Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations ...are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients.
The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.
Systemic sclerosis (SSc) is an uncommon autoimmune disease. Aim of the study was to detect the occult cardiac involvement in asymptomatic SSc patients of recent onset (indicative of a more aggressive ...disease) with unenhanced Cardiac Magnetic Resonance (CMR). Our historical prospective study included naïve SSc patients of recent onset. Modified Rodnan Skin Score (mRSS) and Scleroderma Clinical Trial Consortium Damage Index (SCTC-DI) were calculated. Cardiac volumes and global myocardial strain were assessed and also compared with healthy group values. Pericardial involvement was further recorded. Thirty-one patients met inclusion criteria (54 ± 12 years; 1 M). Mean duration of disease was 6.8 years. All patients showed preserved systolic function. Higher incidence of pericardial involvement was founded in patients with disease accrual damage (OR: 9.6, p-value 0.01). Radial and longitudinal strain values resulted significantly different between healthy and SSc patients. GRS and GLS showed an independent predictive validity on damage accrual (HR: 1.22 and 1.47, respectively). Best C-index for disease progression was reached when strain values and pericardial evaluation were added to conventional risk factors (0.97, p-value: 0.0001). Strain analysis by CMR-TT may show a high capability both in identifying early cardiac involvement and stratifying its clinical aggressiveness, regardless of the standard damage indices and CMR contrast-dependent biomarker.
To evaluate the clinical pictures, laboratory tests and imaging of patients with lung involvement, either from severe COVID-19 or macrophage activation syndrome (MAS), in order to assess how similar ...these two diseases are.
The present work has been designed as a cross-sectional single-centre study to compare characteristics of patients with lung involvement either from MAS or severe COVID-19. Chest CT scans were assessed by using an artificial intelligence (AI)-based software.
Ten patients with MAS and 47 patients with severe COVID-19 with lung involvement were assessed. Although all patients showed fever and dyspnoea, patients with MAS were characterised by thrombocytopaenia, whereas patients with severe COVID-19 were characterised by lymphopaenia and neutrophilia. Higher values of H-score characterised patients with MAS when compared with severe COVID-19. AI-reconstructed images of chest CT scan showed that apical, basal, peripheral and bilateral distributions of ground-glass opacities (GGOs), as well as apical consolidations, were more represented in severe COVID-19 than in MAS. C reactive protein directly correlated with GGOs extension in both diseases. Furthermore, lymphopaenia inversely correlated with GGOs extension in severe COVID-19.
Our data could suggest laboratory and radiological differences between MAS and severe COVID-19, paving the way for further hypotheses to be investigated in future confirmatory studies.
A consistent connection has been increasingly reported between rheumatoid arthritis (RA), insulin resistance (IR), and type 2 diabetes (T2D). The β-cell apoptosis induced by pro-inflammatory ...cytokines, which could be exaggerated in the context of RA, is associated with increased expression pro-apoptotic proteins, which is dependent on JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) activation. On these bases, we aimed to evaluate if the administration of tofacitinib, a potent and selective JAK inhibitor, could simultaneously improve glycaemic parameters and inflammatory markers in patients with RA and comorbid T2D.
The primary endpoint was the change in the 1998-updated homeostatic model assessment of IR (HOMA2-IR) after 6 months of treatment with tofacitinib in RA patients with T2D. Consecutive RA patients with T2D diagnosis were included in this proof-of-concept, open, prospective, clinical study, which was planned before the recent emergence of safety signals about tofacitinib. Additional endpoints were also assessed regarding RA disease activity and metabolic parameters.
Forty consecutive RA patients with T2D were included (female sex 68.9%, mean age of 63.4 ± 9.9 years). During 6-month follow-up, a progressive reduction of HOMA2-IR was observed in RA patients with T2D treated with tofacitinib. Specifically, a significant effect of tofacitinib was shown on the overall reduction of HOMA2-IR (β = - 1.1, p = 0.019, 95%CI - 1.5 to - 0.76). Also, HOMA2-β enhanced in these patients highlighting an improvement of insulin sensitivity. Furthermore, although a longer follow-up is required, a trend in glycated haemoglobin reduction was also recorded. The administration of tofacitinib induced an improvement in RA disease activity, and a significant reduction of DAS28-CRP and SDAI was observed; 76.8% of patients achieved a good clinical response. In this study, no major adverse events (AEs) were retrieved without the identification of new safety signals. Specifically, no life-threatening AEs and cardiovascular and/or thromboembolic events were recorded.
The administration of tofacitinib in RA with T2D led to a simultaneous improvement of IR and inflammatory disease activity, inducing a "bidirectional" benefit in these patients. However, further specific designed and powered studies are warranted to entirely evaluate the metabolic effects of tofacitinib in RA patients with T2D.
In the present study, we aimed to evaluate whole-body insulin sensitivity in systemic sclerosis (SSc) patients and to compare the results with controls with no autoimmune rheumatic disease (non-ARD) ...and with patients affected by rheumatoid arthritis (RA).
In all patients and controls, oral glucose tolerance test (OGTT) was performed according to the World Health Organization (WHO) recommendations. Plasma glucose and insulin concentrations were measured at time 0 and then after 30, 60, 90, and 120 minutes. Whole-body insulin sensitivity (ISI), insulinogenic index (IGI), oral disposition index (ODI), and insulin resistance (HOMA-IR) were estimated accordingly.
