Systemic Sclerosis Research Articles

Microstomia is associated with functional impairment and is a poor prognostic factor in systemic sclerosis - a single center observational study with survival analysis.

Objectives were to assess the mouth opening ability (MOA) among patients with systemic sclerosis (SSc) in comparison to a healthy control population. The impact of microstomia (decrease in any of the MOA parameters) on physical performance and long-term survival was also investigated. Interincisal (ID), interlabial (LD), the intercommissural distances at both opened mouth and closed mouth (OW, CW) and the oral area (OA) and circumference (OC) all were assessed in 131 SSc patients. Microstomia was defined based on the oral aperture values of a healthy control group (n = 63) with similar median age and sex distribution. Tests evaluating functional performance were performed. Survival analysis by univariate and multivariate Cox regression analysis was performed. Microstomia was present in 56.5% of the entire SSc cohort. Patients with microstomia had higher number of contractures compared to those with preserved oral aperture parameters (median 10 vs. 7, p < 0.01). LD, OA and OC correlated negatively with the number of joint contractures, both in the entire SSc cohort and separately in the diffuse (dcSSc) and limited cutaneous subsets (lcSSc), (rho: between - 0.267 and - 0.516, p < 0.05). Reduced ID was associated with worse Health Assessment Questionnaire Disability Index (HAQ-DI) only in dcSSc while reduced LD was linked to increased HAQ-DI scores in both SSc subsets. Decreased OA upon enrollment was associated with an increased risk in mortality by multivariate Cox regression analysis (HR: 2.74; 95% CI, 1.15-6.53). Microstomia was associated with joint damage, and higher overall disability based on HAQ-DI. Interlabial distance was a beneficial, convenient measurable parameter to characterize oral aperture. Oral area was an independent poor prognostic factor regarding long-term survival.

Pulmonary manifestations of juvenile vs. adult systemic sclerosis: insights into pathophysiological and clinical features.

Juvenile systemic sclerosis (jSSc), the pediatric counterpart of systemic sclerosis (SSc), is a rare autoimmune disorder characterized by vasculopathy and fibrotic disorders. It ranks among the rheumatologic diseases with the highest rates of morbidity and mortality, predominantly impacting females. Although a universally accepted classification for jSSc remains elusive, a provisional classification proposed in 2007 integrates major and minor criteria, reflecting the involvement of diverse organs and tissues. Pulmonary manifestations are relatively common in jSSc, occurring in 36% to 55% of cases. Particularly lung complications include children s interstitial lung disease (chILD), pulmonary arterial hypertension (PAH) and nodules. The aim of this paper is to describe the main pulmonary manifestations of patients with jSSc in relation to SSc, highlighting fundamental pathophysiological, and clinical features based on the latest literature data.

Thoracic paravertebral block in ineffective stellate ganglion block in a patient of long-standing systemic sclerosis: A case report

Thoracic paravertebral block in ineffective stellate ganglion block in a patient of long-standing systemic sclerosis: A case report

Immunosuppressive Drugs in Early Limited Cutaneous Systemic Sclerosis May Prevent Global Damage Accrual.

Organ damage in systemic sclerosis (SSc) in individual organs such as the lungs may be prevented by immunosuppressive drugs (IS). A new measure of global organ damage, the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI), has allowed us to investigate whether IS may reduce global organ damage accrual in early SSc. This was a retrospective study of patients with < 2 years disease duration in Canadian and Australian SSc cohorts. Patients with either limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc were observed separately and divided into ever or never exposed to IS groups. The SCTC-DI was the outcome and inverse probability of treatment weighting (IPTW) was used to balance the study groups and to fit a marginal structural generalized estimating equation (GEE) model. In the lcSSc cohort, there were 210 subjects of which 34% were exposed to IS at some time. Exposure to IS was associated with lower damage scores. In the dcSSc cohort, there were 192 subjects of which 76% were exposed to IS at some time. Exposure to IS was not associated with damage scores. In this retrospective observational cohort study, using IPTW to adjust for confounders, we found a protective effect of the use of IS on damage accrual in lcSSc. We were unable to determine such an effect in dcSSc but unknown confounders may have been present and prospective studies of IS in dcSSc should include the SCTC-DI to determine the possible effect of IS on damage accrual.

