Journal of Scleroderma and Related Disorders最新文献

Introduction: The relationship between manometric changes and esophageal dilation on chest high-resolution computed tomography is well established in systemic sclerosis, but its association with extra-esophageal manifestations is inconsistent. This study aims to characterize manometric findings in systemic sclerosis patients and to determine potential associations with esophageal body dysmotility.

Methods: Retrospective single-center study including adult systemic sclerosis patients who underwent conventional or high-resolution esophageal manometry. Demographic and clinical data were collected. Associations between esophageal motility and disease duration, immunologic profile, cutaneous and pulmonary involvement, as well as endoscopic or tomographic esophageal alterations were evaluated.

Results: A total of 76 patients were included. Conventional manometry was performed in 60 (78.9%), with aperistalsis observed in 23 (38.3%) and a normotonic lower esophageal sphincter in 45 (75.0%). Sixteen patients (21.1%) underwent high-resolution esophageal manometry, showing normal motility in 9 (56.3%), normotonic lower esophageal sphincter in 9 (56.3%), and hypotonic lower esophageal sphincter in 7 (43.8%). Overall, 46 patients (60.5%) had esophageal body dysmotility and 54 (71.1%) had normotonic lower esophageal sphincter. Most patients (84.2%) had limited cutaneous disease. Median disease duration was 5 years (interquartile range = 11) with mean age 54.1 ± 12.4 years. Seventy-one patients (93.4%) were females. Potential associations with manometric esophageal involvement were compared between patients with normal motility and dysmotility. Esophageal dilation on chest high-resolution computed tomography was more frequent among those with dysmotility (p = 0.005). No significant differences were found regarding disease duration, immunologic profile, modified Rodnan skin score, esophagitis, Barrett's esophagus, interstitial lung disease, forced vital capacity, or single-breath carbon monoxide diffusing capacity.

Discussion: Esophageal involvement was frequent in our sample, although the lower esophageal sphincter was more commonly spared. An association between esophageal dysmotility and its dilation on chest high-resolution computed tomography was found, highlighting the utility of chest high-resolution computed tomography for identification of upper gastrointestinal involvement in systemic sclerosis. No association was found between manometric changes and extra-esophageal manifestations.

Background: Systemic sclerosis is a severe autoimmune disease characterized by fibrosis of the skin and internal organs. Systemic sclerosis is associated with the presence of three specific autoantibodies: anti-topoisomerase I, anti-centromere, and anti-RNA polymerase III autoantibodies, which have also been identified as prognostic factors. However, it remains unknown whether the prognosis also varies based on their serum levels.

Objectives: We aimed to assess the value of serum levels of systemic sclerosis-specific autoantibodies as biomarkers of disease severity and progression in systemic sclerosis.

Design: We conducted a post hoc longitudinal analysis of data of systemic sclerosis patients included in the Zurich EUSTAR cohort, who were positive for at least one of the three systemic sclerosis-specific autoantibodies.

Methods: The association between the levels of systemic sclerosis-specific autoantibodies and disease severity at baseline and during the follow-up was assessed by univariable and multivariable logistic and linear regressions.

Results: The serum levels of anti-topoisomerase I autoantibodies [β = 0.032 (95% confidence interval = 0.014 to 0.049), p < 0.001], anti-centromere [β = 0.002 (95% confidence interval = 0.001 to 0.003), p < 0.001], and anti-RNA polymerase III autoantibodies [β = 0.143 (95% confidence interval = 0.066 to 0.220), p < 0.001] were associated with the modified Rodnan Skin Score in univariable analysis at baseline. For anti-centromere [β = 0.002 (95% confidence interval = 0.001 to 0.003), p < 0.001] and anti-RNA polymerase III autoantibodies [β = 0.135 (95% confidence interval = 0.053 to 0.217), p = 0.002], this association also remained significant in multivariable analysis. In the longitudinal analysis, the levels of the three systemic sclerosis-specific autoantibodies did not predict changes in mRSS over 1 year.

Conclusion: Increased serum levels of all three autoantibodies predicted a more severe skin fibrosis. The results underscore the relevance of measuring the levels of systemic sclerosis-specific autoantibodies to enhance risk stratification in systemic sclerosis, with particular focus on skin involvement.

Objective: There is still a wide variation in the rehabilitation programs developed for systemic sclerosis, which makes it urgent to develop feasible and easy-to-use protocols using tools capable of measuring the response to rehabilitation. The Glittre-ADL test assesses functional exercise capacity using activities of daily living and is useful due to the hands involvement. This study aimed to evaluate the effects of a physiotherapist-supervised home-based rehabilitation program on functional exercise capacity in women with systemic sclerosis using the Glittre-ADL test. A secondary aim was to evaluate the association between the Glittre-ADL test and handgrip strength, hand function, physical function, quality of life, and lung function.

Methods: This is a quasi-experimental study in which 33 women with systemic sclerosis underwent a physiotherapist-supervised home-based rehabilitation program for 12 weeks. The following pre- and post-physiotherapist-supervised home-based rehabilitation program assessments were performed: Glittre-ADL test, Health Assessment Questionnaire Disability Index, Cochin Hand Functional Scale, Short Form 36 Health Survey, handgrip strength, and spirometry.

Results: There was a significant increase in Glittre-ADL test time after physiotherapist-supervised home-based rehabilitation program (p = 0.036). There was a significant decrease in manual time of the Glittre-ADL test between pre- and post-physiotherapist-supervised home-based rehabilitation program (p = 0.001). For Health Assessment Questionnaire Disability Index, there was a significant decrease from 1.13 (0.5-1.8) points before physiotherapist-supervised home-based rehabilitation program to 1.0 (0.4-1.3) points after physiotherapist-supervised home-based rehabilitation program (p = 0.004). For the Cochin Hand Functional Scale, there was a decrease from 14 (5-35) points before physiotherapist-supervised home-based rehabilitation program to 7 (3-21) points after physiotherapist-supervised home-based rehabilitation program (p = 0.0002). There was a significant increase in handgrip strength between pre- and post-PHPR (p = 0.008). The delta for Glittre-ADL test time (%predicted) was significantly correlated with the delta for handgrip strength (r_s  = -0.360, p = 0.039).

Conclusion: After physiotherapist-supervised home-based rehabilitation program, women with systemic sclerosis require less time to complete the Glittre-ADL test tasks. Physiotherapist-supervised home-based rehabilitation program improves manual function, physical function, handgrip strength, lung function, and quality of life. There is a relationship between Glittre-ADL test time and handgrip strength. These results suggest that a 12-week physiotherapist-supervised home-based rehabilitation program could be a beneficial non-pharmacological therapy that reduces

Objectives: Recent research has highlighted the critical role of monocytes and macrophages in driving both inflammatory and fibrotic processes in systemic sclerosis. This study seeks to elucidate the gene expression profiles of systemic sclerosis monocytes and their potential links to disease complications, with the ultimate goal of uncovering novel therapeutic targets.

Methods: A total of 48 systemic sclerosis patients and 15 controls were recruited and monocytes were isolated using CD14+ magnetic beads. Total RNA was extracted and bulk RNA-seq analysis was performed. Differential gene expression followed by unsupervised hierarchical clustering and pathway analysis was conducted, and correlations with clinical features were analyzed. Interferon signature score (IFN6) was calculated using the log transformed values of six genes (IFIT3, IFIT2, MX1, IFIH1, STAT2, and NCF1).

Results: We identified four distinct patient subgroups, relative to normal, two with inflammatory and two with non-inflammatory gene profiles. The inflammatory subgroups exhibited high expression of interferon-related genes and included all systemic sclerosis patients with pulmonary hypertension and most with cardiac involvement. In these patients, IFN6 was markedly elevated and showed a significant correlation with global longitudinal strain (GLS; r = -0.5, p = 0.006), a key indicator of cardiac function. Furthermore, pathway analysis identified an enrichment of the Notch signaling pathway among genes whose overexpression correlated with impaired global longitudinal strain.

Conclusion: These findings unveil a potential new mechanistic link between interferon activity, Notch signaling, and cardiac complications in systemic sclerosis, offering new insights into disease pathogenesis and potential therapeutic targets.

Background: The purpose of this study is to define the prevalence of, and risk factors associated with sexual dysfunction among individuals with systemic sclerosis, evaluate the frequency of sexual health discussions between patients and rheumatologists, identify patient-perceived barriers to these discussions, and assess screening tools for detecting systemic sclerosis-associated sexual dysfunction.

Methods: The Sexual Function in SSc Questionnaire anonymously surveys individuals with self-reported SSc about their sexual function and sexual health discussions with their rheumatologist. Participants were asked to complete the Sexual Function in SSc Questionnaire and the Female Sexual Function Index or International Index of Erectile Function Questionnaire for females and males, respectively. Comparisons were made between those with versus without self-reported sexual dysfunction (measured by the Sexual Function in SSc Questionnaire) using Fisher's exact and t-test, as appropriate. Logistic regression was used to identify predictors of sexual dysfunction. Agreement to statements about barriers to sexual health conversations were compared between those who reported feeling satisfied versus not satisfied with sexual health discussions using Fisher's exact test.

Results: A total of 41 participants completed the Sexual Function in SSc Questionnaire, and 30 (73%) also completed the Female Sexual Function Index or International Index of Erectile Function. Sexual dysfunction was self-reported in 26 (63%) participants. Age, sex, SSc subtype, and time since systemic sclerosis diagnosis were not significant predictors of sexual dysfunction. Twenty-five percent of participants who self-reported sexual dysfunction did not meet the criteria based on the Female Sexual Function Index/International Index of Erectile Function scored assessment. Thirty-six of 41 participants (88%) reported they had never discussed sexual health with their rheumatologist. Among them, 23 (64%) self-reported sexual dysfunction.

Conclusion: Sexual dysfunction is common in systemic sclerosis, yet most participants had never discussed sexual health with their rheumatologist. Discrepancies between self-reported dysfunction and validated questionnaire scores suggest that existing tools may not capture systemic sclerosis-specific concerns. Future studies developing better screening methods and promoting education related to sexual health in SSc care are needed.

Digital ulcers represent a severe manifestation of digital vasculopathy in systemic sclerosis, occasionally with the contribution of microtrauma and calcinosis. These ulcers are often challenging to heal and extremely painful. Regarding analgesic approaches, there is a lack of consensus on best practices, leading to physician experience-guided approaches rather than standardized protocols. To assess the published evidence on the effectiveness of oral and topical analgesics and local anaesthetics for pain reduction in digital ulcer of systemic sclerosis, we conducted a PRISMA-driven systematic review. A search in PubMed and Cochrane databases was performed using the keyword search terms 'digital ulcers', 'finger ulcers', 'systemic sclerosis', 'scleroderma', 'pain management', 'analgesics', 'anaesthetics' and 'painkillers', with the Boolean terms 'AND' and 'OR'. Original studies and case reports were considered for inclusion. Results were screened by title, abstract and full-text. We identified a total of 26 results, of which 5 original papers were included: 2 prospective observational studies, 1 prospective case series, 1 retrospective case series and 1 case report. The evaluated pharmacological strategies were digital nerve block with lidocaine and mepivacaine (one study), oral extended-release oxycodone (two studies), local lidocaine (one study), local lidocaine and prilocaine, local morphine and sublingual morphine (one study). Overall, digital nerve block appeared to provide complete or near-complete pain relief. Oral and topical strategies resulted in reduced pain intensity, although levels remained in the mild-to-moderate range. Concerning adverse outcomes, all strategies were generally well tolerated, with only mild effects reported across studies. Despite limitations, the available evidence suggests that the evaluated analgesics and anaesthetics may provide pain relief for digital ulcer in patients with systemic sclerosis. Future larger-scale studies employing standardized protocols are necessary to further assess the efficacy, optimal dosing and long-term outcomes of these interventions.

Background: Previous data on the relationship between adiponectin and systemic sclerosis are inconsistent and do not establish a causal link. We aimed to perform an updated meta-analysis to estimate the association between circulating adiponectin and systemic sclerosis. Using a two-sample, bidirectional, Mendelian randomization approach, we also tested for a causal relationship between genetically predicted adiponectin levels and systemic sclerosis risk.

Methods: We conducted a systematic literature search of PubMed, Embase, and Web of Science (up to September 2024) to identify studies for meta-analysis. Pooled standardized mean differences were calculated. For bidirectional Mendelian randomization, genetic instruments for circulating adiponectin levels and liability to systemic sclerosis were constructed using publicly available genome-wide association study summary statistics. Causal estimates were primarily summarized using the inverse variance-weighted method, with weighted median, simple median, MR-Egger, and MR-PRESSO as sensitivity analyses. Both meta- and Mendelian randomization analyses were stratified for systemic sclerosis subtypes: diffuse cutaneous and limited cutaneous systemic sclerosis.

Results: Seven studies (439 systemic sclerosis cases, 274 controls) were included in the meta-analysis, indicating lower circulating adiponectin levels in systemic sclerosis patients (standardized mean difference = -0.16, p = 0.07); however, the decrease was statistically significant in diffuse cutaneous systemic sclerosis (p = 0.003) but not limited cutaneous systemic sclerosis (p = 0.81) subgroup. Forward Mendelian randomization analysis did not suggest a causal effect of adiponectin on systemic sclerosis risk (odds ratio = 1.21, p = 0.57), whereas reverse Mendelian randomization provided evidence for a causal effect of genetic liability to systemic sclerosis on lowering circulating adiponectin levels (ß = -0.027, p = 6.8E-06).

