Clinical and experimental rheumatology最新文献

Objectives: This study compares the performance of three composite pulmonary arterial hypertension (PAH) screening tools in a real-life SSc cohort, according to both the previous 2015 ESC/ERS guideline and the recent 2022 ESC/ERS guideline haemodynamic criteria.

Methods: Consecutive SSc patients without a previous diagnosis of pulmonary hypertension (PH) were screened for PAH using the European Society of Cardiology/European Respiratory Society (ESC/ERS), DETECT, and Australian Scleroderma Interest Group (ASIG) algorithms. Right heart catheterisation (RHC) referral performances for PAH were compared according to the 2022 ESC/ERS PAH criteria.

Results: Thirty-five of the 81 patients required RHC; 15 (18.5%) according to ESC/ERS, 27 (33.3%) according to DETECT, and 25 (31%) according to ASIG. The final diagnoses were no-PH in 17 patients, WHO group 1 PH (PAH) in 8 patients, WHO group 2 PH in 8 patients, and WHO group 3 PH in 2 patients. When the hemodynamic criteria of the previous ESC/ERS guideline were applied, only one patient was diagnosed with PAH. The sensitivities of the algorithms for the diagnosis of PAH were 62.5% for ESC/ERS, 75% for DETECT, 87.5% for ASIG according to the 2022 ESC/ERS guideline definition, and 100% for all according to the previous ESC/ERS guideline.

Conclusions: With the recent criteria, PAH diagnosis in patients with SSc increased by 1.8-fold. Current algorithms for screening PAH are less sensitive with these revised criteria. Although the ASIG algorithm seems more sensitive, it can still miss the diagnosis. The multimodal/algorithmic approach seems to be the best option for predicting PAH.

Objectives: Anti-CENP-B (ACA), anti-topoisomerase I (ATA) and anti-RNA polymerase III (RP3) autoantibodies are included in the 2013 SSc-ACR/EULAR classification criteria. The detection of additional autoantibodies is of interest when those are negative. Additionally, we wonder if the IgA isotype might play a role in SSc. The aims of the study were to assess the prevalence of ACA, ATA, RP3, and Ro52 autoantibodies of IgG and IgA isotype and to describe their association with clinical manifestations in a cohort of patients with SSc.

Methods: Samples from 97 patients with SSc fulfilling the 2013 ACR/EULAR classification criteria, and 50 blood donors were included and tested for IgA and IgG isotypes of ACA, ATA, RP3, and Ro52 by FEIA.

Results: The prevalence of IgG+IgA isotypes for the same specificity was 62.5%, 82.6%, 80.0%, 36.8%, for ACA, ATA, RP3 and Ro52, respectively. Isolated IgG was present in 35.4%, 13.0%, 20.0% and 42.1% of patients for ACA, ATA, RP3 and Ro52, respectively. Only six patients were isolated IgA for a unique specificity. Clinically, ILD tended to be associated with ATA-IgG and ATA-IgG+IgA, telangiectasias with ACA-IgG+IgA and arthritis with ACA-IgA. Indeed, digital ulcers were more frequent in ATA-IgG patients.

Conclusions: Most of the patients presented ACA, ATA, or RP3 autoantibodies of IgA isotype in addition to IgG. Regarding clinical relevance, Ro52-IgG+IgA and ACA-IgG had a tendency towards sineSSc phenotype, while ACA-IgG+IgA to lcSSc phenotype. Thus, if confirmed, the determination of ACA-IgA could provide a tool to stratify patients according to the cutaneous phenotype.

Objectives: Systemic sclerosis (SSc) is a chronic multisystem disease characterised by microcirculatory vascular dysfunction and progressive fibrosis of the skin and internal organs. Interleukin-6 (IL-6) is a proinflammatory cytokine that has been implicated in the pathogenesis of several autoimmune diseases and in the initiation and progression of the cardiovascular disease. In the present work we aimed to study the relationship of IL-6 with clinical manifestations and the cardiovascular risk in patients with SSc.

Methods: We carried out a cross-sectional study that included 53 individuals with SSc. A multivariate analysis was performed to study the relationship between IL-6 and disease characteristics and cardiovascular risk assessed by Systematic Coronary Risk Estimation (SCORE2) in SSc.

Results: The presence of digital ulcers, calcinosis, and anti-Scl70 antibody was associated with higher levels of IL-6. This was also the case for functional respiratory parameters where this association was found to be significant and negative after correction for covariates. In addition, the SCORE2 cardiovascular risk algorithm showed a positive and significant association with circulating IL-6.

Conclusions: IL-6 levels are associated with disease manifestations and cardiovascular risk in patients with SSc.

Objectives: Antinuclear antibodies (ANA) of the IgE-type have been described in several connective tissue disorders (CTD) but not yet in systemic sclerosis (SSc). Aim of the study was, therefore, to establish an ELISA for the demonstration of IgE-autoantibodies to topoisomerase-I (topo-I) and the centromeric proteins A and B (CENP-A/B), to assess their prevalence and reactivity in SSc and to analyse their clinical relevance.

