Arrhythmias and Conduction Disturbances in Patients with Systemic Sclerosis—A Systematic Literature Review

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis and microvascular impairment, which can affect major organs, including the heart. Arrhythmias are responsible for approximately 6% of deaths in patients with SSc, and mainly occur due to myocardial fibrosis, which causes electrical inhomogeneity. The aim of this study was to determine the frequency of arrhythmias and conduction disturbances in SSc cohorts, and to identify the characteristics and risk factors associated with the occurrence of dysrhythmias in patients with SSc. A systematic literature review using PubMed, Embase, Web of Science and Scopus databases was performed. Full-text articles in English with arrhythmias as the main topic published until 21 April 2022 were included. Most prevalent arrhythmias were premature supraventricular and ventricular contractions, while the most frequent conduction disturbance was represented by right bundle branch block (RBBB). Elevated concentrations of N-terminal prohormones of brain natriuretic peptides (NT-pro BNP) were associated with numerous types of atrial and ventricular arrhythmias, and with the occurrence of RBBB. A lower value of the turbulence slope (TS) emerged as an independent predictor for ventricular arrhythmias. In conclusion, dysrhythmias are frequent in SSc cohorts. Paraclinical and laboratory parameters are useful instruments that could lead to early diagnosis in the course of the disease

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Objective: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. / Methods: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering. / Results: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. / Conclusion: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis

CELLULAR AND MOLECULAR ACTIVITY OF A STANDARDIZED SMALL SEA FISH EXTRACT IN AN EXPERIMENTAL MODEL OF PRIMARY HUMAN CARTILAGE CELLS

The inflammatory, degenerative and rheumatic diseases are triggered and evolving at osteoarticular level due to the disruption of functionality of constitutive cells and extracellular microenvironment correlated with systemic responses as synthesis of progressively degradative cytokines. Objectives. The in vitro bioactive efficacy of standardized small sea fish extract has therapeutic relevance on the strength of optimal physiological and structural biologic system rendered by primary cells isolated from human cartilage (HCH, PromoCell) unlike standardized cell lines that may have genetic and functional changes and beside the primary cells directly isolated from animal tissue that do not reproduce an authentic biological response because of metabolic stress adaptation to growing conditions in vitro. The main therapeutic targets in osteoarticular disorders are regeneration of affected cartilage and attenuation of local inflammatory processes. Materials and methods. The in vitro articular matrix reconstruction action was evaluated by molecular tests with relative quantification of gene expression (qPCR) for aggrecan, the predominant component of human cartilage, and for the enzyme responsible for degradation of aggrecan, aggrecanase (ADAMTS4) whose activities were phenotypically measured by ELISA (enzyme-linked immunosorbent assay) test. The anti-inflammatory profile was proved by techniques of quantitative evaluation of mRNA level and detection of extracellular soluble proteins by flow-cytometry (BD™ Cytometric Bead Array) for pro-inflammatory cytokines IL-6, IL-8 and gene expression for nuclear factor NF-κB. Results and discussion. The results prove the matrix regenerator effect of standardized small fish extract by stimulation at gene expression level of aggrecan synthesis in early stages of chondrocytes differentiation, directing cells to a mature functional status, as well as by inhibition of aggrecan degradation by action on gene expression and extracellular activity of ADAMTS4. The standardized small sea fish extract has an anti-inflammatory effect proven by extracellular and transcriptional inhibition of pro-inflammatory cytokines, IL-6, IL-8 and the nuclear factor NF-κB gene. Conclusions. The in vitro anti-inflammatory and regenerative action of standardized small fish extract reflects a significant therapeutic potential for osteoarticular disease sustained both through the effects at gene and phenotypic expression levels and through the reproducible characteristics of dynamics of in vivo chondrocytes evolution evidenced by primary cell lines

Performance of the New 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology Systemic Lupus Erythematosus Classification Criteria in a Large Unicentric Cohort

