Gastrointestinal involvement in very early and established systemic sclerosis: insights from the SPRING-SIR national Italian registry.

Objectives: To describe the prevalence of gastrointestinal (GI) symptoms in systemic sclerosis (SSc) and Very Early Diagnosis of SSc (VEDOSS), identify clinical and serological features associated with GI involvement, and explore a cranio-caudal pattern of symptom distribution, using data from the Italian SPRING-SIR registry.

Methods: This cross-sectional analysis included patients fulfilling 2013 ACR/EULAR SSc or VEDOSS criteria. GI involvement was defined as symptoms in at least one GI tract segment and categorized as upper and lower.

Rare in the rare: Kikuchi-Fujimoto disease associated with connective tissue disorders. A report of our experience.

Kikuchi-Fujimoto disease (KFD) is a rare and benign lymphadenopathy of unknown etiology. Usually, it is an isolated and self-limiting condition requiring no specific therapy; however, in some cases, it may be associated with an autoimmune disease. Here, we report three cases of KFD developing an associated autoimmune connective disorder: the first case presented with Sjögren's syndrome, and the other two had a diagnosis of systemic lupus erythematosus.

Menopause in systemic sclerosis: the impact on clinical presentation in a multicenter cross-sectional analysis from the National Registry of the Italian Society for Rheumatology (SPRING-SIR).

Background: Hormonal changes in menopause might interact with the presentation of underlying autoimmune diseases, such as systemic sclerosis (SSc).

Objectives: Our study aimed to evaluate the association of (1) current menopausal status, (2) early menopause, and (3) disease onset during fertile or post-menopausal age on SSc clinical phenotype in a large SSc cohort from the Italian Systemic sclerosis Progression INvestiGation (SPRING-SIR) registry.

Design: Female SSc patients from the SPRING-SIR registry, fulfilling the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 classification criteria, with data on SSc disease onset, menopausal status, and menopausal age, were eligible.

Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic Sclerosis.

Mesenchymal stem cell (MSC) transplantation has emerged as a potential therapeutic strategy for systemic sclerosis (SSc), a rare autoimmune disease characterized by inflammation, fibrosis, and vasculopathy. Recent evidence suggests that the therapeutic benefits of MSCs do not depend directly on their ability to proliferate but rather on their capacity to release extracellular nanovesicles known as exosomes (MSC-Exos). MSC-Exos are rich in bioactive molecules such as microRNAs, which can modulate gene expression and trigger significant biological responses, playing a central role in modulating immune responses, inhibiting fibrotic pathways and promoting tissue repair and angiogenesis.

First-line diagnostic tests to intercept primary heart involvement in systemic sclerosis: Clinical associations from the SPRING-SIR registry.

Introduction: Primary heart involvement (pHI) is an overlooked and poorly characterised complication of systemic sclerosis (SSc), associated with the risk of heart failure, arrhythmia and death. Despite consensus definition by the World Scleroderma Foundation/Heart Failure Association (WSF/HFA), diagnostic criteria and risk factors remain poorly elucidated.

Methods: Out of 1922 patients in the Italian national SPRING registry, we excluded those with potentially confounding conditions according to WSF/HFA, and those with incomplete ECG or echocardiographic assessment, resulting in 600 subjects with clearly defined parameters to intercept SSc-pHI.

Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?

Microvascular dysfunction is considered one of the main pathogenetic pathways in systemic sclerosis (SSc), and endothelial cells plays a pivotal role even in the early phases of the disease. Endothelial dysfunction results in an early incapacity to adapt the vascular tone and the blood flow under stress conditions, thus losing the important adaptation mechanism that is the vascular reserve.The loss of vascular tone control in systemic sclerosis is clinically evident as Raynaud's phenomenon, one of the earliest signs of the disease.

Prevalence and clinical relevance of digital ulcers in systemic sclerosis patients from the real-life: the experience of the SPRING Registry of the Italian Society for Rheumatology.

Introduction: Digital ulcers (DU) are one of the most frequent manifestations in systemic sclerosis (SSc). The presence of DU seems to be a sentinel sign of internal organ involvement and is related to a poor prognosis of the disease. The aim of this study was to evaluate the prevalence and the relationship of DU with clinical manifestations/variants in a large SSc cohort from the SPRING registry.

Clinicians' perspectives concerning treatment initiation and escalation strategies for digital ulcers in patients with systemic sclerosis.

Objectives: Digital ulcers (DUs) are a major cause of pain and disability in systemic sclerosis (SSc) patients and remain a major treatment challenge. Our aim was to explore clinicians' perspectives towards treatment initiation and escalation, akin to a 'Treat to Target' (T2T) strategy.

Methods: SSc clinicians were invited to participate in an online survey.

Doppler ultrasound unveils splanchnic arteries ischemia allowing early successful revascularization in symptomatic systemic sclerosis patients.

Background: Systemic sclerosis (SSc) is characterized by macro and microvasculopathy, including splanchnic circulation. Chronic mesenteric ischemia (CMI) is a potentially severe condition which can complicate SSc gastrointestinal vasculopathy. Doppler ultrasound (DUS) may be a non-invasive procedure for identifying CMI in symptomatic SSc patients.

What Is New and What Is Next for SAPHO Syndrome Management: A Narrative Review.

Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a rare disease characterized by a sterile inflammatory osteitis and/or arthritis associated with a wide range of dermatological manifestations, such as acne, palmoplantar pustulosis, and psoriasis. This review, providing up-to-date knowledge on this disease, aims at informing researchers and clinicians to help them program future studies in order to improve patients' care. Due to the vast clinical heterogeneity that characterizes this disease, SAPHO syndrome has received various names; among these, chronic recurrent multifocal osteomyelitis represents the most used one.

