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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. PAH was diagnosed with right heart catheterization during the follow-up, and its incidence rate (IR) was calculated. Kaplan-Meier curves were determined, and multivariate regression identified PAH risk factors., Results: Among 727 eligible patients with SSc, followed for a median of 2.0 years, 54 (7.4%) developed PAH (IR 3.71 per 100 patient-years [PYs]). Patients with DU who were never exposed to BOS had a higher incidence of PAH (IR 4.90 per 100 PYs) compared to those exposed to BOS, whose rates matched those without DU and who were never exposed to BOS. Risk factors independently associated with PAH development included DU (hazard ratio [HR] 1.86), age (HR 1.05), modified Rodnan skin score > 4 (HR 2.07), interstitial lung disease (HR 2.29), and acetylsalicylic acid treatment (HR 1.78)., Conclusion: In our cohort, the presence of DU was confirmed as a leading risk factor for PAH development, and BOS use for DU prevention may reduce this risk. Only patients with DU who were not using BOS had an increased PAH incidence.

Objective: Some concerns remain about the safety of nintedanib in patients with rheumatoid arthritis-related interstitial lung disease (RA-ILD), such as in the presence of comorbidities or in combination with biologic, targeted synthetic, and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). In this multicenter study, we retrospectively evaluated the safety of nintedanib in a real-world population of patients with RA-ILD from the Italian Group for the Study of Early Arthritis (GISEA) registry and the possible role of comorbidities and DMARDs on drug safety and withdrawal. Our secondary aim was to investigate the causes of nintedanib discontinuation., Methods: Sixty-five patients treated with nintedanib in accordance with the current therapeutic indications were enrolled in the study. Nintedanib was prescribed in combination with DMARDs and/or steroids in 62 patients (95.4%)., Results: The 12-month retention rate of nintedanib was 76.7% and the drug was effective in about 80% of patients with ≥ 6 months of follow-up. Adverse events (AEs) were recorded in 36 subjects (55.3%), and these were mainly gastroenteric. Thirty-one subjects required a reduction of the nintedanib dose; among them, a transient or permanent reduction of the daily dose of nintedanib allowed the continuation of the treatment in 22, whereas 15 (23.1%) withdrew from the drug. All reductions and discontinuations were owing to treatment-related AEs. Comorbidities were significantly associated with side effects in multivariate analysis, whereas AEs due to nintedanib were the main cause of discontinuation., Conclusion: Combination therapy with DMARDs did not reduce the safety and effectiveness of nintedanib, and AEs were the main cause of drug withdrawal or dose reduction, mainly owing to comorbidities.

The application of chatbots and NLP in radiology is an emerging field, currently characterized by a growing body of research. An umbrella review has been proposed utilizing a standardized checklist and quality control procedure for including scientific papers. This review explores the early developments and potential future impact of these technologies in radiology. The current literature, comprising 15 systematic reviews, highlights potentialities, opportunities, areas needing improvements, and recommendations. This umbrella review offers a comprehensive overview of the current landscape of natural language processing (NLP) and natural language models (NLMs), including chatbots, in healthcare. These technologies show potential for improving clinical decision-making, patient engagement, and communication across various medical fields. However, significant challenges remain, particularly the lack of standardized protocols, which raises concerns about the reliability and consistency of these tools in different clinical contexts. Without uniform guidelines, variability in outcomes may hinder the broader adoption of NLP/NLM technologies by healthcare providers. Moreover, the limited research on how these technologies intersect with medical devices (MDs) is a notable gap in the literature. Future research must address these challenges to fully realize the potential of NLP/NLM applications in healthcare. Key future research directions include the development of standardized protocols to ensure the consistent and safe deployment of NLP/NLM tools, particularly in high-stake areas like radiology. Investigating the integration of these technologies with MD workflows will be crucial to enhance clinical decision-making and patient care. Ethical concerns, such as data privacy, informed consent, and algorithmic bias, must also be explored to ensure responsible use in clinical settings. Longitudinal studies are needed to evaluate the long-term impact of these technologies on patient outcomes, while interdisciplinary collaboration between healthcare professionals, data scientists, and ethicists is essential for driving innovation in an ethically sound manner. Addressing these areas will advance the application of NLP/NLM technologies and improve patient care in this emerging field.

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. The GM was assessed through 16S rRNA sequencing, while SCFAs and FFAs were assessed by gas chromatography-mass spectrometry., Results: In patients with VEDOSS, an increase in Bacteroidales and Oscillospirales orders and a decrease in Bacilli class, Blautia, Romboutsia, Streptococcus and Turicibacter genera was detected in comparison with HC. In patients with SSc, an elevated number of Acidaminococcaceae and Sutterellaceae families, along with a decrease of the Peptostreptococcaceae family and Anaerostipes, Blautia, Romboutsia and Turicibacter genera was found in comparison with HC. Patients with SSc and VEDOSS had a significantly lower butyrate and higher acetate with respect to HC. In VEDOSS, an increase in Oscillospiraceae family and Anaerostipes genus, and a decrease in Alphaproteobacteria class, and Lactobacillales order was identified with respect to SSc. Moreover, patients with VEDOSS exhibited higher acetate and lower valerate compared with definite SSc., Conclusion: A GM dysbiosis with depletion of beneficial anti-inflammatory bacteria (especially butyrate-producing) and a significant decrease in faecal butyrate was identified in patients with VEDOSS. This early GM imbalance may foster the growth of inflammatory microbes, worsening intestinal dysbiosis and inflammation in early SSc stages. The potential butyrate administration in early disease phases might be considered as a novel therapeutic approach to mitigate gastrointestinal discomfort and progression preserving patient's quality of life., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Osteoarthritis (OA) is a chronic, progressive, degenerative joint disease characterized by joint pain, stiffness, and limited movement. It presents significant intra- and inter-individual variability-in particular, between genders. Recent research has increasingly focused on the role of adipokines-especially leptin, adiponectin, and resistin-in the development of OA. Adipokines, peptide hormones primarily secreted by adipose tissue, are involved in crucial physiological processes related to metabolism and immunity. They can also impact bone and cartilage turnover by interacting with joint cells such as osteoblasts, osteoclasts, chondrocytes, and mesenchymal stem cells, thereby linking inflammation with bone cartilage homeostasis. This review aims to elucidate the structure and functions of various adipokines, their serum and synovial levels, and their association with clinical presentation and radiographic progression in OA patients, with a focus on differences between sexes. A narrative literature review was conducted using three databases specifically analyzing sex differences. OA patients generally show elevated serum and synovial levels of leptin, chemerin, and visfatin, as well as high plasma levels of resistin and visfatin. In contrast, synovial levels of adiponectin and omentin are reduced in OA patients compared to healthy individuals, with an inverse relationship to disease severity, suggesting a potential protective role. Resistin and leptin were positively correlated with pain severity and radiographic progression, while adiponectin's role in OA remains controversial. Regarding sex differences, male OA patients exhibited higher serum levels of leptin, chemerin, and omentin compared to healthy controls, with a positive correlation to the BMI and estrogen levels, potentially explaining the sexual dimorphism observed in this condition. Studies on visfatin and lipocalin did not reveal significant differences in synovial or serum levels between the sexes. The role of resistin remains controversial. Adipokines influence the joint microenvironment and contribute to the progression of osteoarthritis (OA). However, the precise biological mechanisms are not yet fully understood due to the complex interactions between the metabolic, mechanical, and immune systems. Further research is needed to clarify their roles in OA and to identify targeted therapies for managing this degenerative disease.

