Correction to: Impact of smoking habit on adult-onset Still’s disease prognosis,findings from a multicentre observational study

Clinical Rheumatology -     

H‐ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

Macrophage activation syndrome (MAS) is hyperinflammatory life‐threatening syndrome, associated typically with high levels of serum ferritin. This is an iron storage protein including heavy (H) and light (L) subunits, categorized on their molecular weight. The H‐/L subunits ratio may be different in tissues, depending on the specific tissue and pathophysiological status. In this study, we analysed the bone marrow (BM) biopsies of adult MAS patients to assess the presence of: (i) H‐ferritin and L‐ferritin; (ii) CD68⁺/H‐ferritin⁺ and CD68⁺/L‐ferritin⁺; and (iii) interleukin (IL)‐1β, tumour necrosis factor (TNF) and interferon (IFN)‐γ. We also explored possible correlations of these results with clinical data. H‐ferritin, IL‐1β, TNF and IFN‐γ were increased significantly in MAS. Furthermore, an increased number of CD68⁺/H‐ferritin⁺ cells and an infiltrate of cells co‐expressing H‐ferritin and IL‐12, suggesting an infiltrate of M1 macrophages, were observed. H‐ferritin levels and CD68⁺/H‐ferritin⁺ cells were correlated with haematological involvement of the disease, serum ferritin and C‐reactive protein. L‐ferritin and CD68⁺/L‐ferritin⁺ cells did not correlate with these parameters. In conclusion, during MAS, H‐ferritin, CD68⁺/H‐ferritin⁺ cells and proinflammatory cytokines were increased significantly in the BM inflammatory infiltrate, pointing out a possible vicious pathogenic loop. To date, H‐ferritin and CD68⁺/H‐ferritin⁺ were associated significantly with haematological involvement of the disease, suggesting biomarkers assessing severity of clinical picture.     

Incidence of venous thromboembolism in rheumatoid arthritis,results from a “real-life” cohort and an appraisal of available literature

Rheumatoid arthritis (RA) is associated with an increased risk of venous thromboembolism (VTE) occurrence. In this work, we assessed the incidence and predictive factors of VTE in our “real-life” cohort of RA patients. To contextualize our results, we reviewed the available literature about this topic.We performed a retrospective analysis of prospectively followed-up patients with RA attending our Rheumatologic Clinic between January 2010 and December 2020. Each patient was investigated for VTE occurrence. Incident cases were reported as incidence proportion and incidence rate per 1000 person-years at risk. Possible predictive factors were also exploited by regression analyses. Available literature about this topic was also assessed.In this evaluation, 347 consecutive patients without previous evidence of VTE, attending our Rheumatologic Clinic from 2010 to 2020, were studied. In our “real-life” cohort, the incidence proportion of VTE was 3.7% (2.7–4.7%) and considering over 1654 person-years, an incidence rate of 7.8 × 1000 (2.5–11.7). Exploratively assessing predictive factors in our cohort, older age (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01–1.14, p = .015), higher body mass index (HR 1.37, 95% CI 1.04–1.80, P = .026), and longer disease duration (HR 1.11, 95% CI 1.03–1.20, P = .006) resulted to be significant predictors of VTE occurrence during the follow-up.In our “real-life” cohort, VTE burden has been suggested in patients with RA. Comparing our results with previous data derived from randomized controlled trials and administrative data, some different findings were retrieved about incidence of VTE. Assessing predictive factors, older age, higher body mass index, and longer disease duration resulted to be significant predictors of VTE occurrence during the follow-up. Taking together these observations, a further evaluation of this issue on specific designed studies is needed to provide more generalizable results to the daily clinical practice.     

Biologic therapies and infections in the daily practice of three Italian rheumatologic units: a prospective,observational study

Since the introduction of biologics, many concerns about the increased risk of infections have been reported and, to date, the real impact of infections on the daily practice in the rheumatologic centers is still largely unknown. In this work, we evaluated the infection rates associated with the use of biologics in a large cohort of patients. A prospective study, between January 2010 and December 2013, enrolling 731 rheumatic patients, was performed. Demographic and disease characteristics, therapies, comorbidities, and infectious events were recorded and statistically analyzed by multivariate analysis. Two-hundred thirty-five infectious episodes were observed in 28.4 % of patients. About total infections, bacteria were identified in 70.6 % of total cases and viruses in 18.3 %. The most common site of not-serious infection was the urinary tract. Duration of disease, longer follow-up, concomitant steroid therapy, and comorbidities were significantly associated with not-serious infection. In our cohort, 17 episodes fulfilled the criteria of serious infection and occurred in 17 different patients (2.3 %), the majority involving the lower respiratory tract. Serious infections were associated with the beginning of biologics in older age. Our prospective, observational study showed that, in daily practice, a lesser rate of serious as well as not-serious infections may be observed in rheumatic patients treated with biologics than those reported in previous papers. The most common sites of not-serious infections are both the urinary and the respiratory tracts, and for serious infections, the respiratory tract. When pathogens were isolated, we did not find any multidrug-resistant organism.     

Beyond the joints,the extra-articular manifestations in rheumatoid arthritis

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.     

The CD68+/H‐ferritin+ cells colonize the lymph nodes of the patients with adult onset Still's disease and are associated with increased extracellular level of H‐ferritin in the same tissue: correlation with disease severity and implication for pathogenesis

In this work, we aimed to evaluate the levels of ferritin enriched in H subunits (H‐ferritin) and ferritin enriched in L subunits (L‐ferritin) and the cells expressing these two molecules in the lymph node (LN) biopsies obtained from adult‐onset Still's disease (AOSD) patients, and the possible correlation among these data and the severity of the disease. Ten patients with AOSD underwent LN biopsy. All the samples were stained by immunofluorescence. A statistical analysis was performed to estimate the possible correlation among both H‐ferritin and L‐ferritin tissue expression and the clinical picture of the disease. Furthermore, the same analysis was performed to evaluate the possible correlation among the number of CD68⁺/H‐ferritin⁺ or CD68⁺/L‐ferritin⁺ cells and the clinical picture. Immunofluorescence analysis demonstrated an increased tissue H‐ferritin expression in the LNs of AOSD patients. This increased expression correlated with the severity of the disease. An increased number of CD68 macrophages expressing H‐ferritin was observed in the LN samples of our patients. Furthermore, we observed that the number of CD68⁺/H‐ferritin⁺ cells correlated significantly with the severity of the clinical picture. Our data showed an imbalance between the levels of H‐ and L‐ferritin in LNs of AOSD patients and the evidence of an increased number of CD68⁺/H‐ferritin⁺ cells in the same organs. Furthermore, a correlation among both the tissue H‐ferritin levels and the CD68⁺/H‐ferritin⁺ cells and the clinical picture was observed.     

Evaluating the multivisceral involvement on adult-onset Still’s disease to retrieve imaging-based differences in patients with and without macrophage activation syndrome: results from a single-centre observational study

Clinical Rheumatology - In this study, we aimed at describing the multivisceral involvement on adult-onset Still’s disease (AOSD) to retrieve imaging-based differences in patients with and...     

Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care.The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments.