Autoimmune Connective Tissue Disease Research Articles

Exosomal miR-126-3p: Potential protection against vascular damage by regulating the SLC7A5/mTOR Signalling pathway in human umbilical vein endothelial cells.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Vascular damage is one of the important features of SSc, which affects the progression and prognosis of the disease. MiR-126-3p is an important microRNA (miRNA) that regulates vascular structure and function, which can be transported through exosomes. However, the role of miR-126-3p in vascular damage in SSc is still unclear. Therefore, we focused on the connection between miR-126-3p and vascular damage in SSc, as well as investigated the potential role of miR-126-3p in vascular damage in SSc. First, this study successfully extracted extracellular vesicles from clinical plasma samples and characterized the exosomes within them. Then, we predicted and screened the target pathway mammalian/mechanistic target of rapamycin (mTOR) and the target gene SLC7A5 of miR-126-3p through online databases. Next, we constructed SSc mice for invivo studies. The results showed that the expression of miR-126-3p was decreased in the plasma exosomes, while the SLC7A5 expression, autophagy, and lipid peroxidation were increased in the aorta. Luciferase reporter gene assays demonstrated that miR-126-3p can bind to SLC7A5, resulting in a decrease in its expression. Invitro experiments have shown that exosomal miR-126-3p can be internalized by human umbilical vein endothelial cells (HUVECs). The miR-126-3p group exhibited enhanced cell viability and tube formation ability, along with increased expression of the vascular formation marker CD31. Additionally, miR-126-3p downregulated the protein expression of SLC7A5 and LC3 in HUVECs, while upregulating the protein expression of mTOR, P62, PPARγ, and CPT-1. However, the effects of miR-126-3p on HUVECs were counteracted by mTOR inhibitors and enhanced by mTOR activators. The results indicated that exosomal miR-126-3p has the potential to protect against vascular injury in SSc by regulating the SLC7A5/mTOR signalling pathway in HUVECs.

Right ventricular-pulmonary arterial coupling ratio derived from 3-dimensional echocardiography predicts outcomes in systemic lupus erythematosus-associated pulmonary arterial hypertension patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune connective tissue disease (CTD) that is an important cause of devastating pulmonary arterial hypertension (PAH), and persistent progression of PAH can lead to right heart failure, predicting a poor prognosis for SLE patients. Right ventricular-pulmonary arterial (RV-PA) coupling with echocardiography has been demonstrated to be a noninvasive alternative method for evaluating PAH patients' predictive outcomes. Whether the ratio of right ventricular stroke volume (RVSV) to right ventricular end-systolic volume (RVESV) measured by three-dimensional echocardiography (3DE) is a new index of RV-PA coupling has not been discussed as a new predictor for the clinical outcome of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). From June 2019 to February 2023, 46 consecutive patients with SLE-PAH were enrolled prospectively, and their clinical data and echocardiographs were studied and analyzed. The control group consisted of 30 healthy subjects matched for age, sex, and body surface area (BSA). The main endpoints of this study were a composite of all-cause mortality and adverse clinical events. Baseline clinical characteristics and echocardiographic assessments were analyzed. During a median of 24months (IQR 18-31), 16 of 46 SLE-PAH patients (34.7%) experienced endpoint-related events. At baseline, patients who experienced mortality or adverse events had a worse WHO functional class (WHO FC) and lower anti-double-stranded DNA (dsDNA) antibody levels. The right ventricular (RV) systolic dysfunction in SLE-PAH subjects was significantly worse than that in the healthy control group, especially in SLE-PAH patients in the endpoint event group. Compared to controls, patients with SLE-PAH had a lower RVSV/RVESV ratio. In the group comparison, patients who had experienced an endpoint event had a sequentially worse ratio (1.86 (1.65-2.3) versus 1.30 (1.09-1.46) versus 0.64 (0.59-0.67), p < .001). There were statistically significant associations between the RVSV/RVESV ratio to routine RV systolic function and clinical parameters. The RVSV/RVESV ratio was negatively correlated with the WHO FC (r = -0.621, p < .001) and positively correlated with the anti-dsDNA level. The ROC curve showed that the optimal cutoff for RVSV/RVESV < 0.712 determined a higher risk of poor prognosis. Kaplan‒Meier survival curves showed that an RVSV/RVESV ratio >0.712 was associated with more favorable long-term outcomes. The 3DE-derived SV/ESV ratio as a noninvasive alternative surrogate of RV-PA coupling was an eximious indicator for identifying endpoint events in SLE-PAH patients and can provide a diagnostic basis for clinical intervention.

