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The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lung fibrosis and a long standing SSc pulmonary involvement have been largely proposed as lung cancer risk factors, and the exposure to cyclophosphamide and an upper gastrointestinal involvement have been traditionally linked to bladder and oesophagus cancers, respectively. Furthermore, immune checkpoint inhibitors used for cancer therapy can induce immune-related adverse events, which are more frequent and severe in patients with pre-existing autoimmune diseases such as SSc. The strong association between SSc and cancer occurrence steers clinicians to carefully survey SSc patients performing periodical malignancy screening. In the present review, the most relevant bilateral relationships between SSc and cancer will be addressed.

Objectives We characterized the microbiota in systemic sclerosis (SSc), focusing on the skin-oral-gut axis and serum and faecal free fatty acid (FFA) profile. Methods Twenty-five SSc patients with ACA or anti-Scl70 autoantibodies were enrolled. The microbiota of faecal, saliva and superficial epidermal samples was assessed through next generation-sequencing analysis. Gas chromatography-mass spectroscopy was used to quantity faecal and serum FFAs. Gastrointestinal symptoms were investigated with UCLA GIT-2.0-questionnaire. Results The ACA+ and anti-Scl70+ groups displayed different cutaneous and faecal microbiota profiles. The classes of cutaneous Sphingobacteria and Alphaproteobacteria, the faecal phylum of Lentisphaerae, the classes of Lentisphaeria and Opitutae, and the genus of NA-Acidaminococcaceae were significantly higher in faecal samples of the ACA+, compared with anti-Scl70+ patients. The cutaneous Sphingobacteria and the faecal Lentisphaerae were significantly correlated (rho = 0.42; p= 0.03). A significant increase in faecal propionic acid was observed in ACA+ patients. Moreover, all faecal medium-chain FFAs and hexanoic acids were significantly higher in ACA+ compared with anti-Scl70+ group (p< 0.05 and p< 0.001, respectively). In the ACA+ group, the analysis of serum FFA levels showed an increasing trend in valeric acid. Conclusions Different microbiota signatures and FFA profiles were found in the two groups of patients. Despite being in different body districts, the cutaneous Sphingobacteria and faecal Lentisphaerae appear interdependent.

No abstract available

Background: The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAK-inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD). Methods: We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centers from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months of the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests. Results: We included 43 patients with RA-ILD and 23 males (53.48%) with a median age (interquartile range, IQR) of 68.87 (61.46–75.78) treated with JAKi. The median follow-up was 19.1 months (11.03–34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing capacity of lung for carbon monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%). Discussion: This study suggests that JAKi therapy might be a safe therapeutic option for patients with RA-ILD in a short-term follow-up.

Summary Background Preliminary criteria for the very early diagnosis of systemic sclerosis (VEDOSS) have been previously proposed to identify signs and symptoms in patients with Raynaud's phenomenon. Patients with all signs or symptoms of the VEDOSS criteria already fulfil the 2013 American College of Rheumatology–European League Against Rheumatism (ACR–EULAR) classification criteria for systemic sclerosis. However, prospective data for the evolution to fulfilling these criteria do not exist. We therefore aimed to determine the clinical value of the VEDOSS criteria to identify patients with Raynaud's phenomenon who progress to systemic sclerosis within 5 years. Methods The VEDOSS project was a multicentre, longitudinal registry study done in 42 European Scleroderma Trial and Research group centres located in 20 countries in Europe, North America, and South America. Patients with Raynaud's phenomenon were eligible for enrolment. Those who had fulfilled the 1980 ACR or the 2013 ACR–EULAR classification criteria for systemic sclerosis, as well as of any other ACR or EULAR classification criteria for other definite connective tissue diseases at enrolment were excluded. Data were recorded each year during follow-up visits and included the four VEDOSS criteria (ie, positivity for antinuclear antibodies [ANAs], puffy fingers, systemic sclerosis-specific autoantibodies, and abnormal nailfold capillaroscopy). The primary endpoint was the fulfilment of the 2013 ACR–EULAR classification criteria for systemic sclerosis (ie, progression from enrolment to follow-up). Proportion of progressors and VEDOSS criteria interaction were reported descriptively. Predictors of progression of the distinct VEDOSS criteria interactions were determined based on the point prevalence at 5 years. To investigate the intermediate course of progression of the distinct VEDOSS criteria and their combinations, Kaplan-Meier analysis was done. Results Between March 1, 2010, and Oct 4, 2018, we enrolled 1150 patients with Raynaud's phenomenon in the VEDOSS database. 764 (66·4%) of 1150 patients met the VEDOSS criteria for study inclusion. Of the 764 patients, 553 (72·4%) had at least one available follow-up visit and the median duration of follow-up was 3·6 years (IQR 1·7–5·8). The mean age was 45·9 years (SD 15·0), 507 (91·7%) of 553 participants were female, and the median time since the onset of Raynaud's phenomenon was 4·0 years (IQR 1·7–10·0). At baseline, 401 (73·7%) of 544 patients with Raynaud's phenomenon had detectable ANA, with 208 (39·5%) of 527 patients positive for systemic sclerosis-specific autoantibodies. Nailfold capillaroscopy abnormalities were present in 182 (36·0%) of 505 patients and puffy fingers were detected in 96 (17·8%) of 540 at baseline. 1885 follow-up visits were recorded. 254 (45·9%) of 553 patients completed the study with progression or a 5-year follow-up; of whom, 133 reached the primary endpoint, resulting in an overall progression rate of 52·4%. The absence of ANA at baseline was the factor most strongly associated with a lack of progression within 5 years, with only four (10·8%) of 37 ANA-negative patients progressing. Conversely, positivity at baseline for systemic sclerosis-specific autoantibodies and puffy fingers was the combination having the highest risk of progression (16 [94·1%] of 17). Interpretation Our results from the VEDOSS project offers a useful tool for a stratified risk approach to patients with Raynaud's phenomenon. The absence of ANA is a strong protective factor that identifies patients with very low risk of developing systemic sclerosis whereas the presence of one or two VEDOSS criteria in patients with Raynaud's phenomenon confers a progressively higher risk for systemic sclerosis over time. This stratification tool can be used both for clinical management and to inform early interventional trials. Funding European Scleroderma Trial And Research and World Scleroderma Foundation.

Patients and health workers were at high risk of infection during the Sars-Cov-2 pandemic lockdown. For this reason, other medical and clinical approaches such as Telemedicine were necessary. Despite Telemedicine was born before COVID-19, the pandemic was the opportunity to accelerate a process already underway for at least a decade and to blow all the barriers away. Our aim is to describe the experience of Telemedicine during and immediately after the first lockdown to assure the follow-up in a 'virtual' outpatient clinic dedicated to Rheumatic and Musculoskeletal Diseases (RMDs) and to give an overview of Telemedicine in the rheumatology field. We retrospectively evaluated the patient flow to our rheumatology division from March to September 2020 and, in accordance with local restrictions, three periods were selected. In the 1st period, 96.96% of the outpatient clinic cases were shifted to Telemedicine; these decreased to 52.45% in the 2nd period, while the 3rd period was characterized by the return of the patients at the clinic (97.6%). Diagnostic procedures were postponed during the 1st period, reduced drastically during the 2nd and performed regularly during the third period. Intravenous infusions were maintained as much as possible during the three periods, to assure therapeutic continuity. Shifting stable patients to Telemedicine has the potential to allow continuity of care, while reducing the risk of contagion during a pandemic. In the next future, the integration of Telemedicine as standard of care for specific clinical applications might assure assistance for RMDs patients also in non-pandemic conditions.

Osteoporosis (OP) can complicate the course of rheumatic musculoskeletal diseases (RMDs) and connective tissue diseases (CTDs). Denosumab, a monoclonal antibody against RANK-L, showed beneficial effect in rheumatoid arthritis in inhibiting radiographic progression and erosive burden. We tested the efficacy, safety, and persistence on the treatment of the combination of biologic disease-modifying antirheumatic drugs (bDMARDs)/denosumab versus bDMARD in patients with RMD and CTD.This is a retrospective evaluation of a single center, including patients with RMD/CTD (including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, and overlap syndromes) treatment with bDMARD/denosumab, compared to age, gender, disease, bDMARD, and conventional synthetic disease-modifying antirheumatic drugs-matched controls.Twenty-eight bDMARD/denosumab patients and 49 bDMARD patients were eligible. Despite a statistically significant difference during the first-year efficacy (due to the different baseline timepoint), there was no difference in the efficacy profile in the second year of treatment and in the safety profile (including local, systemic, and serious adverse events). Moreover, no statistically significant difference in the persistence of bDMARD treatment over 2 years of evaluation was found. The combination of bDMARD and denosumab was not an independent predictor of disease flare or bDMARD treatment withdrawal.The combination of bDMARD and denosumab does not alter the efficacy and the safety profile of the bDMARD in patients with RMD/CTD. Future studies verifying the radiological disease inhibition could support denosumab use in RMD/CTD other than rheumatoid arthritis, when complicated by OP.

Background: In recent years, the involvement of the soluble urokinase Plasminogen Activator Receptor (suPAR) in the pathophysiological modulation of Rheumatoid Arthritis (RA) has been documented, resulting in the activation of several intracellular inflammatory pathways. Methods: We investigated the correlation of urokinase Plasminogen Activator (uPA)/urokinase Plasminogen Activator Receptor (uPAR) expression and suPAR with inflammation and joint damage in RA, evaluating their potential role in a precision medicine context. Results: Currently, suPAR has been shown to be a potential biomarker for the monitoring of Systemic Chronic Inflammation (SCI) and COVID-19. However, the effects due to suPAR interaction in immune cells are also involved in both RA onset and progression. To date, the literature data on suPAR in RA endorse its potential application as a biomarker of inflammation and subsequent joint damage. Conclusion: Available evidence about suPAR utility in the RA field is promising, and future research should further investigate its use in clinical practice, resulting in a big step forward for precision medicine. As it is elevated in different types of inflammation, suPAR could potentially work as an adjunctive tool for the screening of RA patients. In addition, a suPAR system has been shown to be involved in RA pathogenesis, so new data about the therapeutic response to Jak inhibitors can represent a possible way to develop further studies.

