Clinical and experimental rheumatology最新文献

Objectives: Progressive organ damage accrual in patients with systemic sclerosis (SSc) can be measured using the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI). We aimed to evaluate the long-term evolution of organ damage accrual in SSc patients with at least 10 years of follow-up, identifying clinical and laboratory features associated with moderate and severe damage, and the association of SCTC-DI with "late mortality" (death >10 years after diagnosis).

Methods: In this single-centre retrospective study, patients with SSc were included when fulfilling the following characteristics: 1) a baseline visit corresponding to the time of diagnosis; 2) a minimum of 10 years of follow-up after diagnosis; 3) available follow-up visits at predefined timepoints.

Results: In 253 patients included in the study, SCTC-DI progressively increased from the baseline to 10 years after diagnosis, with 34% of patients showing moderate or severe damage at this time point. During the follow-up, the SCTC-DI score was higher, and had a higher annual rise, in dcSSc patients than in lcSSc and in ACA-negative patients than in ACA+. Multivariable analyses identified dcSSc, lack of ACA, and the SCTC-DI scores at previous timepoints as independent variables associated with moderate or severe damage. In patients with "late mortality", as compared to surviving patients, the SCTC-DI score was demonstrated to be significantly higher at the baseline and at every timepoint, with a higher annual rise.

Conclusions: Factors associated with damage accrual in SSc patients with long-term follow-up were identified. Higher SCTC-DI and higher SCTC-DI annual rise were associated with late mortality in SSc.

Objectives: BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis.

Methods: BAG3 serum levels were measured in 106 patients with SSc, 47 with the limited (lc) and 59 the diffuse (dc) SSc, and in age- and sex-matched healthy controls (HC). BAG3 levels were then compared according to their clinical subset, nailfold video-capillaroscopic (NVC) patterns, interstitial lung disease (ILD, and correlated with modified Rodnan skin score (mRSS) and global disease activity. BAG3 expression was also investigated in skin biopsies of 8 dcSSc patients.

Results: BAG3 serum levels were significantly higher in dcSSc (143.3 pg/mL, 95%CI 78-208.5) than in HC (0.68 pg/mL, 95%CI 0.13-1.23), and were significantly higher in patients with late NVC pattern and ILD but did not correlate with disease activity and mRSS. Of note, BAG3 was strongly expressed in the skin biopsies of dcSSc patients.

Conclusions: BAG3 is overexpressed in dcSSc patients and may contribute to skin and organ fibrosis by prompting the transition of fibroblasts into myofibroblasts and increasing their survival. Thus, BAG3 may play an important role in SSc fibrotic pathogenesis and be a potential biomarker of fibrosis. Further research on its role as a therapeutic target is warranted.

Objectives: To compare the microRNAs (miRNAs) contained within serum exosomes isolated from patients with Raynaud's phenomenon (RP) and negative antinuclear antibodies (ANA) to the miRNA contained in serum exosomes isolated from patients with RP and positive ANA.

Methods: Serum exosomes were isolated employing a polymer precipitation procedure. Next Generation Sequencing (NGS) was used to identify the miRNAs contained in the exosomes isolated from the two clinical cohorts and to analyse the differences in their contents.

Results: The NGS results identified six miRNAs that displayed significant differences in their content between serum exosomes from patients with RP with negative serum ANA compared to miRNAs contained in serum exosomes from patients with ANA-positive RP.

Conclusions: A comparative analysis of miRNAs contained within serum exosomes of patients with RP and negative ANA vs. samples from patients with RP and positive ANA identified several differentially expressed miRNAs that may represent non-invasive biomarkers to assist in the identification of patients with RP at risk of evolving into systemic sclerosis.

Systemic sclerosis (SSc) is characterised by a heterogeneous clinical expression probably reflecting the different genetic background of each patient. Progress has been made in the definition of the principal pathogenetic events of the disease that can be summarised in endothelial damage and dysfunction, inflammation with activation of immune system and fibrosis. The aetiology of the disease still remains to be clarified and probably the first events are attributable to the repeated action of environmental stimuli in genetically predisposed subjects.The aim of the present manuscript is to review the most recent and relevant data regarding the association of SSc with environmental factors.

Objectives: Hand involvement in patients with systemic sclerosis (SSc) is responsible for 75% of the overall disability but varies greatly among individuals. No study has yet compared the functionalities between the two hands of SSc patients. We thus evaluated the joint limitations and extent of skin involvement in the dominant and contralateral hands.

Methods: This prospective, descriptive, comparative single-centre study enrolled SSc patients diagnosed using the ACR/EULAR criteria. We assessed limitations in the joint range of motion during active and passive mobilisation; the first commissure opening angles; the Kapandji scale and Rodnan hand scores; the digital pressures; the finger brachial pressure indices; and the number of telangiectasias, calcinosis, digital ulcerations, and painful joints on each hand.

Results: Thirty patients were included. Spontaneous flexion joint limitations were significantly greater in the dominant hand (p<0.0001). The Kapandji score was lower (p<0.001) and the Rodnan hand score significantly higher, for the dominant hand (p<0.001). The digital pressure was similar between the hands.

