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Interstitial lung disease (ILD) is a common and potentially devastating complication of systemic sclerosis (SSc), a chronic autoimmune disorder characterized by fibrosis and vascular abnormalities. The association between SSc and ILD underscores the intricate interplay between immune dysregulation, vasculopathy, and tissue fibrosis. This review provides a comprehensive overview of the immunological, clinical, and radiological features of ILD in the context of SSc. It highlights the diverse spectrum of ILD patterns observed in SSc patients, ranging from non-specific interstitial pneumonia to usual interstitial pneumonia. The intricate pathogenic mechanisms linking SSc and ILD involve aberrant immune responses, endothelial dysfunction, profibrotic cytokine signaling, and genetic factors. Immunological alterations, diagnostic challenges, and prognostic implications are discussed, underscoring the need for multidisciplinary management strategies. By elucidating the complex relationship between SSc and ILD, this review aims to contribute to a deeper understanding of the underlying mechanisms and facilitate the development of interdisciplinary interventions for improved patient outcomes.

• Diffuse SSc patients with improvement of skin fibrosis had a lower probability of lung function progression and all-cause mortality than skin progressive patients.

Background: Real-world evidence supporting a safe and effective transition from rituximab originator (RTX-O) to its biosimilars (RTX-B) in autoimmune rheumatic diseases (ARDs) is still limited.Objectives: The primary aims of this study were to evaluate the long-term persistence of RTX-B after the non-medical switch (NMS) from RTX-O in ARD patients, and to explore the RTX-B safety profile. The secondary aims were to evaluate the impact of different factors on RTX-B drug retention rate (DRR) and to identify any factors associated with RTX-B discontinuation.Design: Retrospective observational study.Methods: We included consecutive ARD patients undergoing NMS from RTX-O to GP2013 or CT-P10 from January 2018 to December 2020. RTX-B DRR was estimated by Kaplan–Meier plot analysis and compared according to different factors by the Log-rank test; the Cox proportional hazard model was used to detect factors associated with RTX-B discontinuation in the first 36?months.Results: We enrolled 181 patients switching to RTX-B: GP2013 in 143 (79.0%) cases and CT-P10 in 38 (21.0%). The estimated DRR for RTX-B was 81.5% at 12?months, 80.6% at 24?months, and 77.4% at 36?months. The incidence of adverse events with RTX-B was 12.6/100?patients/year. In the Log-rank test, no statistically significant differences were observed in the RTX-B DRR according to sex (p?=?0.171), ARD diagnosis (p?=?0.281), and concomitant immunosuppressive therapy (p?=?0.054); on the contrary, patients on GP2013 showed a higher DRR than those on CT-P10 (p?

Interstitial lung disease (ILD) is a common and potentially devastating complication of systemic sclerosis (SSc), a chronic autoimmune disorder characterized by fibrosis and vascular abnormalities. The association between SSc and ILD underscores the intricate interplay between immune dysregulation, vasculopathy, and tissue fibrosis. This review provides a comprehensive overview of the immunological, clinical, and radiological features of ILD in the context of SSc. It highlights the diverse spectrum of ILD patterns observed in SSc patients, ranging from non-specific interstitial pneumonia to usual interstitial pneumonia. The intricate pathogenic mechanisms linking SSc and ILD involve aberrant immune responses, endothelial dysfunction, profibrotic cytokine signaling, and genetic factors. Immunological alterations, diagnostic challenges, and prognostic implications are discussed, underscoring the need for multidisciplinary management strategies. By elucidating the complex relationship between SSc and ILD, this review aims to contribute to a deeper understanding of the underlying mechanisms and facilitate the development of interdisciplinary interventions for improved patient outcomes.

Patients affected by systemic sclerosis (SSc) develop functional and structural microvascular alterations and progressive fibrosis of the skin and internal organs. Evaluation of skin microcirculation is an important clinical step in the workup of SSc patients. Near infrared (NIR) spectroscopy is a well-established non-invasive technique to assess haemoglobin oxygen saturation (StO_2) in the illuminated tissue. The recent development of NIR spectroscopic two-dimensional (2D) imaging offers the possibility of visualising StO_2 distribution in large tissue areas. This is particularly important in SSc characterised by a very heterogeneous spatial distribution of the microvascular abnormalities. In addition, the short acquisition time of NIR spectroscopic images allows microvascular “dynamic” conditions, such as the vascular response to physical or pharmacological stimuli, to be evaluated. The present study reports the results of the test application of NIR spectroscopic 2D imaging of the palmar whole-hand surface for the evaluation of peripheral microcirculatory dysfunction in one patient with SSc, as compared with a healthy control, both in “static” (resting) and in “dynamic” (ischaemia-reperfusion) conditions. Spatial heterogeneity of microvascular alterations associated with temporal heterogeneity in vascular reactivity to ischaemic challenge make 2D NIR spectroscopic imaging a promising tool in the assessment of SSc, as compared with the current available techniques. A NIR spectroscopic camera by Kent Imaging Inc, Calgary, Canada was used.

