alterations. This review will conclude with an overview of future research directions that may improve our understanding of systemic sclerosis–gastrointestinal involvement and ultimately help to alleviate suffering from this devastating dimension of systemic sclerosis

Current and future perspectives on management of systemic sclerosis-associated interstitial lung disease

Introduction: Systemic sclerosis (SSc) is a rare and complex connective tissue disease characterized by fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is a common complication of SSc and the leading cause of SSc-related death. No drugs are licensed for the treatment of SSc-ILD. Areas covered: This review provides an overview of the current treatment of SSc-ILD and a perspective on investigational therapies, focusing on those studied in randomized controlled trials. Expert opinion: There is substantial room for improvement in the treatment of SSc-ILD. Current treatment focuses on immunosuppressant therapies, particularly cyclophosphamide and mycophenolate. Hematopoietic stem cell transplantation has been shown to improve long-term outcomes, but the risk of treatment-related mortality restricts its use to select patients at specialized centers. Modifying the course of disease to improve outcomes remains the goal for new therapies. Several drugs are under investigation as potential therapies for SSc-ILD, providing hope that the limited treatment armamentarium for SSc-ILD will be expanded and improved in the near future. Expert consensus is needed on how to screen for and monitor SSc-ILD and on when to initiate and escalate therapy

Natural history and screening of interstitia lung disease in systemic autoimmune rheumatic disorders

Interstitial lung disease (ILD) is a relatively frequent manifestation of systemic autoimmune rheumatic disorders (SARDs), including systemic sclerosis (SSc), rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. Interstitial pneumonia with autoimmune features (IPAF) has been proposed to describe patients with ILD who have clinical or serological findings compatible with SARDs but they are not sufficient for a definite diagnosis. ILD may present with different patterns among patients with SARDs, but most commonly as nonspecific interstitial pneumonia (NSIP), with the exception of RA and ANCA vasculitis that more often present with usual interstitial pneumonia (UIP). The natural history of ILD is quite variable, even among patients with the same SARD. It may present with subclinical features following a slow progressively course or with acute manifestations and clinically significant rapid progression leading to severe deterioration of pulmonary function and respiratory failure. The radiographic pattern of ILD, the extent of the disease, the baseline pulmonary function, the pulmonary function deterioration rate over time and clinical variables related to the primary SARD, such as age, sex and the clinical phenotype, are considered prognostic factors for SARDs-ILD associated with adverse outcomes and increased mortality. Different modalities can be employed for ILD detection including clinical evaluation, pulmonary function tests, high resolution computed tomography and novel techniques such as lung ultrasound and serum biomarkers. ILD may determine the clinical outcome of SARDs, since it is associated with significant morbidity and mortality and therefore screening of patients with SARDs for ILD is of great clinical importance

Setting the international standard for longitudinal follow-up of patients with systemic sclerosis: a Delphi-based expert consensus on core clinical features

Background Systemic sclerosis (SSc) is a severe, progressive multiorgan disease but to date, there are no established standardised international guidelines for follow-up of patients with SSc. The goal of this project was to develop an expert consensus for annual systematic investigations in patients with SSc to enhance their standard-of-care. Material and methods The Delphi method was applied. All SSc experts from the European Scleroderma Trials and Research group network and the Scleroderma Clinical Trial Consortium were invited to participate. All experts were asked to answer questionnaires in five Delphi steps to determine the domains of interest and tools for each domain for an annual systematic assessment of patients with SSc. Each item was rated on a scale between 0% and 100% (not and very important), and parameters rated >80% by more than 75% of the experts were regarded as acceptable. Results In total, 157 experts worldwide participated with 71.3% experts seeing >50 patients with SSc annually. In the first round, 23 domains and 204 tools were suggested. After five Delphi steps, experts agreed on 10 domains including (1) Raynaud's phenomenon; (2) Digital ulcers; (3) Skin and mucosa; (4) Lung; (5); Heart; (6) GI domain, (7) Renal; (8) Musculoskeletal; (9) Laboratory and (10) Treatment. Overall, 55 tools were identified including clinical assessments, laboratory measurements and imaging or functional investigations. Conclusion Through five Delphi steps with world leading experts, a consensus was established on strongly suggested tools for a minimum annual systemic assessment of organ involvement in SSc. This work should enhance the standardisation and homogenisation of the practices