Updates in Dermatomyositis: Newer Treatment Options and Outcome Measures From Dermatologic Perspectives.

Dermatomyositis (DM) is a rare autoimmune connective tissue disease with characteristic skin manifestations and possible muscle involvement. Recent advances in classification system to include skin-predominant subtypes, understanding underlying pathogenic mechanisms and the relationship between clinical phenotypes and myositis-specific autoantibodies have led to development of novel therapeutic options. This corresponds with efforts to develop better outcome measures to accurately catch the patients' current disease status and treatment-induced improvements. This report will review the updates in newer treatments and outcome measures of DM, specifically from a dermatologic point of view.

Systemic Sclerosis in Males-Deciphering the Enigma of Erasmus Syndrome.

Systemic sclerosis is an autoimmune connective tissue disease characterized by fibrosis in skin and internal organs. Chronic exposure to silica may not only lead to silicosis of lungs but also systemic sclerosis. Systemic sclerosis is relatively commoner in females; however, occupational exposure to silica in males makes them vulnerable to silica--associated systemic sclerosis (Erasmus syndrome). To describe the clinico-epidemiological aspects of systemic sclerosis in males in a retrospective cohort study. The data were analysed retrospectively for demographic profile and clinical characteristics including examination findings, laboratory investigations, and treatments of all male patients diagnosed with systemic sclerosis with or without silica exposure, managed from January 2018 to December 2021. Eight out of twelve patients were having silica exposure in the form of stone cutting, cement exposure, and working with concrete. The average age was 55 ± 10.72 years with average smoking exposure of around 24.4 ± 12.8 pack years. Skin thickening was reported by all patients with an average modified Rodnan score of 18.33/51 in diffuse and 7/51 in limited cutaneous systemic sclerosis. Raynaud's phenomenon and sclerodactyly were universal findings, while 9 (75%) patients had digital pitted scars. Antinuclear antibodies were present in all patients and specific antibodies substantiated the clinical assessment in almost all patients. Interstitial lung disease was the most common systemic finding present in 11 (91%) patients and tuberculosis was diagnosed in 2 (25%) cases with silica exposure. Gastrointestinal and cardiac system involvement was seen in 5 (41.6%) and 4 (33.3%) patients, respectively. Systemic sclerosis in males against the gender predilection indicates the role of occupational exposure. Silicosis and systemic sclerosis synergistically add to lung damage, and at the same time, these patients are more prone to infections like tuberculosis.

Manifestations of systemic connective tissue diseases on the oral mucosa: a literature review

Annotation. Despite the modern high level of medical care, autoimmune connective tissue diseases cause a lot of questions among scientists and are a significant problem for society. At the same time, in the scientific works available today, little attention is paid to the manifestations of connective tissue diseases in the oral cavity and modern diagnostics of the main types of dental pathology in such patients, which would have great scientific and practical importance. Therefore, the purpose of the review article was to perform an analysis of the scientific literature regarding orofacial manifestations of autoimmune connective tissue diseases. When using the following databases: PubMed, Google Scholar, Scopus, Web of Science and various combinations of keywords and subject headings of MESH such as “oral manifestations”, “oral mucosal lesions”, “autoimmune diseases”, “rheumatic diseases”, “connective tissue diseases”, “systemic lupus erythematosus”, “rheumatoid arthritis”, “systemic sclerosis”, “Sjögren’s syndrome”, “dermatomyositis”, 40 articles were chosen, which corresponded to the purpose of the study. The search results indicate that there is a direct correlation between the duration of the main disease and the severity of oral symptoms. Pronounced hyposalivation and dryness of oral mucosa are the most similar common signs of autoimmune diseases, which contributes to functional disorders and diseases of oral cavity. Oral manifestations are quite often a side effect of the treatment of connective tissue diseases. The pathology of oral mucosa in autoimmune diseases remains not well-understood, so makes it difficult to clarify its pathogenesis in detail, that would allow for the development of justified measures of prevention and treatment.

