Systemic Sclerosis Patients Research Articles

The evaluation of gastrointestinal involvement and nutritional status in systemic sclerosis: identifying risk factors for malnutrition in a cross-sectional study

Aims: Gastrointestinal (GI) involvement is frequently observed in Systemic sclerosis (SSc). Considering the effect of GI involvement on SSc patients, the risk of malnutrition might be increased. The study aimed to evaluate GI involvement and the risk for malnutrition and to demonstrate the relationship between disease-related features and risk factors for malnutrition in SSc patients. 
 Methods: SSc-related clinical features and disease severity evaluated with Physician Global Assessment (PGA) were recorded. Detailed GI symptoms and the impact of GI involvement on patients were assessed with the UCLA SCTC GIT 2.0 questionnaire. Nutritional status was evaluated with Body Mass Index (BMI) and the Malnutritional Universal Screening Tool (MUST).
 Results: 104 SSc patients were involved in the study. Mean age of patients with SSc was 52.24±12.82 years. GI involvement was found in 85.7% of patients. 76% of patients had GI symptoms. The median BMI of patients was 25.3 (9) kg/m² with 4.8% of patients categorized as underweight. The assessment of risk for malnutrition using MUST showed 74% of patients at low risk, 16% at moderate risk, and 9.6% at high risk. No important association was detected between risk groups for malnutrition and UCLA GIT 2.0 score. A significant association was found between moderate to high risk for malnutrition and dcSSc (OR 3.12, %95 CI:1.26-7.73; P=0.01), the presence of GI symptoms (OR 5.32, %95 CI:1.16-24.36; P=0.03), the decrease in oral aperture (OR 0.35, %95 CI:0.15-0.79; p:0.02), and severity of the disease investigated by PGA score (OR 1.52, %95 CI:1.09-2.13; p=0.01).
 Conclusion: GI involvement is a common manifestation in SSc patients. Approximately 26% of patients were at moderate to high risk for malnutrition. Several SSc-specific clinical features, including disease severity, the presence of GI symptoms, dcSSc, and a decrease in oral aperture were related to a higher risk for malnutrition.

Respiratory tract lining fluid copper content contributes to pulmonary oxidative stress in patients with systemic sclerosis

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs, mostly affecting young and middle-aged women. Significant questions remain as to its pathogenesis, especially the triggers for the associated interstitial lung disease (SSc-ILD). We examined the extent to which SSc and SSc-ILD were related to oxidative stress and altered metal homeostasis at the air-lung interface. Methods In this case-control study, we recruited 20 SSc patients, of which 11 had SSc-ILD. Eighteen healthy individuals were recruited as age-matched healthy controls, for a total of 38 study participants. Low molecular weight antioxidants (ascorbate, urate and glutathione), metal transport and chelation proteins (transferrin and ferritin) and metals (Fe and Cu) concentrations, including a measure of the catalytically active metal pool, were determined in respiratory tract lining fluid (RTLF) collected by bronchoalveolar lavage from the SSc group and compared with healthy controls. Results In the SSc group, 14 individuals were of female sex (70%) and the median age was 57 years (range 35-75). We observed evidence of oxidative stress in the RTLFs of SSc patients, characterised by increased concentrations of glutathione disulphide (GSSG, P<0.01), dehydroascorbate (DHA, P<0.05) and urate (P<0.01). This was associated with elevated RTLF Fe (P=0.07) and Cu (P<0.001), and evidence of a catalytic metal pool, demonstrated by an enhanced rate of ascorbate oxidation in the recovered lavage fluid (p<0.01). Cu concentrations were significantly associated with the ascorbate depletion rate (r=0.76, P<0.001), and GSSG (r=0.38, P<0.05) and protein carbonyl (r=0.44, P<0.01) concentrations. Whilst these markers were all increased in SSc patients, we found no evidence for an association with SSc-ILD. Conclusions These data confirm the presence of oxidative stress in the airways of SSc patients and, for the first time, suggest that an underlying defect in metal homeostasis at the air-lung interface may play a role in disease progression.

