Interstitial Lung Disease In Systemic Sclerosis Research Articles

Relevance of immunomodulatory therapy for interstitial lung disease in systemic sclerosis.

Systemic sclerosis is an autoimmune disease that prominently leads to skin and tissue fibrosis. The efficacy of autologous stem cell transplantation not only attests to the autoimmune pathophysiology for systemic sclerosis, but also for interstitial lung disease as its most frequent manifestation of fatal organ involvement. Accordingly, a variety of immunomodulatory therapies were tried on patients with systemic sclerosis-interstitial lung disease. Until very recently, all of these therapeutic approaches constituted off-label treatment for systemic sclerosis, given that neither of these therapies was approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency. For tocilizumab, this has now changed with FDA approval in March 2021. Already 2020, nintedanib, which is an antifibrotic drug that does not target autoimmunity, became the first approved drug for interstitial lung disease in systemic sclerosis. The present review analyzes the evidence for immunomodulatory treatment of systemic sclerosis-associated interstitial lung disease. The review focuses on randomized controlled trials, which provides evidence for the effects of drugs such as cyclophosphamide, mycophenolate, rituximab and tocilizumab.

Treatment for systemic sclerosis-associated interstitial lung disease.

This review provides an overview of the current treatments for systemic sclerosis-interstitial lung disease (SSc-ILD) and proposes a conceptual framework for disease management with case scenarios. Broad treatment categories include traditional cytotoxic therapies, biologic disease-modifying rheumatic drugs, antifibrotic agents, autologous hematopoietic stem cell transplant, and lung transplantation. The optimal use of each option varies depending on SSc-ILD severity, progression, and comorbidities of individual patients. A high-quality randomized controlled trial demonstrated nintedanib's ability to retard decline of lung function in patients with limited and diffuse cutaneous disease, with established ILD. Tocilizumab, recently approved by the FDA, provides a unique intervention in those with early SSc associated with ILD with elevated acute-phase reactants: two well designed trials showed lung function preservation in phase 2 and phase 3 trials. Stratifying patients based on key SSc-ILD characteristics (e.g. severity, risk of progression, comorbid disease presentation) may provide a useful guide for practitioners treating SSc-ILD.

Molecular imaging for systemic sclerosis-interstitial lung disease.

Molecular imaging for systemic sclerosis-interstitial lung disease.

Demographic characteristics and clinical manifestations of interstitial lung disease with systemic sclerosis in eastern part of Libya

Abstract Introduction: Pulmonary involvement, such as Interstitial Lung Disease (ILD) and Pulmonary Hypertension (PH ), accounts for significant morbidity and is the leading cause of Systemic sclerosis (SSc)-related morbidity and mortality. The aim of the current study was to study the frequency of occurrence of ILD in SSc and to describe the clinical and radiological picture of pulmonary involvement in SSc. Patients and Methods: Forty patients attending different rheumatology clinics in eastern part of Libya between January 2018 and September 2020 were included. Basic details including age, gender, disease duration, detailed history, and clinical examination were noted. Autoimmune profiling included rheumatoid factor, antinuclear antibodies, and anti-Scl-70 antibodies. Pulmonary function test, chest X-ray (CXR), and high-resolution computed tomography of the chest (HRCT) in all patients were recorded. Data presented either as frequencies and percentages or as means ± standard deviation. Results: The male: female ratio was 1:9 with a mean age of 37.5 ± 9.6 years and duration of illness 6 ± 4 years. diffuse cutaneous SSc was seen in 62.5% of the patients. 77.5% of the participants had bilateral crepitation and 57.5% had loud P2. Presenting complaints included gastrointestinal reflux in 72.5%, digitalis ulcerations in 40%, and synovitis/arthritis of all patients. Other comorbidities included congestive heart failure in 12.5%, PH in 15%, and renal impairments in 7.5% of all patients. Anti-Scl-70 antibody was the most common in all patients (45%), followed by anti-centromere Ab (25%), anti-U3 RNP (10%), and anti-U1 RNP (5%). 72.5% of the participants had reticulonodular shadows on CXR. HRCT showed honeycombing as the predominant finding (37.5%). Echocardiograms showed that 15% of all patients have signs of PH. Duration of disease, dyspnea, cough, bilateral crepitations, and CXR were found to be significantly associated with extensive ILD (P < 0.05). Conclusion: ILD is a serious complication of SSc, it is more common among patients with dcSSc. Chest HRCT is very sensitive to detect ILD. A significant association was found in Libyan patients between the severity of ILD and the duration of disease, dyspnea, cough, bilateral crepts, and CXR.

