Clinical Manifestations Of Systemic Sclerosis Research Articles

Clinical Aspects of Overlap Syndrome - Case Report and Literature Review

We report a patient with overlap syndrome (systemic sclerosis (SSc) and polymyositis (PM)). The heterogeneous nature of systemic sclerosis may lead to a great diversity in the clinical presentation of the disease. With this case report we aim to demonstrate clinical manifestations of systemic sclerosis and polymyositis in an overlap-syndrome, with support from antibody profile and laboratory data.

Environmental Pollution by Benzene and PM10 and Clinical Manifestations of Systemic Sclerosis: A Correlation Study.

Atmospheric air pollution has been associated with a range of adverse health effects. The environment plays a causative role in the development of Systemic Sclerosis (SSc). The aim of the present study is to explore the association between particulate (PM10) and benzene (B) exposure in Italian patients with systemic sclerosis and their clinical characteristics of the disease. A correlation study was conducted by enrolling 88 patients who suffer from SSc at the Fondazione Policlinico “A. Gemelli” in Rome (Italy) in the period from January 2013 to January 2014. The average mean concentrations of B (in 11 monitoring sites) and PM10 (in 14 sites) were calculated using data from the Regional Environmental Protection Agency’s monitoring stations located throughout the Lazio region (Italy) and then correlated with the clinical characteristics of the SSc patients. Of the study sample, 92.5% were female. The mean age was 55 ± 12.9 years old and the mean disease duration from the onset of Raynaud’s phenomenon was 13.0 ± 9.4 years. The Spearman’s correlation showed that concentrations of B correlate directly with the skin score (R = 0.3; p ≤ 0.05) and inversely with Diffusing Lung Carbon Monoxide (DLCO) results (R = −0.36; p = 0.04). This study suggests a possible role of B in the development of diffuse skin disease and in a worse progression of the lung manifestations of SSc.

CD16-positive circulating monocytes and fibrotic manifestations of systemic sclerosis.

The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p<0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p<0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071Giga/L (±0.034) vs HD 0.039Giga/L (±0.030), p<0.01, and dSSc 0.071Giga/L (±0.034) vs lSSc 0.048Giga/L (±0.024), p<0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p<0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p<0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p<0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p<0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.

Association between Clinical Manifestations of Systemic Sclerosis and Esophageal Dysmotility Assessed by High-Resolution Manometry

Purpose To characterize esophageal involvement according to high-resolution manometry (HRM) findings using the 3rd version of the Chicago Classification, in a French population of patients fulfilling the ACR/EULAR 2013 classification criteria for systemic sclerosis (SSc). Methods Thirty-six patients were consecutively included in this cross-sectional non-interventional study and had HRM performed in Rennes University hospital. Demographic and clinical characteristics, SSc history and interstitial lung disease (ILD) on CT-scan were assessed, and compared with esophageal motility. Results Sixty-one percent of SSc patients had ineffective peristalsis (55.6% failed peristalsis and 5.6% weak peristalsis), 33.3% had hypotensive esophagogastric junction pressure, 75% did not have a physiologic contraction following multiple rapid swallow (MRS), and 44.4% had an abnormal peristaltic reserve. One patient had type 1 achalasia and another one had Jackhammer esophagus. Failed peristalsis was associated with pyrosis (odds ratio [OR] 7.28, 95% confidence interval [CI] 1.51-35.21, p = 0.009), a higher modified Rodnan skin score (MRSS) (without failed peristalsis: 4.68 ± 2.95 vs. with failed peristalsis: 10.68 ± 9.23; p&lt;0.05), the presence of telangiectasia (OR 7, 95% CI 1.59-30.8, p = 0.007), and low diffusing capacity of the lung for carbon monoxide (DLCO) (p = 0.013). Food in the esophagus and esophageal dilation on CT-scan were associated with failed contractions on HRM (respectively, OR 6.85, 95% CI 1.12-40.82, p = 0.05, and OR 14.67, CI 2.4-88.5, p = 0.002). Conclusions This study confirms that failed peristalsis is frequent in SSc and associated with other organ involvement. We found a concordance between HRM results and CT-scan findings regarding esophageal involvement.

