scholarly journals Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies

2021 ◽  
Vol 8 ◽  
Author(s):  
Djúlio César Zanin-Silva ◽  
Maynara Santana-Gonçalves ◽  
Marianna Yumi Kawashima-Vasconcelos ◽  
Maria Carolina Oliveira
Keyword(s):  
Systemic Sclerosis ◽  
Cellular Therapy ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Pulmonary Artery Hypertension ◽  
Endothelial Damage ◽  
Therapeutic Interventions ◽  
Scleroderma Renal Crisis ◽  
Digital Ulcers ◽  
Endothelial Repair

Systemic Sclerosis (SSc) is an autoimmune disease marked by dysregulation of the immune system, tissue fibrosis and dysfunction of the vasculature. Vascular damage, remodeling and inadequate endothelial repair are hallmarks of the disease. Since early stages of SSc, damage and apoptosis of endothelial cells (ECs) can lead to perivascular inflammation, oxidative stress and tissue hypoxia, resulting in multiple clinical manifestations. Raynaud's phenomenon, edematous puffy hands, digital ulcers, pulmonary artery hypertension, erectile dysfunction, scleroderma renal crisis and heart involvement severely affect quality of life and survival. Understanding pathogenic aspects and biomarkers that reflect endothelial damage in SSc is essential to guide therapeutic interventions. Treatment approaches described for SSc-associated vasculopathy include pharmacological options to improve blood flow and tissue perfusion and, more recently, cellular therapy to enhance endothelial repair, promote angiogenesis and heal injuries. This mini-review examines the current knowledge on cellular and molecular aspects of SSc vasculopathy, as well as established and developing therapeutic approaches for improving the vascular compartment.

scholarly journals Demyelinating Syndrome in Systemic Sclerosis and Neuromyelitis Optica

2019 ◽  
Author(s):  
khaled Deeb ◽  
Jessika Eby ◽  
Jose Labault-Santiago
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Neuromyelitis Optica ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Transverse Myelitis ◽  
Clinical Findings ◽  
Therapeutic Interventions ◽  
High Dose ◽  
Scleroderma Renal Crisis

Abstract INTRODUCTION: The objective of this study is to report a case of a 44-year-old female who presented with intractable hiccups, vomiting, and later complicated with paraplegia. Imaging and sero/immunological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity and transverse myelitis on MRI. Further investigation revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes, namely systemic sclerosis and neuromyelitis optica, and their underlying clinical manifestations and therapeutic interventions, are seldom reported in literature and are worth reporting. CASE REPORT: The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified as steroid induced scleroderma renal crisis on renal biopsy. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received consent forms from the participant in our study, and we have them on file in case they are requested. We have also received patient’s consent for the data presented in this article and Figure 1. CONCLUSION: This report expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.

scholarly journals Demyelinating syndrome in systemic sclerosis and neuromyelitis optica

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Khaled Deeb ◽  
Jessika Eby ◽  
Jose Labault-Santiago
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Neuromyelitis Optica ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Transverse Myelitis ◽  
Clinical Findings ◽  
Therapeutic Interventions ◽  
High Dose ◽  
Scleroderma Renal Crisis

Abstract Background This article reports a case diagnosis of a 44-year-old female who presented with intractable hiccups and vomit complicated with an acute onset of paraplegia. Transverse myelitis was evident on MRI and serological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity. Further studies revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes and their underlying clinical manifestations and therapeutic interventions are seldom reported in literature and are worth reporting. Case presentation The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified on biopsy as steroids-induced scleroderma renal crisis. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where the patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received a written consent forms from the participant in our study, and we have them on file in case they are requested. We have also received the patient’s written consent for the data and images presented in this article. Conclusion This article expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.

scholarly journals Demyelinating Syndrome in Systemic Sclerosis and Neuromyelitis Optica

2019 ◽  
Author(s):  
khaled Deeb ◽  
Jessika Eby ◽  
Jose Labault-Santiago
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Neuromyelitis Optica ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Transverse Myelitis ◽  
Clinical Findings ◽  
Therapeutic Interventions ◽  
High Dose ◽  
Scleroderma Renal Crisis

Abstract INTRODUCTION: The objective of this study is to report a case of a 44-year-old female who presented with intractable hiccups, vomiting, and later complicated with paraplegia. Imaging and sero/immunological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity and transverse myelitis on MRI. Further investigation revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes, namely systemic sclerosis and neuromyelitis optica, and their underlying clinical manifestations and therapeutic interventions, are seldom reported in literature and are worth reporting. CASE REPORT: The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified as steroid induced scleroderma renal crisis on renal biopsy. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received consent forms from the participant in our study, and we have them on file in case they are requested. We have also received patient’s consent for the data presented in this article and Figure 1. CONCLUSION: This report expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.

