Journal of Scleroderma and Related Disorders最新文献

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.

Autonomic dysfunction is a common and early complication among patients with systemic sclerosis, suggesting that it may play a role in the pathogenesis of the disease and be a potential target for therapeutic interventions. Although the true prevalence of autonomic dysfunction among patients with systemic sclerosis is still unclear, it is estimated that as many as 80% of patients may be affected. Autonomic dysfunction may lead to widespread multi-organ dysfunction through its effects on the cardiovascular system, gastrointestinal tract, urinary tract, sweat and salivary glands, and pupils. Early identification of systemic sclerosis associated with dysautonomia may guide prompt diagnosis in this complex patient population and lay the groundwork for future research in this area. Furthermore, the current landscape of targeted interventions for autonomic dysfunction is rapidly expanding; therefore, prioritizing patients who may benefit from such interventions or candidates for related clinical trials is paramount. Our scoping review details timely updates in the extant literature, including findings from recent studies on autonomic dysfunction in systemic sclerosis, and integrates these updates to identify critical gaps in the field.

Background: Systemic sclerosis is a chronic and rare connective tissue disease with multiorgan effects, including interstitial lung disease (ILD). Navigating systemic sclerosis-interstitial lung disease presents a challenge for patients due to the gaps in patient education, which can impact patient health and quality of life. This study utilized the nominal group technique to identify priority knowledge gaps among patients with systemic sclerosis-interstitial lung disease and inform future educational interventions and research.

Methods: We conducted four structured group sessions using the nominal group technique. Patients with systemic sclerosis-interstitial lung disease were presented with two questions that aimed to identify knowledge gaps. Following participant ranking, investigators performed a thematic analysis of the patients' responses to categorize the generated knowledge gaps.

Results: Twenty-one patients were interviewed and ranked the top three themes for the first question (What questions about your scleroderma-lung disease that you have keep you awake at night?), based on total points, as: (1) Understanding progression, its impacts on the body, and managing health changes (39.7%); (2) anticipating future symptoms and implementing strategies for management and coping (19.8%); and (3) employing and understanding non-pharmacological interventions and self-management strategies (17.5%). The top three themes for the second question (What information do you want about your scleroderma-lung disease that you cannot find?) ranked by total points were: (1) understanding progression, its impacts on the body, and managing health changes (41.3%); (2) navigating health system barriers (16.7%); and (3) research efforts toward treating scleroderma (10.3%).

Conclusions: Our study underscores the importance of understanding the educational needs of patients with systemic sclerosis-interstitial lung disease. Patient responses emphasize the need to comprehensively address concerns about disease management, coping with impacts on social life, and navigating the healthcare system. By addressing these multifaceted concerns, we can design and implement patient-centered education to empower patients through increased support.

Objectives: To evaluate (1) the association between nailfold capillaroscopy pattern and 5-year risk for incident interstitial lung disease and (2) the association between transition in nailfold capillaroscopy pattern and risk of incident interstitial lung disease.

Methods: Data of adult patients from the EUSTAR database fulfilling the ACR-EULAR criteria with a disease duration ⩽5 years, having a scleroderma pattern at nailfold capillaroscopy with high-resolution computed tomography confirmed absence of interstitial lung disease (i.e. baseline) was used. Interstitial lung disease-free survival was assessed for up to 5 years of follow-up with a Cox proportional hazards model stratified on nailfold capillaroscopy pattern at baseline. The association of annual transition in nailfold capillaroscopy pattern on the risk to develop interstitial lung disease was assessed with a mixed logistic regression analysis.

Results: Out of 771 eligible patients, 283 (37%) had an early pattern, 377 (49%) had an active pattern, and 111 (14%) had a late pattern. The Cox proportional hazard model including the identified confounders did not show an association between severity of nailfold capillaroscopy pattern at baseline and increased risk for interstitial lung disease during 5-year follow-up (hazard ratio (95 confidence interval; p value): 1.09 (0.86-1.39; 0.47)). The mixed logistic regression analysis revealed an increased annual risk for incident interstitial lung disease with increasing severity of capillaroscopic pattern (odds ratio (95% confidence interval); p value 3.76 (1.99-7.11; <0.01)).

Conclusion: Our study shows that worsening of nailfold capillaroscopy has a strong association with an increased annual risk to develop interstitial lung disease. Of note, a worse scleroderma pattern at nailfold capillaroscopy is not associated with the long-term risk to develop interstitial lung disease.

Aim: Systemic sclerosis is associated with significant morbidity and mortality. It remains unclear from the literature if there are differences between the subtypes of systemic sclerosis and the rate of hospitalization. Our study investigates the rates of all types of hospitalizations between limited and diffuse cutaneous systemic sclerosis.

Methods: Patients have been collected prospectively using the European Scleroderma Trials and Research Group database at the Waikato Hospital, and were screened for inclusion criteria. Data were collected retrospectively on hospitalizations (total, acute, elective and infusion-related) for all patients.

Results: Overall, 140 patients were included in the analysis with 84 (60.0%) with limited cutaneous systemic sclerosis, 40 (28.6%) with diffuse systemic sclerosis, 3 (2.1%) with systemic sclerosis sine scleroderma and 13 (9.3%) with overlap syndrome. The mean number of total hospitalizations in 12 months was 0.9 (SD 3.0) for patients with limited disease versus 1.7 (SD 3.0) for diffuse disease (p = 0.062). The mean number of acute hospitalizations in 12 months was 0.6 (SD 1.3) for limited and 1.2 (SD 2.4) for diffuse (p = 0.061). Patients with diffuse systemic sclerosis were more likely to be admitted for reasons relating to systemic sclerosis than patients with limited disease (p < 0.001).

Conclusion: Diffuse and limited systemic sclerosis subtypes appear to have similar rates of hospitalizations though there is a trend in favour of diffuse disease towards more total and acute hospitalizations. There are clear differences in causes of hospitalization between the two main subgroups.

Image-guided thermal ablation is an alternative treatment for non-small cell lung cancer and can be performed in patients for whom general anaesthesia is not desired or contraindicated. This minimally invasive treatment is a promising approach in patients with early-stage lung cancer who are considered inoperable due to comorbidities. This short report describes an improved thermal ablation technique that considers the complexity of treating lung carcinoma in scleroderma-associated interstitial lung disease.

Introduction: Evidence has demonstrated that autoimmune diseases tend to coexist at a higher rate than expected, reflecting a common pathogenic pathway. In this study, we investigate the co-occurrence of systemic sclerosis, systemic lupus erythematosus, and Sjogren syndrome in patients with type 1 and type 2 diabetes mellitus.

Methods: Our data were obtained using the 2019 Healthcare Cost and Utilization Project, and International Classification of Diseases, 10th Revision diagnosis codes were used to identify patients with systemic sclerosis, systemic lupus erythematosus, lupus nephritis, and Sjogren syndrome, as well as patients with type 1 and type 2 diabetes. We utilized Statistical Analysis System 9.4 for all analyses and included designated weight values to produce nationally representative estimates.

Results: The prevalence of systemic sclerosis among patients with type 1 diabetes mellitus and type 2 diabetes mellitus was significantly lower than that for the non-diabetes mellitus control group (0.0007% vs 0.09%, p-value = 0.0064 and 0.01% vs 0.07%, p-value < 0.0001), respectively. Similarly, there was a significant decrease in the prevalence of systemic sclerosis with lung involvement in patients with type 1 and type 2 diabetes mellitus, with a statically significant difference in type 2 diabetes mellitus versus nondiabetic group (0.001% vs 0.006%, p-value < 0.0001). We noted a similar pattern regarding the prevalence of systemic lupus erythematosus and lupus nephritis in patients with type 1 and 2 diabetes. Similarly, there was a significant decrease in the prevalence of Sjogren syndrome in patients with type 1 diabetes and type 2 diabetes.

Conclusion: The collected data demonstrates an inverse relation between some autoimmune connective tissue diseases and diabetes. This suggests that these diseases and diabetes mellitus may have different immune pathogenesis. There was also a significantly lower incidence of organ complications such as lupus nephritis and systemic sclerosis lung disease among patients with diabetes, suggesting that diabetes and treatment of diabetes may alter the clinical expression of these disorders.

Advances in pulmonary arterial hypertension therapies have led to improvements in the quality of life and survival for patients with idiopathic pulmonary arterial hypertension, but these trends have not uniformly translated to patients with systemic sclerosis-associated pulmonary arterial hypertension. In order to better understand the heterogeneity in treatment response and survival, we aimed to examine the histological and immunophenotypic differences between the systemic sclerosis-associated pulmonary arterial hypertension and idiopathic pulmonary arterial hypertension pulmonary vasculopathies. We performed a semi-quantitative lung morphometry-based analysis comparing sections obtained from systemic sclerosis-associated pulmonary arterial hypertension (n = 24), idiopathic pulmonary arterial hypertension (n = 9), and control (n = 13) bio-banked lung tissue specimens. H&E (Hematoxylin and Eosin) and VVG (Verhoeff-Van Gieson)-stained lung sections were analyzed for interstitial and vascular pathology. Immunohistochemistry was used to stain for an array of inflammatory and fibrosis mediators. Baseline demographic and hemodynamic data for each patient were collected via chart review at the time of lung explantation. Plexiform lesions were present in 5/9 (55%) of idiopathic pulmonary arterial hypertension samples, but absent in all systemic sclerosis-associated pulmonary arterial hypertension samples (0/24). Systemic sclerosis-associated pulmonary arterial hypertension lungs demonstrated significantly worse interstitial fibrosis (p = 0.0001) and interstitial cellularity (p = 0.0002) compared to idiopathic pulmonary arterial hypertension lungs. The degree of smooth muscle hypertrophy and pulmonary artery intimal proliferation were not different between systemic sclerosis-associated pulmonary arterial hypertension and idiopathic pulmonary arterial hypertension lungs. Immunohistochemistry analysis revealed that systemic sclerosis-associated pulmonary arterial hypertension lungs exhibited increased interstitial infiltration of CD3 T-cells (p = 0.009), CD20 B-cells (p = 0.01), and CD163 macrophages (p = 0.048) when compared to idiopathic pulmonary arterial hypertension and control lungs. Systemic sclerosis-associated pulmonary arterial hypertension lungs display a distinct pulmonary vascular pathology as well as significant interstitial fibrosis when compared to idiopathic pulmonary arterial hypertension lungs.