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Keywords = modified Rodnan skin score

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25 pages, 1504 KiB  
Article
Systemic Sclerosis with Interstitial Lung Disease: Identification of Novel Immunogenetic Markers and Ethnic Specificity in Kazakh Patients
by Lina Zaripova, Abay Baigenzhin, Zhanar Zarkumova, Zhanna Zhabakova, Alyona Boltanova, Maxim Solomadin and Alexey Pak
Epidemiologia 2025, 6(3), 41; https://doi.org/10.3390/epidemiologia6030041 - 6 Aug 2025
Abstract
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: [...] Read more.
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article
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15 pages, 1666 KiB  
Article
Serum Metabolomic Profiling Reveals Differences Between Systemic Sclerosis Patients with Polyneuropathy
by Kristine Ivanova, Theresa Schiemer, Annija Vaska, Nataļja Kurjāne, Viktorija Kenina and Kristaps Klavins
Int. J. Mol. Sci. 2025, 26(15), 7133; https://doi.org/10.3390/ijms26157133 - 24 Jul 2025
Viewed by 220
Abstract
Metabolome studies have already been carried out in patients with systemic sclerosis (SSc). However, polyneuropathy (PNP) as a complication of SSc has been overlooked in these studies. To the best of our knowledge, this is the first study to examine metabolic changes in [...] Read more.
Metabolome studies have already been carried out in patients with systemic sclerosis (SSc). However, polyneuropathy (PNP) as a complication of SSc has been overlooked in these studies. To the best of our knowledge, this is the first study to examine metabolic changes in SSc patients with PNP. Patients with SSc (n = 62) and a healthy control group (HC) (n = 72) were recruited from two Latvian hospitals. Blood plasma samples were collected and analyzed using an LC-MS-based targeted metabolomics workflow. Our plasma sample cohort consisted of 62 patients with SSc, 42% of whom had PNP. Differences between SSc patients and the HC group with fold changes > 2 were observed for aspartic acid, glutamic acid, valine, and citrulline, all of which were reduced. In contrast to the SSc to HC discrimination, no metabolites had a high fold change; only minor changes were observed using FC > 1.3. We identified elevated concentrations of kynurenine, asparagine, and alanine. Changes in metabolite regulation in patients with SSc, compared to controls, are not identical to those observed in SSc patients with PNP, with elevated concentrations of kynurenine and alanine specific to the SSc subgroup. SSc patients with PNP should probably be considered a distinct population with important metabolomic features. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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19 pages, 719 KiB  
Article
Redefining Systemic Sclerosis Classification: Anti-Topoisomerase Antibody as a Superior Predictor of Interstitial Lung Disease and Skin Progression Compared to Limited Cutaneous Systemic Sclerosis Subset
by Chana Chaovanitkul, Tippawan Onchan, Patnarin Pongkulkiat, Ajanee Mahakkanukrauh, Siraphop Suwannaroj and Chingching Foocharoen
Life 2025, 15(7), 1067; https://doi.org/10.3390/life15071067 - 4 Jul 2025
Viewed by 530
Abstract
Background: Currently, no information exists on the clinical course of anti-topoisomerase I antibody (ATA)-positive limited cutaneous systemic sclerosis (lcSSc). We aimed to evaluate the incidence of and time to the development of interstitial lung disease (ILD), pulmonary hypertension (PHT), scleroderma renal crisis (SRC), [...] Read more.
Background: Currently, no information exists on the clinical course of anti-topoisomerase I antibody (ATA)-positive limited cutaneous systemic sclerosis (lcSSc). We aimed to evaluate the incidence of and time to the development of interstitial lung disease (ILD), pulmonary hypertension (PHT), scleroderma renal crisis (SRC), and maximal modified Rodnan skin score (max-mRSS) in patients with lcSSc and dcSSc, with and without ATA. Methods: This cohort study included 522 patients with systemic sclerosis (SSc). The incidence of and time to the development of ILD, PHT, SRC, and max-mRSS were assessed. Results: ATA-positive dcSSc (dcSSc-posATA) was the most common presentation among Thai patients (321 cases; 61.5%). The median time to the development of ILD was shorter than that in lcSSc-posATA, comparable to that in dcSSc-posATA (1.0 vs. 1.8 years, p = 0.21), and shorter than that in ATA-negative dcSSc (dcSSc-negATA) (1.0 vs. 4.8 years, p = 0.001). The time to max-mRSS in lcSSc-posATA was comparable to that in dcSSc-posATA (p = 0.17) but shorter than that in dcSSc-negATA (p < 0.001). Conclusions: Patients with lcSSc-posATA had a similar risk of ILD development and time to reach max-mRSS as those with dcSSc, regardless of the presence of ATA, but had earlier ILD development and max-mRSS compared to those with dcSSc-negATA. Their prognosis appeared to be better than that of dcSSc-posATA. Full article
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14 pages, 990 KiB  
Article
Performance of Ultra-High-Frequency Ultrasound in the Evaluation of Skin Involvement in Systemic Sclerosis: A Cross-Sectional Pilot Study
by Olga Barbara Krammer, Martin Fleck, Boris Ehrenstein, Wolfgang Hartung and Florian Günther
Diagnostics 2025, 15(13), 1600; https://doi.org/10.3390/diagnostics15131600 - 24 Jun 2025
Viewed by 474
Abstract
Objective: The aim of this study was to assess the performance and feasibility of ultra-high-frequency ultrasound (UHF-US) in clinical practice for measuring skin thickness in patients with systemic sclerosis (SSc) compared to age- and sex-matched controls. Materials and Methods: A total [...] Read more.
