Limited Systemic Sclerosis Research Articles

Small Intestinal Bacterial Overgrowth Complicating Gastrointestinal Manifestations of Systemic Sclerosis: A Systematic Review and Meta-analysis

Systemic sclerosis (SSc) often is complicated by small intestinal bacterial overgrowth (SIBO). A systematic review and meta-analysis thus examined the prevalence of SIBO in SSc (SSc-subtypes), identify risk factors for SIBO in SSc and the effects of concomitant SIBO on gastrointestinal symptoms in SSc. We searched electronic databases until January-2022 for studies providing prevalence rates of SIBO in SSc. The prevalence rates, odds ratio (OR) and 95% confidence intervals (CI) of SIBO in SSc and controls were calculated. The final dataset comprised 28 studies with 1112 SSc-patients and 335 controls. SIBO prevalence in SSc-patients was 39.9% (95% CI, 33.1-47.1; P = 0.006), with considerable heterogeneity, (I2 = 76.00%, P < 0.001). As compared to controls, there was a 10-fold increased SIBO prevalence in SSc-patients (OR, 9.6; 95% CI, 5.6-16.5; P < 0.001). The prevalence of SIBO was not different in limited cutaneous SSc as compared to diffuse cutaneous SSc (OR, 1.01; 95% CI, 0.46-2.20; P = 0.978). Diarrhea (OR, 5.9; 95% CI, 2.9-16.0; P = 0.001) and the association between SIBO in SSc and proton pump inhibitor use (OR, 2.3; 95% CI, 0.8-6.4; P = 0.105) failed statistical significance. Rifaximin was significantly more effective as compared to rotating antibiotic in eradicating SIBO in SSc-patients (77.8% [95% CI, 64.4-87.9]) vs 44.8% [95% CI, 31.7-58.4]; P < 0.05). There is a 10-fold increased prevalence of SIBO in SSc, with similar SIBO prevalence rates in SSc-subtypes. Antimicrobial therapy of SIBO-positive SSc-patients with diarrhea should be considered. However, the results must be interpreted with caution due to substantial unexplained heterogeneity in the prevalence studies, and the low sensitivity and specificity of the diagnostic tests suggesting that the reliability of the evidence may be low.

Semaphorin 3A levels in vascular and nonvascular phenotypes in systemic sclerosis.

Semaphorin 3A (Sema3A) plays a regulatory role in immune responses. The aim of this study was to evaluate Sema3A levels in patients with systemic sclerosis (SSc), especially in major vascular involvements such as digital ulcer (DU), scleroderma renal crisis (SRC), pulmonary arterial hypertension (PAH), and to compare Sema3A level with SSc disease activity. In SSc patients, patients with DU, SRC, or PAH were grouped as major vascular involvements and those without as nonvascular, and Sema3A levels were compared between the groups and with a healthy control group. The Sema3A levels and acute phase reactants in SSc patients, as well as their association with the Valentini disease activity index and modified Rodnan skin score, were evaluated. The Sema3A values (mean ± SD) were 57.60 ± 19.81ng/mL in the control group (n=31), 44.32 ± 5.87ng/mL in patients with major vascular involvement SSc (n=21), and 49.96 ± 14.00ng/mL in the nonvascular SSc group (n= 35). When all SSc patients were examined as a single group, the mean Sema3A value was significantly lower than controls (P=.016). The SSc with major vascular involvement group had significantly lower Sema3A levels than SSc with nonmajor vascular involvement group (P=.04). No correlation was found between Sema3A, acute phase reactants, and disease activity scores. Also, no relationship was observed between Sema3A levels and diffuse (48.36 ± 11.47ng/mL) or limited (47.43 ± 12.38ng/mL) SSc types (P = .775). Our study suggests that Sema3A may play a significant role in the pathogenesis of vasculopathy and can be used as a biomarker in SSc patients with vascular complications such as DU and PAH.

