Thymic stromal lymphopoietin and digital microvascular damage in systemic sclerosis patients: A pilot study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: TSLP might have a key role in digital microvascular damage of SSc patients.

Epidemiology of systemic sclerosis in Quebec, Canada: a population-based study.

Background: Systemic sclerosis (SSc) is a systemic life-threatening autoimmune rheumatic disease. We aimed to assess the incidence, prevalence, mortality and spatiotemporal trends of SSc in Quebec, Canada with stratification by sex and age. Methods: SSc cases were identified from Quebec populational databases from 1989 to 2019. Negative Binomial (NB) Generalized Linear Models were used for age-standardized incidence rates (ASIR) analyses and NB random walk for prevalence and mortality. A Poisson Besag-York-Mollié regression model was used for spatial analysis. Findings: 8180 incident SSc cases were identified between 1996 and 2019 with an average age of 57.3 ± 16.3 years. The overall ASIR was 4.14/100,000 person-years (95%, Confidence Interval (CI) 4.05-4.24) with a 4:1 female predominance. ASIR increased steadily over time with an Average Annual Percent Change (AAPC) of 3.94% (95% CI 3.49-4.38). While the highest incidence rates were in those aged 60-79 years old among females and >80 years old among males, the highest AAPC (∼10%) was seen in children. Standarized incidence ratios varied geographically between 0.52 to 1.64. The average prevalence was 28.96/100,000 persons (95% CI 28.72-29.20). The Standardized Mortality Ratio (SMR) decreased from 4.18 (95% CI 3.64-4.76) in 1996 to 2.69 (95% CI 2.42-2.98) in 2019. Females had a greater SMR until 2007 and males thereafter. The highest SMR was in children and young adults [31.2 (95% CI 8.39-79.82) in the 0-19-year age group]. Interpretation: We showed an increasing trend in SSc incidence and prevalence and a decline in SMR over a 25-year period in Quebec. An uneven geographic distribution of SSc incidence was demonstrated. Funding: National Scleroderma Foundation, Canadian Dermatology Foundation/Canadian Institutes of Health Research.

Systemic Sclerosis With a Normotensive Scleroderma Renal Crisis: A Diagnostic Dilemma.

Systemic sclerosis (SSc), also called scleroderma, is an auto-immune rheumatic disease that is characterized by fibrosis of the skin and internal organs and vasculopathy. Three of the severe manifestations of the disease include a scleroderma renal crisis (SRC), pulmonary arterial hypertension, and digital ulceration. Vascular manifestations like Raynaud's phenomenon are an almost universal symptom in patients with SSc and are often the earliest manifestation of the disease. An SRC occurs in approximately 10% of all patients with scleroderma. It is characterized by malignant hypertension and progressive renal failure. However, about 10% of SRC cases present with normal blood pressure or a normotensive renal crisis. A 65-year-old man with a history of peripheral vascular disease and newly diagnosed heart failure presented to the emergency department on account of progressive discoloration of the left big toe and intermittent confusion. Initially, he was noted to be hemodynamically stable, with bluish discoloration of his left lower extremity and left big toe, which was tender to palpation with palpable distal pulses. His left toe progressively became dusky and gangrenous, necessitating ray amputation by vascular surgery. His hospital course was further complicated by worsening acute kidney injury, requiring initiation of hemodialysis, and progressive hypoxia with the transition from room air to high-flow oxygen. As part of his workup for acute kidney injury (AKI), his antinuclear antibody (ANA) was found to be positive, with high titers, as well as elevated SCl-70 IgG. Despite the initiation of hemodialysis, and post-surgical revision, he continued to deteriorate. His family opted for comfort care measures, and he died a few days later. Although SSc is a rare disease, it is associated with significant morbidity and has one of the highest mortality rates among connective tissue diseases. SSc can present with heterogeneous manifestations, mimicking several isolated organ-specific conditions. This makes the diagnosis challenging, especially early in the course of the disease. A high index of suspicion, especially in the setting of rapidly progressing multi-organ involvement without a clear cause, should prompt further evaluation of systemic sclerosis.

Whole phenotype of patients with systemic sclerosis and sicca manifestations: Comparison with sicca manifestations from other causes.