Ethnic Differences in Autoantibody Diversity and Hierarchy: More Clues from a US Cohort of Patients with Systemic Sclerosis.

To determine the autoantibody repertoire and clinical associations in a multiethnic cohort of American patients with systemic sclerosis (SSc). There were 1000 patients with SSc (196 Hispanic, 228 African American, 555 white, and 21 other) who were screened for antinuclear antibodies (ANA), including anticentromere antibodies (ACA) by indirect immunofluorescence assay, antitopoisomerase-1 (topo-1/Scl-70) by immunodiffusion, and anti-RNA polymerase III (RNAP III) by ELISA. Sera from 160 patients with mainly nucleolar and/or speckled ANA pattern, but negative for ACA, Scl-70, and RNAP III, were further characterized by immunoprecipitation for SSc-specific antibodies. The prevalence of antibodies against RNAP III, Th/To, and PM/Scl did not differ significantly among the ethnic groups. The frequency of anti-Scl-70 was lowest in whites (18.0%) compared with 24.0% and 26.8% in Hispanics and African Americans (p = 0.01), respectively. Compared with African American patients, Hispanic and white subjects had a higher frequency of ACA (p < 0.0001) and lower frequency of U3-RNP (p < 0.0001). U3-RNP antibodies were uniquely higher in African American patients, independent of clinical subset, while Th/To autoantibodies were associated with limited cutaneous SSc in white subjects. Overall, Hispanic and African American patients had an earlier age of onset and a predominance of diffuse cutaneous SSc compared with their white counterparts. SSc-specific antibodies may predict disease subset; however, the hierarchy of their prevalence differs across ethnic groups. This study provides the most extensive analysis to date on the relevance of autoantibodies in the diagnosis and clinical manifestations of SSc in Hispanic American patients.

Scleroderma overlap syndrome with interstitial lung disease and pulmonary artery hypertension

Abstract Scleroderma overlap syndrome is a rare condition that presents as two or more connective tissue disorders in the same patient. Some of these connective tissue diseases are associated with a specific autoantibody profile, while others do not show any serological association. We report a case of a patient with scleroderma overlap syndrome who presented with fever, breathlessness, pulmonary fibrosis, pulmonary hypertension, interstitial lung disease, anaemia and clinical manifestations of systemic sclerosis and rheumatoid arthritis. The patient's laboratory results were strongly positive for antinuclear antibody (ANA) and anti-topoisomerase-1 antibody and seropositive for rheumatic fever and CCP antibodies.

Olfactory impairment in patients with the fibromyalgia syndrome and systemic sclerosis.

Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of female patients with fibromyalgia (FM) compared with patients with systemic sclerosis (SSc) and with healthy female controls. Olfactory functions were assessed in 24 patients with FM, 20 patients with SSc and 21 age-matched healthy controls. The sense of smell was evaluated using the Sniffin' Sticks test including the three stages of smell: threshold, discrimination, and identification (TDI) of the different odors. The severity of fibromyalgia was assessed using the fibromyalgia impact questionnaire (FIQ). The short form 36 (SF-36) questionnaire was also completed in order to seek a relationship between the patients perception of quality of life and the different aspects of the smell sense. Depression was evaluated in both FM and SSc patients utilizing the Beck depression inventory-II (BDI-II) questionnaire. Patients with FM had significantly lower TDI smell scores compared with both SSc patients and healthy controls (p < 0.005, One-Way ANOVA). Hyposmia (defined as TDI scores below 30) were observed in 14 of 24 (42 %) patients with FM compared to 3 of 20 (15 %) patients with SSc and 1 of the healthy controls (4.3 %) (p < 0.02). FM patients had significantly lower thresholds of smell compared to both healthy controls and patients with SSc (p < 0.001), whereas for patients with SSc only the ability to discriminate between odors was impaired (p < 0.006). We could not detect any statistical correlation between smell abilities and clinical manifestation of SSc or the FIQ and SF-36 scores among FM patients. However the correlation between depression, defined by the BDI-II score, and the sense of smell differed between patients with FM and patients with SSc. As only among SSc patients a lower sense of smell correlated with a higher BDI-II score (p = 0.02). Our findings suggest that there is a decrease in the sense of smell both in FM and SSc patients compared with healthy controls. However these impairments differ between patients group and might represent different mechanisms that affect the sense of smell.