Oral glucocorticoids for skin fibrosis in early diffuse systemic sclerosis: a target trial emulation study from the European Scleroderma Trials and Research group database.

The objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc). We performed an emulated randomized trial comparing the changes from baseline to 12±3 months of the modified Rodnan skin score (mRSS: primary outcome) in early dcSSc patients receiving either oral glucocorticoids (≤20 mg/day prednisone-equivalent) combined with immunosuppression (treated), or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary endpoints were the difference occurrence of progressive skin or lung fibrosis, and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups. We matched 208 patients (age 49 years; 33% male; 59% anti-Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12±3 months was similar in the two groups (decrease of 2.7 [95% CI 1.4 - 4.0] in treated vs. 3.1 [95% CI 1.9 - 4.4] in control, p = 0.64). Similar results were observed in patients with shorter disease duration (≤ 24 months) or with mRSS ≤22. There was no between-group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups. We did not find any significant benefit of adding low-dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis.

Analysis of hsa_circ_0136256 as a biomarker for fibrosis in systemic sclerosis.

Exploration of whether circRNAs in the skin of systemic sclerosis (SSc) model mice interact with 4E-BP1 protein to mediate the mTOR signaling pathway to regulate SSc fibrosis is crucial to identify homologous human circRNAs as markers to guide the diagnosis and treatment of SSc. C57BL/6 mice aged 6-8 weeks and weighing approximately 20 g were subcutaneously injected with bleomycin (BLM) to establish an SSc model. High-throughput sequencing was used to screen the differentially expressed circRNA in the skin of SSc model mice and control mice. RNA immunoprecipitation and RNA pulldown confirmed the interaction between circRNA and 4E-BP1 protein. SSc model mice were treated with empty plasmid (OE-NC), overexpression plasmid of mmu_circ_0005372 (OE-circ_0005372), interference plasmid of mmu_circ_0005372 (sh-circ5372), mutant plasmid of mmu_circ_0005372 (circ5372-MT), mTOR activator (MHY1485), mTOR inhibitor (omipalisib), or JAK1/2 inhibitor (ruxolitinib). Sections of mouse skin tissue were stained with Hematoxylin and eosin and Masson's stain. The collagen volume fraction (CVF) was calculated as CVF = area of blue collagen/total area with ImageJ. The correlation between homologous human circRNAs and clinical data was analyzed. Compared to the control group, 21,839 circRNAs were upregulated and 27, 946 circRNAs were downregulated in the skin tissue of mice in the SSc model group. Among them was mmu_circ_0005372, which is derived from the FZD3 gene, is closely related to fibrosis, and is involved in the mTOR signaling pathway. Hsa_circ_0136256 was identified as the homologous human circRNA of mmu_circ_0005372. RT-qPCR confirmed that the expression of mmu_circ_0005372 was significantly reduced in the skin tissue of SSc mice, and the expression of hsa_circ_0136256 was significantly reduced in the peripheral blood mononuclear cells of patients with SSc. The interaction between mmu_circ_0005372 and 4E-BP1 protein was inhibited in the skin tissue of SSc model mice. The results showed that the CVF of OE-circ_0005372 group was significantly lower than that of the sh-circ5372, circ5372-MT, and MHY1485 groups, indicating that OE-circ5372 significantly improved skin fibrosis in the SSc mice. ROC curve analysis was performed on hsa_circ_0136256 (AUC = 0.719, P = 0.035). The expression of hsa_circ_0136256 was negatively correlated with COL IV, RDW-SD, and RDW-CV, and positively correlated with VC, PLT, and PCT. The results suggested that hsa_circ_0136256 may have important roles in the clinical diagnosis of SSc. Mmu_circ_0005372 and homologous human hsa_circ_0136256 may be biomarkers and therapeutic targets for SSc fibrosis.

