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Objective Gout treatment is largely suboptimal in clinical practice. We aimed to assess the predictors of disease-activity at 12 months in a real-life setting. Methods Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre-cohort study. Only patients with clinical diagnosis of gout were eligible. Disease-activity was evaluated by the Patient Acceptable Symptom State (PASS) on a visual analogue scale (VAS, 0=unsatisfactory, 100=satisfactory) at 0 (T0) and 12 months (T12), and the composite score called Gout Activity Score (GAS) calculated on the number of arthritic attacks (flare count), serum uric acid (sUA), cumulative number of tophi, VAS (T12), PtGA (T12). Multivariate linear regression model was performed to assess predictors of gout disease-activity at T12 with PASS and GAS as outcomes. Results: 201 patients had gout (diagnosis on synovial fluid in 45%, tophi in 26%, mean sUA 7.4±1.9 mg/L, 85% with urate-lowering therapy (ULT) in progress/initiated at T0); mean age 63±13 years, 88% men, median (interquartile range) disease duration 2.9 years (0.7-9.4). Follow-up visits were performed in 113 (56%) patients at T12. Mean PASS observed at T0 and at T12 were 38±27 and 74±23, respectively, whereas GAS at T12 was 10±8. A significant association was observed between the presence of tophi and PASS at T12 (-15.3, 95% CI -25.5, -5.2; p=0.003) and GAS at T12 (+4.0, 95% CI 0.6,7.4; p=0.02), adjusted for age, sex, disease duration, sUA

Osteoarthritis (OA) most commonly affects knee joints, and the next most commonly affected sites are the hands and hips. Three distinct hand OA phenotypes have been described: erosive hand OA (EHOA), nodal hand OA - also known as non-erosive hand OA (non-EHOA) - and first carpometacarpal joint OA. EHOA predominantly affects women and is the most aggressive form of hand OA, characterized by a severe clinical onset and progression, leading to joint damage, disability and reduction of quality of life. Clinical signs of inflammation associated with EHOA include the acute onset of pain, swelling and redness. Moreover, EHOA is characterized by radiographic features such as central erosion, saw-tooth and gull-wing lesions and, rarely, ankylosis. The aim of this Review is to report the latest findings on epidemiology, clinical features, pathology and aetiopathogenesis, biomarkers, imaging modalities and treatments for EHOA. The ongoing development of new hand OA classification criteria should facilitate standardization between studies.

Patients with psoriatic arthritis (PsA) have an increased prevalence of obesity, but mechanisms underlying this association remain unknown and it is unclear if obesity is the cause or effect of PsA. For PsA patients, comorbid obesity may influence their clinical response to systemic treatment, and especially targeted immunomodulators such as anti-tumor necrosis factor (TNF)α. Weight gain has also been associated with anti-TNFα treatment. Consequently, modification of the therapeutic approach may be needed for patients with an inadequate response to TNFα inhibitors. In recent years, interleukin (IL)-12/IL-23 inhibitors have entered clinical practice as a new class of drug for the treatment of PsA, with some data suggesting a lower effect of body weight on their effectiveness. Recent findings demonstrate effective and sustained responses in patients with PsA to ustekinumab, an IL-12/IL-23 inhibitor. This narrative review critically discusses the link between PsA, obesity, and response to therapy. The current role of ustekinumab in this setting is also discussed.

Objective We aimed to assess the performance of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in an Italian cohort of patients with crystal-induced arthritis stratified by disease duration and gender in a real-life setting. Methods Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre cohort study by the Italian Society of Rheumatology which was designed to improve the management of crystal-induced arthritis (ATTACk). To test the performance of the criteria (sensitivity and specificity), the presence of monosodium urate (MSU) crystals in synovial fluid (SF) was used as gold standard. Subgroup analyses by gender and disease duration were performed. Results Two hundred and seventy-seven patients were enrolled. SF analysis was available in 137 (49%) patients. Complete SF analysis and ACR/EULAR scores were obtained in 44% of patients. MSU crystals were found in 66% of patients. The sensitivity and the specificity of all criteria sets were 78% (95%CI, 67–86) and 98% (95%CI, 87–100), respectively; only clinical criteria yielded 70% (95%CI, 59–80) sensitivity and 93% (95%CI, 80-98) specificity, respectively. In early-stage disease (

BackgroundLittle evidence is available about the impact of diet on disease activity of axial spondyloarthritis (axSpA). This study evaluated the impact of a 6-month nutritional advice based on the Mediterranean diet on the disease activity of axSpA.MethodsWe prospectively collected the information of a group of axSpA patients who were offered nutritional advice for a 6-month period, who were compared to axSpA patients followed at the same center who were not on a specific diet. A nutritionist gave suggestions for dietary modification at baseline and thereafter every 2 months until month 6. Adherence to the Mediterranean diet was evaluated with the PREDIMED questionnaire ranging from 0 (no adherence) to 10 (optimal adherence); disease activity was evaluated with ASDAS-CRP. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement (improvement ≥ 20% of each score).ResultsA total of 161 patients were included: 81 receiving nutritional advice and 80 controls; 47 in the nutritional group and 63 controls had complete information until month 6. Overall, 40 (36.4%) were females, the mean age was 51.7 ± 1.3 years, and 58 (52.7%) were affected with psoriasis. No relevant change of anthropometric or laboratory measures was observed in either group. Adherence to the Mediterranean diet was moderate (PREDIMED score 6.7 ± 1.8 at baseline; 7.6 ± 2.1 at month 6) and improved more in the nutritional group compared to controls (p= 0.020). Predictors of a PREDIMED improvement ≥ 20% were receiving nutritional advice (OR 4.53, 1.36–15.1,p= 0.014), age (per 10-year increase OR 1.05, 1.02–1.68,p= 0.007), and BMI (OR 0.77, 0.63–0.9,p= 0.006). An ASDAS-CRP improvement ≥ 20% was more frequent in the nutritional group compared to controls (p= 0.020). A PREDIMED improvement ≥ 20% was associated with a ASDAS-CRP improvement ≥ 20% (OR 6.75,1.8–25.3,p= 0.005). Psoriasis and disease duration were negatively but not significantly associated to the ASDAS-CRP improvement.ConclusionsImproving adherence to the Mediterranean diet may have a beneficial impact on the activity of axSpA. Patients with a lower BMI and older patients are more prone to modify their diet towards the Mediterranean diet following nutritional advice. Patients with psoriasis may have a limited benefit from dietary improvement.Study registrationProtocol No. 52723, Padova Hospital Medical Ethical Committee (October 11, 2010).

Axial spondyloarthritis (axSpA) is a group of debilitating, chronic, rheumatic conditions characterized by inflammation and new bone formation, mainly involving the spine and the sacroiliac joints. The lack of biomarkers in axSpA is well known. Despite significant treatment advances in recent years thanks to the introduction of drugs with a new mode of action, such as new biologic and targeted synthetic disease-modifying antirheumatic drugs, no relevant improvement in the identification of disease biomarkers has been achieved. Common parameters, such as erythrocyte sedimentation rate and C-reactive protein, which are routinely used to measure systemic inflammation, are the sole markers available to date and are not adequate to assess disease activity in all patients. The aim of this study is to review the most promising serum biomarkers that may help treatment decision in axSpA via a proper assessment of disease activity and identification of negative prognostic factors.

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

Background:Mediterranean diet (MD) proved to be beneficial on disease activity in patients affected by rheumatoid arthritis. A few data are available in other rheumatic conditions.Objectives:A prospective monocentric study was conducted to evaluate the effect of a nutritional intervention based on the MD and to investigate the impact of such modification on disease activity of axial spondyloarthitis (ax-SpA).Methods:Patients affected by ax-SpA randomized to a nutritional intervention arm (N) or a control arm (C) and were assessed at baseline (T0) and at month 6 (T6). Patients in N underwent a nutritional evaluation and received suggestions for dietary modification at T0, and then every 2 months. Adherence to the MD was evaluated with the PREDIMED questionnaire (range 0-10) [1]. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement at T6.Results:Eligible patients (161) were randomized to either N (81) or C (80); 47 in N and 63 in C completed the study. No relevant change of anthropometric or laboratory measures was observed at T6 in either group. A ≥20%PREDIMED improvement was more frequent in N (22/47, 46.8%) compared to C (13/63, 20.6%) (pConclusion:A nutritional intervention is effective in improving adherence to the MD in ax-SpA. A higher adherence to the MD may have a beneficial impact on activity of ax-SpA. Patients with psoriasis may have a limited benefit from the dietary improvement.References:[1]Martínez-González, M.A. et al. A 14-item mediterranean diet assessment tool and obesity indexes among high-risk subjects: The PREDIMED trial.PLoS One2012,7.Table 1.Characteristics of the patients.All patientsNutritionControlsAll patientsNutritionControlsBaselineMonth 6Females, n, (%)40 (36.4)18 (38.3)22 (34.9)Age, years, mean±SD51.7±1.353.0±1.349.6±1.3HLA-B27 positivity, n (%)58 (52.7)22 (46.8)37 (57.1)Psoriasis, n (%)58 (50.7)26 (55.3)32 (50.8)Disease duration (years), mean±SD15.3±9.715.7±1015±9.5Duration of b/tsDMARD treatment overall, years, mean±SD5±4.15.8±4.54.5±3.8NSAID, n (%)76 (69.1)30 (63.8)46 (73)csDMARD, n (%)14 (12.7)5 (10.6)9 (14.3)BMI, Kg/meters2, mean±SD26.5±5.426.5±4.326.6±6.126.4±5.326.3±426.6±6.1ASDAS-CRP, mean±SD2.1±12.1±0.92.1±12±1.11.8±0.92.1±1.2BASDAI, mean±SD37.6±2337.4±23.237.7±22.939.3±24.137.3±23.641.2±24.6BASFI, mean±SD20.5±21.421.6±19.219.7±2319.8±19.619.1±18.820.5±20.4BASMI, mean±SD1.6±21.9±2.21.4±1.71.8±2.11.9±2.41.7±1.9Tender joint count, mean±SD1.1±2.30.8±2.11.4±2.50.9±20.8±20.9±1.9Swollen joint count, mean±SD0.3±1.30.4±20.1±0.50.2±1.30.3±1.80.2±0.8Leeds Enthesitis Index, mean±SD0.2±0.80.3±10.2±0.61.1±21.3±2.21±1.8CRP, mg/L, mean ±SD3.4±6.23.2±3.93.7±7.43.5±5.62.6±3.14.1±6.9LDL-c, mg/dl, mean ±SD130.8±36.5132.3±35129.7±38.4130.6±34.7125.7±34.8134.4±34.5PREDIMED score, mean ±SD6.7±1.87±2.16.6±1.67.6±2.18.6±1.96.8±2b/tsDMARD biological/targeted synthetic DMARDs; csDMARD conventional DMARDs. PREDIMED questionnaire to assess adherence to the Mediterranean diet.Disclosure of Interests:None declared.

The study aimed to evaluate biomarkers facilitating early diagnosis of axial spondyloarthritis (axSpA) and correlations between them and disease activity parameters and imaging indexes. Patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early SPACE study underwent a physical examination, questionnaires, laboratory tests, X-rays and MRI of the spine and sacroiliac joints (SIJ). An expert rheumatologist formulated axSpA diagnosis in accordance with Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers using the SPARCC, mSASSS and NY-criteria. Patients were classified as: subjects with signs of radiographic sacroiliitis (r-axSpA), subjects with signs of sacroiliitis on SIJ-MRI but not on X-rays (nr-axSpA MRI SIJ+) or subjects with no signs of sacroiliitis on MRI/X-rays but with >2 SpA features and signs of bone oedema on MRI spine (nr-axSpA MRI SIJ-/undifferentiated SpA). Significant differences were found in the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ scores. Biomarker levels were not significantly increased in any of the patient groups. The correlations between IL-17 and IL-23 and other indices were not significant; correlations were found between IL-22 and BASFI, BASG1, HAQ, VAS pain, between mSASSS and MMP3, and between the latter and hsCRP. Although not significantly higher in any of the three groups, IL-22, MMP3 and hsCRP values were correlated with some disease activity indexes and with mSASSS. Large observational studies are required to confirm these preliminary findings.

The Osteoarthritis Quality of Life scale (OAQoL) is specific to individuals with osteoarthritis. The present study describes the adaptation of the OAQoL for use in the following five European languages: German, Hungarian, Italian, Spanish and Turkish. The study involved three stages in each language; translation, cognitive debriefing (face and content validity) and validation. The validation stage assessed internal consistency (Cronbach's alpha), reproducibility (test-retest reliability using Spearman's rank correlations), convergent and divergent validity (correlations with the Health Assessment Questionnaire, The Western Ontario and McMaster Universities Index of osteoarthritis and Nottingham Health Profile) and known group validity. The OAQoL was successfully translated into the target languages with minimal problems. Cognitive debriefing interviewees found the measures easy to complete and identified few problems with content. Internal consistency ranged from 0.94 to 0.97 and test-retest reliability (reproducibility) from 0.87 to 0.98. These values indicate that the new language versions produce very low levels of measurement error. Median OAQoL scores were higher for patients reporting a current flare of osteoarthritis in all countries. Scores were also related, as expected, to perceived severity of osteoarthritis. The OAQoL was successfully adapted for use in Germany, Hungary, Italy, Spain and Turkey. The addition of these new language versions will prove valuable to multinational clinical trials and to clinical practice in the respective countries.

Background: The 5-item Compliance Questionnaire for Rheumatology (CQR5) allows the identification of patients likely to be high adherers (HAs) to anti-rheumatic treatment (i.e. taking ≥80% of their medications correctly), or “low” adherers (LAs). An Italian version of the questionnaire was validated (I-CQR5) [1]. Objectives: The objective was to investigate what factors are associated with high treatment adherence according to I-CQR5 in RA patients treated with biologic DMARDs (bDMARDs). Methods: RA patients (with disease duration >1 year, undergoing treatment with ≥1 self-administered biological disease-modifying anti-rheumatic drug (bDMARD), willing and capable of completing the questionnaire unaided) were enrolled in the study. I-CQR5 were anonymous and clinical data were collected from the local database. Factors included were demographic, social characteristics of the patients, clinical and treatment variables. Factors achieving a p Results: Among 604 RA patients, 193 patients were included in the validation analysis. Median age of the patients was 57 years (46-65), 142 (73.4%) were females, median disease duration was 15 years (9-21); 82 (42.7%) patients were treated with low dose bDMARDs; 174 (91.1%) patients were in low disease activity or remission (Fig.1). HAs were 40.9% (79/193) of patients: 100% (193/193) of patients treated with bDMARDs and 22.4% (57/193) of those treated with bDMARDs in combination with conventional synthetic DMARDs. Female gender, no employment, lower education level, positive Rheumatoid Factor and/or Anti-Citrullinated Peptides Antibodies, low bDMARD dose, higher patient-VAS were significantly more frequent in LAs compared with HAs. In the multivariate analysis, employment was also positively and significantly associated with high adherence: OR 2.89 (1.3-6.44), p=0.009 (Tab.1). Conclusion: As previously reported only one third of RA patients treated with bDMARDs were found to be HAs to treatment according to the I-CQR5. Employment status was the major determinant, increasing by almost 3-fold the likelihood of being adherent. Education level and female gender might be also taken into account as factors influencing treatment adherence. Reference: [1] Ometto F., et al. Treatment adherence in rheumatoid arthritis italian patients using a validated version of the 5-item compliance questionnaire for rheumatology (I-CQR5). EULAR18-4294. Disclosure of Interests: None declared

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.

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 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 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.

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.

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.

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

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

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.

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.