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Objectives: To update the 2011 Italian Society of Rheumatology (SIR) recommendations for the use of biologics and other novel agents in the treatment of psoriatic arthritis (PsA)., Methods: To create this new set of recommendations, the SIR "Spondyloartritis and Psoriatic Arthritis study group - A. Spadaro" went through the following steps: literature search, identification of the items of interests for each of the four previously identified clinical domains of PsA and the different treatment phases, achievement of the consensus on all topics, and generation of the recommendations., Results: An update on the available evidence on all of the biologics and new small molecules tested in PsA is reported, comprising the data for each of the individual articular manifestation. Indications for therapy inclusion criteria, choice of the drug, disease assessment, response definition, therapy failure management, and disease remission management for PsA peripheral joint arthritis, enthesitis, dactylitis, and spondylitis are provided. Suggestions for the treatment of patients with PsA and concomitant extra-articular manifestations are also given., Conclusions: These evidence-based recommendations may be used for guidance in the complex and fast-evolving field of the treatment of PsA.

Background: Recent evidence suggested a potential role of complement fraction C3 as a biomarker of nonalcoholic fatty liver disease (NAFLD) in the general population. Aim of this study was to evaluate the performance of C3 for prediction of NAFLD in RA patients., Materials and Methods: For the present study, consecutive RA patients were recruited. NAFLD was diagnosed according to predefined ultrasonographic (US) criteria. For comparison, the hepatic steatosis index (HSI) was calculated., Results: Of 164 consecutive RA patients, 41 (25%) were diagnosed with NAFLD. The NAFLD group had a significant lower proportion of females (P = 0·04), higher BMI (P < 0·0001), C-reactive protein (P = 0·04), complement C3 (P = 0·001) and HSI (P = 0·003). In a logistic regression model, only male sex (OR 2·65, 95% CI: 1·08-6·50, P = 0·03), increasing BMI (OR 1·22, 95% CI: 1·02-1·46, P = 0·03) and complement C3 (OR 5·05, 95% CI: 1·06-23·93, P = 0·04) were associated with higher likelihood of being diagnosed with NAFLD. Finally, we built ROC curves for BMI, complement C3 and their combination for prediction of having NAFLD. The best cut-off for BMI was 28·5 kg/m 2 and yielded a sensitivity of 66% and a specificity of 71%; the best cut-off for complement C3 was 1·23 g/L and yielded a sensitivity of 76% and a specificity of 64% for classification of NAFLD cases., Conclusions: Our results provide preliminary evidence for a potential role of complement C3 as a surrogate biomarker of NAFLD in RA patients., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Objectives: Hepatitis B (HBV) infection, which is prevalent worldwide, is also frequently seen in patients with rheumatoid arthritis (RA). The Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) endorsed a national consensus process to review the available evidence on HBV management in RA patients and to produce practical, hospital-wide recommendations., Methods: The consensus panel consisted of infectious disease consultants, rheumatologists and epidemiologists and used the criteria of the Oxford Center for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations., Results: A core-set of statements has been developed to help clinicians in the management of patients with RA and HBV infection. Vaccination and prophylaxis of RA patients treated with biological drugs have been also discussed., Conclusions: HBV infection is not rare in clinical practice; a screening for HBV in all patients with early arthritis is not universally accepted, while it is considered mandatory before starting any immunosuppressive or hepatotoxic treatment. In fact, a specific risk, associated with the use of biologic treatments, exists for patients with HBV infection, although longitudinal studies of viral reactivation are generally reassuring. RA patients with HBV infection should be referred to the hepatologist and correctly classified into active or inactive carriers. Patients with active hepatitis B should undergo antiviral treatment before starting immunosuppressive treatments. Occult HBV carriers should be monitored or receive prophylaxis on the basis of the risk of reactivation associated with the administered treatment., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Rheumatoid arthritis (RA) has been associated with endothelial dysfunction, a pathophysiological feature of atherosclerosis. Our aim was to determine whether TNF-α blockade has a beneficial effect on endothelial function in RA. We performed a systematic review with meta-analysis to evaluate the effect of anti-TNF-α agents on endothelial function in RA patients. MedLine, Cochrane CENTRAL and SCOPUS were searched up to March 2016. Inclusion criteria were: 1) randomised controlled trial (RCT), quasi-RCT, before-after cohort study; 2) including RA patients; 3) treatment with anti-TNF-α medications; 4) evaluating the change from baseline in endothelial function. The search strategy retrieved 180 records, of which 20 studies were included in the systematic review. Pooled analysis using a random-effects model demonstrated a significant improvement in endothelial function following anti-TNF-α treatment (SDM 0.987, 95%CI [0.64-1.33], p < 0.0001). Generalisation of the results of the meta-analysis may be limited due to the presence of heterogeneity (I2 = 82.65%, p < 0.001) and evidence of possible publication bias. Meta-regression showed that endothelial function measurement technique was a significant contributor to heterogeneity. In conclusion, although limited by the methodological quality of the included studies, our meta-analysis suggests that anti-TNF-α treatment may improve endothelial function in RA patients.

Background: Aim of this study was to evaluate the prevalence of plantar fascia (PF) enthesopathy in Type 2 diabetes mellitus (T2DM) patients without distal peripheral neuropathy (DPN)., Methods: We recruited 50 T2DM patients without DPN and 50 healthy controls. DPN was excluded using the Michigan Neuropathy Screening Instrument (MNSI). All patients underwent a bilateral sonographicevaluation of the enthesealportion of the PF., Results: PF thickness was significantly higher in T2DM patients (p<0.0001). T2DM patients presented a higher prevalence of entheseal thickening (p = 0.002), enthesophyte (p = 0.02) and cortical irregularity (p = 0.02). The overall sum of abnormalities was higher in T2DM patients (p<0.0001), as was the percentage of bilateral involvement (p = 0.005). In a logistic regression analysis, retinopathy predicted entheseal thickening (OR 3.5, p = 0.05) and enthesophytes (OR 5.13, p = 0.001); reduced eGFR predicted enthesophytes (OR 2.93, p = 0.04); body mass index (BMI) predicted cortical irregularity (OR 0.87, p = 0.05); mean glucose predicted enthesophyte (OR 1.01, p = 0.03); LDL cholesterol predicted cortical irregularity (OR 0.98, p = 0.02)., Conclusions: Our data suggest that T2DM is associated with PF enthesopathyindependently of DPN.

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Metabolic disorders are known to alter the mechanical properties of tendons. We sought to evaluate the prevalence of asymptomatic Achilles tendon enthesopathic changes in patients with type 2 diabetes mellitus (T2DM) without peripheral neuropathy., Methods: We recruited 43 patients with T2DM and 40 controls. Neuropathy was excluded with the Michigan Neuropathy Scoring Instrument. Bilateral ultrasonography of the Achilles tendon enthesis was performed., Results: Patients with T2DM had a higher prevalence of hypoechogenicity (26.7% versus 2.5%; P = .0001), entheseal thickening (24.4% versus 8.7%; P = .007), and enthesophytes (74.4% versus 57.5%; P = .02). No differences were found in the number of patients with erosions (1.2% versus 0%; P > .99), cortical irregularities (11.6% versus 3.7%; P = .09), bursitis (5.8% versus 3.7%; P = .72), or tears (2.3% versus 1.2%; P > .99). The mean ± SD sum of abnormalities was higher in patients with T2DM (1.5 ± 1.1 versus 0.7 ± 0.6; P < .0001), as was the percentage of bilateral involvement (72.1% versus 45.0%; P = .01). Mean ± SD thickness did not differ between patients and controls (4.4 ± 1.1 mm versus 4.2 ± 0.8 mm; P = .07)., Conclusions: According to our data, there is an elevated prevalence of asymptomatic Achilles tendon enthesopathic changes in patients with T2DM independent of peripheral neuropathy.

Objectives: Accurate diagnosis and appropriate management of psoriatic arthritis (PsA) is essential to avoid unnecessary morbidity. Our aim in this study was to evaluate the current approach to the management of PsA among rheumatologists., Methods: A 16-item online questionnaire, produced using the Delphi method, was submitted to a panel of rheumatologists who anonymously expressed their opinions on a scale from 1 (maximum disagreement) to 5 (maximum agreement). Positive consensus was defined by ≥66% of the respondents scoring an item 3, 4 or 5. Negative consensus was defined by ≥66% of the respondents scoring an item 1 or 2., Results: The surveyed rheumatologists agreed that in its early stage, PsA is characterised by the involvement of few joints and/or entheses and that psoriasis, although possibly absent, will be present in a patient's past personal or family history. There was no consensus among the rheumatologists regarding normalisation of C-reactive protein levels and erythrocyte sedimentation rates defining remission. The specialists believed that clinical remission was achieved more frequently and for longer among patients with PsA than rheumatoid arthritis. The participants believed that neutralising antibodies altered the efficacy of anti-tumour necrosis factor agents and that monoclonal antibodies induced greater production of neutralising antibodies than receptor proteins. However, knowledge was somewhat lacking in relation to the prophylaxis of latent tuberculosis., Conclusions: The data collected showed that the surveyed rheumatologists had a good knowledge of the diagnosis of early-stage PsA and a good understanding of its management in relation to its clinical phenotype, with the exception of the form having predominantly axial involvement.

Purpose of Review: This study aims to provide an update on current status of pharmacological therapies in early and advanced stages of axial spondyloarthritis (axSpA), as well as its late onset forms, and to discuss the need for treat to target strategies in this entity., Recent Findings: Efficacy of TNF inhibitors has been assessed in randomized controlled trials in axSpA, which included patients who had non-radiographic axSpA according to the ASAS classification criteria. The role of IL17/23 pathway as a therapeutic target in ankylosing spondylitis (AS) has been the focus of phase III studies of secukinumab (named MEASURE 1 and MEASURE 2) and a proof-of-concept study of ustekinumab. Potential efficacy of novel small molecules such as apremilast and tofacitinib has been explored in recent phase II trials. All the trials of TNF inhibitors in non-radiographic axSpA have achieved their primary endpoints, which resulted in their approval for this indication in Europe, but not in USA. The phase III trials of secukinumab have demonstrated significant therapeutic benefit as compared to placebo, resulting in its approval as the first non-TNF biologic for the treatment of AS, both by the US Food and Drug Administration and the European Medicines Agency.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis of unknown origin. Its autoimmune origin has been suggested but never proven. Several reports have implicated Klebsiella pneumoniae as a triggering or perpetuating factor in AS; however, its role in the disease pathogenesis remains debated. Moreover, despite extensive investigations, a biomarker for AS has not yet been identified. To clarify these issues, we screened a random peptide library with pooled IgGs obtained from 40 patients with AS. A peptide (AS peptide) selected from the library was recognized by serum IgGs from 170 of 200 (85%) patients with AS but not by serum specimens from 100 healthy controls. Interestingly, the AS peptide shows a sequence similarity with several molecules expressed at the fibrocartilaginous sites that are primarily involved in the AS inflammatory process. Moreover, the peptide is highly homologous to a Klebsiella pneumoniae dipeptidase (DPP) protein. The antibody affinity purified against the AS peptide recognizes the autoantigens and the DPP protein. Furthermore, serum IgG antibodies against the Klebsiella DPP121-145 peptide epitope were detected in 190 of 200 patients with AS (95%), 3 of 200 patients with rheumatoid arthritis (1.5%) and only 1 of 100 (1%) patients with psoriatic arthritis. Such reactivity was not detected in healthy control donors. Our results show that antibodies directed against an epitope of a Klebsiella pneumoniae-derived protein are present in nearly all patients with AS. In the absence of serological biomarkers for AS, such antibodies may represent a useful tool in the diagnosis of the disease., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: Behcet's syndrome is more common in certain geographic regions, however, can be seen outside of these areas and need to be included in the differential diagnosis of many patients, as it has overlapping features with many rheumatologic conditions., Recent Findings: Especially in regions with immigrant populations, there seem to be similarities to originating countries in Behcet's prevalence, but the syndrome is not limited to those from certain backgrounds and can be seen in others also. There is emerging evidence that even though the prevalence of Behcet's may be similar to that of endemic areas, in nonendemic regions the condition may be less severe, suggesting potential environment agents in determining the severity of the disease. In addition, women seem to be overrepresented in nonendemic areas and may explain part of the reason for less severe symptoms, as Behcet's tends to be more severe in men., Summary: The somewhat different presentation of Behcet's syndrome in nonendemic areas needs to be considered when thinking about Behcet's in the differential diagnosis of patients. Research into potentially less severe form of the disease in nonendemic areas may provide new clues to the pathogenesis of this condition.

