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Sol-gel and gel-sol thermal transition of methylcellulose/water, kappa-carrageenan/water and methylcellulose/kappa-carrageenan/water mixtures was investigated utilizing small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) and oscillatory rheological experiments in temperature regime from 20 to 80 degrees C. Methylcellulose (E461) and kappa-carrageenan (E407) are well-known additives used for gelation in various nutrition and other products. The formulation and characterization of a mixed thermoreversible methylcellulose/kappa-carrageenan/water gel with very interesting double thermal transition gel-sol-gel upon heating was possible. This specific thermal behavior provides a liquid state of the system between the low-temperature and high-temperature gel-state and at the same time allows for the easy temperature tuning of the system's state. As such this system is suggested to be further tested as potential carrier for various functional colloidal systems.

The effects of different therapies on enthesitis/osteitis in active ankylosing spondylitis (AS) were evaluated by magnetic resonance imaging (MRI). The aim was to assess the role of quantitative MRI in the evaluation of AS treatment efficacy.Thirty patients with active spondylitis or bilateral sacroiliitis were selected and followed up for 1 year. Ten of the patients were treated only with non-steroidal anti-inflammatory drugs, 10 patients additionally received at baseline an intravenous pulse of glucocorticoids and 10 patients were treated with regular infusions of infliximab. Disease activity was measured according to clinical instruments and laboratory tests. For each patient, one selected inflamed lesion was followed from baseline through control visits quantitatively by diffusion-weighted imaging (DWI) measuring the apparent diffusion coefficient (ADC) and by dynamic contrast-enhanced imaging (DCEI) with evaluation of the enhancement factor (f(enh)) and enhancement gradient (g(enh)).Clinical and quantitative MRI parameters diminished significantly with regression of the inflammatory activity. The improvement in AS was most pronounced in patients treated with infliximab; after 12 months the ADC diminished from an average of 1.31 to 0.88 x 10(-3) mm(2)/s, f(enh) from 1.85 to 0.60, and g(enh) from 3.09 to 1.40 %/s.Diffusion-weighted imaging and DCEI were shown to be effective in quantifying changes in inflammation in skeletal lesions during the treatment of AS, and could therefore be convenient for assessing treatment efficacy. To the best of our knowledge this is the first time DWI was used to evaluate the activity of skeletal inflammation in rheumatic diseases such as AS.

Background Permanent visual loss, one of the most severe ischemic complications of giant cell arteritis (GCA), affects 6% of patients at our secondary/tertiary rheumatology center despite a fast track GCA diagnostic procedure. Objectives To determine potential clinical and laboratory markers forecasting visual complications in GCA. Methods We performed a paper chart review of GCA cases diagnosed between 01.09.2011 and 31.12.2014. Descriptive statistics was used to describe our cohort and appropriate post hoc tests to compare characteristics of patients with/without visual complications. Results During the 40-month observation period, 83 new GCA cases (70% female) were identified. The median (interquartile range (IQR), range) symptom duration at presentation was 30 days (IQR 14-78 days, range 2-880). 28 patients (33.7%) reported of visual symptoms: blurred vision (16), diplopia (8), amaurosis fugax (5); permanent visual loss (5; all unilateral; in 1 patient after glucocorticoids), and ptosis (1). Conventional cardiovascular risk factors: obesity, arterial hypertension, hyperlipidemia, diabetes mellitus were not associated with visual complications in our cohort. Visual manifestations were significantly more common in patients with permanent atrial fibrillation (AF) (p=0.027). 80% of patients with AF were on anticoagulants. The mean erythrocyte sedimentation rate (69 vs 85 mm/h; p=0.007), C reactive protein (31 vs 93 mg/l, p=0.011) and platelet count (372 vs 405×10 9 /l, p=0.001) were lower in patients with visual symptoms than in those without them. Antiphospholipid antibodies were not associated with visual symptoms. Conclusions Visual complications were significantly more common in patients with AF which has so far not been reported. The presence of the conventional cardiovascular risk factors, antiphospholipid antibodies seem not to contribute to visual complications. Disclosure of Interest None declared

Background Smoking is a negative predictor of response to antirheumatic therapy. Objectives To assess whether smoking influence the response to rituximab (RTX) in Rheumatoid Arthritis (RA). Methods Pooled data from the Collaborating European Registries for RTX in RA (CERERRA) were used. Patients who received at least 1 cycle with RTX were included. Smoking status was defined as smokers (current smokers) and non-smokers (never and ex-smokers). Analysis of co-variance (ANCOVA) was performed with DeltaDAS28 at 6 months as the dependent variable and smoking status as well as other baseline variables (age, sex, disease duration, number of prior biologic DMARDs) as covariates. Separate analyses were made for anti-CCP positive and negative patients. Results A total of 2274 patients were included - 1815 (80%) non-smokers and 459 (20%) smokers. 81% were female and 80% (out of 1199 patients with available anti-CCP) were anti-CCP positive. Smokers had shorter disease duration than non-smokers (median (IQR) 8 (4-13) years vs. 10 (5-16), p Smokers had less improvement in disease activity than non-smokers at 6 months (mean ± SD DeltaDAS28 -1.5±1.7 vs. -1.8±1.7, respectively, p=0.04). However, the difference was no longer significant after adjustment for baseline differences (p=0.40). When the analysis was stratified by anti-CCP status, smoking did not influence the response to therapy in the anti-CCP negative subset (p=0.39) but there was a trend in the anti-CCP positive subset (p=0.06, figure 1). For the anti-CCP negative patients, 67% of non-smokers and 69% of smokers achieved EULAR response (p=0.6), while in the anti-CCP positive the respective response rates were 76% among non-smokers and 70% among smokers (p=0.09). Conclusions Smoking was negatively associated with the response to rituximab therapy in RA patients who were anti-CCP positive. References Khan A. et al. Smoking, rheumatoid factor status and responses to rituximab. Ann Rheum Dis 2012;71:1587-1588 doi:10.1136/annrheumdis-2012-201758 Saevarsdottir S. et al. Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedis Reumatology register cohorts. Arthritis Rheum 2011;63:26–36. Chatzidionysiou K. et al. Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed. Pooled data from 10 European registries. Ann Rheum Dis 2011;70:1575–80. Disclosure of Interest K. Chatzidionysiou: None declared, E. Lie: None declared, E. Nasonov: None declared, G. Lukina: None declared, M. Hetland: None declared, E. Hauge: None declared, K. Pavelka Consultant for: MSD, AbbVie, Pfizer, Roche, BMS, C. Gabay Grant/research support from: Roche, Merck, Abbvie, Consultant for: Roche, Abbvie, Pfizer, BMS, Sanofi-Aventis, Merck, AB2 Bio, D. Nordstrom Consultant for: AbbVie, BMS, MSD, Pfizer, Roche, UCB, H. Canhao: None declared, M. Tomsic: None declared, P. van Riel: None declared, J. Gomez-Reino: None declared, I. Ancuta: None declared, T. Kvien: None declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, S. Saevarsdottir: None declared

Background The optimal strategy to use biologic DMARDs (bDMARDs) after rituximab (RTX) in RA is unknown. Objectives To evaluate the effectiveness of switching to alternative modes of action (i.e. tumor necrosis factor alpha inhibitor (TNFi), abatacept (ABA) or tocilizumab (TCZ)) after RTX discontinuation. Methods Patients of the prospective, longitudinal and multinational CERERRA (European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) database were analyzed with respect to the effectiveness of TNFi, ABA or TCZ as a new bDMARD after RTX. Patients were included, if they had stopped RTX no longer than 6 months prior to the new bDMARD, had a baseline visit within 21 days of commencement of the new bDMARD, and at least 1 follow up visit. Baseline characteristics were compared across bDMARD classes. The effectiveness of the new bDMARD was assessed by the decline in DAS28-ESR and CDAI after 6 months follow up. Multivariable linear regression was used to adjust for potential confounders. EULAR response rates after 6 months were compared for the treatments and drug discontinuation rates were calculated by the Kaplan-Meier method and compared across bDMARD classes. Results The demographics and baseline disease characteristics as well as the use of concomitant methotrexate, leflunomide, or other sDMARDs were similar between the treatment groups. At baseline, the median DAS28-ESR was 5.7 (IQR 4.8-6.6) among all patients and was similar across treatment groups (p=0.97). Patients on TCZ had a significantly greater decline of DAS28-ESR, than patients on TNFi or ABA after 6 months (Figure 1A). After adjusting for age, sex, baseline prednisone use and the number of previous bDMARDs, the average decline was 1.0 (95% CI 0.2-1.7) units smaller in patients on TNFi and 1.8 (95% CI 1.0-2.5) units smaller in patients on ABA compared to patients on TCZ. The median CDAI in all patients was 25.1 (IQR 17.6-34.9) at baseline and was similar across the three treatment groups (p=0.41). The greatest decline was present in the TCZ group (Figure 1B). After adjusting for age, sex, baseline prednisone use and the number of previous bDMARDs, the average decline was 9.4 (95%CI 1.7-16.1) units smaller in patients on TNFi and 8.1 (95%CI 0.9-15.3) units smaller in patients on ABA compared to patients on TCZ. Six months after the commencement of the new bDMARD, 34% of all subjects had a good EULAR response, 39% had a moderate response and 27% no response. The rates of EULAR responses varied significantly between treatment groups (p The HAQ-DI improved in all treatment groups (p Conclusions The results of this multinational cohort suggest that in clinical practice IL-6 blockade may be superior to alternative bDMARD classes following RTX discontinuation and represents a feasible strategy in the attainment of remission or low disease activity using a treat-to-target approach. Disclosure of Interest U. Walker Consultant for: AbbVie, BMS, MDS, Pfizer, Roche, UCB, V. Jaeger: None declared, K. Chatzidionysiou: None declared, M. Hetland: None declared, E.-M. Hauge: None declared, K. Pavelka Consultant for: MSD, AbbVie, Pfizer, Roche, BMS, D. Nordstrom Consultant for: AbbVie, BMS, MSD, Pfizer, Roche, UCB, H. Canhao: None declared, M. Tomsic: None declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, C. Gabay Grant/research support from: Roche, Merck, Abbvie, Consultant for: Roche, Abbvie, Pfizer, BMS, Sanofi-Aventis, Merck, AB2 Bio