The term “axial spondyloarthritis” (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium.

Multicentric reticulohistiocytosis (MRH) is the most frequently described form of reticulohistiocytosis (RH), and it is classified as a class IIb non-Langerhans cell histiocytosis. It has been designated as multicentric, being characterized by multisystemic involvement. In fact, although mainly involving the skin, along with the joints, it is a systemic inflammatory condition potentially involving every internal organ. As MRH-related skin findings can mimic rheumatoid nodules or Gottron papules, the histopathology of the cutaneous lesions is often necessary for the correct diagnosis. Approximately one-third of MRH patients have confirmed concomitant autoimmune disorders. A wide variety of autoimmune disorders associated with the disease have been reported in the literature, suggesting immune dysfunction as a factor in the pathophysiology of MRH. A case of MRH associated with autoimmune manifestation is reported in the context of a mini review of the literature, with a focus on clinical presentation, treatments, and treatment outcomes. Moreover, eight cases of MRH associated with autoimmune diseases are briefly discussed.

In order to evaluate the importance of pain in systemic sclerosis (SSc), the characteristics of pain reported by patients with SSc were analyzed and compared with the characteristics of pain reported by patients with primary Sjőgren’s syndrome (pSS). Pain was reported by 56 patients (80%) in a group of 70 patients with SSc and by 25 patients (78%) in a group of 32 patients with pSS. Pain severity was assessed by the Pain Rating Index (PRI) and the Present Pain Intensity (PPI) of the McGill Pain Questionnaire (MPQ) and by values obtained by a visual analog scale (VAS) indicating the intensity of pain felt in the moment of the examination and the intensity of pain felt in the week preceding the moment of the examination. No significant difference was detected in the comparison of mean values of pain indices between patients with SSc and patients with pSS and in the comparison among subgroups of patients with SSc. The data indicate that pain is a frequent and important cause of suffering in SSc as in other chronic diseases. The association of different methods may be especially useful to obtain a careful evaluation of pain in clinical research.

Systemic sclerosis (SSc) is an autoimmune disease characterised by microvasculopathy, immune dysregulation, and skin and visceral organ fibrosis. Every year novel insights into the pathogenesis, organ involvement and treatment of this severe disease are published in the scientific community.In this review we report an overview of some of the most relevant contributions published in 2021.

ObjectiveFibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/ clinical factors and symptom severity measures using a web-based registry of patients with FM.MethodsAdult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS)).ResultsData relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared ( F 3.321, p< 0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p

Bullous pemphigoid (BP) represents the most common autoimmune bullous disease and is characterized by IgG autoantibodies targeting collagen XVII (BP180). BP has reportedly been occurred in association with other inflammatory skin diseases. Here, we describe the unusual occurrence of BP in a female patient with a concomitant history of generalized morphea (localized scleroderma, LoS) and cutaneous and genital lichen sclerosus (LiS). The occurrence of BP was associated with elevated serum levels of anti-BP180 IgG autoantibodies, which decreased upon clinical remission. Autoimmune bullous diseases and sclerosing dermatitis are immunologically distinct entities, whose association has been rarely described. In this study, we provide a literature review on cases of BP developed in patients with either LoS or LiS. Further, we discussed immunological mechanisms which may have favored the emergence of BP in our patient.

Background Systemic Sclerosis (SSc) is a chronic autoimmune disease with a complex pathogenesis that includes vascular injury, abnormal immune activation, and tissue fibrosis. We provided a complete epidemiological characterization of SSc in the Tuscany region (Italy), considering prevalence and incidence, survival, comorbidities and drug prescriptions, by using a multi-database population-based approach. Cases of SSc diagnosed between 1st January 2003 and 31st December 2017 among residents in Tuscany were collected from the population-based Rare Diseases Registry of Tuscany. All cases were linked to regional health and demographic databases to obtain information about vital statistics, principal causes of hospitalization, complications and comorbidities, and drug prescriptions. Results The prevalence of SSc in Tuscany population resulted to be 22.2 per 100,000, with the highest prevalence observed for the cases aged ≥ 65 years (33.2 per 100,000, CI 95% 29.6–37.3). In females, SSc was predominant (86.7% on the total) with an overall sex ratio F/M of 6.5. Nevertheless, males presented a more severe disease, with a lower survival and significant differences in respiratory complications and metabolic comorbidities. Complications and comorbidities such as pulmonary involvement (HR = 1.66, CI 95% 1.17–2.35), congestive heart failure (HR = 2.76, CI 95% 1.80–4.25), subarachnoid and intracerebral haemorrhage (HR = 2.33, CI 95% 1.21–4.48) and malignant neoplasms (HR = 1.63, CI 95% 1.06–2.52), were significantly associated to a lower survival, also after adjustment for age, sex and other SSc-related complications. Disease-modifying antirheumatic drugs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors were the drugs with the more increasing prevalence of use in the 2008–2017 period. Conclusions The multi-database approach is important in the investigation of rare diseases where it is often difficult to provide accurate epidemiological indicators. A population-based registry can be exploited in synergy with health databases, to provide evidence related to disease outcomes and therapies and to assess the burden of disease, relying on a large cohort of cases. Building an integrated archive of data from multiple databases linking a cohort of patients to their comorbidities, clinical outcomes and survival, is important both in terms of treatment and prevention.