Bronchoscopy-Associated Cerebral Arterial Air Embolism Presenting with Acute Ischemic Stroke and Status Epilepticus (P12-5.013)

<h3>Objective:</h3> To describe a rare cause of iatrogenic air embolism, causing acute ischemic stroke complicated by status epilepticus. <h3>Background:</h3> The incidence of vascular air embolism during bronchoscopy is estimated to be 2.65 per 100,000 hospitalizations, with 30% of these involving endovascular procedures. A recent case report and literature review identified only 5 cases of cerebral arterial air embolism following bronchoscopy. A small minority of acute ischemic strokes present with seizures, even fewer with status epilepticus. <h3>Design/Methods:</h3> NA <h3>Results:</h3> An 81-year-old woman with past medical history significant for hypertension and CREST syndrome presented to an outside hospital for elective bronchoscopy with biopsy of pulmonary nodules. Post-procedurally, she was noted to have new left-sided hemiparesis. Non-contrast CT head demonstrated a small arterial air embolism in the right frontal lobe. She was brought to the Emergency Department and sustained a bilateral tonic-clonic seizure lasting 30 seconds, resolving with intravenous lorazepam. Prior to returning to her mental status baseline, she had recurrent seizure activity, refractory to benzodiazepines, requiring an intravenous phenytoin load, intubation for airway protection, and sedation with propofol. She was transferred to our institution’s neurocritical care unit where repeat CT head exhibited sulcal effacement and she was treated with hypertonic saline for cerebral edema. Continuous EEG did not reveal any epileptiform patterns but the patient was started on levetiracetam for her acute symptomatic seizures. MRI later revealed small infarcts in multiple vascular territories. She was ultimately extubated and at the time of discharge to short-term rehabilitation, her only deficit was 4+/5 strength throughout the left arm, which normalized by 1-month follow-up. She was eventually weaned off of levetiracetam in the outpatient setting. <h3>Conclusions:</h3> This case adds to our understanding of this rare procedural complication and, given the complications of her stroke by status epilepticus and cerebral edema, highlights the potential severity of these injuries. <b>Disclosure:</b> Dr. Sutherland has received personal compensation in the range of $0-$499 for serving as a Consultant for McGraw-Hill. Dr. Gummerson has nothing to disclose. Dr. Sharma has nothing to disclose.

OA28 CCL24 serum concentration predicts both vascular and fibrotic complications in systemic sclerosis: rationale for a biological target driven basket trial across disease subsets

Abstract Background/Aims CCL24 is a novel target that was found to play a dual role in advancing pro-inflammatory and pro-fibrotic processes in systemic sclerosis (SSc). Previous studies reported that skin and serum CCL24 levels are elevated in SSc and that blocking of CCL24 was effective in preventing and attenuating experimental-induced fibrosis in murine models as well as interfering with endothelial cell activation. Here we tested the concentration of CCL24 in an observational cohort of patients with SSc and available clinical follow-up to determine its clinical value in predicting fibrotic and vascular complications of the disease. Methods Consecutive patients from a single-centre observational cohort were enrolled in this analysis. Clinical data were collected according to the EUSTAR minimal essential data set. Serum Concentration of CCL24 was measured by Luminex assay (Myriad RBM) and defined as “high” for patients over the upper quartile of the healthy control population (110 ng/ml). Interstitial lung disease (ILD) was defined by at least 10% parenchymal involvement at a high-resolution CT scan of the chest, while digital ulcer (DU) disease was defined by the presence of current or history of DU in the previous 6 months. Progressive fibrotic ILD was defined as previously described, according to Erice's criteria within 24 months. Clinical features were compared between CCL24 high vs low by Chi-Square and T-student tests. R software was employed for statistical analysis. Results 189 SSc patients (13% male) fulfilling 2013 ACR/EULAR classification criteria were enrolled in this study. Median (IQR) disease duration was 4 (IQR 2-10) years. 37 (27%) had diffuse cutaneous SSc, 60 (32%) had ILD, and 90 (48%) had DU disease. 52 patients (26%) were CCL24 High. These patients had a higher prevalence of DU (60%, p = 0.042), a higher median (IQR) mRSS [4(2-7) vs 2(0-5), p = 0.036) and showed a higher prevalence of ILD (42% vs 28%, p = 0.055); this was more significant among patients with limited cutaneous SSc (7% vs 12%, p = 0.037). Most importantly, among patients with PF-ILD (19/43 with available 24-month follow-up), 44% had significantly higher CCL24 serum concentration at baseline, compared to stable patients (1150 [817-1593] vs 725 [460-955]; p = 0.017). Consistent with these findings, in patients with ILD, having high CCL24 gave double the chance of progressing within 24 months (66% vs 32% of CCL24 low; p = 0.03). Conclusion We show here that within the context of an observational cohort of unselected patients, CCL24 serum concentration is associated with the presence of DU as well as worse skin and lung fibrotic involvement, suggesting that this molecule may be involved in both vascular and fibrotic manifestations of SSc. These results informed the rationale for a target-enriched basket randomized controlled trial to test the biological and clinical effect of CCL24 inhibition in SSc across cutaneous disease subsets. Disclosure E. De Lorenzis: None. A. Mor: None. R. Ross: None. S. Di Donato: None. R. Aricha: None. H. Levi: None. I. Vaknin: None. F. Del Galdo: Other; FDG received consultancies and research support from Abbvie, AstraZeneca, Boheringer-Ingelheim, Capella, Chemomab, Ergomed, Janssen, Kymab, Mitsubishi-Tanabe.