Association of serum Ly6/PLAUR domain-containing protein 1 levels with skin sclerosis in systemic sclerosis

Systemic sclerosis (SSc) is a connective tissue disease characterized by aberrant immune activation, vascular injury, and fibrosis of the skin and internal organs. Ly6/PLAUR domain-containing protein 1 (LYPD1) was reported to be secreted and to have various physiological functions such as anti-angiogenic effects. Here we investigated serum LYPD1 levels in SSc patients and the association of serum LYPD1 levels with clinical features of SSc. Serum samples were obtained from 75 SSc patients and 22 healthy individuals as controls. We measured serum LYPD1 levels using enzyme-linked immunosorbent assay kits. Then, the relationship between serum LYPD1 levels and clinical features of SSc was analyzed. Serum LYPD1 levels in diffuse cutaneous SSc (dcSSc) patients were significantly higher than those in the limited cutaneous SSc (lcSSc) patients (median [25–75th percentiles], 1693.43 [1086.61–1917.57] vs. 904.55 [714.356–1285.56] pg/mL), while there were no significant differences in the serum LYPD1 levels between lcSSc and healthy controls (904.55 [714.356–1285.56] vs. 750.71 pg/mL [544.00–912.14]). Further analysis revealed that serum LYPD1 levels in patients correlated with skin thickness scores and serum interleukin (IL)-6 levels, which were known to reflect the extent of skin thickening in SSc. Moreover, serum LYPD1 levels showed a decrease with improvement in skin thickness after treatment, along with a decrease in serum IL-6 levels. These results indicate that LYPD1 might be a potential marker for monitoring skin sclerosis and evaluating the efficacy of skin fibrosis treatment in SSc patients.

Immune profiling analysis of double-negative T cells in patients with systemic sclerosis.

To construct a molecular immune map of patients with systemic sclerosis (SSc) by mass flow cytometry, and compare the number and molecular expression of double-negative T (DNT) cell subsets between patients and healthy controls (HC). Peripheral blood mononuclear cells (PBMCs) were extracted from the peripheral blood of 17 SSc patients and 9 HC. A 42-channel panel was set up to perform mass cytometry by time of flight (CyTOF) analysis for DNT subgroups. Flow cytometry was used to validate subpopulation functions. The clinical data of patients were collected for correlation analysis. Compared with HC, the number of total DNT cells decreased in SSc patients. Six DNT subsets were obtained from CyTOF analysis, in which the proportion of cluster1 increased, while the proportion of cluster3 decreased. Further analysis revealed that cluster1 was characterized by high expression of CD28 and CCR7, and cluster3 was characterized by high expression of CD28 and CCR5. After in vitro stimulation, cluster1 secreted more IL-4 and cluster3 secreted more IL-10 in SSc patients compared to HC. Clinical correlation analysis suggested that cluster1 may play a pathogenic role while cluster3 may play a protective role in SSc. ROC curve analysis further revealed that cluster3 may be a potential indicator for determining disease activity in SSc patients. We found a new CCR5+CD28+ DNT cell subset, which played a protective role in the pathogenesis of SSc. Key Points • The number of DNT cells decreased in SSc patients' peripheral blood. • DNT cells do not infiltrate in the skin but secrete cytokines to participate in the pathogenesis of SSc. • A CCR5+CD28+ DNT cell population may play a protective role in SSc.

Insights into the Relationship between Periodontitis and Systemic Sclerosis Based on the New Periodontitis Classification (2018): A Cross-Sectional Study.

(1) Background: This study aimed to assess the periodontitis burden in systemic sclerosis patients and the possible association between them, and the degree to which some potential risk factors and two potential diagnostic biomarkers may account for this association. (2) Methods: This cross-sectional study included a test group (systemic sclerosis patients) and a control group (non-systemic sclerosis patients). Both groups benefited from medical, periodontal examination and saliva sampling to determine the salivary flow rate and two inflammatory biomarkers (calprotectin, psoriasin). A systemic sclerosis severity scale was established. (3) Results: In the studied groups, comparable periodontitis rates of 88.68% and 85.85%, respectively, were identified. There were no significant differences in the severity of periodontitis among different systemic sclerosis severity, or in the positivity for anti-centromere and anti-SCL70 antibodies. Musculoskeletal lesions were significantly more common in stage III/IV periodontitis (n = 33, 86.84%) than in those in stage I/II (n = 1, 100%, and n = 3, 37.5%, respectively) (p = 0.007). Comparable levels of the inflammatory mediators were displayed by the two groups. There were no significant differences in calprotectin and psoriasin levels between diffuse and limited forms of systemic sclerosis. (4) Conclusions: Within the limitations of the current study, no associations between systemic sclerosis and periodontitis, or between their risk factors, could be proven.