Systemic Sclerosis Dermal Fibroblast Exosomes Trigger Type 1 Interferon Responses in Keratinocytes via a TBK/JAK/STAT Signaling Axis.

Activation of type I interferon (IFN) response has been shown to correlate with disease activity in systemic sclerosis (SSc). It is currently unknown whether the tissue-specific type I IFN activation is a consequence of the response observed in blood or rather its source. Exosomes from SSc fibroblasts were recently shown to activate macrophages in vitro. Here, we aimed to determine the source of type I IFN signature in SSc skin biopsies and the potential role of exosomes from SSc dermal fibroblasts in the process. Skin biopsies were obtained from the forearms of healthy patients and of those with SSc and processed for dermal fibroblasts and keratinocytes. Exosomes were isolated from healthy and SSc dermal fibroblast supernatants by ultracentrifugation and added to human skin keratinocytes. Keratinocyte transcriptome was analyzed by RNA sequencing (RNA-seq) analysis. TANK-binding kinase (TBK) and JAK were inhibited using a small molecule inhibitor (GSK8612) and tofacitinib, respectively. SSc skin biopsies showed the highest levels of type I IFN response in the epidermal layer. RNA-seq analysis of keratinocytes transcriptome following exposure to dermal fibroblast exosomes showed strong up-regulation of IFN signature genes induced by SSc exosomes compared to healthy control. Inhibition of TBK or JAK activity suppressed the up-regulation of the IFN signature induced by SSc exosomes. IFN activation of SSc keratinocytes is dependent on their crosstalk with dermal fibroblasts and inducible by extracellular exosomes. Our data indicate that SSc fibroblast exosomes contribute to the type I IFN activation in SSc skin through activation of pattern recognition receptors upstream of TBK.

Abstract 4145861: Systemic Sclerosis is Associated with Sub-Clinical Abnormalities in Myocardial Energetics, Perfusion and Increased Fibrosis

Background: Primary cardiac involvement in systemic sclerosis (SSc) is heterogenous, poorly defined and associated with significant cardiac morbidity and mortality. The underlying mechanism is not well understood but may include the impact of coronary microvascular dysfunction and myocardial inflammation. Myocardial cellular metabolic alterations in SSc are yet to be established. Aims: Using 31 Phosphorous magnetic resonance spectroscopy ( 31 P MRS) and cardiovascular magnetic resonance (CMR), we aimed to establish if myocardial energetics, measured as phosphocreatine (PCr) /ATP ratio, and quantitative myocardial perfusion were reduced in individuals with SSc compared to healthy volunteers (HV). Methods: A total of 35 age and sex matched participants were recruited (25 SSc, 10 HV). All subjects underwent 31 P MRS and comprehensive CMR protocol including volumetric analysis, quantitative myocardial perfusion and T1 mapping. Results: Table-1 shows clinical and CMR / 31 P MRS data. Bi-ventricular volumes, systolic function and left atrial function were similar in both groups. NT-Pro BNP and myocardial extra cellular volume (ECV) were significantly increased in SSc. Both PCr/ATP and myocardial perfusion reserve (MPR) were significantly reduced in SSc compared with controls. The disease activity as measured by the European Scleroderma Trials and Research group (EUSTAR) activity index did not correlate with either NTproBNP (P=0.79), PCr/ATP (P=0.35) or MPR (P=0.6). Conclusions: In addition to validating our previous observations of reduced perfusion and increased myocardial fibrosis in SSc, we have demonstrated for the first time significant reductions in myocardial energetics in patients with SSc. These findings provide further valuable insight into the pathogenesis of primary myocardial disease in SSc.

Intermittent Oral Hemorrhage in Systemic Sclerosis.

Intermittent Oral Hemorrhage in Systemic Sclerosis.