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., Methods: SSc patients who started MMF treatment underwent a retrospective longitudinal assessment for up to 5 years. We documented the incidence, predictors, and impacts of MMF treatment on gastrointestinal intolerance, infections, laboratory abnormalities, and cancer. Rescue strategies implemented after MMF discontinuation were recorded., Results: The 5-year MMF retention rate of 554 patients stood at 70.7% and 19.6% of them stopped MMF due to AEs. One out of every four patients experienced a dose reduction or discontinuation of MMF due to AEs, with gastrointestinal intolerance being the predominant cause. The 5-year cumulative incidence rates for gastrointestinal intolerance, cancer, severe infections, and laboratory toxicity leading to MMF discontinuation were 6.4%, 4.1%, 3.1%, and 2.1%, respectively. Lower respiratory tract was the most affected, with bacteria being the predominant causative agent. Intestinal and pulmonary circulation involvement were tied to elevated AE rates and MMF discontinuation. The most common approaches post-MMF cessation were "watch and wait" and switch to rituximab., Conclusions: MMF use in SSc appears to be limited by the occurrence of AEs, both in terms of persistence and dosing of the drug. Rescue options after MMF discontinuation are limited and many patients remain without immunosuppressant., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

( Background ) Over the years, there has been increasing interest in adopting a quality approach in radiology, leading to the strategic pursuit of specific and key performance indicators (KPIs). These indicators in radiology can have significant impacts ranging from radiation protection to integration into digital healthcare. ( Purpose ) This study aimed to conduct a narrative review on the integration of key performance indicators (KPIs) in radiology with specific key questions. ( Methods ) This review utilized a standardized checklist for narrative reviews, including the ANDJ Narrative Checklist, to ensure thoroughness and consistency. Searches were performed on PubMed, Scopus, and Google Scholar using a combination of keywords related to radiology and KPIs, with Boolean logic to refine results. From an initial yield of 211 studies, 127 were excluded due to a lack of focus on KPIs. The remaining 84 studies were assessed for clarity, design, and methodology, with 26 ultimately selected for detailed review. The evaluation process involved multiple assessors to minimize bias and ensure a rigorous analysis. ( Results and Discussion ) This overview highlights the following: KPIs are crucial for advancing radiology by supporting the evolution of imaging technologies (e.g., CT, MRI) and integrating emerging technologies like AI and AR/VR. They ensure high standards in diagnostic accuracy, image quality, and operational efficiency, enhancing diagnostic capabilities and streamlining workflows. KPIs are vital for radiological safety, measuring adherence to protocols that minimize radiation exposure and protect patients. The effective integration of KPIs into healthcare systems requires systematic development, validation, and standardization, supported by national and international initiatives. Addressing challenges like CAD-CAM technology and home-based radiology is essential. Developing specialized KPIs for new technologies will be key to continuous improvement in patient care and radiological practices. ( Conclusions ) In conclusion, KPIs are essential for advancing radiology, while future research should focus on improving data access and developing specialized KPIs to address emerging challenges. Future research should focus on expanding documentation sources, improving web search methods, and establishing direct connections with scientific associations.

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. Butyrate is essential for colonocyte energy, anti-inflammatory responses, and maintaining intestinal barrier integrity. Studies show reduced butyrate-producing bacteria in SAD patients, suggesting that increasing butyrate levels could have therapeutic benefits. Butyrate's anti-inflammatory effects and its potential therapeutic role have been studied in rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, systemic sclerosis, and Behçet's disease. Despite promising in vitro and animal model results, human studies are limited, and the optimal strategies for modulating dysbiosis in SADs remain elusive. This review explores the current evidence on the immunoregulatory role of butyrate and its potential therapeutic effects in SAD.

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.The aim of the present manuscript is to review the most recent and relevant data regarding the association of SSc with environmental factors.

Systemic sclerosis (SSc) is a rare and chronic connective tissue disease of unknown aetiology and characterised by three main pathogenetic events represented by endothelial damage, inflammation with activation of the immune system leading to production of specific autoantibodies and finally fibrosis. SSc is a heterogeneous disease and the classification in two subsets, the limited cutaneous (lcSSc) subset and the diffuse cutaneous one (dcSSc), is not capable of capturing the broad and different phenotypic expression of the disease. In the last years progress has been made in the knowledge of SSc pathogenesis, in its early diagnosis and new therapeutic strategies have been proposed, however, the management of SSc still represents a challenge for the clinician. For this reason, every year several studies investigate new insights of disease pathogenesis, internal organ involvement and therapeutic approaches. The purpose of this review is to provide an overview of the literature published in 2023.

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. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic, and instrumental data (pulmonary function tests, echocardiographic estimation of sPAP, and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected of pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years., Results: Thirty-five patients were enrolled; the mean disease duration was 12.82 years (SD 5.92). The mean duration of the combination treatment was 81.03 (SD 43.1.3) months, and the total at-risk time was 2674 months. Two patients (5.7%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 9/1000 patients-years (95% CI 7.95-10.12). In one of the two patients, right heart catheterism (RHC) excluded PAH, while the other patient refused to undergo RHC, and PAH could not be confirmed/excluded. The stability of PFTs and echocardiographic sPAP was observed during the observation time., Conclusions: The results of this retrospective study suggest that combination therapy with endothelin receptor antagonists and phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on a larger population are needed to improve knowledge in this field., Competing Interests: The authors declare no conflicts of interest.

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. In this context, lung ultrasound (LUS) showed promising results for at least 10 years, demonstrating correlation with high resolution computed tomography (HRCT) findings in other rheumatic diseases. Here, LUS may represent a screening test providing additional information to clinical examination and pulmonary function tests. The data deriving from LUS experience in other rheumatic diseases could steer the future towards the use of this technique also in RA patients, and in this review, we report the most relevant literature regarding LUS in RA-ILD.

In recent years, the landscape of diagnostic imaging has undergone a significant transformation with the emergence of home radiology, challenging the traditional paradigm. This shift, bringing diagnostic imaging directly to patients, has gained momentum and has been further accelerated by the global COVID-19 pandemic, highlighting the increasing importance and convenience of decentralized healthcare services. This study aims to offer a nuanced understanding of the attitudes and experiences influencing the integration of in-home radiography into contemporary healthcare practices. The research methodology involves a survey administered through Computer-Aided Web Interviewing (CAWI) tools, enabling real-time engagement with a diverse cohort of medical radiology technicians in the health domain. A second CAWI tool is submitted to experts to assess their feedback on the methodology. The survey explores key themes, including perceived advantages and challenges associated with domiciliary imaging, its impact on patient care, and the technological intricacies specific to conducting radiologic procedures outside the conventional clinical environment. Findings from a sample of 26 medical radiology technicians (drawn from a larger pool of 186 respondents) highlight a spectrum of opinions and constructive feedback. Enthusiasm is evident for the potential of domiciliary imaging to enhance patient convenience and provide a more patient-centric approach to healthcare. Simultaneously, this study suggests areas of intervention to improve the diffusion of home-based radiology. The methodology based on CAWI tools proves instrumental in the efficiency and depth of data collection, as evaluated by 16 experts from diverse professional backgrounds. The dynamic and responsive nature of this approach allows for a more allocated exploration of technicians' opinions, contributing to a comprehensive understanding of the evolving landscape of medical imaging services. Emphasis is placed on the need for national and international initiatives in the field, supported by scientific societies, to further explore the evolving landscape of teleradiology and the integration of artificial intelligence in radiology. This study encourages expansion involving other key figures in this practice, including, naturally, medical radiologists, general practitioners, medical physicists, and other stakeholders.

Background: The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR)., Methods: PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported., Results: We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns., Conclusions: The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices., (© 2024. The Author(s).)

(Background) Domiciliary radiology, which originated in pioneering studies in 1958, has transformed healthcare, particularly during the COVID-19 pandemic, through advancements such as miniaturization and digitization. This evolution, driven by the synergy of advanced technologies and robust data networks, reshapes the intersection of domiciliary radiology and mobile technology in healthcare delivery. (Objective) The objective of this study is to overview the reviews in this field with reference to the last five years to face the state of development and integration of this practice in the health domain. (Methods) A review was conducted on PubMed and Scopus, applying a standard checklist and a qualification process. The outcome detected 21 studies. (Key Content and Findings) The exploration of mobile and domiciliary radiology unveils a compelling and optimistic perspective. Notable strides in this dynamic field include the integration of Artificial Intelligence (AI), revolutionary applications in telemedicine, and the educational potential of mobile devices. Post-COVID-19, telemedicine advances and the influential role of AI in pediatric radiology signify significant progress. Mobile mammography units emerge as a solution for underserved women, highlighting the crucial importance of early breast cancer detection. The investigation into domiciliary radiology, especially with mobile X-ray equipment, points toward a promising frontier, prompting in-depth research for comprehensive insights into its potential benefits for diverse populations. The study also identifies limitations and suggests future exploration in various domains of mobile and domiciliary radiology. A key recommendation stresses the strategic prioritization of multi-domain technology assessment initiatives, with scientific societies' endorsement, emphasizing regulatory considerations for responsible and ethical technology integration in healthcare practices. The broader landscape of technology assessment should aim to be innovative, ethical, and aligned with societal needs and regulatory standards. (Conclusions) The dynamic state of the field is evident, with active exploration of new frontiers. This overview also provides a roadmap, urging scholars, industry players, and regulators to collectively contribute to the further integration of this technology in the health domain.

Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data., Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group)., Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, " late " scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis., Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Objectives: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD., Methods: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t 0 ) and after 12 (±4) (t 1 ) and 24 (±4) (t 2 ) months., Results: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t 2 . Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t 2 ( p = 0.0031). Neither the mean t 0 to t 1 change (Δ) of DLCO nor the mean t 0 to t 1 FVCΔ predicted the appearance of ILD at t 2 . Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t 0 DLCO < 80%, stronger than that of FVC < 80%., Conclusions: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Objectives: We characterized the microbiota in SSc, focusing on the skin-oral-gut axis and the serum and faecal free fatty acid (FFA) profile., Methods: Twenty-five SSc patients with ACA or anti-Scl70 autoantibodies were enrolled. The microbiota of faecal, saliva and superficial epidermal samples was assessed through next-generation sequencing analysis. GC-MS was used to quantify faecal and serum FFAs. Gastrointestinal symptoms were investigated with the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (UCLA GIT-2.0) questionnaire., Results: The ACA+ and anti-Scl70+ groups displayed different cutaneous and faecal microbiota profiles. The classes of cutaneous Sphingobacteriia and Alphaproteobacteria, the faecal phylum Lentisphaerae, the levels of the classes Lentisphaeria and Opitutae, and the genus NA-Acidaminococcaceae were significantly higher in faecal samples from the ACA+ patients than in samples from the anti-Scl70+ patients. The cutaneous Sphingobacteria and the faecal Lentisphaerae were significantly correlated (rho = 0.42; P = 0.03). A significant increase in faecal propionic acid was observed in ACA+ patients. Moreover, all levels of faecal medium-chain FFAs and hexanoic acids were significantly higher in the ACA+ group than in the anti-Scl70+ group (P < 0.05 and P < 0.001, respectively). In the ACA+ group, the analysis of the serum FFA levels showed an increasing trend in valeric acid., Conclusion: Different microbiota signatures and FFA profiles were found for the two groups of patients. Despite being in different body districts, the cutaneous Sphingobacteria and faecal Lentisphaerae appear interdependent., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Several studies described the cross-sectional characteristics of systemic sclerosis patients and coexisting primary biliary cholangitis, but longitudinal prognostic data are lacking., Aims: To describe the systemic sclerosis-primary biliary cholangitis phenotype, including baseline characteristics and outcomes., Methods: We performed a multicentre the European Scleroderma Trials and Research Group study of systemic sclerosis patients with primary biliary cholangitis or with primary biliary cholangitis-specific antibodies, matched with systemic sclerosis controls free from hepatobiliary involvement matched for disease duration and cutaneous subset. Data were recorded at baseline and at the last available visit., Results: A total of 261 patients were enrolled (115 primary biliary cholangitis-systemic sclerosis, 161 systemic sclerosis). At baseline, systemic sclerosis-primary biliary cholangitis patients had a higher prevalence of anti-centromere antibodies ( p  = 0.0023) and a lower prevalence of complete absence of digital ulcers. The milder vascular involvement was confirmed at follow-up when crucial differences emerged in the percentage of patients experiencing digital ulcers; a significantly higher number of patients who never experienced digital ulcers were observed among primary biliary cholangitis-systemic sclerosis patients ( p  = 0.0015). Moreover, a greater incidence of pulmonary arterial hypertension ( p  < 0.001) and of conduction blocks ( p  = 0.0256) was observed in systemic sclerosis patients without primary biliary cholangitis. Patients with primary biliary cholangitis had higher levels of liver enzymes at baseline than systemic sclerosis patients; a significant decrease in liver enzymes was observed at follow-up. Out of 18 patients with cholangitis, one received a liver transplant at follow-up., Conclusion: Our data show that systemic sclerosis-primary biliary cholangitis exhibit a mild systemic sclerosis and primary biliary cholangitis phenotype with outcomes being in general favourable., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: G.L., P.A., O.D., K.A., Y.B.-M., E.H., A.B.-G., E.D.L., S.R., F.I., E.R., L.G., R.I., S.B.-R., L.G., L.B., C.B., S.M., P.N., I.S., D.K., V.C., U.A.W., C.M., S.G., M.-E.T., L.T., G.C., M.K., M.M.-C. and Y.A. have no conflict of interests (COIs) to declare. F.I. received honoraria or speaking fees from AbbVie, BMS, Galapagos, MSD, Lilly and Pfizer outside this work. C.B. received consulting fees and/or honoraria from Actelion and Boehringer Ingelheim; research grants from the Gruppo Italiano Lotta alla Sclerodermia (GILS), the European Scleroderma Trials and Research Group (EUSTAR) and the Scleroderma Clinical Trials Consortium (SCTC); educational grants from AbbVie; all outside the submitted work. V.S. is the Senior Clinical Investigator of the Research Foundation – Flanders (Belgium) (FWO) [1.8.029.20N]. The FWO was not involved in study design, collection, analysis and interpretation of data and writing of the report, nor in the decision to submit the manuscript for publication., (© The Author(s) 2023.)

Systemic sclerosis is a rare and chronic connective tissue disease resulting from an intricate pathogenesis and is expressed in very heterogeneous clinical manifestations. Every year many studies try to unravel and shed new insight into the pathogenesis, organ involvement and treatment of this complex and severe disease. We herein provide an overview of the most relevant studies published in the literature in 2022.