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-related connective tissue disease with a complex and unknown pathophysiological mechanism with genes association. Several articles have reported a high prevalence of thyroid disease in SSc patients, while one study suggested a potential contribution of appendicitis to the development of SSc. To investigate this causal association, we conducted Mendelian randomization (MR) analysis using instrumental variables (IVs) to assess exposure and outcome. In the MR study involving two cohorts, all analyses were conducted using the TwoSampleMR package in R (version 4.3.0). Single nucleotide polymorphisms (SNPs) meeting a statistically significant threshold of 5E−08 were included in the analysis. Multiple complementary approaches including MR-IVW, MR-Egger, weighted median, simple mode, and weighted mode were employed to estimated the relationship between the exposure and outcome. Leave-one-out analysis and scatter plots were utilized for further investigation. Based on the locus-wide significance level, all of the MR analysis consequences manifested no causal association between the risk of appendicitis with SSc (IVW OR 0.319, 95% CI 0.063–14.055, P = 0.966). Negative causal effects of autoimmune thyroiditis (AT) on SSc (IVW OR 0.131, 95% CI 0.816–1.362, P = 0.686), Graves’ disease (GD) on SSc (IVW OR 0.097, 95% CI 0.837–1.222, P = 0.908), and hypothyroidism on SSc (IVW OR 1.136, 95% CI 0.977–1.321, P = 0.096) were derived. The reverse MR revealed no significant causal effect of SSc on thyroid disease. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. The consequences indicated no significant association between AT, GD, and hypothyroidism with SSc. Similarly, there was no observed relationship with appendicitis.

Patients' unmet needs and treatment preferences concerning digital ulcers in systemic sclerosis.

Digital ulcers (DUs) significantly impact on quality of life and function in patients with systemic sclerosis (SSc). The aim of our survey was to explore patients' perspectives and their unmet needs concerning SSc-DUs. SSc patients were invited through international patient associations and social media to participate in an online survey. 358 responses were obtained from 34 countries: US (65.6%), UK (11.5%) and Canada (4.5%). Recurrent DUs are common: >10 DUs (46.1%), 5-10 DUs (21.5%), 1-5 DUs (28.5%), 1 DU (3.9%). Fingertip DUs were most frequent (84.9%), followed by those overlying the interphalangeal joints (50.8%). The impact of DUs in patients is broad, from broad-ranging emotional impacts to impact on activities of daily living, and personal relationships. Half (51.7%) of respondents reported that they received wound/ulcer care, most often provided by non-specialist wound care clinics (63.8%). There was significant variation in local (wound) DU care, in particular the use of debridement and pain management. DU-related education was only provided to one-third of patients. One-quarter (24.6%) were 'very satisfied' or 'satisfied' that the provided DU treatment(s) relieved their DU symptoms. Pain, limited hand function, and ulcer duration/chronicity were the main reasons for patients to consider changing DU treatment. Our data show that there is a large variation in DU treatment between countries. Patient access to specialist wound-care services is limited and only a small proportion of patients had their DU needs met. Moreover, patient education is often neglected. Evidence-based treatment pathways are urgently needed for DU management.

The Role of IRF8 Polymorphisms in Systemic Sclerosis Development and Pathogenesis

The Role of IRF8 Polymorphisms in Systemic Sclerosis Development and Pathogenesis

Prediction of progressive fibrosing interstitial lung disease in patients with systemic sclerosis: insight from the CRDC cohort study

BackgroundThis study aims to establish a reliable prediction model of progressive fibrosing interstitial lung disease (PF-ILD) in patients with systemic sclerosis (SSc)-ILD, to achieve early risk stratification and to help...

