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.

Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (hf-SCIg) for inflammatory myositis: a multicenter retrospective real-world observational study.

Background: Subcutaneous immunoglobulin (SCIg) is a promising alternative to intravenous Ig (IVIg) for the treatment of idiopathic inflammatory myositis (IIM), thanks to its more favorable safety profile, reduced costs, and lower impact on patients' quality of life. We assessed the short- and long-term effectiveness and safety of recombinant human hyaluronidase-facilitated SCIg (hf-SCIg) in patients with IIM treated at different referral centers in Italy.

Methods: A multicenter, retrospective, real-life cohort study was conducted on consecutive adult patients diagnosed with IIM according to the EULAR/ACR criteria, treated with hf-SCIg for remission induction or maintenance.

Treatment recommendations for the systemic pharmacological treatment of systemic sclerosis digital ulcers: Results from the World Scleroderma Foundation Ad Hoc Committee.

Introduction: Digital ulcers are an important disease manifestation of systemic sclerosis and are associated with significant morbidity. As such, there is an urgent need for the development of evidence-based recommendations to guide clinicians in the treatment of digital ulcers.

Methods: A steering committee of international experts was established.

Effectiveness of intravenous infliximab versus subcutaneous adalimumab in Takayasu arteritis: multicenter retrospective study.

Objectives: In this large multicentre study, we aimed to compare the effectiveness of intravenous infliximab vs subcutaneous adalimumab in patients with Takayasu arteritis.

Methods: We conducted a retrospective multicentre study across referral centers in France, Italy, Spain, Armenia, Israel, Japan, Tunisia, and Russia, analyzing biological-targeted therapies in TAK from January 2017 to September 2019.

Results: A total of 135 TAK patients who received adalimumab (n = 34) or infliximab (n = 101) for at least 3 months were included.

American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel.

Objective: Vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality.

Methods: Given the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS.

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.

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.

Cluster analysis reveals the clinical spectrum of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a clonal-inflammatory neoplasm driven by mutations in MAPK pathway proto-oncogenes, such as BRAF. Clinical manifestations are protean, affecting virtually every system. This cohort study analyzed 661 patients with ECD to classify them based on clinical features and mutational profiles using unsupervised clustering.

Association of circulating levels of anti-CarP antibodies with disease activity, disability and radiological damage in rheumatoid arthritis patients: an open-label, observational study.

Autoantibodies directed against carbamylated proteins (anti-CarP) have been recently identified as predictors for RA development. The aim of this study was to determine the positivity of anti-CarP antibodies in a real-life cohort of RA patients and their association with radiological damage, disability and disease activity. In this open-label, observational, cross-sectional study 69 RA patients and 16 healthy controls (HC) were recruited.

Clonal hematopoiesis meets an autoinflammatory disease: the new paradigm of VEXAS syndrome.

Introduction: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an acquired autoinflammatory disorder caused by somatic mutations in the UBA1 gene. Predominantly affecting males over 50, the disease presents with systemic inflammation, hematologic abnormalities, and features of clonal hematopoiesis, with nearly half of patients developing myelodysplastic syndromes (MDS). The interaction between inflammation and clonal expansion defines disease progression, emphasizing the need for a comprehensive understanding of its pathogenesis and management.

Recommendations for the local management of digital ulcers in systemic sclerosis: A report from the World Scleroderma Foundation (WSF) 'Ad hoc committee'.

Introduction: Digital ulcers (DUs) stand out as one of the most prevalent and clinically meaningful manifestations of systemic sclerosis (SSc) and are associated with significant morbidity. While systemic (pharmacological) therapy is currently established as the 'standard of care', effective local ulcer management remains crucial for all cases of DUs. This is particularly true for patients who cannot tolerate systemic treatments or in the case of refractory SSc-DUs.

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.

Secukinumab is effective and safe for patients with giant cell arteritis after tocilizumab failure.

Objectives: To evaluate the effectiveness and safety of secukinumab in patients with GCA who experienced an inadequate response to tocilizumab.

Methods: This is a case series of six patients with GCA started on secukinumab after tocilizumab failure from three centres in Italy. Tocilizumab failure was defined as disease relapse, indicated by clinical symptoms and/or vascular inflammation on imaging.

The complex diagnosis of primary heart involvement in systemic sclerosis: red flags to drive the choice of cardiac magnetic resonance.

Objectives: To analyse clinical features and biomarkers associated with primary heart involvement (pHI) confirmed at cardiac magnetic resonance (CMR) in a monocentric cohort of SSc patients.

Methods: A retrospective study. SSc patients who underwent CMR for clinically suspected pHI were identified.

