Systemic Sclerosis Research Articles

The predictive role of the TAPSE/sPAP ratio for cardiovascular events and mortality in systemic sclerosis with pulmonary hypertension.

Reduced TAPSE/sPAP ratio has recently emerged as a predictive parameter risk factor for PH, however its role in SSc has been poorly investigated. The aim of the study was to investigate the prognostic value of the TAPSE/sPAP ratio for the prediction of mortality and cardiovascular events in patients with SSc complicated by PH. A comparison between SSc patients with PAH (SSc-PAH) and those with PH and significant ILD (SSc-PH) was also carried out. A retrospective single-center study in which all patients having SSc-complicated by PH-referring to the Scleroderma-Unit of the AOU Policlinico of Modena, from October 2013 to October 2023 were evaluated. All SSc patients underwent recurrent clinical examination, routine blood chemistry analysis, functional, instrumental evaluation. 61 SSc patients (F/M 52/9) were enrolled. During the follow-up, 60.1% of patients experienced at least one cardiovascular event and 62% died. The main causes of death were PH (39.4%) and other heart-related events (39.4%). The TAPSE/sPAP ratio was significantly lower in deceased patients compared to survivors (mm/mmHg 0.3 ± 0.12SD vs. 0.48 ± 0.17SD, p < 0.001). Compared to the SSc-PAH subgroup, the SSc-PH patients had lower survival rates (55.3 ± 31.2 SD months vs. 25 ± 19 SD, p = 0,05). At the multivariate analysis, TAPSE/sPAP ratio <0.32 mm/mmHg, male gender, and the presence of significant ILD were identified as independent predictors of mortality and cardiovascular events. Our work confirmed the predictive role of the TAPSE/sPAP ratio for mortality and cardiovascular events in patients with SSc complicated by PH.

Case of successful treatment with glucocorticoid for isolated anti-centromere antibody-positive acute interstitial nephritis.

Acute interstitial nephritis (AIN) is known to cause acute kidney injury and is characterized by immunocyte infiltration and interstitial fibrosis. Primary etiologies include drugs, infections, and autoimmune disorders. Herein, we presented the case of a 78-year-old woman patient with AIN with anti-centromere antibody (ACA) positivity, secondary to an idiopathic immune system disorder. Her serum creatinine (sCr) was 0.67mg/dL 2months prior to consulting us, which increased to 2.79mg/dL. The renal biopsy revealed an AIN comprising interstitial infiltration with immunocytes and CD138 + cells. Furthermore, all other antibodies tested negative using immunofluorescence on both glomeruli and tubulointerstitial lesions. The ACA was elevated to a level of ≥ 500 U/mL. The ACA positive has been known to be accompanied by worsening kidney function in patients with systemic sclerosis and primary biliary cholangitis. However, any autoimmune disease were not diagnosed. Successful treatment with an initial dose of 30mg/day of glucocorticoids tapered to 25mg/day resulted in a decrease in the sCr to 1.53mg/dL 4weeks later. Nine months later, glucocorticoids was tapered, based on the threshold of a sCr of 1.03mg/dL and the titer of ACA of 291 U/mL. In this case, glucocorticoid treatment remarkably improved renal function in AIN containing CD138 + cells accompanied by a reduction of ACA titer. The etiology of ACA-positive AIN was unknown; however, the incidence of ACA-positive AIN should always be deliberated.

IL-11 Expression in Systemic Sclerosis Is Dependent on Caspase-1 Activity but Does Not Increase Collagen Deposition

IL-11 Expression in Systemic Sclerosis Is Dependent on Caspase-1 Activity but Does Not Increase Collagen Deposition

Audiovestibular symptoms in systemic sclerosis: a systematic review and meta-analysis.

