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The human meniscus plays a crucial role for transmission and distribution of load across the knee, as well as shock absorption, joint stability, lubrication, and congruity. The aim of this study was to compare the complex geometry, and unique ultrastructure and tissue composition of the meniscus in healthy (control) and pathological conditions to provide understanding of structural changes that could be helpful in the future design of targetted therapies and improvement of treatment indications. We analyzed meniscus samples collected from 3 healthy multi-organ donors (median age, 66 years), 5 patients with traumatic meniscal tear (median age, 41 years) and 3 patients undergoing total knee replacement (TKR) for end-stage osteoarthritis (OA) (median age, 72 years). We evaluated the extracellular matrix (ECM) organization, the appearance and distribution of areas of calcification, and modifications of cellular organization and structure by electron microscopy and histology. The ECM structure was similar in specimens from traumatic meniscus tears compared to those from patients with late-stage OA, showing disorganization of collagen fibers and increased proteoglycan content. Cells of healthy menisci showed mainly diffuse chromatin and well preserved organelles. Both in traumatic and in OA menisci, we observed increased chromatin condensation, organelle degeneration, and cytoplasmic vacuolization, a portion of which contained markers of autophagic vacuoles. Areas of calcification were also observed in both traumatic and OA menisci, as well as apoptotic-like features that were particularly prominent in traumatic meniscal tear samples. We conclude that meniscal tissue from patients with traumatic meniscal injury demonstrate pathological alterations characteristic of tissue from older patients undergoing TKR, suggesting that they have high susceptibility to develop OA.

Resveratol (RES) and its natural precursor polydatin (PD) are polyphenols that may display a broad variety of beneficial effects including anti-inflammatory properties. This study aimed to investigate the role of RES and PD in the inflammatory process induced by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in vitro. A monocytic cell line (THP-1) was primed for 3 hours with phorbol myristate acetate (100 ng/mL) and stimulated with synthetic MSU (0.05 mg/mL) and CPP (0.025 mg/mL) crystals. RES and PD were added to cultures concurrently with the crystals, or as 2-hour pretreatment. The effect of the two polyphenols was evaluated on intracellular and extracellular IL-1&beta, levels, NACHT-LRRPYD-containing protein-3 (NLRP3) inflammasome expression, reactive oxygen species (ROS) and nitric oxide (NO) production, and the assessment of crystal phagocytosis. RES and PD strongly inhibited IL-1&beta, induced by crystals after cell pretreatment. Cell pretreatment was effective also in reducing IL-1 mRNA expression while no effect was observed on NLRP3 gene expression. RES and PD had no effect on crystal phagocytosis when used as pretreatment. Both polyphenols were significantly effective in inhibiting ROS and NO production. Our results demonstrated that RES and PD are effective in inhibiting crystal-induced inflammation. Data obtained after cell pretreatment allow us to hypothesize that these polyphenols act on specific signaling pathways, preventing inflammation.

Aim: Osteoarthritis (OA) is a whole joint pathology involving cartilage, synovial membrane, meniscus, subchondral bone, and infrapatellar fat pad (IFP). Synovitis has been widely documented in OA suggesting its important role in pathogenesis. The aim of this study was to investigate the role of different joint tissues in promoting synovitis. Materials and methods: Conditioned media (CM) from cartilage, synovial membrane, meniscus, and IFP were generated from tissues of five patients undergoing total knee replacement and used to stimulate a human fibroblast-like synoviocytes cell line (K4IM). Cytokines, chemokines, and metalloproteases release was analyzed in all CM by Bio-Plex Assay and sulfated glycosaminoglycan (GAG) content by dimethylmethylene blue assay. Gene expression of several markers was evaluated by real-time PCR in K4IM cells stimulated with the CM obtained from joint tissues. Results: CM from all tissues produced high levels of IL-6, IL-8, and CCL2. CCL21, MMP-3, and −13 levels were detected in all CM except IFP. MMP-10 was present only in CM of cartilage and synovial tissues. IL-1β, IL-15, TNF-α, CCL5, and CCL19 were undetectable. However, only K4IM cells stimulated by the CM from OA synovium showed an increase of IL-6, CXCL-8, CCL21, MMP10, and IL-1β expression. Conclusion: Our study showed that K4IM might be a suitable in vitro model for evaluating different cellular pathways in OA studies. Importantly, we demonstrated that in OA, all joint tissues might be involved in the progression of synovitis with a predominant role of synovial membrane itself compared to the other joint tissues.

Non-alcoholic fatty liver disease (NAFLD), potentially evolving into liver fibrosis (LF), is frequent in psoriasis (PsO), but data in psoriatic arthritis (PsA) are lacking. Our study aimed to investigate the prevalence of NALFD and LF in PsA/PsO and the contribution of arthritis in their onset.PsA and PsO patients were consecutively enrolled. Exclusion criteria were liver diseases causing fibrosis (except NAFLD), alcohol ≥ 20 g/day, daily use of non-steroidal anti-inflammatory drugs and current/previous methotrexate use. Clinical history, biochemical and clinimetrical data and insulin-resistance index HOMA (homeostatic model assessment) were assessed. Patients underwent a liver ultrasound to identify steatosis (therefore NAFLD) and transient elastography, to evaluate LF (stiffness≥ 7 kPa = fibrosis). Statistical analysis included basic statistics, logistic and linear regression analyses (to assess the contribution of arthritis to NAFLD and LF grading, respectively) and Spearman's correlations; p ≤ 0.05 was considered significant.Seventy-six patients were enrolled (PsA/PsO 43/33). MetS and LF prevalence were similar between PsA and PsO (35% vs 33%, p = 0.88; 31% vs 28%, p = 0.77, respectively). NAFLD was more frequent in PsO (65% vs 35%, p = 0.044). In multivariable models with NAFLD and LF grading as outcomes, arthritis was not a significant predictor, while HOMA was independently associated with both (OR 1.34; 95%CI 1.06, 1.69; beta 0.88; 95%CI 0.54, 1.21, respectively). Female sex was independently associated with LF grading (beta 1.81; 95%CI 0.05, 3.57).NAFLD was more frequent in PsO, but MetS and LF prevalence were similar in PsA and PsO. Insulin resistance is the main determinant of NAFLD and LF, while additional contribution of arthritis seems small. Key Points • The prevalence of metabolic comorbidities, including liver fibrosis, is overall quite similar between psoriatic arthritis and psoriasis. • NAFLD is more frequently found in psoriasis than psoriatic arthritis. • The contribution of arthritis in the onset of metabolic comorbidities seems small.

Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA.

The aim of this study was to identify the molecules and pathways involved in the cross-talk between meniscus and synovium that may play a critical role in osteoarthritis (OA) pathophysiology. Samples of synovium and meniscus were collected from patients with early and end-stage OA and cultured alone or cocultured. Cytokines, chemokines, metalloproteases, and their inhibitors were evaluated at the gene and protein levels. The extracellular matrix (ECM) changes were also investigated. In early OA cultures, higher levels of interleukin-6 (IL-6) and IL-8 messenger RNA were expressed by synovium and meniscus in coculture compared with meniscus cultured alone. RANTES release was significantly increased when the two tissues were cocultured compared with meniscus cultured alone. Increased levels of matrix metalloproteinase-3 (MMP-3) and MMP-10 proteins, as well as increased release of glycosaminoglycans and aggrecan CS846 epitope, were observed when synovium was cocultured with meniscus. In end-stage OA cultures, increased levels of IL-8 and monocyte chemoattractant protein-1 (MCP-1) proteins were released in cocultures compared with cultures of meniscus alone. Chemokine (C-C motif) ligand 21 (CCL21) protein release was higher in meniscus cultured alone and in coculture compared with synovium cultured alone. Increased levels of MMP-3 and 10 proteins were observed when tissues were cocultured compared with meniscus cultured alone. Aggrecan CS846 epitope release was increased in cocultures compared with cultures of either tissue cultured alone. Our study showed the production of inflammatory molecules by synovium and meniscus which could trigger inflammatory signals in early OA patients, and induce ECM loss in the progressive and final stages of OA pathology.

The infrapatellar fat pad (IFP) is an intracapsular but extrasynovial structure, located between the patellar tendon, the femoral condyles and the tibial plateau. It consists of white adipose tissue, organised in lobules defined by thin connective septa. The aim of this study is the morphometric and ultrasonographic analysis of IFP in subjects without knee pathology during flexion‐extension movements. The morphometric study was conducted on 20 cadavers (15M, 5F, mean age 80.2 years). Ultrasound was performed on 24 volunteers with no history of knee diseases (5M, 19F, mean age: 45 years). The characteristics of the adipose lobules near the patellar tendon and in the deep portion of the IFP were evaluated. Numerical models were provided, according to the size of the lobules. At histological examination, the adipose lobules located near the patellar tendon were larger (mean area 12.2 mm(2) ± 5.3) than those at a deeper level (mean area 1.34 mm(2) ± 0.7, P 0.05). In the sagittal plane, the reduction of thickness of the superficial layer (with large adipose lobules) during flexion was 20.6%, whereas that of the deep layer (with small adipose lobules) was 1.3%. Numerical simulation of vertical loads, corresponding to flexion of the knee, showed that stress mainly developed within the interlobular septa and opposed bulging of the lobules. The characteristics of the lobular arrangement of the IFP (large lobules with superficial septa in the superficial part and small lobules with thick septa in the deep one), significant changes in the areas and perimeters of the superficial lobules, and the reduced thickness of the superficial layer during flexion all indicate the dynamic role played by the IFP in knee kinematics.

The aim of this study was to analyze the magnetic resonance imaging (MRI) volumetric and morphometric characteristics of the infrapatellar fat pad (IFP) and the suprapatellar fat pad (SFP) in normal controls, moderate and end-stage osteoarthritis (OA) patients. Forty-four MRI images of the three groups were collected: a) 17 patients undergoing meniscectomy with Outerbridge score 0 (control group); b) 15 patients undergoing meniscectomy with Outerbridge score 3/4 (moderate OA group); and c) 12 patients undergoing total knee replacement (end-stage OA group). Volume, depth, femoral and tibial arch lengths of IFP were quantified. The hypointense IFP signals were also scored. The SFP volume, oblique, antero-posterior and cranio-caudal lengths were determined. IFP and SFP characteristics were compared between groups. A decrease of IFP volume, depth, femoral, and tibial arch lengths in moderate and end-stage OA compared to controls were observed. A difference in IFP hypointense signal was found between groups. No differences were found in SFP characteristics between the groups. In controls and moderate OA patients, correlations were found among the different MRI characteristics of both IFP and SFP, while in the end-stage OA group correlations were found only in SFP. We evidenced differences of the IFP MRI morphometric characteristics between the groups analyzed, supporting an important role of IFP in OA pathology and progression. On the contrary, no differences were highlighted in SFP analysis suggesting that this fat pad is not clearly involved in OA, probably due to its peculiar localization and different function.

Background The 5-item Compliance Questionnaire for Rheumatology (CQR5) allows the identification of patients likely to be high adherers (HA) to anti-rheumatic treatment (i.e. taking ≥80% of their medications correctly), or “low” adherers (LA).1 We have previously validated an Italian version of the questionnaire (I-CQR5) following standardised guidelines. Objectives The objective was to investigate what factors are associated with high treatment adherence according to I-CQR5 in RA. Methods RA patients (disease duration >1 year, undergoing treatment with ≥1 self-administered biological or conventional synthetic disease-modifying anti-rheumatic drugs (bDMARDs, csDMARDs), capable of completing the questionnaire unaided) completed I-CQR5 on one occasion. I-CQR5 were anonymous and clinical data were retrieved anonymously from the local database. To investigate what factors were associated with high adherence, we included demographic and social characteristics, clinical and treatment information. Factors achieving a p Results Among 604 RA patients, 328 patients were enrolled, 18 questionnaires were incomplete. Median age of the patients was 57 years,48–67 females were 232 (82%), disease duration was 12 years;7–19 193 (64.3%) patients were treated with bDMARDs and 107 (54.6%) with csDMARD only; 270 (90.3%) were in low disease activity or remission (figure 1). HA were found to be 35.2% (109/310) of the patients.40.2% (79/193) were on bDMARDs and 22.4% (24/107) on csDMARDs. Older age, lower education level, higher prednisone daily dose, use of a csDMARD (particulary hydroxychloroquine and sulfasalazine) and higher patient-VAS were significantly more frequent in LA compared with HA (figure 1). In the multivariate analysis, bDMARD treatment and employment resulted independently associated with high adherence: OR 2.88 (1.36–6.1), p=0.006 and OR 2.36 (1.21–4.62), p=0.012 respectively (table 1). Conclusions Only one third of Italian RA patients were highly adherent to treatment according to I-CQR5. Treatment with bDMARDs and employment status were the major determinants of treatment adherence, increasing by almost 3-fold the likelihood of being highly adherent. Reference [1] Hughes L, et al. A 5 item version of the Compliance Questionnaire for Rheumatology (CQR5) successfully identifies low adherence to DMARDs. BMC Musculoskelet Disord2013;14:286. Disclosure of Interest None declared