Mixed Connective Tissue Disease Presenting as Diabetic Ulcer in a 52 Year Old Female Patient: A Case Report

Mixed connective tissue disease (MCTD) is a rare and complex autoimmune condition characterized by overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis. Due to the varied clinical presentation and the absence of validated classification criteria, early diagnosis can be challenging, often leading to misclassification or delayed recognition. Here, we report a case of a 52-year-old female with MCTD and vasculitis, underscoring the importance of considering uncommon autoimmune etiologies in patients with non-healing ulcers. The patient presented with skin tightening, Raynaud’s phenomenon, and chronic non-healing ulcers, initially attributed to diabetic complications. Diagnostic evaluation revealed high-titre anti-U1-RNP antibodies, confirming MCTD. Treatment with oral steroids, cyclophosphamide, and sildenafil led to significant clinical improvement, particularly in ulcer resolution. This case emphasizes the critical need for early intervention and a multidisciplinary approach in managing autoimmune vasculitis associated with MCTD to prevent progression and optimize patient outcomes.

Cure as a treatment target in rheumatoid arthritis and systemic sclerosis—achievable aim or mission impossible? FOREUM stimulates new industry-academia collaboration

Cure as a treatment target in rheumatoid arthritis and systemic sclerosis—achievable aim or mission impossible? FOREUM stimulates new industry-academia collaboration

Peer mentoring program through a digital platform for people with systemic sclerosis: A feasibility study.

People with systemic sclerosis (SSc or scleroderma), a rare chronic autoimmune disease, often face significant physical and emotional challenges. Peer mentoring, where someone with similar lived experiences offers guidance and support, shows promise in enhancing the well-being of recipients and may benefit individuals with systemic sclerosis. This study aims to evaluate the feasibility and potential health effects of peer mentoring through a digital platform for people with systemic sclerosis. We conducted a one-group study to evaluate a 16-week peer mentoring program for people with systemic sclerosis. Mentors and mentees were matched by demographics and systemic sclerosis characteristics. Feasibility was evaluated using Orsmond and Cohn criteria: recruitment, data collection, acceptability, available resources, and participant responses to the program. Perceptions and usability of the peer mentoring program through a digital platform were assessed at week 16 (post-program). The health effects of peer mentoring were measured at baseline, week 8, and week 16. Five trained mentors and 15 mentees were enrolled. Each mentor was paired with 2-4 mentees. We found that peer mentoring through a digital platform was feasible, acceptable, and had good usability for both mentors and mentees. Mentees reported significantly less anxiety at week 16 (p < 0.001). Other improvements in fatigue, pain interference, depressed mood, and resilience were observed, but did not reach statistical significance. The peer mentoring program through a digital platform was well-received. Results provided preliminary support for the feasibility and potential health benefits of peer mentoring to enhance well-being in people with systemic sclerosis. Findings lay the groundwork for future peer mentoring research in systemic sclerosis.

Scleroderma Renal Crisis and Musculoskeletal Corticosteroid Injections.