Objectives: Rheumatoid arthritis (RA) is characterised by an excess of cardiovascular diseases (CVD) risk, attributable to a synergy between under-diagnosed traditional risk factors (i.e. insulin resistance) and inflammatory disease activity. The aim of the present study was to evaluate the correlation between inflammatory measures and insulin sensitivity in RA patients., Methods: Forty non-diabetic RA patients (19 males) were recruited. All patients underwent anthropometric measurements, laboratory evaluation and oral glucose tolerance test (OGTT). Insulin sensitivity index (ISI) was calculated with the equation proposed by Matsuda et al., from dynamic values of glucose and insulin obtained during OGTT., Results: In the univariate analysis, lnISI correlated inversely with age, BMI, waist circumference, sBP, ESR, lnCRP and complement C3, but not with disease duration, dBP or complement C4. In non-obese patients (BMI <30 kg/m2, n=28), only age, BMI, lnCRP and C3 maintained their correlation with lnISI. In a stepwise multiple regression using lnISI as the dependent variable and BMI, age, lnCRP and complement C3 as predictors, only BMI and C3 entered the equation and accounted for 38.2% of the variance in lnISI. In non-obese patients, only C3 entered the regression equation, accounting for 32.2% of the variance in lnISI. Using a ROC curve, we identified the best cut-off for complement C3 of 1.22 g/L that yielded a sensitivity of 67% and a specificity of 79% for classification of insulin resistant patients., Conclusions: In RA patients, complement C3 correlates strongly with insulin sensitivity, in both obese and non-obese individuals.

The choice of the partner an individual will mate with is expected to strongly impact its fitness. Hence, natural selection has favoured the evolution of cues to distinguish among mates that will provide different fitness benefits to the individual that is choosing. In species with first-male sperm precedence, this is particularly important for males, as mating with mated females will result in no offspring. In the spider mite Tetranychus urticae only the first mating is effective, except if the interval between first and second copulations is shorter than 24 h. In line with this, males prefer to mate with virgin over mated females. They do not, however, choose between females that have mated at different time intervals. Here, we tested which type of cues males use to distinguish between females with different mating status (virgin versus mated). To do so, we firstly confirmed that males prefer virgins over mated females and that they do not select females on the basis of their age or mating interval. Next, we tested whether contact and volatile compounds or chemical trails affected male discrimination between mated and virgin females, by systematically varying the exposure of males to these cues. We found that volatile compounds and chemical trails were sufficient to induce discrimination between virgin and mated females in males. Direct contact with females, however, does not seem to play a role in this discrimination. The composition of such chemical cues (trails and volatiles) remains to be identified.

Introduction: Anti-TNF drugs have represented an epochal revolution in the treatment of rheumatoid arthritis and spondyloarthritis. In the field of axial spondyloarthritis, golimumab, a fully human monoclonal anti-TNFα administered subcutaneously every 4 weeks, has shown significant efficacy and good safety in patients with ankylosing spondylitis. More recently, it was also indicated as an effective treatment for patients suffering from non-radiographic axial spondyloarthitits. Areas covered: A systematic literature search was completed, using the largest electronic databases (Medline, Embase and Cochrane), with the aim to review all data concerning the administration of golimumab in patients suffering from axial spondyloartritis. Expert opinion: In the 16-week GO-AHEAD study, golimumab was effective in patients with non-radiographic spondyloarthritis with high levels of CRP and/or positive MRI findings, but not in subjects with both negative CRP and MRI. This finding allows for the addressing the of anti-TNF treatment more specifically. Preliminary data concerning an open-label extension of the GO-AHEAD study outlined the high retention-rate of the drug at 52 weeks. The production of antibodies against golimumab is rare and it seems to exert scarce influence on the drug performances. In conclusion, golimumab appears as a very useful and well tolerated anti-TNF agent.

Introduction: Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease characterized by a wide clinical spectrum. The early diagnosis of PsA is currently a challenging topic. Areas covered: The literature was extensively reviewed for studies addressing the topic area "diagnosis of psoriatic arthritis". This review will summarize improvements in diagnostic tools, especially referral to the rheumatologist, the role of patient history and clinical examination, laboratory tests, and imaging techniques in getting an early and correct diagnosis of PsA. Expert commentary: Due to the heterogeneity of its expression, PsA may be easily either overdiagnosed or underdiagnosed. A diagnosis of PsA should be taken into account every time a patient with psoriasis or a family history of psoriasis shows peripheral arthritis, especially if oligoarticular or involving the distal interphalangeal joints, enthesitis or dactylitis. Magnetic resonance imaging and ultrasonography are useful for diagnosing PsA early, particularly when isolated enthesitis or inflammatory spinal pain occur.

Objectives: The purpose of this study was to have an overview of the current approach to psoriatic arthritis (PsA) by a group of Italian rheumatologists., Methods: Rheumatologists from all around Italy were asked to participate in a survey to give their opinion on a number of statements made by a panel of rheumatologists who are experts in PsA. The survey was conducted through two rounds using a Delphi-like method. The two rounds yielded a consensus on the management of PsA., Results: Fifty rheumatologist from 50 rheumatology centres participated in the survey. Of the 117 proposed statements, only 10 did not reach the 66% concordance threshold. The main results of the survey were that diagnosis of PsA should be made using both the CASPAR criteria and clinical judgment, that all of the features of the psoriatic disease are relevant in the assessment and therapy of PsA, that treatment recommendations are taken into account, that all of the available biological agents may be used in bio-naïve patients, that anti-drug antibody testing is still not used in daily practice, that both switching or swapping are useful options in the case of bio-failure because of lack or loss of efficacy, and that swapping is considered the best choice in the case of bio-failure due to adverse events., Conclusions: The results of this survey showed that a comprehensive evaluation of the patient and a therapy choice based on both patient clinical features and evidence of drug efficacy and safety are considered the current best of care for PsA patients.

Mycophenolate mofetil (MMF) has been shown to be effective in children with immune thrombocytopenia (ITP) and Evans syndrome (ES), but data from larger series and details on the timing of the response are lacking. We evaluated 56 children treated with MMF for ITP (n = 40) or ES (n = 16), which was primary or secondary to autoimmune lymphoproliferative syndrome -related syndrome (ARS). Thirty-five of the 54 evaluable patients (65%) achieved a partial (18%) or complete (46%) response after a median (range) of 20 (7-137) and 37 (7-192) d, respectively. ITP and ES patients responded in 58% and 81% of cases (P = not significant, ns), with complete response in 32% and 81% (P = 0·01), respectively. 60% and 73% of children with primary disease and ARS responded (P = ns) with complete response in 34% and 68% of cases (P = 0·01), respectively. Six of 35 (17%) children relapsed after a median of 283 d (range 189-1036). Limited toxicity was observed in four patients. The median durations of treatment and follow-up were seven and 12·7 months, respectively. This is the largest reported cohort of patients treated with MMF for ITP/ES. The results show that MMF is effective and safe and provides a relatively quick response, suggesting that it has a potential role as an alternative to more aggressive and expensive second/further-line treatments., (© 2016 John Wiley & Sons Ltd.)