Electrocardiographic Findings in Systemic Sclerosis

Abstract Systemic sclerosis (SSc) is an autoimmune connective tissue disease which affects various tissues and organs, including skin, lungs, kidneys, gastrointestinal tract and cardiovascular system. Cardiac involvement is the most commonly recognized problem and a significant cause of morbidity. Abnormal ECG is present in 25-75% of patients with SSc and is considered to be an independent redictor of mortality. It is known that the supraventricular arrhythmias are considered as more common in SSc patients, occurring in about two-thirds of the cases, and more often than ventricular tachyarrhythmias. It has been established that right bundle branch block is associated with an increased risk of mortality and that it is an independent predictor of mortality, and should be considered as a marker of the severity of the disease in SSc. The prolonged QTc interval is an independent risk factor for a sudden cardiac death reflecting the instability of repolarization and predisposing the onset of cardiac arrhythmias.The prognosis of the disease depends on the SSc subtype and the involvement of internal organs. SSc is a lifelong disease and cannot be cured, but knowing that cardiac dysfunction significantly worsens the prognosis, early detection of cardiac complications and appropriate therapy can influence its progress and improve the patients’ quality of life.

Association of vitamin D level with systemic lupus erythematosus: A case-control study

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune connective tissue disease. SLE patients are more prone to vitamin D deficiency because of their light sensitivity, renal involvement, and prolonged steroid use. This current study aimed to determine the relationship between vitamin D deficiency and SLE. Methods: In this case-control study, 50 SLE patients (cases) and 50 healthy people (controls) were recruited. The reference value of vitamin D is as follows: normal ≥ 30 ng/ml, deficient ≤ 20 ng/ml, and insufficient 21–29 ng/ml. Results: The mean (standard deviation) of vitamin D levels in SLE patients was 19.5 (5.3) ng/mL, which was significantly lower than those in healthy controls, 27.3 (10.0) ng/mL (P&lt;0.001). The healthy controls had a higher proportion of people with normal vitamin D levels (≥ 30 ng/ml). We noticed a moderate negative correlation between vitamin D levels and fatigability, while a moderate positive correlation was seen with hemoglobin levels and the duration of sun exposure. However, in multiple logistic regression analysis, all the associations mentioned above disappeared. Conclusion: Although vitamin deficiency was found to be associated with SLE, its relationship disappears when the confounding by other variables is considered in the analysis.

Prevalence and risk factors of left ventricular diastolic dysfunction in systemic sclerosis patients: insights from new echocardiographic parameters