INTRODUCTION & OBJECTIVES: This study aimed to characterize the whole phenotype of Systemic sclerosis (SSc) patients with sicca symptoms, using major salivary glands Ultrasound (SGUS) parameters, minor salivary glands biopsies (mSGB) and clinical findings, and to compare these characteristics with those from patients with Sjogren's Disease (SjD), and patients with sicca manifestations from other causes. METHODS: Sixty SSc patients fulfilling the 2013 ACR/EULAR classification criteria and with subjective self-declared sicca symptoms were consecutively recruited and had SGUS and mSGB. Fifteen SSc patients without subjective sicca symptoms and 65 patients with sicca symptoms from other causes (including 37 SjD with no SSc). RESULTS: SSc patients with subjective sicca symptoms had frequent objective clinical (up to 83 %), histological (44 % of Focus score≥1/ mm2) and US anomalies (63 % of OMERACT ≥2). 53 % patients without subjective clinical complaint also had abnormal objective tests, suggesting the existence of a sub clinical involvement of salivary glands in SSc. SjD-SSc patients had more severe glandular involvement as compared to patients with isolated SjD and isolated Sicca-SSc patients (70%, 48,6 % and 38% of patients with OMERACT ≥2 respectively) suggesting additive impact of both diseases on glandular physiology and structure. CONCLUSION: SjD-SSc overlap have more severe sicca features as compared to isolated sicca-SSc and isolated SjD, suggesting a specific impact of SSc on salivary gland physiology. Further translational studies are needed to identify the underlying pathways that could serve as therapeutic targets.

2023 Brazilian Society of Rheumatology guidelines for the treatment of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

Metabolomics in systemic sclerosis.

Systemic sclerosis is a rare autoimmune condition leading to incurable complications. Therefore fast and precise diagnosis is crucial to prevent patient death and to maintain quality of life. Unfortunately, currently known biomarkers do not meet this need. To address this problem researchers use diverse approaches to elucidate the underlying aberrations. One of the methods applied is metabolomics. This modern technique enables a comprehensive assessment of multiple compound concentrations simultaneously. As it has been gaining popularity, we found it necessary to summarize metabolomic studies presented so far in a narrative review. We found 11 appropriate articles. All of the researchers found significant differences between patients and control groups, whereas the reported findings were highly inconsistent. Additionally, we have found the investigated groups in most studies were scarcely described, and the inclusion/exclusion approach was diverse. Therefore, further study with meticulous patient assessment is necessary.

Role of intravenous immunoglobulins in systemic sclerosis (SSc): A systematic literature review.

BACKGROUND: Systemic sclerosis (SSc) is a heterogenous, multi-system autoimmune disease that causes progressive fibrosis of the skin and internal organs, resulting in high morbidity and mortality. Intravenous Immunoglobulin (IVIG) is a therapeutic option for SSc; however, reports of its efficacy have been variable, and its use across multiple organ manifestations of SSc has not been comprehensively reviewed. AIM: The aim of this study was to systematically assess the existing literature on the role of IVIG use across a range of SSc manifestations. METHODS: Medline, Embase, Cochrane, Web of Science and Scopus were searched from 01/01/2003-15/04/2024 using terms related to SSc and IVIG. Included studies were English-language full texts, where ≥5 adults with SSc received IVIG, and where a reportable outcome was documented. RESULTS: Of 418 potentially relevant records, 12 were included in this review, comprising 266 patients across one randomised control trial, two pilot studies, one open label study, seven retrospective studies and one case control study. Eighteen outcomes were documented across five different organ systems: cutaneous, respiratory, musculoskeletal, gastrointestinal, and other (clinical improvement and corticosteroid sparing benefit). Results showed a favourable effect of IVIG in reducing the extent of skin thickening, muscle and joint pain, gastrointestinal symptoms, steroid dosing and improving patient/physician reported quality of life. Whilst IVIG may appear to be less beneficial for respiratory disease, the stabilisation in pulmonary function tests and radiological features may be considered a positive outcome in itself. Limitations included a lack of high-quality studies, and the use of concomitant therapies in many studies, rendering the efficacy of IVIG alone difficult to ascertain. CONCLUSION: IVIG showed benefit in treating some manifestations of SSc, however there was a lack of convincing evidence for the efficacy in others. The lack of high-quality data highlights the need for further well-designed clinical trials to confirm these findings and inform guidelines for IVIG use.

Cross-sectional study using the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) for gastrointestinal disorders of systemic sclerosis.