Glomerulonephritis as a renal manifestation in a patient with systemic sclerosis overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis

Introduction and Importance: Systemic sclerosis (SSc) is a systemic immune disorder that may overlap with other rheumatologic disease; however, overlapping with antineutrophil cytoplasmic antibody-associated vasculitis is rare. Case Presentation: A 28-year-old Syrian male patient with SSc diagnosed according to the American College of Rheumatology/European League against Rheumatism 2013 criteria with a disease duration of 4 years, was admitted to the hospital complaining of palpable purpura in the lower limbs and hemoptysis and later, a rise in creatinine level. Laboratory tests showed high levels of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). The renal biopsy results were consistent with the diagnosis of glomerulonephritis. He was treated with methylprednisolone, cyclophosphamide, and rituximab, as he was diagnosed with SSc overlapping antineutrophil cytoplasmic antibody-associated vasculitis. Clinical Discussion: SSc most commonly renal manifestations are proliferative vasculopathy leading to scleroderma renal crisis. However, other types of renal involvement were also reported in SSc patients with comorbid autoimmune diseases such as glomerulonephritis and signs of concurrent vasculitis. SSc may overlap with rheumatoid arthritis, systemic lupus erythromatosus, polymyositis/dermatomyositis (PM/DM), and Sjogren Syndrome. Overlapping with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is mentioned in rare cases. The authors reported a rare case of overlapping SSc with antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. Conclusion: The authors revealed a rare case of overlapping SSc with antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. In SSc, renal involvement as glomerulonephritis is infrequent and should be detect in other rheumatologic disease such as systemic lupus erythematosus or antineutrophil cytoplasmic antibody-associated vasculitis.

Reliability and validity of the Turkish version of Scleroderma Skin Patient-Reported Outcome in patients with systemic sclerosis.

This study aimed to translate the Scleroderma Skin Patient-Reported Outcome (SSPRO) questionnaire to the Turkish (SSPRO-T) language and to assess its validity and reliability. Fifty-four systemic sclerosis (SSc) patients (51 females, 3 males; mean age: 49.8±10.4 years; range, 22 to 65 years) participated in the reliability and validity analysis between October 2022 and December 2022. The translation and cross-cultural adaptation of the SSPRO-T was applied in accordance with the procedure described by the Beaton guidelines. The SSPRO-T, the Scleroderma Health Assessment Questionnaire (SHAQ), the Health Assessment Questionnaire Disability Index (HAQ-DI), Skindex-29, and patient global skin severity were conducted in all participants for construct validity. The SSPRO-T was retested to assess its reliability after seven days. The SSPRO-T had a four-factor structure. The total SSPRO-T score and its subgroups correlated positively with SHAQ, HAQ-DI, Skindex-29, and patient global skin severity. The internal consistency and reliability were excellent in overall SSPRO-T and in the subgroups: physical effect, emotional effect, physical limitation, and social effect (Cronbach's α=0.94, 0.80, 0.95, 0.93, and 0.84, respectively). The SSPRO-T had excellent test-retest reliability (r=0.91, p<0.001). In addition, no floor effect or ceiling effect was observed. The SSPRO-T questionnaire is a reliable and valid tool and can be used in research and clinical practice in Turkish patients with SSc.

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis.

Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long-term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs. SSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey. We gathered 301 valid responses from 14 countries (United Kingdom 19.3% and United States 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in gastrointestinal symptoms from receiving PPIs. Side effects attributed to receiving PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information, and most (85%) had searched online for information about PPIs. Only in the minority (12%) had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms but had important concerns. Despite the frequent use of PPIs in patients with SSc, there is significant heterogeneity in prescription, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (approximately 40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach.

Assessing hand and global disability in a cohort of Algerian patients with systemic sclerosis: Construct validities of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire.

The study aimed to assess the construct validity of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire in Algerian patients with systemic sclerosis. Consecutive Algerian patients who fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for systemic sclerosis were included. In addition to disease characteristics, global disability and hand disability were assessed using the Arabic Health Assessment Questionnaire and the Arab Hand Function Index, respectively. Construct validity was assessed by convergent and divergent validity (Spearman's rank correlation coefficient) and factor analysis. The scale reliability was assessed using the Cronbach's alpha. We evaluated 100 systemic sclerosis patients (83 females) of mean ± standard deviation age 46.7 ± 12.3 years, including 59 limited cutaneous systemic sclerosis and 41 diffuse cutaneous systemic sclerosis. Raynaud's phenomenon was detected in 99 patients and digital ulcers in 25. Gastrointestinal tract involvement and interstitial lung disease were detected in 86/100 (86%) and 46/72 (63.9%) patients, respectively. Anti-topoisomerase I and anti-centromere antibodies were detected in 33/76 (43.4%) and 23/76 (30.3%) patients, respectively. The Arab Hand Function Index had a good construct validity with a total score explaining 61% of the variance of the Arabic Health Assessment Questionnaire which also had a good construct validity. Factor analysis of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire items extracted two factors explaining 64% of the variance for the Arab Hand Function Index and one factor explaining 55% of the variance for the Arabic Health Assessment Questionnaire. The Arab Hand Function Index and the Arabic Health Assessment Questionnaire were reliable questionnaires with a Cronbach's alpha >0.8. In Algerian patients with systemic sclerosis, Arab Hand Function Index and Arabic Health Assessment Questionnaire have a good construct validity and reliability.