Background Determining the cause of a cerebrovascular event (CVE) can greatly influence further management of the patient. Testing for hypercoagulable states is an important part in etiologic evaluation, which comprises also testing for antiphospholipid antibodies (aPL). Objectives The primary aim was to determine the frequency of patients experiencing CVE and fulfilling the criteria for antiphospholipid syndrome (APS) [1] or non-criteria APS (when persistently positive for non-criteria aPL against anti-cardiolipin (aCL) IgA, anti-β 2 glycoprotein I (anti-β 2 GPI) IgA, anti-phosphatidylserine/prothrombin (aPS/PT) and/or anti-annexinV (aANXV) - all isotypes). The second aim was to determine whether persistence of aPL-positivity is a risk factor for experiencing an episode of CVE. Methods Eighty-nine consecutive patients (mean age 48 years, range 18-67) with acute CVE (transitory ischemic attack, ischemic cerebrovascular insult or venous sinus thrombosis) were prospectively followed for one year after the index event. In the comparative group, there were 25 patients with migraine (mean age 40 years, range 18-58) and 20 patients with Huntington9s disease (mean age 53 years, range 32-67 years). Demographic data on smoking, hypertension, hyperlipidemia, diabetes and the use of oral contraceptives were obtained by an interview and examinations. For all patients at least two sera taken 3 months apart were tested for lupus anticoagulants, aCL, anti-β 2 GPI, aPS/PT and aANXV of IgG, IgM and IgA isotypes [2-5]. Data were analysed with multiple logistic regression model. Results We found that 20/89 (22%) CVE patients were persistently positive (at least twice, with the first testing not earlier than 3 months after CVE) for one or more isotypes of tested aPL, 17/20 had criteria aPL and 3/20 non-criteria aPL; comparing to 3/45 (7%) positive in comparative group. Using TOAST CVE classification [6] with aPL, the cause of CVE could be consecutively explained in 16% of the patients with formerly unexplained CVE (Figure 1). We found significant association between persistently present aPL (of any class or isotype) and CVE (cumulative OR 4.62; 95% CI 1.09 to 19.66). Among other risk factors, only hypertension and hyperlipidemia showed a significant association with CVE (OR 4.31; 95% CI 1.33 to 13.92 for hypertension and OR 15.23; 95% CI 4.13 to 56.15 for hyperlipidemia). Conclusions aPL are one of the possible etiologic factors for CVE. In our group of patients 16% of formerly unexplained CVE could be explained with the persistent presence of aPL (as required to fulfill the APS criteria). Furthermore, aPL are not only a diagnostic parameter, but they themselves represent an independent risk factor for thrombosis. They should be tested, especially in cases without other recognized common etiologic factors for CVE. References Miyakis S, et al. J Thromb Haemost 2006; 4: 295-306. Brandt JT, et al. Thromb Haemost 1995; 74: 1185-90. Cucnik S, et al. Clin Chem Lab Med 2000; 38: 777-783. Avcin T, et al. Rheumatology 2001; 40: 565-573. Zigon P, et al. Clin Chem Lab Med 2011; 49: 1011-1018. Adams HP Jr, et al. Stroke 1993; 24; 24: 35-41. Disclosure of Interest None declared

Background Serum cryoglobulins (SC) may be found in many diseases (1), and the presence of serum cryoglobulins is a known risk factor for lymphoma evolution in some non malignant diseases. Objectives The aim of this study was to distiguish the role of cryoglobulinemic vasculitis (CV), classified according to the recent validated criteria (1,2), and primary Sjogren9s syndrome (pSS) as risk factors of lymphoma in patients positive serum cryoglobulins. Importantly, SC, CV and pSS may occur together. Methods 950 charts from consecutive patients with positive SC were evaluated. Patients carrying both pSS and HCV infection, as well as incomplete charts, were excluded. Results 657 patients with SC were selected, 374 with CV and 283 without CV, according to the published criteria (2,3). PSS, classified according to the American-European Group Criteria was present in 96 patients (44 with CV, 52 without). Lymphoma was reported in 61/657 (9.8%) patients with SC. Among them, CV was present in 44/61 (72,1%; 14 also with pSS), and pSS in 17/61 (27,9%; and 14/17 had CV). Patients with SC with CV showed an higher prevalence of lymphoma than patients with SC without CV (44/374, 11.5% vs.17/283, 6.3%; p=0.025, OR=1.93 [95%IC: 1.08-3.39]. Patients with pSS, SC and CV also showed a higher prevalence of lymphoma than patients with pSS, SC but without CV (14/44, 31.8% vs. 3/52, 7.4%; p=0.001, OR=7.62 [95%CI 2.02-28.74]. CV and pSS were confirmed as independent risk factor for lymphoma by multivariate analysis (OR 2,18 95%CI 1,18-3,83, p=0,012; OR 2,65 95%CI 1,04-6,76, p=0,042, respectively). Infection by the hepatitis C virus (HCV) was detected in 467/561 (83,2%) patients with SC without pSS, and did not statistically predispose to lymphoma when associated with CV in this subset (p=1,0). Conclusions Cryoglobulinemic vasculitis and pSS are independent risk factors for lymphoma in patients with evidence of SC. Patients with both the conditions (CV and pSS) have the highest risk. In the follow-up of SC positive patients, a very high attention should be deserved to pSS, in particular when CV is present. References De Vita S, et al. Ann Rheum Dis. 2011; 2) Quartuccio L, et al. Rheumatology (Oxford). 2014 Disclosure of Interest None declared

ObjectivesTo assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design.MethodsInclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures.Results63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; −24.0±5.2% vs −7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs −7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases.ConclusionsThe comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.

Background Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) are strongly correlated with lupus anticoagulant. A Task Force of scientists at the International Congress on Antiphospholipid Antibodies (APLA 2010) accepted that aPS/PT would potentially contribute for a better identification of antiphospholipid syndrome (APS). Accordingly,we carried out an Initial and a Validation retrospective, cross-sectional multi-centre study on aPS/PT. Objectives To ascertain the value of aPS/PT for APS diagnosis. Methods We conducted an initial study involving 8 centres from 7 countries.Demographics and clinical/laboratory data were retrospectively collected.A sample from the subjects was prepared at each institution.Specimens were blinded and determination of IgG aPS/PT performed at Inova Diagnostics, Inc.USA (Inova) using ELISA kits from two manufacturers:Medical and Biological Laboratories Co Ltd, Japan (MBL) and Inova.After completing the initial study, a Validation study with a new sample of subjects (5 different centres from 5 countries) was carried out using the same methodology. Results The Initial study comprised 247 subjects.Statistically significant correlation in the IgG aPS/PT values was obtained with both ELISA kits (r=0.827, p Conclusions The performance of IgG aPS/PT using Inova and MBL ELISA kits is reliable. IgG aPS/PT detection is an easily performed laboratory parameter that may help in the diagnosis of APS. Acknowledgements The authors want to acknowledge the contributions of the late Prof. Silvia Pierangeli, University of Texas Medical Branch, Galveston, TX, USA Disclosure of Interest O. Amengual: None declared, R. Forastiero: None declared, M. Sugiura-Ogasawara: None declared, K. Otomo: None declared, O. Kenji: None declared, C. Favas: None declared, J. Delgado Alves: None declared, P. Žigon: None declared, A. Ambrožic: None declared, M. Tomsic: None declared, I. Ruiz Arruza: None declared, G. Ruiz Irastorza: None declared, M. Bertolaccini: None declared, G. Norman Employee of: Inova Diagnostics, Inc, San Diego, CA USA, Z. Shums: None declared, A. Jiro Employee of: Medical and Biological Laboratories, Co. Ltd, A. Murashima: None declared, A. Tebo: None declared, M. Gerosa: None declared, P. Meroni: None declared, I. Rodriguez-Pintό: None declared, R. Cervera: None declared, J. Swadzba: None declared, J. Musial: None declared, T. Atsumi Grant/research support from: Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Bristol-Myers Squibb Co., Astellas Pharma Inc., Daiichi Sankyo Co., Ltd. and Mitsubishi Tanabe Pharma Co., Speakers bureau: Astellas Pharma Inc. and Mitsubishi Tanabe Pharma Co.