Introduction: The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages., Methods: Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included., Results: The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness., Discussion: This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures., Competing Interests: Conflicts of Interest: None declared.

Purpose: The purpose of this study was to explore the presence of autoimmune manifestations and characterize the autoantibody production in a cohort of patients with Aicardi-Goutières syndrome (AGS)., Methods: Seventeen patients with a genetically-confirmed diagnosis of AGS were recruited. At the time of enrollment, past medical and family history was reviewed, looking for possible signs or symptoms of autoimmune disorders. Blood samples were taken, for the detection of a panel of autoantibodies: anti-nuclear, anti-double-stranded-DNA, anti-nucleosome, anti-extractable nuclear antigens, anti-cardiolipin IgG/IgM, anti-β2glycoprotein I IgG/IgM, and anti-neutrophil cytoplasmic. We also measured complement levels determined as C3 and C4 quantification and total complement activity, measured as CH50., Results: Nine of seventeen patients presented with at least one first- or second-degree relative with a history of autoimmune diseases (the childrens' mother or grand-mother in the majority of cases). A specific autoimmune disease was present in only one AGS patient, namely an autoimmune thyroiditis. Autoantibodies were present in 9/17 patients, with different patterns of positivity. Complement levels were normal in all the patients. There was no correlation between auto-antibody production and personal or family history of autoimmune diseases., Conclusions: Definite autoimmune diseases are not common in patients with AGS. Autoantibodies are mainly directed towards nucleic acids-containing elements but seem not to be pathogenic and, rather, may represent an epiphenomenon of the enhanced interferon production.

Objectives: To evaluate the correlation between inflammatory measures and whole-body insulin sensitivity in psoriatic arthritis (PsA) patients., Methods: For the present study, 40 nondiabetic PsA patients were recruited. A standard oral glucose tolerance test (OGTT) was performed. The insulin sensitivity index (ISI), insulinogenic index (IGI) and oral disposition index (ODI) were calculated from dynamic values of glucose and insulin obtained during OGTT., Results: In our study population, mean ISI was 3.5 ± 2.5, median IGI was 1.2 (0.7-1.8), mean ODI 4.5 ± 4.5. In univariate correlation analysis, ISI correlated inversely with systolic blood pressure (sBP) (R = -0.52, p = 0.001), diastolic blood pressure (dBP) (R = -0.45, p = 0.004) and complement C3 (R = -0.43, p = 0.006) and ODI correlated inversely with sBP (R = -0.38, p = 0.02), dBP (R = -0.35, p = 0.03) and complement C3 (R = -0.37, p = 0.02). No significant correlations were found between analyzed variables and IGI. In a stepwise multiple regression, only complement C3 entered in the regression equation and accounted for approximately 50% of the variance of ISI. Using a receiver operating characteristic (ROC) curve we identified the best cut-off for complement C3 of 1.32 g/L that yielded a sensitivity of 56% and a specificity of 96% for classification of insulin resistant patients., Conclusions: In conclusion, our data suggest that serum complement C3 could represent a useful marker of whole-body insulin sensitivity in PsA patients., Competing Interests: The authors have declared that no competing interests exist.

Anti-tumour necrosis factor (TNF) agents are recommended as second-line therapy for patients with axial spondyloarthropathies. This analysis reviewed data on studies investigating the efficacy and tolerability of anti-TNF agents in patients with non-radiographic axial spondyloarthritis (nr-axSpA) who had failed first-line non-steroidal anti-inflammatory (NSAID) treatment. Efficacy data from RCTs were used to calculate the number needed to treat (NNT) for individual anti-TNFs and then the cost per responder was determined to provide an indication of the value of each therapy. A systematic literature review and analysis of search results over the period January 2008 to September 2014 identified four randomised placebo-controlled trials that were included in the analysis. Adalimumab, etanercept and certolizumab pegol were all effective and well tolerated in patients with nr-axSpA. A patient was more likely to reach ASAS20 or ASAS40 when treated with etanercept or adalimumab, the NNT was lowest for adalimumab, and the risk of adverse events was higher with certolizumab pegol 200 mg every 2 weeks. The cost per responder (NNT) was lowest for adalimumab, followed closely by certolizumab 400 mg every 4 weeks, intermediate for certolizumab 200 mg every 2 weeks and highest for etanercept. Although all anti-TNF agents were associated with clinical improvement in patients with nr-axSpA, adalimumab presented a better cost per responder than etanercept and certolizumab pegol.

Aim: This study was conducted to develop and validate a new self-report questionnaire for measuring quality of life (QoL), at school age, in children with a very low birthweight (VLBW)., Method: Through a focus group approach, children were involved directly in defining the questionnaire items, which were presented as illustrations rather than written questions. This preliminary validation of the questionnaire was conducted in 152 participants with VLBW (aged 7-11y) randomly selected from the five participating Italian centres. The questionnaire was completed by children and parents separately; data on children's demographic and medical history, and intellectual, adaptive, and behavioural functioning were collected using standardized scales. All the children also completed the Paediatric Quality of Life Inventory (PedsQL), another Italian-language measure of QoL in children., Results: Our questionnaire was readily accepted and understood, and quick to complete. The Cronbach's alpha value showed it to be a reliable instrument. The child-compiled version correlated well with the PedsQL, whereas no correlations emerged with the other scales used, IQ, or degree of impairment. Conversely, these variables correlated significantly with the parent-compiled version. Children's and parents' answers were divergent on practically all the items., Interpretation: The results confirm the validity of the new instrument and highlight a poor overlap between parents' and children's perspectives., (© 2016 Mac Keith Press.)

