Abnormalities In Systemic Sclerosis Research Articles

Structural abnormalities associated with glaucoma using swept-source optical coherence tomography in patients with systemic sclerosis.

Vasospasm represents an early event in systemic sclerosis (SSc). Ocular vasospasm may induce optic nerve head (ONH) damage and has been involved in the pathogenesis of glaucoma, especially normal-tension glaucoma (NTG). We aimed to investigate the presence of structural abnormalities associated with NTG using swept-source optical coherence tomography (SS-OCT) and to correlate the OCT parameters with clinical, capillaroscopy and digital blood flow measures in patients with SSc. In this cross-sectional study, 40 patients with SSc and 23 age-matched controls were included. The following parameters were measured using SS-OCT: mean and sectoral retinal nerve fibre layer (RNFL) thickness, macular ganglion cell layer complex (GCC) thickness and ONH morphology. Nailfold capillaroscopy (NFC) and digital blood flow measurements using laser Doppler imaging (LDI) were performed in all subjects. Patients with SSc showed a thinner temporal RNFL than the controls (69.23 ± 11.74 versus 83.35 ± 20.19µm, p = 0.001). The other parameters were similar between the two groups. In SSc patients, there was an inverse correlation between the disease duration and the average, superior and inferior RNFL thickness and the GCC thickness and between Raynaud's phenomenon duration and the average RNFL and GCC thickness (p < 0.05). NFC and LDI measurements did not show correlations with OCT parameters. A thinner temporal RNFL and the correlation between Raynaud's phenomenon and disease duration and structural abnormalities on OCT suggest the presence of early ganglion cell damage in patients with SSc. Although mild, these findings indicate the need to monitor ocular abnormalities in SSc.

Contribution to the peripheral vasculopathy and endothelial cell dysfunction by CXCL4 in Systemic Sclerosis

BackgroundCXCL4, a chemokine with anti-angiogenic property, is involved in systemic sclerosis (SSc) related pulmonary arterial hypertension (PAH). ObjectiveTo investigated the contribution of CXCL4 to SSc development by focusing on the correlation of circulatory CXCL4 levels with their peripheral vasculopathy, and the effect of CXCL4 on endothelial cell dysfunction and the potential signaling. MethodsWe measured the plasma CXCL4 levels in 58 patients with SSc, 10 patients with the very early diagnosis of SSc (VEDOSS), and 80 healthy controls (HCs). Then, CXCL4 concentrations were correlated with clinical features, especially the peripheral vasculopathy. These observations were further validated in an additional cohort. Moreover, we studied the anti-angiogenic effects of CXCL4 and the underlying downstream signaling in human umbilical vein endothelial cells (HUVECs) in vitro. ResultsCirculating CXCL4 levels were 103.62 % higher in patients with SSc and 201.51 % higher in patients with VEDOSS than matched HCs, which were confirmed in two independent cohorts. CXCL4 levels were associated with digital ulcers (DU) and nailfold videocapillaroscopy (NVC) abnormalities in SSc. The proliferation, migration, and tube formation of HUVECs were inhibited by CXCL4 or SSc derived plasma, which reversed by CXCL4 neutralizing antibody, but failed by CXCR3 inhibitor. CXCL4 downregulated the transcription factor Friend leukaemia integration factor‐1 (Fli-1) via c-Abl signaling. Furthermore, CXCL4 blocked the transforming growth factor (TGF) -β or platelet-derived growth factor (PDGF) induced cell proliferation of HUVECs. ConclusionsCXCL4 may contribute to peripheral vasculopathy in SSc by downregulating Fli-1 via c-Abl signaling in endothelial cells and interfering angiogenesis.

Machine learning associated with respiratory oscillometry: a computer-aided diagnosis system for the detection of respiratory abnormalities in systemic sclerosis