Pathologies auto-immunes et inflammatoires associées à la sclérodermie systémique : profils cliniques, sérologiques et pronostiques. Série rétrospective bi-centrique en région PACA

IntroductionSystemic sclerosis (SSc) is a rare auto-immune disease, affecting principally women between 40 and 60 years old. It is caracterised by a cutaneous and visceral fibrosis, an alteration of the microvascular network and the presence of autoantibodies. SSc can be associated with another connectivite tissue disease or to other autoimmune diseases, thus defining the overlap syndrome. The goal of our study is to describe these overlap syndromes. MethodsWe have analysed the data of a retrospective and bicentrique cohort, from the internal medicine unit of Hôpital Nord in Marseille and from the internal medicine unit of the Hôpital Sainte-Anne in Toulon, of patients followed for a SSc between January 1st, 2019 and December 1st, 2021. We have collected clinical, imunological features, associated auto-immune and inflammatory diseases with its morbidity and mortality. ResultsThe cohort included 151 patients including 134 limited cutaneous SSc. Fifty-two (34.4%) patients presented at least one associated auto-immune or inflammatory disease. The association of two connectivite tissue diseases including SSc was found in 24 patients (15.9%), a third with Sjögren's syndrome and a third with autoimmune myositis. The principal associated disease to SSc was the autoimmune thyroiditis found in 17 patients (11.3%). The occurrence of complications (hospitalization, long-term oxygene therapy, death) was not significantly different depending on the existence or not of an overlap syndrom. ConclusionSSc is often associated with other autoimmune diseases. This interrelation between associated pathologies and SSc, modifying sometimes the evolution of SSc, enhances the need of a personalized follow-up.

КЛИНИКО-ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ АНТИНУКЛЕАРНЫХ АНТИТЕЛ В ПРАКТИКЕ ПЕДИАТРА (ЧАСТЬ 2)

Antinuclear antibodies (ANA) are a group of autoantibodies directed against various cell structures such as nucleus, nuclear membrane, mitotic apparatus, components of the cytoplasm and organelles of the cell as well as cell membranes, which has more than 200 varieties. ANA were first discovered in patients with systemic lupus erythematosus (SLE), and ANA-positivity is considered as its diagnostic criterion since then. However, ANA are found highly frequently both in patients with other systemic rheumatic diseases and in healthy people, which determines their relatively low specificity. Determination of the patient's antibody profile is of a greater importance for diagnostic purposes since some ANA are quite highly specific and associated mainly with a single disease e.g., antibodies (abs) to DNA and anti-Sm abs in SLE, abs to topoisomerase I and abs to the centromere with systemic scleroderma and the CREST syndrome. Associations of some types of ANA with variants/subtypes of systemic autoimmune rheumatic diseases (SARDs) with the risk of damage to various organs and systems, the features of the course and prognosis of diseases in this group have been established, which expanded the understanding of the clinical and diagnostic significance of these autoantibodies. The identification of new and further study of the role of already known types of ANA will improve the diagnosis and development of the SARDs’ targeted therapy.