This study aimed to identify severe gastrointestinal ailments in patients with systemic sclerosis (SSc), investigate the role of antibodies in gastrointestinal disorders, and explore the relationship between limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) in terms of gastrointestinal involvement and its association with skin stiffness. We used the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) questionnaire to assess gastrointestinal disturbances in 100 patients with SSc. Gastrointestinal impairment was categorized into three levels: absence of or minor symptoms, moderate symptoms, and severe symptoms, as indicated by the total gastrointestinal tract (GIT) score. Comparing 27 patients with dcSSc and 73 patients with lcSSc, severe gastrointestinal disturbances were found in 7.4% of patients with dcSSc and 4.1% of patients with lcSSc. A total of 18.0% of anticentromere antibody (ACA)-positive patients exhibited moderate to severe symptoms, while 9.1% of antitopoisomerase 1 antibody-positive patients displayed similar symptoms. The average disease duration in patients with severe symptoms was 15.0 years, in those with moderate symptoms was 10.3 years, and in those who were symptom-free or mildly affected was 8.5 years. Among 16 patients with moderate to severe gastrointestinal disorders, a positive correlation was observed between the modified Rodnan skin thickness score (mRSS) and total GIT score. In addition, a positive correlation was identified between fecal incontinence and mRSS, with weaker correlations for reflux and bloating symptoms. Patients with gastrointestinal disorders showed a tendency to worsen over time, particularly in ACA-positive patients with dcSSc. Furthermore, a correlation was observed between mRSS and fecal incontinence, reflux, and abdominal bloating in patients with moderate to severe gastrointestinal disturbances.

A study of the reliability and construct validity of the 1-minute sit-to-stand test for individuals with systemic sclerosis.

OBJECTIVE: This study seeks to assess the reliability and construct validity of the 1-minute sit-to-stand test as an efficient tool for evaluating the functional capacity of individuals with systemic sclerosis, considering its time and space effectiveness. METHODS: This cross-sectional study recruited forty-nine individuals with systemic sclerosis from a university hospital in Denmark. The 1-minute sit-to-stand test was conducted twice on the same day, with an interval of approximately 10 to 15 minutes between administrations, followed by a single administration of the 6-minute walk test. Reliability and validity were estimated using Bland-Altman statistics, intraclass correlation coefficient (ICC2,1), paired t-test, and Spearman's rank correlation coefficient (ρ). RESULTS: The 1-minute sit-to-stand test exhibited excellent test-retest reliability with an ICC2,1 (CI) of 0.97 (0.95-0.99). The minimal metrically detectable change between separate measures on a subject for the difference in the measures to be considered real at the 95% confidence level was 2.9 repetitions and 11%, respectively. A learning effect of one repetition was observed between repeated measures. High construct validity was observed between the 1-minute sit-to-stand and 6-minute walk test (ρ = 0.78, p < .001). CONCLUSIONS: This study demonstrates the 1-minute sit-to-stand test as highly reliable, with an 11% change indicating a true outcome change. It also demonstrates robust construct validity compared to the 6-minute walk test. The 1-minute sit-to-stand test appears feasible for assessing functional capacity in well-functioning individuals with systemic sclerosis, but prior familiarization with the task is recommended, as a small learning effect was observed with one repetition.

Emotional intelligence: a novel predictor of quality of life in patients with systemic sclerosis.

Systemic sclerosis (SSc), a chronic systemic autoimmune disease, affects skin and internal organs compromising organ function and leading to significant morbidity and poor health-related quality of life (HrQoL). This cross-sectional study investigated whether HrQoL is influenced by trait emotional intelligence (TEI). Sixty patients with SSc (Female: 86.67%) completed the socio-demographic characteristics form, TEI Questionnaire Short-Form (TEIQue-SF), and Short-Form Health Survey (SF-36). Sixty healthy controls were also completed the TEIQue-SF. A series of multiple linear regression analyses with correlation matrix was used to analyze SF-36 domains as dependent variables with TEI domains (well-being, self-control, emotionality, sociability) as independent variables. The average age of participants was 57.3 ± 12.9 years with a mean disease duration of 7.7 ± 6.7 years. Patients differed from controls in the sociability domain of TEI. TEI global was found to affect the physical and mental component summaries (p < .001), and all 8 dimensions of the HrQoL (p < .001). Age, disease duration, and gastrointestinal manifestations were negatively associated with various components of SF-36. TEI was positively associated with all dimensions of HrQoL. Understanding the relationship between TEI and HrQoL dimensions is important for the support and empowerment of SSc patients, as well as the establishment and implementation of appropriate psychotherapeutic interventions.