Objective: The aim of this study was to assess the performance and feasibility of ultra-high-frequency ultrasound (UHF-US) in clinical practice for measuring skin thickness in patients with systemic sclerosis (SSc) compared to age- and sex-matched controls. Materials and Methods: A total of 14 patients with SSc and 14 healthy controls (HCs) were enrolled in the study. All subjects underwent US evaluation of the epidermis, dermis and cutis by three experts in the 17 sites of the modified Rodnan skin score (mRSS). All the sonographers were blinded to the mRSS, which was assessed by an experienced rheumatologist who was not involved in, and blinded to, the US assessment. Results: In comparison to HCs, dermal thickness was significantly higher in patients at six sites: the right (p < 0.001) and left (p = 0.001) finger; right (p = 0.027) and left (p = 0.048) hand; left foot (p = 0.010) and face (p < 0.001). The epidermal layer did not differ significantly. At all mRSS sites except for the chest, there were moderate to strong positive correlations between US-assessed dermal thickness and local mRSS. The interobserver reliability for all sites of the mRSS, with the exception of the face, was good to excellent (with an intraclass correlation coefficient [ICC] ranging from 0.724 to 0.939). Conclusions: These data support the use of UHF-US as an objective and reliable tool for the assessment of skin involvement in patients with SSc. Considering its feasibility in clinical practice, we suggest that US assessment of skin in patients with SSc should be restricted to the dermal layer of the fingers and hands, since they are the sites that skin fibrosis typically starts from. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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14 pages, 1022 KiB  
Systematic Review
Efficacy of Mycophenolate Mofetil in Treating Skin Fibrosis in Systemic Sclerosis: A Systematic Review and Meta-Analysis
by Ryuichi Ohta, Yuta Horinishi, Chiaki Sano and Kunihiro Ichinose
J. Clin. Med. 2025, 14(12), 4187; https://doi.org/10.3390/jcm14124187 - 12 Jun 2025
Viewed by 877
Abstract
Background/Objectives: Systemic sclerosis (SSc) is a progressive autoimmune disease characterized by widespread fibrosis, including skin thickening. Mycophenolate mofetil (MMF) is commonly used in SSc-associated interstitial lung disease, but its efficacy in improving skin fibrosis has not been systematically evaluated. This study aimed [...] Read more.
Background/Objectives: Systemic sclerosis (SSc) is a progressive autoimmune disease characterized by widespread fibrosis, including skin thickening. Mycophenolate mofetil (MMF) is commonly used in SSc-associated interstitial lung disease, but its efficacy in improving skin fibrosis has not been systematically evaluated. This study aimed to assess the therapeutic effect of MMF on cutaneous sclerosis in SSc, as measured by the modified Rodnan skin score (mRSS). Methods: A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. PubMed, Embase, and Web of Science were searched from January 2000 to March 2025. Studies reporting mRSS outcomes in SSc patients treated with MMF were included, provided that the effect of MMF could be separately evaluated when used alongside other therapies. Risk of bias was assessed using the Cochrane RoB 2.0 tool for randomized controlled trials and the ROBINS-I tool for non-randomized studies. A random-effects model was used to estimate the pooled mean change in mRSS. Heterogeneity and publication bias were evaluated. Results: Eight studies involving 569 patients were included. The pooled mean reduction in mRSS following MMF treatment was −5.82 (95% CI: −7.46 to −4.19), exceeding the minimal clinically important difference. Heterogeneity across studies was substantial (I2 = 82.6%). A post hoc exploratory subgroup analysis suggested greater improvement in early disease (<2 years), though this finding requires confirmation in prospective studies. MMF was generally well tolerated, with low discontinuation rates due to adverse events. Conclusions: MMF is associated with a statistically and clinically significant improvement in skin fibrosis in patients with SSc. These findings support its use as a frontline therapy for progressive cutaneous involvement, although further prospective studies are needed to identify optimal candidates for treatment. Full article
(This article belongs to the Section Dermatology)
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11 pages, 1441 KiB  
Article
Serum Calprotectin as a Novel Biomarker of Disease Severity and Activity in Systemic Sclerosis Patients
by Chiara Pellicano, Annalisa Villa, Valeria Carnazzo, Giancarlo D’Ippolito, Ilaria Vinante, Federica Laterza, Umberto Basile, Edoardo Rosato and Antonietta Gigante
Int. J. Mol. Sci. 2025, 26(9), 4290; https://doi.org/10.3390/ijms26094290 - 1 May 2025
Viewed by 532
Abstract
A monocentric cross-sectional study was performed to investigate the role of serum calprotectin as a biomarker for disease severity and activity in systemic sclerosis (SSc). Serum calprotectin was measured in 74 consecutive SSc patients admitted to a tertiary hospital in Rome, and in [...] Read more.
