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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 -
Iranian Journal of Allergy, Asthma, and... Apr 2024Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays...
Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays an important role in SSc and can affect several organs such as the dermis, lungs, and heart. Dysregulation of interferon (IFN) signaling contributes to the SSc pathogenesis and interferon regulatory factor 1 (IRF1) has been indicated as the main regulator of type I IFN. This study aimed to clarify the effect of IFN-gamma (-γ) and dexamethasone (DEX) on the IRF1, extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression of alpha-smooth muscle actin (α-SMA) in myofibroblasts and genes involved in the inflammation and fibrosis processes in early diffuse cutaneous systemic sclerosis (dcSSc). A total of 10 early dcSSc patients (diffuse cutaneous form) and 10 unaffected control dermis biopsies were obtained to determine IFNγ and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFNγ and DEX at optimum time and dose. The expression level of genes and proteins involved in the fibrosis and inflammation processes have been quantified by quantitative real-time PCR (RT-qPCR) and western blot, respectively. IFNγ could up-regulate some of the inflammation-related genes (Interleukin-6; IL6) and down-regulate some of the fibrosis-related genes (COL1A1) in cultured fibroblasts of patients with early dcSSc compared to the untreated group. Besides, it has been revealed that IFNγ can induce fibroblast differentiation to the myofibroblast that expresses α-SMA. Concerning the inhibitory effect of IFNγ on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFNγ may play a dual role in SSc.
Topics: Adult; Female; Humans; Male; Middle Aged; Actins; Cells, Cultured; Dexamethasone; Fibroblasts; Fibrosis; Gene Expression Regulation; Interferon Regulatory Factor-1; Interferon-gamma; Interleukin-6; Myofibroblasts; Scleroderma, Systemic
PubMed: 38822514
DOI: 10.18502/ijaai.v23i2.15325 -
Turkish Journal of Medical Sciences 2023B-cell depletion with rituximab (RTX) is widely used as a rescue therapy in patients with systemic sclerosis (SSc). The aim herein was to analyze the progress of...
BACKGROUND/AIM
B-cell depletion with rituximab (RTX) is widely used as a rescue therapy in patients with systemic sclerosis (SSc). The aim herein was to analyze the progress of disease-related outcomes after RTX therapy in severe SSc patients.
MATERIALS AND METHODS
Included in this study were 27 SSc patients who were followed-up between 2012 and 2020 and received at least 1 cycle of RTX for active disease, despite receiving standard immunosuppressives (ISs). In addition to the European Scleroderma Study Group and European Scleroderma Trials and Research Group activity scores, Medsger's severity, and the recently developed Scleroderma Clinical Trials Consortium Damage Index values were evaluated initially and at 1 year after the first infusion. The progress of individual organ damage was also assessed at the end of the follow-up period (at least 6 months after the last infusion) using the data extracted from the medical records.
RESULTS
Disease activity and severity-improved and disease-related overall damage worsened after the first year of RTX therapy (p < 0.001, p = 0.008, and p = 0.005). Some of the disease-related organ damage had improved at the end of the follow-up period, indicating its reversibility. Overall damage scores ≥11 after the first year of RTX therapy were found to be associated with mortality (p = 0.035).
CONCLUSION
RTX contributed to reducing the activity and severity in SSc patients with severe disease, nonetheless the efficacy related to the damage was limited. High damage scores in the first year were found to be associated with mortality. Spontaneous progress of manifestations requiring a longer period to improve and irregular consecutive RTX courses might lead to difficulties in differentiation between activity and damage.
Topics: Humans; Rituximab; Scleroderma, Systemic; Female; Male; Middle Aged; Severity of Illness Index; Adult; Immunosuppressive Agents; Treatment Outcome; Immunologic Factors; Aged
PubMed: 38813512
DOI: 10.55730/1300-0144.5739 -
Turkish Journal of Medical Sciences 2024The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis...
BACKGROUND/AIM
The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19.
MATERIALS AND METHODS
In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews.
RESULTS
The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively.
CONCLUSION
This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases.
Topics: Humans; COVID-19; Scleroderma, Systemic; Female; Male; Middle Aged; Retrospective Studies; Adult; SARS-CoV-2; Risk Factors; Lung Diseases, Interstitial; Hospitalization; Comorbidity; Aged; Respiratory Insufficiency; Disease Progression
PubMed: 38812619
DOI: 10.55730/1300-0144.5768 -
RMD Open May 2024Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge...
OBJECTIVE
Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge this paradigm by hypothesising that ECM biomarkers are already disturbed in patients with very early SSc (veSSc) when fibrosis is not yet clinically detectable.
METHODS
42 patients with veSSc, defined as the presence of Raynaud's phenomenon and at least one of puffy fingers, positive antinuclear antibodies or pathological nailfold capillaroscopy, not meeting the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc, were compared with healthy controls (HCs, n=29). ECM degradation (BGM, C3M, C4M and C6M) and ECM formation biomarkers (PRO-C3, PRO-C4 and PRO-C5) were measured in serum using ELISAs. A cross-sectional analysis at baseline and a longitudinal analysis was performed.
RESULTS
Compared with HC, veSSc patients showed a strongly dysregulated turnover of type III and IV collagens (higher C3M, C4M, both p<0.0001 and PRO-C3, p=0.004, lower turnover ratios PRO-C3/C3M and PRO-C4/C4M, both p<0.0001). The biglycan degradation biomarker BGM was higher in veSSc than in HC (p=0.006), whereas the degradation biomarker for type VI collagen, C6M, was lower (p=0.002). In an ROC analysis, biomarkers of type III and IV collagen excellently distinguished between veSSc and HC: C3M, AUC=0.95, p<0.0001; C4M, AUC=0.97, p<0.0001; turnover ratios PRO-C3/C3M, AUC=0.80, p<0.0001; PRO-C4/C4M, AUC=0.97; p<0.0001.
