Painful Raynaud's mimics.

Raynaud's syndrome is a common finding in many autoimmune conditions. Accurately diagnosing Raynaud's, and differentiating it from mimicking conditions, is imperative in rheumatologic diseases. Raynaud's syndrome and Raynaud's mimickers, especially painful Raynaud's mimickers, can prove a diagnostic challenge for the practicing rheumatologist. Painful Raynaud's mimickers can lead to increased patient stress and unnecessary medical work up; Healthcare providers need to be aware of Raynaud's mimickers when evaluating patient concerns of skin color changes and pain. The present narrative review aims to highlight Raynaud's syndrome, important painful mimickers that may be seen, diagnosis, and updated management recommendations.

Novel Therapeutic Approaches in Connective Tissue Disease-Associated Interstitial Lung Disease.

Connective tissue diseases (CTD) comprise a group of autoimmune diseases that can affect multiple organs in the body including the lungs. The most common form of pulmonary involvement is interstitial lung disease (ILD). CTD-associated ILD (CTD-ILD) can take one of several courses including nonprogressive, chronically progressive, or rapidly progressive. Chronically and rapidly progressive patterns are associated with increased mortality. Limited randomized controlled trial data are available for treatment of CTD-ILD, with most data coming from systemic sclerosis-related ILD. The current first-line treatment for all CTD-ILD is immunosuppression with consideration of antifibrotics, stem cell transplant, and lung transplant in progressive disease. In this article, we review data for ILD treatment options in systemic sclerosis, rheumatoid arthritis, myositis, and primary Sjögren's syndrome-related ILDs.

Impact of a resilience-building energy management intervention for people with systemic sclerosis: a mixed methods study.

Objectives: People with SSc often experience fatigue, which significantly affects daily life functioning and quality of life. We aimed to explore participants' experiences of a peer health-coached resilience-building energy management to enhance well-being (RENEW) intervention on symptoms and well-being and to use mixed methods to compare how SSc duration influenced the experiences of participants who had clinically significant fatigue improvement vs those who did not. Methods: Semi-structured interviews were conducted with 21 participants from the parent clinical trial randomized to the RENEW intervention. Data were analysed using the rigorous and accelerated data reduction technique combined with thematic content analysis. A mixed methods approach used a joint display to identify themes related to the impact of SSc duration on fatigue improvement status. Participants were categorized into short/improvement, short/limited improvement, long/improvement, and long/limited improvement. Results: Our team generated four themes: participant and peer health-coach relationship, physical and psychological well-being improvement, need for a tailored approach and easy program access through technology. Mixed methods analysis revealed that, regardless of SSc duration, participants with improved fatigue reported increasing self-awareness of SSc-related symptoms and learning coping strategies to manage fatigue. Participants in the short/improvement group reported preferences for slower pacing of the program and pairing with a coach with similar symptom severity. Participants in the long/limited improvement group sought SSc-specific symptom management information. Conclusion: Incorporating peer health coaches and technology is beneficial for self-management interventions for people with SSc. Future tailoring of RENEW based on SSc duration and symptom severity is needed. Clinical trial registration number: clinicatrials.gov, NCT04908943.

Peer-Led Symptom Management Intervention to Enhance Resilience in People with Systemic Sclerosis: Mediation Analysis from a Randomized Clinical Trial.

OBJECTIVE: Facilitated self-management interventions have the potential to enhance resilience and well-being. We examined whether resilience is a mediator of improving physical and psychological symptoms for people with systemic sclerosis (SSc) who participated in a 12-week online peer-led symptom management intervention. METHODS: We conducted a secondary data analysis from a randomized control trial comparing a peer health coached intervention to a waitlist control. Participants completed the Connor-Davidson Resilience Scale, the Functional Assessment of Chronic Illness Therapy-Fatigue scale, and the Patient Reported Outcomes Measurement Information System measures of pain interference and depressive symptoms at the baseline and at weeks 6 and 12. Linear mixed effect regression models were used to assess the effect of intervention on changes in resilience. Causal mediation analyses were conducted to examine whether changes in resilience at week 12 mediated intervention effects on changes in fatigue, pain interference, and depressive symptoms at week 12. RESULTS: One hundred and seventy-three eligible participants were enrolled. Participants in the intervention group reported improvements in resilience (p < .001). These changes in resilience mediated the intervention effects on fatigue with indirect effect of -1.41 (95% Confidence Interval [CI], -2.41 to -0.41), pain interference of -0.86 (95% CI, -1.65 to -0.08), and depressive symptoms of -1.99 (95% CI, -3.16 to -0.81). CONCLUSION: For participants in the intervention who had positive improvements in their physical and psychological symptoms, increased resilience was a mechanism for these improvements. These findings support the importance of addressing resilience to improve symptoms in similar SSc interventions.

Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.

OBJECTIVE: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. Alpha smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS: By week 14, cGMP increased by 94 ± 78% with riociguat and 10 ± 39% with placebo (p < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (p = 0.004 and p = 0.008, respectively). There were no differences in skin collagen markers between the 2 groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies were associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION: Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02283762.

Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry.

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry. Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared. Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 (n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 (n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 (n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 (n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters. Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.

Baseline absolute monocyte count predicts lung function decline among patients with systemic sclerosis-associated interstitial lung disease: A post hoc analysis from the focuSSced trial.

OBJECTIVE: Interstitial lung disease (ILD) is the leading cause of death in adults with systemic sclerosis (SSc). The identification of biomarkers to predict progression of SSc-ILD is an important unmet need. The purpose of this study was to determine whether an elevated baseline absolute monocyte count (AMC) is associated with a decline in forced vital capacity (FVC) at 48 weeks among participants with SSc-ILD enrolled in the phase 3 focuSSced trial. METHODS: We performed a post-hoc analysis of the focuSSced trial, a multicenter, double-blind, randomized, placebo-controlled trial of adults with diffuse cutaneous SSc for ≤ 60 months. Participants received subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks. We examined the relationship between baseline AMC and FVC at 48 weeks using a General Linear Model adjusted for potential confounders. RESULTS: The 136 participants with SSc-ILD in focuSSced were included in this study. Among participants assigned to the placebo group, there was a statistically significant inverse association between baseline AMC and change in FVC from baseline at week 48 in both unadjusted (ß coefficient -0.539, 95 % CI -1.032 to -0.047, p-value=0.032) and multivariable-adjusted (ß coefficient -0.573, 95 % CI -1.086 to -0.060, p-value=0.029) models. Among participants with SSc-ILD assigned to the tocilizumab group, there was no statistically significant association between baseline AMC and change in FVC from baseline at week 48 in unadjusted or fully adjusted models. CONCLUSION: AMC may be a biomarker of disease progression in SSc-ILD, especially in those with early SSc with elevated circulating inflammatory markers. These results should be validated in other SSc-ILD cohorts.

Systems-based identification of the Hippo pathway for promoting fibrotic mesenchymal differentiation in systemic sclerosis.

Systemic sclerosis (SSc) is a devastating autoimmune disease characterized by excessive production and accumulation of extracellular matrix, leading to fibrosis of skin and other internal organs. However, the main cellular participants in SSc skin fibrosis remain incompletely understood. Here using differentiation trajectories at a single cell level, we demonstrate a dual source of extracellular matrix deposition in SSc skin from both myofibroblasts and endothelial-to-mesenchymal-transitioning cells (EndoMT). We further define a central role of Hippo pathway effectors in differentiation and homeostasis of myofibroblast and EndoMT, respectively, and show that myofibroblasts and EndoMTs function as central communication hubs that drive key pro-fibrotic signaling pathways in SSc. Together, our data help characterize myofibroblast differentiation and EndoMT phenotypes in SSc skin, and hint that modulation of the Hippo pathway may contribute in reversing the pro-fibrotic phenotypes in myofibroblasts and EndoMTs.

Effects of a Resilience-Building Energy Management Program on Fatigue and Other Symptoms in Systemic Sclerosis: A Randomized Controlled Trial.