Autoantibody Profile and Lung HRCT Scan in Systemic Sclerosis with Restrictive Lung Disease

Objective: To identify auto-antibodies in systemic sclerosis with interstitial lung disease (ILD). Method: This was a descriptive categorical study on auto-antibody profile in systemic sclerosis patients visiting the Rheumatology Clinic of Dr. Hasan Sadikin General Hospital, West Java, and Bandung during the period of January 2018 to December 2019 who were registered in the West Java Systemic Sclerosis Registry. Auto-antibody identification was performed using the Euroline immunoblot assays.Results: Thirty six cases were identified during the study period with most of the cases involved women (n=35, 97.2%). The average age of patients participating in this study was 40 years, with an average duration of disease of 18 months. Diffuse cutaneous systemic sclerosis was found in 22 (61.1%) cases and limited cutaneous systemic sclerosis was observed in 14 (38.9%) cases. Specific autoantibodies were positive in 33 (91.6%) cases, with anti-topoisomerase I as the largest group, positive in 22 (52.9.3%) cases. This was followed by anti-Th/To in eight (15.7%) cases; anti-Ro52 in four (7.8%) cases; anti-centromere in three (5.9%) cases; anti-RNA polymerase in three (5.9%) cases; anti-fibrillarin in three (5.9%) cases; anti-Ku in two (3.9%) cases; and anti-PDGF in one (2.0%) case. High-resolution computed tomography of the lung showed 34 (94.4%) cases with ILD and 22 (61.1%) cases with severe lung fibrosis. Usual interstitial pneumonia was seen in 19 (52.8%) cases and non-specific interstitial pneumonia in 15 (41.7%) cases.Conclusion: Anti-topoisomerase I, anti-Th/To, and anti-Ro52 are the most common autoantibodies observed in systemic sclerosis patients with ILD as the most prevalent feature detected with lung HRCT.

Serum cold-inducible RNA-binding protein levels as a potential biomarker for systemic sclerosis-associated interstitial lung disease

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrotic, inflammatory, and vascular dysfunction. Danger-associated molecular patterns (DAMPs)-mediated inflammasome activation has been reported to be involved in the pathogenesis of SSc. Cold-inducible RNA-binding protein (CIRP) is newly identified as a DAMP. Here we examined the clinical significance of serum levels of CIRP in 60 patients with SSc and 20 healthy control patients (HCs) using an enzyme-linked immunosorbent assay. Serum CIRP levels in diffuse cutaneous SSc (dcSSc) patients were significantly increased compared with limited cutaneous SSc (lcSSc) patients or HCs. When examining the relationship with SSc-specific parameters, serum CIRP levels with the presence of interstitial lung disease (ILD) were higher than those without ILD. In detail, serum CIRP levels correlated negatively with the percent predicted diffusing capacity for carbon monoxide and positively with levels of Krebs von den Lungen-6. In addition, elevated serum CIRP levels declined along with decreased SSc-ILD activity in patients who received immunosuppressive therapy. These results suggest that CIRP may play a role in the development of ILD in SSc. Moreover, CIRP could serve as a useful serological marker of SSc-ILD in terms of disease activity and therapeutic effects.

Periodontal disease and its association to endothelial dysfunction and clinical changes in limited systemic sclerosis: Acase-control study.

Periodontal disease occurs frequently in patients with limited cutaneous systemic sclerosis (lcSSc) while data about underlying pathways contributing to periodontal changes are scarce. The aim of this study was to evaluate periodontal disease and to investigate its association with endothelial dysfunction and clinical changes in patients with lcSSc. In 38 lcSSc patients and 38 controls, periodontal status was evaluated by disease-specific questionnaire, dental examination including bleeding on probing (BOP), pocket depth, and plaque index, and dental panoramic radiograph. Periodontopathogen bacteria were collected subgingivally using paper points and interleukin-1 (IL-1) gene polymorphisms were evaluated using buccal swabs. Endothelial dysfunction was measured by flow-mediated dilatation, pulse-wave velocity and biochemical analysis, including arginine metabolites and endothelial microparticles. Additionally, lcSSc-specific clinical changes and parameters were recorded. Periodontitis was present in 31 patients with lcSSc (81.6%) and in 27 controls (71.1%) (p=.280). LcSSc patients had a lower teeth number (p=.039) and Eikenella corrodens was to a higher degree detectable in patients with lcSSc (p=.041) while the remaining periodontal parameters revealed no differences between both cohorts. Significant correlations between parameters of arterial stiffness, EUSTAR index, number of teeth and BOP were observed (all p < .05). Detection of Prevotella intermedia was associated with selected IL-1 gene polymorphisms (p=.032) and Porphyromonas gingivalis was associated with severe periodontitis (p=.041). Periodontal disease may occur frequently in patients with lcSSc and may be associated with arterial stiffness and with SSc activity.

Native T1 mapping in early diffuse and limited systemic sclerosis, and its association with diastolic function

BackgroundSystemic sclerosis (SSc) is divided into diffuse and limited cutaneous SSc (dcSSc and lcSSc). The dcSSc subtype has more severe internal organ damage. This study aimed to assess whether cardiovascular magnetic resonance (CMR) parametric mapping could detect early cardiac involvement and evaluate differences between these two subtypes. MethodsEighty SSc patients (37 dcSSc and 43 lcSSc) underwent CMR at 3.0 T (Philips Healthcare, Best, The Netherlands) in our hospital between July 2018 and July 2021. We analyzed myocardial damage by CMR parametric mapping and compared it with clinical data. ResultsThe median duration of the disease was 10.2 months. The left ventricular ejection fraction was preserved in both groups. DcSSc had significantly higher native T1 (1333.4 ± 71.2 ms vs. 1295.0 ± 42.7 ms, p = 0.006) and extracellular volume fraction (32.6 ± 4.1 % vs. 30.3 ± 4.0 %, p = 0.018) in the mid-ventricular septum as compared to lcSSc, although there were no differences in T2 values. Native T1 values were positively correlated with the E/e’ ratio and left atrial volume indices evaluated by transthoracic echocardiography in overall SSc and dcSSc, but not in lcSSc. Logistic regression analysis revealed that native T1 was an independent predictor of left ventricular diastolic dysfunction in SSc patients (odds ratio, 1.194; 95 % confidence interval, 1.021–1.396; p = 0.026). Native T1 was higher in SSc patients with progressive skin lesions. Additionally, there were positive correlations between brain natriuretic peptide, New York Heart Association functional classification, and native T1. ConclusionsCMR parametric mapping is a useful tool for detecting myocardial changes. Native T1 was the most sensitive parameter for identifying diffuse myocardial changes in the early stages of SSc and was associated with left ventricular diastolic function. DcSSc had more severe myocardial involvement than lcSSc; therefore, the use of CMR parametric mapping may aid in its prediction.

Brachial artery flow-mediated dilation in patients with systemic sclerosis: an experience from tertiary care center from North India.

Role of flow-mediated dilatation (FMD) testing in the assessment of the macrovascular dysfunction in systemic sclerosis (SS) and correlation of FMD values with disease severity. Twenty-five patients of SS and 25 healthy age-matched controls were recruited. Modified Rodnan skin thickness score (MRSS) was used for skin thickness assessment. FMD values were measured in the brachial artery. FMD values done at baseline before the initiation of treatment were lower in SSc patients (4.044 ± 2.742) compared to the healthy controls (11.076 ± 5.896) (P < 0.05). Comparison of FMD values between patients with limited cutaneous systemic sclerosis (LSSc) and diffuse cutaneous systemic sclerosis (DSSc) showed a trend toward lower in LSSc (3.182 ± 2.482) as compared to DSSc patients (5.111 ± 2.711); however, the difference was not statistically significant. Patients with lung manifestations on high-resolution CT chest showed lower FMD values (2.66 ± 2.23) compared to those without HRCT changes (6.45 ± 2.56) (P < 0.05). We demonstrate that FMD values in SSc patients were lower when compared to healthy controls. Patients with SS having pulmonary manifestations showed a lower value of FMD. Key Points • FMD is a simple non-invasive tool to assess the endothelial function in patients with systemic sclerosis. • Lower values of FMD in systemic sclerosis suggest that the endothelial dysfunction and values can also be correlated with other organ involvement such as lung and skin involvement. So, lower FMD values might be a useful marker for disease severity.

