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Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort.Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets.Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud’s phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1–16.5) than lcSSc (2 years, IQR 0–7), and dcSSc (1 year, IQR 0–3) (p

We reviewed 11 patients with systemic sclerosis‐related ILD who were referred to our Scleroderma Unit from January 2020 to January 2021 and started Nintedanib. Non‐specific interstitial pneumonia (NSIP) was prevalent (45%), usual interstitial pneumonia (UIP) and UIP/NSIP pattern were both 27%. Only one patient had a history of smoking. Eight patients were on mycophenolate mofetil (MMF), eight were treated with corticosteroids (mean dose 5 mg/day of Prednisone or equivalent), and three were on Rituximab. The mean modified British Council Medical Questionnaire (mmRC) decreased from 3 to 2.5. Two patients had to reduce their daily dose to 200 mg/day for severe diarrhoea. Nintedanib was generally well tolerated. [ABSTRACT FROM AUTHOR]

Background. Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. Methods. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Results. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0–156) months. Conclusions. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud’s phenomenon or antinuclear antibodies before the SSc onset.

Objectives It has recently become possible to assess lung vascular and parenchymal changes quantitatively in thoracic CT images using automated software tools. We investigated the vessel parameters of patients with SSc, quantified by CT imaging, and correlated them with interstitial lung disease (ILD) features. Methods SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated. CT images were analysed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio lung texture analysis. Vascular analysis (volumes, numbers and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted. Results A total of 79 patients [52 women, 40 ILD, mean age 56.2 (s. d. 14.2) years, total ILD extent 9.5 (10.7)%, PVV/lung volume % 2.8%] were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-associated ILD (SSc-ILD) patients presented with an increased number and volume of arterial vessels, in particular those between 2 and 4 mm of diameter, and with a higher density of arteries and veins of <6 mm in diameter. Considering radiological and functional criteria concomitantly, as well as the descriptive trends from the longitudinal evaluations, the normalized PVVs, vessel numbers and densities increased progressively with the increase/worsening of ILD extent and functional impairment. Conclusion In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment, and may represent a biomarker of SSc-ILD severity. [ABSTRACT FROM AUTHOR]

Several authors reported an increased risk of cancer in SSc patients, including breast cancer (BC). Nevertheless, the mechanisms underlying this association have not yet been clarified. SSc and BC share several molecular pathways, which seem to play a common etiopathogenetic role. The previously published Sclero-Breast study demonstrated the development of BC with a good prognosis among these patients, which could be explained by an autoimmune background as a possible mechanism for limiting tumor extension. Here, we report the results of an IHC analysis of molecular pathways known to be common drivers for both diseases, with the aim to better define the mechanisms underlying a good prognosis of BC in patients affected by SSc. The analysis demonstrated higher TILs rates in all BC subgroups, with a high rate of PD-L1 expression especially in TNBC and HER2-positive BC, suggesting a less aggressive behavior in these patients compared to the general population. These results support a possible de-escalation strategy of cancer therapies in these fragile patients. These data could represent a starting point for future prospective studies based on the clinical application of these biomarkers with a larger sample size to promote a personalized and targeted oncological treatment for this specific subset of patients. [ABSTRACT FROM AUTHOR]

Here we describe the case of a 60‐year‐old-woman with systemic sclerosis sent to our Scleroderma Unit to treat digital stumps. The stumps were successfully treated with autologous fat grafting (crown-shape infiltration). Our technique of autologous lipotransfer improved wound healing in a scleroderma patient with stump-digital ulcers where all other options failed. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a complex autoimmune and up to 50% of patients develop digital ulcers. We revised fifty consecutive patients with SSc-related digital ulcers (DUs) who referred to our Scleroderma Unit. Thirty-five of them who showed clear signs of DUs infection underwent to cutaneous swab and microbiological data collection. We performed 87 cutaneous swabs overall. DUs were recurrent in 58% of the patients and multiple in 60% of patients. Fourty-four swabs (53%) were positive for Staphylococcus aureus (13% Methicillin-Resistant), 9 (10%) were positive for Pseudomonas aeruginosa, and then the others less frequently isolated. Nine patients (25%) needed hospitalization. Our data support a patient-tailored approached to DUs, particularly those infected. Selfhygiene and asepsis during dressing procedures are mandatory. Patient must be trained to avoid dangerous behaviors and reduce the risk of infection. [ABSTRACT FROM AUTHOR]

Objective: COVID-19 pandemic represents a serious health emergency that severely compromised our Public Health system, resulting in a rapid and forced reorganization and involved the management of chronic diseases too. The Scleroderma Unit of Modena and Reggio Emilia follows more than 600 patients suffering from systemic sclerosis (SSc) and recently became the referral center (HUB) in Emilia-Romagna for this rare connective tissue disease. The aim of the present study was to evaluate the extent by which the lockdown and the pandemic has impacted the activity of admissions to Scleroderma Unit of Modena and Reggio Emilia. Methods: Our daily clinical activity is characterized by outpatient visits, videocapillaroscopy exam, ulcers treatment, therapeutic infusions in day hospital regimen, multidisciplinary visits following our dedicated SSc care pathway, and clinical trials. Our activity has been quickly rescheduled to ensure the proper assistance to our SSc patients during the COVID-19 pressure. Results: The use of telemedicine has certainly assured a robust continuity of health care. Furthermore, telephone pre-triage, nurse/medical triage, proper physical distancing and use of PPE/DPI allowed us to re-organize and continue SSc daily activity. Specifically, therapeutic infusions in day hospital regimen and outpatient visits, including ulcers treatment, was guaranteed and maximized. Conclusion: The management of scleroderma patients by an expert specialist reference center is crucial in order to ensure continuity of care and pursue the best SSc practice. [ABSTRACT FROM AUTHOR]

Adult onset Still’s disease (AOSD) is a rare inflammatory systemic disease that occasionally may affect myocardium. Diagnosis is based on typical AOSD symptoms after the exclusion of well-known infectious, neoplastic, or autoimmune/autoinflammatory disorders. In the case of abrupt, recent onset AOSD, it could be particularly difficult to make the differential diagnosis and in particular to early detect the possible heart involvement. This latter event is suggested by the clinical history of the four patients described here, incidentally observed at our emergency room. All cases were referred because of acute illness (high fever, malaise, polyarthralgias, skin rash, and sore throat), successively classified as AOSD, and they presented abnormally high levels of serum troponin without overt symptoms of cardiac involvement. The timely treatment with steroids (3 cases) or ibuprofen (1 case) leads to the remission of clinicoserological manifestations within few weeks. These observations suggest that early myocardial injury might be underestimated or entirely overlooked in patients with AOSD; routine cardiac assessment including troponin evaluation should be mandatory in all patients with suspected AOSD. [ABSTRACT FROM AUTHOR]

Vasculitis is a heterogeneous group of disorders characterized by the presence of necrotic inflammatory phenomena and destruction of blood vessels. Vasculitis is classified as primary (idiopathic) or secondary to infections, connective tissue diseases and drugs but can also be considered as a paraneoplastic phenomenon. Evidence shows that the increasing use of biological agents results in a growing number of reports of autoimmune diseases induced by these therapies. An inflammatory articular chronic disease such as rheumatoid arthritis may be complicated by extra-articular manifestations, such as cutaneous or systemic vasculitis. Herewith, we describe the case of a great vessels arteritis in a patient affected by rheumatoid arthritis in therapy with an anti-TNF agent (etanercept). [ABSTRACT FROM AUTHOR]

Cat scratch disease (CSD) is a bacterial disease caused by Bartonella henselae and it is mainly characterized by self-limiting lymphadenopathy in the draining site of a cat scratch or bite. We report a patient with history of fever, swelling lymph nodes, vasculitic-like skin lesions, and positivity of Bartonella serology initially considered as expression of a disimmune disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aim: Iloprost is recommend worldwide for the treatment of RP and the healing of DUs. The aim of this study is to report the regimens of Iloprost administered in different rheumatological centers within the same regional Health System Methods: A questionnaire exploring different items related to the use of Iloprost was developed and reviewed by three expert rheumatologists. The questionnaire was distributed as an online survey to all local SSc referral centers in Emilia-Romagna (Italy). Data are reported as percentage or median with interquartile range (IQR), as appropriate. An updated review of world literature on this topic was also carried out., Results: All the invited centers completed the survey. There were both local (8) and university hospitals (4). The majority (58%) had a rheumatologist as head physician. All centers used Iloprost: a single monthly administration was the most common treatment (75%). The cycle lasted 1 [IQR 1-2] days with a 0.5-2.0 ng/Kg/min dose according to the drug tolerance of the patients. There were overall 68 spots (beds, reclining armchair, or simple armchair); 2.0 [1.5-4.0] patients were able to receive Iloprost at the same time. University Hospitals had more physicians at their disposal than local hospitals but less paramedic personnel (respectively: 1.8 vs 1.2 physicians, 1.5 vs 2.1 nurses)., Conclusions: These observations were in line with the majority of previous studies reporting different regimens, comparing similar (but not identical) dose and schedule administration, however, despite differences being at times substantial, no standard infusion method is yet available.

Objective: Systemic sclerosis is characterized by endothelial dysfunction, autoimmunity abnormalities, and fibrosis of the skin and internal organs. The pathogenetic mechanisms underlying systemic sclerosis vasculopathy are still not clarified. A complex cellular and extracellular network of interactions has been studied, but it is currently unclear what drives the activation of fibroblasts/myofibroblasts and the extracellular matrix deposition., Methods: Using RNA sequencing, the aim of the work was to identify potential functional pathways implied in systemic sclerosis pathogenesis and markers of endothelial dysfunction and fibrosis in systemic sclerosis patients. RNA-sequencing analysis was performed on RNA obtained from biopsies from three systemic sclerosis patients and three healthy controls enrolled in our University Hospital. RNA was used to generate sequencing libraries that were sequenced according to proper transcriptomic analyses. Subsequently, we performed gene set enrichment analysis of differentially expressed genes on the entire list of genes that compose the RNA-sequencing expression matrix., Results: Gene set enrichment analysis revealed that healthy controls were characterized by gene signatures related to stromal stem cells proliferation, cytokine-cytokine receptor interaction, macrophage-enriched metabolic network, whereas systemic sclerosis tissues were enriched in signatures associated with keratinization, cornification, retinoblastoma 1 and tumor suppressor 53 signaling., Conclusion: According to our data, RNA-sequencing and pathway analysis revealed that systemic sclerosis subjects display a discrete pattern of gene expression associated with keratinization, extracellular matrix generation, and negative regulation of angiogenesis and stromal stem cells proliferation. Further analysis on larger numbers of patients is needed; however, our findings provide an interesting framework for the development of biomarkers useful to explore potential future therapeutic approaches., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objective: To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort., Methods: Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets., Results: Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001)., Conclusion: The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In psoriatic arthritis (PsA), low disease activity as defined by the Minimal Disease Activity (MDA) index is considered a good treatment target. However, as MDA is based only on clinical findings, it might not capture pauci-symptomatic inflammation. Sensitive imaging such as ultrasound (US) might disclose residual inflammatory signs in PsA patients in MDA., Methods: In this cross-sectional multicentre study, adult PsA patients on biologic treatment in MDA for at least 6 months were consecutively enrolled for a thorough clinical and US examination. Data collection included demographics, personal history, main patient's reported outcomes, clinical and US findings of joints, tendon sheaths, tendons, bursae, and entheses involvement. All centers performed the US investigation in B-mode and Power Doppler (PD)-mode using a similar US machine equipped with a 18-6 and 13-5 MHz multifrequency linear probe. Statistical analysis included comparisons between groups and correlation tests., Results: The 72 PsA patients enrolled in the study had a median duration of MDA of 12 (6-65) months. Overall, US examination revealed a low number of acute lesions. However, 54% of patients had at least one PD signal in the examined tissues. A joint or enthesis positive PD signal was found in about 19 and 24% of patients, respectively. Synovial hypertrophy, at least one acute entheseal lesions, and bursitis were the most common changes, detected in 41.7, 41.7 and 26% of patients, respectively., Conclusions: PsA patients in a stable state of MDA may still have residual inflammation in peripheral articular structures detectable by US examination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Macchioni, Marchesoni, Ciancio, Sandri, Zabotti, Vukatana, Montaguti, Focherini, Govoni, Spinella, Malavolta, Zuliani, Bruschi, Mascella and Salvarani.)