IntroductionThe use of machine learning (ML) methods would improve the diagnosis of respiratory changes in systemic sclerosis (SSc). This paper evaluates the performance of several ML algorithms associated with the respiratory oscillometry analysis to aid in the diagnostic of respiratory changes in SSc. We also find out the best configuration for this task.MethodsOscillometric and spirometric exams were performed in 82 individuals, including controls (n = 30) and patients with systemic sclerosis with normal (n = 22) and abnormal (n = 30) spirometry. Multiple instance classifiers and different supervised machine learning techniques were investigated, including k-Nearest Neighbors (KNN), Random Forests (RF), AdaBoost with decision trees (ADAB), and Extreme Gradient Boosting (XGB).Results and discussionThe first experiment of this study showed that the best oscillometric parameter (BOP) was dynamic compliance, which provided moderate accuracy (AUC = 0.77) in the scenario control group versus patients with sclerosis and normal spirometry (CGvsPSNS). In the scenario control group versus patients with sclerosis and altered spirometry (CGvsPSAS), the BOP obtained high accuracy (AUC = 0.94). In the second experiment, the ML techniques were used. In CGvsPSNS, KNN achieved the best result (AUC = 0.90), significantly improving the accuracy in comparison with the BOP (p < 0.01), while in CGvsPSAS, RF obtained the best results (AUC = 0.97), also significantly improving the diagnostic accuracy (p < 0.05). In the third, fourth, fifth, and sixth experiments, different feature selection techniques allowed us to spot the best oscillometric parameters. They resulted in a small increase in diagnostic accuracy in CGvsPSNS (respectively, 0.87, 0.86, 0.82, and 0.84), while in the CGvsPSAS, the best classifier's performance remained the same (AUC = 0.97).ConclusionsOscillometric principles combined with machine learning algorithms provide a new method for diagnosing respiratory changes in patients with systemic sclerosis. The present study's findings provide evidence that this combination may help in the early diagnosis of respiratory changes in these patients.

High prevalence of salivary gland ultrasound abnormalities in systemic sclerosis

To evaluate salivary gland (SG) involvement in patients with systemic sclerosis (SSc) using SG ultrasound (SGUS). Patients with SSc (n=62), primary Sjögren's syndrome (pSS) (n=59), and idiopathic Sicca syndrome (n=43) were evaluated using the outcome measures in rheumatology clinical trial (OMERACT) definitions of the SGUS scoring system. The hyperechogenic bands using the 0-3 scoring system, intraglandular power Doppler signal (PDS), and SG volumes were also assessed. The proportion of patients with OMERACT grades (≥2) among the four SGs was significantly higher in SSc (51.6%) and pSS (62.7%) groups than those in the idiopathic Sicca syndrome group (4.7%). Patients with SSc and pSS had significantly higher total fibrosis grades than controls. No difference in fibrosis grades was observed between SSc and pSS groups. The PDS scores of SGs were higher in the SSc group than in the idiopathic Sicca syndrome group. SG volumes did not differ between the groups. SSc patients with SGUS grades ≥2 had more anti-centromere antibodies (ACA) (65.6% vs. 30.0%) than individuals with grades 0-1. SSc patients with fibrosis grades ≥2 reported more Sicca symptoms than those with grades 0-1. Inhomogeneity and hyperechogenic bands within the SGs were not associated with organ involvement in SSc. More than half of patients with SSc, specifically with ACA, showed SG involvement. SG fibrosis was more prominent in SSc than in idiopathic Sicca syndrome and was associated with subjective Sicca symptoms. However, hyperechoic bands within the SGs are not features that can differentiate between SSc and pSS.

Anti-annexin V autoantibodies and vascular abnormalities in systemic sclerosis: a longitudinal study

BackgroundAnnexins are a group of conserved proteins which exert several regulatory functions on various cellular activities. Increased frequency and levels of antibodies against annexin V have already been observed in several autoimmune diseases including systemic sclerosis (SSc), but their role as a vascular biomarker is unknown. The aim of this study was to determine the serum levels and the dynamical behavior of anti-annexin V antibodies over a 24 months follow-up in patients with SSc.MethodsIn this bicentric cross-sectional study, 70 patients with SSc were consecutively selected from March 2016 to April 2017. Demographic and clinical features, including the presence of active DUs, were collected. Serum anti-annexin V IgG and IgM antibodies were measured at baseline and after 6, 12 and 24 months of follow-up. Videocapillaroscopy was performed in all patients.ResultsAmong the 70 SSc patients included anti-annexin V IgG was found in 11 patients (15.7%) (range of 15.88–39.48 U/mL) and anti-annexin V IgM in 10 patients (14.3%) (range of 14.16–22.69 U/mL) at baseline. During follow-up, the number of patients who were positive for anti-annexin V IgG and IgM remained stable over 24 months. Among the patients with positive anti-annexin V IgG at baseline the frequency of patients with necrosis or amputation of extremities, forced vital capacity less than 70% and pulmonary arterial hypertension (PAH) was significantly higher than in patients with negative anti-annexin V IgG antibodies. Patients with anti-annexin V IgG had also a higher Raynaud’s Condition Score and a higher Health Assessment Questionnaire Disability Index (HAQ-DI) than patients without these antibodies at baseline. Patients with positive anti-annexin V IgM at baseline presented a higher frequency of PAH, compared to those with negative anti-annexin V IgM at baseline.ConclusionsAnti-annexin V antibodies are stable and do not change their positivity during a 24 month follow-up in SSc patients. Anti-annexin V IgG was associated with more severe interstitial lung involvement and digital microangiopathy, and patients with anti-annexin V IgG or IgM had a higher occurrence of PAH indicating an association of these biomarker with more severe disease.

