Clinical features and prognostic factors of systemic sclerosis in Guangxi, China: Retrospective, single-center study of long-term survival in 470 patients.

OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease the prevalence of which varies among populations. We analyzed SSc patients from Guangxi to improve the clinical understanding of this disease. METHODS: Data of 470 SSc patients admitted to our institution from October 1,2012 to January 1,2019 were examined. The characteristics of these patients were analyzed using Kaplan-Meier survival analysis. Cox proportional-hazard regression was used to identify prognostic factors. RESULTS: The average age was 50.44 ± 12.31 years, 285 patients (60.6%) were women, 2.1% had pneumoconiosis, 58.2% had pulmonary interstitial disease (ILD), 18.7% had pulmonary hypertension (PH), and 3.6% had renal crisis. These patients had diffuse cutaneous systemic sclerosis (dcSSc, 70.2%) or limited cutaneous systemic sclerosis (29.7%), and PH and renal crisis were more common in the dcSSc group. Patients 50 years old or more had greater prevalences of ILD, PH, and musculoskeletal damage, greater positivity of laboratory biomarkers, and increased mortality (all P < .05). Seventy-four patients (15.7%) died. The non-survivors were older, had longer disease duration, had higher prevalences of ILD, restrictive ventilation dysfunction, PH, and renal crisis, and had higher levels of creatine kinase myocardial band (CK-MB), C-reactive protein, and immunoglobin A (all P < .05). Renal crisis, PH, and high CK-MB were independent risk factors for death. CONCLUSIONS: Pneumoconiosis was more common in SSc patients than the general population from this region. Our patients had a 10-year cumulative survival rate of 74.9%, higher than reported for patients from the US. Renal crisis, PH, and high CK-MB level were independent risk factors for death.

Cancer in Systemic Sclerosis: Analysis of Antibodies Against Components of the Th/To Complex.

OBJECTIVE: The aim of this study is to describe 4 of the most common autoantibodies against components of the Th/To complex: human POP1 (hPOP1), RPP25, RPP30, and RPP40. We report their prevalence and clinical characteristics in a systemic sclerosis (SSc) population, and determine whether these specificities are associated with cancer. METHODS: A case-control study was performed using data from the Johns Hopkins Scleroderma Center Cohort. A total of 804 adult patients with SSc were included; 401 SSc patients with no history of cancer after at least 5 years of disease were compared to 403 SSc patients who ever had a history of cancer. Antibodies against hPOP1, RPP25, RPP30, and RPP40 were assayed by immunoprecipitation of 35 S-methionine-labeled proteins generated by in vitro transcription/translation. Demographic and clinical characteristics were compared between groups. RESULTS: Of 804 patients, 67 (8.3%) had antibodies against any component of the Th/To complex. Patients with antibodies to any component were significantly more likely to have limited cutaneous disease, less likely to have tendon friction rubs, and more likely to have findings consistent with interstitial lung disease or pulmonary hypertension. Patients with antibodies against hPOP1, RPP25, RPP30, and/or RPP40 were significantly less likely to develop cancer within 2 years of SSc onset (0% versus 11% of antibody-negative patients; P = 0.009). CONCLUSION: SSc patients who produce autoantibodies to components of the Th/To complex have a clinical phenotype characterized by limited cutaneous disease and pulmonary involvement. Our findings show that the presence of any Th/To autoantibody may have a protective effect against contemporaneous cancer.

State-of-the-art technologies provide new insights linking skin and blood vessel abnormalities in SSc-related disorders.