The soluble urokinase plasminogen activator receptor (suPAR) is the bioactive form of uPAR, a membrane-bound glycoprotein, and it is primarily expressed on the surface of immunologically active cells. Mirroring local inflammation and immune activation, suPAR has gained interest as a potential prognostic biomarker in several inflammatory diseases. Indeed, in many diseases, including cancer, diabetes, cardiovascular diseases, kidney diseases, and inflammatory disorders, higher suPAR concentrations have been associated with disease severity, disease relapse, and mortality. Our review describes and discusses the supporting literature concerning the promising role of suPAR as a biomarker in different autoimmune rheumatic and non-rheumatic diseases.

Background: Several studies described the cross-sectional characteristics of systemic sclerosis patients and coexisting primary biliary cholangitis, but longitudinal prognostic data are lacking. Aims: To describe the systemic sclerosis–primary biliary cholangitis phenotype, including baseline characteristics and outcomes. Methods: We performed a multicentre the European Scleroderma Trials and Research Group study of systemic sclerosis patients with primary biliary cholangitis or with primary biliary cholangitis–specific antibodies, matched with systemic sclerosis controls free from hepatobiliary involvement matched for disease duration and cutaneous subset. Data were recorded at baseline and at the last available visit. Results: A total of 261 patients were enrolled (115 primary biliary cholangitis–systemic sclerosis, 161 systemic sclerosis). At baseline, systemic sclerosis–primary biliary cholangitis patients had a higher prevalence of anti-centromere antibodies ( p = 0.0023) and a lower prevalence of complete absence of digital ulcers. The milder vascular involvement was confirmed at follow-up when crucial differences emerged in the percentage of patients experiencing digital ulcers; a significantly higher number of patients who never experienced digital ulcers were observed among primary biliary cholangitis–systemic sclerosis patients ( p = 0.0015). Moreover, a greater incidence of pulmonary arterial hypertension ( p Conclusion: Our data show that systemic sclerosis–primary biliary cholangitis exhibit a mild systemic sclerosis and primary biliary cholangitis phenotype with outcomes being in general favourable.

Background: Stimulating protective immunity with vaccines appears to be the most promising option for providing widespread moderate to high protection against COVID-19 in people over the age of 18. Regular exercise improves the immune response, transmitting possible benefits against virus infections. The aim of this review is to study the effects of physical activity on vaccine injections, helping to develop new recommendations for COVID-19 vaccination campaigns. Methods: A comprehensive review of the existing literature was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The internal quality of the studies was assessed according to the Physiotherapy Evidence Database (PEDro) scale. The outcomes analyzed were antibody titer, the level of lymphocytes CD4, CD8, InterLeukin 6 (IL6), leukocytes level, the visual analogue scale (VAS) for overall pain rating, arm and forearm circumferences and volume of oxygen (VO2) peak. Results: Fourteen articles were selected for the analysis. The majority of studies were randomized controlled trials (RCT) (n = 8) and controlled trials (CT) (n = 6). According to PEDro, the ‘fair’ category (n = 7) was the most represented, followed by ‘good’ (n = 6) and ‘excellent’ (n = 1). Physical training showed a positive effect on antibody titers of the vaccine; yet, different variables seem to influence antibody titers: higher new vs. old antigen in the vaccine, higher in younger vs. older individuals, and higher in females vs. males. After exercise, when analyzing variables of direct response to the vaccine, such as the amount of CD4, IL-6 and leukocytes, higher levels were observed in the patients who performed physical exercise compared to the control group. In the same way, better results were observed in physiological variables such as VO2 and limb circumferences, or subjective variables such as pain, which showed better results than the control group. Conclusions: The immune response (antibody titers) depends on age, gender and the intensity of physical activity: long-term protocols at moderate intensity are the most recommended. All of these aspects also have to be carefully considered for the COVID-19 vaccination.

The revised Fibromyalgia Impact Questionnaire (FIQR) is a widely used fibromyalgia severity assessment tool that was introduced in 2009 prior to the publication of the American College of Rheumatology (ACR) preliminary fibromyalgia criteria in 2010 and its revision in 2016. In 2020, the modified Fibromyalgia Assessment Scale (FASmod) was published. The Polysymptomatic Distress scale (PSD) of the fibromyalgia criteria and FASmod include assessments of pain location severity and can be used for diagnosis as well as in non-fibromyalgia patients. The aim of this study is to provide equations for the conversion of the FIQR scores to PSD and FASmod as an aid to understanding and sharing fibromyalgia severity information.3089 patients with fibromyalgia, diagnosed according to the ACR 2010/2011 criteria and belonging to the Italian Fibromyalgia Registry completed FIQR, FASmod and PSD questionnaires. Pearson's correlation coefficient was used to test the correlations between indices. The least square regression approach was used to produce predictive equations for each scale based on the remaining scales.FIQR was correlated with PSD (r=0.714) and FASmod (r=0.801); PSD and FASmod showed the highest correlation (r=0.897), expected since they assess the same constructs. Predictive equations showing a linear model were effective in producing mean cohort values, but individual predictions deviated substantially, precluding prediction in the individual patient.Conversion equations that allow for interconversion of multiple scales fibromyalgia severity assessment scales are produced. These can be useful in obtaining mean values for cohorts but are not accurate enough for use in individual patients.

