Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS).

Objective: The Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR study showed that, despite not showing any clinical sign of disease, patients with Raynaud's and antinuclear antibodies and/or capillaroscopy abnormalities often progress to systemic sclerosis (SSc) within 5 years. We aimed to determine whether VEDOSS biosamples show biological SSc activity pre-clinically.

Methods: Skin biopsies were histologically analysed.

Long-term retention rate, adverse event temporal patterns and rescue treatment strategies of mycophenolate mofetil in systemic sclerosis: insights from real-life.

Background: Mycophenolate mofetil (MMF) is a mainstay for the treatment of systemic sclerosis (SSc). The occurrence and implications of MMF-related adverse events on drug retention rates in real life remain poorly defined. We aimed to determine the MMF retention rate and to investigate the causes and patterns of discontinuation, adverse events (AEs) and treatment options used after discontinuation.

The 2024 British Society for Rheumatology guideline for management of systemic sclerosis.

This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives. It is an update of the previous 2015 SSc guideline. The recommendations were developed and agreed by the group and are underpinned by published evidence, assessed by systematic literature review and reinforced by collective expert opinion of the group.

The 2024 British Society for Rheumatology guideline for management of systemic sclerosis-executive summary.

This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives. It is an update of the previous 2015 SSc guideline. The recommendations were developed and agreed by the group and are underpinned by published evidence, assessed by systematic literature review and reinforced by collective expert opinion of the group.

Concordance and Prognostic Relevance of Different Definitions of Systemic Sclerosis Interstitial Lung Disease Progression.

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a common complication that has a varied progression rate and prognosis. Different progression definitions are available, including minimal clinically important worsening of FVC, EUSTAR (European Scleroderma Trials and Research Group) progression, OMERACT (Outcome Measures in Rheumatology Clinical Trials) progression, and Erice ILD working group progression. Pulmonary function and symptom changes may act as specific confounding factors when applying these definitions in SSc.

Rituximab retention rate in systemic sclerosis: a long term real-life multicenter study.

Objectives: to report real-life data on rituximab retention-rate as indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients.

Methods: SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized, and longitudinally monitored. A competing risk analysis with sub-Hazard Ratio(sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation.

Serum CCL24 as a Biomarker of Fibrotic and Vascular Disease Severity in Systemic Sclerosis.

Background: Systemic sclerosis (SSc) is a heterogeneous disease, characterized by variable tissue and vascular fibrosis in the context of autoimmune activation. CCL24 (or Eotaxin2) has been shown to promote microangiopathic, proinflammatory, and profibrotic processes in preclinical models of SSc. Here, we study serum CCL24 levels in a real-life cohort of patients with SSc, to determine its distribution across disease features and its value in predicting disease progression and related mortality.

The β-Secretase BACE1 Drives Fibroblast Activation in Systemic Sclerosis through the APP/β-Catenin/Notch Signaling Axis.

BACE1 is well-known for its role in the development of Alzheimer's disease. Recent publications, including our own, have demonstrated a role for this enzyme in other chronic diseases. The aim of this study was to investigate the role of BACE1 in the autoimmune disease systemic sclerosis (SSc).

Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives.

The alveolar epithelial-to-mesenchymal transition is the process of transformation of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. A partial epithelial-to-mesenchymal transition process can indirectly contribute to lung fibrosis through a paracrine stimulation of the surrounding cells, while a finalized process could also directly enhance the pool of pulmonary fibroblasts and the extracellular matrix deposition. The direct demonstration of alveolar epithelial-to-mesenchymal transition in scleroderma-related interstitial lung disease is challenging due to technical pitfalls and the limited availability of lung tissue samples.

MRI Digital Artery Volume Index (DAVIX) as a surrogate outcome measure of digital ulcer disease in patients with systemic sclerosis: a prospective cohort study.

Background: Vascular fibrosis is a key manifestation of systemic sclerosis that leads to the narrowing of small and medium arteries, causing vascular clinical manifestations including digital ulcers and pulmonary arterial hypertension. We investigated the potential of the MRI-based Digital Artery Volume Index (DAVIX) as a surrogate outcome measure of vascular fibrosis by using it to quantify and predict the burden of digital ulcer disease in patients with systemic sclerosis.

Methods: Two independent cohorts of patients participating in the prospective observational study STRIKE were consecutively enrolled from the Scleroderma Clinic of the Leeds Teaching Hospitals Trust, Leeds, UK.

Clinical trajectories of hand function impairment in systemic sclerosis: an unmet clinical need across disease subsets.