Methods: One hundred fifty-one patients with SSc and 88 with CREST-syndrome, 291 patients with other CTD, and 23 patients with fibromyalgia syndrome (FM) as a control collective were included into the study. Patients' sera were analysed by an in-house-ELISA for IgE autoantibodies against topo-I and CENP-A/B using recombinant antigens. Patients were assessed for median Rodnan skin score(mRSS), different organ and cutaneous manifestations.

Results: Of the patients with CREST syndrome, 67% had IgE-anti-CENP-A- and 77% IgE-anti-CENP-B-antibodies. IgE-anti-topo-I antibodies were found in 56% of patients with SSc. Prevalence and reactivity were significantly higher in CREST and SSc, respectively, than in other CTD or FM. IgE-reactivity strongly correlated with IgG-antibody reactivity. In CRESTsyndrome, IgE-anti-CENP-A (but not CENP-B)-antibodies were significantly higher and more prevalent in patients with skin ulcers, high mRSS, and more than four organ manifestations. They did not correlate with blood eosinophil counts. In contrast, for IgE-anti-topo-I antibodies no correlation with clinical manifestations was observed.

Conclusions: IgE-autoantibodies against CENP-A/B and topo-I occur in SSc underlining the concept that SSc may be a T helper cell type 2 mediated disease. IgE-anti-CENP-A-antibodies correlated with disease activity, but this has to be confirmed in larger studies.

Systemic sclerosis (SSc) is a rare and chronic connective tissue disease of unknown aetiology and characterised by three main pathogenetic events represented by endothelial damage, inflammation with activation of the immune system leading to production of specific autoantibodies and finally fibrosis. SSc is a heterogeneous disease and the classification in two subsets, the limited cutaneous (lcSSc) subset and the diffuse cutaneous one (dcSSc), is not capable of capturing the broad and different phenotypic expression of the disease. In the last years progress has been made in the knowledge of SSc pathogenesis, in its early diagnosis and new therapeutic strategies have been proposed, however, the management of SSc still represents a challenge for the clinician. For this reason, every year several studies investigate new insights of disease pathogenesis, internal organ involvement and therapeutic approaches. The purpose of this review is to provide an overview of the literature published in 2023.

Objectives: To analyse in routine practice the efficacy of targeted therapies on joint involvement of patients with rheumatoid arthritis/systemic sclerosis (RA/SSc) overlap syndrome.

Methods: This was a retrospective analysis of medical records of two academic centres over a 10-year period. Joint response to targeted therapies was measured according to EULAR criteria based on Disease Activity Score (DAS)-28. In addition, changes in CRP level and glucocorticoid consumption were recorded.

Results: Nineteen patients were included. Methotrexate (n=11) and hydroxychloroquine (n=4) were the most used first-line treatments. Targeted therapies were frequently used (n=14). Tocilizumab was the most selected therapy (n=8), then rituximab (n=5), abatacept and anti-tumour necrosis factor (n=4). Twenty-one treatment sequences were assessed, including 18 with EULAR response criteria. Responses were "good" or "moderate" in 100% (4/4) of patients treated with abatacept, 80% (4/5) with rituximab, 40% (2/5) with tocilizumab, and 25% (1/4) with anti-TNF. T and B lymphocyte-targeted therapies (abatacept, rituximab) resulted more frequently in a "good" or "moderate" response compared to cytokine inhibitors (tocilizumab, etanercept, infliximab) with a significant decrease in DAS-28 at 6 months (-1.75; p=0.016) and a trend to a lower consumption of glucocorticoids.

Conclusions: In patients with RA/SSc overlap syndrome refractory to conventional synthetic-DMARDs, T and B lymphocyte-targeted therapies seem to be a promising therapeutic option to control joint activity.

Objectives: The gastrointestinal tract (GIT) is frequently involved in systemic sclerosis (SSc) and is responsible for alteration of quality of life. Many complications can occur, including chronic intestinal pseudo-obstruction, digestive haemorrhage and small-intestinal bacterial overgrowth. Since early development of organ failure is associated with poor prognosis, we need to identify risk factors associated with severe GIT involvement to prevent severe forms of the disease.

Methods: We conducted an observational prospective study, which included 90 SSc patients from December 2019 to September 2021. We collected questionnaires about digestive manifestations and quality of life, blood and stool samples, and performed imaging. At inclusion and throughout the study we assessed the occurrence of malnutrition and severe GIT disorders. We performed statistical analysis to highlight eventual risk factors associated with digestive manifestations, including hierarchical cluster analysis.

Results: A majority of our patients had gastro-oesophageal manifestations (93.3%), followed by intestinal manifestations (67.8%) and anorectal manifestations (18.9%). We found a correlation between anorectal disorders and cardiac disease, and between gastro-oesophageal involvement and impaired pulmonary function tests. Smoking was significantly associated with occurrence of severe GIT disorders. Malnutrition was frequent and associated with more cardiac and pulmonary disease. Cluster analysis identified three groups of patients, including one cluster with cardiac and digestive involvement.