Objective: The aim of this study was to evaluate rate and predictive factors of loss of remission and disease flare in patients with axial spondyloarthritis (axSpA) receiving antitumor necrosis factor (anti-TNF) treatment., Methods: In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria, treated with adalimumab, etanercept, or infliximab with a minimum followup of 12 months and satisfying the ASAS partial remission criteria and/or Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were studied. Disease flare was defined as a Bath Ankylosing Spondylitis Disease Activity Index score > 4.5 or ASDAS score > 2.5 on at least 1 occasion., Results: One hundred seventy-four patients with axSpA were studied. After a median [interquartile range (IQR)] followup of 4 years (2-6), 37 patients (21.2%) experienced a loss of remission and 28 (16.1% of the whole study group) a disease flare. Median (IQR) duration of remission in patients who lost this status was 1 year (0.625-2). Higher median erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, continuous nonsteroidal antiinflammatory drug (NSAID) use, and an ASDAS-CRP ≥ 0.8 during the remission period were significantly associated with both loss of remission and disease flare. At the multivariate analysis, continuous NSAID intake (OR 4.05, 95% CI 1.4-11.74, p = 0.010) and ESR > 15 (OR 2.90, 95% CI 1.23-6.82, p = 0.015) were the only factors predictive of disease reactivation., Conclusion: In this study, loss of remission and disease flares occurred, respectively, in about 21% and 16% of the patients with axSpA who achieved a state of remission while receiving anti-TNF therapy. Residual disease activity was associated with disease reactivation.

Aims: Primary: to investigate Italian rheumatology practice regarding latent tubercular infection (LTBI) detection and tuberculosis (TB) prevention in patients requiring anti-tumor necrosis factor (anti-TNF) therapy. Secondary: to assess the overall number of TB cases over 10 years and their distribution by drug., Methods: An anonymous, 24 multiple-response questionnaire was completed by 393/449 (87.5%) rheumatologists prescribing anti-TNF therapy. Six questions provided setting information, and 18 the compliance with recommendations and the recorded TB cases., Results: The Italian recommendations were used by 323 (82%) and other sets by 60 (15%). TB specialists were always consulted by 81 (21%) and occasionally by 73 (19%). LTBI screening was made using chest radiograph (CR) by 5%, tuburculin skin test (TST) by 5.3%, CR + TST by 35.6%, interferon-gamma release assay (IGRA) by 7.4%, CR + IGRAs by 26% and CR + TST + IGRA by 20.6%. Isoniazid was initiated in the presence of positivity of TST by 97 (24.7%), TST + IGRA by 101 (25.7%) and IGRA by 195 (49.6%). Anti-TNF starting delay was 1 month in 63.1% of the cases, 3 months in 27.7%, concomitantly in 5.6%. Overall, 317 TB reactivation cases occurred in 39 353 patients, with an incidence rate of 80.5 cases/100 000/year (10 times higher than in the Italian general population). TB occurred during TB prophylaxis in 192 (60.6%). TB cases incidence rate divided by drug was: etanercept (ETN) 51 (16%), 28/100 000/year, adalimumab (ADA) 98 (31%), 89/100 000/year, infliximab (IFX) 137 (43.2%), 211/100 000/year, with a significantly lower frequency in the ETN group compared to ADA and IFX groups (χ(2)  = P < 0.001)., Conclusion: Italian rheumatologists are highly aware of anti-TNF-related TB risk with variable LTBI screening and TB prevention strategies. TB outcome was significantly lower in the ETN group., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Objective: To establish the predictive validity of the Assessment of SpondyloArthritis international Society (ASAS) spondyloarthritis (SpA) classification criteria., Methods: 22 centres (N=909 patients) from the initial 29 ASAS centres (N=975) participated in the ASAS-cohort follow-up study. Patients had either chronic (>3 months) back pain of unknown origin and age of onset below 45 years (N=658) or peripheral arthritis and/or enthesitis and/or dactylitis (N=251). At follow-up, information was obtained at a clinic visit or by telephone. The positive predictive value (PPV) of the baseline classification by the ASAS criteria was calculated using rheumatologist's diagnosis at follow-up as external standard., Results: In total, 564 patients were assessed at follow-up (345 visits; 219 telephone) with a mean follow-up of 4.4 years (range: 1.9; 6.8) and 70.2% received a SpA diagnosis by the rheumatologist. 335 patients fulfilled the axial SpA (axSpA) or peripheral SpA (pSpA) criteria at baseline and of these, 309 were diagnosed SpA after follow-up (PPV SpA criteria: 92.2%). The PPV of the axSpA and pSpA criteria was 93.3% and 89.5%, respectively. The PPV for the 'clinical arm only' was 88.0% and for the 'clinical arm'±'imaging arm' 96.0%, for the 'imaging arm only' 86.2% and for the 'imaging arm'+/-'clinical arm' 94.7%. A series of sensitivity analyses yielded similar results (range: 85.1-98.2%)., Conclusions: The PPV of the axSpA and pSpA criteria to forecast an expert's diagnosis of 'SpA' after more than 4 years is excellent. The 'imaging arm' and 'clinical arm' of the axSpA criteria have similar predictive validity and are truly complementary., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The genetic predisposition to a long-term efficacy of anti-tumor necrosis factor (TNF)α treatment in seronegative spondyloarthritis (SpA) was investigated by analysing the possible correlation between several single nucleotide gene polymorphisms and the retention rate of anti-TNFα therapies. We compared patients needing to switch the first anti-TNFα (Sw, No. 64) within at least 12 months of follow-up with patients not needing to switch (NSw, No. 123), observing at least 6 months of treatment to establish anti-TNFα failure, leading to treatment change. Response to treatment was evaluated by standardised criteria (BASDAI for axial involvement, DAS28-EULAR for peripheral involvement). The TNFα -308 A allele and the interleukin (IL)-6 -174GG homozygosis resulted as independent biomarkers predicting survival of the first anti-TNFα therapy in SpA patients (P=0.007, odds ratio (OR): 4.4, 95% confidence interval (CI)=1.5-13.1 and P=0.035, OR: 2.1, 95% CI=1.1-4.4). Also, the male gender (P=0.001, OR: 3.4, 95% CI=1.6-7.1) associated with the NSw phenotype, whereas no association was found either with the specific diagnosis or the predominant joint involvement.

Growing data have provided encouraging results on the use of interleukin (IL)-1 inhibitors in Behçet's disease (BD). This study was aimed at reporting the largest experience with anti-IL-1 agents in BD patients. We evaluated 30 BD patients receiving treatment with anti-IL-1 agents. The primary aims of the study were to evaluate the efficacy of anakinra (ANA) and canakinumab (CAN) in a cohort of BD. The secondary aims were to evaluate the overall safety profile of the treatments, explore the timing of response to therapy and any adjustment of dosage and frequency of drugs studied, and investigate predictive factors of response to therapy. The frequency of first line therapy was 90 % with ANA and 10 % with CAN. The overall number of subjects in complete remission after 12 months of therapy with anti-IL-1 drugs was 13: 6 maintained the initial therapy regimen, 1 maintained the same initial anti-IL-1 drug with further therapeutic adjustments, and the remaining 6 shifted from ANA to CAN. Among them, 3 used CAN for at least 12 months without therapeutic adjustments, 1 had therapeutic adjustments, and 3 had an overall history of a 12-month complete remission. Adverse events (AEs) were reported in 15 % patients who received ANA, represented in all cases by local cutaneous reactions, while no AE were observed in patients who received CAN; we did not observe any serious AEs (SAEs) during the follow-up period. Our data have confirmed that the use of anti-IL-1β drugs is efficacious and safe with an overall acceptable retention on treatment.

Background: The aim was to establish how patients experience the impact of spondyloarthritis (SpA) on work disability and working life., Methods: The survey was performed in 17/20 regions in Italy (1 January to 31 March 2013). A multiple-choice questionnaire was published on the official website of the sponsor - the National Association of Rheumatic Patients (ANMAR) - and hard-copies were distributed at outpatient clinics for rheumatic patients., Results: Respondents (n = 770) were of both sexes (56 % men), educated (62 % at high school or more), of working age (75 % aged ≤60 years), and affected by SpA. The most common types diagnosed were ankylosing spondylitis (AS) (39 %) and psoriatic arthritis (PsA) (36 %). Respondents were working full-time (45 %), part-time (8 %) or had retired (22 %); 15 % were unemployed (for reasons linked to the disease or for other reasons, students or housewives). Patients reported disability (39 %), were receiving disability benefits (34 %), were experiencing important limitations that were hindering their professional development/career (36 %) and some had to change/leave their job or lost it because of SpA (21 %). Employed respondents (n = 383) had worked on average 32.2 h in the last 7 days. More hours of work were lost over the last 7 days due to SpA (2.39 h vs 1.67 h). The indirect costs of the disease amounted to €106/week for patients reporting well-being/good physical conditions/improvement and €216/week for those reporting permanent impairment., Conclusions: Most patients were in the midst of their productive years and were experiencing considerable difficulties in carrying out their job because of the disease: half of them reported disability and one third were experiencing important limitations in their career perspective.

Background: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations., Methods: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated., Results: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used., Conclusions: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an excess of cardiovascular disease (CVD) risk, estimated to be at least 50% greater when compared to the general population. Although the widespread diffusion of type 2 diabetes mellitus (T2DM) awareness, there is still a significant proportion of patients with T2DM that remain undiagnosed. Aim of this cross-sectional study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in RA patients. For the present study, 100 consecutive nondiabetic RA patients were recruited. Age- and sex-matched subjects with noninflammatory diseases (osteoarthritis or fibromyalgia) were used as controls. After overnight fasting, blood samples were obtained for laboratory evaluation including serum glucose, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, uric acid, erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), and anti-Cyclic Citrullinated Peptide Antibodies (ACPA). A standard Oral Glucose Tolerance Test (OGTT) with 75 g of glucose was performed and blood samples were collected at time 0, 30, 60, 90, and 120 minutes, for measurement of plasma glucose concentrations. The prevalence of impaired fasting glucose (IFG) (9/100 vs 12/100, P = 0.49), impaired glucose tolerance (IGT) (19/100 vs 12/100, P = 0.17), and concomitant IFG/IGT (5/100 vs 9/100, P = 0.27) was similar between groups, whereas the prevalence of diabetes was significantly higher in RA patients (10/100 vs 2/100, P = 0.02). In a logistic regression analysis, increasing age (OR = 1.13, 95% CI 1.028-1.245, P = 0.01) and disease duration (OR = 1.90, 95% CI 1.210-2.995, P = 0.005) were both associated with an increased likelihood of being classified as prediabetes (i.e. IFG and/or IGT) or T2DM. A ROC curve was built to evaluate the predictivity of disease duration on the likelihood of being diagnosed with T2DM. The area under the ROC curve was 0.67 (95% CI: 0.56-0.78, P = 0.004). We identified the best cut-off of 33 months that yielded a sensitivity of 61% and a specificity of 70% for classification of T2DM patients. According to our data, RA seems to be characterized by an elevated prevalence of undiagnosed diabetes, especially in patients with longer disease duration., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Hepatitis C virus (HCV) is a hepato- and lymphotropic agent that is able to induce several autoimmune rheumatic disorders: vasculitis, sicca syndrome, arthralgias/arthritis and fibromyalgia. The severity of clinical manifestations is variable and sometimes life-threatening. HCV infection can mimic many primitive rheumatic diseases, therefore, it is mandatory to distinguish HCV-related manifestations from primitive ones because the prognosis and therapeutic strategies can be fairly dissimilar. The new direct-acting antivirals drugs can help to avoid the well-known risks of worsening or new onset of autoimmune diseases during the traditional interferon-based therapies.

Objective: To perform an updated characterization of the neuroradiologic features of Aicardi-Goutières syndrome (AGS)., Methods: The neuroradiologic data of 121 subjects with AGS were collected. The CT and MRI data were analyzed with a systematic approach. Moreover, we evaluated if an association exists between the neuroradiologic findings, clinical features, and genotype., Results: Brain calcifications were present in 110 subjects (90.9%). Severe calcification was associated with TREX1 mutations and early age at onset. Cerebral atrophy was documented in 111 subjects (91.8%). Leukoencephalopathy was present in 120 children (99.2%), with 3 main patterns: frontotemporal, diffuse, and periventricular. White matter rarefaction was found in 54 subjects (50.0%), strongly associated with mutations in TREX1 and an early age at onset. Other novel radiologic features were identified: deep white matter cysts, associated with TREX1 mutations, and delayed myelination, associated with RNASEH2B mutations and early age at onset., Conclusions: We demonstrate that the AGS neuroradiologic phenotype is expanding by adding new patterns and findings to the classic criteria. The heterogeneity of neuroradiologic patterns is partly explained by the timing of the disease onset and reflects the complexity of the pathogenic mechanisms., (© 2015 American Academy of Neurology.)