A monocentric cross-sectional study was performed to investigate the role of serum calprotectin as a biomarker for disease severity and activity in systemic sclerosis (SSc). Serum calprotectin was measured in 74 consecutive SSc patients admitted to a tertiary hospital in Rome, and in 50 healthy controls (HCs) who were healthcare workers, using Aptiva’s particle-based multianalyte technology. In SSc patients, a statistically significant correlation was found between calprotectin and the modified Rodnan skin score (mRSS) (r = 0.402, p < 0.001), disease activity index (DAI) (r = 0.420, p < 0.001), disease severity scale (DSS) (r = 0.365, p < 0.01), forced vital capacity (FVC) (r = −0.459, p < 0.001), and diffusion lung capacity for carbon monoxide (DLco) (r = −0.445, p < 0.001). Calprotectin was higher in SSc patients with digital ulcers (DUs) than in SSc patients without DUs [2.98 mcg/mL (IQR 2.07;4.29) vs. 2.08 mcg/mL (IQR 1.71;2.45), p < 0.01] and in SSc patients with interstitial lung disease (ILD) compared to SSc patients without ILD [2.56 mcg/mL (IQR 1.94;3.03) vs. 1.96 mcg/mL (IQR 1.7;2.35), p < 0.01]. The multivariable stepwise logistic regression analysis showed calprotectin to be independently associated with DUs [OR 2.531 (CI 95%: 1.074;5.961), p < 0.05] and ILD [OR 3.687 (CI 95%: 1.336;10.170), p < 0.05] in SSc patients. Serum calprotectin is associated with DUs and ILD in SSc patients. Full article
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12 pages, 1842 KiB  
Article
A 23-Plex Cytokine/Chemokine Analysis Identifies TNFRII, MMP-8, and sIL-1RII as Potential Biomarkers for Systemic Sclerosis
by Carlo Perricone, Giacomo Cafaro, Roberto dal Pozzolo, Lorenza Bruno, Nicole Sasso, Roberta Cecchetti, Matteo Antonucci, Fabiana Topini, Onelia Bistoni, Patrizia Mecocci, Roberto Gerli and Elena Bartoloni
Biomedicines 2025, 13(4), 967; https://doi.org/10.3390/biomedicines13040967 - 16 Apr 2025
Viewed by 494
Abstract
Background: Reliable biomarkers are urgently needed to aid in the differential diagnosis, prognosis, disease progression monitoring, and prediction of therapeutic response in patients with systemic sclerosis (SSc). This study aimed to evaluate a panel of potentially pathogenic circulating cytokines and chemokines in a [...] Read more.