Background: Hand involvement is an early manifestation of systemic sclerosis (SSc), culprit of diagnosis and classification, and recognised major driver of disability. Impairment of hand function burdens both limited and diffuse cutaneous subsets and therefore could be targeted as 'basket' endpoint in SSc. Nevertheless, its natural history in current standard of care is not well characterised, limiting the design of targeted trials.

Ultrasound in anti-CCP+ at-risk individuals without clinical synovitis: development of a novel 6-joint protocol for feasible risk prediction.

Objectives: To investigate, in anti-CCP antibody-positive individuals with musculoskeletal symptoms but no clinical synovitis (CCP+ at-risk), the additional value of US for the prediction of inflammatory arthritis. Furthermore, to define a concise US protocol for feasible risk prediction.

Methods: Demographic and clinical data were collected in 417 CCP+ at-risk (Leeds CCP cohort) with a baseline US scan assessing synovitis and bone erosions in 36 joints, and a follow-up duration ≥24 months.

Circulating extracellular vesicles in the context of interstitial lung disease related to systemic sclerosis: A scoping literature review.

Background: Interstitial lung disease (ILD) is a significant cause of disability and mortality in systemic sclerosis (SSc), where lung fibrosis stems from the interaction of cells within the epithelial, endothelial, interstitial, and immune cell compartments. Extracellular vesicles (EVs) are particles released by cells capable of transferring functionally active molecules, playing a crucial role in intercellular communication. This scoping review aims to identify and map existing evidence about the role of EVs as biomarkers or pathophysiological actors in SSc-ILD.

Extension of Lung Damage at Chest Computed Tomography in Severely Ill COVID-19 Patients Treated with Interleukin-6 Receptor Blockers Correlates with Inflammatory Cytokines Production and Prognosis.

Elevated inflammatory markers are associated with severe coronavirus disease 2019 (COVID-19), and some patients benefit from Interleukin (IL)-6 pathway inhibitors. Different chest computed tomography (CT) scoring systems have shown a prognostic value in COVID-19, but not specifically in anti-IL-6-treated patients at high risk of respiratory failure. We aimed to explore the relationship between baseline CT findings and inflammatory conditions and to evaluate the prognostic value of chest CT scores and laboratory findings in COVID-19 patients specifically treated with anti-IL-6.

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.

Real-life efficacy and safety of nintedanib in systemic sclerosis-interstitial lung disease: data from an Italian multicentre study.

Introduction: Nintedanib (NTD) has been shown to be effective in systemic sclerosis (SSc)-interstitial lung disease (ILD). Here we describe the efficacy and safety of NTD in a real-life setting.

Methods: Patients with SSc-ILD treated with NTD were retrospectively evaluated at 12 months prior to NTD introduction; at baseline and at 12 months after NTD introduction.

Survival and prognostic factors from a multicentre large cohort of unselected Italian systemic sclerosis patients.

Objectives: Survival and death prognostic factors of SSc patients varied during the past decades. We aimed to update the 5- and 10-year survival rates and identify prognostic factors in a multicentre cohort of Italian SSc patients diagnosed after 2009.

Material And Methods: Patients who received a diagnosis of SSc after 1 January 2009 and were longitudinally followed up in four Italian rheumatologic centres were retrospectively assessed up to 31 December 2020.

Sudden winter iloprost withdrawal in scleroderma patients during COVID-19 pandemic.

Introduction: Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used.

Methods: A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion.

Concepts of Entheseal Pain.

Pain is the main symptom in entheseal diseases (enthesopathies) despite a paucity of nerve endings in the enthesis itself. Eicosanoids, cytokines, and neuropeptides released during inflammation and repeated nonphysiologic mechanical challenge not only stimulate or sensitize primary afferent neurons present in structures adjacent to the enthesis, but also trigger a "neurovascular invasion" that allows the spreading of nerves and blood vessels into the enthesis. Nociceptive pseudounipolar neurons support this process by releasing neurotransmitters from peripheral endings that induce neovascularization and peripheral pain sensitization.

Lung vascular changes as biomarkers of severity in systemic sclerosis-associated interstitial lung disease.

Objectives: It has recently become possible to assess lung vascular and parenchymal changes quantitatively in thoracic CT images using automated software tools. We investigated the vessel parameters of patients with SSc, quantified by CT imaging, and correlated them with interstitial lung disease (ILD) features.

Methods: SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated.

Postural control and disability in patients with early rheumatoid arthritis.

Objectives: Rheumatoid arthritis (RA) may affect the postural control through abnormal sensory inputs and impaired motor responses. Sensory Organization Test (SOT) objectively evaluates contribution of different sensorial afferences in postural control. The aim of the study is to assess mechanisms of postural instability and their relations with disability and disease characteristics in an early RA(ERA) cohort.