RESUMEN

OBJECTIVES: Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory esophagitis. METHODS: We performed a cross-sectional study in a single-center cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an esophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive esophagitis were compared with those with endoscopically normal esophageal mucosa. RESULTS: A total of 69 patients were included, from these, 23 patients (33%) had PPI-refractory esophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal esophageal mucosa. On univariate analysis, patients with PPI-refractory esophagitis were more frequently diffuse SSc subset (43% vs 17%; p= 0.041). Evaluating gastrointestinal motility tests, neither absent esophageal contractility (39% vs 25%, p= 0.292) nor hypotensive lower esophageal sphincter (47% vs 44%, p= 0.980) were significantly associated with PPI-refractory esophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory esophagitis (66 vs 8%, p = <0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (ß = 0.751, p= 0.010) was independently associated with PPI-refractory esophagitis, while absent esophageal contractility (ß = 0.044, p= 0.886) or a hypotensive LES were not (ß=-0.131, p= 0.663). CONCLUSIONS: Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory esophagitis in patients with systemic sclerosis.

RESUMEN

OBJECTIVE: To develop a multivariable model for predicting the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) over 52 weeks. METHODS: We used logistic regression models to analyse associations between candidate predictors assessed at baseline and progression of SSc-ILD (absolute decline in forced vital capacity (FVC) % predicted >5% or death) over 52 weeks in the placebo group of the SENSCIS trial. Analyses were performed in the overall placebo group and in a subgroup with early and/or inflammatory SSc and/or severe skin fibrosis (<18 months since first non-Raynaud symptom, elevated inflammatory markers, and/or modified Rodnan skin score (mRSS) >18) at baseline. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: In the overall placebo group (n=288), the performance of the final multivariable model for predicting SSc-ILD progression was moderate (apparent AUC: 0.63). A stronger model, with an apparent AUC of 0.75, was developed in the subgroup with early and/or inflammatory SSc and/or severe skin fibrosis at baseline (n=155). This model included diffusing capacity of the lung for carbon monoxide (DLco) % predicted, time since first non-Raynaud symptom, mRSS, anti-topoisomerase I antibody status and mycophenolate use. CONCLUSION: Prediction of the progression of SSc-ILD may require different approaches in distinct subgroups of patients. Among patients with SSc-ILD and early and/or inflammatory SSc and/or severe skin fibrosis, a nomogram based on a multivariable model may be of value for identifying patients at risk of short-term progression.

Asunto(s)

RESUMEN

Morphea is a rare autoimmune disease that often affects skin and subcutaneous tissues. The aim of this study was to determine the association between patient demographic parameters, lesion site, clinical subtype of morphea, and histological findings. Between 2016 and 2022, we investigated 78 patients with morphea at the Department of Pathology, Prof. Dr. Cemil Tascioglu City Hospital in Turkey. Case-specific hematoxylin and eosin stain slides were obtained from the pathology archive and assessed blindly by two pathologists. Flattening of rete ridges, location of inflammatory infiltrate, grade of inflammatory infiltrate, presence of plasma cells, presence of eosinophils, homogenization of dermal collagen, decrease of skin appendages, basal pigmentation and melanin incontinence were evaluated. Statistical analyses were performed using SPSS Statistics v.20 (IBM, Armonk, NY, USA). The most common clinical presentation was plaque type (87.5%), while histopathological findings included homogenization of dermal collagen (100%) and decrease of skin appendages (98.7%). Flattening of the rete ridges was observed in 46.2% of patients. Severity of the inflammatory infiltrate was found to be higher in these patients (p=0.028). Basal pigmentation was observed in 59% of patients. Line sign was more common in lower extremity lesions among all localizations (p=0.015). The histopathologic features of morphea are variable and confusing. Particularly, in cases with collagen homogenization, morphea should be considered in differential diagnosis with clinical correlation. In addition, the line sign could be helpful for identifying lesions located in the lower extremities.

