Interstitial Lung Disease in Scleroderma: Clinical Features and Pathogenesis

Luo, Yangyang; Xiao, Rong

doi:10.4172/2161-1149.s1-002

Cited by 4 publications

(11 citation statements)

References 40 publications

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“…The early phase of the disease involves events that may act as a trigger, which could be anything from the lung microbiome to environmental factors such as chemical exposure, recurrent microaspiration, and lung injury [9]. Changes in the lung tissue from these inciting events cause endothelial activation leading to microvascular injury and T and B cell infiltration [8][9][10]. Microvascular damage also induces inflammation and autoimmunity in the lung tissue, which ultimately stimulates the activation of fibroblasts [8][9][10].…”

Section: Pathogenesis Of Systemic Sclerosis-associated Interstitial Lung Diseasementioning

confidence: 99%

“…Changes in the lung tissue from these inciting events cause endothelial activation leading to microvascular injury and T and B cell infiltration [8][9][10]. Microvascular damage also induces inflammation and autoimmunity in the lung tissue, which ultimately stimulates the activation of fibroblasts [8][9][10]. Many profibrotic cytokines, chemokines, and proinflammatory mediators such TGF-B, platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) have been implicated to have a role in the pathogenesis of SSc-ILD through the activation of lung fibroblasts [8][9][10][11].…”

Section: Pathogenesis Of Systemic Sclerosis-associated Interstitial Lung Diseasementioning

confidence: 99%

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Systemic Sclerosis Associated Interstitial Lung Disease and Nintedanib: A Rare Disease and a Promising Drug

Kafle¹,

Magar²,

Patel³

et al. 2021

Cureus

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Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a rare disease with a progressive nature, eventually leading to lung fibrosis. Nintedanib, a tyrosine kinase inhibitor, is a widely accepted drug for treating idiopathic pulmonary fibrosis (IPF), a disease that shares some similarities with SSc-ILD regarding pathological disease processes. In this review, we aim to discuss the pathogenesis of SSc-ILD and the overall role of nintedanib in the management of SSc-ILD. SSc-ILD involves multiple pathological mediators contributing to various pathways that ultimately cause lung fibrosis. The pathogenesis of SSc-ILD is a complex phenomenon and still needs further study. Nintedanib has demonstrated its efficacy in the treatment of SSc-ILD by reducing the progression of the pathological process. It has also proven its clinical significance in the management of SSc-ILD. However, the currently available literature does not have any evidence to compare the effectiveness of nintedanib with the already available treatment modalities such as cyclophosphamide (CYC), mycophenolate mofetil (MMF), and azathioprine (AZT). The current literature also lacks information about nintedanib's long-term consequences on patients with SSc-ILD. Therefore, to create better evidence-based treatment guidelines, we recommend that researchers conduct randomized clinical trials comparing nintedanib to MMF, CYC, AZT, etc., and continue surveillance to explore the longterm consequences of nintedanib.

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Section: Pathogenesis Of Systemic Sclerosis-associated Interstitial Lung Diseasementioning

confidence: 99%

Section: Pathogenesis Of Systemic Sclerosis-associated Interstitial Lung Diseasementioning

confidence: 99%

Systemic Sclerosis Associated Interstitial Lung Disease and Nintedanib: A Rare Disease and a Promising Drug

Kafle¹,

Magar²,

Patel³

et al. 2021

Cureus

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“…ILD is associated with the high rate of mortality, which becomes conspicuous especially after five years of disease onset. Prognosis of patients with severe pulmonary impairment (FVC < 55% and DLCO < 40% of predicted normal values) is unfavorable; up to 42% die within 10 years of disease onset 34 .…”

Section: Interstitial Lung Disease (Ild)mentioning

confidence: 99%

Emergency situations in rheumatology with a focus on systemic autoimmune diseases

Vymětal¹,

Skácelová²,

Smrzova³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background and Aim. Rheumatic diseases are commonly considered chronic conditions. However, acute manifestations can be very severe and represent a diagnostic problem. Examples are systemic lupus erythematosus with acute flare, glomerulonephritis, CNS disorders and catastrophic antiphospholipid syndrome, scleroderma with interstitial lung disease, pulmonary hypertension and renal crisis and polyangiitis with alveolar haemorhage and acute respiratory failure. This aim of this paper is to overview emergency situations which can be encountered in the care of patients with autoimmune systemic diseases and vasculitides. Methods. A Pubmed search for both original and review articles, recent textbooks and current guidelines related to rheumatic diseases with possible acute situations were included in this review article. Relevant image documentation was obtained at the site over the past several years of observation. Conclusions. This paper provides an overview of facts and emergency situations which can be encountered in the care of patients with autoimmune systemic diseases and vasculitides. It is directed at clinicians working in intensive care. It provides a differential diagnostic overview and information which is rare and commonly underestimated.