OBJECTIVE: Supported self-management interventions for individuals with systemic sclerosis (SSc) are needed. We examined the effects of a 12-week resilience-building energy management program (called RENEW) for fatigue and other patient-reported outcomes. METHODS: Participants, who had physician-diagnosed SSc, moderate to severe fatigue, and were ≥18 years old, were randomly assigned to RENEW or waitlist control in a 2:1 ratio. The RENEW intervention included an educational website/application plus nine virtual peer-led health coaching sessions. The primary outcome was change in the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary outcomes were change in Patient Reported Outcomes Measurement Information System measures of pain interference and depressive symptoms and Connor-Davidson Resilience Scale. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. Multiple imputation was conducted; linear mixed models were used to assess group differences. A three-way interaction with group, time, and SSc duration was examined in each model. RESULTS: Among 173 participants (mean ± SD age 54.5 ± 11.7 years; 93% female, 85% White), 47% had diffuse cutaneous SSc; 57% were ≤5 years from diagnosis. At 12 weeks, compared to controls, RENEW participants had a clinically meaningful fatigue improvement (ß = -4.7; 95% confidence interval -6.7 to -2.7; P < 0.001) and improvement in all secondary outcomes. Among RENEW participants, individuals with shorter disease duration had greater improvements in fatigue at 12 weeks. CONCLUSION: An mHealth supported self-management intervention improved fatigue and other outcomes, particularly in newly diagnosed patients. This program may be broadly scalable for SSc symptom management.

Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease.

OBJECTIVES: To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: In the SENSCIS trial, patients with SSc-ILD were randomized to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib. RESULTS: Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (s.e.) of decline in forced vital capacity (FVC; ml/year) over 52 weeks was -74.5 (19.2) in the placebo group and -49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI -28.9, 79.6]). Among 249 patients with data at week 52, mean (s.e.) change in FVC at week 52 was -86.4 (21.1) ml in the placebo group and -39.1 (22.2) ml in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (s.e.) change in FVC from baseline to week 52 of SENSCIS-ON was -41.5 (24.0) ml in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and -45.1 (19.1) ml in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON. CONCLUSION: Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT02597933 and NCT03313180.

Prognostic and predictive markers of systemic sclerosis-associated interstitial lung disease in a clinical trial and long-term observational cohort.

OBJECTIVES: To explore prognostic and predictive markers of SSc-associated interstitial lung disease (SSc-ILD) outcomes in a phase 3 trial (focuSSced) and prognostic markers in a real-world cohort (SMART). METHODS: The focuSSced SSc-ILD subgroup included 68 of 106 placebo-treated and 68 of 104 tocilizumab-treated patients. The SMART cohort included 505 patients with SSc-ILD. Linear mixed-effect models were used to identify factors associated with change in forced vital capacity (FVC). Kaplan-Meier estimation and Cox regression were used for time-to-event analyses. RESULTS: In placebo-treated focuSSced patients, sex was a significant prognostic factor for FVC decline; males had increased risk for absolute decline ≥10% in percent-predicted FVC (ppFVC) and 0.22% faster weekly FVC decline than females (P = 0.0001). FVC was 9.8% lower in patients with CRP >6 mg/ml vs those with CRP ≤6 mg/ml (P = 0.0059). Tocilizumab reduced the risk for ≥10% decline in ppFVC in patients who were male, had earlier disease (<2 years duration), had IL-6 levels <10 pg/ml, or had anti-topoisomerase antibodies (ATA). In the SMART cohort, prognostic factors for ppFVC <70% were male sex, ATA, and low baseline FVC. Males had 3.3% lower FVC 1 year after disease onset (P < 0.001) and 0.6% faster yearly decline (P = 0.03) than females. CONCLUSION: Prognostic markers in SSc-ILD were similar between focuSSced and SMART. Male sex and inflammatory markers were associated with lower FVC but IL-6 ≥10 pg/ml was not predictive of response to tocilizumab. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02453256.

Performance of DETECT Pulmonary Arterial Hypertension Algorithm According to the Hemodynamic Definition of Pulmonary Arterial Hypertension in the 2022 European Society of Cardiology and the European Respiratory Society Guidelines.