Skin ultrasound has shown promising results in the evaluation of skin involvement in patients with systemic sclerosis, as substantiated by a recent systematic literature review from the World Scleroderma Foundation Skin Ultrasound Working Group. In this Viewpoint, we will discuss the role of ultrasound in evaluating skin involvement in patients with systemic sclerosis, particularly the possibility of using this technique to detect an early subclinical skin involvement from the very early phase, suggesting its possible use in both diagnosis and disease follow-up. To detect subclinical skin involvement, it is essential to understand the difference between the skin of patients with systemic sclerosis and that of healthy controls, including defining exactly which structures are affected by the disease and which are spared. The potential of this non-invasive technique might suggest its future role in both clinical practice and clinical trials, possibly replacing invasive and painful procedures such as skin biopsies and promoting patient retention in clinical trials., Competing Interests: Declaration of interests MH reports speaking fees from Actelion pharmaceuticals, Eli Lilly, Janssen, and Pfizer, outside of the submitted work; reports research funding from Janssen; and is a member of a data and safety monitoring board for Certa Therapeutics. YA reports grants from Alpine ImmunoSciences; consulting fees from Horizon, AstraZeneca, Boehringer Ingelheim, Janssen, Prometheus, Medsenic, Galderma, and AbbVie. CPD reports consulting fees from Arxx Therapeutics, Roche, Janssen, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Boehringer Ingelheim, CSL Behring, AstraZeneca, and Acceleron. FDG reports consulting fees and research support from AbbVie, AstraZeneca, Boehringer Ingelheim, Chemomab, Janssen, and MitsubishiTanabe. DK reports grants from Bristol Myers Squibb, Horizon Therapeutics, and Pfizer; consulting fees from AstraZeneca, Boehinger Ingelheim, Bristol Myers Squibb, Chemomab, CSL Behring, Horizon Therapeutics, Janssen, Prometheus, Sanofi, Talaris, and Bauch Health. MMC reports participation on a data safety monitoring board or advisory board for Biogen, Gesynta, Chemomab, and Galapagos. All other authors report no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort., Methods: Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets., Results: Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001)., Conclusion: The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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. CT images were analysed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio lung texture analysis. Vascular analysis (volumes, numbers and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted., Results: A total of 79 patients [52 women, 40 ILD, mean age 56.2 (s.d. 14.2) years, total ILD extent 9.5 (10.7)%, PVV/lung volume % 2.8%] were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-associated ILD (SSc-ILD) patients presented with an increased number and volume of arterial vessels, in particular those between 2 and 4 mm of diameter, and with a higher density of arteries and veins of <6 mm in diameter. Considering radiological and functional criteria concomitantly, as well as the descriptive trends from the longitudinal evaluations, the normalized PVVs, vessel numbers and densities increased progressively with the increase/worsening of ILD extent and functional impairment., Conclusion: In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment, and may represent a biomarker of SSc-ILD severity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

(1) Background: Gut microbiota (GM) is the set of microorganisms inhabiting the gastroenteric tract that seems to have a role in the pathogenesis of rheumatic diseases. Recently, many authors proved that GM may influence pharmacodynamics and pharmacokinetics of several drugs with complex interactions that are studied by the growing field of pharmacomicrobiomics. The aim of this review is to highlight current evidence on pharmacomicrobiomics applied to the main treatments of Rheumatoid Arthritis and Spondyloarthritis in order to maximize therapeutic success, in the framework of Personalized Medicine. (2) Methods: We performed a narrative review concerning pharmacomicrobiomics in inflammatory arthritides. We evaluated the influence of gut microbiota on treatment response of conventional Disease Modifying Anti-Rheumatic drugs (cDMARDs) (Methotrexate and Leflunomide) and biological Disease Modifying Anti-Rheumatic drugs (bDMARDs) (Tumor necrosis factor inhibitors, Interleukin-17 inhibitors, Interleukin 12/23 inhibitors, Abatacept, Janus Kinase inhibitors and Rituximab). (3) Results: We found a great amount of studies concerning Methotrexate and Tumor Necrosis Inhibitors (TNFi). Conversely, fewer data were available about Interleukin-17 inhibitors (IL-17i) and Interleukin 12/23 inhibitors (IL-12/23i), while none was identified for Janus Kinase Inhibitors (JAKi), Tocilizumab, Abatacept and Rituximab. We observed that microbiota and drugs are influenced in a mutual and reciprocal way. Indeed, microbiota seems to influence therapeutic response and efficacy, whereas in the other hand, drugs may restore healthy microbiota. (4) Conclusions: Future improvement in pharmacomicrobiomics could help to detect an effective biomarker able to guide treatment choice and optimize management of inflammatory arthritides.

Background: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is one of the most relevant complications of SSc and the major cause of death. The pathogenesis of SSc-ILD involves a complex interplay of multiple cell types and different molecular pathways, with both inflammation and fibrosis as pathological hallmarks. To date, there are no treatments able to target both components of the disease. Janus kinase inhibitors (JAKinibs) represent an interesting therapeutic option because they exert both anti-inflammatory and anti-fibrotic properties., Methods: Here, we performed a narrative review concerning the potential role of JAKinibs in SSc-ILD to define the state of art and to evaluate the pathogenetic rationale behind this type of treatment., Results: Currently, few studies investigated SSc-ILD response to JAKinibs treatment. Data were analyzed from three clinical studies and four case reports and progression of SSc-ILD was not evident in 93.5% of patients treated with JAKinibs., Conclusions: Available evidence of efficacy of JAKinibs in SSc-ILD is sparse but promising. JAKinibs could be an interesting treatment in SSc-ILD because of their potential inhibition of the fibrotic processes combined with their anti-inflammatory action. Moreover, JAKinibs were also shown in some studies to have a potential effect on pulmonary arterial hypertension (PAH), another threatening complication in SSc. More data are necessary to define JAKinibs role in SSc-ILD treatment.

The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lung fibrosis and a long standing SSc pulmonary involvement have been largely proposed as lung cancer risk factors, and the exposure to cyclophosphamide and an upper gastrointestinal involvement have been traditionally linked to bladder and oesophagus cancers, respectively. Furthermore, immune checkpoint inhibitors used for cancer therapy can induce immune-related adverse events, which are more frequent and severe in patients with pre-existing autoimmune diseases such as SSc. The strong association between SSc and cancer occurrence steers clinicians to carefully survey SSc patients performing periodical malignancy screening. In the present review, the most relevant bilateral relationships between SSc and cancer will be addressed., (© 2022. The Author(s).)

Systemic sclerosis (SSc) is an autoimmune disease characterised by microvasculopathy, immune dysregulation, and skin and visceral organ fibrosis. Every year novel insights into the pathogenesis, organ involvement and treatment of this severe disease are published in the scientific community.In this review we report an overview of some of the most relevant contributions published in 2021.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease that can affect different organs and has extremely heterogenous presentations. This complexity makes it difficult to perform an early diagnosis and a subsequent subclassification of the disease. This hinders a personalized approach in clinical practice. In this context, machine learning (ML), a branch of artificial intelligence (AI), is able to recognize relationships in data and predict outcomes., Methods: Here, we performed a narrative review concerning the application of ML in SSc to define the state of art and evaluate its role in a precision medicine context., Results: Currently, ML has been used to stratify SSc patients and identify those at high risk of severe complications. Additionally, ML may be useful in the early detection of organ involvement. Furthermore, ML might have a role in target therapy approach and in predicting drug response., Conclusion: Available evidence about the utility of ML in SSc is sparse but promising. Future improvements in this field could result in a big step toward precision medicine. Further research is needed to define ML application in clinical practice.

Background: Chest computed tomography (CT) is the gold standard for the evaluation of systemic sclerosis-related interstitial lung disease (SSc-ILD). Lung ultrasound (LUS) is a radiation-free tool that identifies the B-lines as a main feature of ILD. We aimed to investigate the role of LUS in the evaluation of the extent of SSc-ILD. Methods: Adult SSc patients underwent pulmonary function tests (PFTs), LUS and CT. The CT images were qualitatively, semi-quantitatively (the Wells score on five levels and the categorical Goh et al. staging) and quantitatively (histogram-based densitometry) analysed for ILD. LUS quantified B-lines in 21 intercostal spaces on both the anterior and posterior chest wall. Results: Out of the 77 SSc patients eligible for the study, 35 presented with ILD on CT (21 limited, 14 extensive). Total B-lines significantly differentiated ILD vs. no ILD (median 24 vs. 8, p < 0.001). Posterior and total B-lines significantly differentiated limited from absent ILD, while anterior B-lines distinguished extensive from limited ILD. Total B-lines correlated with the Wells score (r = 0.446, p < 0.001) and MLA (r = −0.571, p < 0.001); similar results were confirmed when anterior and posterior B-lines were analysed separately. Conclusions: LUS is a useful tool to identify SSc-ILD and to correlate with different evaluations of ILD extent and severity.