The remains of 12 members of the grand ducal (junior) branch of the Florentine Medici family were exhumed in 2003 as part of the Medici Project, a multidisciplinary study whose aim was to investigate the lifestyles, health status, and possible causes of death of members of one of the richest, most powerful families of the Italian Renaissance. Digital radiography and orthopantomography were performed on the skeletal remains of individuals who lived between 1562 and 1666. The observed bone malformations, deformities, and changes (degenerative, metabolic, and dental) challenge traditional views, based on portraits and historical accounts, about the appearance and lifestyle of some family members. Moreover, the occurrence of a constellation of bone changes related to diabetes (osteoporosis, osteoarthritis, diffuse idiopathic skeletal hyperostosis, cranial hyperostosis, and crystalline arthropathy) suggests that this metabolic disease was common in the grand ducal branch of the Medici family.

Background: The treatment of systemic sclerosis is a difficult challenge because of the present lack of drugs definitely proven to alter the overall course of the disease. Objective: To address the current guidelines and to analyze the perspectives opened by the availability of new drugs and the identification of previously unknown pathways. Methods: The statements on current treatment are based on recently developed EULAR recommendations. The perspectives reflect the opinion of the authors on emerging topics. Results/conclusion: The treatment of systemic sclerosis has improved in recent years because a number of drugs have been shown to influence single disease manifestations. The identification of previously unknown pathways might open the way for further developments.

Patients affected by systemic sclerosis (SSc) develop functional and structural microvascular alterations and progressive fibrosis of the skin and internal organs. Evaluation of skin microcirculation is an important clinical step in the workup of SSc patients. Near infrared (NIR) spectroscopy is a well-established non-invasive technique to assess haemoglobin oxygen saturation (StO2) in the illuminated tissue. The recent development of NIR spectroscopic two-dimensional (2D) imaging offers the possibility of visualising StO2distribution in large tissue areas. This is particularly important in SSc characterised by a very heterogeneous spatial distribution of the microvascular abnormalities. In addition, the short acquisition time of NIR spectroscopic images allows microvascular “dynamic” conditions, such as the vascular response to physical or pharmacological stimuli, to be evaluated. The present study reports the results of the test application of NIR spectroscopic 2D imaging of the palmar whole-hand surface for the evaluation of peripheral microcirculatory dysfunction in one patient with SSc, as compared with a healthy control, both in “static” (resting) and in “dynamic” (ischaemia-reperfusion) conditions. Spatial heterogeneity of microvascular alterations associated with temporal heterogeneity in vascular reactivity to ischaemic challenge make 2D NIR spectroscopic imaging a promising tool in the assessment of SSc, as compared with the current available techniques. A NIR spectroscopic camera by Kent Imaging Inc, Calgary, Canada was used.

To develop criteria for the classification of systemic sclerosis (SSc) in children (juvenile SSc).The study consisted of 3 phases: 1) collection of data on the signs and symptoms of actual patients with juvenile SSc that are useful for defining involvement of a particular organ; 2) selection of the parameters essential for the classification of juvenile SSc and preparation of a set of provisional classification criteria (PCC) using 2 Delphi surveys; 3) consensus conference consisting of 2 steps: discussion and rating of clinical profiles of 160 patients with definite juvenile SSc, possible juvenile SSc, or other fibrosing diseases as “having or not having juvenile SSc,” using nominal group technique, and defining those PCC with the best statistical performance and highest face validity by using the clinical profiles of patients with definite juvenile SSc as the gold standard.In phase 1, 55 centers submitted clinical data on 153 patients with juvenile SSc. A total of 48 signs and symptoms were derived from these patient data and were used to define 9 organ system categories (cutaneous, vascular, gastrointestinal, respiratory, renal, cardiac, neurologic, musculoskeletal, and serologic). During phase 2, these were reduced to 21 criteria (3 major criteria [Raynaud's phenomenon, proximal skin sclerosis/induration of the skin, and sclerodactyly] and 18 minor criteria) and combined to generate 86 different PCC. At the consensus conference, these 86 definitions were tested on the case profiles of 127 patients with juvenile SSc. The PCC with the highest ranking were proximal sclerosis/induration and at least 2 minor criteria.These provisional classification criteria for juvenile SSc will help standardize the conduct of clinical research, epidemiologic and outcome studies, and therapeutic trials.

Clinical, laboratory features and the outcome of 73 children affected with Kawasaki Disease (KD) (62 with typical KD and 11 in which one or more of the Japanese Committee criteria were lacking) were analyzed and compared with those of the literature. All patients, except 14 admitted before 1982, received the current specific treatment with aspirin and intravenous immunoglobulin (WIG) (400 mg/kg/for 5 days or a single infusion of 2 g/kg). Three children underwent a second cycle of IVIG because fever and coronary alterations persisted after the first infusion. The frequency of cardiac involvement in our complete KD (29X) was comparable with that reported in the literature (coronary dilatation 20X and coronary aneurysm 4X), while in the incomplete cases no coronary abnormalities were detected. The outcome of the KD was good in all children. Remodeling of coronary vessels was noted in all patients with coronary artery damage, 2 to 24 months from the disease onset.