Abstract Background Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by excessive extracellular matrix deposition and fibrosis that can affect the skin, blood vessels, and internal organs, including the heart. Primary heart involvement in SSc refers to the presence of cardiac fibrosis, inflammation, and dysfunction in the absence of pulmonary hypertension (PH). Although PH is usually considered the major risk factor for death in SSc patients, diastolic dysfunction has been proposed as an independent predictor of mortality, which may be more robust than PH. Purpose Early identification and management of heart complications in SSc patients are crucial to prevent further deterioration and improve treatment outcomes. However, myocardial damage caused by SSc is often poorly understood, and the long-term effects and prognosis remain unknown. Methods We conducted a cross-sectional study of 69 patients (p) with SSc diagnosis evaluated between February 2022 and February 2023. We analyzed the prevalence of left ventricular diastolic dysfunction (LVDD) as recommended by the 2016 ASE/EACVI guidelines. We compared the presence of risk factors associated with LVDD and its association with other echocardiographic findings. Of the 69p, 24 (34.8%) had LVDD, 41 (59.4%) had normal diastolic function, and 4 (5.8%) had undetermined diastolic dysfunction. Older age (mean age 69.7 ± 11.2 vs 57 ± 12.8; p &amp;lt; 0.01), arterial hypertension (50% vs 22%; p = 0.02), higher body mass index (28.3 ± 8 vs 24.6 ± 4.5; p = 0.02), and higher NTproBNP levels (131 [64-403] vs 97 [45-163]; p = 0.047) were significantly associated with LVDD. The absence of antitopoisomerase (scl70 0% vs 22.2%; p = 0.021) and the presence of anticentromere (CENP-A 81% vs 55.6%; p = 0.05) and (CENP-B 85.7% vs 55.6%; p = 0.02) antibodies were also significantly associated with LVDD. Additionally, classical parameters of ventricular function, such as left ventricular ejection fraction (LVEF 63.5 ± 4.2 vs 63.4 ± 3.7; p = 0.9) or tricuspid annular plane systolic excursion (TAPSE 20.6 ± 2.3mm vs 21.2 ± 2.4mm; p = 0.32), were not associated with LVDD. However, impairment of the right ventricular free wall strain (-23.8 ± 4 vs -27 ± 2.8; p = 0.017), and lower left atrial strain reservoir function (27.7 ± 10 vs 38.4 ± 12.7; p = 0.05) were significantly associated with LVDD. Conclusion LVDD is highly prevalent in patients with systemic sclerosis, particularly in elderly patients with a higher body mass index and those affected by arterial hypertension. These patientes have higher values of NTproBNP. Futhermore, antitopoisomerases antibodies are less likely to be expressed and anticetromere antibodies are more likely to be expressed . These findings highlight the importance of regular cardiovascular monitoring in SSc patients and the potential value of using new echocardiographic parameters to identify those at risk for LVDD.

Treatment of Scleroderma-Related Microstomia Using Hyaluronic Acid: An Interventional Study.

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.

Scleroderma: Difficulties in classification, diagnosis, treatment

Localized scleroderma (LoS) is an autoimmune connective tissue disease with a variety of clinical manifestations. The dermatologist faces the difficulties of establishing a diagnosis and choosing the most appropriate therapy due to the relatively rare prevalence. This review article explores the challenges of classification, diagnosis, and treatment, as well as the factors that contribute to their occurrence. The greatest difficulties in diagnosing LoS that affected the prognosis and progression of the illness are: a delay in diagnosis, including early detection; omission of the active stage of LoS; difficulties in differential diagnosis; lack of association with Lyme borreliosis; low diagnostic value of laboratory and histological tests; limited use of sensitive instrumental methods for diagnosis; and monitoring the activity of LoS in a doctor’s practice. The main difficulties in treatment are the delay in starting treatment; the use of therapy methods with low evidence-based effectiveness; the rare prescription of highly effective approaches; the insufficient effectiveness of systemic drugs and phototherapy; difficulties in determining the volume, timing, and regimen of therapy for each subtype of LoS; the difficulty of achieving a remission; dependence of treatment approach on the doctor’s specialization; the lack of targeted drugs with evidence-based effectiveness in LoS; the lack of high-level evidence-based effectiveness and safety of therapy in LoS; difficulties in the correction of complications of Lo S.

Herbal supplement Spirulina stimulates inflammatory cytokine production in patients with dermatomyositis in vitro

Spirulina, an herbal supplement and popular ingredient in health foods, is a potent stimulant of the immune system. Spirulina use is temporally associated with the onset or exacerbation of Dermatomyositis (DM), an autoimmune connective tissue disease that frequently affects the skin and muscle. In this study, we investigated the effect of Spirulina on peripheral blood mononuclear cells (PBMCs) in DM and Healthy Controls (HCs), showing that Spirulina stimulates Interferon β (IFNβ), Tumor necrosis factor α (TNFα), and Interferon γ (IFNγ) production of DM PBMCs primarily via Toll-Like Receptor 4 (TLR4) activation using ELISA (enzyme linked immunosorbent assay) and flow cytometry. We show that classical monocytes and monocyte-derived dendritic cells are stimulated by Spirulina and are activated via TLR4. Skin from patients with Spirulina-associated DM exhibits an inflammatory milieu similar to that of idiopathic DM but with a stronger correlation of TLR4 and IFNγ.

Mixed Connective Tissue Disease as Different Entity: Global Methylation Aspect.