Background: Reliable biomarkers are urgently needed to aid in the differential diagnosis, prognosis, disease progression monitoring, and prediction of therapeutic response in patients with systemic sclerosis (SSc). This study aimed to evaluate a panel of potentially pathogenic circulating cytokines and chemokines in a cohort of SSc patients. Methods: Serum samples were obtained from 35 SSc patients and 40 age- and sex-matched healthy controls. Twenty-three cytokines/chemokines were quantified using a Luminex® multiplex immunoassay (BioRad-BioPlex 200 System-Lumine x-Map technology R&D Systems, USA) following the manufacturer’s instructions and customized procedures. Data were acquired using Bioplex manager v 6.1. Data analysis was performed using GraphPad Prism v.8 (GraphPad Software, Inc.), with significance defined as p ≤ 0.05. V.8 Results: Levels of TNFRII and MMP-8 were significantly higher in SSc patients compared to healthy controls, while IL-1RII levels were significantly elevated in healthy individuals (p < 0.001 for all comparisons). Patients with elevated ESR at baseline (>30 mm/h) showed higher IL-15 levels (p = 0.019). A strong positive correlation was found between MCP-1 and the modified Rodnan skin score (mRSS) (p = 0.009, r = 0.740), and a moderate correlation between TNFRII and diffusing capacity for carbon monoxide (p = 0.046, r = 0.339). PLS regression identified MMP-8, MCP-1, TNFRII, IL-15, and IL-1RII as key predictors of SSc, with MMP-8 having the strongest influence. The logistic regression model showed high performance (AUC = 0.93, accuracy = 87.5%). Conclusions: TNFRII, MMP-8, and IL-1RII may play a pathogenic role in SSc. TNFRII, in particular, may serve as a biomarker for pulmonary involvement, aligning with its known role in pro-fibrotic pathways. These findings support their utility in diagnosis and disease profiling. Full article
(This article belongs to the Section Cell Biology and Pathology)
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12 pages, 241 KiB  
Article
Correlation Between the Peak of Skin Thickness Progression Rate and Onset of Cardiopulmonary Involvement in Thai Systemic Sclerosis Patients
by Piyanart Rujirawinitchai, Chingching Foocharoen, Ajanee Mahakkanukrauh, Siraphop Suwannaroj, Patnarin Pongkulkiat and Tippawan Onchan
J. Clin. Med. 2025, 14(7), 2281; https://doi.org/10.3390/jcm14072281 - 27 Mar 2025
Viewed by 528
Abstract
Background/Objectives: Rapid skin thickness progression assessed using the modified Rodnan skin score (mRSS) is associated with poor outcomes in systemic sclerosis (SSc). However, the correlation between patterns of skin thickness and the onset of internal organ involvement remains unclear. This study aimed to [...] Read more.
Background/Objectives: Rapid skin thickness progression assessed using the modified Rodnan skin score (mRSS) is associated with poor outcomes in systemic sclerosis (SSc). However, the correlation between patterns of skin thickness and the onset of internal organ involvement remains unclear. This study aimed to determine the correlation between peak skin thickness progression rate (pSTPR) and the onset of internal organ involvement, particularly interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) among Thai SSc patients. Method: A prospective cohort study with retrospective analysis was conducted on adult SSc patients who experienced the onset of their first non-Raynaud phenomenon symptoms between January 2013 and December 2020 and had at least a 2-year follow-up. Patients with an overlap syndrome were excluded from this study. The pSTPR was calculated by dividing the peak of the mRSS by the duration of disease at the peak of the mRSS. Result: A total of 509 patients were included in this study. The majority of cases were female (351; 69.0%) and comprised diffuse cutaneous SSc subsets (353 cases; 69.4%). The respective mean age and median pSTPR was 48.2 ± 11.6 years and 1.63 points/year (interquartile range 0.5–4.4). The respective median durations of disease at the onset of significant ILD (>20% extent), ILD, and mean duration of disease at the onset of PAH were 3.4 (Q1–Q3 1.4–7.7), 5.4 (Q1–Q3 2.4–9.2), and 8.0 ± 4.9 years. pSTPR was negatively correlated with disease duration at the onset of significant ILD (Rho −0.509, p < 0.001), ILD (Rho −0.480, p < 0.001), PAH (Rho −0.372, p = 0.03), and disease duration from onset to death (Rho −0.367, p = 0.03) after adjusting for age, sex, and anti-topoisomerase I. Conclusion: SSc patients with a high skin thickness progression rate reaching the maximum point of mRSS were at risk of developing early ILD, PAH, and death. The pSTPR may be used to assess individuals at risk of experiencing early onset cardiopulmonary involvement in SSc. Full article
(This article belongs to the Section Immunology)
13 pages, 259 KiB  
Article
Associations Between Soluble Cell Adhesion Molecules and Cardiovascular Comorbidities in Systemic Sclerosis: Implications for Insulin Resistance
by Iván Ferraz-Amaro, Zeina Ibrahim-Achi, Antonia de Vera-González, Alejandra González-Delgado, Mónica Renuncio-García, Esther F. Vicente-Rabaneda, J. Gonzalo Ocejo-Vinyals, Santos Castañeda and Miguel Á. González-Gay
J. Clin. Med. 2025, 14(5), 1467; https://doi.org/10.3390/jcm14051467 - 22 Feb 2025
Cited by 1 | Viewed by 696
Abstract
Background: Soluble cell adhesion molecules such as sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), and P-selectin have been implicated in cardiovascular disease pathogenesis in the general population. Cardiovascular disease is prevalent among patients with systemic sclerosis (SSc). This [...] Read more.