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“…SSc pathogenetic processes involve development of fibrosis, vascular injury and autoimmune manifestations [ 6 – 9 ]. SSc patients are more susceptible than the general population to a variety of malignancies [ 10 ] and several possible clinical manifestations, notably interstitial lung disease (ILD) which is a major cause of death in SSc patients [ 11 , 12 ]. In ILD, lung tissue becomes progressively hardened and replaced by scar tissue, resulting in loss of respiratory function.…”

Section: Introductionmentioning

confidence: 99%

“…There are two main obstacles preventing a full understanding of SSc and the development of effective selective therapies. First, there is extreme heterogeneity in clinical manifestations among different SSc patients [ 12 , 16 ]. The disease course is highly variable in terms of onset, timing, intensity of symptoms, patterns of organ involvement and response to therapy.…”

Section: Introductionmentioning

confidence: 99%

A methodology for exploring biomarker – phenotype associations: application to flow cytometry data and systemic sclerosis clinical manifestations

et al. 2015

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BackgroundThis work seeks to develop a methodology for identifying reliable biomarkers of disease activity, progression and outcome through the identification of significant associations between high-throughput flow cytometry (FC) data and interstitial lung disease (ILD) - a systemic sclerosis (SSc, or scleroderma) clinical phenotype which is the leading cause of morbidity and mortality in SSc. A specific aim of the work involves developing a clinically useful screening tool that could yield accurate assessments of disease state such as the risk or presence of SSc-ILD, the activity of lung involvement and the likelihood to respond to therapeutic intervention. Ultimately this instrument could facilitate a refined stratification of SSc patients into clinically relevant subsets at the time of diagnosis and subsequently during the course of the disease and thus help in preventing bad outcomes from disease progression or unnecessary treatment side effects.The methods utilized in the work involve: (1) clinical and peripheral blood flow cytometry data (Immune Response In Scleroderma, IRIS) from consented patients followed at the Johns Hopkins Scleroderma Center. (2) machine learning (Conditional Random Forests - CRF) coupled with Gene Set Enrichment Analysis (GSEA) to identify subsets of FC variables that are highly effective in classifying ILD patients; and (3) stochastic simulation to design, train and validate ILD risk screening tools.ResultsOur hybrid analysis approach (CRF-GSEA) proved successful in predicting SSc patient ILD status with a high degree of success (>82 % correct classification in validation; 79 patients in the training data set, 40 patients in the validation data set).ConclusionsIRIS flow cytometry data provides useful information in assessing the ILD status of SSc patients. Our new approach combining Conditional Random Forests and Gene Set Enrichment Analysis was successful in identifying a subset of flow cytometry variables to create a screening tool that proved effective in correctly identifying ILD patients in the training and validation data sets. From a somewhat broader perspective, the identification of subsets of flow cytometry variables that exhibit coordinated movement (i.e., multi-variable up or down regulation) may lead to insights into possible effector pathways and thereby improve the state of knowledge of systemic sclerosis pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0722-x) contains supplementary material, which is available to authorized users.

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Interstitial Lung Disease in Scleroderma: Clinical Features and Pathogenesis

Cited by 4 publications

References 40 publications

Systemic Sclerosis Associated Interstitial Lung Disease and Nintedanib: A Rare Disease and a Promising Drug

Systemic Sclerosis Associated Interstitial Lung Disease and Nintedanib: A Rare Disease and a Promising Drug

Emergency situations in rheumatology with a focus on systemic autoimmune diseases

A methodology for exploring biomarker – phenotype associations: application to flow cytometry data and systemic sclerosis clinical manifestations

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