Objective: Ultrasound is a promising tool to foster much-needed improvement of skin assessment in systemic sclerosis (SSc). Our aim was to develop evidence and expert opinion-based recommendations to promote the standardisation and harmonisation of technical execution and reporting of skin ultrasound studies in SSc., Methods: A multidisciplinary task force of 16 members from five European countries and Japan was convened under the auspices of World Scleroderma Foundation. First, a systematic literature review (SLR) was performed. Then, each member proposed and formulated items to the overarching principles, recommendations and research agenda. Two rounds of mails exchange for consensus as well as an on-line meeting were performed to debate and refine the proposals. Two Delphi rounds of voting resulted in the final recommendations. Levels of evidence and strengths of recommendations were assigned, and task force members voted anonymously on the level of agreement with each of the items., Results: Five overarching principles and seven recommendations were developed, based on an SLR and expert opinion, through consensus procedures. The overarching principles highlight the promising role of skin ultrasound in SSc assessment, the need for standardisation of technical aspects, sufficient training and adequate equipment. The recommendations provide standards for the execution and reporting of skin ultrasound in SSc. The research agenda includes the need for more research into unmet needs according to Outcome Measures in Rheumatology Algorithm requirements., Conclusion: These are the first recommendations providing guidance on the execution and reporting of skin ultrasound in SSc patients, aiming at improving the interpretability, reliability and generalisability of skin ultrasound, thus consolidating its role in research and practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gastrointestinal (GI) manifestations are frequent in systemic sclerosis (SSc) with an impact on quality of life and morbidity. Bowel vasculopathy is a key pathogenetic factor responsible for GI involvement., Objectives: To compare abdominal ultrasound (US) and Color Doppler Ultrasonography (CDU) features of splanchnic vessels of SSc patients with healthy controls., Methods: The charts of SSc patients who underwent an abdominal US and CDU study were retrospectively analyzed. For Superior Mesenteric Artery (SMA) and Inferior Mesenteric Artery (IMA) caliber, Peak Systolic Velocity (PSV), Reverse Velocity (RV), End-Diastolic Velocity (EDV), Mean Velocity (mV), Blood-flow, Resistive Index (RI) and Pulsatility Index (PI) were recorded., Results: 28 SSc patients and 28 controls were enrolled. In SSc, caliber of SMA was significantly smaller than in controls (5.75 ± 0.62 mm vs. 6.45 ± 0.60 mm, p < 0.0001 - p adj =0.0002). The flow study of SMA and IMA showed a significant reduction of RV (SMA: 7.25 ± 6.37 cm/s vs. 18.52 ± 6.16 cm/s, p < 0.0001 - p adj <0.0001; IMA: 2.69 ± 6.10 cm/s vs. 17.06 ± 5.75 cm/s, p < 0.0001 - p adj <0.0001) and PI (SMA: 3.33 ± 0.75 vs. 4.53 ± 1.03, p < 0.0001 - p adj =0.0002; IMA: 3.54 ± 0.95 vs. 6.08 ± 1.53, p < 0.0001 - p adj <0.0001) in SSc patients than controls., Conclusion: involvement of splanchnic vessels in SSc may be non-invasively investigated with abdominal US and CDU. Morphological and functional changes of Doppler parameters observed in SMA and IMA clearly demonstrate that these vessels are affected by SSc vasculopathy., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: Lung ultrasound (LUS), through assessment of B-lines and pleural line alterations, is able to evaluate interstitial lung disease (ILD), a frequent complication of SSc. Different scanning schemes and counting methods have been proposed but no clear cut-off values have been indicated for screening. We aimed to evaluate the accuracy of different LUS methodological approaches to detect ILD compared with high-resolution CT (HRCT) as the gold standard., Methods: Sixty-nine SSc patients underwent LUS and chest HRCT on the same day. Both exams were scored by expert readers. The accuracy of different scanning schemes and counting methods was assessed and clinical and functional data were compared with imaging findings., Results: B-lines were more numerous in patients with the diffuse skin subset and Scl70 autoantibody positivity. The number of B-lines correlated with the Scleroderma Lung Study (SLS) I HRCT score (R = 0.754, P < 0.0001). A total of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest showed 97% sensitivity for detecting even very early ILD signs (corresponding to an SLS I score of 1). Sensitivity increased to 100% when pleural line alterations were included in the analysis., Conclusions: LUS has a very high sensitivity in detecting SSc-related ILD. A cut-off value of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest can be used for the screening of SSc-ILD. Assessing only the postero-basal chest seems to be mostly effective, combining high sensitivity with a less time-consuming approach., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In women with rheumatic diseases (RDs) menstruation-related disorders have never been investigated. The aim of this study was to evaluate gynecological symptoms/disorders in fertile age women with RDs. Materials and methods: All patients (n = 200) filled up a self-administered questionnaire on their gynecological history, menstrual cycle pattern, menstrual-related symptoms, and quality of life (QoL). The RD group was then compared to a control group of 305 age-matched fertile age women. Results: Among patients with RDs, 58% had arthritis, 40% connective tissue diseases (CTDs), and 1.5% systemic vasculitis. No differences were observed between CTDs and arthritis, except for a family history of HMB which was more common among women with CTDs ( p < .01). When compared to controls, women with RDs reported more frequent heavy menstrual bleeding (HMB) during adolescence (51.7 and 25.4%, respectively; p = .0001) and adult life (37.7 and 25.9%, respectively; p = .0065). Also, dysmenorrhea in adolescence was significantly more common among cases (55.6 and 45.4%, respectively; p = .0338). Gynecological pain (dysmenorrhea, non-menstrual pelvic pain, dyspareunia, dysuria, and dyschezia) in patients with RDs was more frequent than in controls ( p = .0001, .0001, .0001, .0001, .0002, respectively). Considering women who reported moderate and severe symptoms in RDs, dysmenorrhea and dyspareunia remain significantly more frequent in women with RDs than in controls ( p = .0001; p = .0022; respectively). QoL scores were significantly reduced in women with RDs, either in physical ( p = .0001) and mental domains ( p = .0014) of short-form 12. Conclusion: Women affected by RDs frequently presented menstruation-related disorders; thus, female patients with RDs should be questioned about gynecological symptoms and referred to the gynecologist for an accurate evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Orlandi, Vannuccini, El Aoufy, Melis, Lepri, Sambataro, Bellando-Randone, Guiducci, Cerinic and Petraglia.)