Approach to interstitial lung disease associated with systemic sclerosis-A survey to pulmonologists and rheumatologists in Colombia.

INTRODUCTION: Interstitial lung disease is a leading cause of mortality in patients with systemic sclerosis. Currently, there is a lack of consensus regarding screening, rescreening, diagnosis, and follow-up practices in interstitial lung disease associated with systemic sclerosis (SSc-ILD) in Colombia. METHODS: A structured survey focused on clinical practices in patients with SSc-ILD was conducted. Members of the Asociación Colombiana de Neumología y Cirugía de Tórax (Asoneumocito) and the Asociación Colombiana de Reumatología (Asoreuma) were invited to participate from March 2023 to May 2023. RESULTS: We surveyed 51 pulmonologists and 44 rheumatologists. Overall, 51.6% reported having access to multidisciplinary team discussion in ILD. Among the 95 participants, 78.9% would routinely perform a high-resolution computed tomography scan of the chest once a diagnosis of systemic sclerosis was established. This practice is more frequent among rheumatologists (84.1%) than among pulmonologists (74.5%). Approximately half of the participants would rescreen patients annually with computed tomography scan (56.8%) if baseline images were negative. Spirometry (81.1%), diffusing capacity of the lung for carbon monoxide (80.0%), and 6-min walk test (55.8%) were the most frequently performed tests upon diagnosis of systemic sclerosis. During follow-up, participants would consider repeating pulmonary function tests mostly every 6 months. CONCLUSIONS: Screening of SSc-ILD is high among pulmonologists and rheumatologists. Decision-making on diagnosis and follow-up is similar between specialties, but there are variations in their frequency and indications. Further research is needed to evaluate how to adapt recommendations for assessing SSc-ILD in different settings.

Exploring the mechanism of luteolin improving immune and inflammatory responses in systemic sclerosis based on systems biology and cell experiments.

There is a growing trend of applying traditional Chinese medicine (TCM) to treat immune diseases. This study reveals the possible mechanism of luteolin, an active ingredient in the core prescription of TCM, in alleviating systemic sclerosis (SSc) inflammation. Bibliometrics was performed to retrieve the core keywords of SSc inflammation. The key inflammatory indicators in the serum samples of 50 SSc patients were detected by ELISA. Data mining was applied for correlation analysis, association rule analysis, and binary logistic regression analysis on the clinical indicators and medication of 50 SSc patients before and after treatment to determine the core prescription. Network pharmacology was used for identifying candidate genes and pathways; molecular docking was conducted to determine the core monomer components of the prescription, providing a basis for subsequent in vitro molecular mechanism research. The effect of luteolin on SSc-human dermal fibroblasts (HDF) viability and inflammatory factors was evaluated by means of ELISA, RT-PCR, and Western blot. The role of TNF in inflammation was explored by using a TNF overexpression vector, NF-κB inhibitor (PKM2), and SSc-HDF. The involvement of TNF/NF-κB pathway was validated by RT-PCR, Western blot, and immunofluorescence. TCM treatment partially corrected the inflammatory changes in SSc patients, indicating its anti-inflammatory effects in the body. Atractylodes, Yam, Astragalus root, Poria cocos, Pinellia ternata, Salvia miltiorrhiza, Safflower, Cassia twig, and Angelica were identified as the core prescriptions for improving inflammatory indicators. Luteolin was the main active ingredient in the prescription and showed a strong binding energy with TNF and NF-κB. Luteolin exerted anti-inflammatory effects in vitro by reducing inflammatory cytokines in SSc-HDF and inhibiting the activation of TNF/NF-κB. Mechanistically, luteolin inhibited the activation of the TNF/NF-κB pathway in SSc-HDF, as manifested by an increase in extranuclear p-P65 and TNF but a decrease in intranuclear p-P65. Interestingly, the addition of PKM2 augmented the therapeutic function of luteolin against inflammation in SSc-HDF. Our study showed the TCM alleviates the inflammatory response of SSc by inhibiting the activation of the TNF/NF-κB pathway and is an effective therapeutic agent for the treatment of SSc.

Seasonal fluctuation of serum Krebs von den Lungen-6 levels in systemic sclerosis-associated interstitial lung disease.