Background IgA vasculitis (IgAV) is commonly marginalized disease in adults. Clinical data are scarce and mostly limited to patients with significant renal disease. Predictors of severity in acute adult IgAV are unknown. Objectives To create a simple semi-quantitative score predicting the severity of adult IgAV and to aid the management of adult IgAV. Methods We performed a paper chart review of adult, histologically proven IgAV cases, diagnosed between 01.01.2010 and 31.12.2014 at our secondary/tertiary rheumatology center. The disease activity was assessed using BVAS-3. Predictors of severe disease were identified and an IgAV severity score (IgAVSS) was constructed. Results During the 60-month observation period, 129 new IgAV cases (58% male) were identified. The median (interquartile range (IQR), range) age was 64.2 (40.4–77.3, 18-92) years. Skin, gastrointestinal (GI), renal and joint involvement was present in 129 (purpura limited to lower limbs in 54.3% and generalized above waist in 45.7%), 48 (severe in 13), 65 (severe in 16) and 58 patients, respectively. Males and patients with generalized skin purpura had more severe disease (p=0.019 for male vs. female gender and p=0.0005 for generalized vs. limited purpura). Patients aged 45–75 years had more commonly severe GI and severe renal disease than younger ( 75) ones (38.5% vs 31.6% vs 12.5% in case of severe GI disease and in 40.9% vs 9.5% vs 22.7% in case of severe renal disease respectively). The IgAVSS was constructed by assigning weights to patient age, gender and extent of purpura at presentation. It is a simple sum of the three domains (Table 1A). IgAVSS rendered good delineation between mild uneventful and severe IgAV when the cut off was set at ≥1.5 points. The difference in BVAS-3 between IgAVSS Conclusions Gender, patient age and extent of purpura predict the severity of adult IgAV. We propose a semi quantitative score the IgAVSS which is calculated based on clinical characteristics only as a decision making aid to the physician in a busy outpatient clinic setting to distinguish patients who might have a more severe disease requiring hospital management from those who can be managed on the outpatient basis. Disclosure of Interest None declared

Background Studies on antiphospholipid antibodies (aPL) have mainly focused on the IgG and IgM isotypes, with only a few on the pathogenic significance of IgA aPL. Positive IgA anticardiolipin (aCL) and IgA anti-β2glycoprotein I (anti-β2GPI) were reported to be predominantly associated with other aPL, making it difficult to understand the role of IgA alone [1]. Recently, antibodies against phosphatidylserin/prothrombin (aPS/PT) IgG and IgM have been indicated as a potential marker for antiphospholipid syndrome (APS) [2, 3]. Our previous study reported that IgG and IgM aPS/PT showed highest association with lupus anticoagulant (LA) activity of all tested aPL [3], while no studies to date have investigated possible clinical benefits of IgA aPS/PT. Objectives To determine the prevalence of IgA aPS/PT in patients with systemic autoimmune diseases and evaluate their association to thrombosis and obstetric complications. Methods We examined 254 patients with systemic autoimmune diseases: 91 APS, 40 APS secondary to systemic lupus erythematosus (SLE), 47 SLE, 57 rheumatoid arthritis (RA) and 19 Sjogren9s syndrome (SS) patients for LA, aCL, anti-β2GPI and aPS/PT (for IgG, IgM, IgA isotypes) [4]. 55 subjects experienced arterial thrombosis (AT), 60 venous thrombosis (VT) and 54 obstetric complications (OC). Results An overall prevalence of 63/254 (25%) was found for IgA aPS/PT in our cohort of patients. IgA aPS/PT were statistically significantly associated to both AT and VT (p=0.026 and p=0.002, respectively), however no association was found to OC (p=0.534). 19/63 (30%) patients were solely positive for IgA aPS/PT and negative for IgG or IgM aPS/PT. Five of these patients (3 SLE, 1 RA and 1 SS) were concomitantly negative also for LA, aCL and anti-β2GPI. One of the solely positive IgA aPS/PT patients experienced AT, while the other four showed no clinical manifestations significant for APS. IgA aPS/PT showed significant association with LA activity (p Conclusions IgA aPS/PT presented an independent risk factor for thrombosis, and highly correlated to LA activity. Larger studies are needed to confirm whether IgA aPS/PT testing could contribute to the assessment of thrombotic risk, especially in “seronegative” APS patients. References Bertolaccini ML et. al., Autoimmunity reviews. 2014;13(9):917-30. Sciascia S, et al. Thrombosis and haemostasis. 2013;111(2). Zigon P, et al. Clinical and Developmental Immunology. 2013;2013:8. Zigon P, et al. Clin Chem Lab Med. 2011, 49:1011-1018 Disclosure of Interest None declared

Background Glucocorticoids remain the gold standard treatment for giant cell arteritis (GCA). However, the relapses and recurrences in GCA are frequently reported. Objectives To determine the effectiveness of standard GCA treatment at the single secondary/tertiary rheumatology center. Methods We prospectively followed patients diagnosed with GCA between 01.09.2011 and 31.08.2014 at our center. Follow up visits with predetermined clinical and laboratory tests were performed 12, 24, 48 and 96-weeks after diagnosis. All patients who completed at least the first follow up visit were included in the analysis. All patients were treated in line with the EULAR recommendations (Ann Rheum Dis 2009;68:318-23). In short, patients with uncomplicated GCA were treated with initial oral methylprednisolone (MP) 32–48 mg qd, while the patients with ischemic complications or involvement of large vessels first received MP 250 mg on 3 consecutive days intravenously. MP tapering was started 2–4 weeks after treatment initiation slowly to 4 mg qd which was continued for at least 1.5 years. In patients who relapsed during the MP tapering unscheduled visits were arranged and treatment was adjusted. A patient was said to have a relapse if symptoms or signs characteristic of GCA reoccurred or an increase of markers of inflammation that could not be explained by another disease was noted. Results During the observation period 71 (72% female) new GCA cases were identified, with a median (IQR) age 73.1 (67.0–77.1) years and symptom duration 30 (14–84) days. One patient died of cancer during the initial diagnostic work-up, 1 refused the treatment and 1 was lost to follow up. The remaining 68 (95.8%) patients were followed for a median (IQR) 63 (49–111) weeks. During the follow up 29/68 patients relapsed based on clinical (5/29), laboratory (14/29), both clinical and laboratory (10/29) findings. None of the patients suffered visual loss at relapse. Median (IQR) time to relapse was 26.6 (13.4–26.6) weeks. Median (IQR) MP dose at relapse was 6.5 (4.0–12.5) mg. Patients who relapsed had a significantly higher systemic inflammatory activity at baseline (Table 1). Treatment adjustments in patients who relapsed included a temporary increase of MP dose (29/29), and add-on therapy with leflunomide 20 mg qd (15/29) or weekly methotrexate (2/29). Conclusions Even in the short term the glucocorticoids in monotherapy might be inadequate for a sustained remission in GCA. Disclosure of Interest None declared