RESUMEN

OBJECTIVES: The current understanding of survival prediction of lung transplant (LTx) patients with systemic sclerosis (SSc) is limited. This study aims to identify novel image features from preoperative chest CT scans associated with post-LTx survival in SSc patients and integrate them into comprehensive prediction models. MATERIALS AND METHODS: We conducted a retrospective study based on a cohort of SSc patients with demographic information, clinical data, and preoperative chest CT scans who underwent LTx between 2004 and 2020. This cohort consists of 102 patients (mean age, 50 years ± 10, 61% (62/102) females). Five CT-derived body composition features (bone, skeletal muscle, visceral, subcutaneous, and intramuscular adipose tissues) and three CT-derived cardiopulmonary features (heart, arteries, and veins) were automatically computed using 3-D convolutional neural networks. Cox regression was used to identify post-LTx survival factors, generate composite prediction models, and stratify patients based on mortality risk. Model performance was assessed using the area under the receiver operating characteristics curve (ROC-AUC). RESULTS: Muscle mass ratio, bone density, artery-vein volume ratio, muscle volume, and heart volume ratio computed from CT images were significantly associated with post-LTx survival. Models using only CT-derived features outperformed all state-of-the-art clinical models in predicting post-LTx survival. The addition of CT-derived features improved the performance of traditional models at 1-year, 3-year, and 5-year survival prediction with maximum AUC scores of 0.77 (0.67-0.86), 0.85 (0.77-0.93), and 0.90 (95% CI: 0.83-0.97), respectively. CONCLUSION: The integration of CT-derived features with demographic and clinical features can significantly improve t post-LTx survival prediction and identify high-risk SSc patients. KEY POINTS: Question What CT features can predict post-lung-transplant survival for SSc patients? Finding CT body composition features such as muscle mass, bone density, and cardiopulmonary volumes significantly predict survival. Clinical relevance Our individualized risk assessment tool can better guide clinicians in choosing and managing patients requiring lung transplant for systemic sclerosis.

RESUMEN

INTRODUCTION: Systemic sclerosis (SSc) is the rheumatic disease with the highest individual mortality rate with detrimental impact on quality of life. Cell-based therapies may offer new perspectives for this disease as recent phase I trials support the safety of IV infusion of allogeneic mesenchymal stromal cells in SSc and case reports highlight the potential use of Chimeric Antigen Receptor (CAR)-T cells targeting CD19 in active SSc patients who have not responded to conventional immunosuppressive therapies. AREAS COVERED: This narrative review highlights the most recent evidence supporting the use of cellular therapies in SSc as well as their potential mechanisms of action and discusses future perspectives for cell-based therapies in SSc. Medline/PubMed was used to identify the articles of interest, using the key words 'Cellular therapies,' 'Mesenchymal stromal cells,' 'Chimeric Antigen Receptor' AND 'systemic sclerosis.' Milestones articles reported by the authors were also used. EXPERT OPINION: Cellular therapies may represent an opportunity for long term remission/cure in patients with different autoimmune diseases, including SSc who have not responded to conventional therapies. Multiple ongoing Phase I/II trials will provide greater insights into efficacy and toxicity of cellular therapies.

RESUMEN

Juvenile localized and systemic scleroderma are rare autoimmune diseases which cause significant disability and morbidity in children. The mechanisms driving juvenile scleroderma remain unclear, necessitating further cellular and molecular level studies. The Visium CytAssist spatial transcriptomics (ST) platform, which preserves the spatial location of cells and simultaneously sequences the whole transcriptome, was employed to profile the histopathological slides from skin lesions of juvenile scleroderma patients. (1) Spatial domains were identified from ST data and exhibited strong concordance with the pathologist's annotations of anatomical structures. (2) The integration of paired ST data and single-cell RNA sequencing (scRNA-seq) from the same patients validated the comparable accuracy of the two platforms and facilitated the estimation of cell type composition in ST data. (3) The pathologist-annotated immune infiltrates, such as perivascular immune infiltrates, were clearly delineated by the ST analysis, underscoring the biological relevance of the findings. This is the first study utilizing spatial transcriptomics to investigate skin lesions in juvenile scleroderma patients. The validity of the ST data was corroborated by gene expression analyses and the pathologist's assessments. Integration with scRNA-seq data facilitated the cell type-level analysis and validation. Analyses of immune infiltrates through combined ST data and pathological review enhances our understanding of the pathogenesis of juvenile scleroderma.

Asunto(s)

