The Burden of Interstitial Lung Involvement in Rheumatoid Arthritis: Could Lung Ultrasound Have a Role in Its Detection? A Literature Review.

Lung involvement represents a fearful complication in rheumatoid arthritis (RA), potentially involving all compartments of the pulmonary system. Regarding interstitial lung disease (ILD), the HRCT represents the gold standard technique for its diagnosis; however, the examination is burdened by radiation exposure and high costs. In addition, although some risk factors for ILD are known, no algorithms exist to know which patients to submit to HRCT and when. In this context, lung ultrasound (LUS) showed promising results for at least 10 years, demonstrating correlation with high resolution computed tomography (HRCT) findings in other rheumatic diseases. Here, LUS may represent a screening test providing additional information to clinical examination and pulmonary function tests. The data deriving from LUS experience in other rheumatic diseases could steer the future towards the use of this technique also in RA patients, and in this review, we report the most relevant literature regarding LUS in RA-ILD.

Efficacy of physiotherapy treatment in medium and long term in adults with fibromyalgia: an umbrella of systematic reviews.

OBJECTIVES: To summarise the available evidence and assess the effectiveness of medium and long-term physiotherapy treatment in adults with fibromyalgia (FM). METHODS: This systematic review was registered in PROSPERO: CRD42023388356. The databases searched were MEDLINE, PEDro, Scopus, Cinhal, LatinIndex, and Cochrane, using the following keywords: "fibromyalgia", "physiotherapy", "treatment", "therapeutic exercise", "TENS", "laser therapy" and "manual therapy." The included articles analysed treatments with active or passive physiotherapy approaches in patients with FM. The variables included structural characteristics, such as: author, publication year, research question, and main outcome variables. The data on the findings of the articles comprised the following aspects: number of participants, intervention, follow-up, results, and principal conclusions. RESULTS: Thirty-three articles were analysed, with an overall PRISMA score of 18.63±3.36. The active treatment methods analysed were: movement and body awareness therapies (stretching, tai chi, yoga and Pilates); hydrotherapy; physical or aerobic exercise; and multidisciplinary therapy. The passive therapies analysed were: manual therapy; repetitive transcranial magnetic stimulation (rTMS); and other therapies (hyperbaric oxygen therapy, vibration therapy, virtual reality, transcutaneous electric nervous stimulation (TENS), pain neuroscience education, and acupuncture). Evidence was found on the positive effect of physiotherapy treatment on the signs and symptoms of fibromyalgia, such as pain, impairment of physical capacity and worse quality of life. CONCLUSIONS: The effectiveness of the active and passive therapies analysed in the management of the symptoms and signs of the disease was positive in most of the studies. However, more specific descriptions of the treatment protocol, frequency, intensity and treatment dose are required to reach a consensus, as well as primary studies for a more extended follow-up period to better evaluate long-term effects.

Evidence for telemedicine heterogeneity in rheumatic and musculoskeletal diseases care: a scoping review.

Telemedicine and digital health represent alternative approaches for clinical practice; indeed, its potential in healthcare services for prevention, diagnosis, treatment, rehabilitation, and disease monitoring is widely acknowledged. These are all crucial issues to consider when dealing with chronic Rheumatic and Musculoskeletal Diseases (RMDs). The aim was to determine the current state of telemedicine in the field of rheumatology, considering the tools and devices in use as well as the Patient Reported Outcomes. A scoping review was performed following the PRISMA-ScR, retrieving articles through five databases from 1990 to 2022. Inclusion criteria were as follows: (I) adult patients with RMDs, (II) original research papers in the English language with available abstracts, and (III) telehealth and telemedicine are provided as healthcare services. Within the 62 included studies, multiple tools of telemedicine were used: 21/62 websites/online platforms, 18/62 mobile applications, 16/62 telephone contacts, 5/62 video-consultations, and 1/62 wearable devices. Outcomes were classified based on the economic, clinical, and humanistic framework. Clinical outcomes assessed through digital tools were pain, disease activity, and serum uric acid levels. Humanistic outcomes have been grouped according to four categories (e.g., mental and physical function, health management, and health perception). The heterogeneity of digital tools in the field of rheumatology highlights the challenge of implementing reliable research into clinical practice. Effective telerehabilitation models have been presented, and the use of a tight control strategy has also been mentioned. Future research should focus on establishing studies on other RMDs as well as summarizing and formulating clinical guidelines for RMDs. Key Points • Evidence for the usefulness of telemedicine and digital health for managing and monitoring rheumatic and musculoskeletal diseases is progressively increasing. • Several digital tools effectively measure clinical and humanistic and patient reported outcomes in rheumatic and musculoskeletal diseases. • Integrating diverse digital tools in rheumatology is challenging yet promising. • Future research should focus on developing standardized recommendations for practical use of telemedicine in daily practice.