CONCLUSION
These findings indicate ECM remodelling as a very early phenomenon of SSc occurring in parallel with microvascular and autoimmune changes. Biomarkers of type III and IV collagens distinguished between veSSc patients and HC, indicating them as potential biomarkers for the detection of veSSc.
Topics: Humans; Scleroderma, Systemic; Biomarkers; Female; Male; Middle Aged; Adult; Extracellular Matrix; Collagen; Case-Control Studies; Cross-Sectional Studies; ROC Curve; Aged; Biglycan; Collagen Type III
PubMed: 38806188
DOI: 10.1136/rmdopen-2023-003306 -
Seminars in Arthritis and Rheumatism Aug 2024Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions of the portal venules and sinusoids with clinical... (Review)
Review
Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions of the portal venules and sinusoids with clinical manifestations ranging from non-specific abnormalities in serum liver enzymes to clinically overt portal hypertension and related complications. Several reports have documented cases of PSVD in patients with systemic autoimmune conditions, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. It is of note that these diseases share specific pathophysiological features with PSVD, including endothelial dysfunction, vascular inflammation, and molecular signatures. This narrative review aims to summarize the current knowledge on the association between PSVD and systemic autoimmune diseases, emphasizing the importance of promptly recognizing this condition in the rheumatological practice, and highlighting the key aspects where further research is necessary from both pathogenic and clinical perspectives.
Topics: Humans; Autoimmune Diseases; Portal Vein; Hypertension, Portal; Vascular Diseases; Scleroderma, Systemic
PubMed: 38805899
DOI: 10.1016/j.semarthrit.2024.152467 -
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 -
Life (Basel, Switzerland) May 2024Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease that affects more than 2 million people worldwide. It manifests through vasculopathy, an... (Review)
Review
Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease that affects more than 2 million people worldwide. It manifests through vasculopathy, an abnormal immunological response, and fibrosis leading to dysfunction of the multiple organs. The disease is categorized into two subtypes: limited cutaneous SSc and diffuse cutaneous SSc. Scleroderma can affect vital organs with respiratory, cardiac, renal, ocular, and dermatological complications. The ocular manifestations of the disease can occur in the anterior and posterior segments of the eye. Changes in the anterior segment related to the disease include eyelid skin remodeling, dry eye syndrome, and conjunctival abnormalities. The disease's impact on the posterior segment of the eye mostly causes pathologies in the retinal microcirculatory system and abnormalities in the optic nerve. This review provides detailed insights into ocular complications associated with scleroderma.
PubMed: 38792647
DOI: 10.3390/life14050627 -
Journal of Clinical Medicine May 2024This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in... (Review)
Review
This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma, often leads to respiratory failure. Common manifestations include alveolar hemorrhage, interstitial fibrosis, and acute respiratory distress syndrome. Early recognition and treatment of non-malignant conditions are crucial to prevent rapid disease progression, with ICU mortality rates ranging from 30% to 60%. Delayed immunosuppressive or antimicrobial therapy may result in organ system failure. Collaboration with rheumatic specialists is vital for accurate diagnosis and immediate intervention. Mortality rates for rheumatic diseases in the ICU surpass those of other conditions, underscoring the need for specialized care and proactive management. The review emphasizes comprehensive assessments, distinguishing disease-related complications from underlying issues, and the importance of vigilant monitoring to enhance patient outcomes.
PubMed: 38792549
DOI: 10.3390/jcm13103008 -
International Journal of Molecular... May 2024We previously found IQ motif containing GTPase activating protein (IQGAP1) to be consistently elevated in lung fibroblasts (LF) isolated from patients with scleroderma...
We previously found IQ motif containing GTPase activating protein (IQGAP1) to be consistently elevated in lung fibroblasts (LF) isolated from patients with scleroderma (systemic sclerosis, SSc)-associated interstitial lung disease (ILD) and reported that IQGAP1 contributed to SSc by regulating expression and organization of α-smooth muscle actin (SMA) in LF. The aim of this study was to compare the development of ILD in the presence and absence of IQGAP1. Pulmonary fibrosis was induced in IQGAP1 knockout (KO) and wild-type (WT) mice by a single-intratracheal instillation of bleomycin. Two and three weeks later, mice were euthanized and investigated. We observed that the IQGAP1 KO mouse was characterized by a reduced rate of actin polymerization with reduced accumulation of actin in the lung compared to the WT mouse. After exposure to bleomycin, the IQGAP1 KO mouse demonstrated decreased contractile activity of LF, reduced expression of SMA, TGFβ, and collagen, and lowered overall fibrosis scores compared to the WT mouse. The numbers of inflammatory cells and expression of pro-inflammatory cytokines in lung tissue were not significantly different between IQGAP1 KO and WT mice. We conclude that IQGAP1 plays an important role in the development of lung fibrosis induced by bleomycin, and the absence of IQGAP1 reduces the contractile activity of lung fibroblast and bleomycin-induced pulmonary fibrosis. Thus, IQGAP1 may be a potential target for novel anti-fibrotic therapies for lung fibrosis.
Topics: Animals; Bleomycin; ras GTPase-Activating Proteins; Actins; Pulmonary Fibrosis; Mice; Mice, Knockout; Fibroblasts; Lung; Mice, Inbred C57BL; Polymerization; Disease Models, Animal
PubMed: 38791282
DOI: 10.3390/ijms25105244