Background: Soluble cell adhesion molecules such as sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), and P-selectin have been implicated in cardiovascular disease pathogenesis in the general population. Cardiovascular disease is prevalent among patients with systemic sclerosis (SSc). This study aims to investigate potential associations between the serum levels of these adhesion molecules and specific cardiovascular comorbidities in SSc patients. Methods: This cross-sectional study encompassed 81 individuals with SSc. All SSc patients underwent a complete clinical evaluation. Serum sICAM-1, sVCAM-1, and P-selectin levels, lipid profiles and insulin resistance indices, and carotid ultrasound were assessed. Multivariable linear regression analyses were employed to investigate potential associations between adhesion molecule levels (sICAM, sVCAM, and P-selectin) and both SSc-specific manifestations and cardiometabolic parameters. Results: The associations of disease-related parameters with sICAM-1, sVCAM-1, and P-selectin levels were limited. Notably, only the modified Rodnan skin score exhibited a significant positive association with sVCAM-1 levels, while no such associations were observed for sICAM-1 and P-selectin. Regarding cardiovascular disease-related data, sVCAM-1 significantly correlated with higher values of insulin resistance and beta-cell function indices. In the case of P-selectin, although a trend was observed, statistical significance was not reached. Conclusions: In patients with SSc, serum values of sVCAM-1 independently correlate with insulin resistance. The assessment of CAMs in patients with SSc could serve as a valuable clinical tool for identifying individuals with increased insulin resistance and a higher risk of cardiovascular disease. Full article
12 pages, 665 KiB  
Article
Retinal Vascular Abnormalities and Clinical Parameters in Systemic Sclerosis
by Rosario Foti, Marco Zeppieri, Roberta Foti, Elisa Visalli, Giorgio Amato, Roberta Amato, Edoardo Dammino, Fabiana D’Esposito and Caterina Gagliano
J. Clin. Med. 2024, 13(10), 2738; https://doi.org/10.3390/jcm13102738 - 7 May 2024
Cited by 6 | Viewed by 1573
Abstract
Background: Systemic sclerosis is a complex autoimmune disease characterized by vasculopathy, fibrosis, and immune dysregulation. Ocular manifestations in these patients are increasingly recognized, suggesting potential correlations between systemic vascular abnormalities and ocular microvascular changes. Advancements in molecular immunology and imaging technology using [...] Read more.
Background: Systemic sclerosis is a complex autoimmune disease characterized by vasculopathy, fibrosis, and immune dysregulation. Ocular manifestations in these patients are increasingly recognized, suggesting potential correlations between systemic vascular abnormalities and ocular microvascular changes. Advancements in molecular immunology and imaging technology using ocular coherence tomography (OCT) have unveiled intricate pathways underlying possible disease pathogenesis. Understanding the interplay between retinal vascular abnormalities and molecular immunology parameters could provide insights into disease mechanisms and potential biomarkers. Purpose: The aim of this study was to investigate vascular abnormalities, detected with optical coherence tomography angiography (OCT-A), in systemic sclerosis patients and to find correlations between the severity of the disease detected with molecular immunology findings and OCT-A parameters. Methods: A group of 32 systemic sclerosis patients were compared with 9 healthy controls. Ganglion cell complex thickness (GCC), retina thickness of the fovea and parafovea, nerve fiber layer thickness (RNFL) and cup/disc area ratio were investigated using OCT. Vessel density (VD) of the superficial (SCP) and deep capillary plexus (DCP) of the whole macular area and ETDRS grid, size of the foveal avascular zone (FAZ) and vessel density of the radial peripapillary capillary plexus (RPCP) were evaluated using OCT-A. Modified Rodnan skin score (mRSS), capillaroscopy and disease duration were used to stage disease severity. Results: There was a statistically significant reduction in retina thickness of the fovea and parafovea, VD of the whole DCP, VD of the SCP and DCP in ETDRS grid in the patient group compared to controls (p < 0.001). The patients presented a significant enlargement of the FAZ (p 0.005). No significant correlation between OCT and OCT-A parameters and disease severity scores was found. Conclusions: OCT-A could represent a non-invasive tool to detect retinal microvascular damage in systemic sclerosis. Full article
(This article belongs to the Special Issue New Clinical Treatment for Ocular Vascular Disease and Fundus Disease)
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12 pages, 1712 KiB  
Article
Treatment of Scleroderma-Related Microstomia Using Hyaluronic Acid: An Interventional Study
by Ofir Shir-az, Ariel Berl, Din Mann, Biader Samih Bilal, Yair Levy and Avshalom Shalom
Life 2023, 13(11), 2176; https://doi.org/10.3390/life13112176 - 7 Nov 2023
Cited by 3 | Viewed by 2963
Abstract
Systemic sclerosis (SSc) or scleroderma is a rare, systemic, autoimmune connective tissue disease. It causes increased collagen synthesis, leading to multi-organ sclerosis, including the skin and joints. Patients’ overall health and quality of life are harmed dramatically. Involvement of the face and, especially, [...] Read more.