Background The 5-item Compliance Questionnaire for Rheumatology (CQR5) allows the identification of patients likely to be high adherers (HA) to anti-rheumatic treatment (i.e. taking ≥80% of their medications correctly), or “low” adherers (LA). 1 Objectives The objective was to validate the construct of an Italian version of CQR5 in rheumatoid arthritis (RA). Methods Cross-cultural adaptation comprised: forward translation, synthesis of the translations, back-translation, expert committee assessment and field-testing. Validation was conducted administering the adapted version (I-CQR5) to RA patients (disease duration >1 year, treated with ≥1 self-administered disease-modifying anti-rheumatic drug, capable of completing the questionnaire unaided) on one occasion. Questionnaires were anonymous but contained self-reported data. Construct validity and reliability were assessed with Rasch analysis (Partial Credit model Parametrisation, PCM). Martin-Loef Likelihood ratio test assessed invariance for gender, age, education, social status and disease duration. Results The adaptation process was closed by the expert committee assessment. I-CQR5 is reported in Figure 1. Among 604 patients, 274 were included in the validation process, 6 questionnaires were incomplete. Median age was 57 years (48–67), females were 201 (77%), disease duration was 13.5 years (8.8–19.3), most patients lived with partner/family (159,75%) and had a middle/secondary school education (184,69%). HA were 93 (67%) and LA 179 (35%). Factor analysis revealed ordered thresholds in most items, 2 factors were sufficient to explain variability (Chi-square=0.46,p=0.5) (Tab.1). Item-fit statistics showed overall agreement of items with parametrisation (Infit statistics=0.6–1.4; excluding item no.5). Chi-square showed agreement with PCM parametrisation by item (excluding the item no.1). Martin-Loef likelihood ratio test confirmed unidimensionality (Chi-square 65.8, df=53,p=0.11) and Separation Reliability Index confirmed internal consistency (Patient Separation Index 0.91) (Tab.1). I-CQR5 was invariant to age (Chi-square=40.6, df=28,p=0.059), education level (Chi-square=49.9, df=42,p=0.187), social status (Chi-square=10.5, df=15,p=0.79), disease duration (Chi-square=13.6, df=36,p=0.220); Martin-Loef test was significant for gender (Chi-square=25.4, df=14,p=0.031). Conclusions I-CQR5 was well understood by patients and construct validity, unidimensionality and internal consistency were confirmed by factor analysis and PCM. Reference [1] Hughes L, et al. A 5 item version of the Compliance Questionnaire for Rheumatology (CQR5) successfully identifies low adherence to DMARDs. BMC Musculoskelet Disord2013;14:286. Disclosure of Interest None declared

The Infrapatellar Fat Pad (IFP) lies between patella, femur, meniscus and tibia and properly fills the space between these structures. This fatty structure facilitates distribution of synovial fluid and may act to absorb impulsive actions generated through the joint. In case of Osteoarthritis (OA), IFP is found to be affected by inflammation, hypertrophy and fibrosis. The aim of the present study is to analyze the correlation between microscopic characteristics and mechanical properties of the IFP in healthy and OA conditions. The microscopic anatomy of the IFP was analyzed through histological methods, whose results showed that the IFP affected by OA maintains similar lobules configuration but thicker interlobular septa. Geometrical data together with the morphological analysis of lobules and septa represented the basic data to provide numerical micro-models of the IFP. Numerical analyses were developed to evaluate the mechanical behavior considering the characteristic loading conditions as compressive, torsion and shear actions. The results were applied to identify the parameters of a homogenized hyperelastic constitutive formulation that interprets the IFP mechanics. The constitutive formulation was implemented within a finite element model of the knee, which was applied to evaluate the overall mechanical functionality of the knee structures. The results pointed out the actual mechanical relevance of IFP and the loss of proper stress-strain behavior of the OA IFP under mechanical loads.

The current prospective observational study aimed to evaluate the long-term (24 months), real-life effectiveness of ustekinumab in psoriatic arthritis (PsA). Consecutive patients with moderate-severe PsA and active psoriasis who begun ustekinumab treatment were evaluated prospectively (January 2015–March 2017). Clinimetric scores and biochemical values were assessed at baseline (T0), at 6 (T6), 12 (T12), and 24 (T24) months. Friedman test and generalized linear models were used to compare variables over time. Regression analysis to identify determinants of minimal disease activity (MDA) at T6 and of treatment discontinuation was conducted. Sixty-five patients (43.1% men; age 49.4 ± 11.6 years) were enrolled; ustekinumab was prescribed as a first (20%), second (33.8%), third (26.5%), fourth (15.4%), or fifth (4.6%) line biological therapy. Significant decrease in tender/swollen joints, Visual Analogue Scale of pain (VASp) and general health (VASgh), Disease Activity in PsA (DAPSA), Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), Health Assessment Questionnaire modified for spondyloarthritis (HAQ-S), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was achieved. MDA was reached by 30.7, 47.0, and 34.0% of patients respectively at T6, T12, and T24. In multivariable models, mono-oligoarthritis was independently associated to MDA at T6 (OR 9.02; 95% CI 1.41, 57.71), while baseline CRP (OR 1.12; 95% CI 1.00, 1.26) and LEI (OR 0.50; 95% CI 0.25, 0.97) to ustekinumab discontinuation. More patients used disease-modifying antirheumatic drugs at T0 (35.3%) than at T24 (8.5%). Only nine episodes of infection and no serious adverse events were registered. In a real-life clinical setting, ustekinumab was safe and effective in PsA. Comedication tapering was often possible.