OBJECTIVE: The evidence-based DETECT pulmonary arterial hypertension (PAH) algorithm is frequently used in patients with systemic sclerosis (SSc) to help clinicians screen for PAH by using noninvasive data to recommend patient referral to echocardiography and, if applicable, for a diagnostic right-sided heart catheterization. However, the hemodynamic definition of PAH was recently updated in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines. The performance of DETECT PAH in identifying patients with a high risk of PAH according to this new definition was assessed. METHODS: In this post hoc analysis of DETECT, which comprised 466 patients with SSc, the performance of the DETECT PAH algorithm in identifying patients with a high risk of PAH as defined in the 2022 ESC/ERS guidelines (mean pulmonary arterial pressure [mPAP] >20 mm Hg, pulmonary capillary wedge pressure [PCWP] ≤15 mm Hg, and pulmonary vascular resistance >2 Wood units) was assessed using summary statistics and was descriptively compared to the known performance of DETECT PAH as defined in 2014, when it was developed (mPAP ≥25 mm Hg and PCWP ≤15 mm Hg). RESULTS: The sensitivity of DETECT PAH in identifying patients with a high risk of PAH according to the 2022 ESC/ERS definition was lower (88.2%) compared to the 2014 definition (95.8%). Specificity improved from 47.8% to 50.8%. CONCLUSION: The performance of the DETECT algorithm to screen for PAH in patients with SSc is maintained when PAH is defined according to the 2022 ESC/ERS hemodynamic definition, indicating that DETECT remains applicable to screen for PAH in patients with SSc.

Surgical management of digital ulcers in systemic sclerosis: A systematic literature review.

BACKGROUND: There is a strong rationale to develop locally-acting surgical treatments for digital ulcers (DUs) in patients with systemic sclerosis (SSc). Our aim was to examine the safety and efficacy of local surgical management for SSc-DU. METHODS: A systematic literature review was carried out until to August 2022 using 7 different databases. Original research studies concerning adult patients with SSc-DUs, and local surgical treatments were analysed using the PICO framework. We included randomized controlled trials, prospective/retrospective studies, and case series (minimum of 3 patients) References were independently screened by two reviewers including assessment of the risk of bias using validated tools. RESULTS: Out of 899, 13eligible articles were included. Autologous fat (adipose tissue AT) grafting was the surgical modality most identified (7 studies, 1 randomized controlled double blinded trial and 6 prospective open-label single arm studies). The healing rate (HR) with autologous fat grafting (4 studies) was 66-100 %. Three studies reported autologous adipose-derived stromal vascular fraction grafting: HR of 32-60 %. Bone marrow derived cell transplantation in a single study showed 100 % healing rate over 4-24 weeks. Surgical sympathectomy was examined in 3 studies, prospective without comparator with a median healing rate of 81 %. Two surgical studies (of direct microsurgical revascularisation and microsurgical arteriolysis) showed 100 % healing of ulcers, with no complications. CONCLUSION: Several surgical approaches for SSc-DUs have demonstrated some degree of safety and effectiveness for DU healing. However, there are significant methodological issues. Future studies are warranted to rigorously investigate surgical interventions for SSc-DUs.

Economic and Health Care Resource Use Burden of Systemic Sclerosis.

OBJECTIVE: To describe the health care resource use (HCRU) and costs of patients with systemic sclerosis (SSc) prior to and after diagnosis. METHODS: This retrospective study used a claims data set (Merative MarketScan; 2015-2019). Eligible patients with SSc were identified by diagnosis codes and required at least 24 months of enrollment without an SSc diagnosis before their first SSc claim and at least 12 months of enrollment thereafter. Total HCRU and costs were reported for three intervals: 2 years and 1 year before and 1 year after index diagnosis. A general population cohort without SSc was matched 1:1 to the SSC cohort on age and sex for comparison. RESULTS: Eligibility criteria identified 902 patients with SSc (mean age: 54 years old; 85% female). Mean per-member per year costs increased each year from $22,383 to $29,708 to $47,095, 2 years before, 1 year before, and 1 year after index diagnosis versus $10,232 to $9656 to $9714 in the general population cohort. Outpatient settings represented the largest proportion of cost 1 year after SSc diagnosis ($16,392), followed by prescription drugs ($10,692), physician office ($10,523), and inpatient ($9448) settings. CONCLUSION: Patients with SSC accrued greater costs and required more services than a general population cohort. These elevated expenditures and HCRU were observed at least 2 years before an SSc diagnosis and increased over time, reflecting both the progressive, multisystem nature of SSc and potential challenges in diagnosis. These findings suggest that SSc poses a substantial burden on the US health care system and highlights the need for early diagnosis and effective therapies.

Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review.

INTRODUCTION: Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs. METHODS: A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data. RESULTS: Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity. CONCLUSIONS: A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.

An interleukin 6 responsive plasma cell signature is associated with disease progression in systemic sclerosis interstitial lung disease.