Systemic sclerosis (SSc) or scleroderma is a rare, systemic, autoimmune connective tissue disease. It causes increased collagen synthesis, leading to multi-organ sclerosis, including the skin and joints. Patients’ overall health and quality of life are harmed dramatically. Involvement of the face and, especially, the oral opening can limit patients’ ability to speak and eat, oral hygiene, and cosmetic appearance. Profhilo® (NAHYCO®) is an over-the-counter product consisting of pure hyaluronic acid. It is used to improve skin quality by increasing collagen production and adipocyte vitality. This interventional study evaluated the results of perioral injections of hyaluronic acid in terms of improved skin quality, elasticity, and increased oral opening. Patients diagnosed with SSc received an injection of one syringe of Profhilo® (2 mL of hyaluronic acid) at each of two clinic visits at one-month intervals. The oral opening was measured between the upper and lower central incisors before and after treatment. Quality of life was assessed using the modified Rodnan Skin Score and Health Assessment Questionnaire-Disability Index. A total of 14 patients received the first treatment, and 11 received the second treatment. The mean oral opening increased from 31.6 mm (range 17–50 mm) prior to therapy to 35.8 mm (range 21–56) 2 months following the second injection. Statistical analysis showed that there was a significant increase in the oral opening as observed one week (36.2 mm, p = 0.011), one month (36.2 mm, p = 0.007), and three months (31.6 mm, p = 0.023) after the second injection, at the 5-month follow-up. Treatment of SSc patients’ perioral area with Profhilo® can result in significant improvements in oral opening and quality of life. Full article
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12 pages, 621 KiB  
Article
Ultrasonic Evaluation of Diaphragm in Patients with Systemic Sclerosis
by Anja Ljilja Posavec, Stela Hrkač, Josip Tečer, Renata Huzjan Korunić, Boris Karanović, Ivana Ježić, Ivan Škopljanac, Nevenka Piskač Živković and Joško Mitrović
J. Pers. Med. 2023, 13(10), 1441; https://doi.org/10.3390/jpm13101441 - 27 Sep 2023
Cited by 1 | Viewed by 2323
Abstract
The diaphragm is the most important muscle in respiration. Nevertheless, its function is rarely evaluated. Patients with systemic sclerosis (SSc) could be at risk of diaphragmatic dysfunction because of multiple factors. These patients often develop interstitial lung disease (SSc-ILD) and earlier studies have [...] Read more.
The diaphragm is the most important muscle in respiration. Nevertheless, its function is rarely evaluated. Patients with systemic sclerosis (SSc) could be at risk of diaphragmatic dysfunction because of multiple factors. These patients often develop interstitial lung disease (SSc-ILD) and earlier studies have indicated that patients with different ILDs have decreased diaphragmatic mobility on ultrasound (US). This study aimed to evaluate diaphragmatic function in SSc patients using US with regard to the ILD, evaluated with the Warrick score on high-resolution computed tomography (HRCT), and to investigate associations between ultrasonic parameters and dyspnea, lung function, and other important clinical parameters. In this cross-sectional study, we analyzed diaphragm mobility, thickness, lung function, HRCT findings, Modified Medical Research Council (mMRC) dyspnea scale, modified Rodnan skin score (mRSS), autoantibodies, and esophageal diameters on HRCT in patients with SSc. Fifty patients were enrolled in the study. Patients with SSc-ILD had lower diaphragmatic mobility in deep breathing than patients without ILD. The results demonstrated negative correlations between diaphragmatic mobility and mMRC, mRSS, anti-Scl-70 antibodies, esophageal diameters on HRCT, and a positive correlation with lung function. Patients with SSc who experience dyspnea should be evaluated for diaphragmatic dysfunction for accurate symptom phenotyping and personalized pulmonary rehabilitation treatment. Full article
(This article belongs to the Special Issue Novel Challenges and Advances in Diseases of the Respiratory System)
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14 pages, 2917 KiB  
Article
Impaired Regulation by IL-35 in Systemic Sclerosis
by Rubén Osuna-Gómez, Ivan Castellví, Maria Mulet, Mª Àngels Ortiz, Douglas E. Brough, Helen Sabzevari, Roshanak T. Semnani and Silvia Vidal
Int. J. Mol. Sci. 2023, 24(13), 10567; https://doi.org/10.3390/ijms241310567 - 24 Jun 2023
Cited by 4 | Viewed by 1798
Abstract
This study investigated the role of IL-35 in systemic sclerosis (SSc) patients, focusing on CD4+ T cell response and immunomodulatory cytokine production. By comparing the cytokine levels in healthy donors (HD) and SSc patients using ELISAs, we found a significantly lower plasma IL-35 [...] Read more.