A multi-national survey to identify clinicians' perspectives concerning Proton Pump inhibitors in patients with systemic sclerosis.

OBJECTIVES: Proton Pump Inhibitors (PPIs) are widely used in SSc for gastroesophageal reflux disease (GERD). However, there is little evidence to support their empirical use and long-term safety has been questioned. Our objective was to better describe clinicians' attitudes toward PPIs prescription and use in SSc patients. METHODS: Clinicians involved in the care of SSc patients were invited through international physician networks and social media to participate in an online survey. RESULTS: Responses from 227 clinicians from 36 countries were evaluable. The majority 'agreed' (41.4 %) or 'strongly agreed' (45.4 %) that GERD is a major cause of morbidity in SSc. Lifestyle modifications are seldom (16 %) considered effective. Only half 'agreed' (43 %) or 'strongly agreed' (11 %) there is solid evidence supporting PPIs efficacy in SSc. The most common reasons for PPIs prescription were symptomatic GERD unresponsive to lifestyle modification (95 %), objective evidence of GERD (82 %), and hoarseness or respiratory symptoms (71 %). There are variable concerns about PPIs long-term safety in SSc. The three highest (mean) reasons (0-10, here 10 is 'very concerned') were: small intestinal bacterial overgrowth (5.5), osteoporosis (5.4), and drug interactions (5.2). There are significant differences in attitudes towards surgery for refractory GERD, and concerns about potential complications. PPIs may have a putative role for disease modification (e.g., ILD and calcinosis), and the role of immunosuppression is uncertain for GI (gastrointestinal) disease in SSc. CONCLUSION: PPIs are frequently prescribed in SSc. Side effects are a recognized concern, especially regarding long-term therapy. There is significant variation in attitudes towards surgical intervention. Future research and practical treatment recommendation for PPIs in SSc are urgently needed.

The Rising Challenge of Poor Health Literacy of Patients with Systemic Sclerosis: Preliminary Data Identify Important Unmet Needs in an Italian Cohort.

RATIONALE AND AIM: Health literacy (HL) is pivotal for the successful self-management of chronic diseases. Little HL information is currently available in SSc patients; therefore, the present study aims at evaluating the HL levels in an Italian cohort of SSc patients. METHODS: SSc patients were enrolled with the support of Italian patient associations, from September 2022 to March 2023. Health literacy characteristics were derived from the Health Literacy Scale European Questionnaire-16 (HLS-EU-Q16), consisting of 16 items designed on a four-point Likert scale ranging from "very difficult" to "very easy", and three HL levels were identified: inadequate HL (0-8 score); problematic HL (9-12 score); and sufficient HL (13-16 score). RESULTS: Enrolled patients (n = 57, mean age = 59 years, SD = 13.2) were mostly female (98.2%), partnered (73.7%), and unemployed or retired (67.9%). Almost half of SSc patients were diagnosed more than 10 years ago, with first symptoms appearing on average 19 years ago (SD 10.5). In 63% of the participants, the overall health literacy skills were inadequate, or problematic, especially in the health care and disease prevention domains. Indeed, 49.2% of the patients declared difficulty in finding information on treatments for illnesses and where to get professional help (42.1%), 47.6% found difficulty in retrieving information on how to manage mental health problems, and 40.4% declared difficulties in judging whether the information on health risks in the media was reliable. CONCLUSIONS: Our findings show that SSc patients have inadequate or problematic levels of HL, suggesting the need for periodic screenings to uncover poor health literacy skills and to provide tailored and understandable educational material. This study was not registered.

Patients' unmet needs and treatment preferences concerning digital ulcers in systemic sclerosis.

INTRODUCTION: Digital ulcers (DUs) significantly impact on quality of life and function in patients with systemic sclerosis (SSc). The aim of our survey was to explore patients' perspectives and their unmet needs concerning SSc-DUs. MATERIALS: SSc patients were invited through international patient associations and social media to participate in an online survey. RESULTS: 358 responses were obtained from 34 countries: US (65.6%), UK (11.5%) and Canada (4.5%). Recurrent DUs are common: >10 DUs (46.1%), 5-10 DUs (21.5%), 1-5 DUs (28.5%), 1 DU (3.9%). Fingertip DUs were most frequent (84.9%), followed by those overlying the interphalangeal joints (50.8%). The impact of DUs in patients is broad, from broad-ranging emotional impacts to impact on activities of daily living, and personal relationships. Half (51.7%) of respondents reported that they received wound/ulcer care, most often provided by non-specialist wound care clinics (63.8%). There was significant variation in local (wound) DU care, in particular the use of debridement and pain management. DU-related education was only provided to one-third of patients. One-quarter (24.6%) were 'very satisfied' or 'satisfied' that the provided DU treatment(s) relieved their DU symptoms. Pain, limited hand function, and ulcer duration/chronicity were the main reasons for patients to consider changing DU treatment. CONCLUSIONS: Our data show that there is a large variation in DU treatment between countries. Patient access to specialist wound-care services is limited and only a small proportion of patients had their DU needs met. Moreover, patient education is often neglected. Evidence-based treatment pathways are urgently needed for DU management.