Objective: To summarize the published evidence in the literature on the role of ultrasound and elastography to assess skin involvement in systemic sclerosis (SSc)., Methods: A systematic literature review (SLR) was performed within the "Skin Ultrasound Working Group" of the World Scleroderma Foundation, according to the Cochrane Handbook. A search was conducted in Pubmed, Cochrane Library and Embase databases from 1/1/1979 to 31/5/2021, using the participants, intervention, comparator and outcomes (PICO) framework. Only full-text articles involving adults, reported in any language, assessing ultrasound to quantify skin pathology in SSc patients. Two reviewers performed the assessment of risk of bias, data extraction and synthesis, independently., Results: Forty-six studies out of 3248 references evaluating skin ultrasound and elastography domains were included. B-mode ultrasound was used in 30 studies (65.2%), elastography in nine (19.6%), and both methods in seven (15.2%). The ultrasound outcome measure domains reported were thickness (57.8%) and echogenicity (17.2%); the elastography domain was stiffness (25%). Methods used for image acquisition and analysis were remarkably heterogeneous and frequently under-reported, precluding data synthesis across studies. The same applies to contextual factors and feasibility. Our data syntheses indicated evidence of good reliability and convergent validity for ultrasound thickness evaluation against mRSS and skin histological findings. Stiffness and echogenicity have limited evidence for validity against histological findings. Evidence for sensitivity to change, test-retest reliability, clinical trial discrimination or thresholds of meaning is limited or absent for reported ultrasound domains., Conclusion: Ultrasound is a valid and reliable tool for skin thickness measurement in SSc but there are significant knowledge gaps regarding skin echogenicity assessment by ultrasound and skin stiffness evaluation by elastography in terms of feasibility, validity and discrimination. Standardization of image acquisition and analysis is needed to foster progress., Competing Interests: Declaration of Competing Interest TS: No conflict of interest ES: No conflict of interest BR: No conflict of interest GL: No conflict of interest LG: No conflict of interest MW: No conflict of interest SW: No conflict of interest AL: No conflict of interest RH: No conflict of interest FDG: reports grants and/or personal fees from AstraZeneca, Abbvie, Boehringer Ingelheim, Capella, Chemomab, Jannsen, Kymab, Mitsubishi-Tanabe. JDP: reports grants and/or personal fees from Boehringer Ingelheim, Janssen, Permeatus and Sojournix Pharma outside of the submitted work. AI: No conflicts of interest JAP da Silva: No conflicts of interest, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Preliminary criteria for the very early diagnosis of systemic sclerosis (VEDOSS) have been previously proposed to identify signs and symptoms in patients with Raynaud's phenomenon. Patients with all signs or symptoms of the VEDOSS criteria already fulfil the 2013 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) classification criteria for systemic sclerosis. However, prospective data for the evolution to fulfilling these criteria do not exist. We therefore aimed to determine the clinical value of the VEDOSS criteria to identify patients with Raynaud's phenomenon who progress to systemic sclerosis within 5 years., Methods: The VEDOSS project was a multicentre, longitudinal registry study done in 42 European Scleroderma Trial and Research group centres located in 20 countries in Europe, North America, and South America. Patients with Raynaud's phenomenon were eligible for enrolment. Those who had fulfilled the 1980 ACR or the 2013 ACR-EULAR classification criteria for systemic sclerosis, as well as of any other ACR or EULAR classification criteria for other definite connective tissue diseases at enrolment were excluded. Data were recorded each year during follow-up visits and included the four VEDOSS criteria (ie, positivity for antinuclear antibodies [ANAs], puffy fingers, systemic sclerosis-specific autoantibodies, and abnormal nailfold capillaroscopy). The primary endpoint was the fulfilment of the 2013 ACR-EULAR classification criteria for systemic sclerosis (ie, progression from enrolment to follow-up). Proportion of progressors and VEDOSS criteria interaction were reported descriptively. Predictors of progression of the distinct VEDOSS criteria interactions were determined based on the point prevalence at 5 years. To investigate the intermediate course of progression of the distinct VEDOSS criteria and their combinations, Kaplan-Meier analysis was done., Results: Between March 1, 2010, and Oct 4, 2018, we enrolled 1150 patients with Raynaud's phenomenon in the VEDOSS database. 764 (66·4%) of 1150 patients met the VEDOSS criteria for study inclusion. Of the 764 patients, 553 (72·4%) had at least one available follow-up visit and the median duration of follow-up was 3·6 years (IQR 1·7-5·8). The mean age was 45·9 years (SD 15·0), 507 (91·7%) of 553 participants were female, and the median time since the onset of Raynaud's phenomenon was 4·0 years (IQR 1·7-10·0). At baseline, 401 (73·7%) of 544 patients with Raynaud's phenomenon had detectable ANA, with 208 (39·5%) of 527 patients positive for systemic sclerosis-specific autoantibodies. Nailfold capillaroscopy abnormalities were present in 182 (36·0%) of 505 patients and puffy fingers were detected in 96 (17·8%) of 540 at baseline. 1885 follow-up visits were recorded. 254 (45·9%) of 553 patients completed the study with progression or a 5-year follow-up; of whom, 133 reached the primary endpoint, resulting in an overall progression rate of 52·4%. The absence of ANA at baseline was the factor most strongly associated with a lack of progression within 5 years, with only four (10·8%) of 37 ANA-negative patients progressing. Conversely, positivity at baseline for systemic sclerosis-specific autoantibodies and puffy fingers was the combination having the highest risk of progression (16 [94·1%] of 17)., Interpretation: Our results from the VEDOSS project offers a useful tool for a stratified risk approach to patients with Raynaud's phenomenon. The absence of ANA is a strong protective factor that identifies patients with very low risk of developing systemic sclerosis whereas the presence of one or two VEDOSS criteria in patients with Raynaud's phenomenon confers a progressively higher risk for systemic sclerosis over time. This stratification tool can be used both for clinical management and to inform early interventional trials., Funding: European Scleroderma Trial And Research and World Scleroderma Foundation., Competing Interests: Declaration of interests LC has had consultancy relationships with Boehringer Ingelheim, Actelion, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Lilly. FdG has had consultancy relationships or has received research funding, or both, from Actelion, AstraZeneca, Boehringer Ingelheim, Capella Biosciences, Chemomab, GlaxoSmithKline, Kymab, and Mitsubishi-Tanabe in the area of potential treatments of scleroderma and its complications. DEF has received grant or research support from Actelion, Amgen, BMS Corbus, CSL Behring, Galapagos Gilead, GlaxoSmithKline, National Institutes of Health, Novartis, Kadmon, PICORI, Pfizer, Sanofi, Roche–Genentech, Talaris, and Mitsubishi; and consultancy relationships with AbbVie, Acetelion, Amgen, BMS Corbus, Galapagos, Novartis, Pfizer, Talaris, R-Pharm, Sanofi, CSL Behring, and Boehringer Ingelheim; and speakers bureau from CME. YA has had consultancy relationships or has received research funding, or both, from Actelion, Bayer, Boehringer Ingelheim, Genentech–Roche, Inventiva, Medsenic, and Sanofi in the area of potential treatments of scleroderma and its complications. OD reports receiving personal fees from AbbVie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GlaxoSmithKline, Horizon, Inventiva, IQvia, Italfarmaco, Iqone, Kymera Therapeutics, Lilly, Medac, Medscape, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Roivant Siences, Sanofi, Serodapharm, Topadur, Target Bioscience, and UCB, during the conduct of the study; and grants from Mitsubishi Tanabe; and a patent issued mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143). MMC has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer Ingelheim, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, Merck Sharp & Dohme, Chemomab, Lilly, Pfizer, and Roche. DH has received travel funding from Actelion, Boehringer Ingelheim, and Shire. VS reports grants and personal fees from Boehringer Ingelheim and Janssen-Cilag NV; grants from Flanders, the Belgian Fund for Scientific Research in Rheumatic diseases; and personal fees from Accord Healthcare, Celgene, and UCB, outside the submitted work. VS is also the chair (unpaid) of the European League Against Rheumatism Study group on Microcirculation in Rheumatic Diseases, co-chair (unpaid) of the American College of Rheumatology Study Group on Microcirculation, co-chair (unpaid) of the Scleroderma Clinical Trials Consortium Working Group on capillaroscopy, and is a steering committee member (unpaid) of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases. TM has received honoraria and fees for lectures from Actelion, Janssen, Boehringer Ingelheim, Lilly, Pfizer, Roche, AbbVie, and Richter. CB reports personal fees from Actelion and Eli Lilly; and grants from the European Scleroderma Trial and Research group, New Horizon Fellowship, the Foundation for Research in Rheumatology, and Fondazione Italiana per la Ricerca sull’Artrite, outside the submitted work All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In order to evaluate the importance of pain in systemic sclerosis (SSc), the characteristics of pain reported by patients with SSc were analyzed and compared with the characteristics of pain reported by patients with primary Sjőgren's syndrome (pSS). Pain was reported by 56 patients (80%) in a group of 70 patients with SSc and by 25 patients (78%) in a group of 32 patients with pSS. Pain severity was assessed by the Pain Rating Index (PRI) and the Present Pain Intensity (PPI) of the McGill Pain Questionnaire (MPQ) and by values obtained by a visual analog scale (VAS) indicating the intensity of pain felt in the moment of the examination and the intensity of pain felt in the week preceding the moment of the examination. No significant difference was detected in the comparison of mean values of pain indices between patients with SSc and patients with pSS and in the comparison among subgroups of patients with SSc. The data indicate that pain is a frequent and important cause of suffering in SSc as in other chronic diseases. The association of different methods may be especially useful to obtain a careful evaluation of pain in clinical research., Competing Interests: Conflict of Interest Marco Matucci-Cerinic is an Associate Editor-in-Chief of the journal. The article was subject to the journal’s standard procedures, with peer review handled independently of this editor and his research groups., (© 2021 Rossella De Luca et al., published by Sciendo.)