Answer the following PICO question: Are patients diagnosed with systemic sclerosis (SSc) (Population) who are evaluated clinically and audiometrically (Intervention), have a higher prevalence of audiovestibular pathology when compared with non-SSc patients (Comparison), and how do they present symptomatically and on testing audiovestibular symptomatology and testing modalities (Outcome)? A systematic review and meta-analysis was performed. PubMed, Scopus, CINAHL, and Cochrane Library databases were searched from inception to November 27, 2023. Studies of patients diagnosed with SSc and audiologic and vestibular symptoms were selected for review. Studies of non-SSc pathologies, studies without audiovestibular outcomes, and case reports (fewer than four patients) were excluded. A meta-analysis of proportions and comparison of weighted proportions was performed in MedCalc 20.217. Thirteen studies with 414 SSc patients and 390 control patients were included. The mean ± SD symptom duration was 108.5 ± 71.8 (range: 6-600) months for SSc patients. Comparison of proportions showed patients with SSc were significantly more burdened with symptoms of tinnitus (Δ34.1% [95% CI, 27.6-40.5]; p < 0.0001), vertigo (Δ32.4% [95% CI, 24.8-40.3]; p < 0.0001), and subjective hearing loss (Δ26.0% [95% CI, 20.8-31.3]; p < 0.0001) compared to control patients. Findings regarding vestibular testing were not meta-analyzable because of incomplete data and lack of standard reporting. SSc patients showed statistically significant, yet not clinically significant, worse hearing than controls. These differences, along with increased reports of subjective audiological and vestibular symptoms in patients with SSc, emphasize interdisciplinary collaboration and assessment of SSc for audiovestibular pathologies in the appropriate clinical context.

Increased prevalence of osteopenia and osteoporosis in systemic sclerosis patients, including in men and young women- a case-control study.

To investigate bone mineral density (BMD), osteoporosis prevalence and systemic sclerosis (SSc) specific associations of BMD in SSc patients compared with background population. In total, 211 SSc patients (182 women, 29 men; mean age 61.3 and 62.2 respectively) and 505 age and sex matched controls from the same geographic area participated. BMD and T-score at total hip and lumbar spine was measured by Dual-energy X-ray absorptiometry. Osteopenia was defined as T-score -1.0 to -2.5; osteoporosis as T-score ≤-2.5. Associates of low BMD were identified by multiple regression analysis. Women with SSc had lower BMD for total hip (p< 0.001) and spine (p= 0.011), equivalent to ΔT-score -0.56 and -0.35 compared with controls. Osteopenia was present in 51.6% and 16.5% had osteoporosis (p= 0.001, compared with controls). Already in women below age 45, differences in hip BMD were apparent (ΔT-score -0.93, p= 0.005). In addition to expected risk factors for osteoporosis (older age, lower BMI and menopause), finger ulcers (p= 0.009) and diffuse skin involvement (p= 0.027) were associated with lower hip BMD in women. In men with SSc, more than half displayed osteopenia or osteoporosis and had numerically lower hip BMD than their age matched counterparts. SSc patients, including men and younger women, have lower BMD than the background population. Finger ulcers and diffuse skin involvement, in addition to older age, lower BMI and being post-menopausal, are associated with lower BMD in women. The data emphasizes the importance of performing bone health assessment of all SSc patients, including men and young subjects.

Association of serum interferon alpha-2a levels with disease severity and prognosis in systemic sclerosis.

To determine serum type I interferon IFN-α2a concentrations in systemic sclerosis (SSc) patients, explore its association with cytokine/chemokine expressions, and evaluate correlation with the phenotype including the predictive value for interstitial lung disease (ILD) progression. Serum samples were obtained from 200 SSc patients and 29 healthy controls. IFN-α2a levels were measured by ultrasensitive electrochemiluminescence assay. Pro-inflammatory and chemokine panels were determined by Luminex® Discovery Assay multiplex kit. Baseline SSc disease characteristics were recorded together with longitudinal data for determining ILD progression after 2 years. IFN-α2a concentrations were higher in SSc patients compared with controls, although not reaching significance (means ± SD of 49.20 ± 156.8 pg/ml vs 9.606 ± 4.399 pg/ml, respectively; (p = 0.158)). Using the cut-off of 15.9 pg/ml, we identified 62 patients as having a type 1 (T1) IFN signature in their circulation. Patients with an IFN signature had significantly higher levels of chemokines (CCL8, CCL19, CXCL10, CXCL11), and the cytokine IL-1α compared with those without an IFN signature. IFN-α2a concentrations strongly correlated with a T1 IFN related chemokine score supporting activation of this pathway. Phenotyping association queries revealed association between IFN values and both skin and ILD involvements at baseline. Longitudinal data did not identify IFN as a predictive marker for ILD progression. Using serum determinations, the activation of the T1 IFN pathway showed strong correlations with inflammatory mediators and associations with clinical manifestations, especially skin fibrosis and ILD in SSc patients. However, activated IFN pathway was not predictive of ILD progression.

