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Objectives: Lung ultrasound (LUS) and high-resolution CT (HRCT) are commonly used for the evaluation of interstitial lung disease (ILD). Nintedanib (NIN) is an antifibrotic therapy approved for systemic sclerosis-associated ILD (SSc-ILD). We assessed LUS and quantitative HRCT changes in SSc-ILD patients treated with NIN during a 1 year follow-up, evaluating relationships between imaging variations and functional or quality-of-life outcomes., Methods: SSc-ILD patients who started NIN were enrolled and followed for 12 months. Pulmonary function tests and patient-reported outcome measures (PROMs) were assessed half-yearly and quarterly, respectively. LUS was performed quarterly evaluating the presence of B-lines (BL) and pleural line irregularities (PLI). HRCT was repeated after 1 year and quantitatively analysed with CALIPER software., Results: Ten patients (70% female, mean age 62 years) were enrolled. The mean total number of both BL and PLI was constantly decreased during NIN treatment, being significantly reduced after 12 months (from 175.1 [66.7] to 120.8 [70.3] for BL, P = 0.005; and from 50.6 [32.5] to 37.2 [22.4] for PLI, P = 0.05). Male gender, smoking habit and baseline forced vital capacity <70% predicted were associated with worse LUS outcomes. A greater reduction in both BL and PLI was observed in those who improved in PROMs, especially modified Medical Research Council dyspnoea scale (P = 0.016 and P = 0.04, respectively) and Saint George's Respiratory Questionnaire (P = 0.006 and P = 0.026, respectively). No significant changes in the CALIPER percentages of normal parenchyma or ILD elements were observed after 12 months of NIN, thus paralleling the stabilization obtained at pulmonary function tests., Conclusion: We present preliminary results on NIN effects on SSc-ILD as assessed by LUS, a useful method for frequently repeated monitoring, and CALIPER, a valid implementation whenever a HRCT is performed., (© 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.)

Objective: Raynaud phenomenon (RP) and digital ulcers (DUs) are the main signs of digital vasculopathy in systemic sclerosis (SSc). Selexipag is an oral prostacyclin agonist approved for SSc-related pulmonary arterial hypertension. Following our previous preliminary short-course report, we herein present long-term data on selexipag safety and efficacy in the treatment of SSc digital vasculopathy., Methods: Selexipag was administered to patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies. Each subject was assessed at baseline and after 3, 6, and 12 months. Clinical outcomes related to RP and DUs were evaluated along with modified Rodnan skin score of the fingers. Digital perfusion was assessed by laser speckle contrast analysis (LASCA). Nailfold videocapillaroscopy (NVC) was also performed., Results: Eight patients with SSc (63% female, mean age 50.1 years) received selexipag. After 12 months of treatment, RP was reported to significantly decrease in the number of daily episodes and mean duration ( P < 0.001 and P = 0.01, respectively). All patients achieved a complete healing of their DUs ( P = 0.03) within 6 months. A progressive reduction of fingers skin score was observed ( P = 0.03). No structural changes of capillaries were noted on NVC. Conversely, LASCA revealed an important increase in total digital perfusion ( P = 0.004) despite seasonal variability. The safety profile was consistent with that reported in the literature., Conclusion: We observed a sustained efficacy of selexipag on SSc digital vasculopathy during 1 year of administration. Our promising results encourage the design of a new randomized controlled trial to evaluate the effect of selexipag on SSc digital vasculopathy., (Copyright © 2024 by the Journal of Rheumatology.)

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: Nintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects., Methods: Patients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them., Results: Twenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months-p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months-p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN., Conclusion: We presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects., (© 2023. The Author(s).)

Objective: Systemic sclerosis (SSc) is burdened by Raynaud phenomenon (RP) and digital ulcers (DUs), and sometimes standard vasoactive therapies are ineffective or contraindicated. Selexipag is an oral selective IP prostacyclin receptor agonist approved for the treatment of SSc-related pulmonary arterial hypertension. We aimed to evaluate the clinical and instrumental efficacy of selexipag in SSc digital vasculopathy., Methods: Patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies were administered selexipag. RP- and DU-related clinical outcomes were evaluated, and digital perfusion was assessed by laser speckle contrast analysis (LASCA), all at baseline and after 3 months., Results: Selexipag was administered to 9 patients with SSc (66.6% female, mean age 52.3 [SD 16.6] yrs). One patient had to stop the drug because of adverse effects. After 3 months of selexipag administration, there was a significant reduction in RP daily episodes ( P = 0.01) and RP mean duration ( P = 0.04). The number of DUs decreased from 10 to 4 without reaching statistical significance. A significant improvement in mean perfusion of the fingers ( P = 0.02) was observed with LASCA., Conclusion: Selexipag showed good potential for the treatment of SSc digital vasculopathy. Our results are certainly preliminary, yet quite encouraging. New trials for the evaluation of selexipag efficacy in SSc digital vasculopathy are needed., (Copyright © 2023 by the Journal of Rheumatology.)