Background: The recently published 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for systemic lupus erythematosus (SLE) were developed to increase the reliability and identification of SLE, especially in early disease. With the emergence of several new drugs for SLE, identifying and treating patients early are more important than ever. Methods: Data of 446 SLE patients evaluated in our center between 1996–2019 and 226 controls with other autoimmune diseases evaluated between 2001–2022 were retrospectively analyzed. The sensitivity and specificity of the 2019 ACR/EULAR criteria were compared to the 2012 SLICC and the 1997 ACR criteria. Results: The 2019 ACR/EULAR criteria showed very good sensitivity (86.6%) compared to the 1997 ACR criteria (76.7%), p p = 0.072. Their sensitivity remained high (87.6%) in patients with a short disease duration. The specificity of the 2019 ACR/EULAR criteria (91.2%) was statistically lower than the 2012 SLICC (96.0%) and 1997 ACR criteria (95.1%), p = 0.007 and p = 0.012, respectively, but still had a very high value. A total of 22 controls (9.7%) fulfilled at least one set of criteria (15 patients with MCTD, 5 with UCTD, and 2 with SSc). Conclusion: In this large real-life cohort, the 2019 ACR/EULAR criteria had very good performance compared to the 2012 SLICC and 1997 ACR criteria

Anti-MDA5 Amyopathic Dermatomyositis—A Diagnostic and Therapeutic Challenge

Clinically amyopathic Dermatomyositis (CADM) is a rare subtype of idiopathic inflammatory myositis, associated with no muscular manifestations, which is more frequent in Asian women. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are a recently discovered type of specific autoantibodies associated with myositis. The anti-MDA5 DM was initially described in Japan and later it was discovered that the target antigen was a protein implicated in the innate immune response against viruses, that is encoded by the melanoma differentiation-associated gene 5. Anti-MDA5 DM is characteristically associated with distinguished mucocutaneus and systemic manifestations, including skin ulcerations, palmar papules, arthritis, and interstitial-lung disease. Patients with anti-MDA5 positivity have a high risk of developing rapid progressive interstitial-lung disease (RP-ILD), with a poor outcome. As a result, despite high mortality, diagnosis is often delayed, necessitating increased awareness of this possible condition. Despite a severe course of lung disease and an increased mortality rate, there is currently no standard treatment. Recent insights based on observational studies and case reports support combined therapy with immunosuppressive drugs and corticotherapy, as soon as the symptoms appear. The aim of this paper is to describe anti-MDA5 DM, focusing on the recent literature about the unique clinical manifestations and therapeutic options, starting from a severe clinical case diagnosed in our Rheumatology Department

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ABSTRACT. Objective. Several global measures to assess at-work productivity loss or presenteeism in patients with rheumatic diseases have been proposed, but the comparative validity is hampered by the lack of data on test-retest reliability and comparative concurrent and construct validity. Our objective was to test-retest 5 global measures of presenteeism and to compare the association between these scales and health-related well-being. Methods. Sixty-five participants with inflammatory arthritis or osteoarthritis in paid employment were recruited from 7 countries (UK, Canada, Netherlands, France, Sweden, Romania, and Italy). At baseline and 2 weeks later, 5 global measures of presenteeism were evaluated: the Work Productivity Scale-Rheumatoid Arthritis (WPS-RA), Work Productivity and Activity Impairment Questionnaire (WPAI), Work Ability Index (WAI), Quality and Quantity questionnaire (QQ), and the WHO Health and Performance Questionnaire (HPQ). Agreement between the 2 timepoints was assessed using single-measure intraclass correlations (ICC) and correlated between each other and with visual analog scale general well-being scores at followup by Spearman correlation. Results. ICC between measures ranged from fair (HPQ 0.59) to excellent (WPS-RA 0.78). Spearman correlations between measures were moderate (Q quality vs WAI, r = 0.51) to strong (WPS-RA vs WPAI, r = 0.88). Correlations between measures and general well-being were low to moderate, ranging from -0.44 ≤ r ≤ 0.66. Conclusion. Test-retest results of 4 out of 5 global measures were good, and the correlations between these were moderate. The latter probably reflect differences in the concepts, recall periods, and references used in the measures, which implies that some measures are probably not interchangeable