Insights and Future Perspectives in Calcinosis Cutis Associated with Systemic Sclerosis

Insights and Future Perspectives in Calcinosis Cutis Associated with Systemic Sclerosis

Biologic Correlates of Radiologic Features of Systemic Sclerosis Interstitial Lung Disease

Background and objectivesThe extent and pattern of radiological features (e.g., fibrosis, ground glass) can influence treatment approaches for systemic sclerosis-related interstitial lung disease (SSc-ILD). However, the pathobiology underlying these radiologic features is poorly understood and warrants further investigation.MethodsSixty-eight proteins were measured in bronchoalveolar lavage (BAL) fluid from 103 SSc-ILD participants in Scleroderma Lung Study I. Quantitative image analysis calculated the extent of fibrosis (QLF) and ground glass opacity (QGG) from concurrent high-resolution computerized tomography (HRCT) scans. The relationship between BAL proteins and quantitative HRCT scores was assessed by univariate and multivariate analyses.ResultsQLF scores correlated weakly with the extent of QGG, suggesting two distinct processes. In a univariate analysis, 25 proteins from several biologic pathways correlated with QLF scores, including pro-fibrotic factors, tissue remodeling proteins, proteins involved in monocyte/macrophage migration and activation, and proteins linked to inflammation and immune regulation. In contrast, QGG scores correlated with only 6 proteins of which four were unique and related to granulocyte activation, mobilization of bone marrow mesenchymal stem cells, and activation of T cells, B cells, macrophages and eosinophils. In the multivariate models, IL-4, CCL7, receptor activator of NF-κB, and tumor necrosis factor alpha were independently associated with QLF, whereas, IFN-γ was independently associated with QGG.InterpretationQLF and QGG represent distinct radiologic features of SSc-ILD, a conclusion reinforced by the presence of different biologic pathways present within BAL fluid that associate with each. The identified proteins and related biologic pathways may represent important therapeutic targets.

Efficacy and safety of digital nerve block for pain management during sharp debridement of digital ulcers in systemic sclerosis: A prospective observational study.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis and vascular abnormalities, often leading to the development of digital ulcers (DUs). DUs are painful and debilitating, significantly impacting patients' quality of life. Effective pain management during debridement is crucial, yet there is no consensus on the optimal approach. This study evaluates the efficacy and safety of digital nerve block (DNB) using lidocaine and mepivacaine for pain control during sharp debridement of DUs in SSc patients. This prospective observational study was conducted from September 2023 to May 2024 at the Rheumatology Operating Unit, University of Verona. Patients were randomized to receive either 1 mL of 2% lidocaine or 2% mepivacaine for DNB. Pain levels were assessed using a categorical grading scale during the injection and debridement. The outcomes were pain control and performance of lidocaine versus mepivacaine. The cohort developed 46 ulcers. The pain was abolished in almost all patients. Lidocaine achieved faster anaesthesia (127.92 ± 34.32 s) compared with mepivacaine (252.65 ± 49.89 s, p < 0.001). Mepivacaine resulted in less pain during injection (p = 0.006). No significant difference in pain levels during debridement was observed between the two anaesthetics. Three mild adverse effects (Raynaud's phenomenon) were reported. All procedures were completed successfully, and 35 ulcers healed with a mean time of 6.1 ± 7.77 weeks. DNB with mepivacaine provides effective pain control during DU debridement in SSc patients, with lower injection site pain and comparable efficacy to lidocaine. The procedure is safe, well-tolerated and facilitates successful ulcer healing. Further studies with larger cohorts are warranted to confirm these findings.

