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Clinical and Experimental Rheumatology 2018Systemic sclerosis is a rare acquired systemic disease characterised by a complex pathogenesis and multi organ involvement. Every year the scientific world contributes... (Review)
Review
Systemic sclerosis is a rare acquired systemic disease characterised by a complex pathogenesis and multi organ involvement. Every year the scientific world contributes to enrich the knowledge on the pathogenesis, clinical manifestations, diagnosis and treatment of this complex and severe disease. Herewith, we provide an overview of the most significant literature contributions published over the last year.
Topics: Animals; Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; Phenotype; Prognosis; Risk Factors; Scleroderma, Systemic
PubMed: 30277868
DOI: No ID Found -
Frontiers in Immunology 2022Systemic sclerosis (SSc) is a rare intractable systemic disease that causes fibrosis and vasculopathy against a background of autoimmune abnormalities. Although the... (Review)
Review
Systemic sclerosis (SSc) is a rare intractable systemic disease that causes fibrosis and vasculopathy against a background of autoimmune abnormalities. Although the etiology is not yet fully understood, the type of autoantibodies detected in SSc is closely associated with disease severity and prognosis, supporting that those autoimmune abnormalities play an important role in the pathogenesis of SSc. Although the direct pathogenicity of autoantibodies found in SSc is unknown, many previous studies have shown that B cells are involved in the development of SSc through a variety of functions. Furthermore, a number of clinical studies have been conducted in which B-cell depletion therapy has been tried for SSc, and many of these studies have found B-cell depletion therapy to be effective for SSc. However, the involvement of B cells in pathogenesis is complex, as they not only promote inflammation but also play an inhibitory role. This article outlines the role of B cells in the development of SSc, including the latest research.
Topics: Autoantibodies; B-Lymphocytes; Fibrosis; Humans; Lymphocyte Count; Scleroderma, Systemic
PubMed: 35967355
DOI: 10.3389/fimmu.2022.938785 -
Clinical and Experimental Rheumatology 2016Reviewing disease activity indices (DAI) in systemic sclerosis (SSc) and reporting their validation status. (Review)
Review
OBJECTIVES
Reviewing disease activity indices (DAI) in systemic sclerosis (SSc) and reporting their validation status.
METHODS
Literature was systematically reviewed on studies documenting the development of DAI, assessing the validation status of DAI and studies using a DAI in their analysis. The qualitative and quantitative validation status of existing DAI was assessed based on OMERACT and on definitions of the American College of Rheumatology (ACR) committee on quality measures.
RESULTS
Three DAI in SSc have been proposed in literature: the European Scleroderma Study Group (EScSG) activity index, the 12-point DAI and the Combined Response Index for Systemic Sclerosis (CRISS). The EScSG activity index is yet applied as an outcome measure in 48 different studies. The EScSG activity index and the CRISS are provisional partially validated DAI.
CONCLUSIONS
Future studies are needed to fully validate the EScSG activity index and the CRISS and to assess the validation status of the 12-point DAI.
Topics: Decision Support Techniques; Disability Evaluation; Health Status; Health Status Indicators; Humans; Outcome Assessment, Health Care; Predictive Value of Tests; Prognosis; Quality of Life; Reproducibility of Results; Scleroderma, Systemic; Severity of Illness Index; Surveys and Questionnaires
PubMed: 27385265
DOI: No ID Found -
Arthritis Research & Therapy Jan 2023Lack of robust, feasible, and quantitative outcomes impedes Raynaud phenomenon (RP) clinical trials in systemic sclerosis (SSc) patients. Hyperspectral imaging (HSI)...
BACKGROUND/PURPOSE
Lack of robust, feasible, and quantitative outcomes impedes Raynaud phenomenon (RP) clinical trials in systemic sclerosis (SSc) patients. Hyperspectral imaging (HSI) non-invasively measures oxygenated and deoxygenated hemoglobin (oxyHb and deoxyHb) concentrations and oxygen saturation (O sat) in the skin and depicts data as oxygenation heatmaps. This study explored the potential role of HSI in quantifying SSc-RP disease severity and activity.