Racial Disparities in Systemic Sclerosis: Short- and Long-Term Outcomes Among African American Participants of SLS I and II.

ObjectiveTo evaluate short‐ and long‐term outcomes of African American (AA) participants of Scleroderma Lung Studies (SLS) I and II.MethodsSLS I randomized 158 participants with systemic sclerosis‐interstitial lung disease (SSc‐ILD) to 1 year of oral cyclophosphamide (CYC) versus placebo. SLS II randomized 142 participants with SSc‐ILD to 1 year of oral CYC followed by 1 year of placebo versus 2 years of mycophenolate (MMF). Joint models compared the course of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) between AA and non‐AA, and Cox proportional hazard models assessed long‐term morbidity and mortality outcomes.ResultsIn SLS I, there was no difference in the course of the FVC or DLCO between AA and non‐AA in either treatment arm. In SLS II, AA had an improved course of the FVC compared with non‐AA in the CYC arm; in the MMF arm, there was no difference in FVC course. There was no difference in DLCO course in either arm. Time to death and respiratory failure were similar for AA and non‐AA in SLS I. There was a trend for improved survival and time to respiratory failure in AA compared with non‐AA in SLS II. AA race was not independently associated with mortality in the SLS I or II in the Cox models.ConclusionData from two randomized controlled trials demonstrated that AA patients with SSc‐ILD have similar morbidity and mortality outcomes compared with non‐AA patients. These findings contrast with the racial disparities described in prior observational studies and warrant further investigation.

The Association between MUC5B Rs35705950 and Risks of Idiopathic Interstitial Pneumonia, Systemic Sclerosis Interstitial Lung Disease, and Familial Interstitial Pneumonia: A Meta-Analysis.

Background:Interstitial lung disease (ILD) is a category of chronic lung diseases with more than 200 subtypes. Idiopathic interstitial pneumonia (IIP), systemic sclerosis (SSc) ILD, and familial interstitial pneumonia (FIP) are three major groups of lung diseases with different causes or with unknown causes. Mucin5B (MUC5B) belongs to the mucin family, which contribute to the lubricating and viscoelastic properties of the whole saliva, normal lung mucus, and cervical mucus. The association between MUC5B rs35705950 and ILDs risks has been widely studied. However, the results were inconclusive and inconsistent.Methods:In the present meta-analysis, the database PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI and Chinese Biomedical Literature Database were searched till Aug 20th, 2018. Overall 16 publications with 28 studies, 76345 cases and 18402 controls were included.Results:The results indicated a significant increase of overall IIP risk for TT genotype and T allele of the rs35705950 in all genetic models (TT vs GG, OR=9.11; TT vs GT+TT, OR=5.80; GT+TT vs GG, OR=4.34; T vs G, OR=4.03. P<0.0001). Subgroup analysis by subtypes of IIP revealed higher risks of TT genotype and T allele for IPF and iNSIP (P<0.05). A significant increase of FIP risk was also found for the TT genotype and T allele of the rs35705950 (TT vs GG, OR=17.08; GT+TT vs GG, OR=6.02; T vs G, OR=1.64.P<0.05).Conclusion:No significant relations existed between the rs35705950 and SSc-ILD risks. MUC5B rs35705950 might be a predictor for the susceptibility of IIP and FIP.

Rituximab for the treatment of systemic sclerosis-interstitial lung disease.