Analysis of nailfold capillaroscopy images with artificial intelligence: Data from literature and performance of machine learning and deep learning from images acquired in the SCLEROCAP study

ObjectiveTo evaluate the performance of machine learning and then deep learning to detect a systemic scleroderma (SSc) landscape from the same set of nailfold capillaroscopy (NC) images from the French prospective multicenter observational study SCLEROCAP. MethodsNC images from the first 100 SCLEROCAP patients were analyzed to assess the performance of machine learning and then deep learning in identifying the SSc landscape, the NC images having previously been independently and consensually labeled by expert clinicians. Images were divided into a training set (70 %) and a validation set (30 %). After features extraction from the NC images, we tested six classifiers (random forests (RF), support vector machine (SVM), logistic regression (LR), light gradient boosting (LGB), extreme gradient boosting (XGB), K-nearest neighbors (KNN)) on the training set with five different combinations of the images. The performance of each classifier was evaluated by the F1 score. In the deep learning section, we tested three pre-trained models from the TIMM library (ResNet-18, DenseNet-121 and VGG-16) on raw NC images after applying image augmentation methods. ResultsWith machine learning, performance ranged from 0.60 to 0.73 for each variable, with Hu and Haralick moments being the most discriminating. Performance was highest with the RF, LGB and XGB models (F1 scores: 0.75–0.79). The highest score was obtained by combining all variables and using the LGB model (F1 score: 0.79 ± 0.05, p < 0.01). With deep learning, performance reached a minimum accuracy of 0.87. The best results were obtained with the DenseNet-121 model (accuracy 0.94 ± 0.02, F1 score 0.94 ± 0.02, AUC 0.95 ± 0.03) as compared to ResNet-18 (accuracy 0.87 ± 0.04, F1 score 0.85 ± 0.03, AUC 0.87 ± 0.04) and VGG-16 (accuracy 0.90 ± 0.03, F1 score 0.91 ± 0.02, AUC 0.91 ± 0.04). ConclusionBy using machine learning and then deep learning on the same set of labeled NC images from the SCLEROCAP study, the highest performances to detect SSc landscape were obtained with deep learning and in particular DenseNet-121. This pre-trained model could therefore be used to automatically interpret NC images in case of suspected SSc. This result nevertheless needs to be confirmed on a larger number of NC images.

Survey self-report of rheumatoid arthritis and treatments versus specialist clinician confirmation

ObjectiveTo assess agreement between patient survey report and physician recorded arthritic conditions and medication use in order to validate population-based epidemiologic approaches to auto-immune arthritic conditions.MethodsRheumatologists in the U.S. Appalachian region recruited men 50 years or older with a confirmed rheumatoid arthritis (RA) diagnosis. For each participating patient, the treating specialist completed a brief chart abstraction that included rheumatic diagnosis and corresponding treatment. Patients participated in a telephone interview using the same questionnaire as applied in a larger random digit dial survey that queried arthritis diagnosis and treatment. We assessed patient-clinician agreement with the Prevalence Adjusted and Biased Adjusted Kappa (PABAK) statistic.ResultsWe included 36 patient-clinician dyads in this analysis. All clinicians and patients concurred in the RA diagnosis (PABAK = 1). For concomitant systemic lupus and scleroderma, we observed generally concordant responses (PABAK 0.89 and 1, respectively). For medication use, for hydroxychloroquine or sulfasalazine was associated with the lowest PABAK (0.39), intermediate values for methotrexate and for the “other conventional synthetic DMARDs” category (0.67), and with the highest agreement PABAK value for the “biologic DMARD or JAK 2 inhibitor” category (0.89).ConclusionSurvey-based self-report of RA offers a useful approach in epidemiological investigation. This is particularly relevant to population-based approaches to autoimmune arthritis related to occupational and environmental factors.

Elevated Circulating Levels of Gut Microbe-Derived Trimethylamine N-Oxide Are Associated with Systemic Sclerosis.