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.

Objective: To evaluate finger proximal-distal gradient (PDG) perfusion in subjects with primary Raynaud's phenomenon (PRP), then making comparisons with systemic sclerosis (SSc) patients and healthy controls (HC)., Methods: Consecutive adult PRP subjects were enrolled, along with an equal number of SSc and HC. Peripheral blood perfusion of the hands was assessed by laser speckle contrast analysis (LASCA). PDG was then calculated applying a generalizable formula independent of both intra- and inter-personal factors. Non-specific anti-nuclear autoantibody (ANA) isolated positivity was assessed., Results: Fifty PRP patients (88 % female, mean age 45 ± 17.9 years) were enrolled, along with 50 SSc patients and 50 HC. After adjusting mean PDG results for age and sex, no significant differences emerged between PRP and SSc (1.80 ± 0.43 vs 1.76 ± 0.53; p = 0.294). Conversely, PRP values were significantly reduced when compared to HC (2.72 ± 0.37; p < 0.001). Among PRP subjects, no significant differences were found regarding isolated ANA positivity (1.86 ± 0.44 vs 1.74 ± 0.44; p = 0.42)., Conclusion: PRP and SSc seems to share the same basal PDG perfusion impairment assessed by LASCA. Isolated ANA positivity, in the absence of clinical and capillaroscopic suspicion for secondary causes, should not be considered an exclusion criterion for PRP classification., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the performance of oropharyngoesophageal scintigraphy (OPES) in the assessment of dysphagia in patients with systemic sclerosis (SSc), and to compare OPES results with those of barium esophagogram., Methods: Adult SSc patients who underwent OPES for the assessment of dysphagia were enrolled. OPES was performed with both liquid and semisolid boluses and provided information regarding oropharyngeal transit time, esophageal transit time (ETT), oropharyngeal retention index (OPRI), esophageal retention index (ERI), and site of bolus retention. Barium esophagogram results were also collected., Results: Fifty-seven SSc patients (87.7% female, mean age 57.7 years) with dysphagia were enrolled. OPES identified at least one alteration in each patient and findings were generally worse for the semisolid bolus. Esophageal motility was widely impaired with 89.5% of patients with an increased semisolid ERI, and middle-lower esophagus was the most frequent site of bolus retention. However, oropharyngeal impairment was highlighted by widespread increased OPRI, especially in anti-topoisomerase I positivity. Older patients and with longer disease duration presented slower semisolid ETT (p = 0.029 and p = 0.002, respectively). Eleven patients with dysphagia had a negative barium esophagogram: all of them presented some alterations in OPES parameters., Conclusion: OPES revealed a marked SSc esophageal impairment, in terms of both slowed transit time and increased bolus retention, but also shed light on oropharyngeal swallowing alterations. OPES showed high sensitivity, being able to detect swallowing alterations in dysphagic patients with negative barium esophagogram. Therefore, the use of OPES for the assessment of SSc-related dysphagia in clinical practice should be promoted., (© 2023. The Author(s).)

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: To provide a full characterization of proper palmar digital arteries (PPDA) in systemic sclerosis (SSc) with ultra-high frequency ultrasound (UHFUS), and to investigate possible relationships between digital macroangiopathy and microangiopathy., Methods: SSc patients without active digital ulcers and healthy controls (HC) were enrolled. Each subject underwent UHFUS 70 MHz evaluation of PPDA from II to V fingers bilaterally, searching for vessel occlusion and measuring the thickness of the three arterial layers and the systolic-diastolic excursion range. Microcirculation was investigated with capillaroscopy and laser speckle contrast analysis (LASCA)., Results: Forty-six SSc patients (87% female, mean age 55.5 years) and 15 HC comparable for age and sex were enrolled. UHFUS in SSc revealed the occlusion of 124 (16.8%) PPDA, whereas in HC they were all patent. Considering a finger with at least one PPDA occluded as ultrasonographically pathological, 67.4% patients presented ≥1 pathological fingers. All three arterial layers were significantly thicker and excursion range significantly reduced in SSc than in HC (p<0.001 for all). Seventy-three percent of fingers previously affected by digital ulcers, were ultrasonographically pathological. Disease duration was directly correlated to the thickness of all three arterial layers. No significant correlations emerged between capillaroscopy or LASCA findings and UHFUS features., Conclusion: UHFUS allows the characterization of vasculopathic involvement of PPDA in SSc, also showing subclinical vasculopathy. The lack of correlations between UHFUS and capillaroscopy or LASCA likely mirrors non-overlapping vasculopathic processes. UHFUS evaluation of PPDA emerges as complementary to microcirculation assessment for a more accurate and complete characterization of SSc vasculopathy., Competing Interests: Conflict of interest None to declare., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature., Materials and Methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas., Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches., Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

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.

