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Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions of the portal venules and sinusoids with clinical manifestations ranging from non-specific abnormalities in serum liver enzymes to clinically overt portal hypertension and related complications. Several reports have documented cases of PSVD in patients with systemic autoimmune conditions, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. It is of note that these diseases share specific pathophysiological features with PSVD, including endothelial dysfunction, vascular inflammation, and molecular signatures. This narrative review aims to summarize the current knowledge on the association between PSVD and systemic autoimmune diseases, emphasizing the importance of promptly recognizing this condition in the rheumatological practice, and highlighting the key aspects where further research is necessary from both pathogenic and clinical perspectives. [ABSTRACT FROM AUTHOR]

To explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM). PGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function. PGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity. Increased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials. [ABSTRACT FROM AUTHOR]

The development of biologics and small oral molecules has recently changed the scenario of pharmacologic treatment of systemic rheumatic diseases and it has become a real revolution. These drugs have innovative mechanisms of action, based on the inhibition of specific molecular or cellular targets directly involved in disease pathogenesis. This new scenario has lead to a regular update of the management recommendations of several institutions, such as those for Rheumatoid Arthritis treatment that address the use of conventional and biologic therapies including TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, IL-6 inhibitors (tocilizumab and sarilumab), biosimilars and small oral molecules (the JAK inhibitors tofacitinib and baricitinib). Monotherapy, combination therapy, treatment strategies (such as treat-to-target) and the targets of sustained clinical remission or low disease activity are the final goal of the guidelines for rheumatic patients management. In another condition represented by Axial Spondyloarthritis guidelines suggest to start first with non-steroidal anti-inflammatory drugs to improve lifestyle and reduce spine inflammation, but if this is not achieved in 2–4 weeks it is important to consider the use of local therapies (i.e. glucocorticoid injections) or to start biologic therapy such as TNF inhibitors and then eventually switching to another TNF inhibitor or swapping to IL-17 inhibitor. In the case of active Psoriatic Arthritis, guidelines suggest to start with non-steroidal anti-inflammatory drugs and even local glucocorticoid injections especially for oligoarthritis, then to start conventional therapies if lack of efficacy, and finally start biologics or small oral molecules in the presence of drugs toxicity, unfavorable prognostic factors and still active arthritis. In several cases, active Psoriatic Arthritis patients develop a complex clinical condition with comorbidities such as diabetes, inflammatory bowel disease and high risk of infections, and for this reason the American College of Rheumatology and the National Psoriasis Foundation have developed specific guidelines for their management. Biologic and new small molecules therapies are very expensive, but the availability of biosimilars offers the opportunity of reducing the treatment cost and significantly decreasing the cost of originators as well. In fact, we live in a period characterized by the need to rationalize costs of these drugs, to allow treating a higher number of patients and to maintain a homogeneous possibility of treatment choice. For these reasons, we need to follow scientific guidelines and patients' clinical conditions to choose the correct treatment, also based on the economic burden of therapies. • The pharmacological scenario in systemic rheumatic diseases has deeply changed. • Recommendations and guidelines must be followed to choose the correct therapy. • Biosimilars have reduced treatment costs and allowed treating more patients. • Patients clinical conditions and treatment cost must be considered. • The lack of reliable biomarkers is an unmet need in several rheumatic diseases. [ABSTRACT FROM AUTHOR]

Objective To describe a new immunoprecipitation pattern identified in Italian patients affected by systemic sclerosis (SSc), corresponding to the pyruvate dehydrogenase antigen complex recognized by anti-mitochondrial antibodies (AMA) in primary biliary cholangitis (PBC). Methods Autoantibodies in sera from 85 patients with SSc were tested by protein- and RNA-immunoprecipitation. Immunoprecipitation-Western blot was used to determine the identified proteins, and medical records re-evaluated for liver function tests and PBC. Results In 13/85 (15%) SSc sera, a unique set of 75-50-40-34 kD proteins that had not been previously reported, was noted. The four proteins were identified as the proteins X/E3BP, E1α, E1β, and E2/E3 of the pyruvate dehydrogenase antigen complex by immunoprecipitation-Western blot. From clinical record evaluation, 9/13 (69%) SSc patients with this new pattern were positive for AMA by routine indirect immunofluorescence, and 7/13 (54%) had a diagnosis of PBC, while 4/13 (31%) manifested no biochemical signs of cholestasis. Twelve of 13 patients with SSc and AMA by immunoprecipitation have a limited cutaneous form of SSc and anti-centromere antibodies. Conclusions We describe a pattern of 4 proteins in 15% of SSc patients, identified for the first time by protein-immunoprecipitation. This pattern corresponds to serum AMA against the pyruvate dehydrogenase antigen complex and it must be considered in the interpretation of protein-immunoprecipitation results. [ABSTRACT FROM AUTHOR]