AB0201 Cell Surface Expression of DNAM-1 (CD226) on CD8+ T Cells is Increased in Patients with Systemic Sclerosis

BackgroundDNAM-1 (CD226) is well known as a genetic risk factor of many autoimmune diseases such as systemic sclerosis (SSc). More recently, Avouac et al. have reported that mice deficient for...

Environmental pollution and systemic sclerosis manifestations: a pilot study on benzene and particulate exposure

Many works have studied interactions between genetic and autoimmunity but only a few have studied the interactions between autoimmune diseases, such as systemic sclerosis (SSc), and exposure to environmental pollutants, reporting no conclusive. Results This study aims to analyze the relationships between outdoor concentration of benzene (B) and particulate matter ≤ 10 μm (PM10) with clinical manifestations of SSc in a big Italian city. A pilot cohort study of …

SP0045 The Prognostic Value of the Capillaroscopic Analysis

Structural capillary changes in systemic sclerosis (SSc) may be easily investigated and quantified by nailfold videocapillaroscopy (NVC), and in recent years there have been identified disease-specific progressive capillary abnormalities and...

THU0548 Hand Function in Systemic Sclerosis: A Clinical and Ultrasonographic Study

BackgroundHand involvement is one of the earliest clinical manifestations of systemic sclerosis (SSc) that results in major functional compromise. Several factors may be responsible including skin and periarticular thickening, arthralgias...

SP0154 The Prognostic Value of the Capillaroscopic Analysis

Structural capillary changes in systemic sclerosis (SSc) may be easily investigated and quantified by nailfold videocapillaroscopy (NVC), and in recent years there have been identified disease-specific progressive capillary abnormalities and...

New Centromere Autoantigens Identified in Systemic Sclerosis Using Centromere Protein Microarrays

To identify novel centromere protein (CENP) targets of anticentromere antibodies (ACA), and to investigate their association with clinical manifestations of systemic sclerosis (SSc). A CENP-focused protein microarray was fabricated by spotting 14 purified CENP. These microarrays were individually incubated with 35 ACA-positive SSc sera and 20 ACA-negative healthy control samples. Newly identified CENP autoantigens with high sensitivities were selected for validation and characterization. Statistical analysis revealed 11 CENP are potential target antigens of ACA in patients with SSc. Of them, 5 [CENP-P, CENP-Q, CENP-M (isoform I), CENP-J, and CENP-T] are novel, among which CENP-P and CENP-Q showed high sensitivities in ACA-positive SSc sera of 34.3% and 28.6%, respectively. Subsequently, 186 SSc sera (35 ACA-positives and 151 negatives), 69 ACA-positive sera from other various autoimmune diseases (primary Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis), and 31 healthy sera were assayed for the presence of anti-CENP-P and -Q autoantibodies by ELISA followed by Western blotting analysis. CENP-P and -Q autoantibodies were detected in ACA-positive sera of various disease groups; among them, SSc showed the highest detection rate. Anti-CENP-P was also found in 9 of the 151 ACA-negative sera. Analyses of the correlation with clinical information showed anti-CENP-P-positive patients had higher levels of IgG, IgA, and erythrocyte sedimentation rate among the ACA-positive cohort and were more vulnerable to renal disease in the ACA-negative patients with SSc. Regardless of ACA status, anti-CENP-P or Q-negative patients seem to be predominantly affected by interstitial lung disease. CENP-P and CENP-Q were identified as novel ACA autoantigens by CENP microarray assays followed by validation of ELISA and Western blotting. Both of them have prognostic utility for interstitial lung disease. CENP-P was associated with renal disease in an ACA-negative cohort.

