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Objective.The study aim was to determine treatment persistence rates and to identify causes of discontinuation in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients in clinical practice.Methods.Patients treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) were retrospectively included. Treatment persistence rates were analyzed by means of a stepwise logistic regression. Differences between therapy duration were assessed by means of an analysis of variance model (ANOVA), while a chi-square test was used to evaluate relationships between therapies and causes of treatment discontinuation and the administration of concomitant disease-modifying antirheumatic drugs (DMARDs) among therapies and types of disease considering completed courses of therapy versus courses that were discontinued.Results.268 patients received a total of 353 anti-TNF treatment courses (97 ADA, 180 ETA, and 76 INF). Comparison among therapies showed significant difference regarding the treatment persistence rates due to the contrast between ETA and INF (P=0.0062). We observed that 84.7% of patients were still responding after 6 months of follow-up. Comparison among diseases showed that there were significant differences between PsA and AS (P=0.0073) and PsA and PsA with predominant axial involvement (P=0.0467) in terms of duration of the therapy, while there were no significant differences with regard to the persistence rate.Conclusions.In this cohort, anti-TNF-αtherapy was associated with high drug persistence rates. As in rheumatoid arthritis, switching to another anti-TNF-αagent can be an effective option when, during the treatment of AS or PsA, therapy is suspended because of inefficacy or an adverse event. Combination therapy with DMARDs was associated with a better persistence rate.

Autoinflammatory disorders (AIDs) are a novel class of diseases elicited by mutations in genes regulating the homeostasis of innate immune complexes, named inflammasomes, which lead to uncontrolled oversecretion of the proinflammatory cytokine interleukin-1β. Protean inflammatory symptoms are variably associated with periodic fever, depicting multiple specific conditions. Childhood is usually the lifetime in which most hereditary AIDs start, though still a relevant number of patients may experience a delayed disease onset and receive a definite diagnosis during adulthood. As a major referral laboratory for patients with recurrent fevers, we have tested samples from 787 patients in the period September 2007–March 2014, with a total of 1,328 AID-related genes evaluated and a gene/patient ratio of 1.69. In this report, we describe our experience in the clinical approach to AIDs, highlight the most striking differences between child and adult-onset AIDs, and shed an eye-opening insight into their diagnostic process.

Chronic pelvic pain (CPP) is a common condition that has a major impact on the quality of life of both men and women. Male CPP is usually attributable to well-defined urogenital conditions (most frequently infectious/non infectious prostatic diseases) or musculoskeletal or bowel diseases, whereas the features of female CPP are much more complex and are of particular clinical and epidemiological importance. It is a multifactorial syndrome that can be due to diseases of the urogenital, gastrointestinal, or musculoskeletal systems, or to neurological or neuropsychiatric disorders. It is not always easy to identify its predominant pathogenesis, although it often occurs as a central sensitization syndrome triggered by an initial stimulus which is no longer detectable and only manifests itself clinically through pain. In this respect, there are some very interesting relationships between vulvodynia and fibromyalgic syndrome, as identified in a preliminary study of women with chronic musculoskeletal pain in which it was demonstrated that vulvar pain plays an important role, although it is often overlooked and undiagnosed.

Weber-Christian Disease (WCD), also known as relapsing febrile lobular non-suppurative panniculitis, is a rare condition characterized by recurrent subcutaneous inflammatory nodules in the adipose tissue in addition to fever, malaise and other systemic manifestations such as polyarthralgia and polymyalgia. The association with small vessel vasculitis has been rarely reported. We report here an unusual case of WCD associated with small vessels vasculitis also describing the efficacy of Cyclosporin A treatment.

In the present study we assessed the frequency and characteristics of the main causes of morbidity and mortality in SLE during a 5-year period and analyzed the prognostic significance for morbidity and mortality of the main immunologic parameters used in clinical practice. We started in 1990 a multicenter study of 1,000 patients from 7 European countries. All had medical histories documented and underwent medical interview and routine general physical examination when entered in the study, and all were followed prospectively by the same physicians during the ensuing 5 years (1990-1995). Four hundred thirteen patients (41.3%) presented 1 or more episodes of arthritis, 264 (26.4%) had malar rash, 222 (22.2%) active nephropathy, 139 (13.9%) fever, 136 (13.6%) neurologic involvement, 132 (13.2%) Raynaud phenomenon, 129 (12.9%) serositis (pleuritis and/or pericarditis), 95 (9.5%) thrombocytopenia, and 72 (7.2%) thrombosis. Two hundred seventy patients (27%) presented infections, 113 (11.3%) hypertension, 75 (7.5%) osteoporosis, and 59 (5.9%) cytopenia due to immunosuppressive agents. Sixteen patients (1.6%) developed malignancies, with the most frequent primary localizations the uterus and the breast. Several immunologic parameters (anti-dsDNA or antiphospholipid antibodies) were found to have a predictive value for the development of SLE manifestations during the period of the study. Forty-five patients (4.5%) died; the most frequent causes of death were divided similarly among active SLE (28.9%), infections (28.9%), and thromboses (26.7%). A survival probability of 95% at 5 years was found. A lower survival probability (92%) was detected in those patients who presented at the beginning of the study with nephropathy.

Lactoferrin is a multifunctional immunoregulatory protein, stored in specific granules of neutrophil granulocytes, from which it is released following cell activation. As activated neutrophils play a crucial role in the destruction of synovial joints in rheumatoid arthritis, we evaluated lactoferrin concentration in synovial fluid and sera from 21 patients with rheumatoid arthritis and 11 patients with osteoarthritis. We also measured lactoferrin levels in sera from 12 healthy controls. Lactoferrin was measured by a solid-phase inhibition immunoassay. Median lactoferrin levels were significantly higher in synovial fluid from rheumatoid arthritis than from osteoarthritis patients (P = 0.0002). In contrast, no significant difference was found between serum lactoferrin from patients with rheumatoid arthritis or osteoarthritis compared with normal controls. In patients with rheumatoid arthritis, lactoferrin concentrations were higher in synovial fluid than in sera (P = 0.036). In both rheumatoid arthritis and osteoarthritis no correlation was found between serum and synovial fluid lactoferrin (P = 0.51 and P = 0.5, respectively). In synovial fluid from patients with rheumatoid arthritis, lactoferrin concentrations correlated with neutrophil granulocyte count (P0.0001), but neither serum nor synovial lactoferrin levels correlated with disease activity (P = 0.32 and P = 0.25, respectively). In conclusion, lactoferrin is a reliable marker of neutrophil activation at sites of inflammation in rheumatoid synovitis, but does not represent a marker of disease activity.

Objective: To test the prevalences and the clinical associations of anticardiolipin (aCL) and anti-β 2 GPI (aβ 2 GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). Methods: 574 SLE patients from 7 European countries were tested for aCL and aβ 2 GPI by ELISA methods. Results: aCL of IgG, IgM, and IgA isotypes were detected in 22.8%, 14%, and 13.9% of the patients, respectively. IgG and IgM aβ 2 GPI were detected in 20% of the patients. The presence of aCL was highly associated with the presence of aβ 2 GPI. Medium-high titer IgG aCL and aβ 2 GPI were associated with thrombosis, with similar sensitivity, specificity, and positive predictive value. When present at medium-high titer, IgG aCL were associated with thrombocytopenia, IgM aCL with hemolytic anemia, and cerebrovascular accidents, IgA aCL with livedo reticularis and Raynaud's phenomenon. Conclusions: aCL, when present at medium-high titer, are as important as aβ 2 GPI, as a risk factor for thrombosis. Medium-high titer aCL, but not aβ 2 GPI, are associated with other clinical features of the antiphospholipid syndrome.

Objective. To test the prevalences and the clinical associations of anticardiolipin (aCL) and anti-β2GPI (aβ2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). Methods. 574 SLE patients from 7 European countries were tested for aCL and aβ2GPI by ELISA methods. Results. aCL of IgG, IgM, and IgA isotypes were detected in 22.8%, 14%, and 13.9% of the patients, respectively. IgG and IgM aβ2GPI were detected in 20% of the patients. The presence of aCL was highly associated with the presence of aβ2GPI. Medium-high titer IgG aCL and aβ2GPI were associated with thrombosis, with similar sensitivity, specificity, and positive predictive value. When present at mediumhigh titer, IgG aCL were associated with thrombocytopenia, IgM aCL with hemolytic anemia, and cerebrovascular accidents, IgA aCL with livedo reticularis and Raynaud's phenomenon. Conclusion. aCL, when present at medium-high titer, are as important as ab2GPI, as a risk factor for thrombosis. Medium-high titer a...

We describe two cases of rheumatoid arthritis (RA) patients and concomitant hepatitis C virus infection (HCV), treated with cyclosporine A (CsA) and anti-TNF-alpha agents. SGOT/SGPT and HCV-RNA serum levels remained unchanged longer than 1 year of treatment. No side effects were registered. We suggest that combination therapy with CsA and TNF-alpha blockers should be considered safe and well-tolerated in the treatment of HCV-positive RA patients.

Recommendations related to ocular, mucosal and cutaneous involvement of Behçet's disease (BD) are mainly evidence-based, but in cases of vascular, neurological and gastrointestinal involvement there are no guidelines to define the best treatment strategy. We report three adult patients with BD, who received an interleukin-1β inhibitor by subcutaneous injections, canakinumab (at the dosage of 150 mg every 6 weeks), after failure shown by corticosteroids and different combinations of immunosuppressant agents. The prompt and sustained clinical efficacy demonstrated by canakinumab as a monotherapy supports the opportunity of using this specific anti-interleukin-1β agent as a valid therapeutic option for resistant or refractory BD. Open trials and observational studies should be performed to test canakinumab efficacy on a larger number of patients. The most appropriate dosage and intervals between administrations should be decided according to the individual patient, severity or recurrence of clinical manifestations and major organ involvement.

Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists.

Purpose. Ultrasonography (US) has been demonstrated to be an important tool in the diagnosis of calcium pyrophosphate (CPP) crystal deposition disease. The aim of our study was to individuate and describe possible pitfalls in US detection of such deposits in menisci.Patients and Methods. We enrolled all patients waiting to undergo knee replacement surgery due to osteoarthritis, for one-month period. Each patient underwent US examination of the knee, focusing on the menisci. After surgery, the menisci were examined by US, macroscopically and microscopically, using the microscopic analysis as the gold standard for CPP deposition.Results. 11 menisci of 6 patients have been studied. Ex vivo examination of menisci performed better in CPP identification than in vivo examination. The possible reasons of misinterpretation or misdiagnosis of the in vivo exam were identified and are extensively described in the paper. Also a new sign of CPP crystal deposits was found.Conclusions. This study permitted to highlight some difficulties in CPP crystal detection by US in menisci. Further studies are needed to define completely US CPP crystal aspect and to improve the sensibility and specificity of US in CPP deposition diagnosis.

Treatment of monogenic autoinflammatory disorders, an expanding group of hereditary diseases characterized by apparently unprovoked recurrent episodes of inflammation, without high-titre autoantibodies or antigen-specific T cells, has been revolutionized by the discovery that several of these conditions are caused by mutations in proteins involved in the mechanisms of innate immune response, including components of the inflammasome, cytokine receptors, receptor antagonists, and oversecretion of a network of proinflammatory molecules. Aim of this review is to synthesize the current experience and the most recent evidences about the therapeutic approach with biologic drugs in pediatric and adult patients with monogenic autoinflammatory disorders.

Anti-tumor necrosis factor alpha (anti-TNF-α) is used in the treatment of rheumatic diseases not responsive to first-line regimens. Data on the safety of anti-TNF-α in HIV-infected patients are scarce and conflicting. We describe a case of septic shock and multiorgan failure that occurred after etanercept initiation and influenza vaccination in an HIV-infected woman with rheumatoid arthritis.

Clodronate is a bisphosphonate used for the treatment of postmenopausal osteoporosis and all conditions characterized by excess bone resorption. We have previously reported that intramuscular (IM) therapy with clodronate at a dose of 100 mg/week displays significant effects on bone mineral density (BMD) although a plateau effect is observed after 1 year of treatment. Previous reports indicate that the densitometric effects of bisphosphonates directly correlate with the drug dosage and suggest that using IM clodronate at doses higher than 100 mg/week may result in improved efficacy. However, to the best of our knowledge, this has never been proved.The primary endpoint of the study was the effect on BMD of IM clodronate 100 mg once weekly or 100 mg twice weekly in patients with postmenopausal osteoporosis. The incidence of non-traumatic vertebral fractures and adverse events was also reported.The present study was a randomized, open-label, parallel-group trial conducted between January 2007 and December 2009 in the Osteoporosis and Osteoarticular Instrumental Diagnosis Centre (University of Siena, Siena, Italy). The study involved 60 women, aged 57-78 years, with a history of postmenopausal osteoporosis for more than 5 years. Patients were randomized to receive IM clodronate 100 mg once weekly (Group A, 30 patients) or 100 mg twice weekly (Group B, 30 patients), for 2 years.Significant increases compared with baseline in BMD were observed for both groups at 1 and 2 years, with significantly higher increases for Group B compared with Group A. Group B displayed a BMD increase (± SD) at the lumbar spine of +4.0 % (± 2.1) and +5.9 % (± 2.0) at 1 and 2 year(s), respectively, compared with +2.8 % (± 1.7) and +3.5 % (± 2.2), respectively, observed for Group A. Similarly, Group B showed better performance compared with Group A for BMD increase at the femoral neck, with an observed increase of +3.5 % (± 1.7) and +5.4 % (± 1.8) at 1 and 2 year(s), respectively, compared with a change of +2.3 % (± 1.9) and +2.5 % (± 1.9), respectively, registered in Group A. Consistently, the BMD increase measured at the total femur was significantly higher for Group B [+3.4 % (± 1.9) and +4.9 % (± 2.1) at years 1 and 2, respectively] compared with Group A [+1.6 % (± 0.9) and +2.4 % (± 1.9) at years 1 and 2, respectively]. When the change in BMD from year 1 to year 2 was compared, a significant increase of BMD was seen in Group B in all the analysed regions, contrary to that observed for Group A where a plateau effect resulted in no significant change from year 1 to year 2. Three non-traumatic vertebral fractures occurred during the study: two in Group A and one in Group B.The present study indicates the superior performance of IM clodronate 200 mg weekly (100 mg twice weekly) compared with 100 mg once weekly in BMD in women with postmenopausal osteoporosis. This work demonstrated that administration of twice the drug dosage in a week significantly improved the efficacy of the treatment without inducing serious adverse events. Therefore, IM clodronate 200 mg weekly may be considered a valid therapeutic choice for the treatment of postmenopausal osteoporosis.

