Lung ultrasound compared to computed tomography detection and automated quantification of systemic sclerosis-associated interstitial lung disease: preliminary study.

Lung ultrasound (LUS) is a promising tool for detecting systemic sclerosis-associated interstitial lung disease (SSc-ILD). Currently, consensus on the best LUS findings and execution technique is lacking. OBJECTIVES: To compare qualitative and quantitative assessment of B-lines and pleural line (PL) alterations in SSc-ILD with chest computed tomography (CT) analysis. METHODS: During 2021-2022, consecutive SSc patients according to 2013 ACR/EULAR classification criteria underwent pulmonary functional tests (PFTs). On the same day, if a CT was performed over a ± 6 months period, LUS was performed by two certified blinded operators using a 14-scans method. The ≥10 B-lines cut-off proposed by Tardella and the Fairchild's PL criteria fulfilment were selected as qualitative findings. As quantitative assessment, total B-lines number and the quantitative PL score adapted from the semi-quantitative Pinal-Fernandez score were collected. CT scans were evaluated by two thoracic radiologists for ILD presence, with further processing by automated texture analysis software (qCT). RESULTS: 29 SSc patients were enrolled. Both qualitative LUS scores were significantly associated to ILD presence on CT, with Fairchild's PL criteria resulting in slightly more accuracy. Results were confirmed on multivariate analysis. All qualitative and quantitative LUS findings were found to be significantly associated with qCT ILD extension and radiological abnormalities. Mid and basal PL quantitative score correlated with mid and basal qCT ILD extents. Both B-lines and PL alterations differently correlated with PFTs and clinical variables. CONCLUSION: This preliminary study suggests the utility of a comprehensive LUS assessment for SSc-ILD detection compared with CT and qCT.

Heparin-Independent and Heparin-Dependent Anti-CXCL4 Antibodies Have a Reciprocal Expression in a Systemic Sclerosis Patients' Cohort.

Systemic sclerosis (SSc) is a chronic disease characterized by skin/internal organ fibrosis, vasculopathy and autoimmunity. Chemokine (C-X-C motif) ligand 4 (CXCL4) is an early SSc biomarker that predicts worse disease outcome. We previously reported that CXCL4 is an autoantigen in SSc, and anti-CXCL4 antibodies correlated with IFN-I and were more abundant in patients with lung fibrosis. However, it is unclear whether antibodies to CXCL4 in SSc are only directed to CXCL4 or recognize complexes formed by CXCL4 and heparin. Here, by analyzing an SSc cohort, we addressed the occurrence of circulating heparin-dependent VS heparin-independent anti-CXCL4 antibodies and their relationship with a few disease parameters. We found that heparin-dependent, like the heparin-independent antibodies, are higher in SSc as compared to healthy donors; they are detectable in 24% and 30% of the SSc patients, respectively, and appear inversely correlated and mutually exclusive. Like the heparin-independent antibodies, heparin-dependent antibodies correlated with digital ulcers. However, in contrast to heparin-independent antibodies, heparin-dependent antibodies did not correlate with IFN-I, but were largely expressed in patients with pulmonary arterial hypertension. This pilot study indicates that heparin-dependent antibodies are worth studying in larger SSc cohorts to address whether they discriminate SSc sub-groups with different pathological characteristics and outcomes.

Psychological Fragility in an Italian Cohort of Systemic Sclerosis Patients During COVID-19 Pandemic Category: Short Communication.