The infrapatellar pad, a fibro-adipose tissue with peculiar microscopic and mechanical features, is gaining wide attention in the field of rheumatological research. The purpose of this descriptive review is to summarize the most recent published evidence on the anatomic, physiologic and biomechanical inter-relationship between the infrapatellar fat pad and the knee synovial membrane. As an extrasynovial tissue, the infrapatellar fat pad does not directly interact with the articular cartilage; based on its location in close contact with the synovial membrane, and due to the metabolic properties of adipose tissue, it may influence the behavior of the synovial membrane. In fact, considering evidence of macroscopic and microscopic anatomy, the infrapatellar fat pad is the site of insertion of the infrapatellar and medial synovial plicae. Also biochemically, there is much evidence highlighting the interaction among these two structures; in the case of inflammation, the mutual interplay is ascribable to the release of pro-inflammatory mediators stimulating the proliferation of inflammatory cells and promoting tissue modifications in both. All these assumptions could support the emerging idea that the infrapatellar fat pad and the synovial membrane may be considered a morpho-functional unit.

The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients' medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP-crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10% in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.

Synovial inflammation plays an important role in osteoarthritis (OA) pathogenesis. Different biological compounds have been tested mainly on chondrocytes, to treat early stages of OA. However, because OA has been recently defined as "an organ" pathology, investigation on synoviocytes is also needed. Therefore, the aim of the present study was to validate a human fibroblast-like synoviocytes cell line (K4IM) to test the effects of platelet-rich plasma (PRP) and hyaluronan (HA) on anabolic and catabolic gene expression and on HA secretion from cell cultures. In order to determine the effect of PRP and HA, K4IM cells were maintained in culture with or without TNF-α stimulation. In the presence of PRP, unstimulated K4IM cells presented the same expression of IL1B, IL6, CXCL8, VEGF, TIMP1, and hyaluronic synthase isoform HAS3 as primary human synoviocytes, while HA addition did not change their expression pattern, which was similar to control cells. Stimulated cells expressed significantly higher values of IL1B, CXCL8, and VEGF compared with unstimulated ones. PRP did not show any modification, except for VEGF, while HA addition modulated IL1B expression. PRP did not modulate HA release of both stimulated and unstimulated cells. Our study showed the possibility to use K4IM synoviocytes as an in vitro model to test biological compounds useful for the treatment of early OA. Primary cells reflect the phenotype of cells in vivo, but limited recovery from biopsies and restricted lifespan makes experimental manipulation challenging. Therefore, despite cell lines present some limitations, they could be used as an alternative for preliminary experiments.

Background Resveratol (RES) and its natural precursor polydatin (PD) are polyphenol compounds that display a broad variety of beneficial effects including anti-apoptotic and anti-inflammatory properties. Objectives This study aimed to investigate the role of RES and PD in the inflammatory process induced by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in vitro. Their effect was evaluated though IL-1β, NLRP3 inflammasome, reactive oxygen species (ROS), nitric oxide (NO) and the phagocytosis index assessment. Methods A monocytic cell line (THP-1) was primed for 3 hours with phorbol myristate acetate (PMA) (100ng/ml) and stimulated with synthetic MSU (0.05mg/ml) and CPP (0.025mg/ml) crystals. RES and PD were added to cultures at, respectively, 100μM and 200μM. Experiments were carried out either adding RES and PD along with crystals, or pretreating cells (2 hs) with polyphenols and removing them before crystal stimulation. IL-1β were evaluated in cell supernatants and at intracellular level by ELISA assay. IL-1β and NLRP3 expression was assessed by RT-PCR. Reactive oxygen species (ROS) and NO were measured by cytometric analysis using fluorogenic probes (CellROX Deep Red Reagent and DAF-FM, respectively). Crystal phagocytosis index was calculated at different time points using polarized light microscopy. Results RES and PD inhibited IL-1b induced by crystals both at extracellular and intracellular level. This inhibition was more pronounced after polyphenol cell pretreatment. In this case cytokine production was completely suppressed both in control and in stimulated cells. Cell pretreatment was extremely effective also in reducing mRNA expression of IL-1 after crystal stimulation while NLRP3 expression was to some extent affected by RES. RES and PD had a slight inhibitory effect on crystal phagocytosis when added along with the stimulus, while pretreated cells did not show any difference in the phagocytosis index. ROS production induced by MSU crystals was more pronounced (4 fold increase) with respect to CPP crystals (2 fold increase). RES was more effective than PD in inhibiting ROS production (p Conclusions Our results demonstrated that RES and PD are effective in inhibiting crystal-induced inflammation affecting IL-1 production and NLRP3 expression and activation. Data obtained after cell pretreatment allow us to hypothesize that these polyphenols act on specific signaling pathway preventing inflammation, and that this action is independent from crystal phagocytosis. Disclosure of Interest None declared

Osteoarthritis (OA) is characterized by chronic degeneration of joints, involving mainly the articular cartilage and the underlying bone, and severely impairing the quality of life of the patient. Although with limited efficacy, currently available pharmacological treatments for OA aim to control pain and to retard disease progression. Salmon calcitonin (sCT) is a drug which has been shown to have therapeutic effects in experimental arthritis by inhibiting both bone turnover and cartilage degradation and reducing the activities of matrix metalloproteinases (MMP). High molecular weight hyaluronic acid (HA) is used as a lubricant in OA therapy, and, interestingly, HA polymers may normalize the levels of MMP-1, -3 and -13. We demonstrated that sCT rapidly clears from the knee joint of rat animal model, after intra-articular (i.a.) administration, and it induces systemic effects. Here, sCT was conjugated to HA (200kDa) with the aim of prolonging the residence time of the polypeptide in the joint space by reducing its clearance. An aldehyde derivative of HA was used for N-terminal site-selective coupling of sCT. The activity of sCT was preserved, both in vitro and in vivo, after its conjugation and the i.a. injection of HA-sCT did not trigger any systemic effects in rats. The efficacy of HA-sCT treatment was tested in a rabbit OA model and clear chondro-protective effect was proven by macro- and microscopic assessments and histological findings. Our results indicate that HAylation of sCT increases the size of the polypeptide in a stable covalent manner and delays its passage into the blood stream. We conclude that HA conjugation prolongs the anti-catabolic effects of sCT in joint tissues, including the synovial membrane and cartilage.

Background and aims: Knee osteoarthritis (KOA) is a common cause of disability and pain in adults. Obesity is increasingly recognized as the primary modifiable risk factor for the onset and progression of KOA. The mechanisms that link the two conditions are still not fully clarified but recent data suggest an important role mediated by the infrapatellar fat pad (IFP). Accordingly, we aimed to determine the histomorphological characteristics of IFP in individuals affected by KOA and compare them to those obtained from lean healthy individuals using a histological scoring system. Moreover, we determined the expression of certain adipocytokines in IFP of KOA subjects. Materials and Methods: We enrolled 28 subjects (BMI 35.5±5 kg/m2) undergoing total knee replacement for OA. The controls were represented by IFP and adjacent synovial membrane specimens sampled from bodies or bodies part of 8 healthy subjects without history of osteoarthritis involved in the Body Donation Program ‘Donation to Science’ held by the University of Padova. The microscopic anatomy of IFP was analyzed through histological and morphometrical methods. The histology of the synovial membrane adjacent to the IFP was also analyzed. We determined mRNA expression using Quantitative real time PCR for adipokines (leptin, adiponectin, Peroxisome proliferator-activated receptor gamm, fatty acid binding protein4) and cytokines (Interleukin 6 [IL-6], Tumor necrosis factor alfa[TNF-α], Monocyte chemoattractant protein-1[MCP-1], Vascular endothelial growth factor [VEGF]) in the IFP specimens of KOA subjects. Results: All the evaluated IFPs showed microscopical characteristics similar to white adipose tissue. IFPs were organized in adipose lobuli separated by fibrous septa. No differences were detected in the mean diameter of the adipose lobuli of the IFP in KOA patients and controls. Mononuclear infiltration was present in 22 KOA patients while it was not observed in any of the IFP used as control (p = 0.001). The average number of vessels and the thickness of interlobular septa were significantly higher in KOA patients compared to controls (p < 0.0001 and p = 0.004 respectively). BMI correlated positively with the thickness of the interlobular septa in IFP (p= 0.02, r= 0.42). Concerning synovial membrane, the presence of lymphocytic infiltration and hyperplasia was statistically higher in KOA compared to controls (p

Bartter's and Gitelman's syndromes are two different genetic renal diseases, but are both characterised by hypokalaemia and metabolic alkalosis. Bartter's syndrome is characterised by multiple gene mutations (Na-K-2Cl cotransporter; K(+) channels renal outer medullary potassium channel (ROMK); Cl channels, chloride channel Kb (ClCNKb); regulatory protein Barttin; and Ca(2+) -sensing receptor, CaSR) at the thick ascending limb of Henle's loop, while Gitelman's syndrome is caused by a mutation in the gene encoding the renal thiazide sensitive Na(+)-Cl(-) cotransporter, located in the apical membrane of the distal convoluted tubule. The co-existence of hypokalaemia with hypomagnesaemia and hypocalciuria represents the biochemical hallmark of Gitelman's syndrome that distinguishes it from Bartter's syndrome. Calcium pyrophosphate deposition (CPPD) including chondrocalcinosis has been frequently reported in association with Bartter's syndrome. Some authors postulate that these cases were probably due to Gitelman's syndrome and not due to Bartter's syndrome as all patients had hypomagnesaemia. This electrolyte disorder seems to induce CCP crystal deposition. To date, no cases of CPPD have been reported in patients who had Bartter's syndrome without hypomagnesaemia. CPPD may be found in other conditions associated with hypomagnesaemia, such as short bowel syndrome or tacrolimus therapy in liver transplantation patients. As acute CPP crystal arthropathy or pseudogout can be the onset presentation of Gitelman's syndrome, CPPD should be considered a major feature of this disease. Rheumatologists should be aware of the association between Gitelman's syndrome and CPPD, and should consider this metabolic disorder when CPPD occurs in younger patients.

This study aimed to apply the recently proposed Oslo hand osteoarthritis magnetic resonance imaging (MRI) scoring system to evaluate MRI findings in a cohort of patients affected by long-standing erosive hand osteoarthritis (EHOA). Eleven female EHOA patients (median 59 [interquartile range 62-52] years, disease duration 9.5 [interquartile range 13-3.75] years) underwent MRI (1.5 T) of the dominant hand, and synovitis, bone marrow lesions (BMLs), joint space narrowing, osteophytes, cysts, malalignment, and erosions were scored using the Oslo scoring system. Intra- and inter-reader reliability were assessed. The patients also underwent X-ray examination, and bone features were evaluated using the same scoring system. Pain and tenderness were assessed during a physical examination. Spearman's non-parametric test was used to analyze the correlations between variables. MRI intra- and inter-reader reliability were found between good and moderate for many features. No statistical differences were found between the radiographs and MRI with regard to detection of JSN, malalignment, and bone erosions. Synovitis was detected in 39.8 % of the 80 joints examined (in a mild form in 80 %), erosions were found in 51.1 %, and BMLs were identified in 20.5 and 23.9 % at the distal and the proximal side, respectively. BMLs at both the proximal and distal ends were correlated with tender joints (BML distal p = 0.0013, BML proximal p = 0.012). The presence of synovitis was correlated with tenderness (p = 0.004) and erosions at both the distal and proximal joints (p = 0.004). The presence of erosions correlated with tender joints (p

Osteoarthritis (OA), a disease that mainly targets cartilage, also affects ligaments, the subchondral bone and synovium, and, according to recent definitions, it is a disease of the joint as an organ.1 Its most characteristic radiographic features are joint space narrowing, bone sclerosis and osteophytes;2 bone erosions, and in particular subchondral bone erosions, have also been found in some patients.3 Bone erosions that classically affect the interphalangeal (IP) joints identify a disease subset called erosive osteoarthritis (OA).4 The particular localisation of erosive OA is considered so characteristic of the disease that the term has been used, since it was first described by Peter et al ,5 almost interchangeably with erosive hand OA. A growing body of evidence, however, suggests that it is time to re-evaluate the definition, since the term erosive OA can be appropriately applied to other OA localisations including at the thumb base (TB)6 and facet joints.7 These different disease subsets share not only the same classic radiographic features, such as subchondral bone erosions, but also the severity …

This review summarises recent evidence about the interaction between bone, the immune system and cartilage in disabling conditions such as osteoarthritis, rheumatoid arthritis and spondyloarthritis. These topics have been recently discussed at the 'OsteoRheumatology' conference held in Genoa in October 2014. The meeting, at its 10th edition, has been conceived to bring together distinguished international experts in the fields of rheumatic and metabolic bone diseases with the aim of discussing emerging knowledge regarding the role of the bone tissue in rheumatic diseases. Moreover, this review focuses on new treatments based on underlying the pathophysiological processes in rheumatic diseases. Although, a number of issues still remain to be clarified, it seems quite clear that in clinical practice, as well as in basic and translational research, there is a need for more knowledge of the interactions between the cartilage, the immune system and the bone. In this context, 'OsteoRheumatology' represents a potential new discipline providing a greater insight into this interplay, in order to face the multifactorial and complex issues underlying common and disabling rheumatic diseases.

Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible functional loss. The reported incidence varies from 2–5 cases/100,000 person-years in the general population to 70 cases/100,000 person-years among patients with rheumatoid arthritis. In fact, individuals with rheumatoid arthritis are at particular risk for developing SA. This may be due to several reasons: joint disease predisposes to bacterial joint colonization and RA itself and its treatment with corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and biological therapies may decrease the immune function required for protection from pathogens. Steroids and DMARDs seem to affect the leukocyte synovial count; indeed, RA patients with SA have a leukocyte count in synovial fluid (SF) lower than patients with SA without underlying rheumatic diseases. The diagnosis of SA in RA patients can be difficult because the development of a hot painful joint is often confused with a relapse of the underlying joint disease leading to delay in diagnosis. For this reason the microscopic analysis and culture of synovial fluid are crucial to exclude septic arthritis.

Hand osteoarthritis (OA) is a common and potentially disabling disease, with different features from hip and knee OA so that a specific therapeutic approach is required. Evidence based recommendations for the management of hand OA were developed by the European League Against Rheumatism (EULAR) in 2006. The Italian Society for Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the EULAR recommendations for the management of hand OA. The multidisciplinary group of experts included specialists involved in the management of patients with hand OA. In order to maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were reformulated in terms of a search query and for every recommendation a systematic search was conducted updating EULAR recommendations’ review. The propositions were translated in Italian and reformulated basing on collected evidences and expert opinion. The strength of recommendation was measured for each proposition with the EULAR ordinal and visual analogue scales. The original 11 propositions of EULAR recommendations were translated and adapted to Italian context. Further evidences were collected about non-pharmacological therapies, local treatments, intra-articular injection with SYSADOA and corticosteroids, and surgery. The SIR has developed updated recommendations for the management of hand OA adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with hand OA.

Sjogren’s syndrome (SS) is a systemic progressive autoimmune disease characterized by a complex pathogenesis requiring a predisposing genetic background and involving immune cell activation and autoantibody production. The immune response is directed to the exocrine glands, causing the typical ‘sicca syndrome’, but major organ involvement is also often seen. The etiology of the disease is unknown. Infections could play a pivotal role: compared to normal subjects, patients with SS displayed higher titers of anti-Epstein-Barr virus (EBV) early antigens, but lower titers of other infectious agent antibodies such as rubella and cytomegalovirus (CMV) suggest that some infections may have a protective role against the development of autoimmune disease. Recent findings seem to show that low vitamin D levels in patients with SS could be associated with severe complications such as lymphoma and peripheral neuropathy. This could open new insights into the disease etiology. The current treatments for SS range from symptomatic therapies to systemic immunosuppressive drugs, especially B cell-targeted drugs in cases of organ involvement. Vitamin D supplementation may be an additional tool for optimization of SS treatment.

Post-traumatic arthritis (PTA) develops after an acute direct trauma to the joints. PTA causes about 12% of all osteoarthritis cases, and a history of physical trauma may also be found in patients with chronic inflammatory arthritis. Symptoms include swelling, synovial effusion, pain and sometimes intra-articular bleeding. Usually, PTA recoveries spontaneously, but the persistence of symptoms after 6 months may be considered pathological and so-called chronic PTA. A variety of molecular, mechanobiological and cellular events involved in the pathogenesis and the progression of PTA have been identified. The activation of inflammatory mechanisms during the PTA acute phase appears to play a critical role in the chronic disease onset. Human studies and experimental models have revealed that a series of inflammatory mediators are released in synovial fluid immediately after the joint trauma. These molecules have been proposed as markers of disease and as a potential target for the development of specific and preventative interventions. Currently, chronic PTA cannot be prevented, although a large number of agents have been tested in preclinical studies. Given the relevance of inflammatory reaction, anticytokines therapy, in particular the inhibition of interleukin 1 (IL-1), seems to be the most promising strategy. At the present time, intra-articular injection of IL-1 receptor antagonist is the only anticytokine approach that has been used in a human study of PTA. Despite the fact that knowledge in this area has increased in the past years, the identification of more specific disease markers and new therapeutic opportunities are needed.

Background Pain, physical function (PF) and quality of life (QoL) are important aspects of the lived experience of those with chronic disease1. Objectives A EULAR funded study to adapt the Osteoarthritis Quality of Life Scale (OAQoL) into five languages (German, Hungarian, Italian, Spanish, Turkish) gave the opportunity to explore the relationships between these key attributes in osteoarthritis (OA). Methods A Path Model was employed, within a Structural Equation Framework, utilising Rasch-transformed latent estimates as single indicator latent variables. Measures included lower & upper limb joint count (Manikin), pain on function (WOMAC), PF (HAQ) and QoL (OAQoL). The hypothesis was that the impact of pain upon QoL would be partially mediated by PF and this relationship will be invariant by age, gender and country. Results 677 patients with OA were recruited across 5 countries, approximately 20% from each. 76% were female, 33% aged 60 and under. 65% were married, 22% in work. Duration differed significantly across countries, with 10.1% of those in Turkey with duration of 15 years or more, compared with 32.5% of those in Spain. Joint count also varied significantly, e.g. 33.8% of those recruited in Spain reported no lower limb involvement compared with just 1.5% in Hungary. Path model fit was acceptable (χ2 7.52 (df 4) p=0.111; RMSEA 0.036; TLI 0.992, CFI 0.997) (Figure). All path weights were consistent with the basic hypothesis and 43% of the impact of pain upon QoL was mediated through PF (Sobel-Goodman Z 10.93; p 0.01) by age, gender, duration and, to a large extent, by country. In the latter there were slight variations in the magnitude of paths weights between pain and PF. The effect appeared much stronger in Italy and Turkey than elsewhere. Overall, the model appeared robust across countries (Model fit χ2 26.85 (df 20) p=0.14; RMSEA 0.05; TLI 0.985, CFI 0.993). Country-specific adjusted R2 for explained variance in QoL ranged between 0.59–0.71. Conclusions Pain, PF and the consequent reduction in perceived QoL are at the centre of the lived experience of those with OA. The relationship between these three variables, including the mediating role of PF, was found to be consistent across age, gender and, with slight variations, country. This “standard model” for OA opens up the opportunity to further explore potential psychological mediating factors which may improve QoL as well as moderating factors such as different types of intervention. References Parker L, et al. The burden of common chronic disease on health-related quality of life in an elderly community-dwelling population in the UK. Fam Pract 2014;31:557–63. Disclosure of Interest None declared

The human adult articular chondrocyte is a unique cell type that has reached a fully differentiated state as an end point of development. Within the cartilage matrix, chondrocytes are normally quiescent and maintain the matrix constituents in a low-turnover state of equilibrium. Isolated chondrocytes in culture have provided useful models to study cellular responses to alterations in the environment such as those occurring in different forms of arthritis. However, expansion of primary chondrocytes in monolayer culture results in the loss of phenotype, particularly if high cell density is not maintained. This chapter describes strategies for maintaining or restoring differentiated phenotype by culture in suspension, gels, or scaffolds. Techniques for assessing phenotype involving primarily the analysis of synthesis of cartilage-specific matrix proteins as well as the corresponding mRNAs are also described. Approaches for studying gene regulation, including transfection of promoter-driven reporter genes with expression vectors for transcriptional and signaling regulators, chromatin immunoprecipitation, and DNA methylation are also described.

Background: Septic arthritis is a disabling and potentially life-threatening condition that requires prompt diagnosis and treatment. The most important risk factors are joint prosthesis, pre-existing joint disease and immunosuppressive drugs. The aim of our study therefore was to revaluate all septic arthritis cases discharged from our Rheumatologic Unit in the last 12 years, to assess the risk factors, the clinical and laboratory characteristics, the causative microorganisms and its possible increase in frequency. Methods: The medical records of 42 consecutive patients with septic arthritis discharged from our Rheumatology Unit between January 1995 and December 2006 were reviewed. The patients ranged in age from 23 to 90 and there isn’t gender predominance. Septic arthritis was diagnosed based on the finding of purulent material in the joint space and/or the isolation of a bacterial pathogen from joint fluid. Demographic data, risk factors, co-morbidity, clinical manifestations, time interval between symptoms onset and diagnosis, treatment and laboratory data including serum white blood cell count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), synovial white blood cells and culture results were analysed. We considered these parameters in the whole population and in two different age groups (≤60, >60) and tried to determine if there was a change of microorganisms involved in septic arthritis during the years. Results: Of 42 patients, 47% were aged 60 and younger. Only 10 patients were admitted to our unit before 2001. A predisposing factor was recorded in 90,5% of cases: 15 patients had rheumatoid arthritis, 8 were diabetic, 6 had seronegative arthritis, 4 had a connective tissue disease, 8 patients had a prosthetic infection and 3 were subjected recently to arthrocentesis. We found that patients aged 60 and younger were more frequently affected by joint disease and had a synovial white blood cell count lower than patients older than 60. Staphylococcus aureus caused septic arthritis in 70% of cases before 2001, and only in 35,8 % after 2001. Also, after 2001, some infections were caused by more unusual pathogens, prevalently in patients treated with TNF inhibitors. Instead Streptococcus infections were found only in patients aged 70 and older. Conclusion: The incidence of bacterial arthritis has increased in the last six years and there was a modification of microorganisms involved, possibly related to a greater therapeutic aggressiveness. The increased frequency of joint disease and the use of immunosuppressive drugs in patients under the age of 60 could be responsible for a lower synovial white blood cell count in these patients

Wegener’s granulomatosis (WG) is a multisystemic necrotising granulomatous vasculitis of small and medium sized vessels, that primarily involves the upper and lower respiratory tracts, lung tissues and kidneys. Serum antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker of WG. Whereas the peripheral nervous system is often involved in WG, central nervous system manifestations are reported only in 2–8%, and are rarely present at onset. We report on a patient with atypical neurological presentation of ANCA negative WG in whom the diagnosis was made only after a meningeal biopsy.

Human cartilage is a complex tissue of matrix proteins that vary in amount and orientation from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue engineering strategies is the inability of the resident chondrocytes to lay down new matrix with the same structural and resilient properties that it had upon its original formation. This is particularly true of the collagen network, which is susceptible to cleavage once proteoglycans are depleted. Thus, a thorough understanding of the similarities and particularly the marked differences in mechanisms of cartilage remodeling during development, osteoarthritis, and aging may lead to more effective strategies for preventing cartilage damage and promoting repair. To identify and characterize effectors or regulators of cartilage remodeling in these processes, we are using culture models of primary human and mouse chondrocytes and cell lines and mouse genetic models to manipulate gene expression programs leading to matrix remodeling and subsequent chondrocyte hypertrophic differentiation, pivotal processes which both go astray in OA disease. Matrix metalloproteinases (MMP)-13, the major type II collagen-degrading collagenase, is regulated by stress-, inflammation-, and differentiation-induced signals that not only contribute to irreversible joint damage (progression) in OA, but importantly, also to the initiation/onset phase, wherein chondrocytes in articular cartilage leave their natural growth- and differentiation-arrested state. Our work points to common mediators of these processes in human OA cartilage and in early through late stages of OA in surgical and genetic mouse models.

Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible loss of function. The reported incidence varies from 2-5 cases per 100.000 individuals per year in the general populations to 70 cases per 100.000 individuals annually among patients with rheumatoid arthritis (RA). Predisposing factors are immunosuppressive and corticosteroids therapy and RA "itself". The expected decrease in incidence of SA was not seen over the last 20 years period but we can, on the contrary, expect an increase in the frequency of its appearance because of the population ageing, the increasingly prosthetic joint replacement, the ability of the bacteria to evade clearance by the host immune response and the rapidly growing number of patients with RA, ankylosing spondylitis and psoriatic arthritis treated with tumour necrosis factor alpha (TNF alpha) antagonists. Up to now there have been conflicting reports regarding joint infections in patients under anti-TNF therapy but according to data from Deutsch as well as the British register there might be an increase in the incidence of joint infections in anti-TNF treated patients. Microscopic analysis and culture of synovial fluid are fundamental diagnostic tools in the evaluation of possible joint sepsis. Sonographic guidance of arthrocentesis led to successful aspiration of difficult-to-access joints as shoulder and hip. There is controversy over which mode of drainage of septic synovial fluid should be employed but needle aspiration appear to be preferable to surgical treatment as an initial mode of treatment of SA. Rheumatologists should have a central role in the diagnosis and management of SA.

Concepts regarding osteoarthritis, the most common joint disease, have dramatically changed in the past decade thanks to the development of new imaging techniques and the widespread use of arthroscopy that permits direct visualisation of intra-articular tissues and structure. MRI and ultrasound allow the early detection of pre-radiographic structural changes not only in the peri-articular bone but also in the cartilage, menisci, synovial membrane, ligaments and fat pad. The significance of MRI findings such as cartilage defects, bone marrow lesions, synovial inflammation/effusions and meniscal tears in patients without radiographic signs of osteoarthritis is not fully understood. Nevertheless, early joint tissue changes are associated with symptoms and, in some cases, with progression of disease. In this short review, we discuss the emerging concept of early osteoarthritis localised to the knee based on recently updated knowledge. We highlight the need for a new definition of early osteoarthritis that will permit the identification of patients at high risk of osteoarthritis progression and to initiate early treatment interventions.

The human adult articular chondrocyte is a unique cell type that has reached a fully differentiated state as an end point of development. Within the cartilage matrix, chondrocytes are normally quiescent and maintain the matrix constituents in a low-turnover state of equilibrium. Isolated chondrocytes in culture have provided useful models to study cellular responses to alterations in the environment such as those occurring in different forms of arthritis. However, expansion of primary chondrocytes in monolayer culture results in the loss of phenotype, particularly if high cell density is not maintained. This chapter describes strategies for maintaining or restoring differentiated phenotype by culture in suspension, gels, or scaffolds. Techniques for assessing phenotype involving primarily the analysis of synthesis of cartilage-specific matrix proteins as well as the corresponding mRNAs are also described. Approaches for studying gene regulation, including transfection of promoter-driven reporter genes with expression vectors for transcriptional and signaling regulators, chromatin immunoprecipitation, and DNA methylation are also described.

Background Takayasu arteritis (TA) is a chronic large vessel vasculitis of an unknown cause, affecting the aorta and its primary branches, that leads to wall thickening, stenosis and thrombus or anuerysm formation. Therapy consists of the administration of glucocorticoids (CS) but relapse or steroid dependence may lead to associate immunosuppressive agents to achieve remission and prevent new arterial lesions. The pathogenesis of TA includes vessel injury mediated by T cells, NK cells, γ/δ cells and macrophages that secrete pro inflammatory cytokines including TNF-α. Therefore TNF-α antagonist might be useful in TA therapy. Only few cases of the use of anti TNF-α agents in TA patients are reported to date. We report the medium and long-term efficacy and tolerance of TNF-antagonist Infliximab in 4 patients affected by TA refractory to conventional therapies Methods We evaluated 4 patients treated with anti TNF therapy (Infliximab) with a follow-up of 44.25±27.1 months (range from 7 to 72 months).The patients (all females) fulfilled the diagnosis of TA according to the ACR 1990 criteria. Their mean age was 23±3.3 years and mean disease duration was 67.75±78.03 months. All patients underwent detailed clinical examination and laboratory evaluation including complete blood count, ESR, CRP, chest radiograph, ECG, peripheral vascular Doppler and PET-CT. Disease activity was considered by clinical, biological and PET-CT features. All the patients were initially treated with high doses of CS (prednisone 1mg/kg/daily) and immunosuppressive drugs in order to gain a better control of the vasculitis and to rapidly reduce steroid administration. After 3 months patients presented poor respons to clinical and biological features and were dependent on high doses of steroid. Therefore we started with Infliximab 3 mg/kg. The dose was increased to 5mg/kg in all patients due to the temporary efficacy of 3 mg/kg. Results After 4 weeks all patients felt better and they did not complain of fever, carotodynia, tiredness or thoracic pain. Laboratory tests showed a rapidly decrease of CRP from 74.2±21.61 mg/l to 2.25±0.5 mg/l and an improvement of anaemia. After 1 year we were able to reduce steroids to 5 mg/daily and immunosuppressive drugs without disease relapse in three patients and tapered prednisone to 10 mg daily in the fourth. A new PET-CT was performed on all patients after 1 year of therapy with Infliximab and we observed the disappearance of arterial hypermetabolism in three patients. They continue to be treated with Infliximab every 8 weeks without clinical, biological and radiological evidence of recurrence of the disease Conclusions Infliximab demonstrated to be effective in TA in all the parameters reflecting disease activity. Nevertheless, we were forced to administer the dose of 5 mg/kg due to the temporary efficacy of 3 mg/kg. Three of our patients achieved clinical, radiological and biological remission, the fourth tapered the dose of CS and immunosuppressive drug. Using-2-deoxiglucose uptake, arterial hypermetabolism on PET scan disappeared in the remission patients. In all 4 patients, biological markers normalized. During follow-up, no side effects or reaction to the infusion were observed. Our data confirm efficacy and safety of Infliximab in TA therapy Disclosure of Interest None Declared

Objective: Gout is the most common arthritis in adults. Despite the availability of valid therapeutic options, the management of patients with gout is still suboptimal. The Italian Society of Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the 2006 EULAR recommendations for the management of gout. Methods: The multidisciplinary group of experts included rheumatologists, general practitioners, internists, geriatricians, nephrologists, cardiologists and evidence-based medicine experts. To maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were translated in Italian and priority research queries were identified through a Delphi consensus approach. A systematic search was conducted for selected queries. Efficacy and safety data on drugs reported in RCTs were combined in a meta-analysis where feasible. The strength of recommendation was measured by utilising the EULAR ordinal and visual analogue scales. Results: The original 12 propositions were translated and adapted to Italian context. Further evidences were collected about the role of diet in the non-pharmacological treatment of gout and the efficacy of oral corticosteroids and low-dose colchicine in the management of acute attacks. Statements concerning uricosuric treatments were withdrawn and replaced with a proposition focused on a new urate lowering agent, febuxostat. A research agenda was developed to identify topics still not adequately investigated concerning the management of gout. Conclusions: The SIR has developed updated recommendations for the management of gout adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with gout.