Perception of aesthetic impairment in patients with systemic sclerosis determined using a semi-quantitative scale and its association with disease characteristics.

Systemic sclerosis is a fibrotic disease. Body image assessments could be key in optimizing care; however, data are scarce. The main objective was to assess the perception of aesthetic impairment using a visual aesthetic evaluation scale in patients with systemic sclerosis compared with healthy subjects. The secondary objectives were to assess associations between the perception of aesthetic impairment and scores on standardized questionnaires for aesthetic impairment as well as clinical, psychological/quality of life, and functional parameters of patients with systemic sclerosis. This study evaluated and compared the perception of aesthetic impairment in two populations: patients with systemic sclerosis from a referral center at Lille Hospital, France, and healthy controls. This study included 88 patients (69 (78.4%) women) with a median age of 52 years and 88 controls (49 (55.7%) women) with a median age of 45 years. The perception of aesthetic impairment assessed using the aesthetic evaluation scale was poorer in systemic sclerosis patients than in controls (3.7 ± 0.3 vs 2.8 ± 0.3, p = 0.028) and was statistically correlated with assessments using the adapted satisfaction with appearance, a specific aesthetic impact assessment questionnaire for patients with systemic sclerosis. Patients with anxiety or depressive symptoms had significantly higher aesthetic evaluation scale scores. Systemic sclerosis patients with facial involvement and pitting scars had a worse perception of aesthetic impairment. Compared with healthy controls, systemic sclerosis patients had a worse perception of aesthetic impairment, especially systemic sclerosis patients with anxiety or depression and those with facial and hand involvement. The aesthetic evaluation scale appears to be an easy-to-use tool to evaluate body image. Correlations of the aesthetic evaluation scale score with psychological and quality of life parameters reflect the importance of these parameters for body image evaluation and its complex assessment. Clinical Trial NCT03271320 (Registered 9 January 2017, https://www.clinicaltrials.gov/ct2/show/NCT03271320?term=NCT03271320&cntry=FR&draw=2&rank=1).

The effect of systemic sclerosis and its subtypes on ocular anterior and posterior segment parameters.

To evaluate anterior and posterior segment parameters in the eyes of patients with systemic sclerosis (SSc) and examine the effect of disease and disease subtypes on these parameters. This cross-sectional study included 54 eyes of 27 SSc patients and 54 eyes of 27 age- and sex-matched healthy controls. In addition to a complete ophthalmologic examination, all patients were examined using a Scheimpflug camera, specular microscopy, and spectral domain optical coherence tomography. The mean age of the patients was 52.5 ± 11.4years and 19 patients were female. Anterior chamber volume, central corneal thickness, and central macular thickness (CMT) were significantly lower in the eyes of SSc patients compared to healthy controls (p = 0.01, p = 0.03, and p = 0.006, respectively). When evaluated according to SSc subtype, CMT was lower in diffuse SSc patients (p = 0.001), while mean retinal nerve fiber layer (RNFL) and inferior quadrant RNFL values were lower in limited SSc (p = 0.003 and p = 0.005, respectively). In the eyes of patients with SSc, some ocular parameters may show decreases compared to healthy individuals, presumably secondary to disease-related vasculopathy and fibrosis. CMT and RNFL parameters may be affected differently according to disease subtype.

