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Background:The exocrine glands, especially the salivary glands, stand as the central target in primary Sjögren’s syndrome (pSS). In this context, the salivary epithelial cells actively participate in the abnormal immune response by assuming the role of antigen-presenting cells. This dual action unfolds into the production of autoantibodies with potential pathogenic roles and the concurrent destruction of the salivary glands. In the past few years, ultrasound (US) has become a widely used and easily reproducible method for examining salivary glands in pSS. According to recent data [1], more pronounced ultrasound alterations in the parotid and submandibular glands may be indicative of a higher biologic disease activity.Objectives:To assess the association between ultrasonographic alterations of major salivary glands and disease phenotypes in pSS.Methods:Fifty-nine (59) patients (54 females and 5 males) diagnosed with pSS according to ACR/EULAR 2016 criteria for pSS [2] underwent gray scale ultrasound evaluation of the parotid and submandibular glands. The gland echostructure was evaluated using the semi-quantitative OMERACT score [3]: grade 0, normal; grade 1, mild US heterogeneity without hypo-anechoic areas; grade 2, moderate heterogeneity with hypo-anechoic areas; grade 3, severe heterogeneity with hypo-anechoic areas occupying the entire gland or complete fibrosis. The gland with the highest score was considered for each patient. Data on organ involvement, serological profile, xerostomia assessed by VAS scale, comorbidities, disease duration, and demographic information were collected for each patient.Results:More than one-third of patients (21 patients, 35.6%) showed moderate-severe US alterations (grade 2-3 according to OMERACT). These patients did not differ from those with mild US alterations (38 patients with grade 0-1 according to OMERACT) in terms of sex, age, disease duration, smoking exposure, and VAS xerostomia. However, patients with moderate-severe US alterations had a significantly higher risk of connective tissue-related interstitial lung disease (6/21: 4 NSIP, 1 LIP, 1 pulmonary amyloidosis) compared to patients with mild US alterations (2/38: 1 NSIP, 1 NSIP/BOOP; OR 7.2, 95% CI: 1.47 – 36.8; P=0.019). Additionally, patients with pSS and rheumatoid factor (RF) positivity (22/59) had a significantly higher risk of moderate-severe US alterations compared to RF-negative patients (13/22 vs. 8/37 with grade 2-3 according to OMERACT; OR 5.23, 95% CI: 1.67 – 16.3; P=0.0053).Conclusion:The detection of moderate-severe US alterations in major salivary glands in pSS could indicate the presence of a more severe pathology, justifying targeted diagnostic investigations, due to the potential morbidity and often subclinical presentation of lung organ damage. From a pathogenetic standpoint, lung and salivary gland parenchyma might share a common target for the immune response; additional studies could elucidate the causal and temporal immunopathological relationships between the respective organ damages. Finally, the positivity of RF remains a key indicator of the disease’s severity.REFERENCES:[1] Schmidt NS, et al. PLoS One. 2022 Dec 12;17(12):e0265057.[2] Shiboski CH et al. Arthritis Rheumatol. 2017 Jan;69(1):35-45.[3] Finzel S, et al. Rheumatology (Oxford). 2021 May 14;60(5):2169-2176.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Therapeutic strategies in Psoriatic arthritis (PsA) have greatly expanded, over the last decade, beyond conventional synthetic DMARDs (csDMARDs) and TNF inhibitors, to include drugs with different mechanisms of action, among which IL23, IL17 and JAK inhibitors (IL23i, IL17i, JAKi). However, the choice of the right mechanism of action for the right patient is still a challenge, as strong evidence to support the use of a drug over another is still lacking (with few exceptions regarding, as an example, skin involvement, or presence of comorbidities, including IBD). Therefore, it would be important to understand clinical features that guide this choice in clinical practice, and how data coming from therapeutic and strategy trials, are applied in daily practice.Objectives:To compare demographic and clinical characteristics of patients who started treatment with IL17i, IL23i or JAKi according to the rheumatologist’ opinion.Methods:Retrospective study enrolling consecutive PsA patients (CASPAR criteria) attending our PsA clinic, who started treatment with IL17i, anti IL23i and JAKi in the period January 2022-December 2023. Demographic data and antropometric indexes were collected at the moment of the drug initiation (baseline) and at 6 months of follow up. Patients’ comorbidities were assessed through the Rheumatic Disease Comorbidity Index (RDCI). Clinimetric data were collected, including Disease Activity in Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI) and psoriasis severity through Body Surface Area (BSA). DeltaDAPSA (difference in DAPSA between baseline visit and at 6 months) in each group were also collected. Continuous variables were compared through ANOVA, and categorical variables by Chi Square test, among the three groups. P values of <0.05 were considered as significant.Results:145 patients were enrolled in this study, mean age 56.8±12.4, mean disease duration 8.4±7.7: 78 started with IL17i, 34 with IL23i and 33 with JAKi. Among patients treated with IL17i, IL23i and JAKi respectively, 48%, 53% and 48% were male. Demographic differences were noted in the age: patients initiating therapy with JAKi were youngest, while those starting IL23i were the oldest (Table). Considering clinical characteristics at baseline, the following features exhibited a statistically significant difference among the groups: number of tender and swollen joints, VAS pain and VAS disease activity, VAS disease activity according to examiner and DAPSA scores. All these indices were higher in patients starting treatment with JAKi>IL17i>IL23. Patients starting IL23i drugs had a more extensive skin involvement. No significant differences were found in disease phenotype or comorbidities. At 6 months, 7 patient interrupted treatment with IL17i (2 for ineffectiveness, 4 for infections, 1 for surgery), 4 stopped treatment with JAKi (3 for ineffectiveness, 1 for mucocutaneous lesions) and 3 stopped treatment with IL23i (1 for ineffectiveness, 1 for infections and 1 for cancer). The delta DAPSA at 6 months, for the patient who continued the same treatment, was 8.7±9.3 for IL17i vs 3.1±7.6 for IL23i vs 12.0±1.,9 for JAKi groups, respectively.Conclusion:In our cohort, patients starting with JAK and IL17i were younger and with higher disease activity, while patients initiating with IL-23i were older and had a more extensive skin involvement. The preference of a certain mechanism of action based on clinical characteristics is a factor that needs to be considered when comparing patients with different treatments in observational studies. Longitudinal prospective strategy trials are instead needed to determine the best treatment choice for each patient.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Francesco Cristiano: None declared, Giusy Peluso: None declared, Annunziata Capacci: None declared, Giulia Calabrese: None declared, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Pietro Rubortone: None declared, Cesare Gavotti: None declared, Pier Giacomo Cerasuolo: None declared, Raffaele La Ferrara: None declared, Roberta Masnata: None declared, Stefano Di Murro: None declared, Valentina Boni: None declared, Paolina Aquilino: None declared, Maria Antonietta D’ Agostino Jannsen, Novartis, Abbvie, Jannsen, Novartis, Abbvie, Augusta Ortolan Janssen, Abbvie, Novartis, UCB.

Rheumatoid arthritis (RA) is a chronic disease characterized by a high degree of disability and pain. Remission is the optimal goal but, even when it is reached, the pain can persist as “residual pain”. The aims of the study were (i) to characterize the size and perception of residual pain and (ii) to evaluate the possible impact of residual synovitis on pain perception in remission RA patients. One hundred twenty-seven RA patients (defined by 2010 ACR/EULAR criteria), of which 68 in clinical and ultrasound remission (REM-RA) and 29 in high disease activity (HDA-RA) defined by DAS28-CRP were enrolled in the study. Thirty fibromyalgia patients (2016 ACR criteria) were enrolled as a control group (FIBRO). Upon enrolled, demographic, clinical and ultrasound features were collected for each patient and an assessment of pain symptom was performed for each patient according to the RAID, FACIT, GHQ and VAS-pain questionnaires. Patients with RA underwent minimally invasive ultrasound-guided biopsy of the synovial membrane of the knee in order to assess the degree of synovitis, according to the Krenn Score (KSS). Considering the RA group, the synovitis degree is directly correlated with the life quality and disability, as demonstrated by the inverse correlation between FACIT and DAS28-CRP (R2=-0.506, p<0.0001). Furthermore, considering the pain mental aspects, the total GHQ score (R2=0.407; p<0.0001) and the VAS-pain scale (R2=0.402, p<0.0001) are instead directly correlated to the DAS28-CRP in RA patients. Since GHQ value ≥24 identifies a subject requiring psychiatric attention, a higher score was found in 26% of REM-RA patients compared to 52% (p=0.004) and 77% (p<0.0001) in the HDA-RA and FIBRO groups respectively while, considering the VAS-pain, the REM-RA patients had lower values (20) compared to HDA-RA (50; p<0.0333) and FIBRO (70; p<0.0001), suggesting how the underlying pathology could affect psychological well-being and pain perception. Further confirmation was obtained with the RAID questionnaire: REM-RA patients presented lower scores (3.34) than HDA-RA (5.56; p = 0.0003) and FIBRO patients (7.63; p <0.0001). Finally, considering the synovitis degree, the presence of subclinical synovitis (KSS≥2) in REM-RA patients (50%) was not associated with a higher pain score, assessed by VAS-pain, suggesting the possible non-inflammatory nature of residual pain. Remission status in RA is associated with a better psycho-physical state than in HDA patients but, despite that, there is the persistence of a certain degree of residual pain, regardless of the subclinical synovitis degree. It emerges that the features of pain in patients in remission is different from other conditions (high disease activity or fibromyalgia), suggesting different underlying biological mechanisms. NIL. NIL. Simone Perniola Speakers bureau: ABBVIE, ELI LILLY ITALIA, GALAPAGOS BIOPHARMA, PFIZER, NOVARTIS, Consultant of: ABBVIE, ELI LILLY ITALIA, GALAPAGOS BIOPHARMA, Luca Petricca: None declared, Marco Gessi: None declared, Maria Rita Gigante: None declared, Martina Calabretta: None declared, Dario Bruno: None declared, Annunziata Capacci: None declared, Clara Di Mario: None declared, Barbara Tolusso: None declared, Stefano Alivernini Speakers bureau: ABBVIE, ELI LILLY ITALIA, PFIZER, NOVARTIS, Consultant of: ABBVIE, ELI LILLY ITALIA, PFIZER, NOVARTIS, Grant/research support from: PFIZER, Elisa Gremese Speakers bureau: ABBVIE, ELI LILLY ITALIA, GALAPAGOS BIOPHARMA, PFIZER, NOVARTIS, Consultant of: ABBVIE, ELI LILLY ITALIA, PFIZER, NOVARTIS, Grant/research support from: ABBVIE, PFIZER, NOVARTIS.

Female sex has been associated to higher disease impact in psoriatic arthritis (PsA), as measured by the PsA Impact of Disease (PSAID) questionnaire. However, it is unclear whether sex can influence all different PSAID domains (physical and psychological), or some of them, and whether confounders might be responsible for this association. 