Conclusions: The dominant hand exhibited significantly more skin sclerosis and mean flexion deterioration, a lower Kapandji score, and a tendency toward reduced mean extension, compared with the other hand. No vascular pathology was noted in either hand. Larger studies are needed to confirm these results and to draw therapeutic conclusions.

Objectives: To locate the most valuable sites for shear wave elastography (SWE) evaluation and to develop a clinically applicable scoring system based on SWE for systemic sclerosis (SSc) and to verify the accuracy for detection and subdivision and the correlation by modified Rodnan total skin score (mRTSS).

Methods: SSc patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) and symptomatic other rheumatic diseases (ORD) patients were included in this cross-sectional study. We assessed the skin stiffness at forehead, chest, abdomen, and bilateral fingers, hands, forearm, arms, thighs, legs, and feet, by palpation and SWE. Logistic regression was used to screen the most valuable sites for detection of SSc and subdivision of lcSSc and dcSSc, on which a scoring system was developed and verified.

Results: A total of 49 lcSSc, 51 dcSSc, and 36 ORD patients were included. The SWE-derived scoring system, including finger, hand, foot, arm, chest, and abdomen, reached a sensitivity and specificity of 80.0% and 94.4%, respectively, for diagnosing SSc at the cut-off value >24. The scoring system, including arm, chest, and abdomen, reached a sensitivity of 72.5% and specificity of 98.0% for subdividing dcSSc at the cut-off value >11. The kappa coefficient between the SWE-derived diagnosis and clinical diagnosis was 0.636 (P<0.001). The SWE-derived total scores of six sites had a strong correlation with mRTSS (r=0.757, p<0.001).

Conclusions: The SWE-derived scoring system can be valuable in detection and evaluation of SSc in clinical application.

Objectives: The aim of this work is to review the existing literature regarding sexual and reproductive function of women affected by systemic sclerosis and to establish the impact of the disease on the gynaecological-obstetrical field.

Methods: A systematic search has been conducted by means of PubMed, Cochrane, Google Scholar, until January 2024 by the keywords ''systemic sclerosis'', ''fertility'', "sexual dysfunction" and "pregnancy".

Results: Sexual dysfunction has been described in most of the studies. This could be related to dryness and dyspareunia, but also to the psychosocial impact of SSc on body and facial appearance, which impacts on social and sexual relationships. There is conflicting evidence regarding the influence of SSc and fertility. Before the 1980s pregnancies in these patients were rare. This could be linked to the satisfied reproductive desire before the onset of SSc, or to the fact that pregnancy was labelled as high-risk, leading to counsel against it in most patients. Recently, the evidence supporting infertility is conflicting. There is no certain theory on how the disease may interfere with reproductive function, but a possible linkage can be detected in a pro-inflammatory milieu which can impair the ovarian reserve.

Conclusions: Women affected by SSc should be followed-up by a multidisciplinary team to prevent sexual dysfunction. Although there is no consensus on the impact of SSc on fertility, these patients should be provided with adequate pre-conceptional counselling and a strict follow-up in high-risk pregnancy units.

Objectives: To identify the trajectories and clinical associations of functional disability in systemic sclerosis (SSc).

Methods: Australian Scleroderma Cohort Study (ASCS) participants meeting ACR/EULAR criteria for SSc recruited within 5 years of disease onset, with ≥2 Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were included. Group based trajectory modelling (GBTM) was used to identify the number and shape of HAQ-DI trajectories. Between group comparisons were made using the chi-squared test, two-sample t-test or Wilcoxon rank-sum test as appropriate. Multiple logistic regression was used to identify features associated with trajectory group membership. Survival analyses were performed using Kaplan Meier and Cox proportional hazard modelling.

Results: We identified two HAQ-DI trajectory groups within 426 ASCS participants with incident SSc: low-stable disability (n=221, 52%), and high-increasing disability (n=205, 48%). Participants with high-increasing disability were older at disease onset, more likely to have diffuse SSc (dcSSc), cardiopulmonary disease, multimorbidity, digital ulcers, and gastrointestinal involvement (all p≤0.01), as was use of immunosuppression (p<0.01). Multimorbidity was associated with high-increasing trajectory group membership (OR3.1, 95%CI1.1-8.8, p=0.04); independently, multiple SSc features were also strongly associated including dcSSc (OR2.3, 95%CI1.3-4.2, p<0.01), proximal weakness (OR7.3, 95%CI2.0-27.1, p<0.01) and joint contractures (OR2.7, 95%CI1.3-5.3, p<0.01). High-increasing physical disability was associated with an almost two-fold increased risk of mortality (HR1.9, 95%CI1.0-3.8, p=0.05), and higher symptom burden.

Conclusions: Two trajectories of functional disability in SSc were identified. Those with high-increasing functional disability had a distinct clinical phenotype and worse survival compared to those with low-stable functional disability. These data highlight the pervasive nature of physical disability in SSc, and its prognostic importance.