Diagnostic approaches and treatments of systemic sclerosis patient with interstitial lung disease

Background: Systemic sclerosis or scleroderma is a rare disease with multiple complications which may include interstitial lung disease. The findings of diffuse type of systemic sclerosis, moderate restriction in pulmonary function test, interstitial pneumonia in chest x-ray, and ground glass opacity in thoracic CT-scan establish the diagnosis of interstitial lung disease associated with systemic sclerosis. We present a case of interstitial lung disease in a systemic sclerosis case, which was approached and treated comprehensively to slow the progression. Case Presentation: A 40-year-old female was admitted to the rheumatology polyclinic of Dr. Soetomo Hospital Surabaya with persistent dry cough for two years in June 2021. The patient also complained of breathlessness, painful joints, swollen knees, and morning stiffness three months prior to admission. The positive results of antinuclear antibody and rheumatoid factor were identified in 2016, which suggested autoimmune disease of scleroderma and being treated with azathioprine 50 mg twice a day, methylprednisolone 4 mg once a day, chloroquine 200 mg once a day, and calcium lactate once a day. The examinations in 2020 showed moderate restriction from the pulmonary function test, bilateral lung parenchymal infiltrates from the chest x-ray, and ground-glass opacity from the chest computed tomography scan (CT-scan). The patient was monthly prescribed cyclophosphamide 500 mg intravenously for six months as the substitution of azathioprine, methylprednisolone 4 mg once a day, and aspirin 100 mg once a day. The latest worsening condition led the patient to receive the substitution of cyclophosphamide which was mycophenolate mofetil 360 mg twice a day, along with aspirin 100mg and methylprednisolone 4 mg once a day, respectively. Conclusion: As a rare disease, the complications of systemic sclerosis should be anticipated. In this case, interstitial lung disease occurred following nearly five years of systemic sclerosis course which required immunosuppressive agents to enhance the efficacy of treatment. Comprehensive treatment with tight monitoring is necessary to slow the disease progression.

Systemic sclerosis, silica exposure and cellular therapies: The sand in the gears?

Systemic sclerosis (SSc) is a chronic orphan autoimmune disease with the highest mortality rate among rheumatic diseases. SSc-related interstitial-lung disease (ILD) remains among the leading causes of SSc-related mortality with still few therapeutic effective strategies. In patients with crystallin silica exposure, SSc is recognized as an occupational disease according to the French social security system (Table 25A of the general insurance regimen). Lympho-ablative or myeloablative immunosuppression followed by autologous hematopoietic stem-cell transplantation (aHSCT) is the only therapeutic approach with demonstrated efficacy, improved survival with disease modifying effects on SSc-fibrotic manifestations (skin disease and ILD) and quality of life. A documented past and/or present occupational silica exposure, with extensive exposure and/or silica-related ILD and/or with persistent silica content in the broncho-alveolar lavage fluid are contra-indications to aHSCT in SSc patients, due to the risk of silica-related malignancy or of SSc relapse. This article aims to discuss alternative options in SSc patients with a history of silica exposure, and how innovative cellular therapies (mesenchymal stromal cells, CAR cells) could represent new therapeutic options for these patients.

Helicobacter pylori in gastrointestinal manifestation of systemic sclerosis.

To study the prevalence of Helicobacter pylori in systemic sclerosis patients and its gastrointestinal manifestations in comparison with Helicobacter pylori-negative systemic sclerosis patients. Systemic sclerosis gastrointestinal outcome post Helicobacter pylori eradication was evaluated. In total, 70 systemic sclerosis patients and 70 age-, gender- and race-matched healthy controls had their urea breath test done. Gastrointestinal manifestations in systemic sclerosis were assessed using University of California at Los Angeles 2.0 and Leeds Dyspepsia Questionnaire questionnaires. Systemic sclerosis patients with confirmed Helicobacter pylori infection were given standard Helicobacter pylori eradication therapy. Urea breath test was repeated 6 weeks posteradication therapy with their gastrointestinal symptoms reassessed. The prevalence of Helicobacter pylori was low in both systemic sclerosis patients (10%) and healthy controls (2.9%). There was no significant difference in gastrointestinal symptoms between Helicobacter pylori-positive and Helicobacter pylori-negative systemic sclerosis patients. However, the Helicobacter pylori-positive patients reported higher median severity scores for the gastrointestinal symptoms of reflux (0.5 vs 0.35), abdominal distension (1.5 vs 0.75) and social functioning impairment score (0.5 vs 0.16) using the University of California at Los Angeles 2.0 score. The Helicobacter pylori-positive patients also indicated increased upper abdominal pain (3.0 vs 0.0), regurgitation (2.0 vs 0.0) and burping (3.0 vs 0.0), observed from the Leeds Dyspepsia Questionnaire scores. Gastrointestinal outcomes post-Helicobacter pylori eradication showed either an improvement or complete resolution of symptoms. Gastrointestinal symptoms in systemic sclerosis patients are unlikely to be caused by Helicobacter pylori in the recent years in our cohort of patients. No significant difference in gastrointestinal symptoms was seen between Helicobacter pylori-positive and Helicobacter pylori-negative systemic sclerosis patients. Helicobacter pylori can be readily tested by urea breath test to look for present infection.