In refractory inflammatory joint diseases (IJDs) biological disease-modifying anti-rheumatic drugs (bDMARDs) may achieve remission. EULAR recommends bDMARD tapering when remission persists. However, guidelines on tapering modalities and criteria for patient selection are lacking. We aimed to evaluate remission persistency after lengthening the time between injections of golimumab in patients affected by IJD and to identify any patient or disease characteristics associated to flare after lengthening.Patients affected by rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA) treated with golimumab were enrolled in a retrospective observational study. Demographic data, ESR, cRP, DAS28/ BASDAI, were collected at baseline and during the follow-up (T1- defined as a medical check-up after 1 year of treatment or, for patients with longerg exposure, the first medical check-up in 2016, when at our unit we began to experience drug tapering- and T2- 12 months after the lengthening was started). In 22/80 patients in remission at T1, injection time was lengthened.Eighty patients were enrolled, 34 AS, 33 PsA, 9RA and 4 JIA. At baseline, all had an active disease. At T1, 60/80 patients reached remission and 22/60 patients started tapering. At T2, 20/22 pts (91%) were in remission. At T1 BASDAI was higher (2.2, SD 0.28 vs. 0.58, SD 0.47; p0.001) in patients who lost remission at T2.Patients who flared recovered remission once taken back to a 28-day interval. 4/38 patients maintained at the standard dose flared up and switched/swapped bDMARD. The difference in retention rate toward patients on reduced dose was not significant.Results show that golimumab lengthening is safe and successfully maintains remission. In patients who experienced a flare after lengthening, the standard regimen promptly restored remission.

ObjectivesPleuroparenchymal fibroelastosis (PPFE) is characterized by predominantly upper lobe pleural and subjacent parenchymal fibrosis; PPFE features were described in patients with rheumatic autoimmune diseases (RAID). A systematic literature review was performed to investigate the prevalence, prognosis and potential association of PPFE with previous immunosuppression in RAID.MethodsEMBASE, Web of Science and PubMed databases were questioned from inception to 1 September 2019. Articles published in English and addressing PPFE in patients with RAID were selected.ResultsTwenty out of 794 papers were selected with a total of 76 cases of RAID-PPFE patients (20 SSc, 9 RA, 6 IIM6 primary SS, 5 overlap syndromes, 3 ANCA-associated vasculitides, 2 granulomatosis with polyangiitis, 1 microscopic polyangiitis, 1 UCTD, 1 SLE, 1 GCA and 21 patients with non-specified RAID). Dyspnoea was the most frequently reported symptom (37/48 patients, 77%). Patients frequently presented with a restrictive pattern and decline in diffusing lung capacity for carbon monoxide. During the follow-up, 7/12 patients had progression at imaging, 22/39 presented a generic clinical worsening, 19/38 had a functional deterioration and 15/43 remained stable.ConclusionThe present systematic literature review confirms that PPFE features are present in RAID. Rheumatologists should be aware of this new radiological pattern that holds a bad prognosis.

COVID-19 is a world health emergency which may inevitably affect the management of a complex autoimmune disease such as systemic sclerosis (SSc). Several SSc patients are frail and, in this pandemic, need a careful protection. The COVID-19 infection might complicate the clinical scenario of interstitial lung disease (ILD) in SSc because it determines a severe pneumonia characterized by radiological features similar to SSc-ILD. The striking CT similarities between the 2 diseases make it difficult to distinguish a worsening of SSc-ILD from COVID-19-ILD superinfection. Moreover, other aspects, like isolation during lock down, may cause a significant psychological stress which will pile up on the already difficult contact with the patients for a routine check-up. Moreover, the drug shortage is a real problem in these times. For these reasons, the rheumatologist in daily clinical practice should carefully differentiate the possible COVID-19 infection in order to optimize the patient management. Therefore, the challenge in everyday life will be to achieve in due time the differential diagnosis as well as the long-term psychological impact.Key Points• SSc patients should be encouraged to continue their chronic therapy; in case of immunosuppressive therapy it must be discontinued for safety in case of COVID-19 infection.• Psychological support must be guaranteed to every SSc patients.• COVID-19 pneuminia is hard to distinguish from an interstitial lung disease due to SSc lung involvment.• Data sharing is fundamental for an optimal managment of SSc patients during COVID-19 pandemia.