Item does not contain fulltext The study objective was to report treatment with an interleukin (IL)-1 receptor antagonist, anakinra, in patients with multiorgan Behcet's disease (BD). Comparison of clinical manifestations, previous treatments, markers of inflammation, concomitant medications, treatment regimen modifications, relapses, and adverse events before and during anakinra administration among patients with BD were evaluated. Nine BD patients (mean age 34.55 +/- 16.30 years) refractory to tumor necrosis factor blockers and standardized therapies are reported in our survey. Their mean age at disease onset was 25 +/- 13.88 years and their overall disease duration was 9.55 +/- 5.33 years. All patients were positive for the HLA-B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out of nine patients promptly responded, and most of them were maintained on 100 mg of daily anakinra with low doses of prednisone. However, most patients experienced a relapse in one or more clinical manifestations over time (mean time to relapse 29 +/- 21.65 weeks), and only one patient remained completely under control on anakinra monotherapy. Despite a relapse in one or more disease manifestations, treatment was continued in most patients for a mean period of 13.75 +/- 6.49 months. No serious adverse events occurred. Eight out of nine refractory BD patients showed a prompt improvement after starting anakinra, supporting the concept that IL-1 plays a pathological role in this disease. Nevertheless, after several months, most patients experienced a relapse. It remains unclear whether increasing the dose of anakinra would have prevented the reoccurrence of disease activity.

Osteoarthritis (OA), the most common joint disorder, is a disease involving all the articular structures. It presents both degenerative and inflammatory aspects. Recently, the important role of Bradykinin (BK), a phlogistic mediator, has been proposed in the pathophysiology of OA. In our review, we summarized the currently available information on the mechanisms of action of BK in OA by linking its B2 receptors. Then, we analyzed the data about the effects of BK in synoviocytes and chondrocytes cultures. Furthermore, we described the action of B2 receptor antagonists (Icatibant and Fasitibant), presenting them as new promising symptom-anddisease- modifying agents in the treatment of OA. However, more in vitro, animal model and clinical studies, are needed to better understand the mechanisms of action as well as the efficacy and tolerability of the B2 receptor antagonists in OA.

Objective To analyze the clinical manifestations and response to treatment in a cohort of adult patients presenting with recurrent inflammatory attacks and carrying low-penetrance TNFRSF1A variants, as well as to provide data on their long-term follow-up. Methods We performed a retrospective chart review of 36 patients carrying low-penetrance TNFRSF1A variants. Moreover, 60 genetically negative patients treated for recurrent inflammatory attacks and 13 patients with structural TNFRSF1A mutations were also analyzed. Detailed demographic and clinical data were collected at the time of molecular screening and at each follow-up visit. Treatments and markers of inflammation were also assessed. Results Individuals with low-penetrance TNFRSF1A variants have a lower family history for inflammatory attacks and present with a later disease onset compared with patients with structural mutations, but do not differ, in this respect, with genetically negative individuals. Moreover, low-penetrance variants are less frequently associated with a chronic disease course, with clinical manifestations such as abdominal pain and myalgia, and with amyloidosis. A distinctive clinical feature is a higher rate of pericarditis. Interestingly, mutation-negative patients were found to present with a significant history of recurrent pharyngitis during childhood. Patients with low-penetrance variants are mostly managed with short courses of steroids or non-steroidal anti-inflammatory drugs on attacks. Although the need for a biological treatment is significantly lower compared with patients with structural mutations, still approximately 20% of individuals with recurrent inflammatory attacks carrying low-penetrance variants ultimately require these therapies. Conclusions Our study confirms that low-penetrance TNFRSF1A variants can be associated with an autoinflammatory phenotype. Although a chronic disease course is rarely observed, some patients ultimately benefit from a biological treatment.

Background Mevalonate kinase deficiency (MKD) is caused by mutations in the MVK gene, encoding the second enzyme of mevalonate pathway, which results in subsequent shortage of downstream compounds, and starts in childhood with febrile attacks, skin, joint, and gastrointestinal symptoms, sometimes induced by vaccinations. Methods For a history of early-onset corticosteroid-induced reduction of bone mineral density in a 14-year-old boy with MKD, who also had presented three bone fractures, we administered weekly oral alendronate, a drug widely used in the management of osteoporosis and other high bone turnover diseases, which blocks mevalonate and halts the prenylation process. Results All of the patient’s MKD clinical and laboratory abnormalities were resolved after starting alendronate treatment. Conclusions This observation appears enigmatic, since alendronate should reinforce the metabolic block characterizing MKD, but is crucial because of the ultimate improvement shown by this patient. The anti-inflammatory properties of bisphosphonates are a new question for debate among physicians across various specialties, and requires further biochemical and clinical investigation.

Idiopathic recurrent acute pericarditis is the most baffling drawback occurring in around 1/3 of patients who have suffered from acute pericarditis or complicating a host of systemic medical conditions. Various autoimmune diseases can involve the pericardium during the acute phase of the disease, even with no specific signs, and different cases of postviral pericarditis display an autoimmune background. In addition, some autoinflammatory disorders might display self-limited pericardial effusions, which are characterized by chronic recurrence. The clinical efficacy of corticosteroids should give support to the autoimmune origin of idiopathic recurrent acute pericarditis, but the dramatic response to interleukin-1 antagonists in patients with steroid-dependent idiopathic recurrent pericarditis should corroborate its autoinflammatory beginnings. The dividing line between the two medical settings is undefined and both autoimmune and autoinflammatory mechanisms should be advocated in the evaluation of this challenging pericardial disease.

Autoinflammatory diseases are comprehensively caused by aberrant production of proinflammatory cytokines and are revealed by cyclically and spontaneously occurring inflammatory events. Over the last decade, there has been a revolution in the understanding of periodic fever syndromes, cryopyrinopathies, and skin disorders with pyogenic, granulomatous, or dystrophic features, which have been recognized across different countries spanning from the Mediterranean basin to the Japanese archipelago. Many children and adults with autoinflammatory diseases continue to elude diagnosis, and the diagnostic delay of many years puts these patients at risk of long-term severe complications, such as amyloidosis. Any hint of suspicion of autoinflammatory disease thus needs to be highlighted in various medical specialties, and this review examines their frequencies around the world, trying to match them with geographic location, ethnic and genetic data, in an attempt to realize a geoepidemiologic map for most of these conditions.