Inflammatory arthritis frequently affects patients with systemic sclerosis (SSc) but musculoskeletal corticosteroid (MSKC) injections are often avoided due to concerns of scleroderma renal crisis (SRC). This study investigated the incidence of SRC following MSKC injections. In a 136-SSc cohort, 46 subjects underwent a total of 330 MSKC injections each receiving a significant dosage of triamcinolone acetonide (mean, 95.2 ± 44.2 mg per injection session). Blood pressure (BP), serum creatinine and glucose, urine protein, and complications were retrospectively reviewed before and after injection. MSKC and control subjects were similar in age (MSKC: 58.9 ± 12.1 vs. 55.5 ± 14.9 years), female (MSKC: 97.8% [45/46] vs. 89.9% [81/90]), antinuclear antibody (MSKC: 71.7% [33/46] vs. 81.1% [73/90]), anti-centromere antibody (MSKC: 47.8% [22/46] vs. 37.8% [34/90]), anti-topoisomerase antibody (MSKC: 26.1% [12/46] vs. 26.7% [24/90]), and anti-RNA polymerase III antibody (MSKC: 17.4.1% [8/46] vs. 24.4% [22/90]) (all p > 0.05). Pre- and post-MSKC demonstrated nonsignificant changes in systolic BP (pre: 127 ± 22 vs. post: 127 ± 21 mm Hg, p = 1.0), diastolic BP (pre: 71 ± 13 vs. post: 71 ± 11 mm Hg, p = 1.0), creatinine (pre: 0.78 ± 0.56 vs. post: 0.76 ± 0.20 mg/dL, p = 0.64), glucose (pre: 100 ± 21 vs. post: 99 ± 24 mg/dL, p = 0.67), and urine protein-creatinine ratio (pre: 0.14 ± 0.12 vs. post: 0.12 ± 0.11 mg/mg, p = 0.41). One case of SRC with mortality occurred in the controls and none in the MSKC group. No infections, hematologic abnormalities, or tendon rupture were noted. MSKC injections in established SSc are generally safe with low incidences of SRC and complications. However, it is still prudent to monitor high-risk individuals and recent-onset SSc post-MSKC injection.

Skin ultrasound for rheumatologists: Technical issues and challenges.

In several rheumatic diseases, the skin is involved and therefore it is an organ of interest which may be investigated by the rheumatologist. Ultrasound imaging has been proposed for assessing multiple skin conditions providing qualitative and quantitative information about different parameters in distinct skin layers. Our aim was to describe with a pictorial essay the main challenges that the ultrasound imaging may encounter when investigating the healthy skin in different body areas. Fourteen healthy subjects were submitted to skin ultrasound. The body areas that were investigated were decided following the 17 modified Rodnan skin score anatomical areas used in systemic sclerosis. Skin ultrasound was performed with a GE Logiq 10 with two probes (20 and 24 MHz). For an optimal quantification of the skin layers, the dermis interfaces either with the epidermis and hypodermis were investigated. The results of the ultrasound analysis are described and summarized in a pictorial essay which shows that some main factors may significantly influence the quality of the images of the skin layers. Specifically, age, scanning position, probe frequency, and the optimal positioning of some anatomical areas, in particular the hands and digits, emerged as factors that may have a relevance in influencing the quality of the imaging of the skin layers. Moreover, some technical suggestions are proposed to help optimizing and standardizing the performance of skin ultrasound assessment in healthy population. The pictorial essay we performed shows that the performance of skin ultrasound in healthy subjects still presents several issues that need to be addressed. The definition of the interface in different body areas is the first step which should be standardized before any measurement of the thickness of the skin layers is performed in rheumatic diseases.

Guiding pulmonary vasodilatory therapy in systemic sclerosis associated pulmonary hypertension using morphology of the right ventricle outflow tract velocity time integral

AbstractSystemic sclerosis (SSc) is a chronic, autoimmune disease involving small vessels characterized by skin and internal organs fibrosis. Interstitial lung disease (ILD) is one of the main findings, along with pulmonary hypertension, as a marker of morbidity and mortality. Diagnosis is usually late, and therefore treatment is established in the advanced stages of the disease. Point of care ultrasound (POCUS) emerges as a tool at the bedside for shortening diagnostic times and guiding therapy. Here, we performed a multi‐organ POCUS, evidencing the presence of ILD and pulmonary hypertension in a patient with no cardiovascular symptoms suggestive of advanced disease. We did real‐time monitoring of pulmonary vasodilator therapy at the patient's bedside using right ventricle outflow tract velocity time integral morphology (RVOT VTI). Midsystolic notching of RVOT VTI is highly specific for pulmonary hypertension. POCUS is a valuable tool that could improve diagnostic times and optimize therapy monitoring in asymptomatic patients with early manifestations of organic involvement in patients with SSc. This case demonstrates the value of POCUS as a follow‐up tool in treating patients with SSc.