ObjectiveThe role of age in influencing the severity of fibromyalgia (FM) is still controversial. The aim of this study is to define the contribution of age in the severity of FM from data from a large national database.MethodsThis cross-sectional study included adult patients with FM diagnosed according to the 2010/2011 American College of Rheumatology criteria. Disease severity was assessed with the revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FAS 2019mod). Patients were grouped into five age categories (between 18-40 years, between 41- 50 years, between 51-60 years, between 61-70 years, and =71 years). Differences in disease severity between groups were assessed by one-way analysis of variance (ANOVA).ResultsThe study included 2889 patients (199 males and 2690 females), mean age of 52.58 (+/- 11.82) years, with a mean FIQR score of 59.22 (+/- 22.98) and a mean FAS 2019mod of 25.50 (+/- 8.66). Comparing the mean values of the various indices between age categories, there were no statistically significant differences between the groups for FIQR total score and FAS 2019mod. However, the 60-70 years category showed the lowest scores for both scales. The main difference emerged for the FIQR physical function subscale, where the =71 years category showed significantly higher scores (p

ObjectiveThere is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics.MethodsA multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared.ResultsThe overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs.ConclusionOur study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

In the past months, mass vaccination represented the turning point of the global battle against the COVID-19 pandemic, an unprecedented challenge for physicians, healthcare professionals, health systems and pharmaceutical companies. More than 6 billion doses of vaccine have been administered to date, covering nearly 50% of the world’s population. Although the vaccination campaign is still thwarted by spread of fake news disseminated by a ubiquitous antivaxxer movement, accumulating real-life data1 confirm the favourable safety profile already demonstrated in phase III clinical trials.2 Despite the lack of a steady literature evidence,3 the potential role of vaccines in promoting autoimmunity continues to intrigue many researchers. The theoretical basis of this association relies on the possible molecular mimicry between macromolecular components of the vaccine and specific human proteins and the exuberant immune response elicited by adjuvants contained in vaccines.4 Adverse events (AEs) associated with COVID-19 vaccines are usually mild and mainly restricted to injection site reactions. Interestingly, among systemic AEs, arthralgia is one of the most common.2 To the best of our knowledge, only isolated cases5 of arthritis developed after COVID-19 …

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Background: In clinical practice, the striking similarities observed at computed tomography (CT) between the diseases make it difficult to distinguish a COVID-19 pneumonia from a progression of interstitial lung disease (ILD) secondary to Systemic sclerosis (SSc). The aim of the present study was to identify the main CT features that may help distinguishing SSc-ILD from COVID-19 pneumonia. Methods: This multicentric study included 22 international readers divided in the radiologist group (RAD) and non-radiologist group (nRAD). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. Findings: Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p

Psychological concerns in Systemic Sclerosis (SSc) patients represent an important issue and should be addressed through non-pharmacological treatments. Thus, the aim of the present study was to assess the effects of the Mindfulness-Based Stress Reduction (MBSR) program on psychological variables and the perspectives and experiences of patients with an SSc diagnosis. Notably, 32 SSc patients were enrolled and assigned to either the intervention (MBSR) group or the waitlist group. Inclusion criteria were (i) age ≥ 18 years, SSc diagnosis according to EULAR/ACR diagnostic criteria and informed consent. Exclusion criteria were previous participation in any Mind-Body Therapy or psychiatric diagnosis. Quantitative and qualitative outcomes were investigated through clinometric questionnaires and individual interviews. MBSR did not significantly impact outcomes such as physical functionality, anxiety, hopelessness, depression, physical health status, perceived stress, mindfulness and mental health status. For the anger evaluation, statistically significant differences are found for both controlling and expressing anger, indicating that the MBSR program had a favorable impact. As for qualitative results, more awareness of daily activities, stress reduction in terms of recognizing the causes and implementing self-strategies to prevent them, adherence to therapy, and recognition of the effect of medication on their bodies were reported. In conclusion, it is important to highlight the absence of negative or side effects of the MBSR program and the positive impact on patients’ experience and perspective; thus, we suggest this approach should be taken into account for SSc patients.

Objectives Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance. Methods The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0–1.4) year was generated. Results Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence. Conclusion T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients.

Gastrointestinal (GI) manifestations are frequent in systemic sclerosis (SSc) with an impact on quality of life and morbidity. Bowel vasculopathy is a key pathogenetic factor responsible for GI involvement.To compare abdominal ultrasound (US) and Color Doppler Ultrasonography (CDU) features of splanchnic vessels of SSc patients with healthy controls.The charts of SSc patients who underwent an abdominal US and CDU study were retrospectively analyzed. For Superior Mesenteric Artery (SMA) and Inferior Mesenteric Artery (IMA) caliber, Peak Systolic Velocity (PSV), Reverse Velocity (RV), End-Diastolic Velocity (EDV), Mean Velocity (mV), Blood-flow, Resistive Index (RI) and Pulsatility Index (PI) were recorded.28 SSc patients and 28 controls were enrolled. In SSc, caliber of SMA was significantly smaller than in controls (5.75 ± 0.62 mm vs. 6.45 ± 0.60 mm, p 0.0001 - p adj =0.0002). The flow study of SMA and IMA showed a significant reduction of RV (SMA: 7.25 ± 6.37 cm/s vs. 18.52 ± 6.16 cm/s, p 0.0001 - p adj0.0001; IMA: 2.69 ± 6.10 cm/s vs. 17.06 ± 5.75 cm/s, p 0.0001 - p adj0.0001) and PI (SMA: 3.33 ± 0.75 vs. 4.53 ± 1.03, p 0.0001 - p adj =0.0002; IMA: 3.54 ± 0.95 vs. 6.08 ± 1.53, p 0.0001 - p adj0.0001) in SSc patients than controls.involvement of splanchnic vessels in SSc may be non-invasively investigated with abdominal US and CDU. Morphological and functional changes of Doppler parameters observed in SMA and IMA clearly demonstrate that these vessels are affected by SSc vasculopathy.