Systemic sclerosis (SSc) is a connective tissue disease characterized by immune-system alterations, fibrosis involving the skin and internal organs and diffuse microangiopathy. Pulmonary arterial hypertension (PAH) is a severe complication of SSc affecting about 10-15% of the patients and it is a leading cause of mortality. Due to the devastating nature of SSc-PAH, there is a clear need to systematically adopt appropriate screening programs. Nail fold videocapillaroscopy (NVC) studies have shown a more severe peripheral microvascular dysfunction in SSc patients with PAH suggesting that abnormalities in peripheral microcirculation may correlate with pulmonary microangiopathy. This is a cross-sectional study involving four tertiary University Rheumatology Units in the Center-North of Italy. Seventy patients, 35 adults with SSc and PAH confirmed by RHC (F/M 34/1; median age 65.2 ± 8.9 SD yrs), and 35 SSc patients without PAH were enrolled (F/M 3471; median age 63.3 ± 10.3 SD yrs). Clinical, laboratoristic and instrumental data were collected and NVC was performed in all patient. Specific NVC parameters were evaluated and a semi-quantitative rating scale was adopted to score these changes. Finally, patients were distributed into the suitable NVC pattern belonging to the scleroderma pattern. Our aim was to compare the peripheral microangiopathy changes in SSc patients with and without PAH, and to investigate the relationship between NVC findings and the main hemodynamic parameters of pulmonary vasculopathy. Patients with SSc-PAH+ showed a significant higher frequency of interstitial lung disease (ILD). No significant differences regarding clinical and laboratoristic parameters were observed. NVC abnormalities, avascular areas were more frequent in SSc patients with PAH, respect to those without ( p = 0.03), and capillary density was significantly lower when considering grade 3 ( p = 0.02). A higher NVC semiquantitative mean was found in SSc-PAH+ patients and a greater rate of the "late" pattern was detected in SSc-PAH+ subjects in respect to PAH- (57.1% vs. 25.7%) ( p = 0.03). A significant correlations between pulmonary pressure values (sPAP by TTE and mPAP by RHC) and the capillary density (Spearman's rho 0.35, p = 0.04 for both). Our findings provide additional evidence to the literature data, confirming that a higher degree of peripheral nailfold microangiopathy is more common in SSc-PAH patients, and further strengthening the concept that NVC changes may run parallel with similar abnormalities inside pulmonary microcirculation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giuggioli, Riccieri, Cipolletta, Del Papa, Ingegnoli, Spinella, Pellegrino, Risa, de Pinto, Papa, Armentaro and De Angelis.)

Objectives: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation)., Methods: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc., Results: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features., Conclusions: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.

Acute exacerbation (AE) is a possible manifestation of interstitial lung diseases (ILD) associated to very high mortality. It's defined as clinically significant respiratory deterioration with evidence of new widespread alveolar abnormalities on computed tomography scan. AE is better described in idiopathic pulmonary fibrosis (IPF) but also reported in ILD secondary to connective tissue diseases (CTD) and vasculitis. The main features and the real clinical impact of this severe complication in these patients are not well defined. Aim of our study was to prospectively investigate the incidence, clinical features and outcome of AE in a population of patients with ILD related to CTD and vasculitis. We consecutively enrolled all patients, with ILD secondary to rheumatic systemic diseases, referring to our multidisciplinary outpatient clinic for rare lung diseases. All patients were followed for at least 12 months (range, 12-36 months). At baseline, all patients underwent to a core set of laboratory investigations and periodically followed; data about demographic, disease onset, clinical, serological and therapeutic features were also recorded. AE occurred in 9/78 patients, with an incidence of 5.77/100 patients/year, and 5/9 patients died because of AE. The baseline value of DLCO was significantly associated to the risk of AE at Cox regression. In patients with ILD related to rheumatic systemic diseases AE can occur with an incidence similar to IPF. Rheumatologists should carefully consider this life-threatening complication as a possible natural course of all patients with ILD secondary to systemic rheumatic disease., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objectives: Digital ulcers (DU) may develop in half of systemic sclerosis (SSc) patients; they are often resistant to treatments. Deep wound debridement is crucial for DU healing, but very difficult to carry out without adequate procedural pain management. Here, we report the results of our experience on procedural pain management in scleroderma DU., Methods: The study included 51 DU observed in 32 consecutive SSc patients; procedural pain was treated following a definite schedule: local lidocaine and prilocaine (25 mg of either agent per gram of cream, EMLA 5%) were initially used in all cases, followed by local and oral morphine, according to the severity of pain scored on a 10 cm visual analogue scale (VAS)., Results: At baseline, higher pain VAS was recorded in more severe (p=0.0001) and/or infected DU (p=0.0001). Good compliance to DU debridement was observed in patients with mild pain (VAS ≤4) treated with only EMLA, and in 5 cases with moderate-severe pain (VAS >4) at baseline. While, the majority of DU with moderate-severe pain (34/39) needed a combined therapy with EMLA and local morphine (8/34) or with EMLA, local and oral morphine (26/34). On the whole, pain management during DU debridement required only EMLA application in 33% of cases, EMLA plus local morphine in 16%, while combined EMLA, local and oral morphine were necessary in 51%, generally with more severe and/or infected lesions., Conclusions: The present study showed valuable control of procedural pain during DU debridement with sequential, combined analgesic treatment.