Background:Interstitial lung disease (ILD) is associated with a significant increase in morbidity and mortality in patients with rheumatoid arthritis (RA). Therefore, an early diagnosis is fundamental. Anti-carbamylated proteins (Anti-CarP) have been described in different chronic respiratory diseases without a previous history of RA.Objectives:The aim of this study was to analyse the association between Anti-CarP and ILD in RA patients.Methods:We performed a cross-sectional study, including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised 2 groups: 1) RA patients diagnosed with ILD (RA-ILD group) and 2) RA patients without ILD (non-ILD RA group). ILD was diagnosed by high-resolution tomography and confirmed by a multidisciplinary committee. Three IgG Anti-CarP autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib), and fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarPs and ILD were explored using multivariable logistic regression adjusted by a set of variables known to be related to the development of ILD: smoking, sex, age, RA disease duration, RF and ACPA. An independent replication sample was obtained to validate our findings from another hospital.Results:The main population included 179 patients: 37 were included in the RA-ILD group, and 142 in the non-ILD RA group. Most patients were female (79%), with a mean age of 59.7±13 years with a mean disease duration of 6.6±5 years. Baseline features are shown in table 1. The replication sample was composed of 25 patients in the RA-ILD group and 50 patients in the non-ILD RA group. We found that Anti-CarPs specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs. 43%; Anti-Fib 73% vs. 51%; Anti-CFFHP 38% vs. 19%; Anti-CarP-IgA 51% vs. 20%, p<0.05 for all comparisons). Serum mean titers of Anti-CarPs were higher in RA-ILD patients with significant statistical differences for all of them, except Anti-Fib. The multivariate analysis showed that Anti-CarPs specificities were independently associated with ILD (Anti-FCS (OR: 3.42; CI95%: 1.13-10.40), Anti-Fib (OR: 2.85; CI95%: 0.83-9.70), Anti-CFFHP (OR: 3.11; CI95%: 1.06-9.14) and Anti-FCS-IgA (OR: 4.30; CI95%: 1.41-13.04). In the replication sample our findings were validated only for Anti-FCS (OR: 10.42; CI95%: 1.68-64.46).TABLE 1.Main population demographic, clinical, therapeutic, and autoantibody status features.RA-ILDn:37Non-ILD RAn:142p valueFemale (%)25 (68)116 (82)NSAge mean (±SD)67.3 (10.1)57.7 (12.9)<0.005Mean disease duration (±SD)11.6 (7.1)5.3 (13.3)<0.005Ever smokers (%)21 (57)62 (44)NSSmoking cumulative dose (±SD)30.7 (11.1)21.8 (12)<0.005Caucasian (%)31 (84)120 (85)NSTreatmentGlucocorticoids (%)25 (68)81 (57)NScsDMARDs (%)33 (89)132 (86)NSMTX (%)20 (54)95 (67)NSbDMARDs (%)11 (30)36 (25)NSMean DAS28 (±SD)3.71 (1.35)2.74 (1.05)<0.005Erosive disease (%)26 (70)63 (44)<0.005Mean HAQ-DI (CI-95%)0.69 (0.53-0.85)0.31 (0.24-0.38)<0.005ACPA positive (%)29 (78)99 (70)NSMedian titer ACPA (IQR) CU674 (2,215)143 (1,132)NSRF positive (%)28 (76)83 (59)NSMedian titer RF (IQR) IU105 (298)34 (110)NSConclusion:A strong association between RA-ILD and Anti-CarP was found independently of cofounders, including RF and ACPA. Our findings suggest a possible link between Anti-CarP and the development of ILD.Disclosure of Interests:Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Sebastian Rodriguez-Garcia: None declared, Katherine Cajiao: None declared, Gabriela Jimenez: None declared, Maria Jose Gomara: None declared, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Ivette Casafont-Solé: None declared, Julio Ramirez: None declared, José Gomez Puerta Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Susana Holgado Pérez: None declared, Juan de Dios Cañete: None declared, Isabel Haro: None declared, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer

Background:Seronegative (sero-) and seropositive (sero+) Rheumatoid Arthritis (RA) have different genetic, immunopathological and vascular morphology features, but no previous studies have analyzed if US characteristics differ between sero+ or sero- RA. Our preliminary studies suggest that sero+ RA is associated with an expansive synovitis pattern that we have called “proliferative synovitis” (PS)Objectives:To analyze potential differences between patients with RA according to their autoantibody status by using ultrasonography (US). We aimed to assess whether PS is associated with ACPA+ ptsMethods:We collected clinical, epidemiological data and bilateral carpal and hand US images of pts with RA. Synovial hypertrophy (SH), Power Doppler signal (PD) and total score (sum of scores of SH and PD) in wrist and hand (1-5 metacarpophalangeal) were assessed. We evaluated the presence of PS, defined as expansive synovial growth encompassing the concepts of synovial SH grade II and III. We performed synovial biopsies of a subgroup of pts using arthroscopy or US guided in order to see immunohistochemistry differences between “proliferative” and “flat” (non-proliferative) synovitis. Serum levels of angiogenic and inflammatory biomarkers were performedResults:Two hundred and five RA patients were collected. Overall, 173 (84.8%) pts were sero+ for RF (68.7%) or ACPA (74.6%), general characteristics are summarized in Table. No significant differences between sero+ and sero- pts in terms of disease activity or therapy were found. PS was present in 55.5% of sero+ pts (55.3% in RF+ and 58.2% in ACPA+ pts) and 16.1% of sero- pts (p=0.0001). Globally, 101 pts (49.2%) had PS. Ninety-six (95.0%) were RF or ACPA positive. Only 5 pts with sero- RA had PS (p=0.001). In the univariate analysis, significantly more pts with PS had erosive disease (72.3% vs 35.0% p=0.0001), higher US scores (p=0.0001) and more of them were taking conventional synthetic Disease-modifying anti-rheumatic drugs (csDMARD) (81.8% vs 69.6% p=0.05). No differences regarding disease activity were found.In the multivariate analysis erosions [OR 4.90 CI 95% (2.17-11.07) p=0.0001] and ACPA [OR 3.5 CI 95% (1.39-10.7) p=0.09] but not RF status [OR 0.74 CI 95% (0.31-1.71) p=0.483] were independently associated with the presence of PS.We immunostained synovial biopsies from 23 pts with PS (13 pts) or non-PS (10 pts). PS was significantly associated with higher density of vessels (p=0.042) and a strong trend to a higher density of B, T, Mast cells and macrophages (figure 1). Significantly higher serum levels of angiogenic (Activin A, bFGF, IL18, IL20, PIGF, SDF-1 and VEGF-D) and pro-inflammatory (IL23) cytokines were found in patients with PS (figure 2).Conclusion:The presence of “proliferative Synovitis” was significantly associated with ACPA and erosive disease in patients with RA. PS pattern also was associated with higher density of synovial vessels and higher serum levels of angiogenic and inflammatory mediatorsTable .Total US pattern p valueN=205Proliferative (N=101)Non proliferative (N=104)Female, n (%)162 (79.4)79 (78.2)83 (80.6)0.57Age, mean (SD) years57.1 (± 14,1)56.3 (± 12.0)58.0 (± 15.9)0.40Current Smoker, n (%)47 (26.9)22 (25.6)25 (28.1)0.73Disease duration, mean (SD) months113.3 (± 105.7)127.7 (± 111.1)99.3 (± 99.3)0.05Erosion, n (%)108 (53.7)73 (72.3)35 (35.0)0.00ACPA, n (%)153 (75.4)89 (89)64 (62.1)0.00RF, n (%)99 (68.3)78 (78)63 (61.2)0.01DAS 28–CRP, mean (SD)2.55 (±1.03)2.66 (±1.04)2.44 (±1.02)0.17GC, n (%)99 (49.3)45 (45.5)54 (52.9)0.32cDMARDs, n (%)152 (75.6)81 (81.8)71 (69.6)0.05bDMARD, n (%)69 (34.3)35 (35.4)34 (33.3)0.76Total US score14.9 (± 11.5)18.8 (± 11.8)11.1 (± 9.9)0.00*ACPA anti-citrullinated protein antibodies, RF rheumatoid factor, DAS28-CRP Disease Activity Score 28-joint count, CRP C-reactive protein, GC glucocorticoids, bDMARD biological disease-modifying antirheumatic drugsDisclosure of Interests:Ana Belén Azuaga-Piñango: None declared, Beatriz Frade-Sosa: None declared, Roberto Gumucio: None declared, Katherine Cajiao: None declared, Andrea Cuervo: None declared, Raquel Celis: None declared, Jose A. Gómez-Puerta Speakers bureau: Abbvie, BMS, GSK, Lilly, Pfizer, Roche, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Juan de Dios Cañete: None declared, Julio Ramirez: None declared

Background:Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) have a different ultrasound (US) patterns. Synovial changes are characteristic of RA patients and soft tissue changes are more frequently found in PsA. However, no previous studies have analysed if US findings differ between seropositive and seronegative RA patients.Objectives:To analyse differences in the ultrasound pattern among patients with seropositive and seronegative RA. To assess if proliferative globular synovitis is characteristic of seropositive RA.Methods:Retrospective Analysis. We collected clinical, epidemiological and ultrasound images of patients with RA who met American College of Rheumatology/European League Against Rheumatism 2010 criteria1 with bilateral carpal and hand ultrasonography carried out during the last five years. Synovial hypertrophy (SH) and Power Doppler signal (PD) in wrist and hand (1-5 metacarpophalangeal [MCP]) were evaluated. We calculated the SH score (sum of the SH degrees of each joint), PD (sum of the PD degrees of each joint) and the total score (sum of the score of SH and PD) for each patient. We also evaluated the presence of proliferative globular synovitis, defined as big synovial hypertrophy with exophytic growth and a convex upper limit.Results:145 RA patients were collected. 