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Objectives: To explore the within-person fluctuations of fatigue in systemic sclerosis and its association with negative affect, positive affect, pain, perceived exertion of physical activity and quality of sleep., Methods: We performed an ecological momentary assessment study in adult patients with a clinical diagnosis of systemic sclerosis. During 14 days, patients completed daily assessments of fatigue severity, negative affect, positive affect, pain, quality of sleep and perceived exertion of physical activity at four fixed time points. The day-to-day fluctuations in fatigue were quantified by the intra-individual variance and probability of acute change, capturing the magnitude and frequency of clinical relevant within-person day-to-day fluctuations, respectively. Using multilevel models, the within-person association between fatigue and the daily assessments were analysed., Results: Fifty-seven patients with systemic sclerosis participated. The mean (standard deviation) intra-individual variance was 1.08 (0.42) and the probability of acute change was mean (standard deviation) 0.40 (0.14), ranging from 0.08 to 0.77. For fatigue, a within-person variation of 51% was observed. Multilevel analyses showed that higher average levels and daily increases in negative affect, pain and perceived exertion of physical activity were associated with more fatigue, while the opposite was observed for positive affect and quality of sleep. Positive affect demonstrated the strongest association with fatigue fluctuations., Conclusion: This is the first quantitative study showing that fatigue in systemic sclerosis is characterized by a dynamic course and that approximately half of the day-to-day fluctuations within persons are clinically meaningful. Furthermore, our results indicate that integrating activities with positive impact on mood into fatigue treatment strategies might reduce the frequency of fatigue fluctuations., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.C.V. received honorary as speaker from Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, MSD, Novartis and Roche, as consultant from Boehringer Ingelheim and Janssen, Grant/research and received support from Research grants from Boehringer Ingelheim, Janssen, Ferrer and Galapagos, none on the subject of this study. J.E.V. received honorary as speaker from Eli Lilly, but this is not pertaining to this study. The remaining authors have declared no conflicts of interest., (© The Author(s) 2024.)

Objectives: Pulmonary hypertension is one of the leading causes of death in systemic sclerosis. Early detection and treatment of pulmonary hypertension in systemic sclerosis is crucial. Nailfold capillaroscopy microscopy, vascular autoantibodies AT1R and ETAR, and several candidate-biomarkers have the potential to serve as noninvasive tools to identify systemic sclerosis patients at risk for developing pulmonary hypertension. Here, we explore the classifying potential of nailfold capillaroscopy microscopy characteristics and serum levels of selected candidate-biomarkers in a sample of systemic sclerosis patients with and without different forms of pulmonary hypertension., Methods: A total of 81 consecutive systemic sclerosis patients were included, 40 with systemic sclerosis pulmonary hypertension and 41 with no pulmonary hypertension. In each group, quantitative and qualitative nailfold capillaroscopy microscopy characteristics, vascular autoantibodies AT1R and ETAR, and serum levels of 24 soluble serum factors were determined. For evaluation of the nailfold capillaroscopy microscopy characteristics, linear regression analysis accounting for age, sex, and diffusing capacity of the lungs for carbon monoxide percentage predicted was used. Autoantibodies and soluble serum factor levels were compared using two-sample t test with equal variances., Results: No statistically significant differences were observed in quantitative or qualitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibody ETAR and AT1R titer between systemic sclerosis-pulmonary hypertension and systemic sclerosis-no pulmonary hypertension. In contrast, several serum levels of soluble factors differed between groups: Endostatin, sVCAM, and VEGFD were increased, and CXCL4, sVEGFR2, and PDGF-AB/BB were decreased in systemic sclerosis-pulmonary hypertension. Random forest classification identified Endostatin and CXCL4 as the most predictive classifiers to distinguish systemic sclerosispulmonary hypertension from systemic sclerosis-no pulmonary hypertension., Conclusion: This study shows the potential for several soluble serum factors to distinguish systemic sclerosis-pulmonary hypertension from systemic sclerosis-no pulmonary hypertension. We found no classifying potential for qualitative or quantitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibodies., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.P.J.van.D. reports Grants or contracts from Janssen Pharmaceutical Company in the past 36 months, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen Pharmaceutical Company and Bayer. M.C.V. reports Research grants from Boehringer Ingelheim, Janssen, Ferrer and Galapagos in the past 36 months, Consulting fees from Boehringer Ingelheim and Janssen, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, MSD, Novartis and Roche, Participation on a Data Safety Monitoring Board or Advisory Board from Corbus pharmaceuticals, Leadership or fiduciary role in other board, society, committee or advocacy group at the Eustar extended board (unpaid). For the other authors competing interests are not applicable. The Editor/Editorial Board Member of JSRD is an author of this paper; therefore, the peer-review process was managed by alternative members of the Board and the submitting Editor/Board member had no involvement in the decision-making process., (© The Author(s) 2023.)