Objectives: Poor information on long-term outcomes and costs on tumour necrosis factor (TNF) inhibitors in psoriatic arthritis (PsA) are available. Our aim was to evaluate long-term costs and benefits of TNF- inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs)., Methods: Fifty-five out of 107 enrolled patients included in the study at one year, completed the 5-year follow-up period. These patients were enrolled in 8 of 9 centres included in the study at one year. Patients aged older than 18 years, with different forms of PsA and failure or intolerance to tDMARDs therapy were treated with anti-TNF agents. Information on resource use, health-related quality of life (HRQoL), disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before TNF inhibitor therapy and after 1 and 5 years were compared., Results: The majority of patients (46 out of 55; 83.6%) had a predominant or exclusive peripheral arthritis and 16.4% had predominant or exclusive axial involvement. There was a statistically significant improvement of the most important clinical variables after 1 year of follow-up. These improvements were maintained also after 5 years. The direct costs increased by approximately €800 per patient-month after 1 year, the indirect costs decreased by €100 and the overall costs increased by more than €700 per patient-month due to the cost of TNF inhibitor therapy. Costs at 5 year were similar to the costs at 1 year. The HRQoL parameters showed the same trends of the clinical variables. EQ-5D VAS, EQ-5D utility and SF-36 PCS score showed a significant improvement after 1 year, maintained at 5 years. SF-36 MCS showed an improvement only at 5 years., Conclusions: The results of our study suggest that TNF blockers have long-term efficacy. The higher cost of TNF inhibitor therapy was balanced by a significant improvement of HRQoL, stable at 5 years of follow-up. Our results need to be confirmed in larger samples of patients.

We advocate the advantage of an evolutionary approach to conservation biology that considers evolutionary history at various levels of biological organization. We review work on three separate plant taxa, spanning from one to multiple decades, illustrating extremes in metapopulation functioning. We show how the rare endemics Centaurea corymbosa (Clape Massif, France) and Brassica insularis in Corsica (France) may be caught in an evolutionary trap: disruption of metapopulation functioning due to lack of colonization of new sites may have counterselected traits such as dispersal ability or self-compatibility, making these species particularly vulnerable to any disturbance. The third case study concerns the evolution of life history strategies in the highly diverse genus Leucadendron of the South African fynbos. There, fire disturbance and the recolonization phase after fires are so integral to the functioning of populations that recruitment of new individuals is conditioned by fire. We show how past adaptation to different fire regimes and climatic constraints make species with different life history syndromes more or less vulnerable to global changes. These different case studies suggest that management strategies should promote evolutionary potential and evolutionary processes to better protect extant biodiversity and biodiversification.

This review seeks to update the state of the art of axial psoriatic arthritis (axPsA). The definition and assessment of axPsA can be problematic because no agreement and no definitive data on this topic have been published, resulting in uncertainty as to the best approach to deal with these patients. A few recent scientific reports show new data on the possible coincidence of diffuse idiopathic skeletal hyperostosis and axPsA, as well as on the radiological assessment as measured with the validated instruments for axPsA. Moreover, the role of magnetic resonance imaging has also been evaluated for this intriguing subset. All data confirmed that radiological assessment is a useful tool to detect typical findings of axPsA, while other imaging techniques remain to be validated. Finally, there is no evidence to support treatment of axPsA with traditional disease-modifying antirheumatic drugs, while a "leap" to biologic agents is the only treatment after failure with nonsteroidal antiinflammatory drugs.

In the early 1970s, Moll and co-workers formulated the unified concept of spondyloarthritides, a group of conditions sharing similar clinical features. Subsequently, criteria for their classification have been proposed by Amor and coworkers, the European Spondylarthropathy Study Group, and the Assessment in SpondyloArthritis international Society. Opinion, however, is divided between those who believe that the different entities of the complex represent the variable expression of the same disease ("lumpers") and those who think that these should be considered separately but under the same umbrella ("splitters"). Several sets of criteria have been proposed for psoriatic arthritis (PsA), the most recent being the ClASsification for Psoriatic Arthritis (CASPAR) criteria. According to some authors, there are persuasive arguments to support the view of PsA as a distinct entity.

Psoriasis is a common, immune-mediated chronic inflammatory disease with a primary involvement of skin and joints, affecting approximately 2% of the population worldwide. Up to one third of patients with psoriasis are diagnosed with psoriatic arthritis (PsA). Psoriasis and PsA are heterogeneous diseases whose severity depends on a number of clinical factors, such as areas affected and pattern of involvement, and are associated with a range of comorbid diseases and risk factors, including obesity, metabolic syndrome, cardiovascular disease and liver disease. Thus measuring the severity of psoriatic disease needs to take into account the multidimensional aspects of the disease. Subjective measures including the impairment in quality of life or in daily living activities as well as the presence of cardio-metabolic comorbidities, are important for the outcome and add further levels of complexity that, to a certain extent, need to be assessed. Because of the wide range of comorbid conditions associated with psoriasis, comprehensive screening and treatment must be implemented for a most effective managing of psoriasis patients. A joint dermatologist-rheumatologist roundtable discussion was convened to share evidence on the real-life use of methods for measuring psoriasis severity comprehensively. Our objective was to provide an expert position on which clinical variables are to be taken into account when considering patients affected by psoriasis and/or PsA globally and on the assessment tools more suitable for measuring disease activity and/or severity in clinical practice., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: Aicardi-Goutières syndrome (AGS) is an autoimmune disorder that shares similarities with systemic lupus erythematous. AGS inflammatory responses specially target the cerebral white matter. However, it remains uncertain why the brain is the most affected organ, and little is known about the presence of autoantibodies in AGS. Here, we aim to profile specific autoantibodies in AGS and to determine whether these autoantibodies target cerebral epitopes., Methods: Using a multiplex microarray, we assessed the spectrum of serum autoantibodies in 56 genetically confirmed patients with AGS. We investigated the presence of immunoglobulins in AGS brain specimens using immunohistochemistry and studied the reactivity of sera against brain epitopes with proteomics., Results: Serum from patients exhibited high levels of IgGs against nuclear antigens (gP210, Nup62, PCNA, Ro/SSA, Sm/RNP complex, SS-A/SS-B), components of the basement membrane (entactin, laminin), fibrinogen IV and gliadin. Upon testing whether antibodies in AGS could be found in the central nervous system, IgGs were identified to target in vivo endothelial cells in vivo and astrocytes in brain sections of deceased patients with AGS. Using a proteomics approach, we were able to confirm that IgGs in serum samples from AGS patients bind epitopes present in the cerebral white matter., Conclusions: Patients with AGS produce a broad spectrum of autoantibodies unique from other autoimmune diseases. Some of these autoantibodies target endothelial cells and astrocytes in the brain of the affected patients, perhaps explaining the prominence of neurological disease in the AGS phenotype., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Studying antagonistic coevolution between host plants and herbivores is particularly relevant for polyphagous species that can experience a great diversity of host plants with a large range of defenses. Here, we performed experimental evolution with the polyphagous spider mite Tetranychus urticae to detect how mites can exploit host plants. We thus compared on a same host the performance of replicated populations from an ancestral one reared for hundreds of generations on cucumber plants that were shifted to either tomato or cucumber plants. We controlled for maternal effects by rearing females from all replicated populations on either tomato or cucumber leaves, crossing this factor with the host plant in a factorial design. About 24 generations after the host shift and for all individual mites, we measured the following fitness components on tomato leaf fragments: survival at all stages, acceptance of the host plant by juvenile and adult mites, longevity, and female fecundity. The host plant on which mite populations had evolved did not affect the performance of the mites, but only affected their sex ratio. Females that lived on tomato plants for circa 24 generations produced a higher proportion of daughters than did females that lived on cucumber plants. In contrast, maternal effects influenced juvenile survival, acceptance of the host plant by adult mites and female fecundity. Independently of the host plant species on which their population had evolved, females reared on the tomato maternal environment produced offspring that survived better on tomato as juveniles, but accepted less this host plant as adults and had a lower fecundity than did females reared on the cucumber maternal environment. We also found that temporal blocks affected mite dispersal and both female longevity and fecundity. Taken together, our results show that the host plant species can affect critical parameters of population dynamics, and most importantly that maternal and environmental conditions can facilitate colonization and exploitation of a novel host in the polyphagous T. urticae, by affecting dispersal behavior (host acceptance) and female fecundity.