OBJECTIVE: A key unanswered question in systemic sclerosis (SSc) is how microvascular abnormality and fibrosis inter-relate. Our aim was to use state-of-the-art non-invasive imaging methods to gain new insights into pathophysiology, comparing patients with different subtypes of SSc, including early dcSSc, not only to healthy controls but also to patients with causes of Raynaud's phenomenon not progressing to fibrosis. METHODS: Laser Doppler imaging, nailfold capillaroscopy, spectroscopy, and ultrasound measured (respectively) perfusion, microvascular structure, oxygenation/oxidative stress, and skin thickening in the hands of 265 subjects: 31 patients with primary Raynaud's phenomenon (PRP), 35 with undifferentiated connective tissue disease (UCTD), 93 with limited cutaneous SSc (lcSSc), 46 with diffuse cutaneous SSc (dcSSc, including 27 'early') and 60 healthy controls. RESULTS: Mean perfusion was reduced in SSc groups compared to controls (lcSSc 172 perfusion units [standard deviation 157], late-dcSSc 90 [145], early-dcSSc 68 [137] vs. controls 211 [146]; p = 0.0002) as was finger-oxygenation (lcSSc 12.1 [13.6] arbitrary units [AU], late-dcSSc 12.2 [8.4], early-dcSSc 11.1 [11.3] vs controls 14.9 [10.5]; p = 0.0049). Oxidative stress was increased at the hand-dorsum in SSc groups (p = 0.0007). Perfusion positively correlated with oxygenation (r = 0.23, p < 0.001), and capillary density negatively with skin thickness (r = -0.26, p < 0.001). CONCLUSION: Our findings lend support to the hypothesis that in SSc, particularly early dcSSc, (but not in PRP or UCTD), reduced perfusion (together with structural microvascular abnormality) associates with reduced oxygenation, with oxidative stress and with skin thickening/fibrosis, most likely driving a vicious cycle which ultimately results in irreversible tissue injury. Findings in skin may mirror alterations in internal organs.

Exploring the feasibility of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis.

OBJECTIVES: It is suggested that exercise can improve the vascular function and quality of life (QoL) in people with systemic sclerosis (SSc), potentially offering clinical benefits to this population. Yet the feasibility of such an intervention remains untested. Therefore, the purpose of this study is to examine the feasibility of a combined exercise protocol (aerobic and resistance training) in people with limited cutaneous SSc (lcSSc). METHODS: Thirty-two lcSSc patients (66.5 ± 12 years old) were randomly allocated in two groups (exercise and control group). The exercise group underwent a 12-week exercise programme, twice per week. All patients performed the baseline, three- and six-month follow-up measurements where functional ability, body composition and QoL were assessed. Participants' experiences were explored through interviews. RESULTS: Compliance was 92.6% with no dropouts. The individuals' confidence to participate in the study's exercise protocol for twice per week was 95%. The average value for the physical activity enjoyment scale was 103 ± 10 out of 119 (highest score). The mean values for the intention to engage in exercise twice per week were 6.4 ± 1 (likely) out of 7 (very likely). QoL for the exercise group showed to have a better life satisfaction, less anxiety and Raynaud's phenomenon-accompanied pain. CONCLUSIONS: Our results suggest that a combined exercise protocol was feasible for people with lcSSc, with no adverse events, resulting in high adherence and low attrition rates, high enjoyment levels and intentions for future engagement to this exercise. Thus, the specific protocol is a safe adjunct therapy for people with lcSSc. TRIAL REGISTRATION: ClinicalTrials.gov (NCT number): NCT03058887, February 23, 2017, https://clinicaltrials.gov/ct2/show/NCT03058887?term=NCT03058887&rank=1Key Points• High-intensity interval training in combination with resistance training constitutes a feasible exercise protocol for people with lcSSc.• Overall, the exercise programme demonstrated high adherence and enjoyment levels and low attrition rates.• The exercise protocol was proved to be safe with no adverse events for people with lcSSc.

Impact and associates of digital pitting in patients with systemic sclerosis: a pilot study.