Background Influenza is a frequent infectious disease affecting more than 20% of the world population yearly. It can cause severe complications in patients with autoimmune inflammatory diseases, such as rheumatoid arthritis (RA). In immunocompromised patients vaccinations are especially recommended. Influenza vaccines are generally safe and effective. However, RA patients require cautiousness in terms of vaccine immunogenicity especially when treated with immunomodulatory drugs. Objectives To determine the immunogenicity of a seasonal influenza vaccine in RA patients, its timeline and the influence of different medications on patients9 immune response. Methods 137 RA patients (38 males, 99 females, median age 33) and 54 healthy controls (HC; 11 males, 43 females, median age 54) were vaccinated with trivalent seasonal influenza vaccine (Sanofi Pasteur) containing purified haemagglutinins A/Brisbane/59/2007 (H1N1), A/Brisbane/10//2007 (H3N2), B/Brisbane/60/2008 (B). Sera were collected just before vaccination (baseline), 18-90 days and >180 days after vaccination. Measurement of antibodies against surface membrane proteins was performed using haemagglutination inhibition (HI) tests, while detection of antibodies against inner viral proteins of influenza A and influenza B viruses was tested by IgG and IgA ELISA. Results Using HI test, at baseline, RA patients were seroprotected (antibody titres ≥40) against seasonal influenza viruses A(H1N1), A(H3N2) and B in 58% (79/137), 97% (133/137) and 90% (123/137) respectively, versus 74% (40/54), 100% (54/54) and 83% (45/54) in HC. At the time of vaccination the IgG and IgA titres against inner proteins of influenza A and B viruses tested with ELISA showed a distinct elevation in the vaccinated (HC and RA) vs. non-vaccinated groups. After vaccination, significantly increased median titres of HI for A (H1N1), A (H3N2) and B were observed in controls and in RA. Compared to adalimumab, etarnercept, tocilizumab, infliximab, methotrexate and leflunomide, rituximab-treated patients had the lowest % of patients with of HI elevation for all three antigens (44%, H1N1; 22% H3N2, 50% B), which confirmed previous seasonal flu vaccination data (1). Seroconversion (postvaccination antibody titers ≥40 in patients whose prevaccination titres were 180 days. Similarly, the seroresponse (seroconversion or fold increase in antibody titers ≥4 in patients whose prevaccination titers were ≥10) in RA patients did not persist >180 days. Conclusions The seroresponse observed in RA compared to controls was higher for A (H1N1) but not for A (H3N2) and B. We found that vaccination largely tilts the balance from negative ELISA IgG and IgA titres to positive titres in those RA patients who respond with H1N1 >4-fold titre elevation. The immune responses (for all antigens tested) of treated RA patients are higher than non-treated patients for all medications used, except rituximab. References Eisenberg R.A. et al. Rituximab-treated patients have a poorer response to influenza vaccination. J Clin Immunol. 2013 Feb; 33(2):388-396. Disclosure of Interest None declared

Small-angle X-ray scattering technique has been used to study the structural properties of the quaternary microemulsion Tween 40®/Imwitor 308®/isopropyl myristate/water and of five-component system obtained by the addition of the drug ketoprofen to the original quaternary system. The results enlighten the structuration of the studied systems and represent new complementary findings to the previous study [Podlogar, F., Bester-Rogac, M., Gasperlin, M., 2005. The effect of internal structure of selected water–Tween 40 (R)–Imwitor 308 (R)–IPM microemulsions on ketoprofene release. Int. J. Pharm. 302, 68–77] on the correlation between the structuration of these systems and the release rates of the ketoprofen. The present results indicate that in the samples with the moderate to high concentration of water where the latter is a continuous phase the addition of smaller amounts of the ketoprofen does not change their inner structuration significantly. The quaternary sample containing 46.2 wt.% of water seems to be very near the composition where the transition from the bicontinuous to the lamellar structure of the microemulsion occurs. In the samples containing from 46.2 to 62.7 wt.% of water the swelling of lamellar phases with constant thickness of double-layer can be characterized. At approximately the latter composition another noticeable transition in the inner structuration of the microemulsion has been observed. Interestingly, all these changes in the inner structuration of the studied systems did not affect the trend of the drug release rates in this regime of water concentrations.

With the broad employment of immunosuppressive therapy, the incidence of Pseudallescheria boydii infections is rising. We report a first case of the localized subcutaneous P. boydii infection in a patient with microscopic polyangiitis. Favorable outcome related to the treatment with voriconazole adds to the growing body of evidence supporting the use of this particular agent in P. boydii infections.

Objectives. To reveal typical ultrasonographic (US) changes in major salivary glands associated with Sjogren's syndrome (SS) and to determine the diagnostic value of a novel US scoring system. Methods. In 218 consecutive patients with suspected SS, US of both parotid and submandibular salivary glands was performed besides the regular diagnostic procedure following the American-European Consensus Group criteria of 2002. Five US parameters were assessed: echogenicity, inhomogeneity, number of hypoechogenic areas, the hyperechogenic reflections and clearness of the borders of the salivary gland. The grades of these five parameters for all four salivary glands were summed. The final US score ranged from 0 to 48. Results. SS was established in 68 patients. The remaining 150 subjects, in whom SS was not confirmed, constituted our control group. All five US parameters were significantly associated with SS. The patients with SS had significantly higher US scores than those not diagnosed with SS (P< 0.01). Setting the cut-off US score at 17 resulted in the best ratio of specificity (98.7%) to sensitivity (58.8%). Conclusions. Well-defined US changes in the major salivary glands summarized in our novel scoring system were typical of SS patients. Advanced structural changes found on US imaging almost invariably represent SS salivary gland involvement.

Amyloid A (AA) (secondary) amyloidosis represents a severe complication of chronic inflammatory diseases. Since pathogenic mechanisms point to the central role of interleukin 6 (IL-6) in the process of amyloid AA generation, IL-6 blockade seems an attractive therapeutic option. We report a case of a patient with polyarteritis nodosa complicated by AA amyloidosis treated with tocilizumab.

This review paper contains selected aspects of Sjögren’s syndrome. It consists of epidemiology, ultrasound of salivary glands and antimuscarinic antibodies. The first part present studies aimed to determine the prevalence and the incidence of the disease with special emphasize on epidemiological studies performed in Slovenia. This is followed by the demonstration of the role of ultrasound of salivary glands in the diagnosis of Sjögren’s syndrome and the value of antimuscarinic antibodies in global assesment of the secretory failure., U preglednom su članku opisani epidemiologija, ultrazvučni nalaz slinovnica i antimuskarinska antitijela u Sjögrenovom syndromu. U prvomu su dijelu rada prikazani prevalencija i incidencija bolesti u odnosu na epidemiološke studije u Sloveniji. Prikazana je uloga ultrazvučne pretrage slinovnica u dijagnozi Sjögrenova sindroma i vrijednost antimuskarinskih antitijela u općoj procjeni sekrecijske poremetnje.

In the past sicca syndromes were attributed to destruction of glandular tissue. It is now thought that cytokines, autoantibodies, and parasympathetic nervous system dysfunction all have an important role in the xerostomia and xerophthalmia in Sjogren's syndrome.

Leflunomide is a new isoxazole drug with disease modifying properties for the treatment of rheumatoid arthritis (RA). Hypertension has been mentioned as a common side effect of the treatment. It was found in up to 10.6% of patients receiving 25 mg leflunomide in a phase II study.1 New onset hypertension occurred in 3.7% of patients in a phase III European study,2 and in 2.1% of patients, with a mean increase in systolic and diastolic blood pressure of 2.2 and 1.9 mm Hg, respectively, in an American phase III study.3 There was no evidence that hypertension was related to an impairment of renal function or proteinuria. The changes in blood pressure during leflunomide treatment have not been studied in detail. Thirty consecutive patients fulfilling the American Rheumatism Association criteria for RA were recruited into a prospective study and treated with standard doses of leflunomide. Other enrolment criteria included stable treatment with non-steroidal anti-inflammatory drugs up to the maximum recommended dose and/or corticosteroid treatment …