Background: The Movement Disorder-Childhood Rating Scale represents a new tool for assessment of movement disorders during developmental age. In this study, we evaluated a cohort of 68 patients affected by various types of movement disorders and treated with specific drugs over one year to verify the usefulness of the Movement Disorder-Childhood Rating Scale., Method: The participants were divided into two groups according to their ages (0-3 years; 4-18 years) and were evaluated using Movement Disorder-Childhood Rating Scale 0-3 or 4-18 at baseline (i.e., before starting pharmacological treatment [T0], after 6 months [T1], and after 12 months [T2] of treatment. Univariate repeated measures analysis of variance with a Greenhouse-Geisser correction by SPSS 20 was performed to analyze the scale responsiveness for the three indices (e.g., Index I, Index II, Global Index) in each group with time (T0, T1, and T2). In addition, the Bonferroni test was performed to identify the source of significant differences among means., Results: Significant differences were found between time points (T1 versus T0, T2 versus T0, and T2 versus T1) in both scales for all indexes with the exception for T2 versus T1 for Index II in both scales and for T2 versus T1 for the Global Index in the older age group. There was no significant correlation between observed changes in the scores and the age of the children, either for Movement Disorder-Childhood Rating Scale 0-3 or 4-18., Conclusion: Our results suggest that Movement Disorder-Childhood Rating Scale is a suitable tool to detect changes independently from age and could be used as outcome measure for clinical trials., (Copyright © 2015 Elsevier Inc. All rights reserved.)

An impaired expression of interferon-α regulated genes has been reported in patients with either systemic lupus erythematosus (SLE) or Aicardi-Goutières syndrome (AGS), a rare monogenic encephalopathy with onset in infancy. One of mutations causing AGS is located in the TREX1 gene on chromosome 3. Heterozygous mutations in TREX1 were reported in SLE patients. TREX1 is a DNA exonuclease with specificity for ssDNA. An impairment of its activity may result in the accumulation of nucleid acid. A recent study described a significant association between a haplotype including several common single nucleotide polymorphisms (SNPs) of TREX1 and neurological manifestations in European SLE patients. Fifty-one SLE patients were screened for TREX1 gene, and the corresponding data were collected from clinical charts. A novel heterozygous variant (p.Asp130Asn) was identified in one patient and in none of 150 controls. A missense variation was located in one of the three active sites of the gene and was classified as probably damaging. Variations of SNP rs11797 were detected in 33 SLE patients and a variation of rs3135944 in one. A significantly higher rate of the minor allele (T nucleotide) of SNP rs11797 was found in SLE patients with neuropsychiatric manifestations [12/16 (75%) vs 28/86 (32.5%) O=0.002, odds ratio=6.42 95% confidence interval (1.7-26.2)]. Only 1 out of 8 patients (12.5%) with neuropsychiatric SLE carried the wild-type form in homozygosity. Although we analyzed a small number of patients, we found a novel variation of TREX1, which may be pathogenic. The polymorphism of rs11797 was more frequent in SLE patients with neurological manifestations.

Objective: The observational RAPSODIA (RA, PsA and spondylitis including AS) study was planned to assess, in patients with RA, AS and PsA, their involvement in medical decisions, quality of life and unmet needs 15 years after the introduction of biologic therapies in Italy., Methods: Patients completed a questionnaire during their scheduled rheumatology consultation. They rated their satisfaction with disease knowledge on a 5-point scale (1 = not at all satisfied, 5 = totally satisfied). Self-efficacy, defined as judgement of one's own ability to achieve given levels of performance and exercise control over events, was measured using the pain subscale of the Arthritis Self-Efficacy Scale. Patients' global assessments of pain, fatigue and disease activity were recorded on 100 mm visual analogue scales (0 = best status, 100 = worse status). Disease activity status was assessed using standard tools. Health status was measured using the 36-item Short Form Health Survey and the Italian version of the HAQ., Results: Ninety-eight per cent of patients reported that their health care practitioner used understandable terms to explain their condition. Joint issues and general symptoms (e.g. fatigue and malaise) were common. All measures of disease activity and self-efficacy scores were markedly better in patients receiving biologic vs conventional therapy. Biologic therapy recipients were more productive at work., Conclusion: These results confirm that some patients with rheumatic diseases are not satisfied with the level of information they receive about their treatments. Biologic therapy appears to be an important advance, with patients receiving this form of treatment having improved symptoms and productivity. However, patients still report unmet needs. Thus further research, and perhaps new and more effective therapies, along with better education and multidisciplinary collaboration, are required to improve outcomes., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)