Objectives: To compare two algorithms for cardiovascular (CV) risk estimation in systemic sclerosis (SSc) patients, investigating correlations with disease characteristics., Methods: Traditional CV risk factors and SSc-specific characteristics were assessed in a cohort of SSc patients. Framingham and QRISK3 algorithms were used to estimate the risk of developing a CV disease over the next 10 years., Results: Seventy-two SSc patients were enrolled. Among those 56 without previous CV events, Framingham reported a median risk score of 9.6%, classifying 24 (42.9%) subjects at high risk. QRISK3 showed a median risk score of 15.8%, with 36 (64.3%) patients considered at high risk. Both algorithms revealed a significant role of some traditional risk factors and a noteworthy potential protective role of endothelin receptor antagonists (p = .003). QRISK3 was also significantly influenced by some SSc-specific characteristics, such as limited cutaneous subset (p = .01), interstitial lung disease (p = .04), and non-ischemic heart involvement (p = .03), with the first two maintaining statistical significance in the multivariate analysis (p = .02)., Conclusions: QRISK3 classifies more SSc patients at high risk to develop CV diseases than Framingham, reflecting the influence of some SSc-specific characteristics. If its predictive accuracy were prospectively verified, the use of QRISK3 as a tool in the early detection of SSc patients at high CV risk should be recommended., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: In patients with systemic sclerosis (SSc) the perfusion of the fingers shows an alteration of the physiological proximal-distal gradient (PDG). The aim of this study is to provide a generalizable definition of PDG, applying it in a cohort of SSc patients and healthy controls (HC) using laser speckle contrast analysis (LASCA)., Methods: Adult consecutive SSc patients and HC were enrolled. Peripheral blood perfusion of the hands was evaluated by LASCA, subsequently obtaining 3 different regions of interest: from the distal interphalangeal joint to the fingertip (DIST), from the metacarpophalangeal joint to the distal interphalangeal joint (PROX), and of the whole finger (TOT). A PDG formula independent of both intra- and inter-personal factors was then built. The PDG formula so obtained was: [(DIST × 2.63) - PROX]/TOT., Results: Ninety-four SSc patients (79.8% female, mean age 58.7 years) were enrolled. Applying the PDG formula, SSc patients revealed mean PDG values significantly lower than HC (1.82 ± 0.44 PU vs 2.70 ± 0.38 PU; p < 0.0001). Patients with a previous history of digital ulcers presented significant lower PDG values (p = 0.002). The ROC curve analysis identified in 2.28 PU the best PDG cut-off value between SSc and HC, with 86% sensibility and 90% specificity., Conclusion: This study provided a PDG formula generalizable to all kind of subjects, applying it in SSc with great sensibility and specificity using LASCA, the best non-invasive imaging technique for the dynamical evaluation of peripheral perfusion. LASCA-PDG appears also as a tool able to identify a subclinical microangiopathic impairment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics., Methods: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared., Results: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs., Conclusion: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex., (© 2022 by the Journal of Rheumatology.)

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.

Objective: To use bioelectrical impedance vector analysis (BIVA) in a cohort of patients with systemic sclerosis (SSc) in order to assess their nutritional status in comparison to other groups of patients and to find any correlation with clinical characteristics and outcome of the disease., Methods: We retrospectively collected data from 50 SSc patients who underwent BIVA for clinical suspicion of malnutrition and compared them with patients affected by other chronic autoimmune rheumatic diseases (OCAD, n = 27) and those who were only symptomatic of malnutrition but without autoimmune features (n = 15), and with 50 healthy controls (HC)., Results: Patients with SSc presented significantly lower values of phase angle (PhA), basal metabolic rate (BMR), and body cellular mass (BCM), and an increase in extracellular water (ECW; P < 0.01 for all) than HC; instead, there were no significant differences for BMI. No significant differences were found between SSc and OCAD. Among patients with SSc, age directly correlated with ECW (ρ = 0.342, P = 0.015) and inversely with PhA (ρ = -0.366, P = 0.009). Female sex, anemia, hypoalbuminemia, reflux, and early satiety/abdominal distension associated with relevant alterations in BIVA results. BIVA variables were significantly different when cardiopulmonary and microvascular involvement was present. Four patients died during the study: they had significantly ( P ≤ 0.01) lower PhA, BMR, and BCM, with an increased ECW., Conclusion: BIVA, unlike BMI, allowed an accurate characterization of SSc patients at risk of malnutrition, correlating with serological malnutrition markers, with SSc-specific organ manifestations (cardiopulmonary involvement and microvascular damage), and with mortality. BIVA variables might represent a surrogate marker of damage accrual that leads to malnutrition, thus playing a leading role in the prognostic stratification of SSc patients., (Copyright © 2021 by the Journal of Rheumatology.)