Impaired left-ventricular global longitudinal strain by feature-tracking cardiac MRI predicts mortality in systemic sclerosis.

Impaired left-ventricular (LV) and right-ventricular (RV) cardiac magnetic resonance (CMR) strain has been documented in systemic sclerosis (SSc). However, it is unknown whether the CMR strain is predictive of adverse outcomes in SSc. Therefore, we set out to investigate the prognostic value of CMR strain in SSc. Patients with SSc who underwent CMR for clinical indications between 11/2010 and 07/2020 were retrospectively studied. LV and RV strain was evaluated by feature tracking. The association between strain, late gadolinium enhancement (LGE), and survival was evaluated with time to event and Cox-regression analyses. During the study period, 42 patients with SSc (age: 57 ± 14years, 83% female, 57% limited cutaneous SSc, SSc duration: 7 ± 8years) underwent CMR. During the median follow-up of 3.6years, 11 patients died (26%). Compared to surviving patients, patients who died had significantly worse LV GLS (-8.2 ± 6.2% versus -12.1 ± 2.9%, p = 0.03), but no difference in LV global radial, circumferential, or RV strain values. Patients within the quartile of most impaired LV GLS (≥ -12.8%, n = 10) had worse survival when compared to patients with preserved LV GLS (< -12.8%, n = 32, log-rank p = 0.02), which persisted after controlling for LV cardiac output, LV cardiac index, reduced LV ejection fraction, or presence of LGE. In addition, patients who had both impaired LV GLS and LGE (n = 5) had worse survival than patients with LGE or impaired GLS alone (n = 14) and compared to those without any of these features (n = 17, p = 0.003). In our retrospective cohort of patients with SSc undergoing CMR for clinical indications, LV GLS and LGE were found to be predictive of overall survival.

Hypochromic red cells as a prognostic indicator of survival among patients with systemic sclerosis screened for pulmonary hypertension

BackgroundPatients with systemic sclerosis (SSc) are frequently affected by iron deficiency, particularly those with pulmonary hypertension (PH). The first data indicate the prognostic importance of hypochromic red cells (% HRC) > 2% among patients with PH. Hence, the objective of our study was to investigate the prognostic value of % HRC in SSc patients screened for PH.MethodsIn this retrospective, single-center cohort study, SSc patients with a screening for PH were enrolled. Clinical characteristics and laboratory and pulmonary functional parameters associated with the prognosis of SSc were analyzed using uni- and multivariable analysis.ResultsFrom 280 SSc patients screened, 171 could be included in the analysis having available data of iron metabolism (81% female, 60 ± 13 years of age, 77% limited cutaneous SSc, 65 manifest PH, and 73 pulmonary fibrosis). The patients were followed for 2.4 ± 1.8 (median 2.4) years. HRC > 2% at baseline was significantly associated with worse survival in the uni- (p = 0.018) and multivariable (p = 0.031) analysis independent from the presence of PH or pulmonary parenchymal manifestations. The combination of HRC > 2% and low diffusion capacity for carbon monoxide (DLCO) ≤ 65% predicted was significantly associated with survival (p < 0.0001).ConclusionThis is the first study reporting that HRC > 2% is an independent prognostic predictor of mortality and can possibly be used as a biomarker among SSc patients. The combination of HRC > 2% and DLCO ≤ 65% predicted could serve in the risk stratification of SSc patients. Larger studies are required to confirm these findings.

Acute Spontaneous Colonic Perforation in a Case of Newly Confirmed Scleroderma: Case Report.

Scleroderma is a group of autoimmune diseases that principally affects the skin, blood vessels, muscles, and viscera. One of the more well-known subgroups of scleroderma is the limited cutaneous form of the multisystem connective tissue disorder known as CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasis) syndrome. In this report, we present a case of a spontaneous colonic bowel perforation in a patient with incomplete features of CREST. Our patient underwent a complicated hospital course involving broad-spectrum antibiotic coverage, surgical hemicolectomy, and immunosuppressives. She was eventually discharged home with a return to functional baseline status after esophageal dysmotility confirmation via manometry. Physicians managing patients with scleroderma ensuing to an emergency department encounter must anticipate the multitude of complications that can occur, as was seen in our patient. The threshold for pursuing imaging and additional tests, in addition to admission, should be relatively low, given the extremely high rates of complications and mortality. Early multidisciplinary involvement with infectious disease, rheumatology, surgery, and other respective specialties is crucial for patient outcome optimization.