Objective: This work aims to evaluate the prevalence of anxiety and COVID-19-related fear in systemic sclerosis (SSc) patients during the second and third waves of the SARS-CoV-2 pandemic in Italy and their possible associated factors. Methods: A cohort study was carried out on 114 SSc patients referred to our Scleroderma Clinic, matched for sex and age. Twenty-eight of them had missed scheduled examinations during the October 2020-March 2021 period and 86 has attended regular outpatient visits during the same period. Both groups were administered (by telephone for cases and in-person for controls) the Generalized Anxiety Disorder Scale-7 (GAD-7) questionnaire and the validated on SSc patients COVID-19 Fears Questionnaire for Chronic Medical Conditions (COVID-19 Fears). Concurrent factors related to higher scores were investigated in patients who did not have an outpatient follow-up. Results: The missing group had significantly more patients scoring ≥8 on the GAD-7 questionnaire [22 (78.6%) vs 16 (18.6%), p < 0.0001] and significantly higher scores on the COVID-19 Fears questionnaire (median [quartiles] 31.5 [26.25;37.25] vs 20 [13.75;28], p < 0.0001) than the attending group. Multivariate analysis performed on the missing patients group showed a significant association of the lack of work and ongoing therapy for anxiety/depression with GAD-7 (p = 0.0275 and p = 0.0188) and COVID-19 Fears score (p = 0.0016 and p = 0.0099). Conclusion: Anxiety disorder and COVID-19-related fear were greater in SSc patients who missed regular follow-ups and are associated with a lack of work activity. These findings aim to identify a subgroup deserving attention regarding risk factors for missed periodic controls.

New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis.

Chemokine (C-X-C motif) ligand 4 (CXCL4) is a biomarker of unfavorable prognosis in Systemic Sclerosis (SSc), a potentially severe autoimmune condition, characterized by vasculitis, fibrosis and interferon (IFN)-I-signature. We recently reported that autoantibodies to CXCL4 circulate in SSc patients and correlate with IFN-α. Here, we used shorter versions of CXCL4 and CXCL4-L1, the CXCL4 non-allelic variant, to search for autoantibodies exclusively reacting to one or the other CXCL4 form. Moreover, to address whether anti-CXCL4/CXCL4-L1 antibodies were present before SSc onset and predicted SSc-progression, we longitudinally studied two VEDOSS (Very Early Diagnosis of Systemic Sclerosis) patient cohorts, separating SSc-progressors from SSc-non-progressors. We found that anti-CXCL4-specific autoantibodies were present in both SSc and VEDOSS patients (both SSc-progressors and SSc-non-progressors). Anti-CXCL4-L1-specific autoantibodies were especially detected in long-standing SSc (lsSSc). Anti-CXCL4/CXCL4-L1 antibodies correlated with IFN-α and with specific SSc-skin features but only in lsSSc and not in early SSc (eaSSc) or VEDOSS. Thus, a broader antibody response, with reactivity spreading to CXCL4-L1, is characteristic of lsSSc. The early anti-CXCL4 autoantibody response seems qualitatively different from, and likely less pathogenic than, that observed in advanced SSc. Lastly, we confirm that anti-CXCL4 autoantibodies are SSc-biomarkers and uncover that also CXCL4-L1 becomes an autoantigen in lsSSc.

COVID-19 and systemic sclerosis: analysis of lifestyle changes during the SARS-CoV-2 pandemic in an Italian single-center cohort.

The outbreak of SARS-CoV-2 has changed the habits and lives of people worldwide. Patients affected by systemic sclerosis (SSc) experienced constant fear because of their immunocompromised status. The aim of this study was to investigate the prevalence of SARS-CoV-2 infection and to analyze the lifestyle changes in a single-center cohort of SSc patients and if these changes were more severe than in the general population. During the Italian lockdown, we supplied two surveys to our 184 SSc patients. In the first one, filled by 110 patients, we asked if SARS-CoV-2 had infected them or if they experienced signs and symptoms consistent with COVID-19. The second survey, performed by 79 SSc patients and 63 healthy subjects, included questions about the lifestyle adopted during this specific period. Among our patients, COVID-19 was diagnosed only in one case, while three other subjects reported signs and symptoms suggestive for the disease. Regarding the second survey, our patients greatly changed their lifestyle during the pandemic, adopting more restrictive isolation measures, because of their awareness of frailty. To date, we do not dispose of enough data to speculate about the risk of COVID-19 among immunocompromised patients, although in our SSc patients their frailty seems to have been their shelter. Pending more accurate epidemiological studies, it is essential to share as much data as possible to better understand the impact of COVID-19 on SSc patients' health. Key points • The lifestyle adopted by SSc patients during the first months of COVID-19 pandemic was characterized by more stringent isolation rules than general population. • The prudential behavior of patients with SSc during Italian lockdown should be considered as a possible bias when analyzing the risk of SARS-CoV-2 disease in these subjects, as well as a protective factor against infection.