Rheumatology and immunology research最新文献

Early diagnosis of interstitial lung disease (ILD) and pulmonary hypertension (PH) is crucial in systemic sclerosis (SSc) for both management and treatment. However, diagnosing SSc-ILD can be challenging because symptoms of lung involvement are often non-specific at the early stages of disease. High-resolution computed tomography (HRCT) of the chest is recognized as the most accurate imaging modality for baseline and follow-up evaluation of SSc-ILD. Key features of SSc-ILD on HRCT include a non-specific interstitial pneumonia (NSIP) pattern, with peripheral ground-glass opacities and extensive traction bronchiectasis. Less common HRCT manifestations include usual interstitial pneumonia (UIP) pattern, followed by diffuse alveolar damage (DAD), diffuse alveolar hemorrhage (DAH) and organizing pneumonia (OP). The extent of disease on HRCT is known to relate with prognosis and serial assessments can be helpful in monitoring disease progression or treatment response. We discuss the main chest computed tomography (CT) manifestations of SSc, highlighting the role of imaging at both baseline and follow-up evaluations.

Interstitial lung disease (ILD) is a frequent important complication of systemic sclerosis (SSc). Factors relevant to aetiopathogenesis of SSc are also central to SSc-ILD. Severity of SSc-ILD is variable but it has a major impact on morbidity and mortality. Factors determining SSc-ILD susceptibility reflect the genetic architecture of SSc and are increasingly being defined. There are aspects linked to immunogenomics and non-immunological genetic factors that may be less conserved and underlie some of the geographical and racial diversity of SSc. These associations may also underlie important links between autoantibody subgroups and patient level risk of SSc-ILD. Examination of blood and tissue samples and observational clinical research together with integrated analysis of in vitro and in vivo preclinical models have elucidated pathogenic mechanisms of SSc-ILD. These have confirmed the potential importance of immune mechanisms in the innate and adaptive immune systemic as well as a significant role for profibrotic pathways especially transforming growth factor beta (TGFbeta) and its regulators and downstream mediators. Recent analysis of clinical trial cohorts as well as integrated and multilevel high dimensional analysis of bio-samples has shed further light on SSc-ILD. This is likely to underpin future advances in stratified and precision medicine for treatment of SSc.

Interstitial lung diseases (ILD) encompass a wide range of disorders characterized by alveolar inflammation and fibrotic tissue remodeling, marked by significant morbidity and mortality. Systemic sclerosis (SSc), among other connective tissue diseases, is a frequent cause of ILD. Assessment of pulmonary fibrosis is frequently constrained by the delayed manifestations of profibrotic activation of fibroblasts, which results in late macroscopic alterations detectable by standard imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans. 68Ga-labeled fibroblast activation protein inhibitors (68Ga-FAPI [fibroblast activation protein inhibitor]) are novel radionuclides used in the selective positron emission tomography/computed tomography (PET/CT) detection of profibrotic fibroblasts, a key player in fibrotic tissue remodeling. Application of 68Ga-FAPI in different target organs undergoing fibrosis, such as lung and heart, highlights its efficacy in detecting ongoing fibrotic processes, since FAPI tracer uptake has been correlated with clinical disease progression markers in SSc-ILD. This feature could enable physicians to detect subclinical fibrotic activity and tailor an individualised therapy plan on a case by case basis. The use of 68Ga-FAPI in ILD and other fibrotic conditions may emerge as a novel tool in future clinical practice for both activity monitoring and treatment optimisation. Other tracers tested in ILD of different etiologies have shown promising results and may in future also be considered for potential application in SSc-ILD.

Cardiac magnetic resonance imaging (CMR) is the gold-standard non-invasive method of assessing cardiac structure and function, including tissue characterisation. In systemic sclerosis (SSc), heart involvement (SHI) is a leading cause of mortality yet remains poorly understood. SHI is underestimated by conventional echocardiography, and CMR provides an important opportunity to better identify and quantify subtle myocardial changes including oedema and fibrosis. This review summarises current CMR techniques, the role of CMR in SSc and SHI, and the opportunities to further our understanding of its pathogenesis and management.

