scholarly journals Circulating biomarkers of systemic sclerosis – interstitial lung disease

2020 ◽  
Vol 5 (2_suppl) ◽  
pp. 41-47 ◽  
Author(s):  
Anna-Maria Hoffmann-Vold ◽  
Håvard Fretheim ◽  
Chantal Meier ◽  
Britta Maurer
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Clinical Application ◽  
Topoisomerase I ◽  
Early Stage ◽  
Organ Damage ◽  
Disease Diagnosis ◽  
Surfactant Protein D ◽  
Circulating Biomarkers

Interstitial lung disease is a frequent organ manifestation in systemic sclerosis and is associated with high mortality. It is crucial to diagnose interstitial lung disease in systemic sclerosis and to assess severity and identify patients prone to progression at an early stage to ultimately decrease organ damage and improve outcome. Circulating anti-topoisomerase-I autoantibodies have long been associated with the presence and development of systemic sclerosis – interstitial lung disease, evidence on their potential to further predict the clinical course of systemic sclerosis is however conflicting. C-reactive protein is a marker of infection and systemic inflammation with widespread clinical application and is elevated in systemic sclerosis with a tendency towards higher abundancy in patients with early disease. The role of other circulating biomarkers is promising but hampered by the lack of standardized criteria and guidelines for sample/data collection, analyses, reporting and validation and has not reached prime time for clinical application. However, epithelial markers including Krebs von den Lungen-6 and surfactant protein D and several cytokines and chemokines including CCL2 and CCL18 for severity assessment of systemic sclerosis – interstitial lung disease patients at the time of interstitial lung disease diagnosis and to predict interstitial lung disease progression have been reported and seem to be promising candidate biomarkers in the future.

Elevated Serum Krebs von den Lungen-6 in Early Disease Predicts Subsequent Deterioration of Pulmonary Function in Patients with Systemic Sclerosis and Interstitial Lung Disease

2016 ◽  
Vol 43 (10) ◽  
pp. 1825-1831 ◽  
Author(s):  
Masataka Kuwana ◽  
Yuichiro Shirai ◽  
Tsutomu Takeuchi
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Early Stage ◽  
Characteristic Curve ◽  
Elevated Serum ◽  
Initial Assessment ◽  
Baseline Serum ◽  
Disease Modifying Drugs ◽  
Highly Correlated

Objective.To identify predictors of poor prognosis in patients with systemic sclerosis (SSc) associated with interstitial lung disease (ILD).Methods.Fifty patients with early-stage SSc-ILD who had never received disease-modifying drugs and were either observed for ≥ 10 years or died from ILD-related causes were enrolled. The baseline variables of patients who developed endstage lung disease (ESLD) were compared with those of patients who remained ESLD-free, and the Cox proportional hazard model was used to identify initial factors that correlated with ESLD development.Results.Sixteen patients (32%) developed ESLD during 173.5 ± 64.7 months of followup. Elevated serum Krebs von den Lungen-6 (KL-6) at initial assessment was highly correlated with ESLD development (p = 0.0002). Receiver-operating characteristic curve analysis revealed that a KL-6 value of 1273 U/ml effectively discriminated patients who developed ESLD from those who did not. Patients with KL-6 > 1273 U/ml were less likely to remain ESLD-free compared with those with lower KL-6 levels (p < 0.0001). Multivariate analysis showed that KL-6 > 1273 U/ml was the most reliable predictor of ESLD development (OR 51.2, 95% CI 7.6–343, p < 0.0001). Finally, the initial KL-6 level correlated with the forced vital capacity (FVC) decline rate (r = 0.58, p < 0.0001).Conclusion.The natural course of SSc-ILD is highly variable. Baseline serum KL-6 is a biomarker potentially useful for predicting FVC decline.

scholarly journals Predictors of progression in systemic sclerosis patients with interstitial lung disease