Evaluation of choroidal vascularity index in systemic sclerosis patients.

To investigate the comparison of choroidal vascularity index (CVI) between patients with systemic sclerosis and healthy individuals. This study was designed prospective non-randomized cross-sectional study. Eighty-six eyes (43 patients) with limited cutaneous systemic sclerosis (lcSSc), 60 eyes (30 patients) with diffuse cutaneous systemic sclerosis (dcSSc) and 60 eyes (30 subjects) of age-and sex-matched healthy individuals were recruited. Subfoveal choroidal thickness, CVI and modified Rodnan skin score (mRSS) were evaluated. Enhanced depth imaging- optical coherence tomography scans were binarized using Niblack's autolocal threshold and CVI was determined as the luminal choroidal area/total choroidal area ratio. The mean CCT values were 268.00±68.59 µm, 286.90±70.88 µm, 321.73±94.13 µm in lcSSc group, dcSSc group and control group, respectively. The mean CVI was 61.84±2.84% in lcSSc group, 54.62±5.84% in dcSSc group and 62.41±4.13% in control group (p=0.001). The mean CVI of the SSc patients was 58.91±5.58 and there was significant difference between control group (p<0.001). The mean mRSS was 3.84±2.50 in lcSSc group and 14.07±6.81 in dcSSc group (p<0.001). There was a statistically significant negative correlation between mRSS and CVI (r=-0.448, p<0.001) CONCLUSION: Choroidal vascularity index provides valuable information to monitor the disease progression and lower CVI values seem to be related to the disease severity in patients with systemic sclerosis.

Skin biopsy analysis of concurrent keloidal morphoea and systemic sclerosis confirms overlapping pathogenic pathways.

Although localised forms of scleroderma (morphoea) have very different clinical features and outcomes from systemic sclerosis the two conditions can occur together in some patients. In this study we have explored skin gene expression in a series of patients with keloidal morphoea, a distinct clinical variant, concurrently with systemic sclerosis. We compared skin gene expression from the keloidal lesions with that from skin elsewhere. We also examined a series of patients with diffuse or limited cutaneous SSc without morphoea and some healthy control skin biopsies. Keloidal morphoea has a distinct gene expression signature that is mainly driven by differential expression of fibroblast-related genes compared with other cell types. Indeed, the signature reflects a profibrotic pattern seen in diffuse cutaneous SSc but is much more extreme. We propose that keloidal morphoea skin provides unique insight into the profibrotic population of cells driving dcSSc. Understanding the biology of keloidal morphoea may give valuable insight into the molecular and cellular pathology of systemic sclerosis. The discrete nature of keloidal lesions raises the possibility of haematogenous spread and we suggest that the driving cells could represent blood derived cells derived from circulating progenitors.

CARDIO-PULMONARY PROFILE IN LIMITED AND DIFFUSE SYSTEMIC SCLEROSIS.

Background: Scleroderma, systemic sclerosis (SSc), is a chronic multisystem autoimmune disease characterized by a vasculopathy, diffuse brosis of skin and numerous internal organs, and immune abnormalities. The clinical manifestations of this disease are extremely heterogeneous.1 Pulmonary and cardiac involvement of scleroderma are responsible for signicant morbidity and mortality.2 This study aims to evaluate and compare different cardiac and pulmonary manifestations between limited and diffuse systemic sclerosis. Materials And Methods: 54 Systemic Sclerosis patients were studied at Assam Medical College and Hospital, from June 2020 to May 2021. In our study Results: among 54 patients, 46 were female (85.19%) and male (14.81%). Maximum (40.74%) patients were between the age group 41-50 years. 53.70% had diffuse and 46.30% had limited cutaneous systemic sclerosis. Dyspnoea on exertion (59.26%), cough (35.19%) and palpitation (20.37%). Dyspnea was signicantly higher in diffuse SSc (75.86%) compared to limited SSc (40%). 72.22% of the studied population had ILD. Predominant HRCT ndings were ground glass opacity (53.70%). 2D-ECHO abnormalities were observed in (62.96%) patients of diffuse SSc (72.41%); 58.62% of diffuse and 44% of limited cutaneous disease had abnormal ECG. PAH was observed in 28% in limited and 13.79% in diffuse Ssc. Conclusion: From this study we can conclude that though systemic manifestations and organ involvement was more common in diffuse SSc. Thorough evaluation in cases of SSc is essential for early diagnosis, treatment &amp; better prognostic outcome