Cyclophosphamide has been the cornerstone of treatment of systemic sclerosis for a long time and is the first-choice therapy for treating systemic sclerosis-associated interstitial lung disease according to the European League Against Rheumatism recommendations on treatment of systemic sclerosis. However, new therapeutic options are emerging, and treatment with cyclophosphamide is hampered by its toxicity and restricted possible treatment duration. This review has a focus on the evidence of efficacy of cyclophosphamide in different aspects of systemic sclerosis and its organ involvements, reviews its toxicity, and will answer the question whether there is still a role for cyclophosphamide in the treatment of systemic sclerosis, taking the evidence and current therapeutic options into account., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objectives: To gain insight into the experiences of patients with diffuse cutaneous systemic sclerosis during and after autologous hematopoietic stem cell transplantation., Methods: Semi-structured interviews were conducted with patients who underwent hematopoietic stem cell transplantation in four university hospitals in the Netherlands. Interviews were transcribed verbatim and thematically analyzed., Results: Nine male and seven female patients were interviewed, median age 47 years (range: 27-68). Patients mentioned their life was severely disrupted before hematopoietic stem cell transplantation and remained unsettled a long time after treatment. Uncertainty because of disease progression, loss of control over health and the sense of time and fear of treatment-related adverse events were common during hospitalization. After hematopoietic stem cell transplantation, patients experienced more physical limitations than they had expected, and recovery took longer and was mentally taxing. Going back to work and finding a new balance in personal relations and social life was complicated. Patients described various strategies to deal with challenges. Family and friends provided essential support, although many experienced a dwindling social circle. Most patients also appreciated peer support. All patients were satisfied with the low threshold for contact with physicians and nurses during hospitalization. However, aftercare focused on medical aspects rather than on psychological well-being and social issues. Moreover, patients would have preferred to be better prepared on what to expect after discharge, and lacked information about self-management, prognosis, optimal recovery, work, sexuality, and family planning., Conclusion: Hematopoietic stem cell transplantation has a major physical and psychological impact on patients with diffuse cutaneous systemic sclerosis. The course of recovery after this intensive therapy was unexpectedly long for some patients and offer of support was far less pro-active post-HSCT compared to pre-HSCT and during HSCT., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Organ involvement often occurs in early systemic sclerosis and has been related to premature death. Identifying patients at diagnosis at risk of developing early organ involvement would be useful to optimize screening and management strategies., Objective: To develop prediction models for the 5-year development of interstitial lung disease, pulmonary arterial hypertension and death., Methods: A European multicentre inception cohort was created. For modelling, predefined clinical variables with known predictive value at diagnosis were used. Univariate and multivariate regression analysis were done to select baseline predictors and build the prediction models. The models were tested using the area under the receiver operating characteristic curve comparing observed and expected frequencies., Results: Of 735 patients, 23% developed interstitial lung disease, 8% developed pulmonary arterial hypertension 12% died. The interstitial lung disease model included diffuse cutaneous systemic sclerosis (OR = 1.8), systemic sclerosis disease duration < 3 years (OR = 1.4), puffy fingers (OR = 1.6), and anti-topoisomerase-I-antibodies (OR = 1.8). The pulmonary arterial hypertension model included age > 65 years (OR = 3.2), forced vital capacity < 70% (OR = 2.5) and diffusing capacity of the lung for carbon monoxide < 55% (OR = 1.9). Death was predicted best by age > 65 years (OR = 4.1), male gender (OR = 1.9), no anti-centromere antibodies (OR = 0.5), proteinuria (OR = 1.9), forced vital capacity < 70% (OR = 1.8) and pulmonary arterial hypertension at diagnosis (OR = 10.1). The area under the receiver operating characteristic was 0.66 (95% CI 0.64-0.67), 0.66 (95% CI 0.64-0.68) and 0.70 (95% CI 0.69-0.72), respectively., Conclusion: We have shown that it is possible to predict interstitial lung disease, pulmonary arterial hypertension and death using established variables already available at the moment of systemic sclerosis diagnosis. Discriminatory performance of the models was suboptimal. Further research including new variables is necessary to improve performance., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)