2020 ◽  
Vol 55 (5) ◽  
pp. 1902026 ◽  
Author(s):  
Oliver Distler ◽  
Shervin Assassi ◽  
Vincent Cottin ◽  
Maurizio Cutolo ◽  
Sonye K. Danoff ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Disease Progression ◽  
Topoisomerase I ◽  
Diagnostic Tools ◽  
Systemic Autoimmune Disease ◽  
High Resolution Computed Tomography ◽  
Time Period ◽  
Organ Systems

Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the leading cause of death in SSc.There are no valid biomarkers to predict the occurrence of SSc-ILD, although auto-antibodies against anti-topoisomerase I and several inflammatory markers are candidate biomarkers that need further evaluation. Chest auscultation, presence of shortness of breath and pulmonary function testing are important diagnostic tools, but lack sensitivity to detect early ILD. Baseline screening with high-resolution computed tomography (HRCT) is therefore necessary to confirm an SSc-ILD diagnosis. Once diagnosed with SSc-ILD, patients' clinical courses are variable and difficult to predict, although certain patient characteristics and biomarkers are associated with disease progression. It is important to monitor patients with SSc-ILD for signs of disease progression, although there is no consensus about which diagnostic tools to use or how often monitoring should occur. In this article, we review methods used to define and predict disease progression in SSc-ILD.There is no valid definition of SSc-ILD disease progression, but we suggest that either a decline in forced vital capacity (FVC) from baseline of ≥10%, or a decline in FVC of 5–9% in association with a decline in diffusing capacity of the lung for carbon monoxide of ≥15% represents progression. An increase in the radiographic extent of ILD on HRCT imaging would also signify progression. A time period of 1–2 years is generally used for this definition, but a decline over a longer time period may also reflect clinically relevant disease progression.

scholarly journals Serum TARC Levels in Patients with Systemic Sclerosis: Clinical Association with Interstitial Lung Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 660
Author(s):  
Ai Kuzumi ◽  
Ayumi Yoshizaki ◽  
Satoshi Ebata ◽  
Takemichi Fukasawa ◽  
Asako Yoshizaki-Ogawa ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Major Complication ◽  
Serum Levels ◽  
Surfactant Protein ◽  
Th2 Cells ◽  
Surfactant Protein D ◽  
Th2 Cytokine ◽  
Fibrotic Disorder

Systemic sclerosis (SSc) is a multisystem fibrotic disorder with autoimmune background. Accumulating evidence has highlighted the importance of T helper (Th) 2 cells in the pathogenesis of SSc and its complications. Because thymus and activation-regulated chemokine (TARC) is a potent chemoattractant for Th2 cells, we measured serum TARC levels in SSc patients and analyzed their correlation with interstitial lung disease (ILD), a major complication of SSc. Serum TARC levels were significantly elevated in patients with SSc, especially in those with the diffuse subtype, compared with healthy controls. In particular, dcSSc patients with SSc-associated ILD (SSc-ILD) showed higher TARC levels than those without SSc-ILD. However, there was no significant correlation between serum TARC levels and pulmonary function in SSc patients. Serum TARC levels did not correlate with serum levels of interleukin-13, an important Th2 cytokine, either. Furthermore, in the longitudinal study, serum TARC levels did not predict the onset or progression of SSc-ILD in patients with SSc. These results were in contrast with those of KL-6 and surfactant protein D, which correlated well with the onset, severity, and progression of SSc-ILD. Overall, these results suggest that serum TARC levels are not suitable for monitoring the disease activity of SSc-ILD.

scholarly journals Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database

2020 ◽  
pp. annrheumdis-2020-217455 ◽  
Author(s):  
Anna-Maria Hoffmann-Vold ◽  
Yannick Allanore ◽  
Margarida Alves ◽  
Cathrine Brunborg ◽  
Paolo Airó ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Organ Damage ◽  
Disease Course ◽  
Lung Function Decline ◽  
Mixed Effect ◽  
Progression Patterns