scholarly journals Demyelinating Syndrome in Systemic Sclerosis and Neuromyelitis Optica

2019 ◽  
Author(s):  
khaled Deeb ◽  
Jessika Dold ◽  
Jose Labault-Santiago
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Neuromyelitis Optica ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Transverse Myelitis ◽  
Clinical Findings ◽  
Therapeutic Interventions ◽  
High Dose ◽  
Scleroderma Renal Crisis

Abstract INTRODUCTION: The objective of this study is to report a case of a 44-year-old female who presented with intractable hiccups, vomiting, and later complicated with paraplegia. Imaging and sero/immunological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity and transverse myelitis on MRI. Further investigation revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes, namely systemic sclerosis and neuromyelitis optica, and their underlying clinical manifestations and therapeutic interventions, are seldom reported in literature and are worth reporting. CASE REPORT: The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified as steroid induced scleroderma renal crisis on renal biopsy. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received consent forms from the participant in our study, and we have them on file in case they are requested. We have also received patient’s consent for the data presented in this article and Figure 1. CONCLUSION: This report expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.

scholarly journals Demyelinating Syndrome in Systemic Sclerosis and Neuromyelitis Optica

2019 ◽  
Author(s):  
khaled Deeb ◽  
Jessika Eby ◽  
Jose Labault-Santiago
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Neuromyelitis Optica ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Transverse Myelitis ◽  
Clinical Findings ◽  
Therapeutic Interventions ◽  
High Dose ◽  
Scleroderma Renal Crisis

Abstract INTRODUCTION: The objective of this study is to report a case of a 44-year-old female who presented with intractable hiccups, vomiting, and later complicated with paraplegia. Imaging and sero/immunological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity and transverse myelitis on MRI. Further investigation revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes, namely systemic sclerosis and neuromyelitis optica, and their underlying clinical manifestations and therapeutic interventions, are seldom reported in literature and are worth reporting. CASE REPORT: The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified as steroid induced scleroderma renal crisis on renal biopsy. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received consent forms from the participant in our study, and we have them on file in case they are requested. We have also received patient’s consent for the data presented in this article and Figure 1. CONCLUSION: This report expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.

scholarly journals Demyelinating Syndrome in Systemic Sclerosis and Neuromyelitis Optica

2019 ◽  
Author(s):  
khaled Deeb ◽  
Jessika Eby ◽  
Jose Labault-Santiago
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Neuromyelitis Optica ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Transverse Myelitis ◽  
Clinical Findings ◽  
Therapeutic Interventions ◽  
High Dose ◽  
Scleroderma Renal Crisis

Abstract INTRODUCTION: The objective of this study is to report a case of a 44-year-old female who presented with intractable hiccups, vomiting, and later complicated with paraplegia. Imaging and sero/immunological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity and transverse myelitis on MRI. Further investigation revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes, namely systemic sclerosis and neuromyelitis optica, and their underlying clinical manifestations and therapeutic interventions, are seldom reported in literature and are worth reporting. CASE REPORT: The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified as steroid induced scleroderma renal crisis on renal biopsy. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received consent forms from the participant in our study, and we have them on file in case they are requested. We have also received patient’s consent for the data presented in this article and Figure 1. CONCLUSION: This report expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.

scholarly journals Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Sayonara Maria Calado Gonçalves ◽  
Anderson Rodrigues de Almeida ◽  
Rafaela Silva Guimarães Gonçalves ◽  
Maria Clara Pinheiro Duarte Sampaio ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Vascular Involvement ◽  
Digital Ulcers ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear ◽  
Pbmc Culture ◽  
Significant Difference ◽  
Skin Biopsies

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

scholarly journals Endocan and Circulating Progenitor Cells in Women with Systemic Sclerosis: Association with Inflammation and Pulmonary Hypertension

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 533
Author(s):  
Alberto Lo Gullo ◽  
Giuseppe Mandraffino ◽  
Javier Rodríguez-Carrio ◽  
Michele Scuruchi ◽  
Davide Sinicropi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Systemic Sclerosis ◽  
Progenitor Cells ◽  
Inflammatory Markers ◽  
Cell Number ◽  
Pulmonary Artery Hypertension ◽  
Digital Ulcers ◽  
Potential Marker ◽  
Vitamin D Levels ◽  
Cd34 Cells