Background Giant cell arteritis (GCA) is the most common systemic vasculitis in patients over 50 years of age. Recently, the Colour-Doppler Sonography of temporal arteries (CDS-TA) has gained momentum as a potential non-invasive tool for diagnosing GCA.(1, 2) Objectives To evaluate the diagnostic value of CDS-TA in suspected GCA cases in daily clinical practice. Methods Subjects with suspected GCA underwent CDS-TA prior to temporal artery biopsy (TAB) and glucocorticoid treatment. TAs and their branches were assessed in longitudinal and transversal planes. The “halo sign” (dark hypo echoic circumferential wall thickening), stenosis or occlusion were considered a positive finding. In addition to CDS-TA, clinical examination, extensive laboratory work-up, and TAB were performed. Diagnosis was established in accordance with the American College of Rheumatology (ACR) criteria for the classification of GCA. Results From September 2011 to December 2013 94 subjects with suspected GCA were identified. GCA was diagnosed in 56 subjects (59.6%). The remaining 38 subjects (40.4%) who were not diagnosed with GCA served as controls. CDS-TA was performed in 93 subjects (55/56 GCA patients and in 38/38 controls). The characteristic “halo sign” was observed in 44 (80%) of GCA patients and in none of the controls. The “halo sign” was unilateral in 19 (34.5%) and bilateral in 25 (45.5%) of GCA patients. Mean TA wall thickness of the affected vessels was 0.74±0.019 mm vs. 0.27±0.007 mm of the unaffected vessels. Stenoses were found in 28 (50.9%) of GCA patients and in 2 (5.3%) controls. TA occlusion was demonstrated in 6 (10.9%) of GCA patients and in none of the controls. In our population the CDS-TA had an estimated diagnostic sensitivity of 80.0% and specificity of 94.7% with diagnosis based on the ACR criteria serving as a gold standard. A positive CDS-TA had 95.6% positive and 76.6% negative predictive value for GCA. The TAB for the same group had a diagnostic sensitivity of 79.2% and specificity of 88.5%; and a 92.7% positive and a 69.7% negative predictive value. Matching of results from CDS-TA and TAB is shown in Table 1. In comparison, the patients with GCA with a positive CDS-TA vs those with negative CDS-TA the former had more often had clinically (75.0% vs 27.3%; p=0.003) and histologically (86.5% vs. 50%; p=0.01) altered TAs, jaw claudication (36.4% vs. 9.1%; p=0.08) as well as longer time from the onset of symptoms to diagnosis (8.3 vs. 4.5 weeks, p=0.25) Conclusions The diagnostic sensitivity and specificity of CDS-TA for diagnosing GCA is comparable, if not superior to TAB. In case of characteristic sonographic changes, CDS-TA may obviate the need for TAB. References Arida A, Kyprianou M, Kanakis M, Sfikakis PP. The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis. BMC Musculoskelet Disord 2010;11:44. Diamantopoulos AP, Haugeberg G, Hetland H, Soldal DM, Bie R, Myklebust G. Diagnostic value of color Doppler ultrasonography of temporal arteries and large vessels in giant cell arteritis: a consecutive case series. Arthritis Care Res (Hoboken) 2014;66:113-9. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1967

Background Polyarteritis nodosa (PAN) is a necrotising vasculitis of medium and small sized muscular arteries. It is a rare disease, with reported annual incidence rate of 1–8 cases per 10 6 adults. 1,2 In areas where hepatitis B virus (HBV) infection is hyperendemic however, the annual incidence rate is much higher, i.e. up to 77 per 10 6 adults. 3 Objectives To determine the annual incidence rate of PAN within a well-defined adult population of the Ljubljana region of Slovenia. Methods A retrospective chart review of adult patients diagnosed with PAN was performed at the Department of Rheumatology of University Medical Centre Ljubljana, which is a part of an integrated secondary/tertiary university teaching hospital, that is the only referral rheumatology centre in the Ljubljana region, which represents about a quarter of Slovenian population. Potential cases were identified by searching the electronic medical records for ICD-10 codes M30.0. The electronic and paper records of patients who were residents of the Ljubljana region at the time of diagnosis were then thoroughly reviewed. Cases fulfilling the ACR 1990 classification criteria for PAN with either histologically proven vasculitis or characteristic arteriographic abnormalities were included in the analysis. The annual incidence rate of PAN was then calculated. Results Between January 1, 2003 and December 31, 2012 (10 years of observation) five new cases (3 male, 2 female, male:female ratio=1,5; median age 49 (range 27–72) years) of PAN were identified in the Ljubljana region with a population of 527,000 aged 18 years or above. Patients9 clinical characteristics at the time of diagnosis are presented in Table 1. Four patients complained of myalgias and all male patients had testicular pain. Peripheral nerve lesions were identified in two. Three patients had arteriographic abnormalities; two of them had the characteristic microaneurysms. One patient had an active HBV infection. One had a localized cutaneous form of PAN on the basis of nodular skin changes with typical histological picture and no other organ system involvement (Case 1*). During the follow up one patient developed AA amyloidosis. Conclusions The estimated annual incidence rate of PAN was 0.95 per 10 6 adults. References Gonzalez-Gay, MA, et al. Arthrit Care Res, 2003, 49.3: 388-93. Watts, RA, et al. Arthritis Rheum, 2000, 43.2: 414-19. McMahon, BJ, et al. Hepatology, 1989, 9.1: 97-101. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2564

Background Antiprothrombin antibodies bind to prothrombin coated ELISA plates but also recognize prothrombin exposed to immobilized phosphatidylserine, namely phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT). During the 13th International Congress on Antiphospholipid Antibodies (APLA 2010) a Task Force of worldwide scientists agreed that the antiprothrombin antibody assay, in particular, aPS/PT, would potentially contribute to a better recognition of antiphospholipid syndrome (APS). As a result, a retrospective, cross-sectional multi-centre study was designed. Objectives To determine the value of aPS/PT for the diagnosis of APS. Methods The study involved eight centres from 7 countries (Argentina, Japan, Portugal, Slovenia, Spain, United Kingdom and United States). Demographics and clinical/laboratory data from all the subjects were retrospectively collected. A serum/plasma sample from the subjects was prepared at each participant institution. Specimens were blinded and determination of IgG/IgM aPS/PT was performed at INOVA Diagnostics, Inc. San Diego, USA (INOVA) using ELISA kits provided by two manufacturers: Medical and Biological Laboratories Co. Ltd, Nagano Japan (MBL) and INOVA. Results Two hundred forty-seven subjects were included (126 APS patients, 73 non-APS patients and 48 healthy controls). Eighty three percent of samples showed concordant results for IgG and 82% for IgM aPS/PT using ELISA kits from both manufacturers. Statistically significant correlations in the IgG and IgM aPS/PT values were obtained using ELISAs from both manufacturers (r=0.827, r=0.625, p Conclusions Determination of aPS/PT using different commercial assays is reliable. aPS/PT detection offers an additional, easily performed laboratory parameter that may assist in the diagnosis of APS. Acknowledgements The authors want to acknowledge the contributions of the late Prof. Silvia Pierangeli, University of Texas Medical Branch, Galveston, TX, USA Disclosure of Interest O. Amengual: None declared, R. Forastiero: None declared, M. Sugiura-Ogasawara: None declared, K. Oku: None declared, K. Otomo: None declared, J. Alves: None declared, C. Favas: None declared, P. Žigon: None declared, A. Ambrožic: None declared, M. Tomsic: None declared, G. Ruiz-Irastorza: None declared, I. Ruiz-Arruza: None declared, M. Bertolaccini: None declared, G. Norman Employee of: INOVA Diagnostics Inc, Z. Shums Employee of: INOVA Diagnostics Inc., J. Arai Employee of: Medical and Biological Laboratories Co Ltd, T. Atsumi: None declared DOI 10.1136/annrheumdis-2014-eular.2426

Background Giant cell arteritis (GCA) is the most common systemic vasculitis in patients over 50 years of age. In Slovenia it has an annual incidence rate of 10.5 per 10 5 adults aged 50 or above. It affects large and medium-sized arteries, most commonly the extracranial branches of the carotid arteries, the ascending aorta, subclavian, and axillary arteries. Recently, the Colour-Doppler sonography (CDS) has gained momentum as a potential non-invasive tool for evaluation of large arteries in large vessel vasculitides. Objectives To evaluate the involvement of large epiaortic arteries in patients with GCA using CDS. Methods CDS of large epiaortic arteries was prospectively performed by a single assessor (AH) on a Philips IU22 using a 5–17.5 MHz linear probe in patients with newly diagnosed GCA prior to or up to 2 days after starting glucocorticoids. Carotid, vertebral, thyroid, subclavian, and axillary arteries were assessed in longitudinal and transversal planes. The “halo sign” (i.e. a hypoechoic circumferential wall thickening), vascular stenosis (i.e. >50% reduction of the original lumen) or occlusions were considered a positive finding. Results From September 2011 to December 2013 CDS of large epiaortic arteries was performed in 48 GCA patients fulfilling the American College of Rheumatology criteria for the classification of GCA. In 13 (27.1%) patients involvement of epiaortic large arteries was found. A single artery was affected in 6 patients, and 7 patients had more than one epiaortic artery affected. In nine patients bilateral involvement was observed (Table 1). When patients with large artery involvement were compared to the patients with no large artery involvement the former were more commonly female (F:M ratio 5.5 vs. 1.9; p=0.2) and had had a longer disease duration (11.6 weeks vs. 6.4 weeks, p=0.1), yet differences were not statistically significant. Neither were there any statistically significant differences in the clinical presentation (i.e. presence of general symptoms, polymyalgia rheumatica, new onset of headache, jaw claudication, visual disturbances, changes of temporal arteries on physical examination) nor the levels of systemic markers of inflammation between the two groups. 77% and 90% GCA patients with epiaortic vessel disease had positive temporal artery CDS and biopsy respectively (vs. 88% and 83% GCA patients without large vessel disease). Two out of 13 patients with large vessel involvement by CDS had had a negative CDS of temporal arteries as well as a negative temporal artery biopsy. Conclusions Large artery involvement was demonstrated in more than 1/4 of our GCA cases. CDS of epiaortic large arteries in addition to CDS of temporal arteries increases the diagnostic yield in GCA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1964

Background Retreatment with rituximab (RTX) is common clinical practice, although several aspects regarding retreatment, such as frequency, need to be further elucidated. Objectives The aim of this study was to describe the effectiveness of repeated courses of RTX in a large observational cohort of real-life patients with RA. Methods Pooled data from the Collaborating European Registries for Rituximab in RA (CERERRA) project were used. Patients with RA who received at least 4 cycles with RTX were identified and included in the analysis. A covariate-adjusted mixed effects model was fitted to the longitudinal DAS28 for patients with complete covariate information, including country, sex, age, anti-CCP status, number of prior biologics and concomitant DMARD treatment. Results 340 patients met the eligibility criteria for these analyses. At baseline (start of RTX) the mean (SD) age was 53.5 (12.6) years, mean (SD) disease duration 12.1 (8.2) years, 83% were females, 79% RF positive and 74% anti-CCP positive. 60% were treated with corticosteroids and 84% with concomitant DMARD. Patients had failed 2.7 (1.5) prior synthetic DMARDs and 1.1 (1.0) prior biologic DMARDs. The baseline DAS28 was 6.0 (1.4). The mean fixed predicted decrease of DAS28 after the first cycle and after each retreatment (1st, 2nd and 3rd) is shown in figure 1. Significant improvement in DAS28 (p Conclusions Repeated retreatment with RTX can lead to further clinical improvement after the first course of RTX. A trend for stabilization of disease activity score was observed after the 2nd retreatment. Disclosure of Interest K. Chatzidionysiou: None declared, E. Lie Consultant for: AbbVie, BMS, Hospira, Pfizer, UCB, Speakers bureau: AbbVie, BMS, Pfizer, Roche, UCB, E. Nasonov Grant/research support: Roche, G. Lukina Grant/research support: Roche, M. Hetland Speakers bureau: AbbVie, BMS, MSD, Pfizer, U. Tarp: None declared, K. Pavelka: None declared, C. Gabay Consultant for: Roche, D. Nordstrom Grant/research support: Roche, H. Canhao: None declared, M. Tomsic: None declared, P. van Riel: None declared, J. Gomez-Reino: None declared, I. Ancuta: None declared, T. Kvien Grant/research support: to the Diakonhjemmet Hospital from AbbVie, BMS, MSD/Schering-Plough, Pfizer/Wyeth, Roche and UCB, Consultant for: AbbVie, BMS, Celltrion, Eli Lilly, Hospira, MSD/Schering-Plough, Orion Pharma, Pfizer/Wyeth, Roche, UCB, Speakers bureau: AbbVie, BMS, Celltrion, Eli Lilly, Hospira, MSD/Schering-Plough, Orion Pharma, Pfizer/Wyeth, Roche, UCB, R. van Vollenhoven Grant/research support: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex DOI 10.1136/annrheumdis-2014-eular.2584

Background In 2010 EULAR/PRINTO/PRES proposed new classification criteria for IgA vasculitis (IgAV).(1) In paediatric patient population these criteria have a higher diagnostic sensitivity than the older American College of Rheumatology (ACR) criteria.(1, 2) The performance of the new criteria has thus far not been evaluated in adult IgAV patients. Objectives To compare the performance of the ACR and EULAR/PRINTO/PRES classification criteria in adult IgAV. Methods Adult IgAV cases diagnosed using EULAR/PRINTO/PRES classification criteria at a tertiary rheumatology referral centre were critically reviewed in partially retrospective and partially prospective manner to assess whether these patients also fulfilled the ACR criteria. Results Between January 1, 2010 and December 31, 2013 96 new adult IgAV cases (median age 63.4; interquartile range 40.8–77.3 years; 60.4% males; male to female ratio 1.53) were identified according to EULAR/PRINTO/PRES classification criteria. Purpura was present in all patients (generalized in 33/96 (34.3%), necrotic 43/96 (44.8%), bullous 9/96 (9.4%)) and was the only manifestation in 19 (19.8%) cases. Joints were involved (arthralgia or arthritis) in 44/96 (45.8%), gastrointestinal tract in 35/96 (36.4%), and kidneys in 56/96 (58.3%) cases. Lung, heart and testicular involvement was rare - one case of each. In 96/96 cases IgA deposits in vessel walls was documented on direct immunofluorescence staining. 91/96 of cases fulfilled both EULAR/PRINTO/PRES IgAV and ACR classification criteria. However, 5/96 patients (5.2%) fulfilled the EULAR/PRINTO/PRES classification criteria only. The characteristics of these patients are shown in Table 1. Conclusions In an adult population the EULAR/PRINTO/PRES IgAV classification criteria have a higher sensitivity than the previously proposed ACR criteria, analogously to the findings in paediatric population. References Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis 2010;69:798-806. Mills JA, Michel BA, Bloch DA, Calabrese LH, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schonlein purpura. Arthritis Rheum 1990;33:1114–21. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1906

Background Giant cell arteritis (GCA) is the most common systemic vasculitis in adults aged 50 years or above. Annual incidence rates vary widely from 6.9–76.6 per 10 5 of adults in this age group, depending on the region. 1 Objectives To determine the incidence rate of GCA in our population. Methods We prospectively collected incident cases of GCA from January 1st 2011 to December 31st 2012 at our department of rheumatology which is a part of an integrated secondary/tertiary university teaching hospital that is the only referral center serving a region representing approximately a quarter of the national adult population. Additionally, newly diagnosed cases of GCA between January 1st 2009 and December 31st 2010 were retrospectively identified by searching the electronic patient records for ICD-10 codes M31.5 and M31.6 at our department. The retrospective approach and search strategy was also applied on electronic medical records at the departments of infectious diseases and ophthalmology between January 1st 2009 and December 31st 2012. To further reduce possibility of underreporting, the attached medical faculty9s Institute of Pathology provided a list of all temporal artery biopsies examined during the observation period which were then cross-referenced with the hospital9s electronic medical records. Annual incidence rate for GCA was then calculated. Results During the four year observation period we identified 97 new cases of GCA (68% female; mean (SD) age 75.6 (8.1) years) from a well-defined adult white Caucasian population of 232,041 inhabitants aged 50 or above. The temporal artery biopsy was consistent with GCA, negative or not performed in 75.3%, 18.6, and 6.2% of cases, respectively. Thus, the annual incidence of GCA in our population is 10.5 (95% CI 8.5–12.7), and 4.7 (95% CI 3.8–5.7) per 10 5 adults aged 50, and 20 years or above, respectively. Conclusions The annual incidence rate of 10.5 per 10 5 adults aged 50 or above makes GCA the most common systemic vasculitis in this age group of our population. Although the GCA almost exclusively affects adults over 50 years of age, the incidence rate of 4.7 per 10 5 adults aged 20 and above, also makes it the most common systemic vasculitis in the adult population overall, with IgA vasculitis coming a close second with 3.7 per 10 5 adults aged 20 years or above. References Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ et al. Epidemiology of Giant Cell Arteritis and Polymyalgia Rheumatica. Arthritis Rheum 2009;61:1454-61. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1968

Background Clinical trials have shown that tocilizumab (TCZ) is efficacious as monotherapy and in combination with methotrexate (MTX) or other DMARDs. However, longitudinal TCZ retention data from large registry populations have been missing. Objectives To examine retention of TCZ administered alone or in combination with DMARDs in rheumatoid arthritis (RA) patients included in the TOcilizumab Collaboration of European Registries in RA (TOCERRA). Methods RA patients treated with TCZ who had baseline (BL) data and not immediately lost to follow-up were included. Patients were considered as taking TCZ in monotherapy (mono) or combination with DMARDs (combo) based on their BL DMARD co-therapy. Time on TCZ was defined by the time between TCZ start and discontinuation with censoring occurring at date of last visit on TCZ. Crude median TCZ retention with 95% CIs were estimated for mono and combo therapy. The hazard for TCZ discontinuation was modeled using a country-stratified, covariate-adjusted Cox proportional hazards model applied to patients with complete BL covariate information for sex, age, disease duration, number of prior biologics, corticosteroid use, seropositivity (rheumatoid factor or anti-CCP), DAS28, HAQ, and therapy. Results A total of 1271 eligible treatment courses (TCs) were retrieved from 8 registries by April 2013. Of these, 328 (26%) were started as mono and 943 as combo therapy. For 83% of TCs, DMARD co-therapy was stable over time. In 471 TCs (37%) (of which 124 mono) TCZ was discontinued. Main causes of discontinuation were lack of effectiveness (52% for both therapies) or safety issues (34% and 26% for mono and combo). Crude median TCZ retention was 2.2 years (95% CI: 1.7-3) for mono and 3.5 years (95% CI: 2.7-NA) for combo, (P=0.08). Of the 1271 TCs 856 were included in the country-stratified, covariate-adjusted analysis. Significant results were obtained for seropositivity (HR: 0.64 (pos vs neg), 95% CI: (0.49, 0.84), P=0.001) and HAQ (HR: 1.25 (per unit increase), 95% CI: (1.04, 1.49), P=0.014) at BL. Therapy was not significant (HR: 1.16 (mono vs combo), 95% CI: (0.89, 1.52), P=0.27). Conclusions In routine care, TCZ retention is better in patients who are seropositive and have lower HAQ at BL, but comparable for mono and combo therapy. Disclosure of Interest C. Gabay Grant/research support: Roche, M. Riek: None declared, M. Hetland Grant/research support: Roche, E. Hauge Grant/research support: Roche, K. Pavelka Grant/research support: Roche, M. Tomsic Grant/research support: Roche, H. Canhao Grant/research support: Roche, K. Chatzidionysiou Grant/research support: Roche, R. van Vollenhoven Grant/research support: Roche, G. Lukina Grant/research support: Roche, D. Nordstrom Grant/research support: Roche, E. Lie Grant/research support: Roche, I. Ancuta Grant/research support: Roche, E. Loza Santamaria Grant/research support: Roche, P. van Riel Grant/research support: Roche, T. Kvien Grant/research support: Roche DOI 10.1136/annrheumdis-2014-eular.2806

