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The Journal of Rheumatology Jun 2024Concerns regarding offering radiotherapy to patients with systemic sclerosis (SSc) stem from the potential worsening of SSc manifestations and radiotherapy toxicity. We...
OBJECTIVE
Concerns regarding offering radiotherapy to patients with systemic sclerosis (SSc) stem from the potential worsening of SSc manifestations and radiotherapy toxicity. We conducted a systematic review to evaluate the effects of radiotherapy on SSc outcomes and radiotherapy-related toxicity.
METHODS
MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched for SSc and radiotherapy. Inclusion criteria were SSc diagnosis, subsequent cancer development, and radiotherapy exposure. Outcomes were SSc manifestations (cutaneous thickening, pulmonary fibrosis, and SSc flare) and radiotherapy toxicity (acute and late) using Common Terminology Criteria for Adverse Events for grading. Grade 1 and 2 toxicities were categorized as nonsevere and grade 3 to 5 toxicities as severe.
RESULTS
Of 121 patients with SSc undergoing radiotherapy (mean age 56.4 years, 83.3% female, median radiotherapy dose 50 Gy), most did not show worsened SSc skin thickening (74.5%) or pulmonary complications (74%) post radiotherapy. In retrospective studies, the average rates of acute adverse effects were 57.3% for nonsevere and 25.8% for severe, whereas the rates of late adverse effects were 32.4% for nonsevere and 24% for severe.
CONCLUSION
Although most patients with SSc do not exhibit significant worsening of SSc manifestations post radiotherapy, there is a variable risk of acute and late toxicity. These findings suggest that although radiotherapy may be a viable option for patients with cancer with SSc, it requires caution.
PubMed: 38825361
DOI: 10.3899/jrheum.2023-1235 -
Frontiers in Immunology 2024The identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is... (Meta-Analysis)
Meta-Analysis
The association between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio and systemic sclerosis and its complications: a systematic review and meta-analysis.
INTRODUCTION
The identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is routinely assessed in the evaluation of SSc, the diagnostic utility of specific cell-derived inflammatory indices, i.e., neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), has not been critically appraised in this patient group.
METHODS
We conducted a systematic review and meta-analysis of studies investigating the NLR, PLR, and MLR, in SSc patients and healthy controls and in SSc patients with and without relevant complications. PubMed, Scopus, and Web of Science were searched from inception to 23 February 2024. Risk of bias and certainty of evidence were assessed using validated tools.
RESULTS
In 10 eligible studies, compared to controls, patients with SSc had significantly higher NLR (standard mean difference, SMD=0.68, 95% CI 0.46 to 0.91, p<0.001; I = 74.5%, p<0.001), and PLR values (SMD=0.52, 95% CI 0.21 to 0.83, p=0.001; I = 77.0%, p=0.005), and a trend towards higher MLR values (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I = 94.1%, p<0.001). When compared to SSc patients without complications, the NLR was significantly higher in SSc with interstitial lung disease (ILD, SMD=0.31, 95% CI 0.15 to 0.46, p<0.001; I = 43.9%, p=0.11), pulmonary arterial hypertension (PAH, SMD=1.59, 95% CI 0.04 to 3.1, p=0.045; I = 87.6%, p<0.001), and digital ulcers (DU, SMD=0.43, 95% CI 0.13 to 0.74, p=0.006; I = 0.0%, p=0.49). The PLR was significantly higher in SSc patients with ILD (SMD=0.42, 95% CI 0.25 to 0.59, p<0.001; I = 24.8%, p=0.26). The MLR was significantly higher in SSc patients with PAH (SMD=0.63, 95% CI 0.17 to 1.08, p=0.007; I = 66.0%, p=0.086), and there was a trend towards a higher MLR in SSc patients with ILD (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I = 94.1%, p<0.001).
DISCUSSION
Pending the results of appropriately designed prospective studies, the results of this systematic review and meta-analysis suggest that blood cell-derived indices of inflammation, particularly the NLR and PLR, may be useful in the diagnosis of SSc and specific complications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520040.