Incidence, Prevalence and Clinical Manifestations of Systemic Sclerosis in Dukagjini Plain

Introduction:Progressive systemic sclerosis (PSS) is an inflammatory disease of connective tissue, with onset as edema that continues with fibrosis, induration, and skin atrophy, followed by attacks on the joints, internal organs, and secondary proliferation of connective tissue.Purpose:To research in which residence locations and among which group age is the most frequent incidence, prevalence and clinical manifestations of systemic sclerosis in Dukagjini Plain which is inhabited by 698450 resident citizens.Material and methods:51 patients with progressive systemic sclerosis were studied, out them 44 were females (86.3%) and 7 males (13.7%) respectively, during the period from 2005 to 2010. Their illness was active from 18 to 60 months in accordance with EUSTAR criteria. They are of different age, median age is 44.2 ±10.1. Their diagnose is determined based on revised ACR criteria. Prevalence of patients with PSS was 14.61/100.000, while the incidence was 2.8/100.000, whereas CI (Confidence interval) or limit of accuracy was 95%.Results:Largest number of patients per 100.000 citizens has Istog municipality which has the largest number of patients with PSS. It is followed by Mamusha and Rahovec municipalities. The largest examined group age is 35-44 year old, 41.2% respectively.Conclusion:Additional studies are necessary to carry out in order to find the reasons of asymmetrical distribution of patients with systemic sclerosis in the municipalities of Dukagjini Plain.

Concomitância de autoanticorpos na esclerose sistêmica: como interpretar?

Autoantibodies possibly influence clinical manifestations of systemic sclerosis (SSc). This clinical-serological correlation, associated with the paucity of autoantibodies concomitance, gave rise to the historical paradigm of autoantibodies mutual exclusivity. However, one can question this assumption. Does autoantibodies concomitance mean coexistence of two different entities? On the other hand, if considered a unique disease, is this phenomenon a random event or does it represent a distinct subgroup of patients, with peculiar clinical, pathogenic, and immunogenetic characteristics? The autoantibodies' prevalence in early SSc is high. However, anti-centromere antibody (ACA) and antitopoisomerase 1 antibody (ATA) duplicity is a rare event. Similarly, the ACA, ATA, and anti-RNA polymerase (anti-RNA-P) III coexistence have not been described yet in single patient. In the reported case, with ACA, ATA, and anti-RNA-P III positivity, we have noted early vascular manifestations and late limited cutaneous involvement. This is, to our knowledge, the first report of three concomitant specific autoantibodies in a patient with SSc. We do believe this coexistence represents a rare serologic subgroup of a unique disease, with possible clinical and prognostic value, although this remains to be confirmed.

Timing of transition between capillaroscopic patterns in systemic sclerosis

To investigate the timing of transition through different patterns of nailfold microvascular damage in patients with systemic sclerosis (SSc). In this medium-term longitudinal study, 38 SSc patients (median disease duration 12 months) with the early scleroderma pattern of microangiopathy seen on baseline nailfold videocapillaroscopy (NVC) were followed up by NVC for a median of 84 months. The evolution of the NVC pattern over time was monitored and recorded. At the end of followup, the NVC pattern was still that of early scleroderma in 47% of the patients. The active scleroderma pattern was seen in 34%, the late scleroderma pattern in 13%, and a normal pattern in 5%. The mean± SD time of progression from the early to the active pattern and from the early to the late pattern was of 28 ± 20 months and 36± 29 months, respectively. In the subgroup of patients whose microangiopathy progressed from the early to the late NVC pattern, the time of progression from the early to the active pattern was only 8± 1 months (P = 0.01), demonstrating that there is a subset of patients with rapid progression of microangiopathy. Clinical symptoms progressed in accordance with the nailfold morphologic changes in 60% of the SSc patients. The results of this longitudinal study demonstrate dynamic transition of microvascular damage through different NVC patterns of microangiopathy in ∼50% of SSc patients. It is recommended that patients exhibiting rapid progression from the early to the active NVC pattern (<1 year) should be monitored closely, since the evidence suggests that they are at risk of rapid progression to the advanced (late) NVC pattern of microangiopathy that is associated with further clinical manifestations of SSc.