While carpal tunnel syndrome (CTS) is the most common entrapment neuropathy presented at rheumatologic consultation, its ulcerative variant is rarely described. We report of a case of severe bilateral medial nerve palsy, presented to us for diagnosis of chronic digital ulcers which had been suspected to be rheumatologic in origin. Careful examination revealed an unusual case of CTS in an advanced stage, which presented itself with skin changes only, lacking all the typical neurologic symptoms or rheumatologic background. Our case stresses the importance for rheumatologists to be aware of the ulcerative form of CTS as one of the etiologic differential diagnostic options of digital ulcers.

Objective The aim of our study was to determine the prevalence of Sjogren's syndrome (SS) in Slovenia. Methods A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe. The participants were asked six simple questions for assessing both ocular and oral involvement. Information on co-morbidities and related treatment was collected at the same time. All participants were subjected to a Schirmer-I test, an unstimulated salivary flow test, as well as serological studies (rheumatoid factor, antinuclear antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies). When indicated, Rose Bengal score, salivary scintigraphy and histopathological investigation of the minor salivary glands were carried out until three out of the six European classification criteria for SS were shown to be negative or until SS was diagnosed. Results Out of the 889 invited subjects, 332 (37.3%) participated in our study: 183 females, mean age (+/- S.D.) 52.2 +/- 13.7 yr (range 20-84) and 149 males, mean age (+/- S.D.) 56.3 +/- 12.9 yr (range 23-84). After the first visit, 244 of the 332 (73.5%) participants proved to be negative for three out of the six above-mentioned criteria, and were eliminated from further tests. The remaining 88 participants were consecutively subjected to Rose Bengal score, salivary scintigraphy and minor salivary gland biopsy. Fifteen participants refused to perform either one or more of the proposed tests at the second study stage. Two females of the 332 study participants [0.60% (exact 95% CI 0.07%, 2.16%)] fulfilled the criteria for primary SS. Conclusions The estimated prevalence of definite SS in Slovenia is 0.60%.

Background Current recommendations for management of RA propose an 0anti-TNF agent for patients failing to achieve the treatment target with synthetic DMARDs. If 1 st anti-TNF fails, a different anti-TNF, abatacept, rituximab (RTX) or tocilizumab (TCZ) are equally recommended. 1 It has been shown that non anti-TNF agents are at least as effective as the anti-TNF. Little is known about the survival of 2 nd biologic agents, especially RTX and TCZ. Objectives To investigate the survival of the 2 nd biologic after switching from the 1 st anti-TNF agent. Methods Data was extracted from the Slovenian registry (BioRx.si) on Dec 15 th , 2012. Kaplan Meier survival analysis was performed. Statistical significance was determined with the Log-Rank and Wilcoxon tests. Results 688 RA patients (81.5% female, mean age at diagnosis 45.2±11.8 years, 81.8% RF positive, 77% ACPA positive, concomitant methotrexate (MTX) 71.1%, leflunomide (LEF) 10.5%, metilprednisolone (MP) 45.3%, mean DAS28ESR 6.4±1.0) were treated using adalimumab, etanercept, infliximab, certolizumab, and golimumab in 43.6%, 30.7%, 10.7%, 9.9%, and 5.1% as the first biologic, respectively. Median survival of the first anti-TNF was 184 weeks. 242 (35.2%) patients (81.8% female, mean age at diagnosis 45.4±11.4 years, 81.8% RF positive, 77.6% ACPA positive; concomitant MTX 62.8%, LEF 12.4%, MP 47.1%; mean DAS28ESR 6.3±1.1) were switched to a different anti-TNF (55%), rituximab (14%) or tocilizumab (31%). Kaplan Meier survival curves for 2 nd anti-TNF (as a group), RTX and TCZ are presented (Image). 2 nd anti-TNF failed due to insufficient efficacy in 90%, and adverse events in 8%. Image/graph Conclusions After the 1 st anti-TNF’s failure, a 2 nd anti-TNF is more likely to fail earlier than RTX or TCZ (p=0.000). There is a trend of better survival of RTX vs TCZ, which did not reach statistical significance (p=0.057). References Smolen JS, et al. Ann Rheum Dis. 2010;69:964-75. Disclosure of Interest None Declared

Objectives To validate the EULAR scores for assessment of primary Sjogren’s Syndrome (SS): the EULAR SS Disease Activity Index (ESSDAI), the EULAR SS Patient Reported Index (ESSPRI). Methods Prospective international validation study with 2 visits: baseline and 6 months. At each physicians completed ESSDAI, SS disease activity index (SSDAI), Sjogren’s Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Construct validity (using correlations with gold standard), responsiveness (using standardized response mean [SRM]) and reliability (intraclass correlation coefficient [ICC]) were evaluated and compared between each scores. Results 395 patients (96% women, mean age 55.4 ± 13.7 years, 79% with anti-SSA and/or anti-SSB antibodies) from 15 countries have been included. At enrollment, 145 (37%) and 251 (64%) had, respectively, current or either current or past systemic manifestations. EULAR scores had higher correlation with gold standard than other scores (ESSDAI with PhGA: rho=0.59; ESSRPI with PGA: rho=0.70). Correlations between patient and systemic scores were very low (rho ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients (SRM= 0.69 to 0.82). Responsiveness of patients scores was low in patient experiencing improvement of their symptoms but was significantly higher for ESSPRI compared to SSI and PROFAD ((SRM=0.37 vs. 0.04 and 0.16; p=0.006 and 0.049 for SRM comparisons). Reliability was assessed in a subgroup of 47 and 62 patients, for systemic and patients scores, respectively. Reliability was very good for all scores (ICC=0.83 to 0.96). Conclusions ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores were sensitive to change in patients whose disease activity improves. Patient scores had a small sensitivity to change. However, ESSPRI was significantly better than SSI and PROFAD. The poor correlation between systemic and patients scores confirms that these 2 components are different and should be evaluated separately. Disclosure of Interest : None Declared

Background the preliminary Classification Criteria for cryoglobulinemic vasculitis (CV) have been developed in 2011 by an European cooperative study (1). Objectives to validate these Classification Criteria for CV with the participation of non-European Countries. Methods 20 Centres from Europe, Egypt, and Japan partecipated. New consecutive, unselected patients with CV (Group A) and controls (subjects with cryoglobulins without a CV based on the golden standard clinical judgment; Group B) were studied. A sample size of 140 patients for each group was estimated to obtain a sensitivity (SE) and a specificity (SP) of at least 90±5%, according to the previous results (1). A dedicated chart was distributed to the Centres. The sensitivity and specificity of the 2011 Classification Criteria were calculated in the present validation series by comparing Group A versus Group B. Results 251 patients in Group A and 175 controls in Group B were recruited. The questionnaire (at least 2/3 positive answers) showed a SE of 89.2% (95% CI 85.4-93.1) and a SP of 93.7% (95% CI 90.1-97.3); the clinical item (at least 3/4 clinical items among constitutional, articular, vascular and neurologic involvement) showed a SE of 76.1% (95% CI 70.8-81.4) and a SP of 88.6% (95% CI 83.8-93.9), and the laboratory item (at least 2/3 tests, among positive rheumatoid factor, low C4, and the presence of serum monoclonal component) showed 75.1% (95% CI 69.5-80.7) of SE and 71.5% (95% CI 64.6-78.4) of SP. The final 2011 Classification Criteria (at least 2/3 positive items) showed a SE of 89.3% (95% CI 85.3-93.3) and a SP of 93.9 % (95% CI 90.3-97.6). Conclusions: Conclusion : The 2011 International Classification Criteria for the cryoglobulinemic vasculitis have been validated in a new cohort of real cases and controls. Patients where CV is suspected on clinical grounds, but where cryoglobulins are negative, cannot be classified, since positive serum cryoglobulinemia is a conditio sine qua non for classification (1). However, the performance of these criteria on this subset of patients is under evaluation. References De Vita S, et al. Ann Rheum Dis 2011;70:1183-90. Disclosure of Interest None Declared