ObjectivesTo identify overall disease course, progression patterns and risk factors predictive for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD), using data from the European Scleroderma Trials And Research (EUSTAR) database over long-term follow-up.MethodsEligible patients with SSc-ILD were registered in the EUSTAR database and had measurements of forced vital capacity (FVC) at baseline and after 12±3 months. Long-term progressive ILD and progression patterns were assessed in patients with multiple FVC measurements. Potential predictors of ILD progression were analysed using multivariable mixed-effect models.Results826 patients with SSc-ILD were included. Over 12±3 months, 219 (27%) showed progressive ILD: either moderate (FVC decline 5% to 10%) or significant (FVC decline >10%). A total of 535 (65%) patients had multiple FVC measurements available over mean 5-year follow-up. In each 12-month period, 23% to 27% of SSc-ILD patients showed progressive ILD, but only a minority of patients showed progression in consecutive periods. Most patients with progressive ILD (58%) had a pattern of slow lung function decline, with more periods of stability/improvement than decline, whereas only 8% showed rapid, continuously declining FVC; 178 (33%) experienced no episode of FVC decline. The strongest predictive factors for FVC decline over 5 years were male sex, higher modified Rodnan skin score and reflux/dysphagia symptoms.ConclusionSSc-ILD shows a heterogeneous and variable disease course, and thus monitoring all patients closely is important. Novel treatment concepts, with treatment initiation before FVC decline occurs, should aim for prevention of progression to avoid irreversible organ damage.

Rapidly Progressive Systemic Sclerosis–associated Interstitial Lung Disease After Intravesical Bacillus Calmette-Guérin Therapy for Early-stage Bladder Cancer

2021 ◽  
pp. jrheum.201625
Author(s):  
Gonçalo Boleto ◽  
Jérôme Avouac ◽  
Yannick Allanore
Keyword(s):  
Bladder Cancer ◽  
Systemic Sclerosis ◽  
Respiratory Failure ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Early Stage ◽  
Wide Spectrum ◽  
Progressive Systemic Sclerosis ◽  
Bacillus Calmette Guerin ◽  
Common Cause

Despite recent advances in the management of systemic sclerosis–associated interstitial lung disease (SSc-ILD), it remains the most common cause of death and a significant contributor to morbidity.1,2 SSc-ILD is characterized by a wide spectrum of disease courses, with some patients having limited nonprogressive fibrosis, whereas others develop rapid and extensive fibrosis leading to respiratory failure.3

scholarly journals Circulating Biomarkers of Interstitial Lung Disease in Systemic Sclerosis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Harpreet K. Lota ◽  
Elisabetta A. Renzoni
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Disease Severity ◽  
Prospective Studies ◽  
Predictive Ability ◽  
Early Response ◽  
Response To Treatment ◽  
Circulating Biomarkers ◽  
Patients At Risk

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc). Although a large proportion of SSc patients have only limited interstitial involvement with an indolent course, in a significant minority ILD is progressive, requiring prompt treatment and careful monitoring. One of the main challenges for the clinician treating this highly variable disease is the early identification of patients at risk of progressive ILD, while avoiding potentially toxic treatments in those whose disease is inherently stable. Easily available and repeatable biomarkers that allow estimation of the risk of ILD progression and early response to treatment are highly desirable. In this paper, we review the evidence for circulating biomarkers with potential roles in diagnosis, monitoring of disease activity, or determining prognosis. Peripheral blood biomarkers offer the advantages of being readily obtained, non-invasive, and serially monitored. Several possible candidates have emerged from studies performed so far, including SP-D, KL-6, and CCL18. Presently however, there are few prospective studies evaluating the predictive ability of prospective biomarkers after adjustment for disease severity. Future carefully designed, prospective studies of well characterised patients with ILD, with optimal definition of disease severity and outcome measures are needed.