METHODS
Patients with SSc-RP (n = 13) and healthy control participants (HC; n = 12) were prospectively recruited in the clinic setting. Using a hand-held camera, bilateral hand HSI (HyperMed™, Waltham, MA) was performed in a temperature-controlled room (22 °C). OxyHb, deoxyHb, and O sat values were calculated for 78-mm regions of interest for the ventral fingertips and palm (for normalization). Subjects underwent a cold provocation challenge (gloved hand submersion in 15 °C water bath for 1 min), and repeated HSI was performed at 0, 10, and 20 min. Patients completed two patient-reported outcome (PRO) instruments: the Raynaud Condition Score (RCS) and the Cochin Hand Function Scale (CHFS) for symptom burden assessment. Statistical analyses were performed using the Mann-Whitney U test and a mixed effects model (Stata, College Station, TX).
RESULTS
Ninety-two percent of participants were women in their 40s. For SSc-RP patients, 69% had limited cutaneous SSc, the mean ± SD SSc duration was 11 ± 5 years, and 38% had prior digital ulcers-none currently. Baseline deoxyHb was higher, and O sat was lower, in SSc patients versus HC (p < 0.05). SSc patients had a greater decline in oxyHb and O sat from baseline to time 0 (after cold challenge) with distinct rewarming oxyHb, O sat, and deoxyHb trajectories versus HCs (p < 0.01). There were no significant correlations between oxyHb, deoxyHb, and O sat level changes following cold challenge and RCS or CHFS scores.
CONCLUSION
Hyperspectral imaging is a feasible approach for SSc-RP quantification in the clinic setting. The RCS and CHFS values did not correlate with HSI parameters. Our data suggest that HSI technology for the assessment of SSc-RP at baseline and in response to cold provocation is a potential quantitative measure for SSc-RP severity and activity, though longitudinal studies that assess sensitivity to change are needed.
Topics: Humans; Female; Male; Hyperspectral Imaging; Scleroderma, Systemic; Scleroderma, Localized; Raynaud Disease
PubMed: 36670487
DOI: 10.1186/s13075-023-02990-3 -
BMC Pediatrics Dec 2022Juvenile Scleroderma is a rare autoimmune disease of the connective tissue. Its concurrence with COVID-19 can lead to limb ischemia as both disease entities are...
BACKGROUND
Juvenile Scleroderma is a rare autoimmune disease of the connective tissue. Its concurrence with COVID-19 can lead to limb ischemia as both disease entities are pro-inflammatory and pro-thrombotic. To date, there is no case report describing the symptomatology and course of disease in patients with juvenile Scleroderma and COVID-19.
CASE PRESENTATION
An adolescent with acute limb ischemia presented with a history of generalized hypo-and-hyperpigmented skin lesions and mild, non-productive cough. She tested positive for SARS-CoV-2 on nasopharyngeal swab RT-PCR. Further work-up revealed elevated anti-phospholipid antibodies, anti-nuclear antibody, and D-dimer; low Protein S activity; and evidence of peripheral arterial disease on imaging studies. She was started on peripheral vasodilators, Methotrexate, and anticoagulation. Close monitoring of the affected limbs and other organs involved was done. Control of limb ischemia was achieved after 4 months of regular Cyclophosphamide infusion. Continued multi-disciplinary care was ensured for this patient.
CONCLUSION
There is evolving knowledge about the interplay of COVID-19 hyperinflammatory state and rheumatologic disorders. COVID-19 is thought to exacerbate cutaneous manifestations of autoimmune disorders via antigen protein mimicry and cytokine imbalance. Moreover, COVID-19 is characterized by complex hematopathologic processes that put a patient in a hypercoagulable state. Elevated D-dimer can be seen in both COVID-19 and systemic sclerosis owing to their pro-thrombotic sequela. There is scarcity of data on the association of Protein S activity with COVID-19 and systemic sclerosis. More studies need to be carried out to ultimately arrive at a consensus on thrombosis prophylaxis for patients with Scleroderma and COVID-19.