(1) Background: Gut microbiota (GM) is the set of microorganisms inhabiting the gastroenteric tract that seems to have a role in the pathogenesis of rheumatic diseases. Recently, many authors proved that GM may influence pharmacodynamics and pharmacokinetics of several drugs with complex interactions that are studied by the growing field of pharmacomicrobiomics. The aim of this review is to highlight current evidence on pharmacomicrobiomics applied to the main treatments of Rheumatoid Arthritis and Spondyloarthritis in order to maximize therapeutic success, in the framework of Personalized Medicine. (2) Methods: We performed a narrative review concerning pharmacomicrobiomics in inflammatory arthritides. We evaluated the influence of gut microbiota on treatment response of conventional Disease Modifying Anti-Rheumatic drugs (cDMARDs) (Methotrexate and Leflunomide) and biological Disease Modifying Anti-Rheumatic drugs (bDMARDs) (Tumor necrosis factor inhibitors, Interleukin-17 inhibitors, Interleukin 12/23 inhibitors, Abatacept, Janus Kinase inhibitors and Rituximab). (3) Results: We found a great amount of studies concerning Methotrexate and Tumor Necrosis Inhibitors (TNFi). Conversely, fewer data were available about Interleukin-17 inhibitors (IL-17i) and Interleukin 12/23 inhibitors (IL-12/23i), while none was identified for Janus Kinase Inhibitors (JAKi), Tocilizumab, Abatacept and Rituximab. We observed that microbiota and drugs are influenced in a mutual and reciprocal way. Indeed, microbiota seems to influence therapeutic response and efficacy, whereas in the other hand, drugs may restore healthy microbiota. (4) Conclusions: Future improvement in pharmacomicrobiomics could help to detect an effective biomarker able to guide treatment choice and optimize management of inflammatory arthritides.

The role of Bronchoalveolar Lavage (BAL) in the evaluation of systemic sclerosis (SSc) interstitial lung disease (ILD) is still controversial. The aim of this systematic literature review was to investigate the use of BAL in SSc-ILD, and to focus on the pros and cons of its real-life application. Methods: PubMed, Cochrane, and Embase were questioned from inception until 31 December 2021. Results: Eighteen papers were finally analyzed. A positive correlation was observed between lung function and BAL cytology; in particular, BAL neutrophilia/granulocytosis was related to lower diffusing capacity for carbon monoxide (DLCO) values and lower forced vital capacity (FVC). Moreover, a positive correlation between BAL cellularity and high-resolution computed tomography (HRCT) findings has been reported by several authors. Cytokines, chemokines, growth factors, coagulation factors, and eicosanoids have all been shown to be present, more often and in higher quantities in SSc-ILD patients than in the health control and, in some cases, they were related to more severe pulmonary disease. There was no consensus regarding the role of BAL cellularity as a predictor of mortality.

Background: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is one of the most relevant complications of SSc and the major cause of death. The pathogenesis of SSc-ILD involves a complex interplay of multiple cell types and different molecular pathways, with both inflammation and fibrosis as pathological hallmarks. To date, there are no treatments able to target both components of the disease. Janus kinase inhibitors (JAKinibs) represent an interesting therapeutic option because they exert both anti-inflammatory and anti-fibrotic properties. Methods: Here, we performed a narrative review concerning the potential role of JAKinibs in SSc-ILD to define the state of art and to evaluate the pathogenetic rationale behind this type of treatment. Results: Currently, few studies investigated SSc-ILD response to JAKinibs treatment. Data were analyzed from three clinical studies and four case reports and progression of SSc-ILD was not evident in 93.5% of patients treated with JAKinibs. Conclusions: Available evidence of efficacy of JAKinibs in SSc-ILD is sparse but promising. JAKinibs could be an interesting treatment in SSc-ILD because of their potential inhibition of the fibrotic processes combined with their anti-inflammatory action. Moreover, JAKinibs were also shown in some studies to have a potential effect on pulmonary arterial hypertension (PAH), another threatening complication in SSc. More data are necessary to define JAKinibs role in SSc-ILD treatment.