The prevalence of ANA and anti-ENA in the general population is not well established, especially their clinical significance in healthy subjects. We herein determined the prevalence and predictive value of serum ANA and anti-ENA for connective tissue diseases (CTD), cancer, and mortality. We took advantage of a randomly selected sample of the 1998 general population (Isola I) consisting of 2828 subjects (53% women, age 43 ± 13 years) from a well-defined Northern Italian area. Serum ANA and anti-ENA were tested on the 2690 samples available in 2012 (Isola II, 50% women, age 58 ± 13 years). Administrative databases were searched for CTD, cancer diagnosis, and death cases occurring between enrollment and December 31, 2013. The hazard ratio (HR) was calculated for incident cases. Serum ANA is positive in 18.1% for any titer and 6.1% for titers ≥ 1:160, 23% in subjects over 50 years and 13.1% and 6.1% for any titer and titers ≥ 1:160, respectively, in women. The HR for CTD development was significantly high for all ANA titers, with the highest for ANA ≥ 1:160 (HR 14.19, 95% CI 3.07–65.68). ANA positivity was not associated with cancer (HR 1.03; 95% CI 0.75–1.43), or with mortality (HR adjusted for age and sex 1.40; 95% CI 0.94–2.09). Serum anti-ENA is positive in a minority of subjects with highest figures for anti-nucleosome (1.9%), -histone (1.6%) and -PM/Scl (1.5%). In conclusion, serum ANA prevalence in the general population is highest in senior subjects and in women, while the female predominance is significantly lower compared to overt CTD. Serum ANA is associated with an increased probability of CTD development over time, but does not influence survival or cancer risk. [ABSTRACT FROM AUTHOR]

Spondyloarthritidies represent a group of conditions affecting the axial and peripheral muscoloskeletal apparatus and are often associated with psoriasis, infections, and inflammatory bowel diseases. Other diseases included in this category are psoriatic arthritis, ankylosing spondylitis, and enteropathic arthritis. Reactive arthritis is an elusive spondyloarthritis, commonly occurring 1 to 3 weeks after a digestive or a genitourinary tract infection, in which microorganisms do not infect the joint directly. Reactive arthritis is classically characterized by large-joint arthritis, urethritis in men and cervicitis in women, and eye inflammation (usually conjunctivitis or uveitis) but encompasses numerous other symptoms and signs, including manifestations of dermatologic interest such as keratoderma blenorrhagicum and circinate balanitis. The diagnosis of reactive arthritis is clinical, and the infectious agent cannot always be identified due to disease latency after the infection. Most cases are self-limiting, but reactive arthritis may become chronic in 30% of cases. Treatment options include anti-inflammatory drugs, steroids, and sulfasalazine; biologic agents, such as tumor necrosis factor α (TNF-α) blockers, have been recently used, but there are only a few randomized clinical trials on the treatment of reactive arthritis. The effectiveness of antimicrobials needs further evaluation. [ABSTRACT FROM AUTHOR]