Rituximab for the treatment of systemic sclerosis-interstitial lung disease.

Osteopontin Links Myeloid Activation and Disease Progression in Systemic Sclerosis

SummaryProgressive lung fibrosis is a major cause of mortality in systemic sclerosis (SSc) patients, but the underlying mechanisms remain unclear. We demonstrate that immune complexes (ICs) activate human monocytes to promote lung fibroblast migration partly via osteopontin (OPN) secretion, which is amplified by autocrine monocyte colony stimulating factor (MCSF) and interleukin-6 (IL-6) activity. Bulk and single-cell RNA sequencing demonstrate that elevated OPN expression in SSc lung tissue is enriched in macrophages, partially overlapping with CCL18 expression. Serum OPN is elevated in SSc patients with interstitial lung disease (ILD) and prognosticates future lung function deterioration in SSc cohorts. Serum OPN levels decrease following tocilizumab (monoclonal anti-IL-6 receptor) treatment, confirming the connection between IL-6 and OPN in SSc patients. Collectively, these data suggest a plausible link between autoantibodies and lung fibrosis progression, where circulating OPN serves as a systemic proxy for IC-driven profibrotic macrophage activity, highlighting its potential as a promising biomarker in SSc ILD.

Elastic Registration-driven Deep Learning for Longitudinal Assessment of Systemic Sclerosis Interstitial Lung Disease at CT.

Background Longitudinal follow-up of interstitial lung diseases (ILDs) at CT mainly relies on the evaluation of the extent of ILD, without accounting for lung shrinkage. Purpose To develop a deep learning-based method to depict worsening of ILD based on lung shrinkage detection from elastic registration of chest CT scans in patients with systemic sclerosis (SSc). Materials and Methods Patients with SSc evaluated between January 2009 and October 2017 who had undergone at least two unenhanced supine CT scans of the chest and pulmonary function tests (PFTs) performed within 3 months were retrospectively included. Morphologic changes on CT scans were visually assessed by two observers and categorized as showing improvement, stability, or worsening of ILD. Elastic registration between baseline and follow-up CT images was performed to obtain deformation maps of the whole lung. Jacobian determinants calculated from the deformation maps were given as input to a deep learning-based classifier to depict morphologic and functional worsening. For this purpose, the set was randomly split into training, validation, and test sets. Correlations between mean Jacobian values and changes in PFT measurements were evaluated with the Spearman correlation. Results A total of 212 patients (median age, 53 years; interquartile range, 45-62 years; 177 women) were included as follows: 138 for the training set (65%), 34 for the validation set (16%), and 40 for the test set (21%). Jacobian maps demonstrated lung parenchyma shrinkage of the posterior lung bases in patients found to have worsened ILD at visual assessment. The classifier detected morphologic and functional worsening with an accuracy of 80% (32 of 40 patients; 95% confidence interval [CI]: 64%, 91%) and 83% (33 of 40 patients; 95% CI: 67%, 93%), respectively. Jacobian values correlated with changes in forced vital capacity (R = -0.38; 95% CI: -0.25, -0.49; P < .001) and diffusing capacity for carbon monoxide (R = -0.42; 95% CI: -0.27, -0.54; P < .001). Conclusion Elastic registration of CT scans combined with a deep learning classifier aided in the diagnosis of morphologic and functional worsening of interstitial lung disease in patients with systemic sclerosis. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.

The MUC5B promoter variant does not predict progression of interstitial lung disease in systemic sclerosis