RESUMEN

The association between systemic scleroderma and malignancy is well-documented, but there is limited data on the relationship between morphea and malignancy. This study aims to assess the incidence and types of malignancies in morphea patients, comparing demographics, clinical characteristics, treatments, and outcomes between those with and without malignancy. We conducted a retrospective study of 204 morphea patients treated at Rabin Medical Center between 2012 and 2023. Data on demographics, clinical subtypes, comorbidities, treatments, and outcomes were collected. Patients were categorized based on malignancy status and the timing of malignancy relative to their morphea diagnosis. Among the 204 patients (154 women and 50 men, mean age 53.7 ± 20 years), 47 (23%) developed malignancies. In 29 patients (61.7%), malignancy occurred before the onset of morphea; in 23 patients (48.9%), it occurred after morphea. Five patients (10.6%) had malignancies both before and after the diagnosis of morphea. Patients with malignancy were significantly older than those without (64.7 ± 15.1 years vs. 50.3 ± 20 years, p < 0.0001). The all-cause mortality rate was higher in the malignancy group compared to those without malignancy (23.4% vs. 3.8%, p = 0.00002). Moreover, mortality was higher in patients whose malignancy occurred after morphea than in those whose malignancy preceded morphea (26% vs. 17.2%). The most common post-morphea malignancies in our cohort included non-melanoma skin cancer, cervical cancer, breast cancer, stomach cancer, and lung cancer. The most common pre-morphea malignancies included breast cancer, non-melanoma skin cancer, colon cancer, prostate cancer, and testicular cancer. This study suggests potential associations between morphea and malignancies, influenced by patient age, sequence of diagnosis, and treatment regimens. Further control studies are needed to explore these relationships more definitively.

Asunto(s)

RESUMEN

Systemic sclerosis (SSc) is a complex, autoimmune connective tissue disease that affects multiple organs in the body, culminating in a variance of severity and a reduced quality of life. Breast cancer (BC) also affects patients with SSc, and these two conditions affect a similar demographic. With this systematic review, we aim to characterize the links between SSc and BC. Characterizing possible links between SSc and breast malignancies is important for advancing the understanding of SSc management and comorbidities. In this systematic meta-analysis, a comprehensive literature search was conducted in PubMed using relevant keywords and MeSH terms. The inclusion criteria included an English-language retrospective analysis that characterized patients with SSc with or without BC. Two independent reviewers assessed the study's eligibility based on predetermined criteria. Data extraction included patient antibody measurements, demographics (age and gender), family history, social behaviors (alcohol use and smoking history), concurrent condition treatments, and adverse effects following treatment. Thirteen articles were identified in the literature with relevant data on SSc and BC patients. Studies encompassed research about SSc patients with or without BC and relevant risk factors being measured. SSc was found to have a link to antibodies widely associated with cancer. Adverse treatment outcomes and concurrent conditions of BC were found when patients had a family history of SSc, BC, or an alcohol or smoking history. Our results suggest that the presence of antinuclear antibodies, anti-centromere antibodies, or anti-topoisomerase antibodies in SSc patients is correlated with BC. Out of the three antibodies, ATA seemed to be found more commonly in patients with SSc and malignancy across the studies. This systematic review discusses the link between SSc and BC through patients with relevant clinical markers, medical histories, and treatments. However, further research is necessary to advance the linkage between SSc and BC and determine whether management of one condition may prevent or alleviate the other.

RESUMEN

An 83-year-old female patient presented to our nephrology outpatient clinic with complaints of weakness, edema, abdominal pain, and constipation, with a preliminary diagnosis of chronic kidney failure related to heart failure. The patient had undergone mitral valve replacement surgery 10 years prior and was diagnosed with chronic renal failure six years prior. Laboratory tests revealed mild normochromic normocytic anemia, consistently high erythrocyte sedimentation rate (ESR) above 100 mm/h, and nephrotic-range proteinuria, prompting suspicion of multiple myeloma. Further investigations, including bone marrow aspiration, confirmed the diagnosis of multiple myeloma. During follow-up, the patient began to complain of difficulty swallowing and symptoms of microstomia. Upon further questioning, it was discovered that these symptoms had been present for more than 10 years. Immunoblot tests revealed positive centromere protein B (CENP-B), suggesting a diagnosis of scleroderma. Subsequently, during follow-up, bullous lesions appeared on the patient's chest. Biopsy samples confirmed a diagnosis of bullous pemphigoid (BP). The co-occurrence of scleroderma, multiple myeloma, and superimposed BP represents a rare and noteworthy case for publication.