A total of 41 SSc patients were evaluated and, for comparison, 41 individuals with RA and 82 non-ARD control patients were recruited. OGTT yielded a proportion of normotolerant individuals among SSc patients higher than in RA controls (p = 0.040) but lower than in the non-ARD group (p = 0.028). The ISI was significantly higher in SSc patients compared with RA controls (p <0.001) and with non-ARD patients (p <0.001). Significant differences emerged also when analysing the HOMA-IR, which was lower in SSc patients than in RA (p <0.001) and non-ARD (p <0.001) groups. Additionally, IGI was lower in SSc patients compared with RA (p = 0.011) and with non-ARD controls (p <0.001), whereas ODI was not significantly different between groups.
Interestingly, we found that SSc patients are more insulin sensitive than those with RA and even than individuals without inflammatory diseases. In contrast, no significant difference was found in terms of β-cell function.
Abstract
Atlantoaxial joint is a possible affected site during rheumatoid arthritis (RA) and, in this work, we evaluated its occurrence and associated characteristics in a “real-life” cohort. By a ...medical records review study of RA patients longitudinally followed-up, the occurrence of severe atlantoaxial joint involvement was estimated (incidence proportion and incidence rate per 1000 person-years at risk). Regression analyses were also exploited to evaluate possible associated factors. Based on these findings, a prospective recruitment was performed to build a descriptive cross-sectional study in evaluating a subclinical atlantoaxial joint involvement in patients with the same clinical characteristics. Retrospectively, 717 patients (female 56.6%, age 64.7 ± 12.3 years) were studied. The incidence proportion of severe atlantoaxial joint involvement was 2.1% 1.5–2.5, occurring in 15 out of 717 patients, and identified by both MRI and CT scan. Considering over 3091 person-years, an incidence rate of 5.2 × 1000 2.9–8.3 person-years was estimated. Regression analyses suggested that male gender, a longer disease duration, ACPA positivity and extra-articular manifestations resulted to be significantly associated with a severe atlantoaxial joint involvement. Given these findings, 30 asymptomatic patients were selected according to these clinical characteristics and underwent MRI of cervical spine. To date, almost 50% of these asymptomatic patients showed a subclinical atlantoaxial joint involvement. The occurrence of the severe atlantoaxial joint involvement in RA patients was estimated in a “real-life” setting. Male gender, ACPA positivity, long disease duration, and extra-articular manifestations could be associated with the severe atlantoaxial joint involvement in RA. MRI could provide a useful clinical tool to early evaluate the atlantoaxial joint involvement in RA, also in asymptomatic patients.
Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown aetiology affecting young adults, which is burdened by life-threatening complications, mostly macrophage activation ...syndrome (MAS). Interferons (IFNs) are signalling molecules that mediate a variety of biological functions from defence against viral infections, to antitumor and immunomodulatory effects. These molecules have been classified into three major types: IFN I, IFN II, IFN III, presenting specific characteristics and functions. In this work, we reviewed the role of IFNs on AOSD and MAS, focusing on their pathogenic role in promoting the hyperinflammatory response and as new possible therapeutic targets. In fact, both preclinical and clinical observations suggested that these molecules could promote the hyperinflammatory response in MAS during AOSD. Furthermore, the positive results of inhibiting IFN-γ in primary hemophagocytic lymphohistiocytosis may provide a solid rationale to arrange further clinical studies, paving the way for reducing the high mortality rate in MAS during AOSD.
The idea of psoriatic disease continuum has been progressively prompted based on the advances of the knowledge about the pathogenic steps underpinning the occurrence of psoriasis (PSO) and psoriatic ...arthritis (PSA). To evaluate biomolecules (inflammatory cytokines, inflammatory chemokines, cell adhesion and cellular mediators) in naïve patients with PSO, PSA with PSO, and PSA sine PSO. To stratify the results considering the presence of psoriatic nail involvement, extensive skin disease and obesity evaluating all involved patients.
By multiplex technology, 20 serum biomolecules were assessed with the inclusion of pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-12p70, IL-17A, IL-23, TNF), anti-inflammatory cytokines (IFN-α, IL-4, IL-10, IL-13), inflammatory chemokines (IP-10, MCP-1, MIP-1α, MIP-1β), cell adhesion and cellular mediators (ICAM-1, E-selectin, P-selectin). The assessment of possible statistical differences between the means of the three groups was performed by One-Way ANOVA. In addition, by non-parametric T-tests, we stratified the results according to selected clinical characteristics (psoriatic nail involvement, PASI ≥ 10, BMI ≥ 30).
In 80 assessed naïve patients, patients with PSO showed significant increases of E-selectin (p=0.021) and IL-8 (0.041) than other groups. In patients with PSA with PSO, significant higher levels of ICAM-1 were observed (p=0.009) than other groups. We did not observe further differences comparing pro-inflammatory and anti-inflammatory cytokines, inflammatory chemokines, and cell adhesion and cellular mediators in patients with PSO, PSA with PSO, and PSA sine PSO. Patients with psoriatic onychopathy showed significant increased levels of ICAM-1 (p=0.010) and IP-10 (0.030) than others. In patients with PASI ≥ 10, significantly enhanced values of IL-8 (p=0.004), TNF (p=0.013), E-selectin (p=0.004), MIP-1α (p=0.003), and MIP-1β (p=0.039). In patients with BMI ≥ 30, significantly higher levels of E-selectin were pointed out (p=0.035) than others.
Our findings may suggest that a similar cytokine profile may characterize naïve patients with PSO, PSA with PSO, and PSA sine PSO, reinforcing the concept of psoriatic disease continuum. However, some differences may be also shown, underlying possible pathogenic differences and leading to the clinical heterogeneity of these patients.
Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and ...safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis.
This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal.
Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline 2.00 (4.00) and 6 month-follow-up 0.00 (0.00) (p=0.003) and between baseline and last follow-up assessment 0.00 (0.00) (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003).
TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.
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