Haematological abnormalities in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterised by extremely high heterogeneity. This heterogeneity concerns the organ involvement, course of disease and prognosis. Unlike in some other systemic connective tissue diseases, especially systemic lupus erythematosus, in SSc haematological disorders occur rarely. When they develop, they affect erythrocytes, leucocytes and platelets. The most common cause of this pathology of erythrocyte abnormalities is microcytic anaemia resulting from micro-haemorrhages with telangiectasias within the digestive mucosa in patients with SSc. In SSc patients with severe haematological disturbances, the differential diagnosis should include overlapping with another systemic connective tissue disease or a haemato-oncological disease (lympho/myeloproliferative syndrome). In SSc patients with monoclonal proteins or cryoglobulins, it is essential to consider a haemato-oncological disease. In such cases, the differential diagnosis should be focused on a paraneoplastic syndrome, especially when the haematological symptoms develop shortly after the diagnosis of SSc and in the elderly.

Rheumatology Clinic, University “Politecnica delle Marche”, Italy

Nailfold capillaroscopy is currently the best method to investigate microvascular abnormalities in systemic sclerosis and related conditions, and in other rheumatic conditions in which there is a clinical suspicion of microangiopathy. Although easy to perform, it is essential that the operators have been properly trained about correct method of images acquisition and interpretation. There are some parameters to indicate a normal/healthy capillaroscopic picture, but it is important to consider that there is a great variability in the capillary structure both interindividual and intraindividual. The early differential diagnosis between primary and secondary RP is the best advantage that the technique may offer. Remarkable capillaroscopic alterations are found in the majority of cases of systemic sclerosis and the so-called “scleroderma spectrum disorders” (dermatomyositis, mixed connective tissue disease, undifferentiated connective tissue disease). Nevertheless, some capillaroscopic changes have been observed in systemic lupus erythematosus, Sjogren’s syndrome, psoriatic and rheumatoid arthritis. Discussion about controversies on this topic should be encouraged, leading to a progressive development of capillaroscopy as a routine investigation in rheumatology.

Nailfold capillaroscopy in systemic sclerosis - state of the art: The evolving knowledge about capillaroscopic abnormalities in systemic sclerosis.

Capillaroscopy is a unique method for morphological evaluation of the nailfold capillaries that plays a crucial role for early diagnosis of systemic sclerosis. The first description of the pathological capillaroscopic changes in systemic sclerosis was made by Brown and O'Leary in 1925. Several decades later they have been validated and accepted as a diagnostic criterion in the current 2013 EULAR/ACR classification criteria. This article summarizes the evolving knowledge about the use of nailfold capillaroscopy in systemic sclerosis. Initially, Maricq et al. suggested two major categories of capillaroscopic findings in systemic sclerosis - an 'active'and 'slow' capillaroscopic pattern. Their description and terminology suggested a correlation between capillaroscopic changes and disease activity and progression. In the later classification of Cutolo et al., three phases were defined, i.e. 'early', 'active' and 'late' that reflect the time-related evolution of the capillaroscopic changes suggesting their association with disease duration. Current knowledge about the microvascular changes in systemic sclerosis supports both associations with disease activity and disease duration. The general opinion about the association of capillaroscopic findings with clinical involvement and disease activity in systemic sclerosis is not uniform. This is supposedly because the phase changes of systemic sclerosis-related microangiopathy are almost a universal feature in scleroderma and are not specific for a certain type of an accompaning clinical manifestation. Thus, the speed of progression of microvascular alterations might be a decisive criterion, and in cases of rapid dynamics of capillaroscopic findings, it could be considered as an indicator of disease activity. Interestingly, vascular 'recovery' has been observed after treatment with immunosuppressive drugs, haematopoietic stem cell transplantation, and the endothelin receptor antagonist - bosentan. The evolving knowledge about nailfold capillaroscopy in systemic sclerosis will further spread its application from a mainly diagnostic tool to an established, reliable method for evaluation of disease activity, prognosis and therapeutic response.