Background/Objectives: Alterations in fecal microbial communities in patients with systemic sclerosis (SSc) are common, but the clinical significance of this observation is poorly understood. Gut microbial production of trimethylamine (TMA), and its conversion by the host to trimethylamine N-oxide (TMAO), has clinical and mechanistic links to cardiovascular and renal diseases. Direct provision of TMAO has been shown to promote fibrosis and vascular injury, hallmarks of SSc. We sought to determine levels of TMAO and related metabolites in SSc patients and investigate associations between the metabolite levels with disease features. Methods: This is an observational case:control study. Adults with SSc (n = 200) and non-SSc controls (n = 400) were matched for age, sex, indices of renal function, diabetes mellitus, and cardiovascular disease. Serum TMAO, choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine were measured using stable isotope dilution liquid chromatography tandem mass spectrometry. Results: Median TMAO concentration was higher (p = 0.020) in SSc patients (3.31 [interquartile range 2.18, 5.23] µM) relative to controls (2.85 [IQR 1.88, 4.54] µM). TMAO was highest among obese and male SSc participants compared to all other groups. Following adjustment for sex, BMI, age, race, and eGFR in a quantile regression model, elevated TMAO levels remained associated with SSc at each quantile of TMAO. Conclusions: Patients with SSc have increased circulating levels of TMAO independent of comorbidities including age, sex, renal function, diabetes mellitus, and cardiovascular disease. As a potentially modifiable factor, further studies examining the link between TMAO and SSc disease severity and course are warranted.

Increased prevalence of inflammatory arthritis, systemic lupus erythematosus and systemic sclerosis, during 2020-2023 versus 2016-2019 in a Nation-Wide Cohort Study.

Although several studies have explored the geoepidemiology of autoimmune rheumatic diseases (ARD), trends of their frequency overtime are under-investigated. Herein, in a nation-wide study, we examine trends in the prevalence of various ARD over-time, taking also into account the Covid-19 pandemic. In this retrospective study in the entire Greek adult population (approximately 10.000.000 people), we searched the electronic prescription database of the e-Government Centre for Social Security Services using prespecified ICD-10 codes to capture all adult patients with Psoriatic Arthritis (PsA), Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc) and Polymyalgia Rheumatica or Giant Cell Arteritis (PMR/GCA). Two sequential 4-year periods, namely 2016-2019 and 2020-2023 were compared. Prevalence of RA, PsA, AxSpA, SLE and SSc increased significantly during 2020-2023 compared to 2016-2019. This applies to both genders and to all age groups for RA, PsA and AxSpA, to female patients in SLE and SSc and to patients 18-39years in SLE and ≥ 60years in SSc. Overall, there was 47% increase in prevalence for AxSpA (0.100% in 2016-19 vs 0.147% in 2020-23), 36.5% for PsA (0.148% vs 0.202%), 20.6% for RA (0.467% vs 0.563%), 19% for SLE (0.137% vs 0.163%) and 13% for SSc (0.023% vs 0.026%). A 16.3% decrease was evident in GCA/PMR, limited to those ≥ 40years old. In a nation-wide study we confirm that ARD prevalence increases over-time, whereas a contribution of Covid-19 pandemic to our results during 2020-2023, cannot be excluded. Additional human, medical and financial resources will be needed to cover the increased needs of ARD patients.

Improving organisation to improve care: ERN ReCONNET organisational reference model for systemic sclerosis patients' care pathway.

To optimise the organisation of care and encourage the adoption of good clinical practices, the RarERN Path© methodology was designed within ERN ReCONNET. The aim of our work was to report the application of RarERN Path© on systemic sclerosis within the ERN ReCONNET centres, providing a feasible and flexible organisational reference model for optimising the systemic sclerosis care pathway in different countries. RarERN Path© is a six-phase methodology which enables the creation of a reference organisational model co-designed on the basis of the expertise of different stakeholders. It foresees six phases, ranging from the map of existing patients' care pathways and patients' stories, to the consensus on a common organisational patient care pathways, and its key performance indicators definition. The agreed reference model highlights the importance of having an organisational flow for referrals that foresees how patients may access directly the specialised unit from the different referrals. Specific specialised visits were considered as mandatory to be organised and they included cardiologist, pneumologist, gastroenterologist, psychologist, nephrologist, dermatologist, wound care specialist/nurses and other healthcare professionals (such as nurses, social workers and nutritional counselling). Moreover, specific services related to therapy were highlighted as strongly recommended to be organised, mainly represented by infusion therapy and wound care, as well as occupation therapy and physiotherapy. The organisational model emerged from our investigation emphasises that the organisation of specific services for systemic sclerosis treatment should be organised as a solid support for implementing the existing recommendations on systemic sclerosis management in real life.