Systemic sclerosis is a multisystemic disease for which the heart can be affected leading to cardiac complications and mortality. Up to 80% of patients with systemic sclerosis have cardiac involvement with varying levels of severity. Several molecules have been identified that can be used as markers of cardiac involvement. These biomarkers can arise directly from the heart due to cardiac damage from the disease such as cardiac troponins or from the underlying dysregulated immune process itself such as the proinflammatory cytokines including interleukin (IL)-6. This review aims to summarize the evidence on currently known biomarkers that are can be diagnostic, prognostic or predictive of primary cardiac involvement in systemic sclerosis. We also highlight potential new biomarkers based on the current understanding of the disease process. Clinical use of these markers can benefit patients through earlier identification of those with cardiac involvement, many of whom can be asymptomatic in the early stage, with higher risk of complications, with the overall goal to improve outcomes of these affected patients.

Background and objectives: The functional disability status of Indian children with juvenile idiopathic arthritis is unidentified. In this cross-sectional study functional capacity of 60 juvenile idiopathic arthritis patients was assessed by the Childhood Health Assessment Questionnaire.

Methods: A total of 60 juvenile idiopathic arthritis patients aged ranges from 1 to 12 years were recruited from a teaching hospital in eastern India. A childhood health assessment questionnaire was used to assess the functional health of children. Pain, patient's/parent's global assessment of general well-being, and physician's global assessment were assessed.

Results: Childhood health assessment questionnaire disability index for oligoarticular juvenile idiopathic arthritis differed significantly from polyarticular juvenile idiopathic arthritis (P < 0.001), systemic-onset juvenile idiopathic arthritis (P = 0.018) and undifferentiated juvenile idiopathic arthritis (P < 0.001). There was a good to a strong positive correlation between the childhood health assessment questionnaire disability index with pain score, patient's/parent's global assessment score, and physician global assessment score for the total juvenile idiopathic arthritis cohort. regarding juvenile idiopathic arthritis subtypes, significant correlations were noted between the childhood health assessment questionnaire disability index with the patient's/parent's global assessment and physician's global assessment (except for enthesitis-related arthritis).

Conclusions: Assessment and documentation of the functional health status of juvenile idiopathic arthritis patients will improve the management of the disease.

Background and objectives: Left ventricular systolic dysfunction (LVSD) is a cardiac involvement that is the leading cause of death among patients with systemic sclerosis (SSc). We aimed to define the clinical course and predictors of LVSD among SSc patients.

Methods: We conducted a cohort study among adult patients with SSc who were followed up from 2013 to 2020. Semiparametric Cox regression analysis with robust clustering by cohort identification number was used to evaluate the predictors of LVSD.

Results: Among the 3, 987 person-years, LVSD was defined in 35 of 419 SSc patients for an incidence of 0.88 per 100 person-years. The median duration of the disease was 8.5 (interquartile range (IQR) 4.9-12.9) years. Every 1-point increase in the modified Rodnan skin score (mRSS) and salt and pepper skin were strong predictors of LVSD, with a respective adjusted hazard ratio (HR) of 1.05 and 3.17. During follow-up, 26 cases (74.3%) had unimproved LVSD. The strong predictors of the unimprovement of LVSD were every 1-point increase in mRSS (HR 1.05), every 1 mg increase in prednisolone treatment (HR 1.05), and every 1 U/L increase in creatine kinase (CK) (HR 1.001). Mycophenolate treatment was a protective factor against the unimprovement of LVSD in SSc (HR 0.15).

Conclusions: LVSD was frequently found in patients with diffuse cutaneous SSc, and in most cases, it remained unimproved during follow-up. High mRSS, steroid use, and high CK levels were predictors of unimproved LVSD, whereas mycophenolate treatment might prevent the progression of LVSD. Steroids should be prescribed with caution in patients with longer disease duration.