Antinuclear Antibodies in Systemic Sclerosis: an Update.

Systemic sclerosis is an autoimmune disease characterized by fibrosis of skin and internal organs, vasculopathy, and dysregulation of immune system. A diagnostically important feature of immunological abnormalities in systemic sclerosis is the presence of circulating antinuclear antibodies, which may be detected in 90-95% of patients with either of the four main laboratory methods: immunofluorescence, enzyme-linked immunosorbent assay, immunodiffusion, and immunoblotting. There are several antinuclear antibodies specific for systemic sclerosis. These include antibodies against topoisomerase (anti-TOPO I), kinetochore proteins (ACA), RNA polymerase enzyme (anti-RNAP III), ribonuclear proteins (anti-U11/U12 RNP, anti-U1 RNP, anti-U3 RNP) and nucleolar antigens (anti-Th/To, anti-NOR 90, anti-Ku, antiRuvBL1/2, and anti-PM/Scl). Autoantibodies specific for systemic sclerosis have been linked to distinct clinical features. Therefore, detecting a particular antibody type is important in predicting a possible organ involvement and prognosis and may have an impact on monitoring and treatment.

Anti-nuclear autoantibodies in systemic sclerosis : News and perspectives.

Systemic sclerosis is a connective tissue disorder characterized by microvascular damage and excessive fibrosis of the skin and internal organs. One hallmark of the immunological abnormalities in systemic sclerosis is the presence of anti-nuclear antibodies, which are detected in more than 90% of patients with systemic sclerosis. Anti-centromere antibodies, anti-DNA topoisomerase I antibodies, and anti-RNA polymerase III antibodies are the predominant anti-nuclear antibodies found in systemic sclerosis patients. Other systemic sclerosis-related anti-nuclear antibodies include those targeted against U3 ribonucleoprotein, Th/To, U11/U12 ribonucleoprotein, and eukaryotic initiation factor 2B. Anti-U1 ribonucleoprotein, anti-Ku antibodies, anti-PM-Scl, and anti-RuvBL1/2 antibodies are associated with systemic sclerosis overlap syndrome. Anti-human upstream binding factor, anti-Ro52/TRIM21, anti-B23, and anti-centriole antibodies do not have specificity to systemic sclerosis, but are sometimes detected in sera from patients with systemic sclerosis. Identification of each systemic sclerosis-related antibody is useful to diagnose and predict organ involvement, since the particular type of systemic sclerosis-related antibodies is often predictive of clinical features, severity, and prognosis. The clinical phenotypes are largely influenced by ethnicity. Currently, an immunoprecipitation assay is necessary to detect most systemic sclerosis-related antibodies; therefore, the establishment of an easy, reliable, and simple screening system is warranted.

Pathogenic roles of B lymphocytes in systemic sclerosis

Systemic sclerosis (SSc) is a collagen disease characterized by autoimmunity and excessive extracellular matrix deposition in the skin and visceral organs. Although the pathogenic relationship between systemic autoimmunity and the clinical manifestations of SSc remains unknown, SSc patients show a variety of abnormal immune activation including the production of disease-specific autoantibodies and cytokine production. Many recent studies have demonstrated that immune cells, including T cells, B cells, and macrophages, have a variety of immunological abnormalities in SSc. So far, several groups and our group reported that B cells play a critical role in systemic autoimmunity and disease expression through various functions, such as cytokine production, lymphoid organogenesis, and induction of other immune cell activation in addition to autoantibody production. Recent studies show that B cells from SSc patients demonstrate an up-regulated CD19 expression, a crucial regulator of B cell activation, which induces chronic hyper-reactivity of memory B cells and SSc-specific autoantibody production and also causes fibrosis of several organs. Furthermore, in SSc-model mice, such as tight-skin mice, bleomycin-induced SSc model mice, and DNA topoisomerase I and complete Freund’s adjuvant-induced SSc model mice, have abnormal B cell activation which associates with skin and lung fibrosis. Indeed, B cell depletion therapy using anti-CD20 Ab, Rituximab, is considered to one potential beneficial treatment for patients with SSc. However, there is no direct evidence which can explain how B cells, especially autoantigen-reactive B cells, progress or regulate disease manifestations of SSc. Collectively, B cell abnormalities in SSc is most likely participating in fibrosis and tissue damage of SSc. If the relationship between SSc-specific tissue damage and B cell abnormalities is revealed, these findings lead to novel effective therapy for SSc.