This study investigated the role of IL-35 in systemic sclerosis (SSc) patients, focusing on CD4+ T cell response and immunomodulatory cytokine production. By comparing the cytokine levels in healthy donors (HD) and SSc patients using ELISAs, we found a significantly lower plasma IL-35 concentration in the SSc patients (52.1 ± 5.6 vs. 143 ± 11.1, p < 0.001). Notably, the IL-35 levels showed a negative correlation with TGF-β (p < 0.001) and IL-17 (p = 0.04). Assessing the IL-35R expression across cell types in the SSc patients and HDs via flow cytometry, we found higher levels on monocytes (40.7 + 5.7 vs. 20.3 ± 1.9, p < 0.001) and lower levels on CD8+ T cells (61.8 ± 9.2 vs. 83.4 ± 0.8, p < 0.05) in the SSc patients. The addition of recombinant IL-35 to stimulated peripheral blood mononuclear cells reduced the IL-17+CD4+ T cell percentage (9.0 ± 1.5 vs. 4.8 ± 0.7, p < 0.05) and increased the IL-35+CD4+ T percentage (4.1 ± 2.3 vs. 10.2 ± 0.8, p < 0.001). In a Treg:Tresponder cell Sco-culture assay with HD and SSc samples, rIL35 decreased the cell proliferation and levels of IL-17A (178.2 ± 30.5 pg/mL vs. 37.4 ± 6.4 pg/mL, p < 0.001) and TGF-β (4194 ± 777 pg/mL vs. 2413 ± 608 pg/mL, p < 0.01). Furthermore, we observed a positive correlation between the modified Rodnan skin score (mRSS) and TGF-β (p < 0.001), while there was a negative correlation between mRSS and IL-35 (p = 0.004). Interestingly, higher levels of plasmatic IL-35 were detected in individuals with limited disease compared to those with diffuse disease (60.1 ± 8.0 vs. 832.3 ± 4.1, p < 0.05). These findings suggest that IL-35 exhibits anti-inflammatory properties in SSc and it may serve as a marker for disease severity and a therapeutic target. Full article
(This article belongs to the Special Issue Autoimmune Diseases: A Swing Dance of the Immune Cells)
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21 pages, 3423 KiB  
Article
αvβ3 Integrin as a Link between the Development of Fibrosis and Thyroid Hormones in Systemic Sclerosis
by Maia Yamila Kohon, Mor Zaaroor Levy, Tzipi Hornik-Lurie, Avshalom Shalom, Ariel Berl, Liat Drucker, Yair Levy and Shelly Tartakover Matalon
Int. J. Mol. Sci. 2023, 24(10), 8927; https://doi.org/10.3390/ijms24108927 - 18 May 2023
Cited by 3 | Viewed by 2126
Abstract
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Key players mediating fibrosis are myofibroblasts (MF) that, following transforming growth factor β (TGFβ) exposure, produce a collagen-rich extracellular matrix (ECM) that induces myofibroblast differentiation. Myofibroblasts express [...] Read more.