Objective: Despite being a cardinal clinical sign of systemic sclerosis (SSc), digital pitting has been little studied. Our objective was to test, in a pilot study, the hypothesis that pitting is painful and associated with digital vascular disease severity.Method: Fifty patients with SSc were recruited: 25 with and 25 without digital pitting. Fingertip pain was assessed on a 0-10 scale. Thermography of both hands assessed surface temperature, allowing calculation of the distal-dorsal difference (temperature gradient) for each finger. Nailfold capillaroscopy was performed in each finger using a dermatoscope, and graded on a 0-3 scale (0 = normal; 3 = grossly abnormal).Results: In the 25 patients with digital pitting, 65 fingers in total were affected (mainly the index and middle fingers). Pain scores were higher in 'pitting' patients [median 4 (interquartile range 3-8) vs 0 (0-2), p < 0.001], and pitting patients reported that pitting impacted on activities of everyday living. Temperature gradients along the fingers did not differ significantly between patients with and without pitting (p = 0.248). Pitting patients were more likely to have 'grossly abnormal' capillaries than those without pitting, and less likely to have 'no/mild' nailfold capillary changes.Conclusions: Digital pitting is painful and impacts on hand function. Capillaroscopy findings provide further support for an association between pitting and severity of digital vascular change. Larger, more comprehensive studies are required to examine the pathophysiology of pitting and to pave the way to therapeutic intervention, ideally including preventive strategies.

Colonic Manifestations and Complications Are Relatively Under-Reported in Systemic Sclerosis: A Systematic Review.

OBJECTIVES: Although systemic sclerosis (SSc) is known to affect the gastrointestinal (GI) tract, most of the literature focuses on esophageal, small intestinal, or anorectal manifestations. There have been no reviews focused on large bowel SSc complications in over 30 years. The aim of this study is to perform a systematic review of colonic manifestations and complications of SSc. METHODS: An experienced librarian conducted a search of databases, including English and Spanish articles. The search used keywords including "systemic sclerosis," "scleroderma," and "colon." A systematic review was performed using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Case reports/series were screened for validity by adapting from criteria published elsewhere. RESULTS: Of 1,890 articles, 74 met selection criteria. Fifty-nine of the 77 articles were case reports/series. The most common article topics on colonic SSc complications were constipation/dysmotility (15), colonic volvulus (8), inflammatory bowel disease (7), microscopic colitis (6), megacolon (6), and telangiectasia (6). Colonic manifestations constituted 24% of articles on GI complications of SSc. There were a total of 85 cases (84% women, with a median age of onset of colon complication of 52 years). Limited cutaneous SSc phenotype (65.6%) was more common than diffuse (26.2%). Patients frequently had poor outcomes with high mortality related to colonic complications (27%). Recent studies explore contemporary topics such as the microbiome in SSc and prucalopride for chronic constipation in SSc. DISCUSSION: Colonic complications comprise a large proportion of the published reports on GI symptoms afflicting patients with SSc and require raised diagnostic suspicion and deliberate action to avoid potentially serious complications including death.

Individuals With Scleroderma May Have Increased Risk of Sleep-Disordered Breathing.

STUDY OBJECTIVES: Scleroderma is associated with abnormal skin thickening, interstitial lung disease, pulmonary hypertension, and abnormalities of the upper airway. These changes can cause cardiopulmonary complications, potentially including sleep-disordered breathing. The objective of this study is to examine the risk of sleep-disordered breathing in patients with scleroderma. METHODS: We retrospectively identified patients with documented scleroderma. We abstracted data from their electronic health records, including findings from antibody tests, serial pulmonary function tests, transthoracic echocardiography, high-resolution computed tomography, and overnight forehead oximetry. RESULTS: We identified 171 patients with scleroderma. Mean age at the time of initial consult was 56.5 years (range, 18-96 years), and 150 (86.7%) were women. Scleroderma was categorized as limited disease for 108 (62.4%), diffuse disease for 59 (34.1%), and mixed connective tissue disease for 6 (3.5%). Fifty-four patients (31.2%) had abnormal overnight forehead oximetry results, defined as an oxygen desaturation index greater than 5 or a baseline mean arterial oxygen saturation level less than 90%. CONCLUSIONS: Cardiopulmonary complications are common in patients with scleroderma, one of which may be sleep-disordered breathing. In our cohort, approximately one-third of individuals with scleroderma had evidence of sleep-disordered breathing. Moreover, the rate of sleep-disordered breathing in our population of scleroderma patients was twice the rate of pulmonary hypertension and was approximately the same as the rate of interstitial lung disease. Future prospective studies are needed to further assess the role of sleep-disordered breathing in scleroderma clinical outcomes.

Exploring the microcirculatory effects of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis.