Fingerprint abnormalities in systemic sclerosis: Results of a single center pilot study

Background: Fingertip abnormalities in the form of digital ulcers and gangrene is well known in systemic sclerosis (SSc), but little has been described about the frequency and systemic associations of finger print (FP) abnormalities in these patients. Our objective was to study the FP abnormalities in SSc patients and find possible association with digital vasculopathy. Methods: Patients with SSc and SSc overlap with other connective tissue diseases were screened for FP abnormalities using a Standardization Testing and Quality Certification Directorate-certified biometric FP scanner. FP quality assessment was done by recording the National Institute of Standards and Technology FP Image Quality (NFIQ) scores. NFIQ's 5 levels of quality are intended to be predictive of fingerprint matching. NFIQ = 1 indicates high quality and NFIQ = 5 indicates poor quality FPs. Social difficulties due to fingerprint abnormalities were noted. Ten healthy controls were included for comparison. Results: Of 37 patients, 29 with SSc and 8 with overlap syndromes, 15 (40.5%) had FP abnormalities in the form of nonrecognition of at least one finger with a median of 2 fingers (range 1–6). The mean NFIQ score of these patients was 4.5 (poor) while mean NFIQ scores in SSc was 3.8. All FPs of 10 controls were recognized, and the mean NFIQ score was 2.2 indicating a better FPs quality. There was no association of FP abnormalities with digital vasculopathy. Conclusions: In this pilot study, we found that fingerprint abnormalities occur frequently in SSc patients. Documentation of this abnormality should allow the use of other biometric tools for personal identification.

Assessment of modified Rodnan skin score and esophageal manometry in systemic sclerosis: a study correlating severity of skin and esophageal involvement by objective measures

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by immune-mediated activation of tissue fibroblasts and consequent fibrosis, vascular abnormalities, and inflammation. The skin and esophagus are the two most frequently involved organs in this disease. Data regarding the correlation between the severity of skin and esophageal involvement in SSc by objective measures are negligible so far. Thirty-one patients with SSc were subjected to esophageal manometry. A correlation between modified Rodnan skin score (MRSS) and esophageal manometric parameters of lower esophageal sphincter pressure (LESP), percentage relaxation of the lower sphincter, amplitude, and duration of the peristaltic waves was established. The mean MRSS was found to be 16.9 ± 8.7. There was no statistical correlation between MRSS and LESP (p = 0.496), percentage relaxation (p = 0.070), amplitude (p = 0.531), and duration (p = 0.459) of the contractions. No difference between these manometric parameters was found if the patients were divided into limited and diffuse subsets. There exists no correlation between the severity of skin involvement measured by MRSS and manometric abnormalities in SSc. All patients with SSc should undergo esophageal manometry irrespective of the extent of skin involvement.

Altered expression of CD63 and exosomes in scleroderma dermal fibroblasts

BackgroundExosomes are small vesicles shed from various cells. They contain proteins, lipids, and nucleic acids, and are regarded as a tool of cell-cell communication. ObjectivesTo reveal the putative role of exosomes in systemic sclerosis (SSc), and to elucidate the effect of exosomes on wound healing. MethodsThe expression of common markers for exosomes (CD63, CD9, and CD81) and type I collagen were examined with real-time PCR, immunohistochemical analysis, ELISA, immunoblotting, and flow cytometry. The effect of serum-derived exosomes on wound healing was tested on full-thickness wounds in the mid-dorsal skin of BALB/c mice. ResultsThe expression levels of CD63 as well as CD9 and CD81 tended to be increased in SSc dermal fibroblasts compared to normal fibroblasts. Increased exosomes in a cultured media of SSc fibroblasts stimulated the expression levels of type I collagen in normal fibroblasts. As the mechanism, collagen-related microRNA levels in SSc fibroblast-derived exosomes were dysregulated, indicating that both the amount and the content of exosomes were altered in SSc. On the other hand, SSc sera showed significantly decreased exosome levels compared to normal sera. The frequencies of vascular involvements, including skin ulcers or pitting scars, were significantly increased in patients with decreased serum exosome levels. The healing of mice wounds was accelerated by treatment with serum-derived exosomes. ConclusionsVascular abnormalities in SSc may account for the decreased serum exosome levels by the disturbed transfer of exosomes from the skin tissue to the blood stream. Our study suggests the possibility that SSc patients with vascular involvements have decreased serum exosome levels, which causes the delay of wound healing due to down-regulation of collagen, resulting in higher susceptibility to pitting scars and/or ulcers. Exosome research will lead to a detailed understanding of SSc pathogenesis and new therapeutic approaches.