Background: Systemic sclerosis (SSc) is characterized by early vasculopathy and fibrosis in the skin, lungs, and other tissues. Vascular manifestations of SSc include Raynaud’s phenomenon, digital ulcers, and pulmonary artery hypertension (PAH). PAH is the second most common cause of mortality in SSc. Circulating CD34+ cells associated with cardiovascular health status in several conditions, including chronic immune-inflammatory disease. CD34+ cell numbers have been found inconstantly reduced in SSc. Endocan, a proteoglycan expressed by endothelial cells, was recently suggested as a marker of vascular stress. We tested the relationships among CD34+ cells, endocan, inflammatory markers, vitamin D levels, and clinical parameters in SSc patients with PAH. METHODS: Standard echocardiography was performed. Vitamin D levels, CD34+ cells, inflammatory markers, endocan plasma levels were determined in 36 female SSc patients (24 diffuse/12 limited) and 36 matched controls (HC). RESULTS: We found no difference in CD34+ and vitamin D levels in SSc as compared to controls; ESR, CRP, fibrinogen, endocan, sPAP were higher in SSc with respect to controls. We found a correlation between endocan and: CD34+ cells (r: −0.540, p = 0.002), pulmonary arterial pressure (sPAP) (r: 0.565, p < 0.001), tricuspid annular plane excursion (TAPSE) (r: −0.311, p < 0.01), and E/A ratio (r: −0.487, p < 0.001), but not with ejection fraction (r: −0.057, p = 0.785) in SSc. CD34+ cells correlate with fibrinogen (r: −0.619, p < 0.001), sPAP (r: −0.404, p = 0.011), E/A (r: 0.470, p < 0.005 in SSc. CONCLUSION: CD34+ cell number was significantly correlated with endocan levels and with sPAP in SSc; endocan and CD34+ progenitor cells might be suggested as a potential marker of disease status.

scholarly journals Update of EULAR recommendations for the treatment of systemic sclerosis

2016 ◽  
Vol 76 (8) ◽  
pp. 1327-1339 ◽  
Author(s):  
Otylia Kowal-Bielecka ◽  
Jaap Fransen ◽  
Jerome Avouac ◽  
Mike Becker ◽  
Agnieszka Kulak ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Task Force ◽  
Previous Treatment ◽  
Haematopoietic Stem Cell ◽  
Scleroderma Renal Crisis ◽  
Digital Ulcers ◽  
Eular Recommendations ◽  
Delphi Approach ◽  
The Usa ◽  
Clinical Questions

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.

scholarly journals The clinical value of the delta finger to palm distance in systemic sclerosis

Reumatismo ◽  
2020 ◽  
Vol 72 (1) ◽  
pp. 44-51
Author(s):  
A. Javinani ◽  
S. Mostafaei ◽  
F. Gharibdoost ◽  
A.R. Jamshidi ◽  
R. Atef Yekta ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Manifestations ◽  
Digital Ulcers ◽  
Clinical Value ◽  
Prospective Longitudinal Study ◽  
Linear Effect ◽  
One Year ◽  
The One ◽  
Prospective Longitudinal

Systemic sclerosis (SSc) is a collagen-vascular disorder characterized by fibrosis and vasculopathy. Delta finger to palm distance (delta FTP) is an index measuring the distance between the tip of the third finger to the distal palmar crease in the flexed and extended position. The present study aimed to evaluate the clinical value of delta FTP and to assess the correlation of delta FTP with modified Rodnan skin score (mRSS) and forced vital capacity (FVC) over the 12-month follow-up. This prospective longitudinal study began with 50 participants who were followed for twelve months. Lowess smoothing and linear regression were applied to detect and assess the relationship between delta FTP and mRSS. p-values were adjusted by the Benjamini-Hochberg method (BHM) as a control for false discovery rate. Delta FTP was lower among patients with higher disease duration (p-valueadj: 0.008), diffuse cutaneous SSc (p-valueadj: 0.006), digital ulcers (p-valueadj: 0.003), telangiectasia (p-valueadj: 0.006) and dysphagia (p-valueadj: 0.036). The mRSS has a significant negative linear effect on the delta FTP at the baseline and the end of the follow-up (r: -0.31 and -0.40, respectively). Moreover, changes of mRSS and delta FTP showed a negative linear association over time (r: -0.22). These linear effects remained significant after regrouping the patients based on their SSc subtype. Delta FTP and FVC were not correlated either at the baseline or at the end. It seems that the delta FTP can be a valuable clinical index, supported by its correlated changes with mRSS and other SSc clinical manifestations over the one-year follow-up.

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