RESUMEN

OBJECTIVES: Physician's evaluation of interstitial lung disease (ILD) extension with high-resolution computed tomography (HRCT) has limitations such as lack of objectivity and reproducibility. This study aimed to investigate the utility of computer-based deep-learning analysis using QZIP-ILD® software (DL-QZIP) compared with conventional approaches in connective tissue disease (CTD) -related ILD. METHODS: Patients with CTD-ILD visiting our Rheumatology Centre between December 2020 and April 2024 were recruited. Quantitative scores, including the percentage of lung involvement in ground-glass opacity (QGG), total fibrotic lesion (QFIB), and overall ILD extension encompassing both QGG and QFIB (QILD), calculated by DL-QZIP, were compared with semiquantitative visual method, employing intraclass correlation coefficients (ICC). We compared the capability of QILD scores to distinguish patients with forced vital capacity (FVC) % <70 in both methods determined by the area under the curve (AUC) by the receiver-operating characteristic curve analysis and DeLong's test. RESULTS: Eighty patients (median age, 66 years; 14 men) were included. Median QGG, QFIB, and QILD scores were 3.45%, 2.19%, and 5.35% using DL-QZIP, and 3.25%, 4.06%, and 8.48% using visual method, respectively. Correlations between DL-QZIP and visual method were 0.75 for QGG, 0.61 for QFIB, and 0.75 for QILD. The AUC of QILD scores for FVC% <70 was significantly higher with DL-QZIP (0.833) compared with visual method (0.660) (p < 0.01). CONCLUSION: QZIP-ILD® demonstrates superior capability in distinguishing patients with a radiological scenario correlated to severe physiological impairment, while showing relatively good correlations in quantifying the extent on HRCT compared with conventional method in CTD-ILD.

RESUMEN

Objectives: To comprehensively review systematic reviews of prevalence, incidence, and mortality of Raynaud's, Sjögren's and Scleroderma, and to identify any research gaps. Methods: An umbrella review of English language systematic reviews was undertaken using PubMed and Embase (OVID) covering the period 2000-2023 (PROSPERO CRD42023434865). The estimate and its corresponding 95% confidence interval were reported when available from each systematic review. The quality of systematic reviews was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) tool. A narrative synthesis was undertaken. Results: Seventeen systematic reviews were identified, of which 1 was for RP, 5 for Sjögren's and 11 for Scleroderma. There were some high-quality systematic reviews for Sjögren's and mortality of Scleroderma. However, there were only low-quality systematic reviews of prevalence and incidence of RP and Scleroderma. Furthermore, there were no systematic reviews for the mortality of RP. For RP, the pooled prevalence was 4850 per 100 000; pooled annual incidence was 250 per 100 000. For Sjögren's, prevalence was 60-70 per 100 000; annual incidence was 6.92 per 100 000 and the pooled standardized mortality ratio ranged from 1.38 to 1.48. For Scleroderma, pooled prevalence ranged from 17.6 to 23 per 100 000; annual incidence was 1.4 per 100 000; and the pooled standardized mortality ratio ranged from 2.72 to 3.53. Conclusion: The outcomes of RP were less well described compared with Sjögren's and Scleroderma. There was a lack of high-quality systematic reviews for the prevalence and incidence of RP and Scleroderma. Therefore, further studies and systematic reviews with rigorous case definitions, assessing different ethnic groups are warranted in this area.

RESUMEN

Background: Systemic sclerosis (SSc), as an autoimmune rheumatic disease characterized by immune dysregulation and vasculopathy, affects multiple organs. Due to the high burden of its symptoms on the health care system, this study aims to investigate the effects of probiotic supplements in patients with SSc. Methods: We searched electronic databases with predefined search terms in PubMed, Scopus, and ISI Web of Science up to June 2023. Randomized controlled trials that evaluated the effects of probiotic supplementation in adult patients suffering from SSc were included in the study. Results of the included studies were reported as weighted mean difference (WMD) with a 95 % confidence interval (CI). Results: Four studies met the inclusion criteria and were included in the meta-analysis. There was a total of 176 SSc patients. The results show a significant effect of probiotics supplementation on gastrointestinal (GI) symptoms containing reflux (WMD: -0.36, 95 % CI: -0.51 to -0.22, p-value <0.001), gas and bloating (WMD: -0.88, 95 % CI: -1.05 to -0.7, p-value<0.001). However, the results for constipation (WMD: -0.12, 95 % CI: -0.27 to 0.04, p-value = 0.13), diarrhea (WMD: -0.14, 95 % CI: -0.31 to 0.03, p-value = 0.10), and fecal incontinence (WMD: 0.04, 95 % CI: -0.06 to 0.15, p-value = 0.43) were insignificant. Conclusion: Supplementing with probiotics may alleviate a few numbers of GI complications in SSc. Nevertheless, due to the limited number of studies, more well-designed studies are needed to strengthen these results.

RESUMEN

Background: The application of autologous fat transplantation in facial lesions of patients with localized scleroderma (LoS) has been reported in recent years. Objective: The authors report a case of worsening of active localized scleroderma after autologous fat transplantation. Methods: A man presented with neck and facial skin atrophy and pigmentation with a history of LoS. Appearing 1.5 years ago, the lesion had progressively grown in size and shape. Consent was obtained after the patient was informed of the possible surgical risks during the active phase of the disease. He underwent autologous fat grafting into the right cheek with about 30 ml Coleman fat graft. Results: Skin dyspigmentation and atrophy progressively deteriorated 1 month into therapy, with slightly increased erythema and enlargement of the lesion. Six months after the therapy, the localized scleroderma-related score worsened. Limitations: There are different factors, such as that systemic medications could affect the treatment of localized scleroderma by autologous fat transplantation. Meanwhile, considering the limitation of the 6-month follow-up period, obtaining long-term follow-up data is necessary to evaluate sustained outcomes and potential complications. Conclusion: More clinical research is needed to determine the time interval between disease inactivity and the application of any surgical procedures to avoid reactivation.