The role and mechanism of CRISPLD2 in skin fibrosis of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease involving multiple organs. The most common clinical symptom of SSc is progressive fibrosis of the skin, and the pathologically manifestations of skin were activation and proliferation of fibroblasts and continuous proliferation of extracellular matrix. Transforming growth factor β (TGFβ) can promote the proliferation and activation of fibroblasts, causing excessive deposition of collagen and structural proteins. Therefore, exploring the specific mechanism of TGFβ-related pathway on fibrosis is of great significance for improving skin fibrosis in SSc. Genes related to TGFβ pathway were screened through bioinformatics analysis, and SSc phenotypes were verified in vivo and vitro. The relevant molecular mechanisms were preliminarily discussed in combination with transcriptome sequencing. Human cysteine-rich secreted protein LCCL domain protein 2 (CRISPLD2) was found increased reactivity in TGFβ induced fibroblasts, and the expression of ACTA2 (ɑ-SMA) decreased significantly in TGFβ-mediated fibroblasts with up-regulation of CRISPLD2. CRISPLD2 was found increased reactivity in TGFβ induced fibroblasts, and we further confirmed that CRISPLD2 can participate in TGFβ induced fibroblast fibrosis from multiple perspectives and levels in negative feedback regulation, and investigated the mechanism of CRISPLD2 in fibrosis.

Association between Left Atrial Function and Survival in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multisystemic autoimmune disorder in which cardiac involvement is frequent and portends negative prognosis. Left ventricular (LV) diastolic dysfunction is one of the most common cardiac alterations in these patients, and left atrial (LA) reservoir strain (ƐR) measurement using speckle tracking echocardiography has been proposed as a novel parameter for a better assessment of LV diastolic function. Therefore, the aim of this study was to test the prognostic value of ƐR in a large multicenter cohort of SSc patients. In total, 311 SSc patients (54 ± 14 years, 85% female) were included from two different centers. Echocardiography was performed at the time of first visit, including ƐR measurement. Over a median follow-up of 132 (interquartile range: 110 to 157) months, 67 (21.5%) patients experienced the outcome of all-cause mortality. Spline curve analysis identified an optimal cut-off value of 30% for ƐR, and patients with ƐR ≤ 30% showed a 10-year cumulative survival rate of 71% as compared to 88% for patients with ƐR > 30% (log-rank p < 0.001). At the multivariable Cox regression analysis, ƐR was independently associated with the endpoint (HR 1.830; 95% confidence interval (CI) 1.031-3.246; p = 0.039) together with age (HR 1.071, 95% CI 1.043 to 1.099; p < 0.001), sex (female) (HR 0.444, 95% CI 0.229 to 0.861; p = 0.016), and diffusing lung capacity for carbon monoxide (HR 0.969 95% CI 0.956 to 0.982; p < 0.001). ƐR is of independent prognostic value in SSc and might help optimizing risk stratification in these patients.

Demographics and Clinical Features Associated with Abnormal Small Bowel Motility in Systemic Sclerosis.