Topics: Female; Humans; Adolescent; COVID-19; SARS-CoV-2; Scleroderma, Systemic; Ischemia; Autoimmune Diseases; Thrombosis
PubMed: 36577976
DOI: 10.1186/s12887-022-03761-w -
European Respiratory Review : An... Sep 2017Pulmonary hypertension (PH) is a frequent and severe complication of systemic sclerosis (SSc). PH in SSc is highly heterogeneous because of the various clinical... (Review)
Review
Pulmonary hypertension (PH) is a frequent and severe complication of systemic sclerosis (SSc). PH in SSc is highly heterogeneous because of the various clinical phenotypes of SSc itself and because the mechanisms of PH can vary from one patient to another. PH in SSc may be due to vasculopathy of the small pulmonary arteries (group 1; pulmonary arterial hypertension), interstitial lung disease (group 3; PH due to lung disease or chronic hypoxia) or myocardial fibrosis leading to left ventricular systolic or diastolic dysfunction (group 2; PH due to chronic left-heart disease). Pulmonary veno-occlusive disease is not uncommon in SSc and may also cause PH in some patients (group 1'). There is a high prevalence of each of these conditions in SSc and, as such, it may be difficult to determine the dominant cause of PH in a particular patient. However, careful phenotyping of PH in SSc is important as the therapy required for each of these underlying conditions is very different. In this review, we will decipher the different phenotypes of SSc-PH.
Topics: Arterial Pressure; Humans; Hypertension, Pulmonary; Phenotype; Prognosis; Pulmonary Artery; Risk Factors; Scleroderma, Systemic; Vascular Remodeling
PubMed: 28954767
DOI: 10.1183/16000617.0056-2017 -
Clinical and Experimental Rheumatology Aug 2023The SENSCIS trial of nintedanib versus placebo is the largest trial conducted to date in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).... (Review)
Review
The SENSCIS trial of nintedanib versus placebo is the largest trial conducted to date in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). This trial enrolled 576 patients with an extent of fibrotic ILD on high-resolution computed tomography of >10%. Median time since first non-Raynaud symptom was 3.4 years. Almost half of the patients were receiving a stable dose of mycophenolate at baseline. Key findings of the trial included that at baseline, despite having significant lung fibrosis on HRCT and impairment in lung function, 20% of the patients did not have cough and 30% did not have dyspnoea. Over 52 weeks, a marked decline in forced vital capacity (FVC) was observed (-112.0 mL/year in patients with diffuse cutaneous SSc [dcSSc] and -74.5 mL/year in patients with limited cutaneous SSc [lcSSc] in the placebo group). Loss of FVC was associated with an increased risk of SSc-related hospitalisation or death. Although certain subgroups of patients were at higher risk of progression, it was not possible to make a robust prediction of FVC decline based on baseline characteristics. The relative effect of nintedanib versus placebo on reducing the rate of FVC decline was consistent across subgroups based on factors including anti-topoisomerase I antibody (ATA) status, dcSSc vs. lcSSc, and use of mycophenolate at baseline. The side-effects of nintedanib were mainly gastrointestinal events, particularly diarrhoea. Nintedanib did not have a significant effect on skin fibrosis or health-related quality of life. Overall, the results of the SENSCIS trial support the importance of prompt identification and treatment of SSc-ILD and the consideration of nintedanib as a treatment option.
Topics: Humans; Disease Progression; Fibrosis; Immunosuppressive Agents; Lung Diseases, Interstitial; Quality of Life; Scleroderma, Systemic; Vital Capacity; Clinical Trials as Topic
PubMed: 37534955
DOI: 10.55563/clinexprheumatol/trcv91 -
Cells Mar 2022Autologous hematopoietic stem cells transplantation (AHSCT) has been employed as treatment for severe systemic sclerosis (SSc) with high risk of organ failure. In the... (Review)
Review
Autologous hematopoietic stem cells transplantation (AHSCT) has been employed as treatment for severe systemic sclerosis (SSc) with high risk of organ failure. In the last 25 years overall survival and treatment-related mortality have improved, in accordance with a better patient selection and mobilization and conditioning protocols. This review analyzes the evidence from the last 5 years for AHSCT-treated SSc patients, considering in particular the outcomes related to interstitial lung disease. There are increasing data supporting the use of AHSCT in selected patients with rapidly progressive SSc. However, some unmet needs remain, such as an accurate patient selection, pre-transplantation analysis to identify subclinical conditions precluding the transplantation, and the alternatives for post-transplant ILD recurrence.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Lung Diseases, Interstitial; Scleroderma, Systemic; Transplantation, Autologous
PubMed: 35269465
DOI: 10.3390/cells11050843 -
Arthritis and Rheumatism Feb 2000To describe the demographic, clinical, and laboratory features and natural history of patients with systemic sclerosis sine scleroderma (ssSSc), and to compare them with...