Objectives Lung ultrasound (LUS), through assessment of B-lines and pleural line alterations, is able to evaluate interstitial lung disease (ILD), a frequent complication of SSc. Different scanning schemes and counting methods have been proposed but no clear cut-off values have been indicated for screening. We aimed to evaluate the accuracy of different LUS methodological approaches to detect ILD compared with high-resolution CT (HRCT) as the gold standard. Methods Sixty-nine SSc patients underwent LUS and chest HRCT on the same day. Both exams were scored by expert readers. The accuracy of different scanning schemes and counting methods was assessed and clinical and functional data were compared with imaging findings. Results B-lines were more numerous in patients with the diffuse skin subset and Scl70 autoantibody positivity. The number of B-lines correlated with the Scleroderma Lung Study (SLS) I HRCT score (R = 0.754, P 10 B-lines on the whole chest or >1 B-line on the postero-basal chest showed 97% sensitivity for detecting even very early ILD signs (corresponding to an SLS I score of 1). Sensitivity increased to 100% when pleural line alterations were included in the analysis. Conclusions LUS has a very high sensitivity in detecting SSc-related ILD. A cut-off value of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest can be used for the screening of SSc-ILD. Assessing only the postero-basal chest seems to be mostly effective, combining high sensitivity with a less time-consuming approach.

ObjectiveTo evaluate peripheral nerve involvement in patients with SLE with neuromuscular ultrasonography (NMUS) and understand its role in investigating SLE-related peripheral neuropathy.MethodsThis is an observational cross-sectional study on patients with SLE and healthy controls. Five nerves in each patient were examined bilaterally with NMUS, and the cross-sectional area (CSA) of each nerve at certain sites was estimated. The mean CSA at each site, for each nerve, in each group was statistically analysed and compared between groups.Results370 nerves were evaluated in 37 patients. By nerve conduction study (NCS), 36 patients had polyneuropathy (80.6% mixed type, 19.4% sensory). Significant mean CSA enlargement was present among the ulnar nerve at the Guyon’s canal and mid-humerus (both p=0.001); tibial nerve at the distal leg and proximal to the tarsal tunnel (p=0.003 and p=0.001, respectively); and peroneal nerve at the popliteal fossa (p=0.042). The mean CSA showed high specificity compared with NCS.ConclusionOur study shows that CSA could be a complementary tool to NCS for studying peripheral neuropathy in SLE. Furthermore, NMUS provides data on the different pathophysiological aspects of nerve involvement in SLE. Future studies using more than one sonographic parameter in combination with NCS and nerve histopathology are recommended to further investigate SLE-related neuropathy.Trial registration numberNCT04527172.

In systemic sclerosis (SSc), the gastrointestinal tract (GIT) plays a central role in the patient’s quality of life. The microbiome populates the GIT, where a relationship between the Lactobacillus and gastrointestinal motility has been suggested. In this study, the analysis of oral Lactobacillus species in SSc patients and healthy subjects using culture-independent molecular techniques, together with a review of the literature on microbiota and lactobacilli in SSc, has been carried out. Twenty-nine SSc female patients (mean age 62) and twenty-three female healthy subjects (HS, mean age 57.6) were enrolled and underwent tongue and gum swab sampling. Quantitative PCR was conducted in triplicate using Lactobacillus specific primers rpoB1, rpoB1o and rpoB2 for the RNA-polymerase β subunit gene. Our data show significantly (p = 0.0211) lower LactobacillusspprpoB sequences on the tongue of patients with SSc compared to HS. The mean value of the amount of Lactobacillus ssprpoB gene on the gumsofSSc patients was minor compared to HS. A significant difference between tongue and gums (p = 0.0421) was found in HS but not in SSc patients. In conclusion, our results show a lower presence of Lactobacillus in the oral cavity of SSc patients. This strengthens the hypothesis that Lactobacillus may have both a protective and therapeutic role in SSc patients.

DeSScipher is the first European multicentre study on management of systemic sclerosis (SSc), and its observational trial 1 (OT1) evaluated the efficacy of different drugs for digital ulcer (DU) prevention and healing. The aim of this study was to assess current use of vasoactive/vasodilating agents for SSc-related DU in the expert centres by analysing the baseline data of the DeSScipher OT1.Baseline characteristics of patients enrolled in the OT1 and data regarding DU were analysed.The most commonly used drugs, in both patients with and without DU, were calcium channel blockers (CCBs) (71.6%), followed by intravenous iloprost (20.8%), endothelin receptor antagonists (ERAs) (20.4%) and phosphodiesterase 5 (PDE-5) inhibitors (16.5%). Of patients, 32.6% with DU and 12.8% without DU received two drugs (p 0.001), while 11.5% with DU and 1.9% without DU were treated with a combination of three or more agents (p 0.001). Sixty-five percent of the patients with recurrent DU were treated with bosentan and/or sildenafil. However, 64 out of 277 patients with current DU (23.1%) and 101 (23.6%) patients with recurrent DU were on CCBs alone.Our study shows that CCBs are still the most commonly used agents for DU management in SSc. The proportion of patients on combination therapy was low, even in patients with recurrent DU: almost one out of four patients with current and recurrent DU was on CCBs alone. Prospective analysis is planned to investigate the efficacy of different drugs/drug combinations on DU healing and prevention. Key Points • The analysis of DeSScipher, the first European multicentre study on management of SSc, has shown that the most commonly used vasoactive/vasodilating drugs for DU were CCBs, followed by intravenous Iloprost, ERAs and PDE-5 inhibitors. • More than half of the patients with recurrent DU received bosentan and/or sildenafil. • However, the proportion of patients on combination therapy of more than one vasoactive/vasodilating drug was low and almost one out of four patients with current and recurrent DU was on CCBs alone.

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.