Systemic sclerosis is a rare and chronic connective tissue disease with a multifaceted pathogenesis characterised by heterogeneous multi-organ clinical manifestations. Every year, many studies contribute to enrich the knowledge on the pathogenesis, organ involvement and treatment of this complex and severe disease. We herein provide an overview on the most relevant contributions published in the literature in 2020.

In systemic sclerosis (SSc), the gastrointestinal tract (GIT) plays a central role in the patient's quality of life. The microbiome populates the GIT, where a relationship between the Lactobacillus and gastrointestinal motility has been suggested. In this study, the analysis of oral Lactobacillus species in SSc patients and healthy subjects using culture-independent molecular techniques, together with a review of the literature on microbiota and lactobacilli in SSc, has been carried out. Twenty-nine SSc female patients (mean age 62) and twenty-three female healthy subjects (HS, mean age 57.6) were enrolled and underwent tongue and gum swab sampling. Quantitative PCR was conducted in triplicate using Lactobacillus specific primers rpoB 1, rpoB 1o and rpoB 2 for the RNA-polymerase β subunit gene. Our data show significantly ( p = 0.0211) lower Lactobacillus spp rpoB sequences on the tongue of patients with SSc compared to HS. The mean value of the amount of Lactobacillus ssprpoB gene on the gumsofSSc patients was minor compared to HS. A significant difference between tongue and gums ( p = 0.0421) was found in HS but not in SSc patients. In conclusion, our results show a lower presence of Lactobacillus in the oral cavity of SSc patients. This strengthens the hypothesis that Lactobacillus may have both a protective and therapeutic role in SSc patients.

Ultrasound has been widely explored in systemic sclerosis in the clinical and research settings. Ultrasound allows a non-invasive and ionising radiation-free 'window' into this complex disease and is well-suited to repeated examinations. Ultrasound provides novel insights into the pathogenesis and measurement of disease in systemic sclerosis, including early (preclinical) internal organ involvement. The purpose of this review is to describe the role of ultrasound to foster clinical and research advancements in systemic sclerosis relating to (1) musculoskeletal, (2) digital ulcer, (3) lung disease and (4) skin disease. We also highlight unmet needs which much be addressed for ultrasound to assume a central role in systemic sclerosis clinical care and research., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2020.)

Systemic sclerosis (SSc), an autoimmune connective tissue disease, characterized by skin fibrosis, increased dermal thickness and microvascular involvement. Fibroblasts and myofibroblasts deposit excessive amounts of collagenous and non-collagenous extracellular matrix components in the skin. This leads to microvascular abnormalities and Raynaud's phenomenon, with painful digital ulcers (DU) at the fingertips adding to patient discomfort. The skin involvement and severity in SSc was evaluated by the Modified Rodnan skin score (mRSS). Although high-frequency ultrasound (HUS) has been widely researched in the study of skin thickness and DU in SSc, its adoption into clinical practice is not yet common. However, novel insights into the still relatively unknown disease pathogenesis in SSc and its evaluation may be provided by HUS, including early (pre-clinical) skin involvement. It may also be useful in both the evaluation and follow-up of DU. Indeed, it is a non-invasive, safe, inexpensive and reproducible method able to assess not only SSc patients' cutaneous structural changes, but also their vascular system changes. Moreover, several recent studies have reported that elastosonography (ES) is of use when investigating skin involvement in systemic sclerosis. This review aims at providing information as to role HUS and ES play in research advancements and the clinical perspectives in the evaluation of skin thickness and DU in SSc patients., Competing Interests: The authors report no conflicts of interest in this work. No specific funding was received from any bodies in the public, commercial, or not-for-profit sectors, to carry out the work described in this manuscript. The authors declare that the research was carried out without any commercial or financial relationship that could be construed as a potential conflict of interest., (© 2021 Ruaro et al.)

Objective: The aim of the present retrospective observational study was to evaluate the change of Renal Resistive Index (RRI) over time (ΔRRI) and under treatment in patients with systemic sclerosis (SSc) as well as to correlate these changes with disease complications., Methods: Two hundred thirty patients [29 male, median age 57 (IQR 48-67) yrs] were enrolled. At baseline and follow-up (3.43, IQR 2.81-4.45 yrs), we collected the following data: disease variables, nailfold videocapillaroscopy (NVC) pattern, forced vital capacity (FVC), diffusing lung capacity for carbon monoxide (DLCO), systolic pulmonary arterial pressure (sPAP), presence of interstitial lung disease, RRI, evaluation of glomerular filtration rate, and new onset of pulmonary arterial hypertension (PAH)., Results: RRI value is high in SSc patients with digital ulcers and anticentromere antibodies, active and late NVC patterns, and limited cutaneous SSc. A significant correlation was observed between ΔRRI and ΔsPAP (R = 0.17, P = 0.02), with statistically higher ΔRRI (0.08 ± 0.02 vs 0.03 ± 0.05, P = 0.04) in patients complicated by PAH onset. No other new-onset complication was associated with ΔRRI. The receiver-operating characteristic curve analysis confirmed the predictive role of ΔRRI in development of new PAH (area under the curve 0.84, 95% CI 0.75-0.93, P = 0.02). In patients with SSc never exposed to sildenafil, ΔRRI was higher (0.04 ± 0.05) compared to both patients exposed to sildenafil during the study period (0.01 ± 0.05, P = 0.03) or in those exposed at the time of baseline evaluation (0.00 ± 0.05, P = 0.01)., Conclusion: RRI and its variation in time are a reliable marker of SSc-related vasculopathy, both in renal and extrarenal compartments., (Copyright © 2021 by the Journal of Rheumatology.)

