Glucocorticoids prescribing practices in systemic sclerosis: an analysis of the EUSTAR database.

OBJECTIVES: To estimate the prevalence of long-term exposure to glucocorticoids (GCs) and to identify factors associated with, and variations in prescribing practices over time and across recruiting countries. METHODS: We included patients with SSc having a visit recorded in the EUSTAR database from January 2013 onward. We analysed the prevalence and the main features of GCs users, their exposure to GCs over time, and their GCs dosages. Multivariable linear regression was used to analyse the factors identified as associated with GCs intake duration. Time trends, and variations in GCs utilization across recruiting countries were explored. Missing data were imputed using multiple imputation with chained equations. RESULTS: The 9819 patients included were mostly females (85%), the majority had lcSSc (73%), and the median age was 58 years. At baseline, 34% of patients (n = 2769/8109) (48% dcSSc vs 29% lcSSc) were on GCs, and the median dose was 7.5 mg/day. GCs users were more frequently males and anti-Scl70 positive, and more commonly had dcSSc and more severe disease. On average, GCs users spent 25% of their follow-up time (median 33.2 months) on GCs, with no significant between-subsets difference. Notably, 33% (n = 971/2959) and 22% (n = 647/2959) of patients followed up for >1 year had received GCs for >6 and >12 months, respectively. Multivariable analysis showed that patient and disease characteristics poorly explained the variability in GCs exposure (adjusted-R2 = 0.06, P < 0.001). GCs utilization varied within and across countries, and gradually decreased over time (36% in 2013 vs 23% in 2018). CONCLUSIONS: GCs are widely and long-term prescribed in SSc, with significant between-countries and within-country differences. A gradual decrease in their utilization has been observed.

Clinical and Serological Profiles in Cryoglobulinemia: Analysis of Isotypes and Etiologies.

Objectives: Cryoglobulinemia (CG) is marked by abnormal immunoglobulins (Ig) in serum, precipitating at temperatures below 37 °C. Current classification categorizes CG into three subtypes (types I, II, and III) based on Ig clonality. The features distinguishing patients with CG based on their etiology remain unidentified. Aiming to characterize clinical and serological profiles of CG individuals, we conducted an observational analysis of a large cohort of patients and compared their characteristics based on underlying causes: hepatovirus (HV) infections, rheumatic diseases (RD), hematological disorders, and unidentified etiology (essential CG). Methods: We analyzed 252 cryoglobulin-positive serum samples from 182 patients and classified these into the four etiological groups. A separate sub-analysis was carried out for 10 patients meeting criteria for multiple diseases. We collected demographic, clinical, and laboratory data: CG characterization, complement (C3 and C4) levels, antinuclear antibodies (ANA), and rheumatoid factor (RF). Kruskal-Wallis and Wilcoxon-Mann-Whitney U-tests were used for comparisons. Results: Most patients (93.3%) had mixed cryoglobulinemia (types II + III), with 6.7% having type I. HV infection, predominantly hepatitis C, was the main (52.9%) associated condition within the cohort, followed by rheumatic (27.3%) and hematological (9.8%) disorders. In our cohort, ANA were frequent (45.3%) and often associated with RF positivity (43.6%) and decreased complement levels (C3: 42.4%, C4: 32.5%). Essential CG and CG associated with RD had a higher prevalence of cutaneous manifestations (p < 0.01) and renal involvement (p = 0.017). Hematological disorder-related CG showed higher cryoglobulin and RF concentrations (p < 0.01), despite milder symptoms. Conclusions: Our study underscores a mixed prevalence of CG across disease subgroups, with hepatitis-C virus as the primary factor, followed by rheumatic and hematological disorders. Four clinical and serological profiles of CG were identified based on their etiologies.

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.

Introduction: This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). Methods: The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. Results: A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Discussion: Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

Does the Impact of COVID-19 on Patients With Systemic Sclerosis Change Over Time?

OBJECTIVE: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. METHODS: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. RESULTS: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. CONCLUSION: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.

The phenotype of mixed connective tissue disease patients having associated interstitial lung disease.

OBJECTIVE: We aimed to compare two matched populations of patients with MTCD with and without associated ILD and to identify predictive factors for ILD progression and severity. METHODS: This international multicenter retrospective study (14 tertiary hospitals), included MCTD patients who fulfilled at least one historical MCTD classification criteria. ILD was defined by the presence of typical chest high-resolution computed tomography (HRCT) abnormalities. Factors associated with ILD were assessed at baseline. Long-term progressive ILD was assessed in MCTD-ILD patients with multiple forced vital capacity (FVC) measurements. RESULTS: 300 patients with MCTD were included. Mean age at diagnosis was 39.7 ± 15.4 years and 191 (63.7%) were women. Mean follow-up was 7.8 ± 5.5 years. At baseline, we identified several factors associated with ILD presence: older age (p = 0.01), skin thickening (p = 0.03), upper gastro-intestinal (GI) symptoms (p<0.001), FVC <80% (p<0.0001), diffusing capacity for carbon monoxide <80% (p<0.0001), anti-topoisomerase antibodies (p = 0.01), SSA/Ro antibodies (p = 0.02), cryoglobulinemia (p = 0.04) and elevated C-reactive protein (p<0.001). Patients with MTCD-ILD were more likely to be treated with synthetic immunosuppressant agents (p<0.001) in particular mycophenolate mofetil (p = 0.03). Digital ulcers (DU) were identified as a risk factor for FVC decline >10%. During follow-up mortality was higher in the MTCD-ILD group (p<0.001). CONCLUSION: In this large international cohort of patients with MTCD, we identified different factors associated with ILD. Our findings also provide evidence that MCTD-ILD patients have increased mortality and that DU are associated with progressive lung disease.

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach.

BACKGROUND: Juvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce. METHODS: We conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone. RESULTS: A total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206). According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%). CONCLUSIONS: More than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

Systemic sclerosis and gastrointestinal involvement / Esclerosis sistémica y participación gastrointestinal

ABSTRACT Systemic sclerosis (SSc) is a systemic autoimmune disease in which gastrointestinal manifestations are a frequent complication. Gastrointestinal involvement is present in up to 90 % of patients. The most affected areas are the esophagus and the anorectal tract. Reflux, heartburn and dysmotility are the leading causes of gastrointestinal discomfort. Disordered anorectal function can occur early in the course of SSc and is an important factor in the development of fecal incontinence. Current recommendations to treat gastrointestinal disorders in SSc include the use of proton pump inhibitors, prokinetics and rotating antibiotics. This review discusses the proposed pathophysiological mechanisms, the clinical presentation, the different diagnostic techniques and the current management of the involvement of each section of the gastrointestinal tract in SSc.

RESUMEN La esclerosis sistémica (ES) es una enfermedad autoinmune sistémica en la que las manifestaciones gastrointestinales son una complicación frecuente. El compromiso gastrointestinal está presente hasta en 90% de los pacientes. Las áreas más afectadas son el esófago y el tracto anorrectal. El reflujo, la pirosis y la dismotilidad son las principales causas de malestar gastrointestinal. La función anorrectal alterada puede presentarse temprano en el curso de la ES y es un factor importante en el desarrollo de incontinencia fecal. Las recomendaciones actuales para tratar los trastornos gastrointestinales en la ES incluyen el uso de inhibidores de la bomba de protones, procinéticos y de antibióticos en forma rotativa. Esta revisión discute los mecanismos fisiopatológicos propuestos, la presentación clínica, las diferentes técnicas de diagnóstico y el manejo actual del compromiso de cada sección del tracto gastrointestinal en la ES.