Background The risk of sudden cardiac death is increased in chronic inflammatory arthritis, particularly rheumatoid arthritis (RA). To evaluate the putative effect of systemic inflammation on heart rate variability (HRV) and ventricular repolarization in chronic inflammatory arthritis, we analyzed in these patients the possible relationship among HRV parameters, QT interval, and high sensitivity C-reactive protein (hsCRP). Methods One hundred-one patients with chronic inflammatory arthritis underwent a 15-minute ambulatory twelve-channel electrocardiogram-recording, to evaluate HRV and QT interval, as well as a venous withdrawal for hsCRP as an estimation of ongoing systemic inflammation. Results In patients with chronic inflammatory arthritis, hsCRP is inversely correlated with HRV and directly with QTc duration, but while hsCRP is associated with HRV independently from any other investigated factor, the association between hsCRP and QTc seems to be an indirect consequence of the autonomic dysfunction itself. Within the whole cohort of patients, those subjects having elevated hsCRP levels displayed both a significant reduction in HRV and a prolongation of QTc with respect to patients with a normal hsCRP value. A similar, although less marked, degree of HRV depression and QTc prolongation was found in RA patients when compared to subjects with spondyloarthritis (SpA) and healthy controls. Conclusions These data provide evidence of a link between systemic inflammation and the arrhythmic risk in patients with chronic inflammatory arthritis, also putatively explaining, at least in part, how the different inflammatory load characterizing RA and SpA parallels the different risks of cardiovascular death in these two conditions.

Hereditary autoinflammatory disorders encompass manifold dysfunctions of innate immunity caused by mutations in genes coding for the main characters of the inflammatory scene: most of these conditions have an early onset, ranging from the first days of life to the first decades, and include hereditary periodic fevers, NLRP-related diseases, granulomatous and pyogenic syndromes, which are basically characterized by upturned inflammasome activity and overproduction of bioactive interleukin (IL)-1β and other proinflammatory cytokines. The discovery of a causative link between autoinflammation and IL-1β release has improved our understanding of the intimate mechanisms of innate immunity, and has likewise led to the identification of extraordinary treatments for many of these disorders.

Tumor necrosis factor-receptor associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder characterized by recurrent episodes of long-lasting fever and inflammation in different regions of the body, such as the musculo-skeletal system, skin, gastrointestinal tract, serosal membranes and eye. Our aims were to evaluate circulating microRNAs (miRNAs) levels in patients with TRAPS, in comparison to controls without inflammatory diseases, and to correlate their levels with parameters of disease activity and/or disease severity. Expression levels of circulating miRNAs were measured by Agilent microarrays in 29 serum samples from 15 TRAPS patients carrying mutations known to be associated with high disease penetrance and from 8 controls without inflammatory diseases. Differentially expressed and clinically relevant miRNAs were detected using GeneSpring GX software. We identified a 6 miRNAs signature able to discriminate TRAPS from controls. Moreover, 4 miRNAs were differentially expressed between patients treated with the interleukin (IL)-1 receptor antagonist, anakinra, and untreated patients. Of these, miR-92a-3p and miR-150-3p expression was found to be significantly reduced in untreated patients, while their expression levels were similar to controls in samples obtained during anakinra treatment. MiR-92b levels were inversely correlated with the number of fever attacks/year during the 1(st) year from the index attack of TRAPS, while miR-377-5p levels were positively correlated with serum amyloid A (SAA) circulating levels. Our data suggest that serum miRNA levels show a baseline pattern in TRAPS, and may serve as potential markers of response to therapeutic intervention.

Background. Bone damage in rheumatoid arthritis (RA) and in psoriatic arthritis (PsA) includes an accelerated bone mineral density (BMD) reduction. The objective was to evaluate BMD variations of the metacarpophalangeal joints (MCPs) in patients starting treatment with methotrexate (MTX) or etanercept. Methods. Patients affected by RA or PsA with hand joints involvement and with moderate or high disease activity, were enrolled in this study. All patients underwent clinical examination, laboratory exams, and a DXA scan of the most affected hand, as assessed with an ultrasound examination at the baseline, at the time of enrolment and after 1, 3, 6, and 12 months. Patients non-responders to MTX received combination therapy, while patients with no previous treatment initiated MTX. Results. 22 patients were enrolled. In both RA and PsA groups, BMD increased independently of the treatment. However, in the patients affected by RA, a slight BMD decrease was observed at the last checkup. Globally, the BMD variations of the MCPs were strongly correlated with the disease activity. At the reduction of DAS28, the scores corresponded an increase of BMD. Conclusions. MCPs BMD is inversely correlated to disease activity. BMD increase seems to be correlated with the response to treatment and not with the drug itself.

Whether a genetic predisposition to develop the antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC) exists has been addressed by family studies and by population studies on primary APS and on aCL in diseases other than primary APS. Various studies suggest a familial occurrence of aCL and LAC, with or without clinical evidence of APS. This familial tendency could be genetically determined, because APS, aCL, and LAC occur in families carrying haplotypes which contain HLA-DR4, -DR7, and -DRw53. Population studies on primary APS also indicate that HLA genes have a role in conferring susceptibility to develop primary APS. Again, DR4, DR7, and DRw53 are the relevant loci. Population studies on aCL in diseases other than primary APS indicate that aCL are associated with DR4, DR7, and DRw53, at least when they are found in patients with systemic lupus erythematosus. Because HLA-DR4, -DR7, and -DRw53 are in linkage disequilibrium, the genetic association of aCL could be with DRw53 and, depending on the regional frequency of DR4 or DR7, it could be linked with either DR4 or DR7. HLA-DR4 seems to be more important in Anglo-Saxons, whereas DR7 emerges in populations of Latin origin. In this report we review our studies and the pertinent literature in this field.

Background Behcet9s disease (BD) is a rare and poorly understood condition characterised by systemic inflammation. Current biomarkers are still largely insensitive and unable to predict disease progression and response to treatment in BD patients. Objectives The specific aims of this study were i) to explore serum levels of soluble CD40L (sCD40L), soluble intracellular-adhesion-molecule (sICAM-1), monocyte-chemoattractant-protein-1 (MCP-1), myeloperoxidase (MPO), leptin, resistin, osteoprotegerin (OPG), soluble-type 1 tumour-necrosis-factor-receptor (sTNFR), interleukin-6 (IL-6) and serum-amyloid-A (SAA); ii) to evaluate potential correlations between the putative circulating biomarkers with the demographic profile, disease activity, organ involvement, genetical background, and different therapeutic regimes. Methods 57 serum samples were collected from 27 BD patients and 35 healthy controls (HC) after written consent. Demographic and clinical data are summarized in Table 1. Adipocytokines were analyzed using the bead-based-analyte-detection-system. Data were acquired by flow-cytometry. SAA serum concentration was determined with a enzyme linked-immunosorbent assay (ELISA). We used ANOVA test to identify statistical differences. P Results BD patients showed higher levels of circulating sTNFR (p=0.008), leptin (p=0.0011), sCD40L ( Conclusions The identification of a specific meta-immunological profile associated with disease status and response to therapy may contribute to our understanding of the physiopathology processes underlying BD activity and damage as well as to provide useful tools for prognostic purposes and a personalized treatment approach. Disclosure of Interest None declared

Background An articular involvement is reported in Behcet disease up to 70% of patients, varying from referred arthralgia to arthrtitis, generally non-erosive, poly- or oligoarticular. Some authors compared this joint involvement to Seronegative Spondyloarthritis, reporting prevalent involvement of entheses and sacroiliitis. Few US studies has been conducted in Behcet, focusing on tendon and enthesal evaluation Objectives To evaluate the presence of US pathological findings of joints, tendons and entheses of patients affected by Behcet disease Methods We enrolled consecutive patients with Behcet disease reaching the Rheumatologic Unit of our hospital between Feb 2014 and Jan 2016, irrespective of disease activity status and therapy. US exams was performed by a single operator with 8–18 MHz linear transducers (Esaote MyLab70). 42 joints (shoulders, elbows, wrists, MCPs, PIPs, hips, knees, ankles, MTPs), 12 entheses (triceps tendons,common extensor tendons, knee entheses, Achilles tendons) and 20 tendon sheats (flexor digitorum tendons, wrist9s flexor and extensor tendons, anterior and posterior tibialis and peroneal tendons) were evaluated for each patient, using a stardardized technique. Grey scale (GS) and power Doppler (PD) US exam was performed to detect joint effusion, synovial hypertrophy and PD, classified with dicotomic and semiquantitative score (grade 0–3); effusion and synovial hypertrophy were combined in a single score and defined as synovitis. The presence/absence of tenosynovitis was evaluated for each site. At the entheseal level, we evaluated the presence of GS abnormalities of tendon structure (hypoechogenicity/thickness), enthesophytes and Doppler signal within the tendon or at the entheseal site, all classified as present/absent Results We evaluated a total amount of 1596 joints, 760 tendons and 456 entheses from 38 patients (20 women). A grade 1 synovitis was observed in 158 joints (9,9%): 87 MTPs, 21 knees, 19 MCPs, 14 wrists, 11 ankles, 4 PIPs and 2 elbows; in 72 patients the finding was monolateral while in 43 patients it was observed bilaterally, notably at I and II MTPs and knees joints. A grade 2 synovitis was observed in 18 joints (1,12%): 16 MTPs, 1 knee and 1 MCP; no grade 3 synovitis was observed. A grade 1 PD was detected in 2 wrists, 2 MCPs and 7 MTPs joints and a grade 3 PD was observed in a single MCP joint. We observed the presence of tenosynovitis in 36 cases, all involving hand or wrist tendon structures. 12 entheses presented altered fibrillar pattern with hypoecogenicity (8 common extensor tendons and 4 knee entheses), while the presence of enthesophytes was observed at the common extensor in 4 cases, at triceps in 8, at quadriceps in 6, at proximal patellar insertion in 2, at Achilles tendon in 21; the presence of at least 1 grey scale abnormality was observed in 63 entheseal sites (13,81%). An intratendineous PD signal was observed in 27 cases (5,9%): 16 common extensor tendons, 4 quadriceps, 3 proximal patellar insertion, 4 Achilles tendons Conclusions In a population of patients with Behcet disease we observed the presence of joint effusion in 11% and PD signal in 0,7% of examined joints, notably involving hands and feet joints. GS alteration of tendon structure was detected in 13,81% and an intratendineous PD signal in 5,9% of entheseal sites.A mild tenosynovitis was observed in 4,7% of examined tendons Disclosure of Interest None declared

Background Neutrophil extracellular traps (NETs) are web-like structures, composed of nucleic acids, histones and granular enzymes, including myeloperoxidase and elastase, that have a physiological crucial role in innate immunity response by trapping microbes. In addition, NETs have been identified as regulators of many inflammatory and autoimmune disorders, including crystal-induced arthritis.[1,2] In particular, a key role in the pathogenesis of gout flares has been postulated for NETs. During gout attacks, NET aggregates should package MSU crystals with a concomitant degradation of proinflammatory cytokines, leading to the rapid resolution of the inflammatory phase.[3] Objectives To evaluate NET expression in synovial fluid from acute CPPD arthritis and to compare NET release between acute MSU and CPPD arthritis. Methods Synovial fluid was collected from patients with active gout or pseudogout attack (n=5 for each group) and immediately centrifuged (805 rad) to separate cells from supernatant. Polymorphonuclear leukocytes were counted and immediately processed for morphological evaluation under transmission electron microscopy (Zeiss EM 109; 4000x). NET expression was evaluated by fluorescence microscopy using SYTOX Green (Life Technologies) and neutrophil elastase specific antibody (ABCAM). Fluorometric quantification of NET components, DNA and neutrophil elastase, was performed in supernatant (Cary Eclipse Varian; exc/em 503/526). Results were normalized to cells/mm 3 . Peripheral blood neutrophils from healthy donors stimulated with PMA were used as positive controls whereas PMA-untreated neutrophils were used as negative ones. All the experiments were performed according with Helsinki guidelines. Results Extracellular material morphologically compatible with NETs was observed by electron microscopy in samples from both acute MSU and CPPD arthritis. NET structures were confirmed by the presence of extracellular DNA and neutrophil elastase at immunofluorescence. Fluorometric quantification of extracellular DNA and neutrophil elastase showed an increased NET release in both gout and pseudogout samples compared with negative controls (p Conclusions Beyond confirming NETs in acute MSU arthritis, we have evidence of NET release in synovial fluid from acute CPPD arthritis. Our preliminary data suggest that the release of NETs could be a common physiophatological pathway to both crystral induced arthropaties. Disclosure of Interest None declared

Background F8-IL10 (Dekavil) is a human immunocytokine composed of the vascular targeting antibody F8, specific to the extradomain A of fibronectin, fused to the cytokine interleukin-10. F8-IL10 is being investigated in a dose-finding, PK phase Ib study and in a randomized, double blind, placebo-controlled phase II study, as a new therapeutic strategy for rheumatoid arthritis (RA). Objectives The primary objective of the phase Ib study is to determine the safety, tolerability and MTD of Dekavil in combination with methotrexate (MTX). The primary objective of the phase II study is to assess the superiority of Dekavil plus MTX over MTX by measuring the mean change from baseline of DAS28-CRP. Immunogenicity of F8-IL10 and its PK and PD profile will also be explored. Methods Patients with active RA despite MTX therapy and who failed anti-TNFα treatment are the target population of both studies. In the phase Ib, cohorts of 3–6 patients are treated with escalating doses of Dekavil (6, 15, 30, 60, 110, 160, 210, 300, 450 and 600 μg/kg) in combination with a fixed dose of MTX (10–15 mg). In the phase II, patients are randomized to Dekavil 30 or 160 μg/kg plus MTX or placebo plus MTX. Dekavil is administered by s.c. injection once weekly for a maximum of 8 weeks in both studies. Results The first 9 cohorts of the phase Ib study have been completed, 32 patients were treated and 31 are evaluable for DLT. One DLT (G2 purpura) was observed in one patient of the 9th cohort. The same patient had G1 thrombocytopenia and G3 ALT increase. Both events were considered related to the study drug and resolved within ten days. Neither SUSAR nor treatment-related deaths occurred. Mild injection site reactions were reported in 59% of patients and 2 cases of anemia (G2 and G3) were considered related to the study drug. All adverse reactions resolved after the end of treatment. Currently, the MTD has not been reached and the 600 μg/kg dose is ongoing. To date, 59.3% of the 27 patients analyzed for efficacy had ACR and EULAR responses, 29.6% and 11.1% had ACR50 and ACR70, respectively, at the low dosages of 15, 30 and 60 μg/kg. Two patients benefited from ACR70 response for 12 months after the last drug administration. In the phase II study, 13 out of 87 patients have been enrolled so far. To date, neither SUSAR nor treatment-related deaths were recorded. Conclusions The promising safety and efficacy results, even at low dosages, of Dekavil in the phase Ib study led to the start of the phase II study to verify the efficacy of Dekavil in combination with MTX in the same patient population. The currently available data suggest that the targeted delivery of IL-10 to the sites of inflammation is a promising therapeutic approach for RA. Disclosure of Interest M. Galeazzi: None declared, R. Voll: None declared, G. Sebastiani: None declared, L. Bazzichi: None declared, O. Viapiana: None declared, J. Dudler: None declared, P. Sarzi-Puttini: None declared, E. Selvi: None declared, A. Iuliano: None declared, M. Pedretti Employee of: Philogen, L. Giovannoni Employee of: Philogen, I. Bindi Employee of: Philogen, C. Bettini Employee of: Philogen, N. Ravenni Employee of: Philogen, J. Wilton Employee of: Philogen, P. Zufferey: None declared, G. Ferraccioli: None declared, R. Caporali: None declared, C. Specker: None declared, J. Wollenhaupt: None declared, D. Neri Shareholder of: Philogen