AIM: To evaluate whether seasonal changes influence fluctuations in serum Krebs von den Lungen-6 (KL-6) levels in systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS: Summer was defined as the period between July and September, and winter as between December and February. The study was conducted between 2015 and 2016, with a focus on these two seasons. A diagnosis of ILD and ILD progression overtime were evaluated using chest computed tomography. Among patients with SSc-ILD, those with data on serum KL-6 and lactate dehydrogenase (LDH) levels in the 2015 winter, 2015 summer, and 2016 winter seasons were included. Patients with comorbidities that could affect serum KL-6 levels were excluded. RESULTS: Of 60 patients with SSc-ILD, 52 (86.7%) had stable ILD, 5 (8.3%) had worsened ILD, and 3 (5.0%) had improved ILD. Serum KL-6 levels were significantly higher during the winter than those during the summer (2015 winter vs. 2015 summer: 649 U/mL vs. 585 U/mL, p < .0001; 2016 winter vs. 2015 summer: 690 U/mL vs. 585 U/mL, p < .0001). No significant differences were observed between the winters of 2015 and 2016 (649 U/mL vs. 690 U/mL, p = .78). However, serum LDH levels did not exhibit seasonal fluctuations (2015 winter vs. 2015 summer: 203 U/L vs. 199 U/L, p = .3; 2016 winter vs. 2015 summer: 201 U/L vs. 199 U/L, p = .6; 2015 winter vs. 2016 winter: 203 U/L vs. 201 U/L, p = .24). CONCLUSION: Seasonal fluctuations in serum KL-6 levels were observed in patients with SSc-ILD.

Exploring the complexity of systemic sclerosis etiology by trio whole genome sequencing.

Systemic sclerosis (SSc) is a heterogeneous rare autoimmune fibrosing disorder affecting connective tissue. The etiology of systemic sclerosis is largely unknown and many genes have been suggested as susceptibility loci of modest impact by genome-wide association study (GWAS). Multiple factors can contribute to the pathological process of the disease, which makes it more difficult to identify possible disease-causing genetic alterations. In this study, we have applied whole genome sequencing (WGS) in 101 indexed family trios, supplemented with transcriptome sequencing on cultured fibroblast cells of four patients and five family controls where available. Single nucleotide variants (SNVs) and copy number variants (CNVs) were examined, with emphasis on de novo variants. We also performed enrichment test for rare variants in candidate genes previously proposed in association with systemic sclerosis. We identified 42 exonic and 34 ncRNA de novo SNV changes in 101 trios, from a total of over 6000 de novo variants genome wide. We observed higher than expected de novo variants in PRKXP1 gene. We also observed such phenomenon along with increased expression in patient group in NEK7 gene. Additionally, we also observed significant enrichment of rare variants in candidate genes in the patient cohort, further supporting the complexity/multi-factorial etiology of systemic sclerosis. Our findings identify new candidate genes including PRKXP1 and NEK7 for future studies in SSc. We observed rare variant enrichment in candidate genes previously proposed in association with SSc, which suggest more efforts should be pursued to further investigate possible pathogenetic mechanisms associated with those candidate genes.

Senescence and tissue fibrosis: opportunities for therapeutic targeting.

Cellular senescence is a key hallmark of aging. It has now emerged as a key mediator in normal tissue turnover and is associated with a variety of age-related diseases, including organ-specific fibrosis and systemic sclerosis (SSc). This review discusses the recent evidence of the role of senescence in tissue fibrosis, with an emphasis on SSc, a systemic autoimmune rheumatic disease. We discuss the physiological role of these cells, their role in fibrosis, and that targeting these cells specifically could be a new therapeutic avenue in fibrotic disease. We argue that targeting senescent cells, with senolytics or senomorphs, is a viable therapeutic target in fibrotic diseases which remain largely intractable.

The treatment effect of endovascular therapy for chronic limb-threatening ischemia with systemic sclerosis.