Intercalated Disc Abnormalities Are Linked to Arrhythmias in Inflammatory Cardiomyopathy.

Background: The relationship between intercalated disc abnormalities (IDAs) and arrhythmias in inflammatory cardiomyopathy (ICM) remains incompletely understood.

Objectives: This study presents a pilot research that aimed to: 1) investigate the link between IDAs and arrhythmias in humans with ICM; and 2) compare findings in humans and mice with experimental autoimmune myocarditis (EAM).

Methods: Humans with ICM (N = 316) investigated for either genetic or autoimmune IDAs were identified at a referral center.

Mechanisms of hematopoietic clonal dominance in VEXAS syndrome.

Clonal dominance characterizes hematopoiesis during aging and increases susceptibility to blood cancers and common nonmalignant disorders. VEXAS syndrome is a recently discovered, adult-onset, autoinflammatory disease burdened by a high mortality rate and caused by dominant hematopoietic clones bearing somatic mutations in the UBA1 gene. However, pathogenic mechanisms driving clonal dominance are unknown.

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.

Immune checkpoint inhibitors-induced large vessel vasculitis: clinical characteristics and management from a European multicentre study.

Objective: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but frequently cause immune-related adverse events (IrAEs). ICI-induced large vessel vasculitis (LVV) is a rare IrAE, with limited available data. We aimed to describe and compare clinical characteristics and evolution of ICI-induced LVV to primary LVV.

Interstitial lung disease in anti-U1RNP systemic sclerosis patients: A European Scleroderma Trials and Research analysis.

Background: Interstitial lung disease is the leading cause of morbidity and mortality in systemic sclerosis, but it is characterized by significant heterogeneity in patient outcomes. So far, little is known about the influence of anti-U1RNP antibodies on lung outcomes in systemic sclerosis-associated interstitial lung disease patients.

Methods: European Scleroderma Trials and Research group systemic sclerosis patients with radiological-confirmed interstitial lung disease, available %predicted forced vital capacity, and autoantibody status were included.

Efficacy and safety of conventional disease-modifying antirheumatic drugs in VEXAS syndrome: real-world data from the international AIDA network.

Background: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory condition resulting in severe, often treatment-refractory inflammation. Currently, there are no established treatment guidelines for VEXAS syndrome.

Objectives: To assess the efficacy and safety of conventional disease-modifying antirheumatic drugs (cDMARDs) in a cohort of VEXAS patients.

Efficacy and safety profile of biotechnological agents and Janus kinase inhibitors in VEXAS syndrome: data from the international AIDA Network VEXAS registry.

Background: VEXAS syndrome, a recently identified systemic autoinflammatory disorder, poses new diagnostic and management challenges. Based on experience with other autoinflammatory diseases, anti-interleukin (IL)-1, anti-IL-6, anti-tumor necrosis factor (TNF) biotechnological agents, and Janus kinase inhibitors (JAKis) have been widely employed in VEXAS patients. The aim of this study is to evaluate the global effectiveness and safety of biotechnological agents and JAKis using data from the real-world context.

Cardiac Sarcoidosis: Clinical Insights, Diagnosis, and Management Strategies.

Cardiac sarcoidosis (CS) is a multifaceted inflammatory disease that affects the heart, leading to complications such as arrhythmias, heart failure, and sudden cardiac death. Endomyocardial biopsy is the diagnostic gold standard, but its low sensitivity and risks limit its utility. Imaging modalities, such as cardiac magnetic resonance and positron emission tomography, are critical for diagnosing and managing CS.

A coding single nucleotide polymorphism in the interleukin-6 receptor enhances IL-6 signalling in CD4 T cells and predicts treatment response to tocilizumab in giant cell arteritis.

Objectives: The study objective was to determine if a common single nucleotide polymorphism in the interleukin 6 (IL-6) receptor (rs2228145, p.Asp358Ala) predicted treatment response to tocilizumab in giant cell arteritis (GCA).

Methods: Genetic sequencing of the rs2228145 locus was performed in 2 independent cohorts of patients with GCA.

Immunosuppressive therapy to treat newly diagnosed primary heart involvement in patients with systemic sclerosis: An Italian cardiac magnetic resonance based study.

Background: Primary heart involvement (pHI) is frequent in systemic sclerosis (SSc), and is associated with a poor prognosis. Therapeutic strategies to treat SSc-pHI are not yet defined.

Objectives: To evaluate the efficacy of immunosuppressive therapy on cardiac magnetic resonance (CMR) features in patients with CMR-proven SSc-pHI.