Background Open-label clinical trials have shown that patients with RA can switch from IV to SC abatacept therapy with no efficacy loss or safety concerns;1,2 however, findings from single-centre, real-world studies are unclear.3,4 Objectives To examine characteristics at baseline and before switching, and reasons for switching, in patients who switched from IV to SC abatacept in the real-world ACTION study. Methods ACTION is a 2-year, prospective, observational study of patients with moderate-to-severe RA who initiated IV abatacept across Europe and Canada. Enrolment periods: May 2008–Dec 2010 (biologic naive or failed prior biologics); Sept 2010–Dec 2013 (biologic naive); Oct 2011–Dec 2013 (failed prior biologics). This was an interim analysis of 1-year data. Assessments: baseline characteristics; reasons for switching; efficacy at the time of switch measured by EULAR response, DAS28 (ESR), DAS28 (CRP), CDAI and SDAI. Results 2364 patients were enrolled and 2350 were evaluable. A total of 91 patients (3.9%) switched from IV to SC abatacept during their first study year: 19 were biologic naive and 72 had failed prior biologics at study entry. Compared with non-switchers, the switch group had numerically higher percentages of patients with BMI ≥35 kg/m2, ≥1 co-morbidity and ≥2 prior anti-TNF failures, and lower mean disease activity, at baseline. Most patients (62.6%) who switched did so after >6 months in the study (Figure). Reasons for switching from IV to SC abatacept were available for 86 patients (94.5%; some patients had >1 reason): patient wish (53.5%), physician9s preference (24.4%), safety (9.3%), poor compliance (4.7%), efficacy (2.3%), remission (2.3%), surgery (1.2%) and other (16.3%). Only 3/91 (3.3%) patients re-switched to IV abatacept; reasons were: patient wish, safety, efficacy (1 patient each). Prior to switching to SC abatacept, 64% of patients had a good/moderate EULAR response. According to mean (SD) values, disease activity before switching was moderate: DAS28 (ESR) 3.85 (1.09), DAS28 (CRP) 3.46 (1.07), CDAI 12.49 (7.70) and SDAI 13.6 (8.13). Conclusions Few patients switched from IV to SC abatacept and most who did so switched after >6 months allowing them to first achieve stable disease activity. Switching from IV to SC abatacept was primarily driven by patient or physician preference for the SC formulation. The very low rate of return to IV (3.3%) suggests that switching from IV to SC abatacept had no adverse clinical impact. References Keystone EC, et al. Ann Rheum Dis 2012;71:857–61. Mueller R, et al. Arthritis Rheumatol 2015;67(Suppl. 10):651–52. [Abstract 449] Reggia R, et al. J Rheumatol 2015;42:193–5. Monti S, et al. J Rheumatol 2015;42:1993–4. Disclosure of Interest R. Alten Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, H. Nuslein Consultant for: Bristol-Myers Squibb, AbbVie, Celgene, Chugai, UCB, Pfizer, MSD, Novartis, Roche, Speakers bureau: Bristol-Myers Squibb, AbbVie, Celgene, Chugai, UCB, Pfizer, MSD, Novartis, Roche, M. Galeazzi: None declared, H. M. Lorenz Consultant for: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, Sobi, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, Speakers bureau: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, Sobi, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, X. Mariette Grant/research support from: Biogen, GSK, Pfizer, Speakers bureau: Bristol-Myers Squibb, GSK, Pfizer, sanofi, UCB, A. Cantagrel Grant/research support from: UCB, Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Chugai, Lilly, MSD, Novartis, Pfizer, Roche, M. Chartier Consultant for: Bristol-Myers Squibb, Y. Elbez Employee of: Bristol-Myers Squibb, C. Rauch Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

Background drugs targeting tumor necrosis factor-α (TNF) biological activity deal with an increased risk of infections. Few papers address whether TNF blockers in rheumatic patients with potential HBV occult infection are safe (1–9). Objectives to evaluate the safety of anti-TNF agents in cases of spondyloarthritis with resolved hepatitis B (HBsAg negative, HBcAb±anti-HBs positive) through a close monitoring of a possible HBV reactivation and/or rise in the aminotransferase levels. Methods the medical records for 992 outpatients with rheumatic inflammatory diseases attending two Italian Rheumatology Units between 2007–2015 were retrospectively reviewed for diagnosis of spondyloarthritis, current treatment with anti-TNF agents and seropositivity for past HBV infection. 131 patients (70 men, 61 women; mean age:60,63±9,59 years) were included in the study: 55 with ankylosing spondylitis, 65 psoriatic arthritis, 9 inflammatory bowel disease-associated arthritis, 2 non-radiographic axial spondyloarthritis. Mean disease duration was 98,64±42,60 months. 64 patients were currently in treatment with Etanercept (29 in monotherapy, 31 with MTX, 3 with SSZ, 1 with CsA); 32 with Infliximab (18 as monotherapy, 10 with MTX, 3 with SSZ, 1 with CsA); 31 with Adalimumab (16 in monotherapy, 12 with MTX, 2 with LEF, 1 with CsA); 4 with Golimumab (3 with MTX, 1 as monotherapy). 101 patients received only 1 TNF inhibitor (54 Etanercept, 27 Infliximab, 20 Adalimumab); 23 patients switched to a second and 7 patients switched to a third anti-TNF agent. 51 patients had concomitant prednisone Results at the end of the follow-up (mean of 75,50±33,37 months of anti-TNF therapy), no case of viral reactivation was observed in anti-HBc+ patients, no matter anti-HBs positivity. HBV-DNA remained undetectable, HBsAg negative, aminotransferases normal, nor it was necessary to stop biologic therapy because of viral infection. Conclusions our retrospective analysis supports the safety of TNF inhibitors for spondyloarthritis patients with a serological pattern of previous HBV infection during a follow-up >6 years. Pre-emptive antiviral prophylaxis is not necessary routinely, but strict monitoring for AST/ALT increase, as well as for changes in HBV serology and HBV-DNA, is necessary and seems a cost-effective approach to identify early viral reactivation, whose occurrence is low, but not negligible, and consequently start antiviral therapy. References Kim et al. J Rheumatol 2010;2)Vassilopoulos et al. ARD 2010;3)Caporali et al. Arthritis Care Res 2010;4)Giannitti et al. J Rheumatol 2011;5)Lan et al. ARD 2011;6)Lee et al. Clin Exp Rheumatol 2013;7)Cantini et al. Int J Rheumatol 2014;8)Biondo et al. Eur J Intern Med 2014;9)Barone et al. Hepatology 2015 Disclosure of Interest None declared