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Key players mediating fibrosis are myofibroblasts (MF) that, following transforming growth factor β (TGFβ) exposure, produce a collagen-rich extracellular matrix (ECM) that induces myofibroblast differentiation. Myofibroblasts express αvβ3 integrin (a membrane receptor for thyroid hormones) and miRNA-21 that promotes deiodinase-type-3 expression (D3), causing the degradation of triiodothyronine (T3) that attenuates fibrosis. We hypothesized that αvβ3 affects the fibrotic processes through its thyroid hormones (THs) binding site. To test this, dermal fibroblasts (DF) were cultured with/without TGFβ and removed with a base, leaving only normal/fibrotic ECMs in wells. Then, DF were cultured on the ECMs with/without tetrac (αvβ3 ligand, T4 antagonist), and evaluated for pro-fibrotic characteristics, αvβ3, miRNA-21, and D3 levels. Blood free-T3 (fT3), miRNA-21 levels, and the modified Rodnan skin score (MRSS) were evaluated in SSc patients. We found that the “fibrotic-ECM” significantly increased the pro-fibrotic characteristics of DF and the levels of miRNA-21, D3, and αvβ3, compared to the “normal-ECM.” Tetrac significantly inhibited the effects of the “fibrotic-ECM” on the cells. In accordance with tetrac’s effect on D3/miRNA-21, a negative correlation was found between the patients’ fT3 to miRNA-21 levels, and to the development of pulmonary arterial hypertension (PAH). We conclude that occupying the THs binding site of αvβ3 may delay the development of fibrosis. Full article
(This article belongs to the Special Issue Autoimmune Diseases: A Swing Dance of the Immune Cells)
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13 pages, 1366 KiB  
Article
Liver Involvement in Patients with Systemic Sclerosis: Role of Transient Elastography in the Assessment of Hepatic Fibrosis and Steatosis
by Giovanna Cuomo, Carlo Iandoli, Raffaele Galiero, Alfredo Caturano, Claudio Di Vico, Danilo Perretta, Pier Vincenzo Adamo, Roberta Ferrara, Luca Rinaldi, Ciro Romano and Ferdinando Carlo Sasso
Diagnostics 2023, 13(10), 1766; https://doi.org/10.3390/diagnostics13101766 - 17 May 2023
Cited by 2 | Viewed by 3968
Abstract
Background Systemic sclerosis (SSc) is a rare, multisystemic disorder of connective tissue characterized by widespread inflammation, vascular abnormalities, and both skin and visceral organ fibrosis. Tissue fibrosis is the final phase of a complex biological process of immune activation and vascular damage. Objectives [...] Read more.
Background Systemic sclerosis (SSc) is a rare, multisystemic disorder of connective tissue characterized by widespread inflammation, vascular abnormalities, and both skin and visceral organ fibrosis. Tissue fibrosis is the final phase of a complex biological process of immune activation and vascular damage. Objectives The aim of the study was to assess hepatic fibrosis and steatosis in SSc patients by transient elastography (TE). Methods Fifty-nine SSc patients fulfilling the 2013 ACR/EULAR classification criteria were recruited. Clinical and laboratory findings, modified Rodnan skin score (mRSS), activity index, videocapillaroscopy, echocardiography, and lung function data were analyzed. Liver stiffness (LS) was measured by transient elastography (TE), with 7 kPa used as the cut-off value for significant liver fibrosis. In addition, hepatic steatosis was evaluated by means of controlled attenuation parameter (CAP) findings. Specifically, CAP values ≥ 238 ≤ 259 dB/m were considered consistent with mild steatosis (S1), values ≥ 260 ≤ 290 dB/m were compatible with moderate steatosis (S2), and values ≥ 291 dB/m were indicative of severe steatosis (S3). Results The median age of patients was 51 years, with a median disease duration of 6 years. The median LS was 4.5 (2.9–8.3) kPa; 69.5% of patients had no evidence of fibrosis (F0); 27.1% displayed LS values between 5.2 and 7 kPa; and only 3.4% of patients had LS values > 7 kPa (F3). The median CAP value for liver steatosis was 223 dB/m (IQR: 164–343). Overall, 66.1% of patients did not show evidence of steatosis (CAP values < 238 dB/m); 15.2% showed values consistent with mild (S1) steatosis (CAP value ≥ 238 ≤ 259 dB/m); 13.5% had moderate (S2) steatosis (CAP value ≥ 260 ≤ 290 dB/m); and 5.1% were deemed to have severe steatosis (S3) due to CAP values ≥ 291 dB/m. Conclusions Although systemic sclerosis is associated with fibrosis of the skin and several organs, only 3.4% of our patient population showed evidence of marked liver fibrosis, which is the same prevalence as that expected in the general population. Therefore, fibrosis of the liver did not appear to be a significant concern in SSc patients, albeit moderate fibrosis could still be detected in a significant proportion of subjects. A prolonged follow-up may clarify whether liver fibrosis in SSc patients may still progress. Likewise, the prevalence of significant steatosis was low (5.1%) and depended on the same variables associated with fatty liver disease in the general population. TE was shown to be an easy and valuable method for detection and screening of hepatic fibrosis in SSc patients with no additional risk factors for liver disease and may be useful to assess the potential progression of liver fibrosis over time. Full article
(This article belongs to the Special Issue Advances in Identification and Management of Systemic Sclerosis)
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