The small bowel is affected in up to 50% of systemic sclerosis (SSc) patients, and some patients experience severe complications. Our aim was to use specific statistical methods to compare demographic and clinical features of SSc patients with and without abnormal small bowel to better characterize patients at risk for this complication. SSc patients with gastrointestinal symptoms were prospectively enrolled and underwent a scintigraphy-based whole gut transit (WGT) study. A cross-sectional analysis was performed comparing clinical features between patients with and without abnormal small bowel transit by WGT. Univariate logistic regression models and multivariable models were used to examine the relationship between clinical features and abnormal small bowel transit. Of 130 patients enrolled in this study, 22 had abnormal small bowel transit. SSc patients with abnormal small bowel transit were more likely to be male [Odds Ratio(OR)=3.70, Confidence Interval(CI) 1.07-12.50, p= 0.038], and have more severe cardiac involvement (OR = 3.98, CI 1.10-14.38, p= 0.035), while they were less likely to have sicca symptoms (OR = 0.30, CI 0.10-0.94, p= 0.039). In multivariable analyses, sicca symptoms (OR = 0.28, CI 0.08-0.96, p= 0.043) remained negatively associated with abnormal small bowel transit. Additionally, SSc patients with abnormal small bowel transit had higher mortality than patients with normal small bowel transit [Hazard ratio(HR)=4.57, CI 1.58-13.24, p= 0.005]. These findings suggest that patients with abnormal small bowel transit in SSc are more likely to be male, have more severe cardiac involvement, higher mortality, and less sicca symptoms. Recognizing this patient subgroup is essential for risk stratification and optimizing clinical care.

The diagnostic value and clinical relevance of high frequency ultrasound and shear wave elastography in systemic sclerosis: an observational monocentric study.

To unravel the features of skin involvement in patients with systemic sclerosis (SSc) by high frequency ultrasound (HFU) and shear wave elastography (SWE). To assess the ultrasound capabilities to distinguish SSc patients from healthy controls (HCs). We recruited a cohort of SSc patients in this cross-sectional study. HFU and SWE were used to quantify skin thickness and skin stiffness. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capabilities of ultrasound in SSc. The correlation analysis was used to evaluate the clinical relevance of ultrasound measurements in SSc. 20 consecutive SSc patients and 20 age-, gender- and body mass index-matched HCs were included. The skin thickness and stiffness were significantly greater in SSc patients compared with HCs. Patients with high disease activity had higher skin thickness and stiffness compared with patients with low disease activity. The area under the ROC curve (AUC) of the dorsum of middle fingers assessed by HFU was 0.847 (95% CI, 0.761-0.933). The AUC of the forearms and dorsum of hands assessed by SWE were 0.909 (95% CI, 0.829-0.989) and 0.879 (95% CI, 0.807-0.951). Further, the combined HFU and SWE tests displayed the best diagnostic performance with an AUC of 0.980 (95% CI, 0.939-1.000). A significant positive correlation between the ultrasound measurements and the modified Rodnan skin score (mRSS) was observed. The application of ultrasound can assist with disease diagnosis, it is necessary to develop a standard operating protocol to help with future implementation of ultrasound in SSc.

7148 Fake Fingerstick: Artifactual Hypoglycemia in a Hospitalized patient with Systemic Sclerosis

Abstract Disclosure: S. Shteyman: None. F. Mirza: None. Introduction: Artifactual hypoglycemia is a problem in hospitalized patients. It often leads to unnecessary use of resources and creates anxiety for the patient and medical team. We describe a case of a 60-year-old female with history of systemic sclerosis (Raynaud, telangiectasias, esophageal dysmotility, interstitial lung disease, pulmonary hypertension), rheumatoid arthritis, autoimmune hepatitis and hypothyroidism who initially presented to the hospital emergency department with bilateral lower extremity radiculopathy, and new onset urine incontinence. She underwent spine surgery initially, followed by emergent left upper extremity thrombectomy two days later. Postoperatively, she was noted to have fingerstick glucose of 34 mg/dL. Dextrose and juice were given, and endocrinology service was consulted. The patient was monitored with 2 hourly fingerstick glucose and was noted to have frequent hypoglycemia on fingerstick monitoring. Serum glucose in AM labs was consistently within normal limits. Patient denied both adrenergic and neuroglycopenic symptoms during periods of “hypoglycemia”. She was asked to fast till fingerstick glucose was noted to be at 43 mg/dl, when blood was drawn for serum glucose, insulin, proinsulin, C-peptide, B-hydroxybutyric acid, IGF-2, insulin AB, and sulfonylurea panel, prior to giving her any dextrose. She was asymptomatic at the time. All labs were within normal limits, with serum glucose at 119 mg/dL. At that point, artifactual hypoglycemia was suspected. Serum glucose was checked twice again when fingerstick glucose was noted to be &amp;lt;45mg/dL, and corresponding serum glucose was noted to be normal at both times (&amp;gt;100 mg/dL). Decision of artifactual hypoglycemia was made and fingerstick glucose monitoring was discontinued in this non-diabetic patient, with recommendation to check serum glucose only if symptoms of hypoglycemia occur, as fingerstick glucose values were not reliable. Fasting serum glucose continued to be normal for the remainder of the hospitalization. Discussion: There have been a handful cases of artifactual hypoglycemia reported in patients with CREST, systemic sclerosis, and Raynaud’s disease. It is thought to be due to abnormal small vasculature causing delayed transit of blood through capillaries, and increased uptake of glucose into the interstitial tissue. Some recommend using earlobe sticks as a replacement for fingerstick glucose monitoring in these patients. Future research can explore if continuous glucose monitoring can be used reliably in these patients. Presentation: 6/1/2024