Background ACTION (NCT02109666) is an ongoing study to provide prospective, real-world data on IV abatacept (ABA) retention in RA. Prognostic factors for IV ABA retention were previously identified in a 12-month interim analysis of patients (pts) enrolled May 2008–Jan 2011 who failed ≥1 prior biologic DMARD.1 Objectives To compare rates and identify predictors of IV ABA retention by treatment line (biologic naive vs biologic failure) in a 12-month interim analysis. Methods ACTION is a 2-year, observational study of pts with moderate-to-severe RA who initiated IV ABA in Europe and Canada. Enrolment periods: May 2008–Dec 2010 (biologic naive/failed prior biologics); Sept 2010–Dec 2013 (biologic naive); Oct 2011–Dec 2013 (failed prior biologics). Data cut-off was May 2015. Crude retention rates were estimated by Kaplan–Meier analysis and compared using a log-rank test. Known risk factors and factors with significance in univariate models (p≤0.20) and no collinearity were entered into a multivariate Cox proportional hazards regression model. Factors with p≤0.10 after backward selection were retained. Efficacy assessments at 12 months included EULAR response and DAS28 (CRP) score. Results 2364 pts were enrolled and 2350 were evaluable: 674 (28.7%) were biologic naive and 1676 (71.3%) had failed ≥1 prior biologic: 728/1676 (43.4%) failed 1 biologic, 948/1676 (56.6%) ≥2 biologics; 1605/1676 (95.8%) had failed anti-TNFs. Biologic-naive pts had similar baseline characteristics vs biologic-failure pts, except for shorter disease duration, fewer erosions in combination with RF or anti-citrullinated protein antibody (ACPA) positivity, prior conventional DMARDs failed and ABA monotherapy, and more co-morbidities (COPD, cardiac disorders and neoplasms). Crude retention rates over 12 months were statistically higher in biologic-naive (78.1%; 95% CI 74.7, 81.2) vs biologic-failure pts (69.9%; 95% CI 67.6, 72.1; p A numerically greater proportion of biologic-naive vs biologic-failure pts had a good/moderate EULAR response (83.8 vs 73.3%) and DAS28 (CRP) Conclusions These data confirm the high levels of IV abatacept retention in the real world, particularly when used in earlier lines of treatment. Poor prognostic factors in RA, including RF/ACPA double positivity combined with erosions at baseline, positively impact retention, independently of treatment line. References Nuslein HG, et al. BMC Musculoskeletal Disorders 2015;16:176. Disclosure of Interest R. Alten Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, H. Nuslein Consultant for: Bristol-Myers Squibb, AbbVie, Celgene, Chugai, UCB, Pfizer, MSD, Novartis, Roche, Speakers bureau: Bristol-Myers Squibb, AbbVie, Celgene, Chugai, UCB, Pfizer, MSD, Novartis, Roche, M. Galeazzi: None declared, H. M. Lorenz Consultant for: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, Sobi, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, Speakers bureau: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, Sobi, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, X. Mariette Grant/research support from: Biogen, GSK, Pfizer, Speakers bureau: Bristol-Myers Squibb, GSK, Pfizer, sanofi, UCB, A. Cantagrel Grant/research support from: UCB, Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Chugai, Lilly, MSD, Novartis, Pfizer, Roche, M. Chartier Consultant for: Bristol-Myers Squibb, Y. Elbez Employee of: Bristol-Myers Squibb, C. Rauch Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

INTRODUCTION: Prolonged glucocorticoid use may increase the risk of adverse safety outcomes, including cardiovascular events. The European League Against Rheumatism and the Canadian Rheumatology Association advise tapering glucocorticoid dose as rapidly as clinically feasible. There is a paucity of published data on RA that adequately describe concomitant treatment patterns.METHODS: ACTION (AbataCepT In rOutiNe clinical practice) is a non-interventional cohort study of patients from Europe and Canada that investigated the long-term retention of intravenous abatacept in clinical practice. We assessed concomitant glucocorticoids in patients with established RA who had participated in ACTION and received ≥1 biological agent prior to abatacept initiation.RESULTS: The analysis included 1009 patients. Glucocorticoids were prescribed at abatacept initiation in 734 (72.7%) patients at a median 7.5 mg/day dose (n=692). Of the patients who remained on abatacept at 24 months, 40.7% were able to decrease their dose of glucocorticoids, including 26.9% who decreased their dose from >5 mg/day to ≤5 mg/day.CONCLUSION: Reduction and/or cessation of glucocorticoid therapy is possible with intravenous abatacept in clinical practice.

Relaxin (RLX) is involved in extracellular matrix and collagen remodelling. The therapeutic role of the circulating isoform RLX-2 as an anti-fibrotic factor in systemic sclerosis (SSc) has been investigated. Several RLX family peptide receptors (RXFPs) are recognized in humans: RLX-2 is a ligand for RXFP1/LGR7 and RXFP2/LGR8. The aim of this study was to define the pattern of expression of LGR7 in different types of human skin cells and to compare normal skin with lesional and unaffected skin from patients with limited SSc (lSSc).We analysed RXFP1 immunolocalization on skin biopsies and cultured fibroblasts from lSSc patients and control subjects. Western blot analysis was carried out on fibroblast lysates.RXFP1 showed cytoplasmic localization on skin cells from control subjects and non-lesional skin from lSSc patients: keratinocytes, gland epithelial cells, endothelium, smooth muscle cells, and fibroblasts. Immunogold electron microscopy confirmed a diffuse epithelial cytoplasmic localization of RXFP1. A substantially lower RXFP1 expression was observed in scleroderma skin, with a lack of staining in most cells. Occasional weak reactivity was observed in cultured scleroderma fibroblasts, while control fibroblasts showed a diffuse cytoplasmic immunoreactivity of RXFP1, confirmed by Western blot analysis.The decreased cellular expression of RLX-2 receptor RXFP1 in scleroderma skin might represent a pro-fibrotic factor and contribute to the substantial inefficacy of RLX treatment in SSc, as reported in the literature. The pathophysiology of the decrease in RXFP1 may be linked to high RLX-2 serum levels previously detected in SSc, but it has yet to be elucidated.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder characterized by periodic fever episodes, arthralgia, myalgia, abdominal pain, serositis, and skin rash. TRAPS is caused by mutations in the gene encoding the TNF Receptor Super Family 1A (TNFRSF1A) on chromosome 12p13. The identification of TNFRSF1A mutations as the genetic cause of TRAPS coincided with the wider use of biological agents in medicine and raised the possibility that blocking TNF could potentially represent the primary therapeutic goal in TRAPS, thus disclosing new treatment choices for this complex disease. Anti-TNF therapy in TRAPS has been based on etanercept, a recombinant human TNFR (p75)-Fc fusion protein comprising two receptors linked by an IgG(1) Fc fragment. However a decrease in responsiveness to etanercept over time has been described, and it may be due to a non-specific action of etanercept in TRAPS; its efficacy may reflect 'generic' anti-inflammatory properties. Long-term adherence to etanercept is poor and a significant number of patients need to switch to anti-interleukin (IL)-1β therapy. In fact, the IL-1 receptor antagonist anakinra has recently been shown to prevent disease relapses both in the short- and in the long-term, and to induce a prompt and stable disease remission.