OBJECTIVE
To describe the demographic, clinical, and laboratory features and natural history of patients with systemic sclerosis sine scleroderma (ssSSc), and to compare them with those of patients with SSc and limited cutaneous involvement (IcSSc).
METHODS
The University of Pittsburgh Scleroderma Databank served as the data source. Patients were divided into those who had no skin thickening (ssSSc) and those who had skin thickening only distal to elbows or knees and/or of the face (IcSSc) during their disease course. These two groups were compared with regard to demographic characteristics, clinical, laboratory, and serologic features, and survival rates. Chi-square and Student's t-test analyses were performed, and Fisher's exact test was used as appropriate.
RESULTS
Of 555 consecutive patients without diffuse cutaneous SSc, 48 (9%) had ssSSc and 507 (91%) had IcSSc. The ssSSc patients had a mean total disease duration of 18.6 years (15.1 years before study entry and 3.5 years of followup after study entry), and had not developed IcSSc or another connective tissue disease. Other than the absence of skin thickening, the ssSSc group had no significant differences in individual internal organ involvements, laboratory features, serum autoantibody type, or survival rate compared with patients with IcSSc. Within the category of lung involvement, patients with ssSSc had a significantly greater frequency of dyspnea with mild exertion or at rest, and a tendency toward reduced carbon monoxide diffusing capacity (<70% of predicted normal) and primary pulmonary arterial hypertension. Patients with IcSSc had significantly more frequent individual manifestations of digital pitting scars, digital-tip ulcers, telangiectasia, and calcinosis than those with ssSSc, in part related to increased time of observation. Puffy fingers and finger joint contractures were detected significantly more often in IcSSc patients.
CONCLUSION
Systemic sclerosis sine scleroderma should be included in the spectrum of SSc with limited cutaneous involvement and should not be considered a distinct or separate disorder.
Topics: Adolescent; Adult; Aged; Autoantibodies; Female; Gastrointestinal Diseases; Humans; Joint Diseases; Lung Diseases; Male; Middle Aged; Muscular Diseases; Scleroderma, Localized; Scleroderma, Systemic; Survival Rate
PubMed: 10693887
DOI: 10.1002/1529-0131(200002)43:2<444::AID-ANR27>3.0.CO;2-G -
Current Opinion in Rheumatology Jul 2022Raynaud's phenomenon (RP) is a common vasospastic condition that results in digital hypoperfusion in response to cold and/or emotional stress and is associated with... (Review)
Review
PURPOSE OF REVIEW
Raynaud's phenomenon (RP) is a common vasospastic condition that results in digital hypoperfusion in response to cold and/or emotional stress and is associated with significant pain and disability. The aim of our review is to provide a practical approach for clinicians to inform assessment and management of patients with RP.
RECENT FINDINGS
Autoantibodies and nailfold capillaroscopy are key investigations to stratify the risk of progression to systemic sclerosis (SSc) in patients RP, which was recently confirmed in the multicenter, very early diagnosis of systemic sclerosis (VEDOSS) project. Research has explored the complex lived-patient experience of RP including digital vasculopathy in SSc and has highlighted the need for outcome measure development to facilitate research in the field. Pharmacological treatment strategies vary significantly internationally and there is continued interest in developing surgical approaches.
SUMMARY
We provide a practical and up-to-date approach to inform the assessment and management of patients with RP including guidance on drug initiation and escalation. Calcium channel blockers are first-line treatment and can be initiated by primary care physicians. We also highlight second-line drug therapies used for refractory RP and the potential role for surgical intervention.
Topics: Autoantibodies; Humans; Microscopic Angioscopy; Multicenter Studies as Topic; Physicians; Raynaud Disease; Scleroderma, Systemic
PubMed: 35699336
DOI: 10.1097/BOR.0000000000000877