Impact of Season, Environmental Temperature, and Humidity on Raynaud Phenomenon in an Australian Systemic Sclerosis Cohort.

The aim of this study was to determine the impact of season, temperature and humidity on the severity of Raynaud phenomenon (RP) in systemic sclerosis. Data from the Australian Scleroderma Cohort Study were used to assess associations of patient-reported worsened RP in the month preceding each study visit. Mean monthly weather data were obtained from the closest weather station to the patient's address. We evaluated the relationship between worsened RP and health-related quality of life (HRQoL) measured using the Short Form 36 instrument. Among 1,972 patients with systemic sclerosis, RP was a near-universal finding, and worsened RP in the preceding month was reported in 26.7% of 9,175 visits. "Worsened RP" showed significant environmental variability. On multivariable analysis, worsened RP was associated with low mean maximum temperatures (odds ratio [OR] 0.91, 95% confidence interval [95% CI] 0.90-0.92, P < 0.001), high relative humidity (OR 1.05, 95% CI 1.04-1.05, P < 0.001) and lower mean daily evaporation (OR 0.77, 95% CI 0.73-0.81, P < 0.001). Worsened RP was strongly associated with telangiectasia, calcinosis, and digital ulceration, as well as demonstrating an association with anticentromere antibody and gastroesophageal reflux disease and a negative correlation with diffuse disease. Worsened RP was also strongly associated with worse HRQoL. Lower environmental temperature and higher relative humidity had significant associations with worsened RP in this systemic sclerosis cohort, suggesting an important role for dry warmth in managing this condition.

Nutritional disorders and nutrition-related conditions: an underestimated clinical problem in systemic sclerosis

Nutritional disorders are significant but often underestimated complications in patients with systemic sclerosis (SSc). The most prevalent nutritional disorders in SSc are malnutrition, affecting up to 62.5% of patients, and sarcopenia, with a frequency of up to 42%. Thus, clinical vigilance is recommended for the detection of eating disorders in SSc patients, particularly those with gastrointestinal involvement, cardiopulmonary complications, an advanced disease stage, and high disease activity. Nutritional treatment should be carefully tailored to the patients’ clinical condition to ensure that it effectively addresses their specific needs. Studies focusing on enteral nutrition in SSc patients demonstrate its effectiveness in stabilizing or improving nutritional status in malnourished patients. In severe cases, parenteral nutrition offers viable options to support patient health. The findings highlight the importance of early nutritional assessment and intervention in improving patient outcomes and suggest that individualized nutritional therapy can be a critical component of comprehensive care for SSc patients.

Automatic assessment of nailfold capillaroscopy software: a pilot study

IntroductionCapillaroscopy is a simple method of nailfold capillary imaging, used to diagnose diseases from the systemic sclerosis spectrum. However, the assessment of the capillary image is time-consuming and subjective. This makes it difficult to use for a detailed comparison of studies assessed by various physicians. This pilot study aimed to validate software used for automatic capil­lary counting and image classification as normal or pathological.Material and methodsThe study was based on the assessment of 200 capillaroscopic images obtained from patients suffering from systemic sclerosis or scleroderma spectrum diseases and healthy people. Dinolite MEDL4N Pro was used to perform capillaroscopy. Each image was analysed manually and described using working software. The neural network was trained using the fast.ai library (based on PyTorch). The ResNet-34 deep residual neural network was chosen; 10-fold cross-validation with the validation and test set was performed, using the Darknet-YoloV3 state of the art neural network in a GPU-optimized (P5000 GPU) environment. For the calculation of 1 mm capillaries, an additional detection mechanism was designed.ResultsThe results obtained under neural network training were compared to the results obtained in manual analysis. The sensitivity of the automatic tool relative to manual assessment in classification of correct vs. pathological images was 89.0%, specificity 89.4% for the training group, in validation 89.0% and 86.9% respectively. For the average number of capillaries in 1 mm the precision of real images detected within the region of interest was 96.48%.ConclusionsThe pilot software for fully automatic capillaroscopic image assessment can be a useful tool for the rapid classification of a normal and altered capillaroscopy pattern. In addition, it allows one to quickly calculate the number of capillaries. In the future, the tool will be developed and will make it possible to obtain full imaging characteristics independent of the experience of the examiner.

