Targeting inflammation, fibrosis, and vascular dysfunction in systemic sclerosis: the role of diet and complementary and alternative medicine.

Purpose Of Review: Patients with systemic sclerosis (SSc) often seek advice regarding diet including functional foods, and complementary and alternative medicine (CAM) as adjunctive therapies. This review summarizes existing literature regarding these approaches.

Recent Findings: Study results of low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols (FODMAP), Mediterranean and ketogenic diets suggest symptom reduction and beneficial microbiota modulation in SSc, though sample sizes are small.

Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease.

Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesis of pulmonary fibrosis in animal models where their persistence in the niche requires signaling through Colony Stimulating Factor 1 Receptor (CSF1R). We hypothesized that the presence and proportion of MoAM in bronchoalveolar lavage (BAL) fluid from patients with SSc-ILD may be a biomarker of ILD severity.

Gastrointestinal manifestations of systemic sclerosis: current approaches and emerging therapies.

Purpose Of Review: This review highlights recent advances in the understanding and management of gastrointestinal manifestations in systemic sclerosis (SSc). It is intended for clinicians and researchers aiming to improve diagnostic accuracy and therapeutic strategies in managing SSc-related gastrointestinal disease.

Recent Findings: Gastrointestinal involvement in SSc is highly variable in terms of clinical presentation, symptom severity, progression, timing of onset, and response to treatment.

Machine Learning Analysis of Electronic Health Records Identifies Interstitial Lung Disease and Predicts Mortality in Patients with Systemic Sclerosis.

Background: Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc), affecting more than 40% of this population. Despite the availability of effective treatments to stabilize or improve lung function, survival for patients with SSc-ILD remains poor. Poor outcomes have been attributed to delayed diagnosis and initiation of treatment for SSc-ILD.

Cyclic GMP-AMP synthase expression is enhanced in systemic sclerosis-associated interstitial lung disease and stimulates inflammatory myofibroblast activation.

Objective: The lungs of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) contain inflammatory myofibroblasts that arise in association with fibrotic stimuli and perturbed innate immunity. The cytosolic DNA-binding receptor cyclic GMP-AMP synthase (cGAS) is implicated in inflammation and fibrosis, but its involvement in SSc-ILD remains unknown. We examined cGAS expression, activity and therapeutic potential in SSc-ILD using human biospecimens, cultured fibroblasts, precision-cut lung slices and a well-accepted animal model.

Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis.

Background: The modified Rodnan skin score (mRSS), a measure of systemic sclerosis (SSc) skin thickness, is agnostic to inflammation and vasculopathy. Previously, we demonstrated the potential of neural network-based digital pathology applied to SSc skin biopsies as a quantitative outcome. Here, we leverage deep learning and histologic analyses of clinical trial biopsies to decipher SSc skin features 'seen' by artificial intelligence (AI).

Gastroesophageal Intussusception Treated With Combined Transoral Incisionless Fundoplication in a Patient With Systemic Sclerosis.

We present a case of a 49-year-old woman with diffuse cutaneous systemic sclerosis with refractory gastroesophageal reflux disease and dysphagia for pills and solid foods. Esophagogastroduodenoscopy revealed gastroesophageal intussusception. Despite several interventions including esophageal stent placement, dysphagia persisted.

Serum type I interferon score as a disease activity biomarker in patients with diffuse cutaneous systemic sclerosis: a retrospective cohort study.

Background: Type I interferon (IFN) pathway activation has been associated with severe systemic sclerosis. We aimed to examine the association of serum IFN scores with disease activity and outcomes in two cohorts of patients with diffuse cutaneous systemic sclerosis.

Methods: In this retrospective cohort study, we included adult (aged >18 years) patients with diffuse cutaneous systemic sclerosis enrolled in the US Prospective Registry of Early Systemic Sclerosis (PRESS; incident cohort) or in the UK observational cohort (Stratification for Risk of Progression in Scleroderma [STRIKE]; prevalent cohort) registries and healthy controls (volunteers).

Acute Systemic Sclerosis-Associated Cardiomyopathy That Improved With Glucocorticoids and Cyclophosphamide.

Background: Systemic sclerosis (SSc) cardiomyopathy has a prevalence of 7 to 39% and is associated with increased mortality. Despite this, little evidence informs SSc cardiomyopathy treatment.

Case Summary: We present a patient with diffuse cutaneous SSc with acute heart failure.

An international perspective on the future of systemic sclerosis research.

Systemic sclerosis (SSc) remains a challenging and enigmatic systemic autoimmune disease, owing to its complex pathogenesis, clinical and molecular heterogeneity, and the lack of effective disease-modifying treatments. Despite a century of research in SSc, the interconnections among microvascular dysfunction, autoimmune phenomena and tissue fibrosis in SSc remain unclear. The absence of validated biomarkers and reliable animal models complicates diagnosis and treatment, contributing to high morbidity and mortality.

Atgl-Dependent Adipocyte Lipolysis Promotes Lipodystrophy and Restrains Fibrogenic Responses during Skin Fibrosis.

During skin fibrosis, extracellular matrix proteins are overproduced, and resident lipid-filled mature dermal adipocytes are depleted in both human disease and mouse models. However, the mechanisms underlying this reduction in lipid-filled adipocytes during fibrosis are poorly understood. In this study, we found that adipocyte lipolysis through the rate-limiting enzyme Atgl is required for loss of adipose tissue during skin fibrosis in mice.

Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis.

Background: The modified Rodnan skin score (mRSS), used to measure dermal thickness in patients with systemic sclerosis (SSc), is agnostic to inflammation and vasculopathy. Previously, we demonstrated the potential of neural network-based digital pathology applied to stained skin biopsies from SSc patients as a quantitative outcome. We leveraged deep learning and histologic analyses of clinical trial biopsies to decipher SSc skin features 'seen' by artificial intelligence (AI).

A Nerve-Fibroblast Axis in Mammalian Lung Fibrosis.

Fibrosis contributes to incurable pathologies in vital organs including the lung. Myofibroblasts are fibrogenic effector cells that accumulate via incompletely understood mechanisms. We discovered that α1-adrenoreceptor expressing myofibroblasts receive sympathetic nerve-derived noradrenergic inputs in fibrotic mouse and human lungs.

cGAS Expression is Enhanced in Systemic Sclerosis Associated Interstitial Lung Disease and Stimulates Inflammatory Myofibroblast Activation.

Objective: The lungs of patients with Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD) contain inflammatory myofibroblasts arising in association with fibrotic stimuli and perturbed innate immunity. The innate immune DNA binding receptor Cyclic GMP-AMP synthase (cGAS) is implicated in inflammation and fibrosis, but its involvement in SSc-ILD remains unknown. We examined cGAS expression, activity, and therapeutic potential in SSc-ILD using cultured fibroblasts, precision cut lung slices (PCLS), and a well-accepted animal model.

Gastrointestinal disease in systemic sclerosis: the neglected organ system?

Purpose Of Review: Identifying outcomes and clinical trial endpoints enabled the discovery of new inflammatory bowel disease (IBD) treatments. Herein, we describe efforts to advance the study of gastrointestinal (GI) manifestations in systemic sclerosis (SSc).

Recent Findings: Insights into the scope of the problem, as well as advancements in the measurement and treatment of SSc-GI, are underway.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

Objective: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs).

Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

Objective: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs).

Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

Objective: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease.

Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

Objective: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease.

Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology.