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The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1β, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p

Objective.The purpose of the ULISSE study was to evaluate the prevalence of clinical and ultrasonographic (US) entheseal involvement in patients with psoriatic arthritis (PsA), psoriasis, and fibromyalgia syndrome (FMS).Methods.In this cross-sectional multicenter study, patients with PsA and psoriasis (not taking systemic therapy) and FMS underwent a clinical evaluation of the entheses, and a B-mode and power Doppler examination of 6 pairs of entheses.Results.The study analyzed 140 patients with PsA, 51 with psoriasis, and 51 with FMS. Clinical and US examinations were performed in 1960 and 1680 entheses in the PsA group, and 714 and 612 entheses both in the psoriasis group and in the FMS group. In both per-patient and per-enthesis evaluation, the frequency of entheseal tenderness was higher in patients with FMS (92% of the patients and 46% of the entheses, compared with 66%/23% in the PsA group and 59%/18% in the psoriasis group). With US examination, signs of entheseal involvement were more frequent in both the per-patient and per-enthesis evaluation in PsA and psoriasis (about 90% of patients in both the PsA and psoriasis groups and 75% of patients in the FMS group had at least 1 site affected, and 54%, 41%, and 27% of the pairs of entheses in, respectively, PsA, psoriasis, and FMS patients showed at least 1 enthesis involved).Conclusion.The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.

The current study aimed to investigate the association of calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals in synovial fluid (SF) of patients with osteoarthritis (OA) with disease severity, clinical symptoms, and synovial inflammation. One-hundred-and-ten patients with knee OA completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) self-assessment questionnaire, the Lequesne algofunctional index survey, and the visual analogic scale forms; they also underwent power Doppler ultrasonography (PDUS) to assess synovial inflammation. Scanning electron microscopy (SEM) was used to detect SF crystals. SEM analyses uncovered CPP crystals in 26 patients (23.6%), BCP crystals in 24 patients (21.8%), and both types of crystals in 7 patients (6.3%). Categorizing patients according to SF crystal type, a strong association between BCP crystal presence, and higher WOMAC and Lequesne index scores has been uncovered. Classifying our patients according the severity Kellgre-Lawrence score, we found that the prevalence of CPP alone (27.8%) or in combination with BCP (11.1%) was higher in the late stage group with respect to the early one (CPP 21.6% and CPP + BCP 4.1%, respectively). The prevalence of BCP crystals alone was, instead, higher in the early (23%) with respect to the late group (19.4%). No association between the presence of crystals and the radiographic scores has been observed. Considering the growing evidence supporting a role of low-grade inflammation in OA pathogenesis, the results of this study suggest a role for calcium crystals in the development of the disease.

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.

Aim To compare hand osteoarthritis (HOA) subtypes and to examine possible links with local bone mineral density (BMD). Method Fifty-five patients with erosive hand osteoarthritis (EHOA) and 21 patients with nodal hand osteoarthritis (NOA) fulfilling American College of Rheumatology criteria for HOA were evaluated. Subjects showing at least two erosions of the interphalangeal joints were assigned to the EHOA group; the others were considered NOA. Disease duration, number of active joints and radiological scores were assessed. All patients and 174 controls underwent phalangeal radiographic absorptiometry (pRA) of the middle phalanges of the non-dominant hand to assess BMD, T- and Z-scores. Results BMD was higher in EHOA with respect to NOA and controls (P = 0.05); T- and Z-scores were significantly higher in EHOA (P = 0.01 and P

The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orphan receptor gamma T (RORγt)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1β, IL-2, IL-6, IL-21 and interferon (INF)-γ were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4(+)CD25(-), CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg, and either mean fluorescence intensity (MFI) of FOXP3(+) on CD4(+) Treg or MFI of classic IL-6 receptor (IL-6R) α expression on CD4(+)CD25(-) helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-γ were not detectable, whereas IL-6 and IL-1β levels were higher than in SF of non-inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORγt proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg cells and brighter MFI of IL-6Rα were observed both on CD4(+)CD25(high)- and CD4(+)CD25(-) T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1β and γC cytokines in the polarization and plasticity of Th17 and Treg cells, which might participate in the perpetuation of joint inflammation in PsA patients.

This study aimed to investigate, using an in vitro model, the mechanisms involved in the effects linked to a novel hexadecylamide derivative of hyaluronic acid (HA), HYADD®4 (HS), on some inflammatory aspects related to the osteoarthritis process. The human leukemic monocytic cell line THP-1 was stimulated with calcium pyrophosphate (CPP) crystals or lipopolysaccaride (LPS) and cultured in the presence of HS or two unmodified HAs (500–730 kDa and >1500 kDa, respectively). The effects of the three HA derivatives were compared by examining the inhibition of IL-1s and IL-8 release, the phagocytic capacity of THP-1, and HA's physical interference with the cytokines and their biological activity. Adding HS simultaneously with the stimuli led to a marked (nearly 100%) decrease in cytokine release and biological activity with respect to the two unmodified HAs. The effect was not altered when a CD44 function-blocking monoclonal antibody was used. Incubation of the three derivatives with IL-1s and IL-8 led to a reduced bioavailability of the cytokines in the medium in the presence of HS but not of unmodified HA. This study examines a novel mechanism inhibiting cytokine bioactivity. The HA hexadecylamide derivative was found to suppress, in vitro, the inflammatory response induced by CPP crystals and LPS by reducing the bioavailability of the two cytokines that were analyzed. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2823–2829, 2015.

Crystal-induced arthritis (CIA) is characterized by an intense inflammatory reaction triggered by the deposition of monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals in articular and periarticular tissues. Severe, acute pain constitutes the most important clinical symptom in patients affected by these diseases. Pain along with redness, warmness, swelling, and stiffness in the affected joint arises abruptly in gout and disappears when the acute phase of the attack resolves. While an acute joint attack caused by calcium pyrophosphate crystals can mimic a gout flare, basic calcium phosphate crystal arthritis gives rise to a series of clinical manifestations, the most severe of which are calcific periarthritis, mostly asymptomatic, and a highly destructive arthritis known as Milwaukee shoulder syndrome, which is characterized by painful articular attacks. Pain development in CIA is mediated by several inflammatory substances that are formed after cell injury by crystals. The most important of these molecules, which exert their effects through different receptor subtypes present in both peripheral sensory neurons and the spinal cord, are prostaglandins, bradykinin, cytokines (in particular, interleukin (IL)-1β), and substance P. The pharmacological treatment of pain in CIA is strictly associated with the treatment of acute phases and flares of the disease, during which crystals trigger the inflammatory response. According to international guidelines, colchicines, nonsteroidal anti-inflammatory drugs, and/or corticosteroids are first-line agents for the systemic treatment of acute CIA, while biologics, namely anti-IL-1β agents, should be used only in particularly refractory cases.

Microcrystals are responsible for some of the most common and complex arthropathies which are often accompanied by intense, severe pain and inflammatory reactions. The main pathogens are crystals of monosodium urate (MSU), responsible for the gout, calcium pyrophosphate (CPP), which deposits also in various clinical forms of arthopathies, and basic calcium phosphate associated with osteoarthritis. In this context, the microcrystal arthritis is characterized by multiple, acute attacks followed by chronic pain, disability, impaired quality of life, and increased mortality. Given their chronic nature, they represent an ever more urgent public health problem. MSU and CPP crystals are also able to activate nociceptors. The pain in mycrocrystalline arthritis (MCA) is an expression of the inflammatory process. In the course of these diseases there is an abundant release of inflammatory molecules, including prostaglandins 2 and kinins. Interleukin-1 represents the most important cytokine released during the crystal-induced inflammatory process. Therefore, clinically, pain is the most important component of MCA, which lead to functional impairment and disability in a large proportion of the population. It is fundamental to diagnose these diseases as early as possible, and to this aim, to identify appropriate and specific targets for a timely therapeutic intervention.

Background Spondyloarthritis often affects young people, typically in their working years. The aim of our study was to investigate work productivity and its relationship with disease activity and physical functioning in Italian patients with axial spondyloarthritis (axSpA) with chronic back pain (CBP) for ≥3 months and ≤2 years, and onset

BACKGROUND The identification of calcium crystals in synovial fluid (SF) of patients with osteoarthritis (OA) represents an important step in understanding the role of these crystals in synovial inflammation and disease progression. OBJECTIVES This study aimed to investigate the presence of calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals in SF collected from patients with symptomatic knee OA by scanning electron microscopy (SEM) coupled to x-ray energy dispersive spectroscopy, compensated polarized light microscopy (CPLM), and alizarin red staining. METHODS Seventy-four patients with knee OA were included in the study. Synovial fluid samples were collected after arthrocentesis and examined under CPLM for the assessment of CPP crystals. Basic calcium phosphate crystals were evaluated by alizarin red staining. All the samples were examined by SEM. The concordance between the 2 techniques was evaluated by Cohen κ agreement coefficient. RESULTS Calcium pyrophosphate and BCP crystals were found, respectively, in 23 (31.1%) and 13 (17.5%) of 74 OA SFs by SEM analysis. Calcium pyrophosphate crystals were identified in 23 (31.1%) of 74 samples by CPLM, whereas BCP crystals were suspected in 27 (36.4%) of 74 samples. According to κ coefficient, the concordance between CPLM and SEM was 0.83 for CPP, and that between alizarin red and SEM was 0.68 for BCP. CONCLUSIONS The results of our study showed a high level of concordance between the 2 microscope techniques as regards CPP crystal identification and a lower agreement for BCP crystals. Although this finding highlights the difficulty in identifying BCP crystals by alizarin red staining, the use of SEM remains unsuitable to apply in the clinical setting. Because of the in vitro inflammatory effect of BCP crystals, further work on their analysis in SF could provide important information about the OA process.

Our aim was to determine the prevalence of spine and sacroiliac joint (SIJ) lesions on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (axSpA) and their correlation with disease activity indices. Sixty patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years), attending the SpA-clinic of the Unità Operativa Complessa Reumatologia of Padova [SpondyloArthritis-Caught-Early (SPACE) study], were studied following a protocol including physical examination, questionnaires, laboratory tests, X-rays and spine and SIJ MRI. Positive spine and SIJ MRI and X-rays images were scored independently by 2 readers using the SPARCC method, modified Stoke ankylosing spondylitis spine score and New York criteria. The axial pain and localization of MRI-lesions were referred to 4 sites: cervical/thoracic/lumbar spine and SIJ. All patients were classified into three groups: patients with signs of radiographic sacroiliitis (r-axSpA), patients without signs of r-axSpA but with signs of sacroiliitis on MRI (nr-axSpA MRI SIJ+), patients without signs of sacroiliitis on MRI and X-rays (nr-axSpA MRI SIJ-). The median age at LBP onset was 29.05±8.38 years; 51.6% of patients showed bone marrow edema (BME) in spine-MRI and 56.7% of patients in SIJ-MRI. Signs of enthesitis were found in 55% of patients in the thoracic district. Of the 55% of patients with BME on spine-MRI, 15% presented presented a negative SIJMRI. There was a significant difference between these cohorts with regard to the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ score. The site of pain correlated statistically with BME lesions in thoracic and buttock districts. Since positive spine-MRI images were observed in absence of sacroiliitis, we can hypothesize that this finding could have a diagnostic significance in axSpA suspected axSpA.

Summary Objective Erosive osteoarthritis of the hand (EHOA) is thought to be an aggressive variant of hand osteoarthritis (HOA) characterised by prominent local inflammation and radiographic aspects of bone erosions in interphalangeal (IP) joints. However, rare studies have until now investigated the value of biomarkers in these patients. Thus, we determined Coll2-1, a marker of type II collagen denaturation, its nitrated form (Coll2-1NO2) and myeloperoxidase (MPO) levels in serum of patients with EHOA vs non-EHOA and subsequently evaluated their relationships with disease indices of severity and activity. Methods Coll2-1, Coll2-1NO2 and MPO were measured using specific immunoassays in 82 patients, 57 with EHOA, all females, median age 59 (41–74yrs) and 20 with non-EHOA, all females, median age 55 (43–73yrs), fulfilling the American College of Rheumatology (ACR) criteria for hand OA. EHOA was characterized by the presence of at least one central bone erosion on radiograph in the IP joints. Patients were also evaluated for disease duration, number of affected (swollen and painful or tender) joints, radiographic score (RS) by Kallman scale and high sensitivity C-reactive protein (hsCRP). Results Serum levels of MPO were higher in EHOA (230.0±152.1ng/ml) than in non-EHOA (160.2±111.5ng/ml, P =0.037). Coll2-1NO2 levels trended towards an elevation in EHOA compared non-EHOA (0.40±0.86 vs 0.22±0.14nmol/l, P =0.06), while Coll2-1 levels were not different. Correlations were found for disease duration and both MPO ( R 2 =0.48, P =0.001) and Coll2-1NO2 ( R 2 =0.73, P =0.01) after the splitting of the population in subgroups according to a cut off value above the 50th percentile. A correlation was found between hsCRP and MPO ( R 2 =0.57, P =0.01). Conclusions This study clearly demonstrates an elevation of some serum biomarkers in EHOA, in comparison with non-EHOA. In particular, MPO, hsCRP and the ratio Coll2-1NO2/Coll2-1 discriminated the two subsets of hand osteoarthritis (HOA), and a trend was also observed for Coll2-1NO2. These data suggest that these biomarkers could be helpful for the diagnosis of EHOA.

Resume L’arthrose des mains (AM) erosive (AME), dite aussi arthrose erosive des doigts ou arthrose digitale erosive, est une entite clinique encore en quete d’une definition satisfaisante. Selon les recentes recommandations de l’Eular, l’AME doit etre consideree comme un sous-groupe de l’arthrose de la main ciblant les articulations interphalangiennes et caracterise par une apparition brusque avec douleur intense et associe a une deficience fonctionnelle, des symptomes et signes inflammatoires (rigidite, gonflement des tissus mous, erytheme, paresthesies, legere augmentation de la proteine C-reactive) et une evolution plus defavorable que celle de l’arthrose non erosive de la main. Il est aussi specifie que l’AME est defini radiographiquement par l’erosion sous-chondrale, la destruction corticale et la reaction reparatrice secondaire, qui peut inclure l’ankylose osseuse. Toutefois, puisque les moyens d’imagerie plus sensibles, tels que l’IRM, retrouvent des erosions plus frequemment que la radiographie standard, un consensus est necessaire pour definir l’AME. Dans la plupart des cas, les traitements classiques sont decevants, raison pour laquelle des nouveaux moyens therapeutique sont en evaluation, incluant des medicaments biologiques anti-cytokines qui, dans les essais preliminaires non controles, semblent interessants.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects the axial skeleton and evolves in stiffness followed by ankylosis and disability. However, it may be difficult to exactly establish the natural history of the disease and the influence of risk factors of progression, since most patients are treated with various pharmacologic or non-pharmacologic agents, which may potentially influence the natural progression of the disease. In this context, we report here a very interesting case of a 40 year old man, presented to our outpatient clinic, 28 years after the onset of AS. Previously for personal reasons, did not choose not to undergo any treatment. This case allows us to evaluate the natural radiological progression of the disease and the influence of predictive risk factors.

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 …

Background The advent of anti-tumor necrosis factor-α (TNFα) drugs has changed the course of ankylosing spondylitis (AS). While data are available concerning the long term effectiveness of single anti-TNF agents, little has been published about predictors of treatment response in AS. The aim of this retrospective study was to evaluate the survival, effectiveness, and safety of infliximab over a 5-year period and to identify predictors of disease outcome. Methods Seventy AS patients attending the Rheumatology Clinic of the University of Padua who were treated with intravenous infliximab at 0, 2, 4 weeks and then every 6, 8, or up to 16 weeks were studied retrospectively. Demographic information, laboratory inflammatory and disease indices (BASDAI, BASFI, BASMI) were collected (at baseline, 3, 6, 12 months and once a year thereafter). Clinical improvement, drug tolerability, adverse events/side effects and causes leading to discontinuation were recorded. Results Infliximab caused a rapid, persistent improvement at all the assessment times in the BASDAI 50 (71.4 %) and ASDAS scores (97.1 % in ASAS20, 80 % in ASAS40, 80 % in ASAS5/6), and already within 6 months of beginning treatment in 50 % percent of the patients. The other 50 % withdrew because of: adverse events (12 = 34.3 %), side effects (5 = 14.3 %), drug inefficacy (12 = 34.3 %), spontaneously (4 = 11.4 %). Those who did not respond were prevalently females (34.3 % vs 17.1 %). Conclusion Factors such as female sex, use of steroids, persistently high inflammatory levels, BASFI and BASDAI indices were found to be negative predictors of treatment response. Infliximab was found to be safe, effective and well-tolerated; it elicited satisfactory long term response and drug survival rates.

Anti-tumor necrosis factor (TNF) alpha therapy has changed the course of psoriatic arthritis (PsA), but clinical experience about lengthening of time intervals between drug administrations is still limited. The aims of the study were to evaluate: (1) the long-term efficacy (over a 4-year period) of etanercept/adalimumab in a subset of PsA patients who did not require switches; and (2) the progressive lengthening of time intervals between treatments in patients who achieved minimal disease activity (MDA). PsA outpatients attending the Rheumatology Clinic-University of Padova who took a single anti-TNF agent (etanercept/adalimumab) for a 4-year period were studied. Therapy efficacy was assessed using clinical, biochemical, and disease activity (DA) indexes. The intervals between treatments were empirically and progressively lengthened after MDA was reached and maintained. One hundred and forty-one patients (mean age, 51.22 ± 12.34 years; mean disease duration, 12.1 ± 8.42 years) treated with etanercept/adalimumab (47.5% and 52.5%, respectively) were studied. DA indexes showed a marked, persistent improvement in all the patients throughout 4 years. The interval between injections could be extended in 46.1% of the patients (35% for adalimumab, 58% for etanercept) without provoking relapses. The mean therapy interval at the end of the study period was 3.12 weeks for adalimumab 40 mg (with respect to 2 weeks) and 2.75 weeks for etanercept 25 mg (with respect to 0.5 weeks). The new therapy timetable also led to cost savings. In conclusion, lengthening the time intervals between injections of anti-TNF agents in PsA patients who reach MDA is safe, effective, cost-effective, and facilitates patient compliance.

We assessed signaling protein mapping in total T cells, to analyze the proportions of T regulatory (Treg) and TCD4+ effector (Teff) cell phenotypes, and the respective interleukin 6Rα (IL-6Rα) expression in the inflammatory microenvironment of synovial fluid (SF) of patients with sustained psoriatic arthritis (PsA). Our approach was to measure the IL-6 level in SF using a multiplex bead immunoassay. Reverse-phase protein array was used to assess Janus kinase (JAK) 1 and JAK2, extra-cellular regulated kinase (ERK) 1 and 2, protein kinase Cδ (PKCδ), signal transducer and activator and transcription (STAT) 1, STAT3, and STAT5 phosphoproteins in total T cell lysates from SF of patients with PsA. Frequencies of CD4+IL-17A-F+IL-23+ CD4+ Th cells producing IL-17A and IL-17F (Th17) and CD4+CD25high intracellular forkhead box transcription factor+ (FOXP3+) phenotypes, and the percentage of Treg- and Teff- cells were quantified in SF and matched peripheral blood (PB) of patients with PsA and PB of healthy controls (HC) by flow cytometry. Our results were the following: In PsA SF samples, a coordinate increase of JAK1, ERK1/2, STAT1, STAT3, and STAT5 phosphoproteins was found in total T cells in SF of PsA; where IL-6 levels were higher than in PB from HC. Expanded CD4+IL-17A-F+IL-23+ Th17, CD4+ CD25- Teff- and CD4+CD25(high) FoxP3+Treg subsets, showing similar levels of enhanced IL-6Rδ expression, were confined to PsA joints. In our studies, the transcriptional network profile identified by ex vivo signaling protein mapping in T lymphocytes in PsA joints revealed the complex interplay between IL-1, IL-6, and IL-23 signaling and differentiation of Th17 cells and CD4+Tregs in sustained joint inflammation in PsA.

a b s t r a c t Objective: To evaluate the progression of subclinical atherosclerosis in Psoriatic Arthritis (PsA) patients treated with anti-tumor necrosis factor (TNF)- agents. Methods: Thirty-two PsA patients classified according to the CASPAR criteria and attending the Rheuma- tology Unit of the University of Padua Medical Center were enrolled in a two-year prospective, observational study. In accordance with the ASAS/EULAR recommendations on the management of these patients, those studied were prescribed biological agents (etanercept (n = 21), adalimumab (n = 6), inflix- imab (n = 5)). Plasma lipids, inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), vessel endothelium growth factor (VEGF), osteoprotegerin (OPG), and TNF-, as well as Disease Activity Score 28 calculated with CRP (DAS 28-CRP) were evaluated at baseline and after two years of treatment. Bilateral carotid B-mode ultrasound measurements (the mean-intima media thickness (mean- IMT), the mean maximum-IMT (M-Max)) of each carotid artery segment (common, bulb, and internal carotid artery) and the post-occlusion flow-mediated dilation (FMD) of the brachial artery were also assessed at baseline and after two years. Results: Despite an improvement in the DAS 28-CRP score (P < 0.0005) and lower low-density lipoprotein cholesterol (P < 0.013) and triglyceride (P < 0.036) values, there was a significant progression in both the mean-IMT (P < 0.0005) and M-Max (P < 0.0005). Moreover, no recovery in FMD (P = ns) was observed after two years of anti TNF- treatment. Serum TNF- levels were increased (P = 0.003) and OPG values were decreased (P = 0.011) at the end of follow- up with respect to baseline values. Conclusions: Despite improvement in clinical status, arterial remodelling was observed in the PsA patients who were treated with anti TNF- agents for two years. © 2014 Published by Elsevier Masson SAS on behalf of the Societe Francaise de Rhumatologie.

Background Erosive OA involves interphalangeal joints (IPJs), resulting in a high disease burden, for which treatment options are limited. Although it is characterized by joint inflammation, earlier treatment with TNF blockers was equivocal. Objectives To investigate the 1-year efficacy of ETN in erosive OA. Methods In a European multicentre study (NTR 1192) patients were equally randomized to subcutaneous ETN (24 weeks 50 mg weekly, thereafter 25 mg weekly) or placebo. Patients with erosive (≥1 IPJ with radiographic pre(erosive) anatomical phase (“J”/“E”) according to Verbruggen-Veys system) inflammatory (≥1 IPJ with soft swelling/erythema and with positive power Doppler at US) symptomatic (VAS pain >30/100 on NSAID use, flare after NSAID washout) OA were included. VAS pain, hand function (FIHOA), quality of life (SF-36), no. of tender joints and grip strength were assessed after 4, 8, 12, 24, 36 weeks and 1 year. Radiographic progression of IPJs was scored blindly in paired order (baseline, 24 weeks and 1 year) following the quantitative Ghent University Scoring System (GUSS, 0–300 per IPJ). With linear mixed models VAS pain was compared between treatment groups at 24 weeks (primary outcome), and 1 year in intention-to-treat (ITT) analyses. With general estimated equations secondary outcomes were analysed. Adjustments were made for centre, baseline values and patient effects were appropriate. Completers fulfilling the extensive inclusion criteria were included in per-protocol (PP) analyses. Results Of 284 screened patients, 90 (mean age 60 years, 81% women, 96% fulfilled ACR hand OA criteria) were randomized; 22 discontinued the study prematurely. At baseline patient characteristics did not differ between the groups. VAS pain in all patients decreased -24.8 mm (95%CI -29.2;-20.5 (P Conclusions In erosive OA ETN was not superior over placebo on VAS pain at 24 weeks. However in the symptomatic and inflammatory patients completing the study ETN was superior over placebo both on pain and structural damage assessed by GUSS; ETN was especially effective in joints with signs of inflammation. Acknowledgement Pfizer for supply of study medication and research grant. Disclosure of Interest None declared

Background Recently studies have focused on the role of new markers to diagnose early axial spondyloarthritis (axSpA), to evaluate disease activity (DA) and to predict patients (pts) at higher risk for a worse outcome. Common biomarkers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are often ineffective in assessing DA. Objectives To evaluate some biomarkers and their correlation with clinical parameters, DA indexes and imaging in pts with early axSpA. Methods Sixty pts with low back pain (≥3 months, ≤2 years, onset ≤45 years) attending the SpA-UOC Rheumatology of Padua (SpondyloArthritis-Caught-Early SPACE study), were studied following a protocol including physical examination, questionnaires9, lab tests, X-rays and MRI of spine and sacroiliac joints (SIJ)at baseline.An experienced rheumatologist made axSpA diagnosis according to ASAS criteria. The DA and physical functioning were assessed using: Bath Ankylosing Spondylitis Metrology Index (BASMI); Maastricht Ankylosing enthesitis Spondilities Score (MASES); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); Bath Ankylosing Spondylitis Functional Index (BASFI); Ankylosing Spondylitis disease activity score (ASDAS); Visual Analogue Scale (VAS pain); VAS night pain; VAS disease activity;Bath Ankylosing Spondylitis Patient Global Score (BASG1); BASG2; Health Assessment Questionnaire (HAQ); ESR; serum ultrasensitive CRP (hs-CRP); matrix metalloproteinase (MMP3); interleukin (IL) IL-22, IL-17, IL-23.Positive spine and SIJ MRI images were scored independently by 2 readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method; the spine and SIJ X-rays images were scored using mSASSS and NY-criteria. After the X-rays and MRI images of all pts were read, they were classified into the following cohorts: pts with signs of radiographic sacroiliitis (r-axSpA), pts without signs of radiographic sacroiliitis but with signs of sacroiliitis on SIJ-MRI (nr-axSpA MRI SIJ+), pts without signs of sacroiliitis on MRI and X-rays (nr-axSpA MRI SIJ-).The Spearman test and Kruskal Wallis test were used to compare all indexes in these cohorts. Results There was a significant difference between the three cohorts with regard to the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and the SPARCC SIJ score (Table 1). There were no differences in these groups in IL-17, IL-22, IL-23, MMP-3 and hsCRP. ILs remained below detection value in all cohorts. The correlation of IL-17 and IL-23 with other indexes was not significant. There was instead a correlation between IL-22 and some clinical indexes (BASFI, BASG1, HAQ, VAS pain). The correlation between mSASSS and MMP3 and hsCRP was an interesting finding. Conclusions ILs, MMP-3 and hsCRP values were not significantly increased in any of the study groups and were not related to radiographic SIJ involvement or to clinical and DA indexes. This finding can probably be explained by the fact that pts had early stage axSpA and by the small sample size. Further studies are needed to analyze the validity and reproducibility of these biomarkers in early axSpA. Disclosure of Interest None declared

Background Calcium pyrophosphate deposition (CPPD) disease is a chronic arthropathy caused by calcium pyrophosphate (CPP) crystal formation and deposition in joints (1). It can be divided into different clinical subtypes: asymptomatic CPPD, osteoarthritis with CPPD, acute CPP crystal arthritis, and chronic CPP crystal inflammatory arthritis (2). In this latter form, colchicine (Co), nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids (GCs) are commonly used with good effects.Some unresponsive cases, however, need alternative pharmacological treatments. Some authors suggested that methotrexate (MTX) could represent a good option in refractory patients (3). Objectives The aim of this study was to evaluate the effectiveness of MTX in patients with severe chronic CPP polyarthritis, who did not respond to NSAIDs and/or Co and GCs. Methods Twenty one outpatients (11 male; mean age 63.38 ±5.27) with resistant chronic CPP arthritis, were treated with MTX in dose between 7.5–12.5 mg/week. All patients fulfilled the EULAR diagnostic criteria for CPPD (2). Tender (TJC) and swollen joints count (SJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed at baseline, before MTX initiation (M0), and at three, six and nine months (M3, M6, M9). Clinical and biologic side effects of MTX were evaluated. The statistical analysis was performed using Friedman with Dunn9s Multiple Comparison Test. Results At M0 the mean of TJC and SJC were 18.00±3.41 and 10.38±1.96, respectively. These parameters decreased considerably at M3 (TJC=9.62±2.52; SJC=7.95±2.84), reaching a significance at M6 (TJC=4.62±1.88; SJC=3.05±2.06) and at M9 (TJC=1.38±1.28;SJC=0.67±0.66) with respect to M0 (p Conclusions This study confirms that MTX is a valid therapeutic alternative in severe chronic CPP arthritis patients, refractory to previous conventional drugs. According to this study, we observed an excellent response, with a good safety profile. Further additional studies are necessary to expanding the knowledge and identifying the patients in which MTX could be effective. References Johnson K, Terkeltaub R. Inorganic pyrophosphate (PPI) in pathologic calcification of articular cartilage. Front Biosci 2005;10:988–97 Zhang W, Doherty M, Bardin T, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis 2011;70 563–70 Andreas M, Sivera F, Pascual E. Methotrexate is an option for patients with refractory calcium pyrophosphate crystal arthrytis. J Clin Rheumatol 2012;18:234–6 Disclosure of Interest None declared

Background Anti-Tumor Necrosis Factor (TNF)alpha drugs play a fundamental role in Ankylosing Spondylitis (AS) therapy. Nevertheless their use is associated to potential side effects, such as a higher frequency of infection, and high healthcare costs. On these bases, a dose reduction strategy (lengthening drug administration interval) is often attempted in clinical practice. Objectives 1) to retrospectively compare the features of anti-TNFalpha-treated AS patients who could lengthen the administration interval (group A) with those of patients who needed to maintain standard dosage (group B); 2) to evaluate the impact of dose reduction on infection frequency; 3) to evaluate cost-savings in group A. Methods All AS patients attending the spondyloarthritis outpatients clinic- Rheumatology Unit of University of Padova and of University of Rome “Tor Vergata” between January 2011 to April 2015 who were treated with anti-TNFalpha (infliximab, adalimumab, etanercept) at a standard dose for at least 6 months with a good control of disease activity (ASDAS Results Data from 96 AS patients (25 females, 26.04%; mean age 47.62±13.39 years) were examined. Drug administration interval, which could be lengthened in 66 (68.75%) patients (group A) without flare-ups or functional worsening, was associated to an improvement in ASDAS [t0=2.1 (1.49) vs t48=1.00 (0.29); p Conclusions Lenghtening anti-TNFalpha administration interval appears to be a valid approach in patients with a less severe inflammatory status, and a negative family history of spondyloarthritis. Dose reduction regimen is associated to lower infection frequency and less expense for National Health Care System. References Arends S, van der Veer E, Kamps FB, et al. Patient-tailored dose reduction of TNF-α blocking agents in ankylosing spondylitis patients with stable low disease activity in daily clinical practice. Clin Exp Rheumatol. 2015;33:174–80. Disclosure of Interest None declared

This review focuses on biomarkers in erosive hand osteoarthritis (EHOA), a subset of hand osteoarthritis (HOA), that primarily affects interphalangeal joints and is characterized by abrupt onset, severe pain and functional impairment, as well as signs of inflammation, in particular stiffness, swelling, erythema, paraesthesiae, and worse outcome. Inflammatory features and radiographic erosions are the main diagnostic hallmarks of this particular disease subset. As in other fields of OA, EHOA biomarkers can be classified as dry and soluble. Soluble biomarkers which are found in serum, synovial fluid and urine can be specific indicators of joint inflammation and degradation. With regard to inflammatory markers, C-reactive protein and myeloperoxidase have been found to be increased in EHOA, with respect to non-erosive HOA. All these markers have, moreover, been found to be correlated with disease activity. Another interesting marker linked to inflammation is hyaluronic acid, considered to be a marker of synovitis, which is frequently found in EHOA. The most useful cartilage markers in both erosive and non-erosive HOA, seems to be collagen (Coll) 2-1, Coll 2-1NO(2) and Col2-3/4C(short). Immunogenetic markers were also determined and an association between EHOA and a single nucleotide polymorphism on the gene encoding interleukin-1β was found in HLA and there was an increased frequency of HLA-B44 and HLA-DRB1*07 in EHOA.

The main aim of this study was to investigate the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid (SF) obtained from patients with previously diagnosed joint diseases.We reviewed the results of SF analysis of 5020 samples identifying those collected from patients with a previously definite diagnosis (2370 samples). SF analysis results, age, sex, diagnosis and disease duration were recorded from computerized records of patients' archives.The prevalence of CPP crystals in SF was 22.28% in osteoarthritis (OA), 8.28% in rheumatoid arthritis (RA), 3.82% in psoriatic arthritis (PsA), 2.79% in other spondyloarthropathies (SpA), 10% in septic arthritis (SeA), 0.66% in gout and 9.18% in the miscellanea of joint diseases, respectively. The prevalence of MSU crystals in SF was 0.30% in RA, 3.34% in PsA, 0.70% in other SpA, 0.80% in acute CPP crystal arthritis (CPP-CA), 0% in OA, reactive arthritis (ReA), SeA, juvenile idiopathic arthritis (JIA) and miscellanea. In OA group, we observed that age and SF inflammatory indices were higher in SF positive to CPP crystals with respect to those without crystals (P0.0001). In RA, we found that the group of patients with CPP crystals was significantly older (P=0.001) and had a SF less inflammatory (P=0.022) with respect to that without crystals but with a higher disease duration than those without crystals.Crystals can be detected more frequently than expected in SF from joint diseases with a previous established diagnosis. This highlights the importance of SF analysis for the diagnosis of possible comorbidities linked to the presence of crystals.

Objective.Anterior chest wall (ACW) involvement is difficult to evaluate in patients with spondyloarthritis (SpA). Bone scan is sensitive to ACW involvement, while magnetic resonance imaging (MRI) detects early alterations in SpA. We compared the sensitivity and specificity of bone scans and MRI in assessing ACW in early SpA.Methods.Out of 110 patients with early SpA attending the Outpatient Rheumatology Unit Clinic of Padua University from January 2008 to December 2010, the 40 complaining of pain and/or tenderness [60% with psoriatic arthritis (PsA), 12.5% with ankylosing spondylitis, and 27.5% with undifferentiated SpA] underwent bone scans and MRI.Results.At clinical examination, sternocostoclavicular joints were involved in 87.5% on the right, 77.5% on the left, and 35% on the sternum. Bone scan was positive in 100% and MRI in 62.5% of these patients. Early MRI signs (bone edema, synovial hyperemia) were observed in 27.5%, swelling in 5%, capsular structure thickness in 37.5%, erosions in 15%, bone irregularities in 15%, osteoproductive processes in 12.5%, and osteophytes in 5%. A higher prevalence of Cw6, Cw7, B35, and B38 was found in 15%, 48%, 28%, and 12%, respectively, of the patients with PsA who had bone scans.Conclusion.Noted mainly in women, ACW involvement was frequent in early SpA. Both bone scans and MRI are useful in investigating ACW inflammation. Bone scans were found to have high sensitivity in revealing subclinical involvement, but a low specificity. MRI provides useful information for therapeutic decision making because it reveals the type and extent of the process. The significant associations of HLA-Cw6 and Cw7 with PsA could suggest that genetic factors influence ACW involvement.

There is evidence from randomized controlled trials (1) as well as from observational studies (2) that there are more infections in patients treated with anti-tumour necrosis factor (TNF)-α agents....

Sjögren's syndrome (SS) is a chronic inflammatory disease with an autoimmune etiology, that affects exocrine glands, in particular salivary and lacrimal glands. Among the diagnostic criteria of SS, imaging techniques play an important role. The aim of our study is to compare three imaging techniques, such as sonography, scintigraphy and sialography in the evaluation of major salivary glands. The use of the these techniques is of great importance for the diagnosis of SS. Sonography is the most frequently used for its prompt execution, non invasivity, great acceptance by the patient and low cost. In the diagnostic patient management of SS, sonography results are eventually confirmed by the other imaging techniques, sialography and scintigraphy.

Erythema nodosum (EN) is an inflammatory disease of the skin and subcutaneous tissue that may be found in association with many systemic diseases such as infectious diseases, sarcoidosis, Behcet disease, inflammatory bowel diseases and tumours, in particular lymphoma. EN may be also induced by some drugs, including mainly estroprogestinics, salicylic acid, minocycline and sulfamidic acid. Due to the numerous possible causes, sometimes it may be very difficult to achieve a correct diagnostic interpretation, especially when an isolated EN represents the revealing feature, as in the following case. We describe the case of a patient, of young age and good clinical condition, who developed EN during the course of abdominal tuberculosis. The diagnosis was obtained by histologic examination of the abdominal formation since positron emission tomography and total body axial tomography were not useful in discriminating EN from malignancies.

To compare the distribution of human leucocyte antigen (HLA) class I and II alleles in patients with erosive hand osteoarthritis (EHOA) to that of patients with non-erosive hand OA (non-EHOA) and in healthy Italian Bone Marrow Donors (IBMDs), in order to evaluate possible immunogenetic associations with EHOA. In the EHOA group we also sought possible associations between HLA alleles and disease severity.Ninety-four patients with EHOA (82 women, 12 men; mean age 61.4 ± 8.45 years) and 37 with non-EHOA (28 women, nine men; mean age 59.21 ± 9.07 years) were studied. Disease severity was measured by the number of clinically active joints (NCAJ) and by the radiographic score (RS) using the Kallman scale. HLA typing was undertaken for A, B, C, and DRB1 loci; HLA-DRB1* genotyping was determined using polymerase chain reaction (PCR) with sequence-specific primers. Frequencies were compared with those of the healthy IBMDs.The alleles found more frequently in EHOA patients than in non-EHOA patients and healthy controls were: A23, A26, and A29; B38, B44, and HLA DRB1*01 and *07. The RS was more severe in the EHOA compared to the non-EHOA group (63.60 ± 23.14 vs. 34.34 ± 20.24, p0.001). Within the EHOA group, HLA-DRB1*07 was associated with a higher RS (67.36 ± 23 vs. 64.5 ± 18.5, p = 0.029).In this study of North Italian patients affected with EHOA, the HLA-DRB1*07 allele was found to be associated with both the development and greater severity of the disease.

Inflammatory or erosive are terms used interchangeably to define a clinical subset of osteoarthritis of the hand (HOA), targeting interphalangeal joints and characterised by an abrupt onset, marked pain and functional impairment, inflammatory symptoms and signs, including stiffness, soft tissue swelling, erythema, paraesthesiae, mildly elevated C-reactive protein and a worse outcome than non-erosive HOA. This subset is defined radiographically by subchondral erosion, cortical destruction and subsequent reparative change, which may include bony ankylosis. Although the presence of both clinical and radiographic aspects are very suggestive for the diagnosis in most cases, doubts have been recently raised from some studies which, by means of sensitive imaging techniques such as magnetic resonance imaging (MRI) and sonography, had found erosive changes in most patients with HOA, including those without signs of erosions at conventional radiography. However, many findings suggest that subjects with erosive HOA exhibit more inflammatory features than those with non-erosive HOA in different ways, including clinical, laboratory and sonographic aspects. Thus, it is probably preferable to use the double term inflammatory/erosive to better define this particular subset of HOA.

Background The role and the significance of calcium crystals (CC) in synovial inflammation and in Osteoarthritis (OA) progression is somewhat debated. Calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) are the most common CC in OA. Objectives The aim of this study was to evaluate the presence of CC in synovial fluid (SF) using ultrasensitive analysis by scanning electron microscopy (SEM) in the various stages of symptomatic and radiographic knee OA (KOA). Methods One hundred twenty consecutive outpatients with KOA underwent knee arthrocentesis. Of these, 49 (40.8%) were in an early stage ( Results CC were detected by SEM in 62/120 (51.6%) samples. The patients positive to CC (CC+) were older (p=0.036), had a greater difficulty in moving (p=0.0041), a higher SF PMN percentage (0.0041) and a higher USPD (p≤0.0001) with respect to the group of patients negative to CC (CC-). CPP crystals were positive in 37/120 patients (30%) by SEM. Age (p=0.0002), disease duration (p=0.041), pain (p=0.039), KLRS (p=0.0334) and USPD (p=0.0001) were significant different in the 2 groups of patients subdivided by the presence of CPP. BCP were detected in 33/120 patients (27.5%) by SEM. Subdividing patients by the presence of BCP, we found a significant differences as regard WOMAC (p=0.0001), pain (p=0.0001), stiffness (p 5 yrs (N.44) late KOA. Univariate analysis highlighted a significant difference in age and USPD. In the I group, patients BCP+ significant differences were found in pain (p=0.0002), stiffness (p=0.045), functional impairment (p=0.0014), WOMAC (p=0.0002) and USPD (p=0.0009), all higher with respect to patients negative to BCP. (Figure 1a, b, c) Conclusions The presence of CC was found to be correlated with a more severe clinical status, worse imaging findings, and positive USPD. The presence of BCP crystals in the early KOA group, which was associated to inflammatory aspects, suggests a possible role of BCP crystals in the pathogenesis of the disease. References Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012;51:249-57 Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!) Osteoarthritis Cartilage.2013;21:16-21 Rosenthal AK. Crystals, inflammation, and osteoarthritis. Curr Opin Rheumatol.2011;23:170-3 Disclosure of Interest None declared

Background Crystal-induced inflammation is characterized by a marked release of cytochines, chemokines and other factors in the synovial compartments. The resolution of this process is quite easy to achieve in patients through the use of NSAIDs and other more specific drugs such as colchicines and anti-IL1β biologics. In view of the potential long term adverse effects of these drugs, we aimed to investigate the role of a small polyphenolic compound, resveratrol (RES), best known as a constituent of grapes and wine. Objectives We used a monocytic cell line to assess the effect of RES in monosodium urate (MSU) and calcium pyrophosphate (CPP) crystal-induced inflammation. Methods THP-1 cells were stimulated with synthetic MSU (0.05mg/ml) and CPP (0.025mg/ml) crystals after a 3h priming with phorbol myristate acetate (PMA) (100ng/ml). Resveratrol was added to cultures at 10μM. Epigallocatechin-3-gallate (EGCG), an already known nutraceutic inhibitor of crystal-induced inflammation (1), was used as control at the same concentration. The cytokines IL-1β, IL-8 and TGFβ were determined in the culture supernatants by ELISA assays. To assess whether RES could interfere with crystal internalization, the phagocytosis index was calculated at different time points. These experiments were preceded by the evaluation of the role of phagocytosis on cytokine release by using cytochalasin D at 1μM. Results After the 3h of priming with PMA, THP-1 cells produced high basal levels of both IL-1β and IL-8 and these further increased after 24h treatment with MSU and CPP crystals. The addition of RES together with the stimulus lead to a marked decrease in IL-1β (3 fold and 5 fold in presence of CPP and MSU respectively) and IL-8 release (2 fold and 3 fold in presence of CPP and MSU respectively). The inhibition of the inflammatory response by RES was dose-dependent. As regards TGFβ, EGCG showed a greater inhibition with respect to RES which, in any case, showed a 1.7 and 1.5 fold inhibition when added to cultures simultaneously to CPP and MSU respectively. The kinetic study showed a rapid internalization of crystals. Within 24 hours 50% of crystals were actively phagocytized by the cells and RES did not show any inhibitory effect on crystal phagocytosis. Conclusions The results of this study highlighted the anti-inflammatory potential of resveratrol in crystal-induced inflammation. Although the possible mechanism by which resveratrol exerts its biological functions is under evaluation (using sirtuin inhibitors), the direct effect on the inflammatory outcome may have important implications in the prevention and treatment of crystal-related arthropathies. References Oliviero F, Sfriso P, Scanu A, Fiocco U, Spinella P, Punzi L. Epigallocatechin-3-gallate reduces inflammation induced by calcium pyrophosphate crystals in vitro. Front Pharmacol 2013;4:51 Disclosure of Interest None declared

Background Several studies show that work productivity is related to disease activity and functional ability in patients with axial spondyloarthritis (axSpA). Also socioeconomic status of patients can have an impact on the work productivity. However, these are studies in patients with sustained axSpA. Objectives Investigate work productivity and wheter there is a correlation with disease activity in Italian patients with early axSpA. Methods Baseline data was used of patients with BP (≥3 months, ≤2 years, onset 3.5)). Functional ability was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI; high ( Results Out of 51 patients 21 are male (41.2%), average age at onset back pain is 29.7 (±8.7) years, average duration of back pain is 12.9 (±8.7) months, 16 (31.4%) are HLA-B27+ and 48 (94.1%) have IBP. Average scores for BASDAI (4.5±2.6), ASDAS (2.3±1.0) and BASFI (1.7±2.1) are found. There are 16 patients doing only unpaid activities and 35 patients have paid jobs, of which 6 patients combine this with unpaid activities. On average patients work 36.4 hours/week, absenteeism is 8.3%, presenteeism 28.6% and WPL 33.7%. Presenteeism is statistically significant different between patients with paid (32.6%) and unpaid (18.6%) work. Absenteeism (paid; 7.9% and unpaid; 8.3%) and WPL (paid; 36.6% and unpaid; 25.6%) are not. A decrease in work productivity is seen with an increase in disease activity and functional ability. Correlations are found between disease activity (ASDAS/BASDAI) and absenteeism (β=6.08**/2.65**), presenteeism (β=16.04**/5.80**) and work productivity loss (β=18.86***/7.12***). Also functional ability and absenteeism (β=4.32***), presenteeism (β=4.62*) and work productivity loss (β=7.31***) are correlated. *p Conclusions Work productivity impairment is related to disease activity and functional ability in Italian patients with early onset of axSpA. Disclosure of Interest None declared

Background Several genes besides HLA-B27 have shown to confer a predisposition to develop of the disease and different clinical manifestations within the spectrum of spondyloarthritides (SpA). A specific polymorphism of the enhancer HS1.2A of the Ig Heavy 39 regulatory region was previously described as associated to autoimmune conditions such as rheumatoid arthritis, 1 systemic sclerosis 2 and systemic lupus erythematosus 3 , while no genes related to the regulation of the autoimmune response have been yet identified to be associated with SpA. Objectives To evaluate the frequency of polymorphisms in the enhancer HS1.2A of the Ig Heavy 39 regulatory region in patients with axial-SpA from two different italian cohorts, and to identify a correlation of this genetic factor with a specific phenotype or with a different clinical presentation of the disease. Methods We evaluated 153 patients from the Rheumatology Division of the Catholic University in Rome (Cohort 1) and 75 patients from the University of Padua (Cohort 2), for a total of 228 patients, all with a diagnosis of axial SpA according to the ASAS criteria. The patients were differentiated, according to their clinical phenotype, in ankylosing spondylitis, psoriatic spondyloarthritis, IBD-associated spondyloarthritis or undifferentiated spondyloarthritis. BASDAI, CRP and ASDAS-CRP were used to asses the inflammatory burden and the disease activity at the clinical presentation. Selective polymerase chain reaction of the region containing polymorphic HS1.2A alleles was performed 4 on all patients after informed consent and on 573 healthy subjects, matched for age, sex, and from the same geographical area, that were enrolled as control group. Results The frequency of allele *2 of the HS1.2A enhancer in SpA patients from both the Cohort 1 and the Cohort 2 was significantly increased compared to healthy controls [Cohort 1: 64.7% vs 40.8%, p Conclusions Our data show an association of SpA with the allele 2 of the gene enhancer HS1.2A, similarly for what already observed in other autoimmune diseases. The presence of this specific polymorphism of gene HS1.2A might be a marker of autoimmunity or a sign of possible B cell involvement in SpA. References Tolusso B et al., Ann Rheum Dis 2009 Frezza D et al., Ann Rheum Dis 2007 Frezza D et al., Ann Rheum Dis 2012 Giambra V et al., Gene 2005. Disclosure of Interest None declared

Background Monosodium urate (MSU) crystal deposition in joints promotes leukocyte infiltration and release of inflammatory mediators, in particular IL-1β. However, the induction of IL-1β production by MSU crystals requires a costimulus. Recently, we have demonstrated that serum and plasma are able to induce differently crystal-induced inflammation, hypothesizing that plasma proteins could play a role in triggering this inflammatory reaction. Afterwards, we have observed that factors with molecular weight (MW) >50 kDa contained in synovial fluid (SF) synergize with MSU crystals to induce an inflammatory response in mononuclear cells. Objectives The aims of this study were to investigate whether three of the high abundant proteins in SF with MW>50 KDa, i.e. Albumin (HSA) (MW: 66.5 KDa), Haptoglobin (Hp) (MW: 100 kDa) and Fibrinogen (F) (MW: 340 kDa), may provide help to MSU crystals in induction of inflammation, and to determine whether ATP is one of the involved etiologic agents. Methods MSU crystals were prepared by Denko9s method and sterilized by heating at 180°C for 2 h before each experiment. The human leukemic monocytic cell line THP-1 was stimulated for 24 h with MSU crystals (0.5 mg/ml) in the presence or absence of one of the three proteins. In some experiments apyrase (1 U/ml) was added to degrade extracellular ATP. Culture supernatants were tested by ELISA for IL-1β and IL-8 production. IL-1β mRNA was isolated from cells and analyzed by quantitative RT-PCR (qPCR). Results Exposure of THP-1 cells to MSU crystals or F (1 mg/ml) induced a moderate release of IL-8 (MSU: 211.66±32.00 pg/ml; F: 466.08±49.16 pg/ml), but not of IL-1β. Cotreatment of cells with MSU crystals and HSA or Hp (0.1 mg/ml) did not affect the cytokine production, while F led to a significantly enhanced IL-1β (71.15±5.64 pg/ml) and IL-8 (2649.62±55.91 pg/ml) secretion. HSA and Hp alone did not cause changes on the cytokine levels. qRT-PCR analysis indicated consistently increased IL-1β mRNA expression in THP-1 cells treated with fibrinogen compared with non-treated cells (49.75±3.54 fold); this was markedly amplified by MSU crystals (103.25±5.73 fold). IL-1β mRNA levels was not enhanced by crystals alone. Apyrase significantly reduced the secretion of IL-1β (20%) and IL-8 (47%) induced by costimulation with MSU and F. Conclusions This study shows that in the presence of MSU crystals, F but not HSA and Hp, induces an inflammatory response in mononuclear cells. F could account for the synergizing effect of SF with MSU in the gouty joint. This component increases the production and expression of pro-inflammatory cytokines, in particular of IL-1β and IL-8, and its effect may be in part mediated by extracellular ATP. This work is supported by FIRA foundation and IBSA foundation Disclosure of Interest None declared

Background Osteoarthritis (OA) is characterized by a progressive loss of articular cartilage, osteophyte formation, thickening of the subchondral bone, along with frequent signs of intraarticular inflammation with moderate synovitis (1). The role of inflammation in the pathogenesis of OA especially in its early phases is becoming increasingly evident (2). The role of calcium crystals (CC) in synovial inflammation and their significance in OA progression in this context continues to be debatable (3). Objectives The aim of this study was to evaluate the presence of CC in synovial fluid (SF) using ultrasensitive analysis with scanning electron microscopy (SEM) at early and later stages of symptomatic and radiographic knee OA (KOA). Methods Seventy-four consecutive outpatients with KOA, 35 (47.3%) of whose were in an early stage ( Results CC were detected by SEM in SF in 35.1% of the patients; a higher polymorphonuclear (PMN) percentage was found in these patients with respect to those without CC. On the basis of disease duration, the patients were subdivided into three groups (A 5 yrs). In group A, patients with CC had a higher number of SF WBC and percentage of PMN than those without. No significant findings were identified in groups B and C. PD resulted positive in 43.24% of all the patients, 62.5% of these were CC + by SEM. When KL I-II were compared to KL III-IV patients, a significant difference was found with regard to: disease duration (35.79±54.13 vs 82.19±74.90; p=0.0017), disability (929.19±218.47 vs 1117.35±259.11; p=0.0272), WOMAC total index (1244.69±302.82 vs 1362.46±338.53; p=0.0584) and the Lequesne index (8.60±2.46 vs 9.81±2.48; p=0.0367). PD positivity was significant in the patients with CC + KL I and II with respect to those without CC- (p Conclusions The sensitive SEM method used permitted us to identify CC+ in SF which were associated with an increased degree of joint inflammation (WBC and PMN) in early KOA. PD detected local inflammation in 62.5% of the patients with CC. Curiously, the PD decreased about 30%, in group C patients with CC. These data lead us to hypothesize that in patients with a longer disease duration the CC + have less pro-inflammatory properties. These results suggest that CC, which may be crucial in the early phase of OA pathogenesis, may play a role in inducing inflammatory reactions. References Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012;51:249-57 2. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!) Osteoarthritis Cartilage. 2013;21:16-21. Rosenthal AK. Crystals, inflammation, and osteoarthritis. Curr Opin Rheumatol. 2011;23:170-3. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5956

Background Among the main subsets of osteoarthritis of the hand (HOA): there are nodal OA (NOA) and erosive (EHOA). Although this last form affects most frequently middle-aged women only few data are still available on bone mineral density (BMD) of these patients. Objectives To study the prevalence of low BMD in patients with EHOA and NOA, who consecutively underwent phalangeal radiographic absorptiometry (pRA) in our outpatient clinic, compared to matched healthy subjects. Methods Two cohorts of subjects for a total of 76 patients fulfilling ACR criteria for hand OA were studied. Patients showing at least one erosion in interphalangeal (IP) joints were included in the EHOA group, while patients with erosions in the metacarpophalangeal joints were excluded. Patients were also evaluated for disease duration, number of affected active (swollen and painful or tender) joints (NAAC), radiographic in Kellgren & Lawrence score (RS), Body Mass Index (BMI) (kg/m2) was also calculated (Table 1). All the patients and 190 healthy subjects (N) (mean age 67.8±7.7 years) underwent pRA scanning at the 2nd, 3rd and 4th finger of the non-dominant hand by means of a monoenergetic X rays (60 kV) equipment (Alara Metriscan, Hayward, Ca, USA). BMD was estimated in the three middle phalanges and the average expressed as mineral mass/area (g/cm2). T and Z scores were also provided by the instrument using local reference data. The local Ethics Committee granted approval of the study protocol and all patients gave their informed consent. Results A reduction of BMD fitting osteopenia was found in 35% of patients with EHOA, 21% with NOA, and 43% of N (p=0.03, EHOA vs NOA), while osteoporosis affected 20% with EHOA, 28% with NOA, and 20% N. BMD was higher in EHOA with respect to both the NOA and N groups (p=0.025 and p Image/graph Conclusions Phalangeal BMD was higher in EHOA patients with respect to both N and NOA subjects. Joint erosion and inflammation do not appear to determine sufficient phalangeal bone loss to discriminate EHOA vs NOA. To a certain extent, higher mineral density could be explained by more pronounced osteoreparative processes in EHOA than in NOA. This issue needs further investigation to better understand the relationship between osteoarthritis and local osteoporosis and the possible interferences with instrumental evaluation. Disclosure of Interest None Declared

Background Psoriatic arthritis (PsA) is a progressive chronic inflammatory disease which affects both the axial and peripheral joints and often causes patient impairment; patients function and health-related quality of life could be compromised. Following the introduction of anti tumor necrosis factor-α (TNFα) agents in the treatment of active spondyloarthritis, several aspects including disease activity, spinal mobility, peripheral arthritis and enthesitis as well as quality of-life have improved considerably. Objectives The aim of this study was to evaluate the long-term efficacy of adalimumab and etanercept treatment in clinical practice in PsA patients and to assess the percentage of patients with progressive lengthening of therapy interval administration in the event of optimal treatment response. Methods A retrospective study was carried out on 127 PsA outpatients receiving adalimumab and etanercept treatment over a 4 year period (March 2003-October 2012) attending the Rheumatology Unit, University of Padua. Age, sex, onset age, disease and therapy duration were evaluated. The therapy efficacy was determined using the Bath Ankylosing Spondylitis Activity Score (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Health Assessment Questionnaire (HAQ), DAS28, the patient global assessment, the pain global assessment, the erytrocite sedimentation rate (ESR) and C-reactive protein (CRP). The percentage of patients in whom therapy interval administration was prolonged was also evaluated. Results One hundred twenty-seven patients (79 male 62.2 %; median age 50.14±11.81 yrs; mean disease duration 11.9±8.35 yrs; mean follow-up 52.3±24.92 months) were treated with etanercept and adalimumab (respectively 48.8% and 51.2%). Average baseline and of treatment values were: BASDAI 51.05±22.30 vs BASDAI 26.70±19.55 (p Conclusions A clinical, functional and bioumoral improvement was observed in both patients treated with adalimumab as well as etanercept. Treatment with anti-TNFα agents provokes a satisfactory prolonged, clinical response. It was possible to extend the interval between injections in a high percentage of PsA patients. Disclosure of Interest None Declared

Background Osteoarthritis (OA) is the most common joint disease and the knee is frequently involved. OA is characterized by a progressive loss of articular cartilage, osteophyte formation, thickening of the subchondral bone, but as well as some signs of intraarticular inflammation with synovitis. Multiple factors such as mechanical factors, genetics and aging are involved in the pathogenesis of OA. However there is still some debate about the role of inflammation in pathogenetic mechanisms of OA (1). Only a few studies have recently recognized the potential role of calcium crystals (CC) in synovial inflammation and in OA progression (2-4). The most common CC in OA are calcium pyrophosphate dihydrate (CPP) and basic calcium phosphate (BCP), including hydroxyapatite, octacalcium and tricalcium phosphate. Several studies demonstrated that CC occur in up to 60% of SF in OA patients. Although it is difficult to identify CC in SF of OA, the relationship between pathogenetic mechanisms or disease progression and the presence of CC is very interesting. Recognition of CPP, which range in length from 2-20 μm, is a relatively simple procedure. Nevertheless they are not always released in a uniform manner and it is not simple to detect them even when the most sensitive methods are been used in. Due to their sub-microscopic size BCP (70-250 A) detection is particularly difficult. Objectives The aim of the study was to identify CC in SF of OA patients through compensated polarized light microscopy (CPML) and alizarin red S staining (AS), and by ultrasensitive analysis with scanning electronic microscopy (SEM), to detect whatever concordance exists between them. Methods We analyzed the SF74 patients with knee osteothritis (KOA) (48 F, mean age 64.85±9.33, range 50-89 yrs) by CPML, AS and by SEM. The concordance between CPML and SEM was evaluated by Cohen’s kappa coefficient Results CPP crystals were found in 28.4% by CPML and in 32.4% by SEM. BCP crystals were suspected in 32.4% of the samples that were positive according to AS, while they we found by SEM in 10.8% of SF. By according to kappa coefficient, the concordance between CPML and SEM was 0.78% for CPP and 0.69% for BCP. CPP and BCP were simultaneously positive in 26% of the samples by SEM. Conclusions CPML and AS are tecniques routinely used to detect CC in SF of OA patients. However use of a highly sensitive method such as SEM, ensures accurate detection of CC and this could help to clarify the its potential role in pathogenetic mechanisms and in progression of OA. References AK Rosenthal. Crystls, inflammation, and osteothritis 2011;Curr Opin Rheumatol 23:170-3 S Nalbant, JAM Martinez, T Kitumnuaypong, G Clayburnet, M Sieck and HR Jr. Synovial fluid features and their relations to osteothritis severity: new findings from sequential atudies. Osteoarthritis and Cartilage 2003;11:54-4 GM McCarthy, HS Cheung. Point: Hydroxyapatite crystal deposition is intimately involved in the pathogenesis and progression of human osteoarthritis. Curr Rheumatol Rep. 2009;11:141-7. YZ Liu, AP Jackson and SD Cosgrove. Contribution of calcium-containing crystals to cartilage degradation and synovial inflammation in osteothritis. Osteoarthritis and Cartilage 2009;17:1333-40 Disclosure of Interest None Declared