Conclusions: GIT manifestations are frequent and severe in SSc. Smoking appears to be associated with severe disease. Anorectal manifestations may be associated with cardiac disease, but we need more studies to validate these results.

Objectives: Scleroderma is a heterogeneous chronic autoimmune disease affecting connective tissue, characterised by chronic inflammation and fibrosis, particularly affecting internal organs and skin. Orofacial involvement is common, leading to facial atrophy, mask-like appearance and difficulties in function that significantly impact patients' quality of life. This systematic review evaluates different autologous regenerative treatments of facial manifestations of scleroderma, aiming to provide comprehensive understanding of their effectiveness in reducing fibrosis, and thereby improving function and skin quality.

Methods: A search in PubMed, Embase, Web of Science Core Collection, Cochrane CENTRAL, and CINAHL was conducted. Studies assessing autologous regenerative treatments in cutaneous manifestations of the face in scleroderma patients were included. Outcomes of interest were treatment characteristics, characterisation of biomaterials, outcome measurements and patient satisfaction. Methodological quality was assessed with the Effective Public Health Practice Project tool.

Results: In total 18 studies were included. Methodological quality of studies was weak (n=15) and moderate (n=3). Treatments consisted of autologous fat grafting, platelet-rich plasma, stromal vascular fraction, and adipose-derived stem cells. In general, most studies showed improvements of symptoms, but no treatment was considered superior.

Conclusions: Autologous regenerative treatments hold potential for alleviating cutaneous manifestations of the face in scleroderma. Further clinical trials should be well-designed to improve the quality of clinical evidence.

Objectives: To investigate the burden and clinical associations of fatigue in systemic sclerosis (SSc) as measured by FACIT-Fatigue scores.

Methods: Australian Scleroderma Cohort Study participants with ≥1 FACIT-Fatigue score were included. Participants were divided into those with incident SSc (≤5 years SSc duration at recruitment and FACIT-Fatigue score recorded within 5 years of disease onset) or prevalent SSc (first FACIT-Fatigue score recorded >5 years after SSc onset). Generalised estimating equations were used to model change in FACIT-Fatigue scores over time, expressed as an increasing (improving) or decreasing (worsening) score.

Results: Of 859 participants, 215 had incident SSc and 644 prevalent SSc. First-recorded FACIT-Fatigue scores were similar in those with incident (37 units, IQR 25-45.5) and prevalent SSc (36 units, IQR 23-44; p=0.17), as were lowest-ever recorded FACIT-Fatigue scores (incident 23 units; prevalent 22 units, p=0.75). In incident SSc, higher skin scores (regression coefficient (RC) -1.5 units, 95%CI -2.3 to -0.8), PAH (RC -8.2, 95%CI -16.5 to 0.1) and reduced left ventricular function (RC -10.6, 95%CI -18.3 to -2.8) were associated with more severe fatigue. In prevalent SSc, higher skin scores (RC -0.6, 95%CI -1.3 to 0), gastrointestinal symptoms (RC -6.6, 95%CI -9.0 to -4.2), hypoalbuminaemia (RC -2.8, 95%CI -5.0 to -0.7), BMI<18.5kg/m2 (RC -6.3, 95%CI -10.3 to -2.2), raised CRP (RC -3.1, 95%CI -4.7 to -1.5), and anaemia (RC -1.7, 95%CI -3.5 to 0.1) were associated with more severe fatigue.

Conclusions: The burden of fatigue is substantial in both incident and prevalent SSc. Cardiopulmonary and gastrointestinal involvement are associated with worse fatigue.

Objectives: There is a lack of quantitative and objective methods for measuring skin hardness. This study aimed to verify whether SOFTGRAM, a device that can measure elastic modulus using the Hertz elastic contact theory, could be used to evaluate skin hardness in systemic sclerosis (SSc).

Methods: Skin score according to the modified Rodnan total skin thickness score and elastic modulus of the skin using SOFTGRAM were measured for 20 patients with SSc and 20 healthy controls on 8 parts of the body, both of the cheeks, forearms, fingers, and hands. Five observers shared to measure skin score 320 times (40 participants × 8 parts). Elastic modulus was measured 1600 times (40 participants × 8 parts × 5 times each). As an additional examination to compare differences between observers, the skin score of another healthy control was measured 40 times (5 observers × 8 parts). Elastic modulus was measured 200 times (5 observers × 8 parts × 5 times each).

Results: There was a significant correlation between elastic modulus and skin score (correlation coefficient=0.67, p<0.001) and a significant difference in elastic modulus (8 parts: healthy controls vs. limited cutaneous SSc vs. diffuse cutaneous SSc: 22.6±15.7 vs. 32.0±27.7 vs. 44.8±39.8, p<0.001). Intraobserver reliabilities were sufficient in 6 out of 7 observers; however, interobserver was less satisfactory.

Conclusions: This study showed the practicality of SOFTGRAM as an accurate measurement method of skin hardness but also revealed points to be improved. More studies are needed to find an accurate measurement method of skin hardness.