ObjectiveTo investigate the prevalence of the MUC5B promoter variant rs35705950 in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) and whether its presence predicts response to immunosuppression with cyclophosphamide (CYC) and mycophenolate (MMF). MethodsSSc-ILD patients who participated in Scleroderma Lung Study (SLS) II (MMF versus CYC) were included in this study (N = 142). TaqMan Genotyping Assays were used to determine the MUC5B rs35705950 single nucleotide polymorphism. Joint models were created to examine how the presence of this variant affected the course of the forced vital capacity (FVC) over 2 years. Linear regression models were used to investigate the relationship between the presence of this variant and the change in quantitative radiographic fibrosis. ResultsAmong 128 participants who were tested for this variant, 18% possessed at least one copy of the MUC5B minor allele. Patients with at least one copy of this allele were similar to those without the allele with respect to age, sex, SSc subtype, ILD disease severity; however, this variant was rare among African Americans (3.7%). The presence of the MUC5B variant did not affect the course of the FVC, nor the change in quantitative radiographic fibrosis, ground glass or ILD scores in either treatment arm. ConclusionIn the context of a randomized controlled trial for SSc-ILD, the presence of the MUC5B variant did not predict disease severity, nor affect treatment response to MMF or CYC. Future studies are needed to determine whether this variant affects ILD progression in other SSc cohorts and in patients receiving anti-fibrotic therapy.

Thoracic lymphadenopathy as possible predictor of the onset of interstitial lung disease in systemic sclerosis patients without lung involvement at baseline visit: A retrospective analysis.

To evaluate clinical, laboratory, or radiographic predictors of the onset of interstitial lung disease in systemic sclerosis. Sixty-five out of 220 systemic sclerosis outpatients, without interstitial lung disease at baseline and with ⩾3 chest high resolution computed tomography scans during follow-up were recruited. Thoracic lymphadenopathy and interstitial lung disease were assessed by chest high resolution computed tomography. Hazard ratio (95% confidence interval) of interstitial lung disease occurrence was assessed by Cox regression models, adjusting patient's demographics and disease characteristics. Sensitivity, specificity, and accuracy of the interstitial lung disease predictors were evaluated by receiver operating characteristic analysis. The development of interstitial lung disease was observed in 44/65 (68%) patients. Thoracic lymphadenopathies was detected in 40/65 (61%) patients, of whom 36 (82%) developed interstitial lung disease, but only four patients with thoracic lymphadenopathies did not develop ILD at last visit of follow-up (19%) (p = 0.0001). Adjusted hazard ratio of systemic sclerosis-interstitial lung disease onset was 5.8 (95% confidence interval, 2.0-16.5) for thoracic lymphadenopathy, which preceded by 108 ± 98 weeks the systemic sclerosis-interstitial lung disease detection. Thoracic lymphadenopathy had 84% specificity, 81% sensitivity, and 0.82 accuracy to predict interstitial lung disease. In particular, anticentromere antibodies or limited cutaneous subset of systemic sclerosis patients with thoracic lymphadenopathy showed earlier interstitial lung disease onset than those without lymphadenopathy. In addition, patients who developed interstitial lung disease had higher frequency of anti-Scl-70 (57% vs 19%; p = 0.009) and diffuse cutaneous subset (29% vs 3%; p = 0.02) than those who did not. Thoracic lymphadenopathy was the strongest independent predictor of systemic sclerosis-interstitial lung disease, mostly in anticentromere antibodies and limited cutaneous subset of systemic sclerosis patients. Further prospective studies are needed to confirm our preliminary data and to understand whether thoracic lymphadenopathies may have a pathogenetic role in interstitial lung disease development.

Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders

Background Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). Aims To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications of SS and SSD. Methods In a cross-sectional observational study, we recruited 125 consecutive patients, affected by SS and SSD and referred to a tertiary-level pulmonary hypertension outpatient clinic. All patients underwent a comprehensive evaluation for identification of PAH and ILD. Gas6, sMer, and sAxl concentrations were measured with ELISA protocols, and concentrations were compared according to PAH or ILD. Results Nineteen subjects had pulmonary hypertension (PH) (14 PAH), and 39 had ILD (6 severe). Plasma sMer was increased in PAH (18.6 ng/ml IQR [11.7-20.3]) with respect to the absence (12.4 [8.0-15.8]) or other form of pulmonary hypertension (9.6 [7.4-12.5]; K–W variance p < 0.04). Conversely, Gas6 and sAxl levels were slightly increased in mild ILD (25.8 ng/ml [19.5-32.1] and 24.6 [20.1-32.5]) and reduced in severe ILD (16.6 [15.0-22.1] and 15.5 [14.9-22.4]) in comparison to no evidence of ILD (23.4 [18.8-28.1] and 21.6 [18.1-28.4]; K–W, p ≤ 0.05). Plasma sMer ≥ 19 ng/ml has 50% sensitivity and 92% specificity in PAH identification (area under the ROC curve (AUC) 0.697, p < 0.03). Values of Gas6 ≤ 24.5 ng/ml and of sAxl ≤ 15.5 ng/ml have 100% and 67% sensitivity and 47% and 86% specificity, respectively, in identifying severe ILD (Gas6 AUC 0.787, p < 0.001; sAxl AUC 0.705, p < 0.05). Conclusions The assay of Gas6 sAxl and sMer may be useful to help in the identification of PAH and ILD in SS and SSD patients. The Gas6/TAM system seems to be relevant in cardiopulmonary complications of SS and SSD and merits further investigations.

Pathogenesis of systemic sclerosis associated interstitial lung disease.

Systemic sclerosis is an autoimmune disease leading to vasculopathy and fibrosis of skin and internal organs. Despite likely shared pathogenic mechanisms, the patterns of skin and lung fibrosis differ. Pathogenesis of interstitial lung disease, a major cause of death in systemic sclerosis, reflects the intrinsic disease pathobiology and is associated with distinct clinical phenotypes and laboratory characteristics. The commonest histological pattern of systemic sclerosis–interstitial lung disease is non-specific interstitial pneumonia. Systemic sclerosis–interstitial lung disease pathogenesis involves multiple components, including susceptibility and triggering factors, which could be genetic or environmental. The process is amplified likely through ongoing inflammation and the link between inflammatory activity and fibrosis with IL6 emerging as a key mediator. The disease is driven by epithelial injury, reflected by markers in the serum, such as surfactant proteins and KL-6. In addition, mediators that are produced by epithelial cells and that regulate inflammatory cell trafficking may be important, especially CCL2. Other factors, such as CXCL4 and CCL18, point towards immune-mediated damage or injury response. Monocytes and alternatively activated macrophages appear to be important. Transforming growth factor beta appears central to pathogenesis and regulates epithelial repair and fibroblast activation. Understanding pathogenesis may help to unravel the stages of systemic sclerosis–interstitial lung disease, risks of progression and determinants of outcome. With this article, we set out to review the multiple factors, including genetic, environmental, cellular and molecular, that may be involved in the pathogenesis of systemic sclerosis–interstitial lung disease and the mechanisms leading to sustained fibrosis. We propose a model for the pathogenesis of systemic sclerosis–interstitial lung disease, based on the available literature.

The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements.

Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. An unrestricted grant from Boehringer Ingelheim International.

A Real-World Experience of Mycophenolate Mofetil for Systemic Sclerosis: A Retrospective Multicenter Observational Study.

Objectives This study aims to assess the efficacy and safety of mycophenolate mofetil (MMF) on lung function and skin thickness in Korean patients with systemic sclerosis-interstitial lung disease (SSc-ILD) in a real-world setting.Patients and methods This retrospective, medical chart-based study was performed at four centers in South Korea and included 34 patients (2 males, 32 females; median age 50.5 years; range, 25 to 72 years) with SSc-ILD. We investigated changes in forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), and modified Rodnan skin score (mRSS) according to MMF treatment for 24 months.Results The mean dose and treatment duration of MMF were 1,338.2±439.0 mg/day and 13.1±9.3 months, respectively. Although FVC decreased significantly at 15 months, FVC and DLCO did not change significantly during treatment with MMF. Median mRSS decreased significantly from 17.5 (2-40) to 10.5 (2-40) units (p<0.0001). Thirteen patients (38.24%) discontinued treatment with MMF [treatment duration 8.00 (3.0-24.0) months]; the predominant cause of discontinuation was of economic nature (46.15%). No serious adverse events were reported.Conclusion This real-world based study supports the role of MMF in the stabilization of lung function and the improvement in skin thickness with an acceptable safety profile in patients with SSc. Economic burden is the main cause of discontinued treatment with MMF.