1) to assess the impact of sex on each of the 12 PSAID domains, and 2) to correct this association for known confounders, including fibromyalgia, to evaluate the independent effect of sex on each of them. Consecutive PsA patients, classified according to CASPAR criteria, attending our tertiary center between January and December 2022 were included. Demographic data, patient history, disease activity indices [Visual Analogue Scale (VAS) of pain and disease activity, Disease Activity in PsA (DAPSA) score) and functional indices (Health Assessment Questionnaire, HAQ) were collected. Impact of the disease was assessed by PSAID 12. Patients' characteristics were compared between men and women with descriptive statistics. Multiple linear regression models were built, having the 12 PSAID domains and total PSAID as outcomes (=13 outcomes), and sex as main independent variable. The crude and adjusted association between sex and each of the outcomes were studied. Namely, models were adjusted for: 1) age and DAPSA; 2) age, DAPSA and fibromyalgia. R[2] was used to measure the proportion of PSAID variance explained by sex. F-change test was used to evaluate if the addition of fibromyalgia as a confounder significantly contributed to improve the model fit. A total of 190 PsA patients were enrolled, 42% males, disease duration was 7.5±7.6 years. VAS pain, VAS disease activity, HAQ, all the 12 PSAID domains, and DAPSA were significantly higher in females (p<0.05). The univariate models having the PSAID domains as outcomes, and sex as independent variable, showed significant negative associations between the two (Table 1). R2 values highlighted that a small proportion of the PSAID variance was explained by sex only (R20.04-0.15). In the models corrected for age and DAPSA (model group 1, Table 1), male sex was a negative independent predictor of some of the PSAID domains (fatigue, work and leisure, functional capacity, discomfort, sleep disturbance, coping and depression). The addition of fibromyalgia as a confounder (model group 2, Table 1) significantly improved the model fit for many of the PSAID outcomes, and male sex remained independently associated only to functional capacity and coping. Sex alone is not able to explain PSAID variability, although it could have a higher impact on functional capacity and coping. More research is needed in order to understand the contextual factors that could explain the differences in PsA impact between men and women. NIL. NIL. None Declared. Table 1Association between male sex (independent variable) and the PSAID domains (outcomes)B-coefficient (95%CI) for male sexOutcomes-PSAID domainsUnadjustedAdjusted models 1Adjusted models 21. pain-1.9 (-3.2 -0.5)-1.0 (-2.0 0.0)NA2. fatigue-2.0 (-3.4 -0.7)-1.4 (-2.7 -0.1)-0.9 (-2.2 0.3)3. skin problems-1.1 (-2.2 -0.1)-0.6 (-1.8 0.6)-0.2 (-1.5 1.0)4. work & leisure-2.1 (-3.5 -0.7)-1.2 (-2.5 -0.5)-0.8 (-2.0 0.3)5. functional capacity-2.2 (-3.5 -0.9)-1.4 (-2.4 -0.4)-1.0 (-2.0 -0.0)6. discomfort-1.9 (-3,2 -0.6)-1.2 (-2.3 -0.1)-0.9 (-2.1 0.2)7. sleep disturbance-2.8 (-4.2 -1.5)-2.8 (-4.2 -1.4)-2.2 (-3.6 0.8)8. coping-2.1 (-3.4 -0.9)-2.1 (-3.4 -0.8)-1.8 (-3.1 -0.5)9. anxiety-1.0 (-2.4 0.3)-0.3 (-1.8 1.1)NA10. embarassment/shame-1.1 (-2.2 0.0)-0.5 (-1.8 0.7)NA11.social participation-1.2 (-2.4 -0.0)-0.4 (-1.6 0.8)NA12. depression-1.8 (-3.1 -0.55)-1.5 (-2.8 -0.1)NAPSAIDtot-1.9 (-2.9 -0.8)-1.0 (-2.0 -0.0)-0.6 (1.6 0.3)Legend. Models 1: corrected for age and DAPSA; Models 2: corrected for age, DAPSA, fibromyalgia. Significant results in bold. NA=Not Applicable (model not presented because the variable “fibromyalgia” did not significantly improve the model's fit)

Fibromyalgia syndrome (FM) is characterised by a complex symptom spectrum, dominated by the presence of chronic widespread pain, fatigue and unrefreshing sleep. FM affects between 2 and 3% of the general population. It is a condition that mainly involves middle-aged women, although it is increasingly being diagnosed in younger people. The severity of symptoms can vary greatly between individual patients, and is influenced by many factors (e.g. sex, body mass index) [1]. To date, there is little information about changes in severity in accordance with patient age. The aim of this study was to investigate variations in symptom severity in FM patients according to age categories. A cross-sectional study of adult FM patients diagnosed according to the American College of Rheumatology 2010/2011 criteria was performed. The case series was included from an Italian national registry [2]. Patients were grouped according to five age categories: 18-40 years, 41-50 years, 51-60 years, 61-70 years, over 71 years. Symptom severity was assessed through the revised Fibromyalgia Impact Questionnaire (FIQR) and domains, including