RESUMEN

This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives. It is an update of the previous 2015 SSc guideline. The recommendations were developed and agreed by the group and are underpinned by published evidence, assessed by systematic literature review and reinforced by collective expert opinion of the group. It considers all aspects of SSc including general management, treatment of organ-based complications, including cardiopulmonary, renal and gastrointestinal tract manifestations, as well as broader impact of disease. Whilst it is focused on adults with SSc we expect that the guideline will be relevant to people of all ages and expert input and review by paediatric rheumatologists and other relevant specialists considered where the guideline was, or may not be, applicable to young people with SSc and juvenile-onset disease. In addition to providing guidance on disease assessment and management the full guideline also considers service organization within the National Health Service and future approaches to audit of the guideline. The lay summary that accompanies this abstract can be found in Supplemental information 1.

RESUMEN

This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives. It is an update of the previous 2015 SSc guideline. The recommendations were developed and agreed by the group and are underpinned by published evidence, assessed by systematic literature review and reinforced by collective expert opinion of the group. It considers all aspects of SSc including general management, treatment of organ-based complications, including cardiopulmonary, renal and gastrointestinal tract manifestations, as well as broader impact of disease. Whilst it is focused on adults with SSc we expect that the guideline will be relevant to people of all ages and expert input and review by paediatric rheumatologists and other relevant specialists considered where the guideline was, or may not be, applicable to young people with SSc and juvenile-onset disease. In addition to providing guidance on disease assessment and management the full guideline also considers service organization within the National Health Service and future approaches to audit of the guideline. The lay summary that accompanies this abstract can be found in Supplemental information 1.

RESUMEN

Excimer light is a subtype of NB-UVB that emits a 308 nm wavelength, and can provide targeted phototherapy treatment. The absorption of 308 nm light by skin cells leads to therapeutic response in various common and ultraviolet-responsive skin diseases, such as psoriasis and vitiligo, and photo-resistant skin diseases such as prurigo nodularis, localized scleroderma, genital lichen sclerosis, and granuloma annulare, cutaneous T-cell lymphomas, among others. Excimer light has few adverse reactions and overall is well tolerated by patients, furthermore, it can be performed in places that are difficult to access. This article aims to explain the therapeutic bases and applications of excimer light in current dermatology.

RESUMEN

Prior evidence suggests that altered energy metabolism plays a crucial role in the development of fibrotic diseases. Recent research indicates that systemic sclerosis (SSc) patients have potentially benefited from energy management, implying that basal metabolic rate (BMR), a vital energy metabolic parameter, may be related to SSc. However, the causal effect of BMR on SSc remains unknown. Thus, we aimed to elucidate the causal links between BMR and SSc. Based on summary statistics from the genome-wide association studies (GWAS) database, two-sample Mendelian randomization (MR) was applied to explore causality between BMR and SSc. The causal relationships were assessed employing inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods. Meanwhile, several sensitivity analyses were carried out to ensure the robustness of the findings. There was an underlying genetic association of BMR on SSc (OR = 0.505, 95% CI: 0.272-0.936, P = 0.030). Moreover, no significant causal effect between SSc and BMR was observed in the reverse MR analysis (OR = 0.999, 95% CI: 0.997-1.001, P = 0.292). According to the sensitivity analysis, the presence of heterogeneity and genetic pleiotropy was not detected. Our findings, derived from a genetic perspective, provide robust evidence of a causal connection between BMR and SSc. To verify these results and clarify the potential mechanisms, further research is warranted.

Asunto(s)

RESUMEN

Morphea, a form of localized scleroderma, can significantly affect individuals by causing skin tightening and discoloration. We describe the case of a 22-year-old woman who presented with progressive skin changes and discomfort in her right gluteal region following a history of an intramuscular injection in the right gluteal region. Clinical examination suggested morphea, prompting us to conduct an MRI to better understand the extent and nature of her condition. The MRI results revealed thickening of the skin layers and signs of inflammation, helping us differentiate between active inflammation and fibrosis. This case illustrates how MRI can provide crucial insights for managing morphea effectively.