Systemic sclerosis (SSc) is a collagen disease with immune abnormalities, vasculopathy, and fibrosis. Ca blockers and prostaglandins are used to treat peripheral circulatory disturbances. Chronic limb-threatening ischemia (CLTI) is a disease characterized by extremity ulcers, necrosis, and pain due to limb ischemia. Since only a few patients present with coexistence of CLTI and SSc, the treatment outcomes of revascularization in these cases are unknown. In this study, we evaluated the clinical characteristics and treatment outcomes of seven patients with CLTI and SSc, and 35 patients with uncomplicated CLTI who were hospitalized from 2012 to 2022. A higher proportion of patients with uncomplicated CLTI had diabetes and male. There were no significant differences in the age at which ischemic ulceration occurred, other comorbidities, or in treatments, including antimicrobial agents, revascularization and amputation, improvement of pain, and the survival time from ulcer onset between the two subgroups. EVT or amputation was performed in six or two of the seven patients with CLTI and SSc, respectively. Among those who underwent EVT, 33% (2/6) achieved epithelialization and 67% (4/6) experienced pain relief. These results suggest that the revascularization in cases with CLTI and SSc should consider factors such as infection and general condition, since revascularization improve the pain of these patients.

Anti-Th/To Antibodies in Scleroderma: Good Prognosis or Serious Concern?

Systemic sclerosis (SSc) represents a rare and intricate autoimmune connective tissue disease, the pathophysiology of which has not been fully understood. Its key features include progressive fibrosis of the skin and internal organs, vasculopathy and aberrant immune activation. While various anti-nuclear antibodies can serve as biomarkers for the classification and prognosis of SSc, their direct role in organ dysfunction remains unclear. Anti-Th/To antibodies are present in approximately 5% of SSc patients, and are particularly prevalent among those with the limited subtype of the disease. Although the presence of these autoantibodies is associated with a mild course of the disease, there is a strong connection between them and severe clinical manifestations of SSc, including interstitial lung disease, pulmonary arterial hypertension and gastrointestinal involvement. Also, the additional clinical correlations, particularly with malignancies, need further research. Moreover, the disease's course seems to be influenced by antibodies, specific serum cytokines and TLR signaling pathways. Understanding the relationships between presence of anti-Th/To, its molecular aspects and response to treatment options is crucial for the development of novel, personalized therapeutic techniques and should undergo profound analysis in future studies.

Pulmonary function in Thai patients with systemic sclerosis; a single center 6-year retrospective study.

Background: Pulmonary involvement is a major cause of internal organ complication and the leading cause of death in patients with systemic sclerosis (SSc). This study aimed to demonstrate the characteristics of pulmonary function (PF) in Thai patients with SSc and the association between PF and body mass index (BMI) and anti-topoisomerase (anti-Scl70). Methods: All patients diagnosed with SSc in our tertiary care teaching hospital database between 2016 and 2021 were reviewed and analyzed. Results: Of 211 SSc patients, 128 patients who underwent the PF test were enrolled; 102 (79.7%) were female. The mean age was 54 years. The median BMI for all patients was 21.7 kg/m 2. Regarding anti-Scl70, 10.9% of patients were positive, 7.8% were negative, and the status was unreported for 81.3%. The mean (SD) forced expiratory volume in one second (FEV1) forced vital capacity (FVC) ratio was 0.8 (0.1). The mean (SD) % predicted values of FEV1, FVC, and diffusing capacity of the lungs for carbon monoxide (DLCO) were 76.3 (16.3), 69.1 (15.8), and 75.5 (22.8), respectively. A restrictive spirometry pattern (RSP) was found in 78.8% of the patients. DLCO had a moderate positive linear correlation with FVC (r=0.50, p <0.001) and a moderate negative linear correlation with BMI (r=-0.36, p <0.001). However, there was no correlation between FVC and BMI. There was no statistical difference in demographic data or the presence of anti-Scl70 among patients with or without RSP. Conclusions: RSP is common among Thai patients with SSc. However, the power of using demographic data and the presence of anti-Scl70 to determine the probability of pulmonary involvement remains limited.

Calcinosis Cutis in Juvenile Systemic Sclerosis.

Juvenile systemic sclerosis (JSSc) is a rare autoimmune disorder that primarily affects children and adolescents. It is thought to be caused by a confluence of immunological, environmental, and genetic variables. The disease is characterized by excessive collagen production. It can result in symptoms such as shortness of breath, chest pain, difficulty swallowing, high blood pressure, and kidney problems. Although calcinosis cutis is common in systemic sclerosis, it is very rare in JSSc. We report the case of a 14-year-old female who presented with complaints of breathlessness for four days and multiple lesions in the sacral region for two months. She underwent surgical excision for calcinosis cutis in dependent regions. Early diagnosis and treatment of the condition are of immense importance in preventing mortality.