PURPOSE OF THE STUDY: High intensity interval training (HIIT) is able to improve the endothelial-dependent microvascular function is people with limited cutaneous systemic sclerosis (lcSSc). Resistance training (RT) alone has shown significant improvements in the function of the vasculature; moreover, a combination of aerobic and RT have shown both in the past and recently to significantly improve the vascular function and the microcirculation. Therefore, the purpose of this study is to explore the effectiveness of a combined exercise protocol (aerobic and resistance training) on microvascular function in people with lcSSc. METHODS: Thirty-two lcSSc patients (66.5 ±â€¯12 years old) were randomly allocated in two groups (exercise and control group). The exercise group underwent a 12-week exercise programme twice per week. All patients performed the baseline, three- and six-month follow up measurements where microvascular function, transcutaneous oxygen tension (ΔTcpO2) and body composition were assessed. RESULTS: The time to peak endothelial-dependent reactivity was significantly improved (91 ±â€¯42 s, d = 1.06, p = 0.007) when compared to control group after the exercise intervention. Endothelial-independent function was also significantly improved (3.16 ±â€¯2, d = 1.17, p = 0.005) when compared to the control group. Baseline (5.71 ±â€¯4.4, p < 0.05)) and peak (15.4 ±â€¯7.5, p < 0.05) transcutaneous oxygen pressure were also significantly improved compared to the control group. CONCLUSIONS: Our results suggest that a combined exercise protocol (aerobic and RT) was effective in improving endothelial-dependent reactivity in people with lcSSc. The next step would be to explore its clinical- and cost- effectiveness. Therefore, we recommend a large, community-based intervention against standard pharmacotherapy only, which would assess these important factors and support a change in therapeutic protocols and guidelines for this clinical population. Trial registration ClinicalTrials.gov (NCT number): NCT03058887, February 23, 2017, https://clinicaltrials.gov/ct2/show/NCT03058887?term=NCT03058887&rank=1.

The evaluation of a home-based program for hands in patients with systemic sclerosis.

STUDY DESIGN: This study used a quasi-experimental design where patients were evaluated before and after participation in the self-management program. INTRODUCTION: Hands are commonly affected in systemic sclerosis (SSc). Strategies to maintain or improve hand function are indicated upon diagnosis and throughout the course of the disease. PURPOSE OF THE STUDY: The purpose of this study was to develop and evaluate a home-based program for hands in patients with SSc. METHODS: A home-based self-management program that consisted of concise instructions about SSc and hand exercises was developed and evaluated in a group of patients with SSc during 8 weeks. Primary outcome measures were hand pain (Visual Analogue Scale) and hand function (Cochin Hand Function Scale). Secondary outcome measures were disability (Scleroderma Health Assessment Questionnaire), finger motion (delta finger-to-palm), grip strength, tip and key pinch strength, Raynaud phenomenon and digital ulcers impact, quality of life (Short Form Health Survey). For comparisons between different times analysis of variance for repeated measures was used. To calculate the effect size (ES), the Cohen's test was performed. To evaluate skin moisturizing and warming habits before and after intervention, the McNemar test was used. Statistical significance was set at P ≤ .05. RESULTS: Twenty-two SSc patients (19 women: 3 men; 16 limited scleroderma: 6 diffuse scleroderma) completed the program. Significant improvements were noted for hand pain (3.97 vs 2.21, ES: 0.69), Cochin Hand Function Scale (19.24 vs 12.48, ES: 0.48), Scleroderma Health Assessment Questionnaire (0.95 vs 0.48, ES: 1.01), delta finger-to-palm (92.86 vs 106.33, ES: 0.40), grip strength (14.43 vs 19, ES: 0.58), tip pinch strength (2.49 vs 4.18, ES: 1.15), key pinch strength (4.01 vs 5.22, ES: 0.76), Raynaud phenomenon impact (0.94 vs 0.47, ES: 0.75), Short Form Health Survey-role physical (47.38 vs 60.14, ES: 0.61), physical functioning (34.62 vs 61.9, ES: 0.18), social functioning (60.71 vs 75.6, ES: 0.64), bodily pain (50.55 vs 63.38, ES: 0.58), vitality (45.95 vs 62, ES: 2.22), mental health (56.62 vs 72.38, ES: 0.84) moisturizing, and cold avoidance habits. Patients considered the program easy to follow with no adverse effects related to exercises. DISCUSSION: We developed a home based hand care program to be offered to SSc patients. Improvements in hand function, strength, disability, motion, and overall quality of life were independent of age, income, education level, disease duration, and skin score. Our findings support those of other studies that reported the benefits of hand exercises in SSc. Some study limitations include the lack of a control group, the small number of subjects and the short-time follow up. CONCLUSIONS: This home-based program for patients with SSc improved hand pain, function, mobility, and strength at the end of 8 weeks. Patient adherence and sustained efficacy is still to be determined.