Serum Elastin-Derived Peptides and Anti-Elastin Antibody in Patients with Systemic Sclerosis

The elastin metabolism in systemic sclerosis (SSc) has been known to be abnormal. The authors investigated relationship between the clinical manifestations of systemic sclerosis (SSc) and serum levels of soluble elastin-derived peptide (S-EDP) and anti-elastin antibodies. Serum samples were obtained from 79 patients with SSc and 79 age- and sex-matched healthy controls. Concentrations of serum S-EDP and anti-elastin antibodies were measured by ELISA. The serum concentrations of S-EDP in SSc patients were significantly higher than in healthy controls (median, 144.44 ng/mL vs 79.59 ng/mL, P < 0.001). Serum EDP concentrations were found to be correlated with disease duration in SSc (P = 0.002) and particularly in diffuse cutaneous SSc (P = 0.005). Levels of anti-elastin antibodies were found to be more elevated in SSc patients than in healthy controls (median, 0.222 U vs 0.191 U, P = 0.049), more increased in diffuse cutaneous SSc than limited cutaneous SSc (median, 0.368 U vs 0.204 U, P = 0.031). In addition, levels of anti-elastin antibodies were also found to be negatively associated with presence of anti-centromere antibody (P = 0.023). The S-EDP levels were not found to be correlated with levels of anti-elastin antibodies. The increased S-EDP and anti-elastin antibody levels and association with clinical and laboratory characteristics may reflect the abnormal metabolism in SSc.

The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis

Regulatory T cells (T(regs)) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor α (IL2RA) is an important T(reg) marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P(FDR)=2.07 × 10(-4), odds ratio=1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc.

Spontaneous skin regression and predictors of skin regression in Thai scleroderma patients

Skin tightness is a major clinical manifestation of systemic sclerosis (SSc). Importantly for both clinicians and patients, spontaneous regression of the fibrosis process has been documented. The purpose of this study is to identify the incidence and related clinical characteristics of spontaneous regression among Thai SSc patients. A historical cohort with 4 years of follow-up was performed among SSc patients over 15 years of age diagnosed with SSc between January 1, 2005 and December 31, 2006 in Khon Kaen, Thailand. The start date was the date of the first symptom and the end date was the date of the skin score ≤2. To estimate the respective probability of regression and to assess the associated factors, the Kaplan-Meier method and Cox regression analysis was used. One hundred seventeen cases of SSc were included with a female to male ratio of 1.5:1. Thirteen patients (11.1%) experienced regression. The incidence rate of spontaneous skin regression was 0.31 per 100 person-months and the average duration of SSc at the time of regression was 35.9±15.6 months (range, 15.7-60 months). The factors that negatively correlated with regression were (a) diffuse cutaneous type, (b) Raynaud's phenomenon, (c) esophageal dysmotility, and (d) colchicine treatment at onset with a respective hazard ratio (HR) of 0.19, 0.19, 0.26, and 0.20. By contrast, the factor that positively correlated with regression was active alveolitis with cyclophosphamide therapy at onset with an HR of 4.23 (95% CI, 1.23-14.10). After regression analysis, only Raynaud's phenomenon at onset and diffuse cutaneous type had a significantly negative correlation to regression. A spontaneous regression of the skin fibrosis process was not uncommon among Thai SSc patients. The factors suggesting a poor predictor for cutaneous manifestation were Raynaud's phenomenon, diffuse cutaneous type while early cyclophosphamide therapy might be related to a better skin outcome.

Aging and Scleroderma

Although rare in the general population, geriatricians and general practitioners should be aware of the clinical manifestations of systemic sclerosis (SSc) as it can present at an older age and may have unique patterns of organ involvement. Furthermore, recent important advances in treatment have improved survival among SSc patients resulting in a distinct population aging with SSc. Symptoms of SSc overlap frequently with those of the aging population (such as gastroesophageal reflux disease and cold sensitivity), however, specific features, such as the new onset of Raynaud phenomenon or the new onset of swelling of the hands and feet, should prompt an evaluation for SSc. Elderly-onset SSc patients may have higher rates of specific organ manifestations (such as pulmonary hypertension) but can present with the whole spectrum of SSc. The diagnosis and care of elderly patients with SSc present unique and challenging issues best approached by a multidisciplinary team focusing on each SSc-specific organ system.