5043 Skeletal Microstructure in Men with Celiac Disease

Abstract Disclosure: A. Rubenstein: None. A. Kondapalli: None. S. Agarwal: None. M. Bucovsky: None. I. Colon: None. N. Kil: None. S. Lewis: None. B. Lebwohl: None. P. Green: None. M. Walker: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc.. The pathophysiology of osteoporosis related to celiac disease (CD) remains incompletely understood. High resolution peripheral quantitative computed tomography (HRpQCT) has revealed microarchitectural deficits in women with CD, but no data exist in men. We prospectively studied bone health using DXA and HRpQCT in 17 men with duodenal biopsy-confirmed CD (mean age 43±16 years; 82% white, 6% Asian, 12% other) and 5 male controls (mean age 40±12 years; 80% white, 20% Asian). Compared to controls, men with CD had lower self-rated health scores (p&amp;lt;0.05), but age, BMI, alcohol use, physical activity, acid blocker use, and vitamin D intake did not differ. Among patients with CD, 23.5% had other autoimmune diseases (type 1 diabetes, hypothyroidism, vitiligo, systemic sclerosis). At CD diagnosis, mean age was 34.3 ± 14.8. CD patients had a mean CD and gluten-free diet duration of 8 years. 29% of patients (n=5/17) were enrolled within 13 months of CD diagnosis. Mean tissue transglutaminase IgA, serum calcium, PTH, Vitamin D, and alkaline phosphatase were normal, but vitamin D levels were &amp;lt; 30 ng/mL in 36% (n=5/14) and PTH was elevated in 11% (n=1/9). T- (-0.5±1.5 vs. 0.8±0.8, p=0.03) and Z-scores (-0.1±1.4 vs. 1.1±0.9, p=0.05) by DXA were normal at all sites but tended to be lower at the 1/3-radius only in CD compared to controls. By HRpQCT, there were no differences. Compared to a larger control group including HRpQCT data from an additional 14 normative database controls (n=19), CD had lower radial cortical (-4.7%, p=0.02) and tibial trabecular (-13.3%, p=0.04) vBMD and a trend toward lower cortical volumetric BMD (vBMD; -3.5%, p=0.06) at the tibia. Within the CD group, longer CD duration was associated with worse tibial cortical vBMD at (r=-0.55, p=0.02). Higher PTH (n=9) correlated with lower lumbar spine areal BMD (r=-0.75, p=0.02), tibial trabecular thickness (Tb.Th; r=-0.77, p=0.02) as well as radial cortical vBMD (r=-0.81, p&amp;lt;0.01), trabecular Tb.Th (r=-0.78, p=0.01), and cortical thickness (r=-0.75, p=0.02). Those with greater dietary vitamin D intake had higher total vBMD (r=0.50, p=0.04) and trabecular thickness at the tibia (r=0.51, p=0.04). Similarly, higher 25-hydroxy vitamin D levels were associated with higher total hip aBMD (r=0.58, p=0.03). In summary, CD in men is associated with lower areal BMD at the 1/3-radius by DXA and lower vBMD at the radius and tibia by HRpQCT. Low vitamin D levels and secondary hyperparathyroidism may contribute. Further work is needed to understand the extent and pathophysiology of skeletal disease in men with CD. Presentation: 6/3/2024