Systemic sclerosis (SSc) interstitial lung disease (ILD) is among the leading causes of SSc-related morbidity and mortality. Tocilizumab (TCZ, anti-IL6RA) has demonstrated a reduced rate of pulmonary function decline in two phase 2/3 trials (faSScinate and focuSSced) in SSc-ILD patients. We performed transcriptome analysis of skin biopsy samples collected in the studies to decipher gene networks that were potentially associated with clinical responses to TCZ treatment. One module correlated with disease progression showed pharmacodynamic changes with TCZ treatment, and was characterized by plasma cell (PC) genes. PC signature gene expression levels were also significantly increased in both fibrotic SSc and IPF lungs compared to controls. scRNAseq analyses confirmed that PC signature genes were co-expressed in CD38 and CD138 expressing PC subsets in SSc lungs. These data provide insights into the potential role of PC in disease progression and mechanisms of action of TCZ in fibrotic interstitial lung diseases.

Consensus on the assessment of systemic sclerosis-associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment.

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Patient-level factors predictive of interstitial lung disease in rheumatoid arthritis: a systematic review.

Objective Interstitial lung disease (ILD) is an important cause of mortality in some patients with rheumatoid arthritis (RA). Patient-level factors may predict which patients with RA are at the highest risk of developing ILD and are therefore candidates for screening for this complication of the underlying disease.Methods A systematic literature review was performed using PubMed, Embase and Scopus over a 10-year period up to July 2021. Publications reporting patient-level factors in patients with RA with and without ILD that were assessed before development of ILD (or were unchanged over time and therefore could be extrapolated to before development of ILD) were retrieved for assessment of evidence. Genetic variation in MUC5B and treatment with methotrexate were not included in the assessment of evidence because these factors have already been widely investigated for association with ILD.Results We found consistent associations of age, sex, smoking status and autoantibodies with development of ILD. For biomarkers such as Krebs von den Lungen 6, which have been shown to be diagnostic for ILD, there were no publications meeting criteria for this study.Conclusions This analysis provides an initial step in the identification of patient-level factors for potential development of a risk algorithm to identify patients with RA who may be candidates for screening for ILD. The findings represent a useful basis for future research leading to an improved understanding of the disease course and improved care for patients with RA at risk of development and progression of ILD.

The Collaborative National Quality and Efficacy Registry for Scleroderma: association of medication use on gastrointestinal tract symptoms in early disease and the importance of tobacco cessation.

OBJECTIVES: Systemic Sclerosis (SSc) is frequently associated with gastrointestinal tract (GIT) involvement. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative study collecting longitudinal follow up data on SSc patients with less than 5-years disease duration enrolled at Scleroderma centres of excellence. This manuscript presents the GIT natural history and outcomes in relation to other scleroderma manifestations and medication exposures. METHODS: CONQUER participants that had completed a minimum of two serial Scleroderma Clinical Trials Consortium GIT Questionnaires (GIT 2.0) were included in this analysis. Patients were categorised by total GIT 2.0 severity at baseline, and by category change: none-to-mild (0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00) at the subsequent visit. Based on this data, four groups were identified: none-to-mild with no change, moderate-to-severe with no change, improvement, or worsening. Clinical features and medications, categorised as gastrointestinal tract targeted therapy, anti-fibrotic, immunosuppression, or immunomodulatory drugs, were recorded. Analysis included a proportional odds modelaccounting for linear and mixed effects of described variables. RESULTS: 415 enrolled CONQUER participants met project inclusion criteria. Most participants had stable mild GIT symptoms at baseline and were on immunomodulatory and anti-reflux therapy. In most patients, anti-reflux medication and immunosuppression initiation preceded the baseline visit, whereas anti-fibrotic initiation occurred at or after the baseline visit. In the proportional odds model, worsening GIT score at the follow-up visit was associated with current tobacco use (odds ratio: 3.48 (1.22, 9.98, p 0.020). CONCLUSIONS: This report from the CONQUER cohort, suggests that most patients with early SSc have stable and mild GIT disease. Closer follow-up was associated with milder, stable GIT symptoms. There was no clear association between immunosuppression or anti-fibrotic use and severity of GIT symptoms. However, active tobacco use was associated with worse GIT symptoms, highlighting the importance of smoking cessation counselling in this population.