Digital ulcers (DUs) represent one of the major burdens for patients with systemic sclerosis (SSc), especially when associated with skin calcinosis (SC). The aim of this work is to evaluate the impact of SC in DUs of patients with SSc for clinical characteristics and prognosis assessed by the wound bed score (WBS). We prospectively enrolled 55 patients with DUs and SSc followed in our dedicated wound care clinic. For all the patients we collected clinical and anthropometric data and characteristics of the DU, and we calculated the WBS for each DU. Ninety-nine DUs were evaluated (24 with SC). SC was prevalent in limited cutaneous SSc (75%) and in patients with longer disease duration (P = 0.02). SC-DUs were prevalent at the fingertip (P = 0.04). The healing time was significantly higher in patients with SC (10.4 ± 7.9 weeks) compared with non-SC (7.0 ± 5.7 weeks) P = 0.03. The WBS negatively correlated with the time to achieve complete healing (r = -0.237 P = 0.023) and the correlation was maintained in the non-SC (r = -0.46, P = 0.033). DUs in SSc patients with SC are common and difficult to heal. When DUs are treated in dedicated centres, the prognosis is good. The WBS is fast and easy and maybe commonly applied in clinical practice., (© 2020 Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

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.)

Systemic sclerosis (SSc) is a connective tissue disease characterised by diffuse microangiopathy and immune dysregulation which ultimately results in widespread fibrosis of the skin and internal organs. This complex autoimmune disease is characterised by heterogeneous clinical manifestations and variable disease course in which the severity of pathology dictates the disease prognosis and course. Every year novel insights into the pathogenesis, organ involvement and treatment of this severe disease are published. Herewith, we provide an overview of the most significant literature contributions published last year, with the aim of helping the clinician in the understanding and management of SSc patients.

Objectives: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation)., Methods: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc., Results: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features., Conclusions: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.

Objective: Digital ulcers (DUs) represent one major burden for patients with systemic sclerosis (SSc). The objectives of our study were to evaluate blood flow in SSc-DUs with laser speckle contrast analysis (LASCA) and to correlate the skin perfusion to clinical and laboratory data., Methods: Forty DUs in 31 consecutive patients with SSc according to 2013 ACR/EULAR criteria (20 with limited cutaneous disease, 3 males) were prospectively examined with LASCA. Clinical and laboratory data were collected at the same time. DUs were classified according to clinical features and presence of infection., Results: At LASCA analysis, patients with diffuse SSc had lower mean values of blood flow compared with those with limited disease at the finger affected by DUs (88.80 vs 44.40, p = 0.036) and at the periulcer area (p = 0.041). The presence of infection was associated to a higher flow at the finger with DU (103.02 vs 58.05 p = 0.04), at the level of ulcer (217.63 vs 67.15, p < 0.001), and at the periulcer area (p = 0.001). The ratio between the blood flow at the ulcer area and the finger base (UA/FB) showed a bimodal trend in patients with infected DUs and in those without infections. Infection was positive correlated to the time of healing (HT) (r = 0.648, p = 0.023), while in DUs without infection a negative correlation to HT (r = - 0.46, p = 0.015) was identified., Conclusions: This study demonstrates for the first time that the UA/FB ratio may predict the healing time of DUs in SSc patients and may be crucial for the prognostic stratification of patients. Infection remains one of the main predictors of DU healing.Key Points• The prognostic value of laser speckle contrast analysis (LASCA) in patients with digital ulcers (DUs) in systemic sclerosis remains to be clarified.• LASCA may be able to predict the haling time of the digital ulcers.• The presence of infection of the wound bed may greatly influence the LASCA parameters and the healing time of the digital ulcer.

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.

Systemic sclerosis (SSc) is a complex disorder characterised by the involvement of small arteries, microvessels and connective tissue, with deposition of fibrotic tissue and microvascular obliteration in the skin and internal organs. Due to the multifaceted nature of the disease, several articles are published in the medical literature every year, aimed at exploring different aspects of the pathogenesis, internal organ involvement and clinical aspects, and possible therapeutic approaches. In this article we have reviewed the literature on SSc of the past year, with the aim of identifying novel approaches that may help the treating physician in the clinical management of patients.

Systemic sclerosis is a rare acquired systemic disease characterised by a complex pathogenesis and multi organ involvement. Every year the scientific world contributes to enrich the knowledge on the pathogenesis, clinical manifestations, diagnosis and treatment of this complex and severe disease. Herewith, we provide an overview of the most significant literature contributions published over the last year.

Systemic sclerosis is a rare acquired systemic disease characterised by heterogeneous evolution and outcome. Each year novel insights into the pathogenesis, diagnosis and treatment of this severe disease have been published. We herewith provide our overview of the most significant literature contributions published over the last year.

Systemic sclerosis is a rare acquired systemic disease characterised by a complex pathogenesis and multi organ involvement. Every year, novel insights into the pathogenesis, diagnosis and treatment of this severe disease are published. Herewith, we provide an overview of the most significant literature contributions published over the last year.

Systemic sclerosis is a complex chronic disease characterised by chronic multisystem involvement of skin and internal organs. We reviewed all the articles published during the last 12 months on systemic sclerosis and in this article we provide a critical analysis of the most relevant studies regarding the pathogenesis, classification and management of the disease.

Herewith we provide a critical digest of the recent literature on systemic sclerosis. The most relevant studies published over the last two years have been reviewed, with particular focus on the diagnosis, pathogenesis and treatment of the disease.

Objectives: To investigate blood flow and microvascular reactivity by laser speckle perfusion imager (Perimed, Jarfalla) in consecutive patients affected by Raynaud's phenomenon at baseline and following dynamic stimulations., Methods: Skin blood flow in the dorsum of the hand was measured at baseline and after cold test and post-occlusive hyperemia test in 56 consecutive subjects affected by Raynaud's phenomenon (RP), 20 primary (PRP) and 36 secondary to systemic sclerosis (SSc). Twenty healthy subjects (HS) were studied as controls., Results: After cold test, SSc had a significant reduction of blood flow (-58%) as compared to HS (-19%) (p=0.01). Recovery time was significantly higher in SSc (58 minutes) as compared to HS (18 minutes) and PRP (19 minutes) (p=0.006 and 0.0016, respectively). Peak flow after ischaemic test was significantly reduced in SSc (+237%) as compared to PRP (+485%) (p=0.0068). Post-ischaemic hyperemic area under the curve (AUC) was blunted in SSc (79U/sec) compared to PRP (167 U/sec) (p=0.0126). Proximal distal gradient was noticed in 74% of HS, 45% of PRP and 36% of SSc (p=0.01). Homogeneous pattern of flux distribution was significantly different between HS (95%), PRP (80%), and SSc (16%) (p<0.0001). Among SSc patients, a significant difference in ischaemic challenge was shown between patients with early-SSc versus patients with definite-SSc., Conclusions: Our preliminary results indicate a clearcut alteration of the dynamic of microcirculation in SSc-RP as compared to PRP and HS. Among SSc patients, early-SSc is a separate entity as compared to established disease.

Objective: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc., Methods: A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198, rs959173, rs9920) displaying the most significant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting., Results: In the French population, the CAV1 rs959173 C minor allele showed a significant protective association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86, p(adjusted)=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95% CI 0.56 to 0.89, p(adjusted)=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran-Mantel-Haenszel meta-analysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased CAV1 protein expression., Conclusions: These results add CAV1 to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.

The aim of the present study was to evaluate the concentration of cell-free DNA (cf-DNA) in the plasma of patients with systemic sclerosis (SSc) and to examine the correlation of cf-DNA with clinical variables of the disease. The study population consisted of 122 SSc patients and 16 healthy controls. Epidemiological and clinical data were collected by direct assessment. The beta-globin gene was used to determine the total amount of DNA in the plasma by real-time quantitative PCR analysis. cf-DNA was found in all patients (mean concentration 1,420.7 copies/ml) and controls (mean concentration 1,462.5), with no significant difference. In SSc patients, no correlation was found between cf-DNA and the type of organ involvement, but patients with active disease presented significantly higher cf-DNA concentrations than those with inactive disease (p < 0.05). Our data suggest that cf-DNA could provide a useful biomarker for the assessment of disease activity in SSc patients.