The effects of upper and lower limb exercise on the microvascular reactivity in limited cutaneous systemic sclerosis patients.

BACKGROUND: Aerobic exercise in general and high-intensity interval training (HIIT) specifically is known to improve vascular function in a range of clinical conditions. HIIT in particular has demonstrated improvements in clinical outcomes, in conditions that have a strong macroangiopathic component. Nevertheless, the effect of HIIT on microcirculation in systemic sclerosis (SSc) patients is yet to be investigated. Therefore, the purpose of the study was to compare the effects of two HIIT protocols (cycle and arm cranking) on the microcirculation of the digital area in SSc patients. METHODS: Thirty-four limited cutaneous SSc patients (65.3 ± 11.6 years old) were randomly allocated in three groups (cycling, arm cranking and control group). The exercise groups underwent a 12- week exercise program twice per week. All patients performed the baseline and post-exercise intervention measurements where physical fitness, functional ability, transcutaneous oxygen tension (ΔTcpO2), body composition and quality of life were assessed. Endothelial-dependent as well as -independent vasodilation were assessed in the middle and index fingers using LDF and incremental doses of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous flux data were expressed as cutaneous vascular conductance (CVC). RESULTS: Peak oxygen uptake increased in both exercise groups (p < 0.01, d = 1.36). ΔTcpO2 demonstrated an increase in the arm-cranking group only, with a large effect, but not found statistically significant,(p = 0.59, d = 0.93). Endothelial-dependent vasodilation improvement was greater in the arm-cranking (p < 0.05, d = 1.07) in comparison to other groups. Both exercise groups improved life satisfaction (p < 0.001) as well as reduced discomfort and pain due to Raynaud's phenomenon (p < 0.05). Arm cranking seems to be the preferred mode of exercise for study participants as compared to cycling (p < 0.05). No changes were observed in the body composition or the functional ability in both exercise groups. CONCLUSIONS: Our results suggest that arm cranking has the potential to improve the microvascular endothelial function in SSc patients. Also notably, our recommended training dose (e.g., a 12-week HIIT program, twice per week), appeared to be sufficient and tolerable for this population. Future research should focus on exploring the feasibility of a combined exercise such as aerobic and resistance training by assessing individual's experience and the quality of life in SSc patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT number): NCT03058887 , February 23, 2017.

Prediction of organ involvement in systemic sclerosis by serum biomarkers and peripheral endothelial function.

OBJECTIVES: To identify prognostic factors among serum biomarkers and endothelial vasodilator function findings in patients with systemic sclerosis (SSc). METHODS: This is a clinical observational study. We assessed 60 consecutive SSc patients (44 limited cutaneous-type, 16 diffuse cutaneous-type). Circulating growth differentiation factor-15 (GDF-15), placenta growth factor (PlGF), endostatin, vascular endothelial growth factor (VEGF), and pentraxin 3 (PTX3) were measured by ELISA. Peripheral endothelial function was measured by forearm blood dilatation response to brachial artery occlusion using noninvasive plethysmography (EndoPAT2000), which is associated with nitric-oxide-dependent vasodilatation and yields a reactive hyperemia index (RHI). We evaluated whether abnormalities in these values were associated with type of SSc - namely, diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc) - or organ involvement including interstitial lung disease (ILD), digital ulcer (DU) and estimated right ventricular systolic pressure (RVSP) by echocardiography >30 mmHg. RESULTS: SSc patients showed significantly elevated serum GDF-15, PlGF, endostatin and VEGF but not PTX3 compared with controls. GDF-15 and PlGF were high in dcSSc patients. EndoPAT-RHI was low, and incidence of RVSP >30 mmHg was high in dcSSc. Multivariate analysis revealed that elevated GDF-15 was highly predictive of dcSSc, ILD or RVSP >30 mmHg. PlGF for DU was also found. Conversely, a low EndoPAT-RHI value was predictive of the presence of dcSSc, ILD or DU. CONCLUSIONS: This is the first study to inclusively investigate the relationships among biomarkers, EndoPAT-RHI and organ involvement in patients with SSc. Our data suggest a complex pathological progression of SSc through fibrotic impairment and microvascular damage.