Objectives: Biologic disease modifying anti-rheumatic drugs (bDMARDs) have significantly improved the care of patients with rheumatic muscle-skeletal disorders (RMDs). Considering their immunosuppressive action, a theoretical increase of malignancy risk has been a major concern in the last few decades. The objective of this study is to analyze the incidence of malignancies in a cohort of patients affected by rheumatoid arthritis (RA), psoriathic arthritis (PsA), and ankylosing spondylitis (AS) treated with bDMARDs., Methods: The charts of bDMARD-treated RMD patients were reviewed, and data about bDMARD exposure and malignant cancers (excluding non-melanoma skin cancer) were collected., Results: 921 patients were included (median age: 50.59 years, 66.67% females); 1374 bDMARD treatments were administered, 87.12% were tumor necrosis factor inhibitors. A total of 21 malignant neoplasms were detected in 21 patients (61.90% females, median age at cancer diagnosis: 64.99 years), 66.67% in RA patients, 19.05% in PsA, and 14.28% in AS. Among them, 10 patients (47.62%) were treated with etanercept, 6 patients (28.57%) with adalimumab, and 1 case each with tocilizumab, certolizumab, golimumab, infliximab, and abatacept. The most common malignancies that we found were lung cancers, ductal mammary carcinomas, melanomas, and lymphomas. The incidence rate (IR) of malignancies in our cohort was 3.47 per 1000 person-years (p-y); the higher IRs were in RA patients (5.13 per 1000 p-y), in males (4.21 per 1000 p-y), and in patients aged >70 years (10.14 per 1000 p-y)., Conclusions: The results of our study showed IR of malignancies in RMD patients treated with bDMARDs that is in agreement with literature data., Competing Interests: Conflict of Interest CB received honoraria from Eli-Lilly; FB received honoraria from Sigma-Tau. LC, SP, LT, GF, FN, GL, MO, DM, LA, AMP: none. MMC reports receipt of grant/research support and/or speaker's bureau attendance from Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Bayer–MSD, Biogen, and Eli Lilly., (© 2020 Laura Cometi et al., published by Sciendo.)

Background: A high percentage of systemic sclerosis (SSc) patients experience interstitial lung disease (ILD) during the disease course. Recent data have shown that lung ultrasound (LUS) can assess ILD by the evaluation of B-lines, the sonographic sign of pulmonary interstitial involvement., Research Question: To establish the prognostic value of B-lines in a large number of patients with SSc., Study Design and Methods: A total of 396 consecutive patients with SSc, who were enrolled at three Rheumatology Departments, underwent a comprehensive LUS examination on the anterolateral and posterior chest for a total of 58 scanning sites. All available clinical, imaging, and functional data were recorded. Patients were followed after enrolment to establish the prognostic role of LUS., Results: The median number of B-lines was higher in patients with the diffuse cutaneous subset (44 vs 17 B-lines; P < .0001), topoisomerase I autoantibodies (39 vs 16 B-lines; P < .0001), and the presence of ILD at chest high-resolution CT (45 vs 9 B-lines; P < .0001). At multivariable analysis, the number of posterior B-lines ≥5 was associated with new development or worsening ILD (hazard ratio, 3.378; 95% CI, 1.137-9.994; P = .028), with additional value over topoisomerase I positivity. The prognostic value was further confirmed in the subgroup of patients with known ILD at baseline (hazard ratio, 1.010; 95% CI, 1.003-1.018; P = .008)., Interpretation: Lung ultrasound B-lines are associated with worsening or development of pulmonary deterioration. In the near future, LUS might become part of the diagnostic and prognostic armamentarium in patients with SSc, which would allow a more sustainable and user-friendly approach to this very fragile population., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

In the last decades lung ultrasound (LUS) has become of crucial importance in the evaluation and monitoring of a widely range of pulmonary diseases. One of the major benefits which favours this examination, is that this is a non-invasive, low-cost and radiation-free imaging modality which allows repeated imaging. LUS plays an important role in a wide range of pathologies, including cardiogenic oedema, acute respiratory distress syndrome and fibrosis. Specific LUS findings have proved useful and predictive of acute respiratory distress syndrome which is of particular relevance in the suspicion and monitoring of patients with lung disease. Furthermore, several studies have confirmed the role of LUS in the screening of interstitial lung diseases in connective tissue diseases. Given these data, LUS will likely play an important role in the management of COVID-19 patients from identification of specific abnormalities corresponding to definite pneumonia phases and CT scans findings. In addition, LUS could allow reduction in the exposure of health-care workers to potential infection. Herein, we provide a summary on emerging role of lung ultrasound in COVID-19 pneumonia.

Pulmonary arterial hypertension (PAH) carries a high morbidity and mortality burden in Systemic Sclerosis (SSc). Therefore, PAH screening and early detection are pivotal. A systematic literature review (SLR) to search for all screening tools and modalities for SSc-PAH was performed in reference to right heart catheterization as diagnostic gold standard. Papers from 2 previously published SLRs and derived from a systematic search on Pubmed, EMBASE, Web of Science for papers published from 03/10/2017 to 31/12/2018 were manually included. A total of 199 papers were reviewed and 32 were extracted, with a low bias risk according to QUADAS2. Echocardiography, pulmonary function tests, clinical features and serum biomarkers were the most frequently tools used for screening, with different parameters combined in a variable fashion, as single item or as part of composite algorithms. Among the composite algorithms, the DETECT score, ESC/ERS 2009 or 2015 guidelines, ASIG and ITINER-air algorithms were the most commonly used in a wide range of patients. In different cohorts, DETECT and ASIG showed higher sensitivity and negative predictive value than ESC/ERS 2009. In conclusion, the literature shows echocardiography as the leading screening tool for SSc-PAH. In particular, systolic pulmonary arterial pressure (sPAP) and tricuspid regurgitation velocity (TRV), both as single items or part of composite algorithms, including also serum biomarkers, clinical and functional items, are the most frequent parameters evaluated., Competing Interests: Declaration of Competing Interest CB received honoraria from Actelion and Eli-Lilly; GDL received honoraria from SOBI, Novartis, Pfizer, MSD, Celgene; MGL: none; EZ: received consultancy fee from GlaxoSmithKline; GL: none; PA received consultancy and/or travel expenses from Bristol-Myers-Squibb, CSL Behring, Janssen, Novartis, Pfizer, Roche, SOBI; LD received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI. AD received honoraria/speaking fees from GSK, Eli-Lilly, Roche, Janssen, Pfizer; MMC reports receipt of grant/research support and/or speaker's bureau attendance from Actelion, Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Bayer - MSD, Biogen Italia, Eli Lilly., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: High frequency ultrasound allows visualization of epidermis, dermis and hypodermis, precise measurement of skin thickness, as well as assessment of skin oedema, fibrosis and atrophy. The aim of this pilot cross-sectional observational study was to assess the performance and multiobserver variability of ultra-high-frequency (UHF) (50 MHz) ultrasound (US) in measuring skin thickness as well as the capacity of UHF-derived skin features to differentiate SSc patients from healthy controls., Methods: Twenty-one SSc patients (16 limited and five diffuse SSc) and six healthy controls were enrolled. All subjects underwent US evaluation by three experts at three anatomical sites (forearm, hand and finger). Dermal thickness was measured and two rectangular regions of interest, one in dermis and one in hypodermis, were established for texture feature analysis., Results: UHF-US allowed a precise identification and measurement of the thickness of the dermis. The dermal thickness in the finger was significantly higher in patients than in controls (P < 0.05), while in the forearm it was significantly lower in patients than in controls (P < 0.001). Interobserver variability for dermal thickness was good to excellent [forearm intraclass correlation coefficient (ICC) = 0.754; finger ICC = 0.699; hand ICC = 0.602]. Texture computed analysis of dermis and hypodermis was able to discriminate between SSc and healthy subjects (area under the curve >0.7)., Conclusion: These preliminary data show that skin UHF-US allows a very detailed imaging of skin layers, a reliable measurement of dermal thickness, and a discriminative capacity between dermis and hypodermis texture features in SSc and healthy subjects., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)