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

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.

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

The Journal of Rheumatology ◽

10.3899/jrheum.201625 ◽

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

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

Journal of Personalized Medicine ◽

10.3390/jpm11060580 ◽

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.

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Prediction of progression of interstitial lung disease in patients with systemic sclerosis: the SPAR model

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-213201 ◽

2018 ◽

Vol 77 (9) ◽

pp. 1326-1332 ◽

Cited By ~ 38

Author(s):

Wanlong Wu ◽

Suzana Jordan ◽

Mike Oliver Becker ◽

Rucsandra Dobrota ◽

Britta Maurer ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Prediction Model ◽

Lung Disease ◽

Validation Cohort ◽

Pulmonary Function Tests ◽

Characteristic Curve ◽

Airflow Obstruction ◽

Derivation Cohort

ObjectivesTo identify the predictive clinical characteristics and establish a prediction model for the progression of mild interstitial lung disease (ILD) in patients with systemic sclerosis (SSc).MethodsPatients with SSc from two independent prospective cohorts were included in this observational study. All patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria, had mild ILD at baseline diagnosed by High-Resolution Computed Tomography (HRCT), available baseline and ≥1 annual follow-up pulmonary function tests and no concomitant pulmonary hypertension or airflow obstruction. ILD progression was defined as a relative decrease in forced vital capacity (FVC)%≥15%, or FVC%≥10% combined with diffusing capacity for carbon monoxide %≥15% at 1-year follow-up. Candidate predictors for multivariate logistic regression were selected by expert opinion based on clinical significance. A prediction model for ILD progression was established in the derivation cohort and validated in the multinational validation cohort.ResultsA total of 25/98 and 25/117 patients with SSc showed ILD progression in the derivation cohort and the validation cohort, respectively. Lower SpO2 after 6 min walk test (6MWT) and arthritis ever were identified as independent predictors for ILD progression in both cohorts. The optimal cut-off value of SpO2 after 6MWT for predicting ILD progression was determined as 94% by receiver operating characteristic curve analysis. The derived SPAR model combining both predictors (SPO2 and ARthritis) increased the prediction rate from 25.5% to 91.7% with an area under the curve (95% CI) of 0.83 (0.73 to 0.93).ConclusionsThe evidence-based SPAR prediction model developed in our study might be helpful for the risk stratification of patients with mild SSc-ILD in clinical practice and cohort enrichment for future clinical trial design.

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Circulating biomarkers of systemic sclerosis – interstitial lung disease

Journal of Scleroderma and Related Disorders ◽

10.1177/2397198319894851 ◽

2020 ◽

Vol 5 (2_suppl) ◽

pp. 41-47 ◽

Cited By ~ 2

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.

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