Conclusion: Our meta-analysis of observational studies confirmed that systemic sclerosis patients have lower adiponectin levels. Using Mendelian randomization, we established a causal link between genetic liability to systemic sclerosis and lower adiponectin levels. These findings, limited to European ancestry, warrant further research to explore the relationship between systemic sclerosis and adiponectin levels in diverse populations.

[This corrects the article DOI: 10.1177/23971983251334505.].

Introduction: Systemic sclerosis is a systemic autoimmune disease that can affect the hands leading to a deterioration in function. Unfortunately, current medical treatments are considered insufficient to improve patients' quality of life. However, innovative surgical and injectable treatments are available.

Patients and methods: A systematic review of the literature on surgical and injectable treatments available to hand surgeons was carried out according to the PRISMA criteria. All the articles selected were analysed qualitatively and descriptively, and where possible the extracted data were summarised quantitatively.

Results and discussion: Twenty-nine articles were therefore included, comprising 704 patients and 546 procedures. Nine different treatments were identified. Botulinum toxin injections have shown promising clinical results in the treatment of Raynaud's phenomenon, digital ulcers and pain, but have not been confirmed in randomised placebo-controlled trials. Injections of adipose-derived stromal vascular fraction showed positive results in Raynaud's phenomenon, digital ulcer, pain and function, but not in randomised placebo-controlled trials. Autologous fat grafting has shown significant results in Raynaud Phenomenon (RP) and digital ulcers (DUs) healing and prevention. Peripheral sympathectomy has shown moderate beneficial effects with frequent adverse events, and should be reserved for severe cases. Transluminal angioplasty has shown encouraging results, but studies with a high level of evidence are needed. Finally, symptomatic calcinosis cutis should be treated by resection or carbon dioxide (CO2) laser. A treatment algorithm is provided in the Supplemental Appendix.

Conclusion: Interventional treatments for scleroderma of the hand have shown an overall trend of efficacy, but some of the beneficial effects have not been found in studies with a high level of evidence. Further well-conducted studies are needed.

Objectives: To investigate the impact of gastrointestinal involvement in systemic sclerosis affecting the quality of life and systemic sclerosis-related disability using patient-reported outcome measurements (PROMs).

Methods: Data from 160 consecutive systemic sclerosis patients were collected, including clinical characteristics and self-assessment questionnaires. The severity of gastrointestinal involvement was determined by the University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA-GIT 2.0): patients were classified as having "none-to-mild" symptoms (total score = 0.00-0.49: Group A), "moderate" symptoms (Group B), and "severe-to-very severe" symptoms (Group C). All investigations were repeated following 1 year to check the reliability (n = 149).

Results: Quality of life (EuroQol-5 Dimension anxiety/depression, Physical Component Summary, and Mental Component Summary of Short-Form Health Survey-36) and disability questionnaires (Health Assessment Questionnaire Disability Index, Scleroderma Health Assessment Questionnaire), Scleroderma Impact of Disease showed moderate significant correlation with UCLA-GIT 2.0 (rho: 0.400, -0.484, -0.468, 0.400, 0.436, 0.646, respectively). These correlations remained significant when tested in the two main subgroups (limited and diffuse cutaneous systemic sclerosis). Disease duration and UCLA-GIT 2.0 score did not show any correlation (rho: .055, p = 0.488). The average gastrointestinal involvement complaint of early systemic sclerosis (disease duration < 3 years, n = 24) subgroup measured by the UCLA-GIT 2.0 was not different from the rest of the cases (0.13 (0.03-0.46) vs 0.22 (0.08-0.45), p = 0.280). All investigated PROMs regarding quality of life and disability showed worse results in Group B when compared with patients in Group A. Similarly, patients in Group C have worse results compared to Group B. These correlations with the UCLA-GIT 2.0 score were confirmed during the 1-year follow-up.

Conclusion: Moderate/severe gastrointestinal involvement symptoms based on the UCLA-GIT 2.0 are associated with worse quality of life and disability. This correlation holds for both systemic sclerosis subgroups and independent of disease duration: moderate/severe gastrointestinal involvement complaints develop early in systemic sclerosis parallel with early onset of decreased quality of life and disability.