Free light chains of immunoglobulins in patients with systemic sclerosis: correlations with lung involvement and inflammatory milieu.

AIM: Humoral immunity and B cells are thought to play an important role in the pathophysiology of the systemic sclerosis (SSc). The production of free light chains (FLC) of immunoglobulins is abnormally high in several pathological autoimmune conditions and reflects B cell activation. Furthermore, FLCs demonstrated different biological activities including their capability to modulate the immune system, proteolytic activity and complement cascade activation. The aims of this study are to determine the FLC levels in patients with SSc compared with healthy controls (HC) and to study their possible association with organ involvement and disease characteristics. METHODS: Sixty-five patients with SSc and 20 HC were studied. Clinical and immunological inflammatory characteristics were assessed for all the patients with SSc. κ-FLC and λ-FLC, interleukin 6 (IL-6) and B cell activating factor levels were measured. RESULTS: The mean serum κ-FLC levels and FLC ratio were significantly higher in patients with SSc compared with HC, while the serum λ-FLC levels were comparable.The levels of FLC were comparable in patients with diffuse skin disease and limited skin involvement, while κ-FLC levels were increased in patients with restrictive lung (forced vital capacity (FVC) <80%) disease (26.4±7.4 mg/L) when compared with patients with FVC ≥80% (19.6±7.3 mg/L, P=0.009). In patients with SSc, the levels of serum κ-FLC level directly correlated with the IL-6 levels (R=0.3, P=0.001) and disease activity (R=0.4, P=0.003). CONCLUSIONS: FLC levels are elevated in SSc and high levels are associated with lung involvement and with a higher degree of inflammation, supporting a possible role of B cell activation in the pathophysiology of the disease.

Interstitial lung disease in systemic sclerosis: data from the spanish scleroderma study group.

OBJECTIVES: To evaluate the clinical characteristics of patients with interstitial lung disease (ILD) in the setting of a large cohort of systemic sclerosis (SSc) patients, and to analyse the differences according to the SSc subtype (following the modification of classification criteria of the American College of Rheumatology for SSc proposed by LeRoy and Medsger), factors are associated with moderate-to-severe impairment of lung function, as well as mortality and causes of death. METHODS: A descriptive study was performed, using the available data from the Spanish Scleroderma Study Group. RESULTS: Twenty-one referral centers participated in the registry. By April 2014, 1374 patients with SSc had been enrolled, and 595 of whom (43%) had ILD: 316 (53%) with limited cutaneous SSc (lcSSc), 240 (40%) with diffuse cutaneous SSc (dcSSc), and 39 (7%) with SSc sine scleroderma (ssSSc). ILD in the lcSSc and the ssSSc subsets tended to develop later, and showed a less impaired forced vital capacity (FVC) and a ground glass pattern on high-resolution computed tomography (HRCT) less frequently, compared with the dcSSc subset. Factors related to an FVC < 70% of predicted in the multivariate analysis were: dcSSc, positivity to anti-topoisomerase I antibodies, a ground glass pattern on HCRT, an active nailfold capillaroscopy pattern, lower DLco, older age at symptoms onset, and longer time between symptoms onset and ILD diagnosis. Finally, SSc-associated mortality and ILD-related mortality were highest in dcSSc patients, whereas that related to pulmonary arterial hypertension was highest in those with lcSSc-associated ILD. CONCLUSIONS: Our study indicates that ILD constitutes a remarkable complication of SSc with significant morbidity and mortality, which should be borne in mind in all three subgroups (lcSSc, dcSSc, and ssSSc).