Topics: Humans; Scleroderma, Systemic; Neutrophils; Lymphocytes; Monocytes; Blood Platelets; Lymphocyte Count; Biomarkers; Platelet Count
PubMed: 38799443
DOI: 10.3389/fimmu.2024.1395993 -
Autoimmunity Reviews May 2024Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a... (Meta-Analysis)
Meta-Analysis Review
Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis.
OBJECTIVES
Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort.
METHODS
Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719).
FINDINGS
In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]).
INTERPRETATION
Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.
Topics: Humans; Scleroderma, Systemic; Autoantibodies; Ribonucleoproteins; France; Phenotype; Antibodies, Antinuclear; Prevalence; Female; Cross-Sectional Studies; Male
PubMed: 38555075
DOI: 10.1016/j.autrev.2024.103536 -
Reumatismo Mar 2024Scleroderma, or systemic sclerosis (SSc), is a chronic autoimmune connective disease with an unknown etiology and poorly understood pathogenesis. The striking array of...
OBJECTIVE
Scleroderma, or systemic sclerosis (SSc), is a chronic autoimmune connective disease with an unknown etiology and poorly understood pathogenesis. The striking array of autoimmune, vascular, and fibrotic changes that develop in almost all patients makes SSc unique among connective tissue diseases. Although no animal model developed for SSc to date fully represents all features of human disease, some animal models that demonstrate features of SSc may help to better understand the pathogenesis of the disease and to develop new therapeutic options. In this review, we aimed to evaluate skin fibrosis and lung involvement in a bleomycin (BLM)-induced mouse model and to evaluate the differences between studies.
METHODS
A systematic literature review (PRISMA guideline) on PubMed and EMBASE (until May 2023, without limits) was performed. A primary literature search was conducted using the PubMed and EMBASE databases for all articles published from 1990 to May 2023. Review articles, human studies, and non-dermatological studies were excluded. Of the 38 non-duplicated studies, 20 articles were included.
RESULTS
Among inducible animal models, the BLM-induced SSc is still the most widely used. In recent years, the measurement of tissue thickness between the epidermal-dermal junction and the dermal-adipose tissue junction (dermal layer) has become more widely accepted.
CONCLUSIONS
In animal studies, it is important to simultaneously evaluate lung tissues in addition to skin fibrosis induced in mice by subcutaneous BLM application, following the 3R (replacement, reduction, and refinement) principle to avoid cruelty to animals.
Topics: Humans; Animals; Mice; Pulmonary Fibrosis; Bleomycin; Skin; Fibrosis; Scleroderma, Systemic; Skin Diseases; Disease Models, Animal
PubMed: 38523580
DOI: 10.4081/reumatismo.2024.1642 -
Respiratory Research Mar 2024The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the... (Review)
Review
BACKGROUND
The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR).
METHODS
PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported.
RESULTS
We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns.
CONCLUSIONS
The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.
Topics: Humans; Female; Adult; Middle Aged; Male; Lung Diseases, Interstitial; Lung; Scleroderma, Systemic; Biopsy; Prognosis
PubMed: 38521926
DOI: 10.1186/s12931-024-02725-1 -
Scientific Reports Mar 2024We aimed to evaluate the association between systemic sclerosis (SSc) and major cerebrovascular/cardiovascular risks through a systematic approach. Databases were... (Meta-Analysis)
Meta-Analysis
We aimed to evaluate the association between systemic sclerosis (SSc) and major cerebrovascular/cardiovascular risks through a systematic approach. Databases were systematically searched from their inception to October 10, 2023 for studies comparing cerebrovascular/cardiovascular event rates between patients with SSc and controls. The primary outcome was the stroke risk in patients with SSc. Secondary outcomes included risk of myocardial infarction (MI), cardiovascular disease (CVD), peripheral vascular disease (PVD), and venous thromboembolism (VTE). Seventeen studies with 6,642,297 participants were included. SSc was associated with a significantly increased risk of stroke (HR, 1.64; 95% confidence interval [CI], 1.35-2.01), CVD (HR, 2.12; 95% CI, 1.36-3.3), MI (HR, 2.15; 95% CI, 1.23-3.77), VTE (HR, 2.75; 95% CI, 1.77-4.28), and PVD (HR, 5.23; 95% CI, 4.25-6.45). Subgroup analysis revealed a significantly increased stroke risk in the non-Asian group (HR, 1.55; 95% CI, 1.26-1.9), while the Asian group displayed a higher but not statistically significant risk (HR, 1.86; 95% CI, 0.97-3.55). The study found that SSc is associated with a significantly increased risk of cerebrovascular/cardiovascular events. These findings highlight the importance of vasculopathy in SSc and suggest the need for enhanced clinical monitoring and preventive measures in this high-risk population.
Topics: Humans; Cardiovascular Diseases; Venous Thromboembolism; Myocardial Infarction; Stroke; Peripheral Vascular Diseases; Scleroderma, Systemic
PubMed: 38499699
DOI: 10.1038/s41598-024-57275-9 -
BMC Medicine Mar 2024Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking.
METHODS
Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies.
RESULTS
A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events.
CONCLUSIONS
Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Celiac Disease; Diabetes Mellitus, Type 1; Fibromyalgia; Gastrointestinal Microbiome; Randomized Controlled Trials as Topic; Autoimmune Diseases; Psoriasis; Scleroderma, Systemic; Spondylarthritis; Lupus Erythematosus, Systemic
PubMed: 38475833
DOI: 10.1186/s12916-024-03303-4 -
BMJ Open Mar 2024This review aims to provide an estimate of sarcopenia prevalence and its impact on clinical characteristics in patients with systemic sclerosis (SSc). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This review aims to provide an estimate of sarcopenia prevalence and its impact on clinical characteristics in patients with systemic sclerosis (SSc).
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Embase, Medline, Web of Science and the Cochrane Central Register of Controlled Trials were systemically searched from inception to 24 May 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
We included observational studies that reported the prevalence of sarcopenia in patients with SSc.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently performed study selection and data extraction using standardised methods. Risk of bias was assessed using the Agency for Healthcare Research and Quality Scale and the Newcastle-Ottawa Scale. Meta-analysis was conducted using random effects models.
RESULTS
A total of 4583 articles were screened and 9 studies with data from 815 patients were included in the analysis (8 cross-sectional studies and 1 retrospective cohort study). The overall prevalence of sarcopenia in patients with SSc was 22% (95% CI 17% to 28%). Patients with SSc with sarcopenia had a poorer quality of life (mean difference -12.02; 95% CI -19.11 to -4.93) and higher C reactive protein (CRP) levels (standardised mean difference 0.67; 95% CI 0.35 to 1.00).
CONCLUSIONS
Sarcopenia is common in patients with SSc. Patients with SSc with sarcopenia had a worse quality of life and higher CRP levels, based on our findings. Given the detrimental impact of sarcopenia on quality of life, future efforts aimed at early identification of sarcopenia in the clinical assessment of patients with SSc may have significance.
PROSPERO REGISTRATION NUMBER
CRD42022368326.
Topics: United States; Humans; Cross-Sectional Studies; Prevalence; Quality of Life; Retrospective Studies; Sarcopenia; Scleroderma, Systemic
PubMed: 38448063
DOI: 10.1136/bmjopen-2023-078034 -
Journal of Scleroderma and Related... Feb 2024Patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) have a poor prognosis, accounting for 30% of all SSc-related deaths. Guidelines...
BACKGROUND AND OBJECTIVE
Patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) have a poor prognosis, accounting for 30% of all SSc-related deaths. Guidelines recommend annual screening for PAH regardless of symptoms, as early treatment improves outcomes. Current protocols include combinations of clinical features, biomarkers, pulmonary function tests, and echocardiography. None include exercise testing, although early-stage PAH may only be evident during exercise. This systematic review assessed the performance of exercise tests in predicting the presence of PAH in patients with SSc, where PAH was confirmed through right heart catheterisation (RHC).
