Journal of Scleroderma and Related Disorders最新文献

Interstitial lung disease is a common complication and cause of mortality in patients with systemic sclerosis. Pharmacotherapy for systemic sclerosis-associated interstitial lung disease was mostly limited to off-label use of immunosuppressive drugs until recently, when two drugs became licenced for this condition: nintedanib, an antifibrotic agent, and tocilizumab, a targeted anti-inflammatory/immunomodulatory therapy licenced in the United States. In chronic diseases, communication between physicians and patients is associated with treatment adherence, patient satisfaction, and clinical outcomes. This review of physician-patient communication during systemic sclerosis-associated interstitial lung disease treatment covers key issues identified by studies in Japan, the United States and Europe, as well as the clinical experience, opinion, and recommendations of the physician and patient advocate authors. As discussed, recent surveys in Japan found low usage of guideline-recommended immunosuppressive drugs for systemic sclerosis-associated interstitial lung disease and physician dissatisfaction with them. Physicians and patients in Japan also had differing perceptions about what had been said during consultations, suggesting the need to improve physician-patient communication. Other studies in Japan, the United States and Europe made several key findings. Notably, most patients feel uneasy at the diagnosis of systemic sclerosis-associated interstitial lung disease, and both physicians and patients avoid discussing prognosis and mortality. Furthermore, a white-coat barrier hinders patients raising topics important to them. For physicians, listening and empathy may be key for building rapport with patients. Importantly, physicians and patients have different cognitive models of systemic sclerosis-associated interstitial lung disease, creating communication challenges. There are also similarities and differences in clinical practice and physician-patient communication between countries that are important to consider. From the patient's perspective, key factors include the quality of the first consultation, physician empathy and active listening, and space to ask questions. Efforts to improve physician-patient communication include peer mentoring, patient self-education (such as the 'Self-Manage Scleroderma' website from the University of Michigan), and shared decision-making - although not all activities will necessarily be appropriate everywhere.

Objective: The aim of this study was to evaluate the level of agreement among international experts on the World Scleroderma Foundation/Heart Failure Association consensus-based definition of systemic sclerosis-associated primary heart involvement (SSc-pHI) and on the guidance for its screening, diagnosis, and follow-up assessment, including feasibility and applicability assessments.

Methods: An online survey was conducted to assess the level of agreement and feasibility/applicability using a 10-point scale (0 = not at all, 10 = completely agree or completely feasible/applicable). The weblink to the survey was shared with 1199 participants worldwide. A high level of agreement was defined by an average score over 7/10.

Results: In total, 161 external experts completed the survey. Most of them were rheumatologists (80.7%), working in Europe (81.4%), and had > 10 years of clinical experience in managing SSc patients (59%). Overall agreement among external experts was high (mean 8.27, SD 1.86). The highest scores regarded items emphasizing the involvement of a multidisciplinary team, personalization of patient management, and initial evaluation techniques. A lower level of agreement was obtained in questions related to cardiac magnetic resonance imaging and endomyocardial biopsy. No factors associated with low level of agreement and feasibility/applicability were identified.

Conclusion: The consensus-based definition and guidance on screening, diagnosis, and follow-up assessment of SSc-pHI provides a basis for application by the wider community. A lower level of agreement on the use of advanced or more invasive diagnostic techniques likely reflects regional differences in access and the need for more evidence on its use. This emphasizes the importance of involving a multidisciplinary team.

Background and aim: Systemic sclerosis was found to be associated with an increase in cancer incidence. The target of this study was to investigate the most common malignancies and to identify factors that increase the cancer risk in systemic sclerosis patients.

Materials and methods: In this single-centre retrospective study, we screened 252 patients attending our outpatient clinic between January 2005 and December 2021.

Results: A total of 252 systemic sclerosis patients were included in the study. Data for the patients were obtained by evaluating their medical records retrospectively. A total of 252 patients with systemic sclerosis were analysed. Nineteen patients were diagnosed with malignancies. Lung cancer was the most common malignancy among patients. Malignancies were not correlated with sex, follow-up period, type of systemic sclerosis, organ involvement, smoking history, serological tests, comorbidities, dose and duration of disease-modifying antirheumatic drugs (DMARDs), but advanced age at systemic sclerosis diagnosis increased the risk of malignancy (p = 0.017) in systemic sclerosis patients.

Conclusion: In the current study, advanced age at systemic sclerosis diagnosis was determined to be an extra risk factor for the initiation of cancer in systemic sclerosis patients. Particularly in this patient group, additional screenings might be helpful for early diagnosis. Treatments such as methotrexate, cyclophosphamide, azathioprine, and mycophenolate mofetil can be used without additional cancer risk.

Background: Interstitial lung disease is the leading cause of morbidity and mortality in systemic sclerosis, but it is characterized by significant heterogeneity in patient outcomes. So far, little is known about the influence of anti-U1RNP antibodies on lung outcomes in systemic sclerosis-associated interstitial lung disease patients.

Methods: European Scleroderma Trials and Research group systemic sclerosis patients with radiological-confirmed interstitial lung disease, available %predicted forced vital capacity, and autoantibody status were included. Baseline demographic and disease features were compared between anti-U1RNP positive and anti-U1RNP negative patients. Moreover, longitudinal analyses were done measuring relative change in %predicted forced vital capacity over 12 ± 6, 24 ± 6, and 36 ± 6 months, and changes were classified into stable (⩽ 4%), mild (5%-9%), and major progression (⩾ 10%). Predictors associated with death of any cause or major interstitial lung disease progression were evaluated in systemic sclerosis-associated interstitial lung disease patients with or without anti-U1RNP antibodies. Logistic regression analyses and Cox proportional hazards models adjusted for age and FVC were applied.

Results: A total of 6043 systemic sclerosis-associated interstitial lung disease patients were included for the analysis, among which 327 (5.4%) were positive for anti-U1RNP antibodies. Mean age was 56.8 ± 13.2 years and 4971 (82.3%) were women. Anti-U1RNP + systemic sclerosis-associated interstitial lung disease patients had more frequently limited cutaneous systemic sclerosis (63.5.5% vs 53.3%, p < 0.001), higher frequency of joint synovitis (18.1% vs 13.9%, p = 0.039), and myositis (24.0% vs 19.5%, p = 0.048). Anti-U1RNP + patients had a baseline lower mean forced vital capacity (82.0% vs 86.0%, p < 0.001) and lower mean %predicted diffusing capacity for carbon monoxide (57.0% vs 60.5%, p = 0.003). Periods of mild or major FVC decline and mortality rates were not statistically different between the groups.

Conclusion: Systemic sclerosis-associated interstitial lung disease patients positive for anti-U1RNP antibodies have more impaired baseline lung function but similar trajectories of forced vital capacity changes and mortality during the first 3 years of follow-up.

Objectives: Interstitial lung disease in systemic sclerosis has a significant impact in the quality of life. This prospective study was designed to determine the correlation between quality of life in systemic sclerosis-interstitial lung disease patients using patient-reported outcome measures and the lung function test parameters, with assessment done at baseline and 1 year.

Methods: In total, 63 consecutive systemic sclerosis-interstitial lung disease patients underwent lung function test, 6-minute walk distance, and quality of life-validated questionnaires (King's Brief Interstitial Lung Disease and Functional Assessment of Chronic Illness Therapy dyspnea). King's Brief Interstitial Lung Disease covers three components, namely chest, breathlessness, and psychological symptoms. The Functional Assessment of Chronic Illness Therapy dyspnea score has Part I (breathlessness symptoms) and Part II (physical limitation due to breathlessness). All assessments except for 6-minute walk distance were done both at baseline and at 12 months.

Results: Both forced vital capacity predicted percentage at baseline and 12 months had significant negative correlation with the Functional Assessment of Chronic Illness Therapy dyspnea score Part I (p values: 0.038 and <0.001, respectively). Both forced vital capacity and diffuse capacity for carbon monoxide predicted percentage at 12 months were also negatively correlated with Functional Assessment of Chronic Illness Therapy dyspnea score Part II (p values: 0.001 and 0.010, respectively). There was no significant correlation between King's Brief Interstitial Lung Disease score and the lung function parameters, at both baseline and at 1-year interval. Positive significant correlation was observed between forced vital capacity predicted percentage at baseline and 6-minute walk distance (p = 0.001).

Conclusion: Systemic sclerosis-interstitial lung disease affects quality of life, which is best assessed using the Functional Assessment of Chronic Illness Therapy dyspnea score as it correlates significantly with the lung function test parameters.

Objective: The impact of disease on women's health-related quality of life has become increasingly important in patients with rheumatic diseases (RDs). Systemic sclerosis (SSc) mostly affects women with a broad spectrum of clinical presentations and severity, and a variable impact on daily living. The objective of the present study was to specifically address "women's health" in systemic sclerosis patients through a dedicated questionnaire.

Methods: An anonymous self-reported questionnaire (only in Italian) was developed in collaboration with obstetricians and gynecologists and subsequently revised and approved by five patient representatives. The questionnaire was administered to SSc patients during scheduled visits in an outpatient Rheumatology SSc Clinic.

Results: Between April 2021 and March 2023, 168 patients accepted to participate; among them, 44.1% had received their SSc diagnosis during reproductive age (<45 years). The questionnaire was composed of 44 questions and included 5 sections encompassing different topics. A high rate of adherence to female cancer screening programs was recorded (86.9% for cervix and 93.6% for breast cancer), while a non-regular gynecological follow-up was observed in 36.4%, mostly in patients with more severe disease phenotype. Only 42.3% accepted to compile the Female Sexual Function Index (FSFI), which indicated a sexual dysfunction (score ⩽ 26.55) in 66.2% of patients. A worse sexual function was shown to be associated with different disease manifestations, including digital ulcers. More than 90% of patients who expressed a desire for pregnancy after diagnosis received medical pre-conception counseling and were satisfied with the information provided. In contrast, discussion about contraception occurred in 37.8% of patients who had been diagnosed during fertile age. Family planning still represents an unmet need, as 43.6% of patients did not achieve their desired family size, mainly due to concerns about their capacity to care for their children.

Conclusion: The newly developed questionnaire provides a unique opportunity to comprehensively assess the experience of women with SSc. Disease burden was shown to negatively impact sexual function and adherence to regular gynecological visits. Furthermore, receiving a diagnosis during reproductive age may increase the likelihood of a reduced family size. Clinicians who take care of women with SSc should implement these domains into routine management, thus improving the health literacy of their patients.

Introduction: Activation of the coagulation cascade leading to generation of thrombin is well documented in various forms of lung injury including systemic sclerosis-associated interstitial lung disease (SSc-ILD). We previously demonstrated that the direct thrombin inhibitor dabigatran inhibits thrombin-induced profibrotic signaling in lung fibroblasts isolated from scleroderma patients. The objective of this study was to characterize and compare lung fibroblasts from an SSc-ILD patient at baseline and after dabigatran treatment to ascertain this therapy's differential effects on fibrogenic gene expression.

Materials and methods: Lung fibroblasts isolated by bronchoalveolar lavage (BAL) from a SSc-ILD patient before and after receiving dabigatran (Pradaxa^®) 75 mg twice daily for 6 months (ClinicalTrials.gov Identifier NCT02426229) were analyzed by RNA sequencing, real-time quantitative reverse transcription polymerase chain reaction (qRT)-PCR, and immunofluorescent staining.

Results: Thrombin inhibition for six-months by oral dabigatran resulted in significantly decreased expression of 708 lung fibroblast genes as compared to basal levels before dabigatran treatment. Using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we determined that thrombin-inhibition by dabigatran primarily affected extracellular matrix (ECM) and ECM-related genes. Fibrosis-associated genes, including smooth muscle alpha-actin (SMA, ACTA2), tenascin C, collagen 1 alpha 1 (COL1A1), collagen 3 alpha1 (COL3A1), collagen 8 alpha 2 (COL8A2), collagen 10 alpha 1 (COL10A1), collagen 5 alpha 1 (COL5A1), fibronectin 1, connective tissue growth factor (CTGF), and procollagen-lysine-2-oxoglutarate-5-dioxygenase-2 (PLOD2) were all significantly down regulated following thrombin inhibition by dabigatran treatment. Real-time qRT-PCR and immunofluorescent staining confirmed significant downregulation of the selected genes at the mRNA and protein levels.