Angiogenic and angiostatic factors in renal scleroderma-associated vasculopathy.

BACKGROUND: The angiogenesis in systemic sclerosis (SSc) is impaired. An imbalance of pro-angiogenic factors and angiogenesis inhibitors has been implicated in the progression of peripheral microvascular damage, defective vascular repair and fibrosis. Intrarenal resistance index are considered markers of renal vasculopathy. The aim of the study is to evaluate angiogenic and angiostatic factors (VEGF and endostatin) in SSc patients and to correlate with intrarenal hemodynamic parameters. METHODS: 91 SSc patients were enrolled in this study. Serum VEGF and endostatin levels were determined. All patients underwent a renal Doppler ultrasound RESULTS: A significant positive correlation was observed between endostatin and renal Doppler parameters (p<0.0001). A negative correlation was observed between serum levels of endostatin and eGFR (p<0.01). In SSc patients with high resistive index, serum levels of endostatin were significantly (p<0.01) higher than in SSc patients with normal resistive index. The serum levels of endostatin significantly increased with progression of nailfold videocapillaroscopy damage (p<0.01) and were significantly (p<0.05) higher in SSc patients with digital ulcers than in SSc patients without digital ulcers. CONCLUSION: This is the first study that assess in SSc patients intrarenal hemodynamic parameters and endostatin. In SSc patients, endostatin represents a marker of renal scleroderma-associated vasculopathy.

Comparison of change in end tidal carbon dioxide after three minutes of step exercise between systemic sclerosis patients with and without pulmonary hypertension.

OBJECTIVES: Pulmonary hypertension (PH) is an important cause of morbidity and mortality in patients with SSc. The submaximal heart and pulmonary evaluation (step test) is a non-invasive, submaximal stress test that could be used to identify SSc patients with PH. Our aims were to determine whether change in end tidal carbon dioxide ([Formula: see text]) from rest to end-exercise, and the minute ventilation to carbon dioxide production ratio ([Formula: see text]), both as measured by the step test, differ between SSc patients with and without PH. We also examined differences in validated self-report questionnaires and potential PH biomarkers between SSc patients with and without PH. METHODS: We performed a cross-sectional study of 27 patients with limited or dcSSc who underwent a right heart catheterization within 24 months prior to study entry. The study visit consisted of questionnaire completion; history; physical examination; step test performance; and phlebotomy. [Formula: see text], [Formula: see text], self-report data and biomarkers were compared between patients with and without PH. RESULTS: SSc patients with PH had a statistically significantly lower median (interquartile range) [Formula: see text] than SSc patients without PH [-2.1 (-5.1 to 0.7) vs 1.2 (-0.7 to 5.4) mmHg, P = 0.035], and a statistically significantly higher median (interquartile range) [Formula: see text] [53.4 (39-64.1) vs 36.4 (31.9-41.1), P = 0.035]. There were no statistically significant differences in self-report data or biomarkers between groups. CONCLUSION: [Formula: see text] and [Formula: see text] as measured by the step test are statistically significantly different between SSc patients with and without PH. [Formula: see text] and [Formula: see text] may be useful screening tools for PH in the SSc population.

Acro-osteolysis and calcinosis in patient with scleroderma: A case report.

Acro-osteolysis is a rare disease characterized by bone resorption involving the distal phalanges of the hand. We present a unique case of progressive acro-osteolysis of the distal phalanges and articular calcifications in a patient with scleroderma. The calcified deposit in a proximal interphalangeal joint was excised under local anesthesia. The medical treatment was arranged under the supervision of a rheumatologist.

Association of Anticentromere Antibodies With More Severe Exocrine Glandular Dysfunction in Sjögren's Syndrome: Analysis of the Sjögren's International Collaborative Clinical Alliance Cohort.