Brain functional alternation in patients with systemic sclerosis: a resting-state functional magnetic resonance imaging study

BackgroundNeuropsychiatric manifestations, such as cognitive impairment, are relatively prevalent in systemic sclerosis (SSc) patients. This study aimed to investigate the resting state (RS) functional alternations of SSc patients and the potential influenced factors.MethodsForty-four SSc patients (mean age, 46.3 ± 11.4 years; 40 females) and 19 age and sex comparable healthy volunteers (mean age, 42.6 ± 11.3 years; 16 females) were recruited and underwent RS functional MR imaging (fMRI) and neuropsychological assessments. Functional segregation analysis was performed to calculate the amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo). Functional integration analysis was conducted using group independent component analysis to calculate intra-network and inter-network functional connectivity (FC). The fMRI measurements were compared between SSc patients and healthy volunteers using voxel-based pairwise two-sample t-tests. The correlations between clinical characteristics and fMRI measurements were also analyzed.ResultsCompared to healthy volunteers, SSc patients exhibited significantly decreased ALFF and increased ReHo (all P < 0.01, FWE corrected). SSc patients predominantly showed decreased intra-network and inter-network FC in the auditory network, visual network, default mode network, frontoparietal network and attention network (intra-network FC: P < 0.01, uncorrected, cluster size > 30; inter-network FC: P < 0.05, FDR correction). Furthermore, clinical characteristics including disease duration (r value ranged from − 0.31 to 0.36), elevated erythrocyte sedimentation rate (r = 0.35), Montreal Cognitive Assessment score (r = 0.43), and Hamilton Depression Scale score (r = -0.40) were significantly associated with fMRI measurements (all P < 0.05).ConclusionsSpontaneous activity and functional connectivity alternations can be seen in SSc patients, which are partially associated with neuropsychiatric manifestations and tend to aggravate with disease duration.

What are Juvenile-onset systemic sclerosis providers thoughts, experiences, and reasons for autologous stem cell transplant? Result of a multinational survey.

Juvenile-onset systemic sclerosis (jSSc) is a rare and life-threatening disease with no formal studies evaluating the indications for, access to, or benefits of autologous stem cell transplantation (ASCT). As a first step toward understanding pediatric jSSc specialist thoughts and experiences with ASCT, we conducted a multinational survey. An electronic survey was developed and distributed in November 2023 to members of the Pediatric Rheumatology European Society (PRES) and/or Childhood Arthritis and Rheumatology Research Alliance (CARRA) pediatric scleroderma workgroups. Twenty-nine (69%) jSSc specialists completed the survey. All participants have considered or would consider ASCT referral for a jSSc patient. Nearly all respondents indicated disease-modifying anti-rheumatic drugs (DMARDs) should be trialed prior to ASCT referral, with most indicating two to four DMARDs. The most common reasons selected for referral were rapidly progressive disease (despite DMARD) (90%), followed by severe disease status (83%), and significant impact on quality of life (83%). All respondents selected pulmonary disease as an indication for referral, followed by cardiac (93%), gastrointestinal (72%), and skin disease (66%). While pulmonary and cardiac involvement were considered individually sufficient for referral for ASCT, only a minority considered musculoskeletal involvement (28%) sufficient on its own. This survey is the first explore thoughts and experience with ASCT for jSSc. Results indicate pediatric rheumatologists were aware of and would consider ASCT for their patients. Our results indicate there is likely some variability in clinical practice regarding who is referred for ASCT, and further research is needed to guide development of evidence-based clinical care guidelines.