The role of microRNAs (miRNAs) in the regulation of many physiological and pathological processes has been intensely studied in recent years. Some miRNAs, such as miR-146a and miR-182, play a dominant role in the regulation of the innate and adaptive immune responses, respectively. Many miRNAs are reportedly deregulated in autoimmune diseases, but miR-146a in particular seems to be consistently altered. The overexpression or underexpression of miRNAs can influence specific targets and pathways, leading to autoimmune disease phenotypes, and this is supported also by some in vivo studies. Targeting miRNAs could represent a valid future therapeutic option for autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objective To analyze the performance of a line blot assay for the identification of autoantibodies in sera of patients affected by myositis, compared with immunoprecipitation (IP) as gold standard. Methods 66 sera of patients with myositis (23 polymyositis, 8 anti-synthetase syndromes, 29 dermatomyositis and 6 overlap syndromes) were tested by commercial LB (Euroimmun, Lubeck, Germany); 57 sera were analyzed also by IP of K562 cell extract radiolabeled with 35 S-methionine. Inter-rater agreement was calculated with Cohen's k coefficient. Results Myositis-specific antibodies (MSA) were detected in 36/57 sera (63%) by IP and in 39/66 sera (59%) by LB. The most frequent MSA found by LB were anti-Jo1 and anti-Mi2 found in 15% (10/66) of sera, followed by anti-NXP2 and anti-SRP detected in 106% (7/66) of sera. Anti-TIF1gamma and anti-MDA5 were found in 6 (9%) and 5 sera (7.6%), respectively. A good agreement between methods was found only for anti-TIF1γ, anti-MDA5 and anti-NXP-2 antibodies, while a moderate agreement was estimated for anti-Mi2 and anti-EJ. By contrast, a high discordance rate for the detection of anti-Jo1 antibodies was evident (k: 0.3). Multiple positivity for MSA were found in 11/66 (17%) by LB and 0/57 by IP (p: 0001). Comparing the clinical features of these 11 sera, we found total discrepancies between assays in 3 sera (27.3%), a relative discrepancy due to the occurrence of one discordant autoantibody (not confirmed by IP) in 5 cases (45.5%) and a total discrepancy between LB and IP results, but with a relative concordance with clinical features were found in other 3 sera (27.3%). The semiquantitative results do not support the interpretation of the data. Conclusions The use of LB assay allowed the detection of new MSA, such as anti-MDA5, anti-MJ and anti-TIF1gamma antibodies, previously not found with routine methods. However, the high prevalence of multiple positivities and the high discondant rate of anti-Jo1 antibodies could create some misinterpretation of the results from the clinical point of view. These data should be confirmed by enlarging the number of myositis cases. [ABSTRACT FROM AUTHOR]

There is no agreement on the prevalence of anti-phospholipid antibodies (aPLs) and the correlation with atherosclerosis and cardiovascular (CV) events in the general population. We performed a cross-sectional study on 1712 randomly enrolled subjects from a Northern Italian city to investigate the presence of aPLs and the association with subclinical atherosclerosis (using the carotid artery intima media thickness measured as inter-adventitia common carotid artery diameters - ICCAD) and retrospectively collected CV factors and events (i.e. acute myocardial infarction, stroke, and peripheral obliterans arterial vasculopathy) using physician-assisted questionnaires. We tested serum IgG, IgM, and IgA anti -cardiolipin, anti-beta2glycoprotein I (aGPI), and anti -phosphatidylserine-prothrombin antibodies. Positive aPLs were found in 15.1% of the subjects, with no differences between sex but with higher rates in older subjects. Carotid subclinical atherosclerosis was more frequent in aPL positive subjects; more specifically, aGPI IgA were associated with higher ICCAD average (adjusted beta 0.51, 95% confidence interval (CI)0.17–0.84; p = 0.003). A positive history of CV events was also more frequent in aPL positive subjects (odds ratio (OR) 1.67, 95%CI 1.08–2.54; p = 0.012), particularly peripheral obliterans arterial vasculopathy (OR 2.02 ; 95%CI 1.14–3.57; p = 0.015). Among subjects with a Framingham risk score >20, and/or diabetes, and/or body mass index >3 5 kg/m 2 , aPL positivity was associated to the highest risk of CV events (OR 2.52, 95%CI 1.24–5.11; p = 0.011). APL prevalence in the general population is higher than previously reported. CV events and subclinical atherosclerosis are more frequent in the presence of aPL, particularly when a high CV risk coexists. • Positive aPL are common in the population but their CV significance is unclear. • CV events are more frequent in subjects with aPL and an elevated CV risk. • aPLs are associated with ultrasound signs of atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age.Methods: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149).Results: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning.Conclusion: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication. [ABSTRACT FROM AUTHOR]