Well-Being Therapy in systemic sclerosis outpatients: a randomized controlled trial.

Systemic Sclerosis (SSc) patients have psychological distress and poor well-being and need a tailored treatment. Psychological interventions, rarely tested for efficacy, showed poor benefits. The present randomized controlled trial tested the efficacy of Well-Being Therapy (WBT) in SSc patients. Thirty-two outpatients were randomized (1:1) to WBT (n = 16) or Treatment As Usual (i.e. routine medical check-ups) (TAU) (n = 16). Primary outcome was well-being. Secondary outcomes included functional ability related to SSc, psychological distress, mental pain, suffering. All participants were assessed at baseline (T0). The WBT group was assessed after two months (end of WBT session 4) (T1), after four months (end of WBT session 8) (T2), after seven months (3-month follow-up) (T3), and after 10 months (6-month follow-up) (T4). The TAU group was assessed two (T1), four (T2), seven (T3), and ten (T4) months after baseline. WBT produced a significant improvement in subjective well-being (p ≤ 0.001), personal growth (p = 0.006), self-acceptance (p = 0.003) compared with TAU, maintained at T3 as what concerns subjective well-being (p = 0.012). WBT produced greater decrease in psychological distress (p = 0.010), mental pain (p = 0.010), suffering (p ≤ 0.001) compared with TAU, maintained at T4 as what concerns suffering (p ≤ 0.001). Participants reported high satisfaction with WBT. The study provides preliminary evidence on the benefits of WBT as short-term approach for in- and out-patient SSc healthcare paths. Studies with larger samples are needed to have the evidence for recommending WBT to SSc patients.

Orofacial Manifestation of Systemic Sclerosis: A Cross-Sectional Study and Future Prospects of Oral Capillaroscopy.

oral alterations in Systemic Sclerosis (SSc) patients are widespread and include microstomia, periodontitis, telangiectasias, mandibular resorption, bone lesions, and xerostomia. This cross-sectional study aims to evaluate the differences between SSc patients (cases) and healthy subjects (controls) regarding oral manifestations, quality of life (QoL), and microcirculation alterations. plaque index (PCR), periodontal index (PSR), DMFT, salivary flow rate, and buccal opening were measured by expert clinicians. S-HAQ test, the Self-Rating Anxiety State (SAS), the Self-Rating Depression Scale (SDS), and the WHOQOL-BREF test were administered to patients to evaluate their QoL. Microvascular alterations were assessed by oral videocapillaroscopy, performed on gingival and labial mucosa. A statistical analysis was conducted to find significant differences between healthy people and SSc patients. 59 patients were enrolled in this study. Standard salivary flow is significantly more frequent in controls, while xerostomia, reduced flow, microstomia, lip retraction, and periodontitis are significantly more frequent in the cases. Gingival capillaroscopy showed differences concerning loop visibility, thickening of the gum, tortuosity of gingival loops, and reduced gingival density. Labial capillaroscopy demonstrates that visibility of the labial loops, the labial ectasias, and the tortuosity of the loops are significantly associated with the presence of scleroderma. Hand and facial deformities, hypomobility of the tongue, cheeks, lips, microstomia, and xerostomia significantly compromised the quality of life of SSc patients, which was significantly worse among them. Moreover, oral videocapillaroscopy could be a proper diagnostic method to detect oral microcirculation alterations. SSc patients often present ectasias, rarefaction of the reticulum, microhemorrhages, and megacapillaries, which negatively impact their oral health. periodontitis, reduced salivary flow, and microstomia could be considered SSc oral manifestations. Joint deformities, facial appearance, and comorbidities significantly reduce the QoL of SSc patients compared to healthy subjects. Oral videocapillaroscopy could be an innovative and reliable technique to detect oral microcirculation anomalies.