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.     

Liver hilar abscesses secondary to gastrointestinal perforation by ingested fish bones: surgical management of two cases

Several hepatobiliary complications secondary to gastrointestinal perforation after ingestion of a fish bone have been described in the literature, the most common being liver abscess, which can be potentially fatal. Treatment involves removal of the foreign body if possible (endoscopically or surgically), drainage of the abscess (radiologically or surgically), and appropriate antibiotic therapy. To our knowledge, no cases of hepatic hilar abscesses secondary to gastrointestinal perforation by a fish bone have been described in the literature. We report surgical management of two cases of abscess localized in the hepatic hilum secondary to the ingestion of fish bones.     

Combined diagnostic imaging of adenomyomatosis of the gallbladder

The consistency of a request for liver MRI and MR-cholangiopancreatography in a patient with an occasional US-finding of mural thickening of gallbladder fundus > or = 3 mm in size was assessed. The differential US diagnosis in case of focal mural thickening was analyzed in combination with the other findings to justify the radiologicoclinical reliability of the request. Overall, these findings suggested the diagnostic hypothesis of adenomyomatosis, then confirmed by a second level in-depth examination, namely liver MRI and MR-cholangiopancreatography.     

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.     

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

Clinical Rheumatology -     

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.     

Vascular complications following liver transplantation: A literature review of advances in 2015

Although vascular complications(VCs) following orthotopic liver transplantation(OLT) seldom occur, they are the most feared complications with a high incidence of both graft loss and mortality, as they compromise the blood flow of the transplant(either inflow or outflow). Diagnosis and therapeutic management of VCs constitute a major challenge in terms of increasing the success rate of liver transplantation. While surgical treatment used to be considered the first choice for management, advances in endovascular intervention have increased to make this a viable therapeutic option. Considering VC as a rare but a major and dreadful issue in OLT history, and in view of the continuing and rapid progress in recent years, an update on these uncommon conditions seemed necessary. In this sense, this review comprehensively discusses the important features(epidemiological, clinical, paraclinical, prognostic and therapeutic) of VCs following OLT.     

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.