Gliddon et al. conducted a randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy of the angiotensin-converting enzyme inhibitor quinapril for the management of vascular damage in systemic sclerosis (SSc). The trial comprised 213 patients with limited cutaneous SSc or Raynaud's phenomenon (mean age 54 years, 182 females) who were randomly assigned to receive 80 mg/day, or the maximum tolerated dose, of quinapril (n = 105) or placebo (n = 108) for 2–3 years. Patients were assessed every 3 months. The number of new ischemic digital ulcers was recorded as the primary end point, while the frequency of Raynaud's phenomenon episodes, skin score, health status, pulmonary artery pressure and treatments for ischemia were also monitored as secondary end points. There were no detectable differences between patients treated with quinapril and those receiving placebo; however, although no severe adverse effects were observed, patients taking quinapril experienced significantly more adverse effects.

Abstract 5126

Systemic sclerosis (SSc) involves the microcirculation, the immune system, and the connective tissue eventually leading to fibrosis. Vascular dysfunction is one of the earliest events in SSc pathogenesis: endothelial damage leads to a dysregulation of angiogenesis and a loss of capillaries. The consequent chronic ischemia provokes a diffuse sufference of the tissues with formation of ulcers. We analyzed BM biopsies in a series of patients undergoing HSCT in our Centre for severe, progressive SSc in order to clarify the association between modification bone marrow angiogenesis and clinical features of this disease.The main clinical feature of the patients are following: modified Rodnan Skin Score was more than 8 in four patients; nailfold videocapillaroscopy was active in three patients; pulmonary arterial hypertension was upper limit only in two patients; carbon monoxide diffusing capacity was more than 40% in all the patients; high resolution computed tomography showed fibrosis or ground glass lesions in all the patients; topoisomerase I and antinuclear antibody was positive in all the patients. Only one patient showed arrhythmia. Eight SSc bone marrow biopsies were studied, compared with five bone marrow biopsies of non malignant controls. To evaluate angiogenesis, following monoclonal antibodies (MoAb) were used: VEGF, KDR, MMP-9, CD34. Bone marrow fibrosis was evaluated by silver impregnation for reticulum. To identify BM microvessel, anti-CD34 was used. Sections were observed at 400x magnification by two different blinded observers. To calculate the number of vessels, vascular mean area expressed in mm2, vascular percent mean area, perimeter and MVD, a multiparametric, semi-automatic computerized imagine analysis was employed. For each section, we evaluated eight consecutive areas and each area was 16001,92 mm2 (total area was 128015,36 mm2). The VEGF, MMP-9, KDR expression was evaluated as percentage of positive cells in a total of eight consecutive areas at 400x magnification.All patients showed a mean cellularity of 40% (SD 5.24, range 30-45%). In four patients bone marrow fibrosis was detected: two patients were classified as I° grade and two as II°grade. The bone marrow biopsy specimens from patients with SSc show a substantial reduction in vascularity. A multiparametric computerized analysis demonstrated significantly reduction of MVD in SSc cases. The mean MVD in SSc bone marrow was 712,63 (SD 392.03, range 124,98-1312,34) whereas in control specimens it was 1364,58 (SD 44.20, range 1312,34-1402,14). The mean number of vessels (p0.004) and percent vascular mean area are lower in sclerosis than controls (p0.0009). A significant increased expression of VEGF was observed. The median VEGF rate was 48,75 (range 30-85%) with expression ≥ 50% in half patients and in two patients with advanced SSc this expression was more than 70%. KDR expression was significantly lower in SSc bone marrow than in controls (p=0,003). The median KDR rate was 13,25% (range 1-40%) and 42% (range 40-45%) in sclerosis and controls respectively. In all cases the expression of MMP-9 was significantly lower than controls (p=0,0009) with median rate of 13,06% (range 1-25%) while median expression in controls was 30% (range 20-40%).We demonstrated in patient with SSc a reduction of bone marrow vascularity despite the stricking increase of a number of angiogenic factors. VEGF expression in SSc bone marrow is high in all cases with a double median rate compared to controls (48,75% vs 4,25%) while MVD is lower in sclerosis than controls (712,63 vs 1364,58). In regard to these alterations in our study we have observed a reduction of KDR and MMP-9. The overproduction of VEGF can generate a negative feedback to KDR while the low levels of MMP9 found in SSc bone marrow may be due to a hyperproduction of MMP inhibitors contributing to the reduction of bone marrow vascularity. In conclusion, our data demonstrate that in SSc the angiogenic potential of bone marrow is reduced, mirroring the systemic microvascular condition characterised by loss of capillaries and desertification despite the increase of VEGF. The amount of reticular fibers, detected in bone marrow, suggests that the fibrotic process may affect also the bone marrow contributing further to the reduction of angiogenic potential.No relevant conflicts of interest to declare.