Sublingual Abnormalities in Systemic Sclerosis.

Sublingual frenulum abnormalities have been observed in systemic sclerosis (SSc), but the clinical significance of such features is not known. The goal of this project was to devise a reliable bedside tool to confirm the presence of sublingual frenulum abnormalities in SSc and explore potential associations with patient demographics and gastrointestinal clinical phenotype. A working group was created to develop a semiquantitative assessment tool for assessing sublingual abnormalities, the Sublingual Abnormalities Index (SAI). Sublingual frenulum thickness, frenulum length, sublingual buccal mucosa pallor, and the presence of oral telangiectasia were each individually scored using 0- to 2-point Likert scales and a composite score of the 4 domains created by summation of the individual scores. Assessment of the sublingual region of 21 patients with SSc and 8 control subjects was undertaken. An image of the sublingual frenulum was obtained using prespecified camera settings to allow assessment of interrater reliability with 2 independent blinded assessors. Scores for each of the SAI domains differed between control subject and SSc population (P = 0.0003). Patients with SSc had a composite SAI score of 4.3 (SD, 0.37). None of the control subjects had a composite SAI score of more than 2. There was excellent interrater reliability between clinician assessment and each blinded assessor (Cohen κ's of 0.72 and 0.82, respectively). This feasibility study confirms the presence of clinical sublingual abnormalities in SSc, which can be categorized using a simple scoring chart with moderate to near-perfect interrater agreement. The functional significance and pathogenesis of this abnormality warrant further study.

Genetic and epigenetic abnormalities in systemic sclerosis.

Systemic sclerosis (SSc) is a complicated autoimmune and connective tissue disease, of which the pathogenesis and treatment have not been fully elucidated. SSc patients may have a genetic predisposition, such as specific human leukocyte antigens and single nucleotide polymorphisms, but can also develop various clinical symptoms with individual differences. Epigenetics, such as DNA methylation, histone modification, long non-coding RNA and miRNA, could explain the crossroad between genetics and environmental factors. For instance, epigenetics is associated with environmental factors, which may cause the breakdown of immune tolerance and the development of SSc in patients with a particular genetic background. In the future, further investigations of the interplay between genetics and epigenetics will be beneficial to elucidate the complex molecular cross-talk and heterogeneity in the SSc pathogenesis. Furthermore, this research will lead to the discovery of new therapeutic approaches and biomarkers.

T and NK Cell Phenotypic Abnormalities in Systemic Sclerosis: a Cohort Study and a Comprehensive Literature Review.

Scleroderma (SSc) is a rare and heterogeneous immune-mediated disease involving the connective tissue and microvasculature whose pathogenesis remains unclear. Data concerning T and natural killer (NK) cell abnormalities and cytokine levels in the peripheral blood (PB) from patients with SSc are scarce, and the results are contradictory. The present study aimed to analyze the changes of T lymphocytes, NK cells, and T helper (Th)-related cytokines in the PB of patients with SSc in comparison to healthy individuals and its relation to disease subtype and stage, organ involvement, and nailfold capillaroscopic changes. A non-random convenience sample of 57 scleroderma patients was utilized. Fifty-five out of the 57 patients studied were women (97 %); 10 patients presented pre-scleroderma (pre-SSc) and 47 SSc: 34 limited cutaneous SSc (lcSSc) and 13 diffuse cutaneous SSc (dcSSc). Patients with SSc were classified in early (n = 7), intermediate (n = 10), and late (n = 30) disease. Blood samples were analyzed by flow cytometry for total T cells, CD4+ and CD8+ T cell subsets, total NK cells, and CD56+low and CD56+high NK cell subsets. T cells were further analyzed for the expression of the CD56 adhesion molecule and activation-related markers (HLA-DR, CD45RO). In addition, the serum levels of Th1-, Th2-, and Th17-related cytokines were measured by flow cytometry. Twenty-five healthy individuals recruited from the blood bank were used as controls. Patients had lower numbers of total lymphocytes and T cells comparing to healthy controls. Both CD4+ and CD8+ T cells were decreased, but differences were statistically significant only for CD8+ and CD8+ CD45RO+ T cells. These alterations were seen in patients with SSc but not in patients with pre-SSc, and, in general, they were more pronounced in patients with dcSSc than in patients with lcSSc, in patients with vascular involvement than in those without, as well as in patients having active and late nailfold capillaroscopic patterns. CD56+ T cells were also decreased in SSc patients, especially in those with active/late capillaroscopic patterns or with severe lung disease. Diminished numbers of circulating NK cells were also observed in patients with lcSSc and in those with early disease. No statistically significant changes were found in serum cytokine levels, as compared with controls. Patients with SSc had major alterations in circulating CD8+ and CD56+ T cells, as well as in NK cells, suggesting that these cells may play a relevant role in SSc pathogenesis, probably operating at different phases and/or at different organs. In addition, the serum levels of Th1, Th2, and Th17 cytokines did not provide useful information for evaluating T cell polarization in SSc.