Mixed connective tissue disease (MCTD) is a very rare disorder that belongs in the rare and clinically multifactorial groups of diseases. The pathogenesis of MCTD is still unclear. The best understood epigenetic alteration is DNA methylation whose role is to regulate gene expression. In the literature, there are ever-increasing assumptions that DNA methylation can be one of the possible reasons for the development of Autoimmune Connective Tissue Diseases (ACTDs) such as systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The aim of this study was to define the global DNA methylation changes between MCTD and other ACTDs patients in whole blood samples. The study included 54 MCTD patients, 43 SSc patients, 45 SLE patients, and 43 healthy donors (HC). The global DNA methylation level was measured by ELISA. Although the global DNA methylation was not significantly different between MCTD and control, we observed that hypomethylation distinguishes the MCTD patients from the SSc and SLE patients. The present analysis revealed a statistically significant difference of global methylation between SLE and MCTD (p < 0.001), SLE and HC (p = 0.008), SSc and MCTD (p ≤ 0.001), and SSc and HC (p < 0.001), but neither between MCTD and HC (p = 0.09) nor SSc and SLE (p = 0.08). The highest % of global methylation (median, IQR) has been observed in the group of patients with SLE [0.73 (0.43, 1.22] and SSc [0,91 (0.59, 1.50)], whereas in the MCTD [0.29 (0.20, 0.54)], patients and healthy subjects [0.51 (0.24, 0.70)] were comparable. In addition, our study provided evidence of different levels of global DNA methylation between the SSc subtypes (p = 0.01). Our study showed that patients with limited SSc had a significantly higher global methylation level when compared to diffuse SSc. Our data has shown that the level of global DNA methylation may not be a good diagnostic marker to distinguish MCTD from other ACTDs. Our research provides the groundwork for a more detailed examination of the significance of global DNA methylation as a distinguishing factor in patients with MCTD compared to other ACTDs patients.

The Impact of Progressive Pulmonary Fibrosis in Systemic Sclerosis-Associated Interstitial Lung Disease.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation and progressive fibrosis, typically affecting the skin, with variable internal organ involvement. Interstitial lung disease (ILD), with a prevalence between 35 and 75%, is the leading cause of death in patients with SSc, indicating that all newly diagnosed patients should be screened for this complication. Some patients with SSc-ILD experience a progressive phenotype, which is characterized by worsening fibrosis on high-resolution computed tomography (HRCT), a decline in lung function, and premature mortality. To assess progression and guide therapeutic decisions, regular monitoring is essential and should include pulmonary function testing (PFT), symptom assessment, and repeat HRCT imaging when indicated. Multidisciplinary discussion allows a comprehensive evaluation of the available information and its consequences for management. There has been a shift in the approach to managing SSc-ILD, which includes the addition of targeted biologic and antifibrotic therapies to standard immunosuppressive therapy (particularly mycophenolate mofetil or cyclophosphamide), with autologous hematopoietic stem-cell transplantation and lung transplantation reserved for refractory cases.

MRI BrainAGE demonstrates increased brain aging in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting multiple organs in the human body, including the central nervous system. Recently, an artificial intelligence method called BrainAGE (Brain Age Gap Estimation), defined as predicted age minus chronological age, has been developed to measure the deviation of brain aging from a healthy population using MRI. Our aim was to evaluate brain aging in SLE patients using a deep-learning BrainAGE model. Seventy female patients with a clinical diagnosis of SLE and 24 healthy age-matched control females, were included in this post-hoc analysis of prospectively acquired data. All subjects had previously undergone a 3 T MRI acquisition, a neuropsychological evaluation and a measurement of neurofilament light protein in plasma (NfL). A BrainAGE model with a 3D convolutional neural network architecture, pre-trained on the 3D-T1 images of 1,295 healthy female subjects to predict their chronological age, was applied on the images of SLE patients and controls in order to compute the BrainAGE. SLE patients were divided into 2 groups according to the BrainAGE distribution (high vs. low BrainAGE). BrainAGE z-score was significantly higher in SLE patients than in controls (+0.6 [±1.1] vs. 0 [±1.0], p = 0.02). In SLE patients, high BrainAGE was associated with longer reaction times (p = 0.02), lower psychomotor speed (p = 0.001) and cognitive flexibility (p = 0.04), as well as with higher NfL after adjusting for age (p = 0.001). Using a deep-learning BrainAGE model, we provide evidence of increased brain aging in SLE patients, which reflected neuronal damage and cognitive impairment.