METHODS
Comprehensive literature searches were performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trails, CINAHL, Scopus and Web of Science from inception to May 2023. Articles were screened for eligibility by two independent reviewers. Eligibility criteria included the use of a non-invasive exercise test to screen adult patients to detect PAH in a population without a previous diagnosis of PAH, with diagnosis confirmed by RHC.
RESULTS
Eight studies met the inclusion criteria, describing at least one of three different non-invasive exercise tests: cardiopulmonary exercise test, six-minute walk test and stress Doppler echocardiography. All studies found that exercise tests had some ability to predict the presence of PAH, with sensitivity between 50% and 100% and specificity from 73% to 91%.
CONCLUSION
Exercise tests are infrequently used for screening for PAH in SSc but can predict the presence of PAH. More data are required to establish which tests are most effective.
PubMed: 38333530
DOI: 10.1177/23971983231199148 -
BMJ Open Respiratory Research Nov 2023Interstitial lung disease (ILD) is an important manifestation of autoimmune diseases that can lead to morbidity and mortality. Although several autoantibodies have been... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Interstitial lung disease (ILD) is an important manifestation of autoimmune diseases that can lead to morbidity and mortality. Although several autoantibodies have been linked with ILD presentation and adverse outcomes, the association of anti-Ro52 antibody with ILD is less studied. Hence, we investigated this association in various autoimmune diseases in the current study.
DESIGN
We designed a systematic review and meta-analysis and did a comprehensive search from inception until 2 January 2023.
DATA SOURCES
A systematic search was conducted in four electronic databases: PubMed, Web of Science, Scopus and Embase.
ELIGIBILITY CRITERIA
Observational studies that reported ILD diagnosis (outcome) and anti-Ro antibody (exposure) status in any autoimmune conditions (population) were included. The association between rapidly progressive ILD (RP-ILD) and anti-Ro52 was studied in idiopathic inflammatory myopathies (IIM).
DATA EXTRACTION AND SYNTHESIS
Collected data included study characteristics and ORs with 95% CIs. Quality assessment was performed using a modified version of the Newcastle-Ottawa Scale for cross-sectional studies. Random effects meta-analysis was used to pool the effect estimates.
RESULTS
A total of 2353 studies were identified, from which 59 articles met the eligibility criteria. Anti-Ro52/SSA positivity was associated with ILD in all autoimmune disease subgroups: IIM (OR=3.08; 95% CI: 2.18 to 4.35; p value<0.001; I=49%), systemic lupus (OR=2.43; 95% CI: 1.02 to 5.79; p=0.046; I=71%), Sjogren (OR=1.77; 95% CI: 1.09 to 2.87; p=0.021; I=73%), systemic sclerosis (OR=1.71; 95% CI: 1.04 to 2.83; p=0.036; I=43%), mixed connective tissue disease (OR=3.34; 95% CI: 1.82 to 6.13; p<0.001; I=0%). Additionally, anti-Ro52-positive myopathy patients were more likely to have simultaneous RP-ILD (OR=2.69; 95% CI:1.50 to 4.83; p<0.001; I=71%).
CONCLUSION
Anti-Ro52/SSA positivity is associated with a higher frequency of ILD diagnosis in various autoimmune diseases. Anti-Ro52/SSA is also linked with a more severe lung involvement (RP-ILD). Future studies can investigate the benefits of screening for anti-Ro52 and its association with ILD development.
PROSPERO REGISTRATION NUMBER
CRD42022381447.
Topics: Humans; Autoantibodies; Cross-Sectional Studies; Autoimmune Diseases; Lung Diseases, Interstitial; Scleroderma, Systemic; Myositis
PubMed: 38030264
DOI: 10.1136/bmjresp-2023-002076