Background Predictors of response to biologic therapy in rheumatoid arthritis (RA) are needed to achieve a more individualized therapy. Seropositivity has been associated with better response to rituximab (RTX). Objectives To assess the 6-month response to the first RTX course in RA according to RF and ACPA status. Methods Ten European registries submitted anonymized datasets from RA patients who had started RTX, and datasets were pooled and analysed. Chi-square test for comparison of categorical variables and t-test for continuous data were used. Predictors of response were identified by logistic regression analysis. Results 3266 patients were included in the cohort. 79.9% of patients were RF (+) (2041 out of 2553) and 73.2% were ACPA (+) (877 out of 1198). 718 patients were double positive (DP) and 147 double negative (DN). 2200 patients were RF (+) and/or ACPA (+). Improvements of DAS28 (ΔDAS28) at 6 months were significantly better for RF (+) than RF (–) patients as well as for ACPA (+) than ACPA (–), DP vs. DN and RF and/or ACPA (+) vs. DN (table 1). A significantly higher percentage of ACPA (+) and DP patients achieved EULAR Good Response at 6 months compared to ACPA (–) and DN, respectively (table 1). The completeness of data was very similar for seropositive and seronegative patients, with the percentage of missing data at 6 months being approximately 50% in all groups. A significantly higher percentage of seronegative patients received retreatment by 6 months than seropositive patients. In univariate analyses adjusted for age and gender ACPA positivity (OR=2.03, p=0.016) and DP (OR=2.43, p=0.03) but not RF positivity (OR=1.53, p=0.07) predicted EULAR good response to therapy with RTX at 6 months after the first treatment. Conclusions In this large observational cohort of RA patients treated with RTX, seropositive patients achieved significantly greater reductions in DAS28 at 6 months compared to seronegative patients. Baseline ACPA positivity may be a better predictor for good response to RTX than RF positivity. Disclosure of Interest None Declared

SUMMARY Conventional radiograms have been used to quantitate the progression of rheumatoid arthritis, mainly through the assessment of bone erosions, but this approach has many limitations. It has been suggested that an advantage of contrast-enhanced Od-DTPA MRI over radiography may be its prognostic value due to its ability to show the natural history of active destructive to inactive fibrous pannus. The aim of this study was to evaluate the possible prognostic value of MRI for future development of bone erosive changes in small hand joints in patients with RA. The results of the study confirm that in joints in which inflammatory active pannus is shown by contrast-enhanced MRI, progression of bone-destructive changes can be expected.

Background/objectives The approved dose of RTX in RA is 1000 mg x2, but some data have suggested similar clinical efficacy with 500 mg x2. The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course. Methods Ten European registries submitted anonymised datasets with demographic, efficacy and treatment data for patients who had started RTX. Efficacy of treatment and retreatment was assessed based on DAS28 reductions and EULAR responses after 6 months. Results Data on RTX dose were available for 2873 out of 3266 patients in CERERRA. 2625 (91.4%) and 248 (8.6%) patients received 1000mg x2 and 500mg x2, respectively. Patients who were treated with the lower dose (LD) were significantly older (mean±SD: 55.2±15.8 vs 52.6±12.6, years, p=0.002), had longer disease duration (13.6±11.9 vs 10.9±8.2, years, p Both dosages lead to significant clinical outcomes at 6 months. Patients with the HD achieved numerically slightly greater DAS28 reductions at 6 months compared to those treated with the LD (mean DeltaDAS28±SD = 1.9±1.4 vs 1.7±1.4, p=0.5 corrected for baseline DAS28). Similar percentages of patients achieved EULAR good response (55.2% vs 50%, p=NS) and remission (10.5% vs 10.7%, p=NS) in the HD and LD groups, respectively. At 6±1.5 months 579 patients received retreatment with HD RTX and 26 patients with LD. Patients who received a different dose at retreatment than at first treatment, as well as patients who were retreated at different time points during the first year, were disregarded from the analysis. Retreatment with HD led to even greater DAS28 reductions at 12 than at 6 months (DeltaDAS28 6 m=1.85±1.19, DeltaDAS28 12 m=2.52±1.47, p by paired t test Conclusion In this large observational cohort initial treatment with RTX at 500 mg x2 and 1000 mg x2 led to comparable clinical outcomes. The HD was associated with further DAS28 reductions when given as a second treatment course.

The case is reported of a 27 year old woman who had mixed connective tissue disease (MCTD) associated with chronic active hepatitis and thyroiditis. Although hepatomegaly is sometimes observed in MCTD, only four cases of MCTD and chronic active hepatitis have been described. It is thought that this is the first report of an association between MCTD, chronic active hepatitis and thyroiditis.

Monte Carlo simulation and theory were used to study the potential of mean force (PMF) between a pair of big colloidal (solute) particles suspended in a sea of smaller particles (solvent) interacting via Baxter's sticky hard sphere (SHS) potential. Simulation results were obtained by applying a special simulation technique developed for sampling the hard sphere collision force, while the theoretical predictions were calculated from the analytic solution of the Percus-Yevick/Ornstein-Zernike integral equation for spatial correlations in a two-component mixture at vanishing solute concentration. Both theory and simulation revealed oscillations of the solute-solute PMF with a period equal to the diameter of the solvent molecules. Further, the attractive PMF between solute particles in the SHS fluid decays slower than in a hard sphere solvent. Upon increasing the strength of attraction (stickiness) between the molecules of solvent, these oscillations gradually disappear, the PMF becoming long ranged and attractive at all separations.

We read with great interest the editorial article by Schett et al ,1 where the authors discuss the role of tumour necrosis factor (TNF) α blockers in reducing new bone formation in ankylosing spondylitis (AS). They described the pathophysiological process, where TNF-α is a key proinflammatory cytokine, but is also a potent inhibitor of bone formation. Therefore, it is unlikely that TNF-α blockers are effective in reducing syndesmophyte growth and bridging. In other words, would TNF-α blockers inhibit the progression of structural damage even though they are proven to be very efficient in diminishing the clinical parameters of AS activity, acute-phase reactants and also active …

Temperature dependence of the self-assembling properties of aqueous solutions of deoxy- and guanosine 5'-monophospate (dGMP and GMP) in the pretransitional region of the I-Ch phase transition was investigated by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). The dGMP molecules start to assemble at lower concentrations and form considerably longer aggregates than GMP molecules. Conversely, the aggregate melting curves of both derivatives are very similar and show three characteristic regions: a low temperature interaction-controlled region, a narrow region of intense aggregate dissociation, and a high temperature region of dissociated species.

Background In 2010, EULAR/PRINTO/PRES proposed new classification criteria for paediatric IgA vasculitis (IgAV) that have a higher diagnostic sensitivity than the 1990 ACR criteria. These criteria have so far not been evaluated in adults, in whom IgAV is considered as a rare disease. Our main objective was to compare the diagnostic performance of EULAR/PRINTO/PRES and ACR classification criteria in adult IgAV. Methods Adult IgAV cases fulfilling the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (ICHCCNV) definition of IgAV at a secondary/tertiary rheumatology referral centre were critically reviewed in a partially retrospective and partially prospective manner. First, we compared the diagnostic sensitivity of ACR and EULAR/PRINTO/PRES criteria in this group of patients. Second, the diagnostic specificity of ACR and EULAR/PRINTO/PRES was determined by applying these criteria to a control group of patients with other systemic vasculitides. Results Between 1 January 2010 and 31 December 2014 350 new cases of systemic vasculitis were identified. IgAV was diagnosed in 129, and other systemic vasculitides in 221 (123 had large, six medium and 92 small vessel vasculitis) cases according to ICHCCNV. The diagnostic sensitivity and specificity of the IgAV EULAR/PRINTO/PRES criteria were 99.2 % (95 % CI 95.4–99.9 %) and 86.0 % (95 % CI 80.7–90.3 %), and of the ACR criteria 86.8 % (95 % CI 79.7–92.1 %) and 81.0 % (95 % CI 75.2–85.9 %), respectively with an inter-criteria agreement of 77.5 % (95 % CI: 70.8–84.1 %). Conclusions In the adult population the EULAR/PRINTO/PRES IgAV classification criteria had a higher sensitivity and specificity than the ACR criteria.