Two-Dimensional near Infrared Spectroscopic Imaging of the Hand to Assess Microvascular Abnormalities in Systemic Sclerosis: A Pilot Study

Patients affected by systemic sclerosis (SSc) develop functional and structural microvascular alterations and progressive fibrosis of the skin and internal organs. Evaluation of skin microcirculation is an important clinical step in the workup of SSc patients. Near infrared (NIR) spectroscopy is a well-established non-invasive technique to assess haemoglobin oxygen saturation (StO2) in the illuminated tissue. The recent development of NIR spectroscopic two-dimensional (2D) imaging offers the possibility of visualising StO2 distribution in large tissue areas. This is particularly important in SSc characterised by a very heterogeneous spatial distribution of the microvascular abnormalities. In addition, the short acquisition time of NIR spectroscopic images allows microvascular “dynamic” conditions, such as the vascular response to physical or pharmacological stimuli, to be evaluated. The present study reports the results of the test application of NIR spectroscopic 2D imaging of the palmar whole-hand surface for the evaluation of peripheral microcirculatory dysfunction in one patient with SSc, as compared with a healthy control, both in “static” (resting) and in “dynamic” (ischaemia-reperfusion) conditions. Spatial heterogeneity of microvascular alterations associated with temporal heterogeneity in vascular reactivity to ischaemic challenge make 2D NIR spectroscopic imaging a promising tool in the assessment of SSc, as compared with the current available techniques. A NIR spectroscopic camera by Kent Imaging Inc, Calgary, Canada was used.

Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis

To date, there are no large studies on videocapsule endoscopy in systemic sclerosis (SSc). Consequently, the prevalence and features of gastrointestinal mucosal abnormalities in SSc have not been determined. To determine both prevalence and characteristics of gastrointestinal mucosal abnormalities in unselected patients with SSc, using videocapsule endoscopy. To predict which SSc patients are at risk of developing potentially bleeding gastrointestinal vascular mucosal abnormalities. Videocapsule endoscopy was performed on 50 patients with SSc. Prevalence of gastrointestinal mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were predominant, including: watermelon stomach (34.6%), gastric and/or small intestinal telangiectasia (26.9%) and gastric and/or small intestinal angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P = 0.02), lower levels of ferritin (P < 0.0001) and anti-centromere antibody. Our study identifies a high frequency of gastrointestinal mucosal abnormalities in SSc, with a marked predominance of vascular mucosal damage. Furthermore, our study shows a strong correlation between gastrointestinal vascular mucosal lesions and presence of severe extra-digestive vasculopathy (digital ulcers and higher nailfold videocapillaroscopy scores). This latter supports the theory that SSc-related diffuse vasculopathy is responsible for both cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold videocapillaroscopy may be a helpful test for managing SSc patients. In fact, nailfold videocapillaroscopy score should be calculated routinely, as it may result in identification of SSc patients at higher risk of developing potentially bleeding gastrointestinal vascular mucosal lesions.

AB0613 Clinical and Laboratory Differences between SSC Patients with and without Diastolic Dysfunction

BackgroundLeft ventricular diastolic dysfunction (LVDD) is the most common cardiac abnormality in systemic sclerosis (SSc). It is known that aging is a primary determinant of LVDD in SSc patients and...