Análisis del índice masa corporal y factores de riesgo de neumopatía intersticial en pacientes con esclerosis sistémica

ObjectiveTo determine the risk factors and the potential relationship between body mass index (BMI) and the development of interstitial lung disease (ILD) in patients with systemic sclerosis. MethodsA cross-sectional, correlational, study with a non-probabilistic sample was conducted on consecutive patients with scleroderma seen in the Rheumatology Division at Hospital Universitario de Caracas during the period April to September 2018. Patients underwent clinical and laboratory assessments, anthropometric measurements, pulmonary function tests, and high-resolution computed axial tomography scan of the chest. ResultsOf 48 patients, 95.8% were female, with a high prevalence of limited cutaneous systemic sclerosis (lcSSc) (64.6%). Underweight (BMI <18.5kg/m2) was a risk factor for the development of ILD (OR 4.60; 95% CI 1.12-18.86). There was directly proportional relationship between BMI and forced vital capacity, with no statistical significance (CC 0.23; P=.1180). However, other predictors of ILD included diffuse systemic sclerosis (OR 6.91, 95% CI; 1.78-26.85), modified Rodnan Skin Score (mRSS) (OR 1.25; 95% CI; 1.04-1.30), and a speckled pattern of antinuclear antibody (OR 5.62; 95% CI; 1.33-23.62). Multivariate analysis showed that mRSS (OR 1.34; 95% CI; 1.04-1.72) and the presence of a speckled antinuclear antibody (OR 25.99; 95% CI; 1.02-16.02) were independent predictors of ILD. The percentage of BMI lost in a period of time of 2008-2018 was 14.3% (P=.0021), which was higher than rheumatoid arthritis (P=.0000), systemic lupus erythematosus (P=.0025), and healthy patients (P=.0331). ConclusionBMI and ILD are inversely correlated. Age, underweight, higher mRSS, and speckled pattern of antinuclear antibody were risk factors for development of ILD in patients with systemic sclerosis. The mRSS could be used as a clinical predictive tool for ILD in systemic sclerosis.

Analysis of body mass index and risk factors of interstitial lung disease in systemic sclerosis patients

ObjectiveTo determine the risk factors and the potential relationship between body mass index (BMI) and the development of interstitial lung disease (ILD) in patients with systemic sclerosis. MethodsA cross-sectional, correlational, study with a non-probabilistic sample was conducted on consecutive patients with scleroderma seen in the Rheumatology Division at Hospital Universitario de Caracas during the period April to September 2018. Patients underwent clinical and laboratory assessments, anthropometric measurements, pulmonary function tests, and high-resolution computed axial tomography scan of the chest. ResultsOf 48 patients, 95.8% were female, with a high prevalence of limited cutaneous systemic sclerosis (lcSSc) (64.6%). Underweight (BMI<18.5kg/m2) was a risk factor for the development of ILD (OR 4.60; 95% CI 1.12–18.86). There was directly proportional relationship between BMI and forced vital capacity, with no statistical significance (CC 0.23; p=0.1180). However, other predictors of ILD included diffuse systemic sclerosis (OR 6.91, 95% CI; 1.78–26.85), modified Rodnan skin score (mRSS) (OR 1.25; 95% CI; 1.04–1.30), and a speckled pattern of antinuclear antibody (OR 5.62; 95% CI; 1.33–23.62). Multivariate analysis showed that mRSS (OR 1.34; 95% CI; 1.04–1.72) and the presence of a speckled antinuclear antibody (OR 25.99; 95% CI; 1.02–16.02) were independent predictors of ILD. The percentage of BMI lost in a period of time of 2008–2018 was 14.3% (p=0.0021), which was higher than rheumatoid arthritis (p=0.0000), systemic lupus erythematosus (p=0.0025), and healthy patients (p=0.0331). ConclusionBMI and ILD are inversely correlated. Age, underweight, higher mRSS, and speckled pattern of antinuclear antibody were risk factors for development of ILD in patients with systemic sclerosis. The mRSS could be used as a clinical predictive tool for ILD in systemic sclerosis.