The Performance of Pulmonary Function Tests in Predicting Systemic Sclerosis-Interstitial Lung Disease in the European Scleroderma Trial and Research Database.

BACKGROUND AND OBJECTIVES: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. METHODS: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. RESULTS: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. CONCLUSIONS: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Practice pattern for the use of intravenous iloprost for the treatment of peripheral vasculopathy in systemic sclerosis: A case-control study from the Italian national multicenter "SPRING" (Systemic Sclerosis Progression InvestiGation) Registry.

Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data. Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group). Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, "late" scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis. Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets.

Advanced and traditional chest MRI sequence for the clinical assessment of systemic sclerosis related interstitial lung disease, compared to CT: disease extent analysis and correlations with pulmonary function tests.

BACKGROUND: MRI is a radiation-free emerging alternative to CT in systemic sclerosis related interstitial lung disease (SSc-ILD) assessment. We aimed to compare a T2 radial TSE and a PD UTE MRI sequence with CT in SSc-ILD extent evaluation and correlations with pulmonary function tests (PFT). MATERIAL AND METHODS: 29 SSc-ILD patients underwent CT, MRI and PFT. ILD extent was visually assessed. Lin's concordance correlation coefficients (CCC) and Kruskal Wallis test (p-value < 0.05) were computed for inter-method comparison. Patients were divided in limited and extended disease, defining extended ILD with two methods: (A) ILD>30% or 10%20% or 20% with FVC%<70%. MRI Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Accuracy were assessed. Pearson correlation coefficients r (p-value<0.025) were computed between ILD extents and PFT (FVC% and DLCO%). RESULTS: Median ILD extents were 11%, 11%, 10% on CT, radial TSE and UTE, respectively. CCC between CT and MRI was 0.95 for both sequences (Kruskal-Wallis p-value=0.64). Sensitivity, Specificity, PPV, NPV and Accuracy in identifying extended disease were: (A) 87.5 %, 100 %, 100 %, 95.5 and 96.6 % with radial TSE and 87.5 %, 95.2 %, 87.5 %, 95.2 and 93.1 % with UTE; (B) 86.7 %, 86.4 %, 66.7 %, 95.0 % and 86.2 % for both sequences. Pearson r of CT, radial TSE and UTE ILD extents with FVC were -0.66, -0.60 and -0.68 with FVC, -0.59, -0.56 and -0.57 with DLCO, respectively (p<0.002). CONCLUSIONS: MRI sequences may have similar accuracy to CT to determine SSc-ILD extent and severity, with analogous correlations with PFT.

The differential crosstalk of the skin-gut microbiome axis as a new emerging actor in systemic sclerosis.

OBJECTIVES: We characterized the microbiota in SSc, focusing on the skin-oral-gut axis and the 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. GC-MS was used to quantify faecal and serum FFAs. Gastrointestinal symptoms were investigated with the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (UCLA GIT-2.0) questionnaire. RESULTS: The ACA+ and anti-Scl70+ groups displayed different cutaneous and faecal microbiota profiles. The classes of cutaneous Sphingobacteriia and Alphaproteobacteria, the faecal phylum Lentisphaerae, the levels of the classes Lentisphaeria and Opitutae, and the genus NA-Acidaminococcaceae were significantly higher in faecal samples from the ACA+ patients than in samples from the 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 levels of faecal medium-chain FFAs and hexanoic acids were significantly higher in the ACA+ group than in the anti-Scl70+ group (P < 0.05 and P < 0.001, respectively). In the ACA+ group, the analysis of the serum FFA levels showed an increasing trend in valeric acid. CONCLUSION: Different microbiota signatures and FFA profiles were found for the two groups of patients. Despite being in different body districts, the cutaneous Sphingobacteria and faecal Lentisphaerae appear interdependent.

Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase.

Introduction: The impact of COVID-19 pandemic represents a serious challenge for 'frail' patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. Patients and method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients (death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001). Conclusions: An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients' population.

In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case-control study.

BACKGROUND: Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM). OBJECTIVES: To assess the significance of DH/BS in patients with IM. METHODS: Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1. RESULTS: 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p<0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p<0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p<0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p<0.05). CONCLUSION: In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis).

Lymphatic Endothelial-to-Myofibroblast Transition: A Potential New Mechanism Underlying Skin Fibrosis in Systemic Sclerosis.