FIQR physical function (items 1-9), FIQR health status (items 10-11), and FIQR symptoms (items 12-21). Between-group characteristics were analysed using one-way analysis of variance (ANOVA). This study included a total of 2889 patients, 403 aged 18-40 years, 756 aged 40-50 years, 1035 aged 50-60 years, 528 aged 60-70 years, and 167 over 70 years, respectively. The mean (standard deviation [SD]) score of the total FIQR was 52.68 (11.82). Total FIQR and individual domains all showed a normal distribution. Analysing the data by age category, there were statistically significant differences between the categories for the total FIQR (p = 0.030). The age categories with the highest disease severity were those above 71 years (FIQR 62.14, SD 22.45), and between 51-60 years (FIQR 60.31, SD 22.89) (Table 1). Significant differences between age categories were also found for the domains physical function (p = 0.006) and health status (p = 0.012), but not for the domain symptoms (p = 0.164). Distinguishing the disease severity in FM patients according to age categories, a bimodal distribution emerges, with the disease severity being greatest in patients over 71 years and in the 51-60 years decade. The main differences in severity, according to what can be detected through the FIQR, are attributable to the domains physical function and health status, which show higher scores in the two classes with higher severity. [1]Sarzi-Puttini P et al., Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nat Rev Rheumatol 2020; 16: 645–660. [2]Salaffi F et al., The Italian Fibromyalgia Registry: a new way of using routine real-world data concerning patient-reported disease status in healthcare research and clinical practice. Clin Exp Rheumatol 2020; Suppl 123: 65-71. Società Italiana di Reumatologia (SIR) and Italian Ministry of Health None declared Table 1Mean values of FIQR total score and domains according to age categories.FIQR and domains18-40 years41-50 years51-60 years61-70 years≥71 yearsp*FIQR total, mean (SD)57.90 (21.76)59.25 (23.30)60.31 (22.89)57.13 (23.59)62.14 (22.45)0.030FIQR physical function, mean (SD)15.51 (7.56)16.44 (7.77)16.77 (7.51)15.96 (7.82)17.68 (7.26)0.006FIQR health status, mean (SD)11.19 (5.85)11.24 (5.99)11.49 (5.93)10.57 (6.11)12.21 (5.97)0.012FIQR symptoms, mean (SD)31.32 (10.48)31.56 (11.32)32.10 (11.01)30.68 (11.47)32.24 (11.34)0.164Abbreviations and legend. FIQR = revised Fibromyalgia Impact Questionnaire; SD = standard deviation; * = one-way analysis of variance (ANOVA).

BackgroundCurrent therapies have transformed the management of rheumatoid arthritis. However, there are still a substantial proportion of patients who do not respond to treatments, and among those who respond, only small proportion achieve disease remission. We showed previously that human synovial tissue macrophages (STMs) are a heterogeneous population; and a sub-population of CD206+MertK+ positive STMs predominates in RA patients in sustained remission, in contrast to patients with active RA. Their surface receptors, e.g. MerTK, and distinct transcriptome suggest that they may play a pivotal role in re-enforcing joint homeostasis during remission.1 Thus, we hypothesise that activation of CD206+MerTK+ human synovial tissue macrophages contribute to the resolution of inflammation. ObjectivesWe aimed to investigate whether activation of MerTK in STM sub-population promotes an anti-inflammatory environment in the synovium.MethodsUsing flow cytometric techniques and with a specific antibody panel design,1 STMs from digested RA synovial biopsies (n=36) were phenotyped and/or harvested. Patients’ group included 28 patients with active disease and 8 patients in remission (DAS28 ESR <2.6 and power doppler negative). After excluding all other cell types, macrophages were gated based on the expression of CD64 and CD11b (CD45posCD64posCD11bposHLA-DRpos).1 Two distinct subpopulations: CD206+MerTK+ and CD206-MerTK- were sorted and cultured on a collagen coated 96-well plate at 1000 cells per well in the presence of with LPS (10 ng/ml)±Gas6, a MerTK ligand (200 ng/ml), for 24 hour. TNF production was measured with a high sensitivity ELISA.ResultsAs previously shown,1 RA patients in sustained remission have a majority of CD206+MerTK+ STMs whilst patients with active RA show an increased number of CD206-MerTK- macrophages. The percentage of