Subclinical Interstitial Lung Disease in Patients with Systemic Sclerosis. A Pilot Study on the Role of Ultrasound.

Interstitial lung disease (ILD) is a common comorbidity present in patients with systemic sclerosis (SSc). Employment of high-resolution computed tomography (HRCT) is very limited and lung ultrasound (LUS) can be an alternative tool for the early evaluation of ILD. To determine the validity of LUS in the early detection of ILD in patients with SSc. Sixty-eight patients with SSc ≥18 years without respiratory symptoms were included. A rheumatologist rated the subclinical respiratory condition, another rheumatologist blinded to the clinical assessment performed the LUS. To determine validity HRCT was performed as well. Prevalence of ILD in SSc patients was 41.2% in contrast to the 4.8% healthy controls (P=.0001). Variables associated with LUS and HRCT findings were anti-centromere antibodies (P=.005) and the Rodnan skin score (P=.004). A positive correlation was present between the findings of HRCT and LUS (P=.001). Sensitivity and specificity were 91.2% and 88.6% respectively. Good reliability in the LUS findings was found between observers (k=.72). By proving to be a valid, trustworthy and feasible alternative tool, we consider that LUS can be implemented for the early detection of ILD in SSc.

In Silico Detection and Characterization of microRNAs and Their Target Genes in microRNA Microarray Datasets from Patients with Systemic Sclerosis-Interstitial Lung Disease.

Interstitial lung disease (ILD) is the main reason of death in patients with systemic sclerosis (SSc). The potential microRNA (miRNA)-messenger RNA (mRNA) interaction networks of SSc-ILD from a systematic biological perspective are unclear. To characterize differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DEGs) likely related to SSc-ILD, we downloaded the miRNA microarray dataset (GSE81923) and mRNA datasets (GSE76808 and GSE81292) from the Gene Expression Omnibus database. Comprehensive bioinformatic analyses were conducted to predict target genes for DE-miRNAs and generate an miRNA-hub gene network with SSc-ILD. In total, 26 DE-miRNAs were detected in SSc-ILD, among which 2 were upregulated and 24 were downregulated. Additionally, 178 common DEGs (55 upregulated and 123 downregulated) were identified. miRNAs were primarily enriched in pathways involving inflammation and regulation of fibroblasts. The hub genes identified were MMP7, IER2, HBEGF, CCL4, NFKBIA, JUNB, LIF, SERPINE1, FOSL1, and NAMPT. We discovered the miRNA-mediated regulatory network in SSc-ILD using an integrated bioinformatic analysis. The findings provide novel insight and expand our comprehension of the molecular mechanisms participating in the pathogenesis of SSc-ILD, along with identification of new potential diagnostic biomarkers.

Management of systemic sclerosis-associated interstitial lung disease.

To review the recently published data and provide a practical overview for management of systemic sclerosis-interstitial lung disease (SSc-ILD). Published evidence shows considerable practitioner variability in screening patients for ILD. Recent published data support use of cyclophosphamide or mycophenolate mofetil as first-line treatment of SSc-ILD. For patients not responding to first-line therapies, consideration is given to rituximab as rescue therapy. Recent trials of hematopoietic autologous stem cell transplantation have demonstrated benefit in patients with progressive SSc-ILD. Antifibrotic agents are approved in idiopathic pulmonary fibrosis; studies with antifibrotics are underway for SSc-ILD. The specter of rapidly progressive lung disease requires clinicians to risk stratify patients according to known predictors for progression and rigorously monitor for symptoms and advancing disease. The abovementioned therapies promise improved efficacy and favorable side-effect profiles compared to cyclophosphamide.