The aim of this in vitro study was to examine the possible effect of [2-methyl-5-(4-methylsulphonyl)phenyl-1-phenyl-3-(2-n-propyloxyethyl)]-1H-pyrrole (VA441), a new selective cyclooxygenase (COX)-2 inhibitor, on human osteoarthritic (OA) chondrocyte cultivated in the presence or absence of interleukin-1β (IL-1β). In particular, we assessed the effects of 1 and 10 μM of VA441, celecoxib, and indomethacin on cell viability, COX-2 and inducible nitric oxide synthase (iNOS) gene expression, prostaglandin E2 (PGE2) production, and nitric oxide (NO) and metalloproteinase-3 (MMP-3) release. Furthermore, we carried out morphological assessment by transmission electron microscopy (TEM). The presence of IL-1β led to a significant increase in PGE2, MMP-3, and NO production, as well as a significant increase in gene expression of COX-2 and iNOS. All the drugs tested had a statistically significant inhibitory effect on PGE2 production and gene expression of COX-2 stimulated by IL-1β. VA441 and celecoxib significantly suppressed IL-1β-stimulated MMP-3 and NO and iNOS gene expression in a dose-dependent manner, while indomethacin did not show any significant effect on MMP-3 and NO production or on iNOS gene expression. TEM demonstrated that IL-1β severely alters the structure of chondrocytes; after coincubation with VA441 or celecoxib, the cells recovered their ultrastructure. Our data suggest that VA441 and celecoxib may have a beneficial effect on chondrocyte metabolism. Keywords:: VA441, celecoxib, indomethacin, cyclooxygenase-2 inhibitor, chondrocyte

Fibromyalgia syndrome (FS) is a common musculo-skeletal disorder characterized by otherwise unexplained chronic widespread pain, a lowered pain threshold, high tender point counts (tenderness on examination at specific, predictable anatomic sites known as tender points), sleep disturbances, fatigue, headache, irritable bowel syndrome, morning stiffness, paraesthesias in the extremities, often psychological distress and depressed mood (Mease, 2005).

Objective Obesity is a mild, long-lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity represents a risk factor for a poor remission rate in RA patients requiring anti–tumor necrosis factor α (anti-TNFα) therapy for progressive and active disease despite treatment with methotrexate or other disease-modifying antirheumatic drugs. Methods Patients were identified from 15 outpatient clinics of university hospitals and hospitals in Italy taking part in the Gruppo Italiano di Studio sulle Early Arthritis network. Disease Activity Score in 28 joints (DAS28), body mass index (BMI; categorized as 30 kg/m2), acute-phase reactants, IgM rheumatoid factor, and anti–cyclic citrullinated peptide antibody values were collected. DAS28 remission was defined as a score of 30 kg/m2 was recorded in 66 (10.3%) of 641 RA patients. After 12 months of anti-TNFα treatment, a DAS28 of

The aims of this study were to evaluate whether balneotherapy with mineral sulphate-bicarbonate-calcium water could determine substantial symptomatic improvement, and to detect any changes in the quality of life (QoL) of patients with symptomatic knee osteoarthritis (OA). This was a prospective randomized, single blind controlled trial. Sixty outpatients with primary bilateral knee OA, according to ACR criteria, were included in the study and randomized to one of two groups: group I (30 patients) was treated with a daily sulphate-bicarbonate-calcium mineral water bath; group II (30 patients), the control group, continued their regular outpatient care routine. At baseline, after 15 days and after 12 weeks, patients were evaluated by Visual Analogue Scale (VAS) for spontaneous pain, Lequesne and Womac Index for gonarthrosis, SF-36, Arthritis Impact Measurement Scale (AIMS) and symptomatic drugs consumption. We observed a significant improvement of all parameters at the end of the cycle of balneotherapy which persisted throughout the follow-up period, whereas in the control group no significant differences were noted. This symptomatic effect was confirmed by the significant reduction of symptomatic drugs consumption. The differences between the two groups were significant for all considered parameters already from the 15th day and persisted during follow-up. Tolerability of balneotherapy seemed to be good, with light and transitory side effects. Our results confirm that the beneficial effects of balneotherapy in patients with knee OA last over time, with positive effects on the painful symptomatology, a significant improvement on functional capacities and QoL. Balneotherapy can represent a useful backup to pharmacological treatment of knee OA or a valid alternative for patients who do not tolerate pharmacological treatments.

To translate the functional index for hand osteoarthritis (FIHOA) into Italian and to evaluate its reliability and validity in Italian patients with hand osteoarthritis (HOA).The original French FIHOA was translated into Italian according to the guidelines for cross-cultural adaptation and then administered to 72 outpatients with HOA, together with the visual analogue scale of pain (VAS), the Health Assessment Questionnaire (HAQ) and the Short Form Health Survey (SF-36). Test-retest reliability was verified by having all patients fill out the Italian version of FIHOA again 1 week later. Item-item analysis was performed. The Wilcoxon signed-rank test and Spearman's rank correlation coefficient were calculated to compare test and retest responses and to evaluate the degree of correlation. Internal consistency reliability was evaluated by Cronbach's alpha coefficient, and internal structure validity was appraised through factor analysis, also taking a varimax rotation into consideration. Construct validity was assessed by correlating FIHOA with other measures of functional impairment and pain using Spearman's rank correlation coefficient.Internal consistency was high (Cronbach's α = 0.87). Test-retest reliability showed a Spearman's rho of 0.942 (p0.001). A significant correlation (p0.001) between FIHOA, VAS and HAQ and a significant negative correlation between FIHOA and SF-36 subscales were observed. FIHOA was confirmed to be a non-unidimensional scale, but in addition to the total score of the index, three subtotals of item scores were considered to provide better evaluations of finger functionality (items 3, 6, 8 and 10), wrist functionality (items 2 and 7) and hand strength (items 4 and 5) in single individuals.The Italian version of FIHOA is a reliable and valid instrument for evaluating functional disability in Italian-speaking HOA patients.

Systemic juvenile idiopathic arthritis (SJIA) is a disorder characterized by arthritis in children starting before 16 years of age associated with daily high fever, persisting for more than 2 weeks, and at least one of the following clinical features: evanescent cutaneous rash, lymphadenopathy, serositis or hepatosplenomegaly. SJIA patients carry a significantly higher frequency of MEFV mutations, the gene responsible for familial Mediterranean fever, and may be characterized by a more aggressive disease. In this line, we describe a 9-year-old girl affected with SJIA who carried a heterozygous G196W mutation in MEFV. Our patient was characterized by an aggressive disease course, resistance to conventional immunosuppressive agents and developed renal amyloidosis just 2 years after the disease onset.

The potential clinical expression of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), in the form of idiopathic recurrent acute pericarditis (IRAP) has not been explored in the medical literature. The aim of this study was to evaluate the incidence of TRAPS mutations in patients with recurrent pericarditis and identify possible clues to TRAPS diagnosis. Therefore, 131 consecutive Caucasian IRAP patients were investigated for mutations of the TRAPS gene and prospectively evaluated. Out of 131 patients, 8 (6.1%) carried a mutation in the TNFRSF1A gene. Compared with those without genetic mutations, patients with TRAPS mutations had more frequently a positive family history for pericarditis and periodic fever syndromes (p