Conclusion: Inhibition of thrombin in this SSc-ILD patient treated with low-dose dabigatran etexilate downregulated profibrotic proteins in lung fibroblasts, providing further support for the use of thrombin inhibitors as a therapeutic approach for the treatment of patients with SSc-ILD.

Cardiovascular complications are observed in up to one-third of patients with systemic sclerosis (SSc). Early identification and management of SSc-associated primary cardiac disease is often challenging, given the complex disease pathophysiology, significant variability in clinical presentation, and scarce disease-modifying therapeutics. Here, we review the molecular mechanisms involved in SSc-associated cardiac disease pathogenesis, novel diagnostic tools and emerging therapies.

Background: Pain is a prevalent symptom of systemic sclerosis. While previous studies have demonstrated a correlation between higher pain intensity and lower physical function in individuals with systemic sclerosis, the potentially moderating effect of psychosocial factors on the association has yet to be explored.

Methods: This cross-sectional study used data from a fatigue self-management trial for adults with systemic sclerosis. Baseline questionnaire instruments measured pain intensity (11-point scale), physical function (PROMIS 4a short form), and psychosocial factors: positive and negative affect (Positive and Negative Affect Schedule), resilience (Connor-Davidson Resilience Scale), anxiety, depression (PROMIS short forms), and self-efficacy domains (PROMIS item banks). Linear regression quantified the pain intensity-physical function association with interaction terms for candidate psychosocial moderators included in separate models (adjusted for age, systemic sclerosis subtype, and disease duration).

Results: Among 173 participants (mean age 54.5, Standard Deviation 11.7, 93% female, 83% White), 47% had diffuse cutaneous systemic sclerosis, 35% limited, 13% overlap, and 5% other/unsure. Mean pain intensity was 4.9 (Standard Deviation 2.3) and mean physical function T-score was 38.5 (Standard Deviation 6.4). Pain intensity accounted for 31% of the variability in physical function (B -1.34, 95% confidence interval -1.69, -0.99). Statistically significant interactions were found between pain intensity and negative affect and anxiety, with higher levels of these factors amplifying the negative pain-physical function association.

Conclusion: These findings suggest that higher levels of negative affect and anxiety exacerbate the negative effect of pain on physical function in individuals with systemic sclerosis. Interventions targeting these factors may help improve overall physical function regardless of pain intensity.

Gastric antral vascular ectasia is a frequent and potentially severe complication of systemic sclerosis. Management is presently limited to supportive care, acid suppression and endoscopic treatment. Many cases of gastric antral vascular ectasia tend to be refractory or partially responsive to standard treatment and require multiple endoscopic procedures to control the recurrent bleeding. Immunosuppression is not part of the recommended management of gastric antral vascular ectasia: limited data exist on the role of cyclophosphamide or autologous stem cell transplant in severe cases, but no prospective data or randomised controlled trial supports its routine use. Here, we present a case of an adult male patient with diffuse cutaneous systemic sclerosis complicated by arthritis and severe gastric antral vascular ectasia. The latter required multiple endoscopic procedures and remained transfusion-dependent. Due to progressive skin disease and active arthritis refractory to conventional synthetic disease-modifying antirheumatic drugs, the patient was started on tocilizumab. While he showed an early response in terms of scores related to skin involvement and arthritis, response to gastric antral vascular ectasia was unexpected. As soon as the biologic therapy was started, the patient was no longer transfusion-dependent and haemoglobin levels started to rise. Subsequent endoscopic investigations confirmed resolution of gastric antral vascular ectasia. This case is illustrative of an unexpected response to tocilizumab, and this observation is supported by the biological rationale of interleukin-6 in vascular remodelling.