Erectile Dysfunction in a Male Patient With Limited Cutaneous Systemic Sclerosis

A 24-year-old male with a 3-year history of limited cutaneous systemic sclerosis (LcSS) was referred to the urology clinic by his rheumatologist because of erectile dysfunction (ED). He complained of his worsening ED over the past two years. His international index of erectile function (IIEF) score was 5, indicating severe ED. He reported no morning erection and experienced some degree of turgidity without rigidity in sexual occasions. Digital ulcers and gastroesophageal reflux were his only presentations other than ED. His history was negative for pulmonary hypertension and renal crisis.

Periodontitis Burden in Diffuse Versus Limited Systemic Sclerosis Subtypes: A Pilot Study.

This study aimed to evaluate the periodontal status of a group of Romanian systemic sclerosis (SSc) patients and to investigate the relationships between periodontitis and SSc subtypes. This observational study included patients diagnosed with limited SSc (lcSSc) and diffuse SSc (dcSSc). Demographic data were collected from medical records. Each participant underwent a full-mouth periodontal examination including Bleeding on Probing (BoP) index, Oral Hygiene (OH) index, Probing Depth (PD), Gingival Recession (GR), and Clinical Attachment Loss (CAL). The periodontal status was defined according to presently recognised case definition system. The study included 30 patients with lcSSc and 30 patients with dcSSc with a mean age of 52.45±11.75 years. The overall periodontitis frequence in our SSc group was 95%. The frequency of stage III/IV periodontitis was higher in the dcSSc group (90%) than in the lcSSc group (60%). Within the group of SSc patients, significant positive correlations were observed between age, BoP index, OH index, the number of missing teeth, mean PD, mean CAL on one side and periodontitis diagnosis on the other side (r=0.588, p=0.001; r=0.399, p=0.002; r=0.388, p=0.002; r=0.574, p=0.001; r=0.444, p=0.001; r=0.571, p=0.001). A significant positive correlation existed between the diagnostic of periodontitis and SSc subtypes (r=0.327, p <0.001). Periodontitis was highly prevalent in both lcSSc and dcSSc groups. More stage III/IV periodontitis cases were detected dcSSc group of patients.

Prevalence of erectile dysfunction in Thai scleroderma patients and associated factors.

Erectile dysfunction (ED) has been reported among patients with systemic sclerosis (SSc) and primarily limited cutaneous SSc in Caucasians. While there is no data on ED among Thais in whom the diffuse cutaneous SSc subset is common. We aimed to estimate the prevalence of ED among Thais with SSc, evaluate its severity, and determine the associated factors. We did a cross-sectional study among adult Thai male SSc patients. All eligible patients: a) completed the IIEF-15 questionnaire by themselves; b) underwent a genital examination by an experienced urologist to evaluate skin tightness of the penis, scrotum, and phimosis; and, c) were evaluated for Erection Hardness Score. A total of 60 male SSc patients were included. The respective mean age and median disease duration was 54.8±7.2 years and 3.1 years (IQR 1.2-7.2). The definition of ED was fulfilled in 53 cases for a prevalence of 88.3% (95%CI 77.4-95.2), while 65% had severe ED, and none had skin tightness of the genitalia. Eight cases had acquired phimosis, and all were in the ED group. The patients with ED vs. those without ED had significantly lower scores for orgasm, sexual desire, and intercourse satisfaction, and trended to be older, have more severe skin tightness and have higher BMI. ED is a common problem in men with SSc and is mainly categorized as severe. The severity of SSc might increase the risk of developing ED. We found phimosis was a common genital abnormality co-occurring with ED in SSc.