CD206+MerTK+ macrophages negatively correlated with the disease activity score. Stimulation of FACS-Aria sorted CD206+MerTK+ and CD206-MerTK- macrophages with TLR4 ligand induced TNF production. However, activation of MerTK pathway by Gas6 inhibited LPS-induced TNF production by CD206+MerTK+ subpopulation.ConclusionsCD206+MERTK+ macrophages, which predominate in RA patients in remission, have Gas6-mediated negative feedback mechanism limiting TNF production. Thus, Gas6/MerTK pathway in synovial tissue macrophages could drive the resolution of inflammation and synovial tissue homeostasis. Further functional and transcriptomics studies will reveal the therapeutic potential of CD206+MERTK+ macrophages.Reference[1] Elmesmari A, et al. Synovial tissue of RA patients in remission contains a unique population of regulatory macrophages. Annals of the Rheumatic Diseases2017;76(Suppl2):138–139.Disclosure of InterestNone declared

Background Heart involvement is common in Systemic Sclerosis (SSc), even though it is often clinically silent, and represents one of the leading causes of death in these patients. Objectives The aim of the study was to define the role of troponin T (TnT) in the identification of a subclinical cardiac involvement and to correlate these levels to cardiac function and disease characteristics. Methods Cardiac enzymes were measured at least twice in 200 consecutive SSc patients (mean age: 58.7±13.9 years; mean disease duration: 11.1±9.0 years; diffuse disease: 38.0%; anti-Scl70 positivity: 45.5%) from 2008 to 2013. Data regarding disease subtypes and organ involvement were available for the entire cohort and all patients underwent: electrocardiogram (EKG), echocardiogram and pulmonary function test (PFTs). All SSc-related death were registred. Results Troponin T (TnT) levels were above the normal limit in 79 (39.5%) SSc patients (mean levels in positive patients:0.06±0.08 ng/ml), while only 42 patients (21%) presented raised CK-MB levels and 27 patients (13.5%) had an increase of NT-proBNP>600 pg/ml. The increase of TnT levels was associated with diffuse skin involvement and myositis (p<0.0001; p=0.006 respectively) and directly correlated with skin score (R=0.27; p<0.0001). Patients with high TnT levels presented a lower ejection fraction (59.5±9.3%) and an higher pulmonary artery systolic pressure on echocardiography (37.7±16.8 mmHg) compared to patients with normal TnT values (63.1±4.1%, p=0.04;28.3±6.8 mmHg,p<0.0001).These patients, furthermore, more frequently presented right bundle brunch block and/or fascicular heart block on EKG with respect to patients without increase of TnT (34.7% vs.10.5%; p<0.0001).Patients with high TnT levels had a more impaired lung function (DLCO 46.2±23.7%, FVC 88.3±22.5%, TLC 82.5±18.0) compared to patients with normal TnT (DLCO 56.1±22.3%, FVC 99.9±23.4%, TLC 93.2±19.3) (p<0.0001 for all comparisons). Interestingly, avascular areas at nailfold capillaroscopy were more frequently present in patients with high TnT levels compared to patients with normal TnT values (68.7% vs.46.9%; p=0.003). Moreover, TnT levels directly correlated with activity and severity indices (R=0.31; p<0.0001 for both correlations), C-reactive protein levels (R=0.31; p<0.0001), NT-proBNP and CK-MB (R=0.4; p<0.0001). During our follow-up, 16 SSc-related death occurred and 10 of these were directly related to cardiac involvement (sudden cardiac death or heart failure). All dead patients presented increased TnT levels. None of the patients with normal TnT values died for cardiac complications. At multivariate analysis, NT-proBNP >600 pg/ml (RR=12.6, CI=2.6-60) and troponin T>0.014 ng/ml (RR=9.5,CI=1.1-89) emerged as independent predictors of SSc-related death. Conclusions Our data suggest that subclinical myocardial involvement is more relevant in Scleroderma disease than appreciated previously, as revealed by the frequent detection of high TnT levels in SSc patients, especially in those with a more aggressive disease. As supported by the presence of a more impaired systolic function and more frequent EKG abnormalities in SSc patients with high TnT levels, this cardiac enzyme can be considered a useful biomarker of cardiac damage and a prognostic biomarker of cardiac-related death. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4477

