Over the years several lines of evidence have implied a pathological involvement of autonomic nervous system (ANS) in systemic sclerosis (SSc). However, the relationship between autonomic dysfunction and SSc is not yet fully understood. The aims of this scoping review were to map the research done in this field and inform future research to investigate pathogenic hypotheses of ANS involvement. We performed a scoping review of publications collected through a literature search of MEDLINE and Web of Science databases, looking for dysautonomia in SSc. We included original data from papers that addressed ANS involvement in SSc regarding pathogenesis, clinical presentation and diagnostic tools. 467 papers were identified, 109 studies were selected to be included in the present review, reporting data from a total of 2742 SSc patients. Cardiovascular system was the most extensively investigated, assessing heart rate variability with 24 h HolterECG or Ewing's autonomic tests. Important signs of dysautonomia were also found in digital vasculopathy, gastrointestinal system and SSc skin, assessed both with non-invasive techniques and histologically. Research hypotheses mainly regarding the relationship between sympathetic system - ischemia and the role of neurotrophins were then developed and discussed. We described the currently available evidence on pathogenesis, clinical presentation and diagnostic assessment of dysautonomia in SSc patients. A strong influence of ANS deregulation on SSc clearly emerges from the literature. Future research is warranted to clarify the mechanisms and timing of autonomic dysfunction in SSc.

Objectives: Lung ultrasound (LUS) and high-resolution CT (HRCT) are commonly used for the evaluation of interstitial lung disease (ILD). Nintedanib (NIN) is an antifibrotic therapy approved for systemic sclerosis-associated ILD (SSc-ILD). We assessed LUS and quantitative HRCT changes in SSc-ILD patients treated with NIN during a 1 year follow-up, evaluating relationships between imaging variations and functional or quality-of-life outcomes. Methods: SSc-ILD patients who started NIN were enrolled and followed for 12 months. Pulmonary function tests and patient-reported outcome measures (PROMs) were assessed half-yearly and quarterly, respectively. LUS was performed quarterly evaluating the presence of B-lines (BL) and pleural line irregularities (PLI). HRCT was repeated after 1 year and quantitatively analysed with CALIPER software. Results: Ten patients (70% female, mean age 62 years) were enrolled. The mean total number of both BL and PLI was constantly decreased during NIN treatment, being significantly reduced after 12 months (from 175.1 [66.7] to 120.8 [70.3] for BL, P = 0.005; and from 50.6 [32.5] to 37.2 [22.4] for PLI, P = 0.05). Male gender, smoking habit and baseline forced vital capacity <70% predicted were associated with worse LUS outcomes. A greater reduction in both BL and PLI was observed in those who improved in PROMs, especially modified Medical Research Council dyspnoea scale (P = 0.016 and P = 0.04, respectively) and Saint George's Respiratory Questionnaire (P = 0.006 and P = 0.026, respectively). No significant changes in the CALIPER percentages of normal parenchyma or ILD elements were observed after 12 months of NIN, thus paralleling the stabilization obtained at pulmonary function tests. Conclusion: We present preliminary results on NIN effects on SSc-ILD as assessed by LUS, a useful method for frequently repeated monitoring, and CALIPER, a valid implementation whenever a HRCT is performed.

Objectives: To assess the relationship between disease duration and the prevalence/distribution of nailfold videocapillaroscopy (NVC) patterns, named according to the current classification as ‘early’, ‘active’ and ‘late’, in a large cohort of systemic sclerosis (SSc) patients. Methods: A cross-sectional analysis was conducted on 1689 patients undergoing standardized NVC. Clinical-serological data and treatments were collected. Statistical comparisons and multivariable logistic regression models were applied, including analyses based on disease duration. Results: The prevalence of NVC patterns was as follows: ‘early’ 21.6%, ‘active’ 47.4%, ‘late’ 25.7% and normal/non-specific 5.3%. The distribution by disease duration showed that the three main patterns were always present. While the ‘early’ and ‘active’ progressively decreased (from 30.3% and 51.9% in patients with ≤5 yrs, to 14.6% and 43.5% in those >10 yrs, P < 0.01), the ‘late’ pattern increased from 13.2% (≤5 yrs) to 36.0% (>10 yrs) (P < 0.001) and was associated with internal organ involvement, anti-topoisomerase antibodies and more therapies (P < 0.01). Conversely, the ‘early’ and ‘active’ patterns were associated with the limited-cutaneous subset (P < 0.01) and anti-centromere antibodies (P < 0.001). Multivariable analysis confirmed a strong association between the ‘late’ pattern and skin/peripheral vascular involvement. Notably, the presence of the ‘late’ pattern in patients with ≤2 yrs (10.9%) was significantly associated with scleroderma renal crisis (P = 0.012). Conclusion: SSc-NVC patterns are not strictly time-dependent and can be observed at any stage of the disease, suggesting that microvascular damage progression is heterogeneous across different disease periods. Therefore, a revised classification of NVC changes considering both disease duration and NVC severity could improve its prognostic accuracy.

Objectives: To describe the prevalence of gastrointestinal (GI) symptoms in SSc and Very Early Diagnosis of SSc (VEDOSS), identify clinical and serological features associated with GI involvement and explore a cranio-caudal pattern of symptom distribution, using data from the Italian SPRING-SIR registry. Methods: This cross-sectional analysis included patients fulfilling 2013 ACR/EULAR SSc or VEDOSS criteria. GI involvement was defined as symptoms in at least one GI tract segment and categorized as upper and lower. Associations between GI involvement and clinical variables were assessed using logistic and ordinal regression models, adjusting for demographics, disease characteristics and autoantibodies. Results: Among 1917 SSc patients, 56% had GI symptoms, associated with longer disease duration, dcSSc, interstitial lung disease (ILD), digital ulcers (DU), telangiectasias and tobacco exposure. Extensive GI involvement correlated with more severe disease. Ordinal regression identified female sex, dcSSc, ILD, DU, telangiectasias, tobacco exposure and anti-centromere antibodies as variables significantly associated with more extensive GI involvement. Disease duration did not show a significant association with GI symptom extent. Among 211 VEDOSS patients, 41.2% reported GI symptoms (mostly oesophageal), significantly associated with puffy fingers and dyspnoea. Among VEDOSS, puffy fingers and anti-centromere antibodies were independent predictors of presence of oesophageal symptoms. Conclusion: GI involvement in SSc is linked to more severe disease and longer disease duration. Disease duration resulted linked to the presence of GI symptoms rather than extent of GI involvement. Puffy fingers and anti-centromere antibodies may associate with presence of early oesophageal symptoms in VEDOSS.