Pulmonary Arterial Hypertension Incidence in Patients With Systemic Sclerosis Treated With Bosentan for Digital Ulcers: Evidence From the SPRING-SIR Registry.

Objective: Bosentan (BOS) is approved for treating pulmonary arterial hypertension (PAH) and preventing digital ulcers (DU) in systemic sclerosis (SSc). Our study aimed to evaluate whether BOS prescribed for DU could reduce the incidence of PAH in a large SSc cohort from the Systemic Sclerosis Progression Investigation (SPRING) registry.

Methods: Patients with SSc from the SPRING registry, meeting 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria with data on PAH onset, DU status, BOS exposure, and at least 1 year of follow-up between 2015 and 2020, and having no known PAH at baseline, were included.

Gut microbiota in very early systemic sclerosis: the first case-control taxonomic and functional characterisation highlighting an altered butyric acid profile.

Objectives: In systemic sclerosis (SSc), gastrointestinal involvement is one of the earliest events. We compared the gut microbiota (GM), its short-chain fatty acids (SCFAs) and host-derived free fatty acids (FFAs) in patients with very early diagnosis of SSc (VEDOSS) and definite SSc.

Methods: Stool samples of 26 patients with SSc, 18 patients with VEDOSS and 20 healthy controls (HC) were collected.

Improving organisation to improve care: ERN ReCONNET organisational reference model for systemic sclerosis patients' care pathway.

Objective: To optimise the organisation of care and encourage the adoption of good clinical practices, the RarERN Path methodology was designed within ERN ReCONNET. The aim of our work was to report the application of RarERN Path on systemic sclerosis within the ERN ReCONNET centres, providing a feasible and flexible organisational reference model for optimising the systemic sclerosis care pathway in different countries.

Methods: RarERN Path is a six-phase methodology which enables the creation of a reference organisational model co-designed on the basis of the expertise of different stakeholders.

The B-cells paradigm in systemic sclerosis: an update on pathophysiology and B-cell-targeted therapies.

Systemic sclerosis (SSc) is considered a rare autoimmune disease in which there are alterations of both the innate and adaptive immune response resulting in the production of autoantibodies. Abnormalities of the immune system compromise the normal function of blood vessels leading to a vasculopathy manifested by Raynaud's phenomenon, an early sign of SSc . As a consequence of this reactive picture, the disease can evolve leading to tissue fibrosis.

The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases.

The gut microbiota is a complex ecosystem of microorganisms residing in the human gastrointestinal tract, playing a crucial role in various biological processes and overall health maintenance. Dysbiosis, an imbalance in the composition and function of the gut microbiota, is linked to systemic autoimmune diseases (SAD). Short-chain fatty acids (SCFAs), especially butyrate, produced by the gut microbiota through the fermentation of dietary fibers, play a significant role in immunomodulation and maintaining intestinal homeostasis.

Systemic sclerosis and environment: an intriguing and still debated association.

Systemic sclerosis (SSc) is characterised by a heterogeneous clinical expression probably reflecting the different genetic background of each patient. Progress has been made in the definition of the principal pathogenetic events of the disease that can be summarised in endothelial damage and dysfunction, inflammation with activation of immune system and fibrosis. The aetiology of the disease still remains to be clarified and probably the first events are attributable to the repeated action of environmental stimuli in genetically predisposed subjects.

Towards a comprehensive approach to the management and prognosis of systemic sclerosis's patients: The role of comorbidities in the SPRING-SIR registry.

Objectives: The current knowledge about the role of comorbidities in systemic sclerosis (SSc) is limited. Therefore, the aim of this study was to evaluate the prevalence of comorbidities and their impact on disease activity and prognosis in the Systemic sclerosis PRogression INvestiGation (SPRING) registry.

Methods: SSc patients from the SPRING registry, fulfilling the ACR/EULAR 2013 classification criteria, with complete data on baseline comorbidities were enrolled.

Can Combination Therapy with Endothelin Receptor Antagonist and PDE5 Inhibitors Prevent Echocardiographic Findings Suspicious for Pulmonary Arterial Hypertension? Description of a Real-Life Case Series.

Objective: To retrospectively evaluate the incidence rate (IR) of elevated echocardiographic estimated systolic pulmonary artery pressure (sPAP), suspected for pulmonary hypertension (PH), in systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers.

Methods: Patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old with a history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months, were included.

The Burden of Interstitial Lung Involvement in Rheumatoid Arthritis: Could Lung Ultrasound Have a Role in Its Detection? A Literature Review.

Lung involvement represents a fearful complication in rheumatoid arthritis (RA), potentially involving all compartments of the pulmonary system. Regarding interstitial lung disease (ILD), the HRCT represents the gold standard technique for its diagnosis; however, the examination is burdened by radiation exposure and high costs. In addition, although some risk factors for ILD are known, no algorithms exist to know which patients to submit to HRCT and when.

Evidence for telemedicine heterogeneity in rheumatic and musculoskeletal diseases care: a scoping review.

Telemedicine and digital health represent alternative approaches for clinical practice; indeed, its potential in healthcare services for prevention, diagnosis, treatment, rehabilitation, and disease monitoring is widely acknowledged. These are all crucial issues to consider when dealing with chronic Rheumatic and Musculoskeletal Diseases (RMDs). The aim was to determine the current state of telemedicine in the field of rheumatology, considering the tools and devices in use as well as the Patient Reported Outcomes.