Background Endothelial dysfunction is a key feature of systemic sclerosis (SSc) and the involvement of the microvasculature is one of the earliest features of the disease. Recent new criteria for very early diagnosis of systemic sclerosis (VEDOSS) have been proposed. Objectives The aim of this study was to investigate brachial artery endothelial-dependent flow-mediated dilation (FMD), IL-6 and VEGF levels in patients with primary Raynaud's phenomenon (RP) and SSc. Methods In this study we enrolled 59 patients: 10 VEDOSS patients fulfilling the proposed VEDOSS criteria, 28 SSc patients fulfilling the 1987 ACR criteria, 11 gender and age matched healthy individuals as first control group and 10 gender and age matched primary RP patients with normal capillaroscopic findings as the second control group. Demographic, clinical and immunological parameters have been collected at the beginning of the study. Ultrasound assessment of FMD was performed in all RP subjects and in healthy subjects to evaluate endothelial dysfunction. VEGF, VEGF-RII, IL-6 and IL-6R plasma were determined by ELISA. Results Scleroderma patients showed a reduced FMD (5.8±4.7%) compared to healthy controls (18.9±6.7%) (p<0.0001), and to subjects with RP (1.6±5.6%),(p=0.001). FMD of scleroderma patients and VEDOSS patients was comparable (6.6±3.8%). VEDOSS patients showed values of FMD significantly compromised compared to those of RP (p=0.05) and healthy controls (p<0.001). Finally, patients with primitive RP showed reduced FMD values compared to healthy controls (p=0.008). The values of FMD correlated inversely with disease duration (r=-0.46, p=0.004) and directly with the levels of KCO (r=0.47, p=0.007). The plasma levels of VEGF in patients with SSc (29.8±40.7 pg/ml) were significantly higher than in healthy controls (13.0±24.8 pg/ml,(p=0.03) while they were similar to those of patients with VEDOSS (22.6±21.7 pg/ml). Plasma levels of IL-6 were higher in SSc patients (5.7±11.1 pg/ml) compared to VEDOSS (1.5±1.2 pg/ml) (p=0.04),RP (1.1±0.5 pg/ml), (p<0.0001) and healthy controls (1.9±3.1 pg/ml) (p<0.001). Levels of VEGF-R2 and sIL-6R were comparable in all groups. IL-6 levels were higher in dcSSc patients than in lcSSc patients (7.9±13.0 pg/ml vs 1,9±0,6 pg/ml) (p=0,0027). Finally in patients with SSc the capillaroscopic density inversely correlated with the levels of IL-6, the Activity and Severity Indices, the Skin Score and the duration of the disease. Conclusions An impairment of FMD was present in patients with RP, in particular in SSc and VEDOSS patients, suggesting a contemporary impairment of microvascular and macrovascular compartments. The deeper FMD impairment that characterize either SSc and VEDOSS patients, suggests that the endothelial dysfunction is already established since the early phases of the disease and it worses during the disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4446

Background Previous studies have shown that about 7% of unselected systemic sclerosis (SSc) patients are positive for ANCA1. Some case reports have also described an ANCA–associated vasculitis in SSc patients with progressive renal and lung function deterioration and poor outcome. Objectives To evaluate the prevalence of ANCA positivity in a SSc cohort and to study its association with clinical characteristics, major organ involvement and risk of mortality. Methods We evaluated the positivity and the levels of p- and c-ANCA in our cohort of 294 SSc patients according with age, immunological characteristics, disease duration and clinical manifestations. Only patients with almost two positive ANCA assessments have been considered ANCA positive. Specifically we evaluated the presence of digital ulcers, glomerulonephritis, myositis and myocarditis. Myocarditis was defined as the presence of increasedcardiac enzymes associated with the presence of enhancement at late gadolinium-enhanced cardiac magnetic resonance imaging and/or myocarditis on myocardial biopsy. The mortality in the last 12 years was also recorded. Results 17 patients out of 294 (5.8%) of the entire SSc cohort were identified as ANCA-positive. Six patients (35.3%) were c-ANCA positive with a mean level of 70.4±50.7 U/ml, while 11 patients (64.7%) were p-ANCA positive with a mean level of 65.8±47.7 U/ml. Out of the 17 ANCA positive patients, 58.8% presented anti-topoisomerase antibodies, 41.2% anticentromere antibodies. Sixteen patients (5.4%) presented myocarditis which was more frequent in patients with ANCA positivity than in ANCA negative patients (41.7% vs 3.2%, p<0.0001). Overall mortality was 6.8%. Mortality in ANCA positive patients was higher than in ANCA negative patients (29.4% vs 5.4%, p=0.003). There was no association between ANCA positivity and complement consumption, glomerulonephritis, myositis and digital ulcers. Conclusions The prevalence of ANCA positivity in our cohort was 5.8% and, as previously reported, the majority of patients was positive for anti-topoisomerase antibodies. ANCA positivity was associated with myocarditis and with an increased risk of mortality. Considering the high mortality associated with cardiac involvement in SSc patients, our preliminary data suggest that ANCA positivity in SSc patients should be a warning biomarker to identify patients at risk of myocarditis and of a poor survival. References Akimoto S, Ishikawa O, Tamura T, Miyachi Y. Antineutrophil cytoplasmic autoantibodies in patients with systemic sclerosis. Br J Dermatol 1996;134(3):407-10. Disclosure of Interest None Declared

Background The association of systemic sclerosis (SSc) with the exposure to environmental agents is supported by a number of case reports and some case-control studies. No conclusive results have been reported, but there are some evidences that exposure to vinyl-chloride-polymers (PVC), silica dust or organic solvents such as benzene (B) and xylene (X) may be implicated. Furthermore a higher prevalence of scleroderma in boroughs in close proximity to a major airport, has been reported, but few data on air pollution exposure and risk of systemic sclerosis are available. Recently, particulate air pollution has been consistently linked to increased risk of arterial cardiovascular disease. Objectives We studied relationships between outdoor concentration of B and particulate with clinical manifestations of SSc based, for the exposure, on the urban residence of patients. Methods Before patient administration, the questionnaire was validated by Delphi technique (4 rheumatologists, 4 statisticians and 2 common people). A cohort study of 88 SSc patients, filled the validated self administered questionnaire (analyzing drug, work and environmental exposure) to investigate potential risk exposure before and after the onset of the disease. The average mean concentrations of B (11 monitoring sites) and environmental particulate matter with aerodynamic diameter ≤ 10 μm(PM10) (14 sites) were computed using data from monitors located throughout the Lazio region, in Italy. In a sample of 33 patients we performed correlations between the concentrations of PM10 and B with the demographic and clinical characteristics, going back to a prior exposure of 2 years before the onset of Raynaud’s phenomenon (RP). Results The questionnaire resulted in an agreement of the overall experts of about 94% (according to11/190 disagreement for comprehension, only few lexical modifications were done to improve the questionnaire after the consensus between the experts), with an Inter-observer agreement (measured throughout K Cohen test) of 0.8019(p<0.01) showing a very good concordance. The mean disease duration from the RP onset was 13.0±9.4 years and the mean age was 55.0±12.9 years. 92.5% of patients were female. No correlations were found between different clinical disease characteristics and drug assumption and work exposure. Considering patients that lived in Lazio, SSc patients with diffuse skin disease were exposed 2 years, before the onset of RP, to a higher concentrations of benzene (8.5±1.5µg/m3) with respect to patients with limited skin disease (4.97±2.7µg/m3), which was statistically significant of p=0.02. Furthermore the concentrations of benzene correlated directly with the skin score (R=0.3, p≤0.05) and inversely with DLCO (R=-0.36, p≤0.05). SSc patients with ulcers were exposed 2 years before the onset of RP to higher concentrations of B (6.4±3.2 µg/m3), than the patients without ulcers (4.9±2.3µg/m3), but the difference did not reach statistical significance. Conclusions This study, on the role of environmental agents in the manifestations of SSc, suggests an increased exposure to benzene in the development of a diffuse skin disease and a possible predisposing effect on the occurrence of ulcers. Disclosure of Interest None Declared