Cell Cultures as a Versatile Tool in the Research and Treatment of Autoimmune Connective Tissue Diseases.

Cell cultures are an important part of the research and treatment of autoimmune connective tissue diseases. By culturing the various cell types involved in ACTDs, researchers are able to broaden the knowledge about these diseases that, in the near future, may lead to finding cures. Fibroblast cultures and chondrocyte cultures allow scientists to study the behavior, physiology and intracellular interactions of these cells. This helps in understanding the underlying mechanisms of ACTDs, including inflammation, immune dysregulation and tissue damage. Through the analysis of gene expression patterns, surface proteins and cytokine profiles in peripheral blood mononuclear cell cultures and endothelial cell cultures researchers can identify potential biomarkers that can help in diagnosing, monitoring disease activity and predicting patient's response to treatment. Moreover, cell culturing of mesenchymal stem cells and skin modelling in ACTD research and treatment help to evaluate the effects of potential drugs or therapeutics on specific cell types relevant to the disease. Culturing cells in 3D allows us to assess safety, efficacy and the mechanisms of action, thereby aiding in the screening of potential drug candidates and the development of novel therapies. Nowadays, personalized medicine is increasingly mentioned as a future way of dealing with complex diseases such as ACTD. By culturing cells from individual patients and studying patient-specific cells, researchers can gain insights into the unique characteristics of the patient's disease, identify personalized treatment targets, and develop tailored therapeutic strategies for better outcomes. Cell culturing can help in the evaluation of the effects of these therapies on patient-specific cell populations, as well as in predicting overall treatment response. By analyzing changes in response or behavior of patient-derived cells to a treatment, researchers can assess the response effectiveness to specific therapies, thus enabling more informed treatment decisions. This literature review was created as a form of guidance for researchers and clinicians, and it was written with the use of the NCBI database.

Back to the future: targeting the extracellular matrix to treat systemic sclerosis.

Fibrosis is the excessive deposition of a stable extracellular matrix (ECM); fibrotic tissue is composed principally of highly crosslinked type I collagen and highly contractile myofibroblasts. Systemic sclerosis (SSc) is a multisystem autoimmune connective tissue disease characterized by skin and organ fibrosis. The fibrotic process has been recognized in SSc for >40 years, but drugs with demonstrable efficacy against SSc fibrosis in ameliorating the lung involvement have only recently been identified. Unfortunately, these treatments are ineffective at improving the skin score in patients with SSc. Previous clinical trials in SSc have largely focused on the cross-purposing of anti-inflammatory drugs and the use of immunosuppressive drugs from the transplantation field, which address inflammatory and/or autoimmune processes. Limited examination has taken place of specific anti-fibrotic agents developed through their ability to directly target the ECM in SSc by, for example, alleviating the persistent matrix stiffness and mechanotransduction that might be required for both the initiation and maintenance of fibrosis, including in SSc. However, because of the importance of the ECM in the SSc phenotype, attempts have now been made to identify drugs that specifically target the ECM, including some drugs that are currently under consideration for the treatment of cancer.

Erythroderma as a Presenting Sign of Juvenile Overlap Syndrome

Abstract Juvenile dermatomyositis (JDM), which is rarely presented with erythroderma, and juvenile morphea are both autoimmune connective tissue diseases. We report a 14-year-old male child with resistant generalized erythroderma and mild proximal muscle weakness who was diagnosed with dermatomyositis. Later, the patient developed morphea. The diagnosis of overlap syndrome was made by fulfilling Bohan and Peter’s criteria for JDM as well as clinical manifestations of morphea.