OBJECTIVE: Anticentromere antibodies (ACAs) define a subset of primary Sjögren's syndrome (SS) with a unique phenotype, including features of limited cutaneous systemic sclerosis and a lower frequency of anti-SSA/SSB antibodies. We sought to determine whether ACAs are associated with more severe exocrine glandular dysfunction in a large cohort of primary SS subjects. METHODS: We performed a cross-sectional analysis of 1,361 subjects with primary SS from the Sjögren's International Collaborative Clinical Alliance Registry, stratified by the presence or absence of ACAs. ACAs were assayed by immunofluorescence staining on HEp-2 cells. RESULTS: ACAs were present in 82 of the 1,361 SS subjects (6%) and were associated with older age, female sex, and lower frequencies of anti-SSA/SSB, rheumatoid factor, and hyperglobulinemia. Among ACA-positive versus ACA-negative subjects, there was a higher frequency of a focus score ≥2 (71% versus 53%; P = 0.002), a higher median focus score (2.8 versus 2.5; P = 0.0440), and greater exocrine gland dysfunction: Schirmer's test value: median 4 versus 5 mm/5 minutes; P = 0.0003, and unstimulated whole saliva (UWS) flow rate: median 0.08 versus 0.37 ml/5 minutes; P < 0.0001. ACA-positive subjects had an increased risk of UWS <0.1 ml/minute (odds ratio [OR] 12.24 [95% confidence interval (95% CI) 4.91-41.02]) and Schirmer's test value <5 mm/5 minutes (OR 2.52 [95% CI 1.50-4.36]) after correcting for age, sex, anti-SSA/SSB, and focus score. Labial gland fibrosis was not different between the 2 groups. CONCLUSION: In a large international registry of SS, ACA had an independent association with more severe exocrine glandular dysfunction. This dysfunction was associated with more pronounced labial salivary glandular inflammation but not fibrosis.

Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients.

OBJECTIVES: To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients. METHODS: Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated. RESULTS: SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (p<0.0001), but not at the level of face and dorsum of hands. A gradual decrease of BP at fingertips, periungual and palm areas, was found in SSc patients with progressive severity of NVC patterns of microangiopathy ("early", "active", or "late") (p<0.01). A negative correlation was observed between MES and BP values, as well as between loss of capillaries and BP, at the same areas (p<0.001 and p<0.01, respectively). Patients with diffuse cutaneous SSc (dcSSc) showed lower BP than those with limited cutaneous SSc (p<0.04). CONCLUSIONS: LASCA detects a significant reduction of BP only in those areas usually affected by Raynaud's phenomenon (fingertips, periungual and palm areas), especially in dcSSc patients, and BP values significantly correlate with the nailfold capillaroscopy scores of microangiopathy.

Evaluation of choroidal thickness in patients with scleroderma.

PURPOSE: To investigate the choroidal thickness in patients with scleroderma and to compare them with healthy control subjects. METHODS: Forty-six patients with scleroderma (3 male and 43 female) and 31 healthy controls (6 male and 25 female) were included in the study. Twenty-five patients had limited-type and 21 patients had diffuse-type scleroderma. Only left eyes of the patients and control subjects were used in the analysis. Demographic features of all the patients and control subjects were recorded. Each subject underwent ophthalmological examinations including refraction, visual acuity, intraocular pressure, axial length (AXL) measurement, slit-lamp biomicroscopy, and fundus examination. Body mass index (BMI) was estimated for all participants. RESULTS: There were no significant differences between the patients with scleroderma and the control subjects in terms of age, gender, BMI, mean AXL, and mean spherical equivalent refractive error (SE) (P=0.1, P=0.086, P=0.37, P=0.55, and P=0.072 respectively). The patients with scleroderma had significantly thinner nasal, temporal, and subfoveal choroid than the healthy control subjects (P1=0.012, P2=0.046, and P3<0.001, respectively). There were no significant differences between the patients with limited-type and diffuse-type scleroderma in terms of age, gender, BMI, mean AXL, mean SE, nasal, temporal, and subfoveal choroidal thicknesses (all P>0.05). CONCLUSIONS: Choroidal thickness in patients with scleroderma was significantly less than healthy control subjects. Vasculopathy in scleroderma is characterized by obliteration of arterioles and reduced capillary density may cause atrophy of choroid in patients with scleroderma.