At present, only a few reports have addressed the possible contribution of the lymphatic vascular system to the pathogenesis of systemic sclerosis (SSc). Based on the evidence that blood vascular endothelial cells can undertake the endothelial-to-myofibroblast transition (EndMT) contributing to SSc-related skin fibrosis, we herein investigated whether the lymphatic endothelium might represent an additional source of profibrotic myofibroblasts through a lymphatic EndMT (Ly-EndMT) process. Skin sections from patients with SSc and healthy donors were immunostained for the lymphatic endothelial cell-specific marker lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) in combination with α-smooth muscle actin (α-SMA) as the main marker of myofibroblasts. Commercial human adult dermal lymphatic microvascular endothelial cells (HdLy-MVECs) were challenged with recombinant human transforming growth factor-ß1 (TGFß1) or serum from SSc patients and healthy donors. The expression of lymphatic endothelial cell/myofibroblast markers was measured by quantitative real-time PCR, Western blotting and immunofluorescence. Collagen gel contraction assay was performed to assess myofibroblast-like cell contractile ability. Lymphatic endothelial cells in intermediate stages of the Ly-EndMT process (i.e., coexpressing LYVE-1 and α-SMA) were found exclusively in the fibrotic skin of SSc patients. The culturing of HdLy-MVECs with SSc serum or profibrotic TGFß1 led to the acquisition of a myofibroblast-like morphofunctional phenotype, as well as the downregulation of lymphatic endothelial cell-specific markers and the parallel upregulation of myofibroblast markers. In SSc, the Ly-EndMT might represent a previously overlooked pathogenetic process bridging peripheral microlymphatic dysfunction and skin fibrosis development.

Systemic sclerosis and primary biliary cholangitis: Longitudinal data to determine the outcomes.

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 < 0.001) and of conduction blocks (p = 0.0256) was observed in systemic sclerosis patients without primary biliary cholangitis. Patients with primary biliary cholangitis had higher levels of liver enzymes at baseline than systemic sclerosis patients; a significant decrease in liver enzymes was observed at follow-up. Out of 18 patients with cholangitis, one received a liver transplant at follow-up. 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.

Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology.

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.

Nursing interventions for patients with rheumatic and musculoskeletal diseases on biological therapies: a systematic literature review.

Investigating unmet needs and identifying the necessary interventions for patients affected by rheumatic and musculoskeletal diseases (RMDs) may help significantly to ensure the continuity and quality of the chronic care pathway. To this aim, the contribution of rheumatology nurses requires further evidence. The aim of our systematic literature review (SLR) was to identify the nursing interventions directed towards patients with RMDs undergoing biological therapy. To retrieve data, a search was carried out in the MEDLINE database, the Cumulative Index to Nursing and Allied Health Literature (CINAHL database), the APA PsycINFO database and the Excerpta Medica Database (EMBASE) from 1990 to 2022. The systematic review was carried out in accordance with the relevant PRISMA guidelines. Inclusion criteria were as follows: (I) adult patients with RMDs, (II) undergoing therapy with Biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs), (III) original and quantitative research papers in English with available abstract, (IV) specific to nursing interventions and/or outcomes. Two independent reviewers screened the identified records for eligibility according to their title and abstract, full texts were subsequently assessed and, finally, data was extracted. Critical Appraisal Skills Programme (CASP) tools were used to evaluate the quality of the studies included. Among the 2348 records retrieved, 13 articles met the inclusion criteria. These consisted of six randomised controlled trials (RCTs), one pilot study and six observational studies on RMDs. In a total population of 2004 patients, 43% (862/2004) of the cases concerned rheumatoid arthritis (RA) and 56% (1122/2004) of the cases concerned spondyloarthritis (SpA). Three major nursing interventions were identified, namely education, patient-centred care and data collection/nurse monitoring, which were correlated with high satisfaction rates regarding care, increased self-care capacity and treatment adherence among patients. All interventions followed a protocol defined in collaboration with rheumatologists. The large degree of heterogeneity in the interventions did not allow the performance of a meta-analysis. Rheumatology nurses are part of a multidisciplinary team caring for patients with RMDs. Following an accurate initial nursing evaluation, rheumatology nurses can plan and standardise their interventions focusing primarily on patient education and personalised care based on actual needs, such as psychological well-being and disease control. However, the training for rheumatology nurses should define and standardise, as much as possible, the competencies required for the detection of disease parameters. Key Points • This SLR provides an overview of nursing interventions for patients with RMDs. • This SLR considers the specific population of patients on biological therapies. • Training for rheumatology nurses should standardise, as much as possible, the knowledge and methods required for detecting disease parameters. • This SLR highlights the various competencies of rheumatology nurses.

Systemic Sclerosis Patients Experiencing Mindfulness-Based Stress Reduction Program: The Beneficial Effect on Their Psychological Status and Quality of Life.

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.

Persistence of remission after lengthening of golimumab in inflammatory joint diseases.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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; p<0.001) 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. CONCLUSIONS: 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.