Proteomic aptamer analysis reveals serum biomarkers associated with disease mechanisms and phenotypes of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that affects multiple organs, leading to elevated morbidity and mortality with limited treatment options. The early detection of organ involvement is challenging as there is currently no serum marker available to predict the progression of SSc. The aptamer technology proteomic analysis holds the potential to correlate SSc manifestations with serum proteins up to femtomolar concentrations. This is a two-tier study of serum samples from women with SSc (including patients with interstitial lung disease - ILD - at high-resolution CT scan) and age-matched healthy controls (HC) that were first analyzed with aptamer-based proteomic analysis for over 1300 proteins. Proposed associated proteins were validated by ELISA first in an independent cohort of patients with SSc and HC, and selected proteins subject to further validation in two additional cohorts. The preliminary aptamer-based proteomic analysis identified 33 proteins with significantly different concentrations in SSc compared to HC sera and 9 associated with SSc-ILD, including proteins involved in extracellular matrix formation and cell-cell adhesion, angiogenesis, leukocyte recruitment, activation, and signaling. Further validations in independent cohorts ultimately confirmed the association of specific proteins with early SSc onset, specific organ involvement, and serum autoantibodies. Our multi-tier proteomic analysis identified serum proteins discriminating patients with SSc and HC or associated with different SSc subsets, disease duration, and manifestations, including ILD, skin involvement, esophageal disease, and autoantibodies.

Comparison of telerehabilitation methods for patients with systemic sclerosis in the COVID-19 Era: A randomized controlled study

Study DesignThis was a single-blinded randomized clinical trial. IntroductionSystemic sclerosis (SSc) is an autoimmune connective tissue disease that progresses with fibrosis. Patients with SSc need to be protected against epidemic diseases and provided for in terms of rehabilitation needs. Purpose of the StudyTo compare the effects of real-time telerehabilitation (RTT) and asynchronous telerehabilitation (AT) on individuals with SSc. MethodsForty-two participants with SSc with a mean age of 44.17 ± 11.05 years were included in the study. The patients were randomly divided into three groups, RTT (n = 16), AT (n = 16), and control (n = 16) groups. A structured rehabilitation program was performed in real-time (RTT group) and asynchronously (AT group) for 40 minutes per day, in three sessions per week for 8 weeks. The participants' finger and wrist joint range of motion (ROM), upper extremity functions, grip strength, superficial sense of touch, activities of daily living (ADL), and general health status were assessed at baseline and after treatment. ResultsAfter 8 weeks, there were improvements in finger ROM (effect size [ES] = 0.23 to 0.60), wrist ROM (ES = 0.45 to 0.83), upper extremity functions (ES = 0.61 to 1.00), and ADL parameters (ES = 0.74) in the RTT group (p < 0.05). Also, there were improvements in finger ROM (ES = 0.16 to 0.45) and hand functions (ES = 0.54 to 0.55) in the AT group (p < 0.05). The RTT and AT groups had better hand functions and finger ROM than the control group in (p < 0.05). In addition, the RTT group had better wrist ROM than the control group (p = 0.008). RTT was superior to AT only in lateral pinch strength (p = 0.025). DiscussionExperimental groups achieved a statistically significant change in ROM, upper extremity functions and ADL over time in concordance with prior investigations. Changes in grip strength, superficial sense of touch, and general health status scores differed from previous investigations and the between-group comparison was not statistically significant. ConclusionsBoth RTT and AT may be effective in individuals with SSc, and RTT has additional benefits.

Systemic Scleroderma: A Deep Dive into the Complexity of a Multi-System Autoimmune Connective Tissue Disease

Systemic scleroderma, a complex and rare autoimmune connective tissue disease, represents a significant clinical and scientific challenge due to its clinical heterogeneity, multisystem involvement, and potential for severe disability and complications. This article examines in depth the epidemiological, clinical, diagnostic and therapeutic aspects associated with this complex condition. Through a comprehensive review, it highlights the importance of a multidisciplinary medical approach to properly evaluate and manage the disease, from early detection to the implementation of specific therapeutic strategies targeting affected organs and systems. It also emphasizes the need for continued research to better understand the underlying pathogenic mechanisms and develop more effective therapies, with the goal of improving the outcomes and quality of life of patients affected by this complex autoimmune condition.