To look for the spectrum of infections and the factors predisposing to infection in patients with systemic sclerosis (SSc). In this retrospective study, demographic, clinical features, details of infections, immunosuppressive therapy, and outcomes of patients with SSc attending clinics at department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India from 1990 to 2022 were captured. Multivariable-adjusted logistic regression was applied to identify independent predictors of infection. Data of 880 patients, mean age 35.5 ± 12 years, and female: male ratio 7.7:1, were analyzed. One hundred and fifty-three patients had at least 1 infection with a total of 233 infectious episodes. Infections were most common in lung followed by skin and soft tissue. Tuberculosis was diagnosed in 45 patients (29.4%). Klebsiella was the commonest non-tubercular organism in lung and Escherichia coli in urinary tract infections. In comparison to matched control group, patients with infection had a greater number of admissions due to active disease, odds ratio (OR) 6.27 (CI 3.23-12.18), were receiving immunosuppressive medication OR, 5.05 (CI 2.55-10.00), and had more digital ulcers OR, 2.53 (CI 1.17-5.45). Patients who had infection had more likelihood for death OR, 13.63 (CI 4.75 -39.18). Tuberculosis is the commonest infection and lung remains the major site of infection in patients with SSc. Number of hospital admissions, digital ulcers and immunosuppressive therapy are predictors of serious infection in patients with SSc. Patients with infections had more likelihood of death.

Systemic sclerosis (SSc) is a complex autoimmune connective-tissue disease, characterised by vasculopathy and fibrosis of the skin and internal organs. Activation of microvascular endothelial cells (ECs) causes the intimal hyperplasia that characterises the vascular remodelling in SSc. The most frequent complication of SSc is the development of digital ulcers (DUs). Thymic stromal lymphopoietin (TSLP) may trigger fibrosis and sustain vascular damage. Aim of this study was to evaluate the correlation between serum level of TSLP and DUs.
75 consecutive SSc patients were enrolled and serum TSLP levels were measured. The presence of history of DUs (HDU) was evaluated. Recurrent new DUs were defined as the presence of at least 3 episodes of DUs in a 12-months follow up period. The risk of developing new DUs was calculated by applying the capillaroscopic skin ulcer risk index (CSURI).
The median value of TSLP was higher in patients with HDU than patients without HDU [181.67 pg/ml (IQR 144.67; 265.66) vs 154.67 pg/ml (IQR 110.67; 171.33), p < 0.01]. The median value of TSLP was higher in patients with an increased CSURI index than patients without an increased CSURI [188 pg/ml (IQR 171.33; 246.33) vs 159.33 pg/ml (IQR 128.67; 218), p < 0.01]. Kaplan-Meier curves demonstrated that free survival from new DUs was significantly (p < 0.01) lower in SSc patients with increased TSLP serum levels.
TSLP might have a key role in digital microvascular damage of SSc patients.

BACKGROUND: This study aimed to investigate the associations of digital ulcers (DUs) in patients with systemic sclerosis (SSc).
METHODS: This retrospective study investigated the demographic characteristics, specific autoantibodies, organ involvement, and laboratory tests in patients with SSc from our hospital.
RESULTS: This study enrolled 144 patients with SSc. The DU+ group consisted of 15 (10.4%) patients. Patients with SSc having DUs have longer disease duration, higher fibrinogen, higher fibrin degradation product, and lower cholesterol. None of the patients used cholesterol-lowering drugs before onset of DUs. The study also demonstrated a higher prevalence of anti-dsDNA and anti-histone antibodies in patients with SSc with DUs. Anti-dsDNA antibody is a specific antibody for SLE with a specificity of 96-99%. A total of 86.1% (124/144) of patients suffered from diffuse cutaneous SSc, and 28.5% (41/144) of patients suffered from overlap syndrome.
CONCLUSIONS: Our study indicated that patients with SSc with fibrinogen of >2.895 g/L (p = 0.043) and cholesterol of <3.340 mmol/L (p = 0.036), which is equal to 129.258 mg/dL, are at high risk of developing DUs.

Digital ulcers (DU) are a common, severe vascular manifestation of systemic sclerosis (SSc) with few effective treatment options. Using data from the Australian Scleroderma Cohort Study (ASCS), we sought to evaluate the effect of calcium channel blockers (CCB) on the treatment and prevention of DU.Using data from 1953 participants, with a median of 4.34 years of follow-up, we used generalised estimating equations to evaluate the clinical characteristics associated with CCB use and ascertain the risk factors for the presence of DU at subsequent study visits. A time-dependent Cox-proportional hazard model was applied to evaluate the risk of future occurrence of DU with CCB use.Sixty-six percent of participants received CCB and patients with a history of DU were more likely to be prescribed a CCB (76.76% vs 53.70%, p < 0.01). CCB use was more frequent in patients with severe complications of DU including chronic DU (OR 1.47, p = 0.02), need for hospitalisation for iloprost (OR 1.30, p = 0.01) or antibiotics (OR 1.36, p = 0.04) and digital amputation (OR 1.48, p < 0.01). Use of CCB was more likely in patients who experienced DU at subsequent study visits (OR 1.32, p < 0.01) and was not associated with a decreased risk of the development of a first DU (HR 0.94, p = 0.65).CCB are frequently used in the management of SSc in the ASCS and their use is associated with severe peripheral vascular manifestations of SSc. However, our results suggest that CCB may not be effective in the healing or prevention of DU.

Systemic sclerosis (SSc) -related calcinosis can be a debilitating, constantly painful, poorly understood vascular complication of calcium hydroxyapatite deposition in soft tissue structures that affects approximately 40% of both limited and diffuse cutaneous SSc subtypes. This publication describes the iterative and multitiered international qualitative investigations that yielded remarkable insights into natural history, daily experience, and complications of SSc-calcinosis providing pivotal information for health management. Patient-driven question development and field testing, according to Food and Drug Administration guidance, propelled the development of a patient-reported outcome measure for SSc-calcinosis, the Mawdsley Calcinosis Questionnaire.

Patients with systemic sclerosis (SSc) develop various vascular disorders, including digital ulcers (DUs), which are sometimes intractable. Bosentan is a dual endothelin receptor antagonist expected to suppress the development of new DUs. The objective of this study was to analyze retrospectively Japanese SSc patients treated with bosentan and investigate its efficacy and safety. We analyzed 40 patients who visited our department from 2009 to 2022 and were treated with bosentan. Of the 25 patients who were able to continue bosentan, 64% (16 patients) were cured by 16 weeks . New DUs occurred in 5.9% (2/34) of patients and the number of new DUs per person was 0.1. Adverse events occurred in 45% (18/40), and hepatic dysfunction was occurred most frequently at 32.5% (13/40). In univariate analysis, hepatic dysfunction was significantly high in patients with low modified Rodnan total skin thickness score. Antimitochondria-antibody-positive patients were more likely to develop liver dysfunction. Hepatic dysfunction was improved without the reduction or discontinuation, dose reduction, discontinuation, or concomitant use of ursodeoxycholic acid. These results suggest that bosentan can be selected as an additional treatment for DU, which is difficult to treat with existing therapies, while carefully monitoring hepatic function.

UNASSIGNED: Clinical trials assessing systemic sclerosis (SSc)-related digital ulcers have been hampered by a lack of reliable outcome measures of healing. Our objective was to assess the feasibility of patients collecting high-quality mobile phone images of their digital lesions as a first step in developing a smartphone-based outcome measure.
UNASSIGNED: Patients with SSc-related digital (finger) lesions photographed one or more lesions each day for 30 days using their smartphone and uploaded the images to a secure Dropbox folder. Image quality was assessed using six criteria: blurriness, shadow, uniformity of lighting, dot location, dot angle and central positioning of the lesion. Patients completed a feedback questionnaire.
UNASSIGNED: Twelve patients returned 332 photographs of 18 lesions. Each patient sent a median of 29.5 photographs [interquartile range (IQR) 15-33.5], with a median of 15 photographs per lesion (IQR 6-32). Twenty-two photographs were duplicates. Of the remaining 310 images, 256 (77%) were sufficiently in focus; 268 (81%) had some shadow; lighting was even in 56 (17%); dot location was acceptable in 233 (70%); dot angle was ideal in 107 (32%); and the lesion was centred in 255 (77%). Patient feedback suggested that 6 of 10 would be willing to record images daily in future studies, and 9 of 10 at least one to three times per week.
UNASSIGNED: Taking smartphone photographs of digital lesions was feasible for most patients, with most lesions in focus and central in the image. These promising results will inform the next research phase (to develop a smartphone monitoring application incorporating photographs and symptom tracking).

To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor.
We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors.
Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs.
The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

UNASSIGNED: Raynaud\'s phenomenon (RP) and digital ulcers (DU) are frequent manifestations of Systemic Sclerosis (SSc). Despite being very common in SSc patients, both conditions have proven to be notoriously difficult to study. There are very few available approved drugs with varying efficacy. It has been shown that the presence of DU is associated with increased whole blood viscosity (WBV). Rheopheresis (RheoP) is an extracorporeal apheresis technique used to treat microcirculatory disorders by improving blood viscosity. Improved blood flow and wound healing after RheoP treatments have been reported in single case reports.
UNASSIGNED: We report the clinical trial protocol of \"A randomized controlled prospective single-center feasibility study of Rheopheresis for Raynaud\'s syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT).\" RHEACT aims to investigate the efficacy of RheoP on the Raynaud Condition Score (RCS) as the primary efficacy outcome measure after 16 weeks from baseline. Thirty patients will be randomized in a 1:1:1 ratio to one of two RheoP treatment groups or assigned to the standard of care (SoC) control group (intravenous iloprost). Secondary endpoints include changes in DU, changes in nailfold video capillaroscopy and patient-reported-outcomes (Scleroderma Health Assessment Questionnaire, FACIT-Fatigue, and the Disability of Arm, Shoulder, and Hand, quick version).
UNASSIGNED: Apheresis techniques have been investigated in SSc but mainly in observational, retrospective studies, or single case reports. RheoP is a pathophysiologically driven potential new therapy for heavily burdened patients with SSc-associated secondary RP with or without DU.
UNASSIGNED: The study was registered at clinicaltrials.gov (Identifier: NCT05204784). Furthermore, the study is made publicly available on the website of the German network of Systemic Sclerosis \"Deutsches Netzwerk Systemische Sklerodermie (DNSS).\"

Systemic sclerosis (SSc) is a complex autoimmune and up to 50% of patients develop digital ulcers. We revised fifty consecutive patients with SSc-related digital ulcers (DUs) who referred to our Scleroderma Unit. Thirty-five of them who showed clear signs of DUs infection underwent to cutaneous swab and microbiological data collection. We performed 87 cutaneous swabs overall. DUs were recurrent in 58% of the patients and multiple in 60% of patients. Fourty-four swabs (53%) were positive for Staphylococcus aureus (13% Methicillin-Resistant), 9 (10%) were positive for Pseudomonas aeruginosa, and then the others less frequently isolated. Nine patients (25%) needed hospitalization. Our data support a patient-tailored approached to DUs, particularly those infected. Selfhygiene and asepsis during dressing procedures are mandatory. Patient must be trained to avoid dangerous behaviors and reduce the risk of infection.