scholarly journals Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study

2021 ◽  
Vol 11 (6) ◽  
pp. 580
Author(s):  
Angela Toss ◽  
Amelia Spinella ◽  
Chrystel Isca ◽  
Caterina Vacchi ◽  
Guido Ficarra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Early Stage ◽  
Fold Increase ◽  
Breast Conserving Surgery ◽  
Pathological Features ◽  
Luminal A ◽  
Clinical And Pathological Features

Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients.

scholarly journals AB0451 TO EVALUATE THE PREVALENCE OF INTERSTITIAL LUNG DISEASE (ILD) AND/OR PULMONARY ARTERIAL HYPERTENSION (PAH) IN PATIENTS AFFECTED BY SYSTEMIC SCLEROSIS (SSC) AND TO DETERMINE THE FACTORS ASSOCIATED WITH ILD

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1253.1-1253
Author(s):  
R. Ortega Castro ◽  
R. Mariscal-Ocaña ◽  
M. Rojas-Giménez ◽  
J. Calvo Gutierrez ◽  
A. Escudero Contreras ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Topoisomerase I ◽  
Systolic Pressure ◽  
University Hospital ◽  
Pulmonary Artery Systolic Pressure ◽  
Skin Involvement ◽  
Factors Associated ◽  
Anticentromere Antibodies

Background:Systemic sclerosis (SSc) is a chronic autoimmune disease that carries significant mortality. Despite diagnostic and therapeutic advances in recent years, there is still a significant percentage of patients who do not present a complete clinical response, with the associated increase in morbidity and mortality. Specifically, pulmonary disease is frequent and entails a poor prognosis, with interstitial lung disease (ILD) and pulmonary hypertension (PAH) being the two most important complications, the first and second cause of mortality, respectively.Objectives:To evaluate the prevalence of ILD and/or PAH in patients affected by SSc and to determine the factors associated with ILD.Methods:Cross-sectional observational study of 102 patients diagnosed with SSc (Limited, Diffuse, SSc without scleroderma or Pre-scleroderma), treated between 1975 and 2020 at the Reina Sofia University Hospital in Cordoba. A descriptive study of the cohort was carried out and factors independently associated with ILD were evaluated using a multiple logistic regression model.Results:102 patients were included, 87.3% of these were female with an average age of 50.8 (14) years. There were 20 deaths (19.8%), from which 55% died because of SSc and the main reason was ILD and/or PAH. Respiratory complications (as ILD or as PAH) were present in 59 patients (57.8%), of whom 52 were diagnosed with ILD (90.4% with a pattern of non-specific interstitial pneumonia) and 25 PAH, whose mean pulmonary artery systolic pressure was 47.16 (18.54) mmHg. Anti-topoisomerase I antibodies were positive in 34.6% of patients who developed ILD, while anticentromere antibodies were more frequent in SSc without interstitial lung disease (80%). Independent factors associated with ILD were type of SSc, proximal skin involvement, anticentromere antibodies, current treatment with corticoids and the death.Conclusion:Just over half of the patients with SSc have lung disease (as ILD or as PAH). The main risk factors associated with ILD are proximal skin involvement and treatment with glucocorticoids, probably in the context of more severe forms that require more treatment. Anticentromere antibodies are more prevalent in patients with Limited SSc and their expression decreases the risk of developing ILD in these patients.References:[1]Orlandi M, Barsotti S, Lepri G, et al. Clin Exp Rheumatol 2018 Jul-Aug; 36 Suppl 113: 3-23[2]Hao Y, Hudson M, Baron M, et al. Arthritis Rheumatol. 2017;69(5):1067-1077.[3]Furue M, Mitoma C, Mitoma H, et al. Immunol Res. 2017 Aug; 65: 790-7.[4]Nihtyanova SI, Schreiber BE, Ong VH, et al. Arthritis Rheumatol. 2014 Jun; 66: 1625-35.Disclosure of Interests:None declared.

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