80% were women. Mean age was 59.06 (14.8) years and the mean time of disease evolution was 114.6 (112.8) months. 68.3% were RF positive and 74.5% ACPA positive. Overall, 115 of the 145 (79.3%) patients were seropositive for RF/ACPA. 53.1% had radiographic erosions, 73.1% used conventional synthetic Disease-modifying drugs (DMARDs), 29.7% biological therapy, and 57.2% low doses of corticosteroids (<5 mg prednisone). The mean DAS28 was 2.81 (1.14), the number of swollen joints was 3 (3.4), and the C reactive protein (CRP) was 0.99 mg/dl (1.6).No significant differences between seropositive and seronegative patients in terms of disease activity (swollen joints count [SJC], tender joint count [TJC], CRP, DAS28), treatment (use of corticosteroids, DMARDs, biological), time of evolution or US scores (SH, PD and total scores) were found. Globular synovitis was present in 62% and 13.7% of seropositive and seronegative RA patients, respectively (p<0.0001).Globally, 75 (51.7%) out of 145 patients had ”globular” synovitis by US (Figure 1). 71 out of 75 patients were FR/ACPA positive (94.6%). Only four patients with seronegative RA had this US pattern (p <0001). Furthermore, patients with ”globular” synovitis had more erosions (72% vs 33%, p <0.0001), higher SJC (3.3 vs 2.5, p = 0.013) and higher SH and PD scores (p=0.0001).Conclusion:The presence of proliferative globular synovitis was significantly associated with the presence of RF/ACPA in patients with RA. This US pattern identified a subgroup of RA patients with poor prognosis: more erosions and greater inflammatory activity both at clinical and ultrasound level.References:[1] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Hawker G, et al. 2010rheumatoid arthritis classificatio...

BackgroundHypertrophic osteoarthropathy (HOA) is characterized by several clinical findings, including arthralgia/arthritis, periostosis, and digital clubbing. It can occur as a congenital condition called pachydermoperiostosis, and more commonly, as a secondary manifestation of pulmonary or extrapulmonary diseases or malignancy. Genomic studies support the role of prostaglandin E2 (PGE2) in the pathogenesis of primary HOA, with mutations in the 15-hydroxyprostaglandin dehydrogenase encoding gene resulting in increased PGE2 levels.ObjectivesTo analyse the clinical characteristics, comorbidities, and the potential role of PGE2 in primary and secondary forms of HOA and/or clubbing and also evaluate the clinical evolution of these patients.MethodsEighteen patients (10 men/8 women) aged 15 to 78 years (49,9 ± 15,6) diagnosed with clubbing and/or HOA were attended in our Rheumatology Department over an 11-year period. We reviewed the clinical characteristics of the patients, including associated comorbidities, image findings, bone turnover markers (BTM), and serum and urinary levels of PGE2, among others. Additionally, we evaluated the treatment and the clinical evolution of these subjects.ResultsMost patients presented associated clinical conditions for HOA and/or clubbing, with only one, the youngest (15 years old), having primary HOA (pachydermoperiostosis). Pulmonary disorders were the most frequent associated conditions, with interstitial lung disease (4 cases), COPD (3 cases), and lung cancer (4 cases) being the most frequent, followed by liver diseases including primary biliary cirrhosis (1 patient), liver cirrhosis (2 patients) and chronic hepatitis C virus (2 patients). All the subjects evaluated (15/18) presented increased urinary PGE2 levels (the highest being observed in primary HOA), with most also presenting increased serum PGE2 values. BTM were evaluated in most subjects (17/18) showing increased values in most (11/17), particularly in PINP and CTx. 4 patients were treated with selective inhibitors of cyclooxygenase-2 (COX-2) presenting, when evaluated, a small decrease in urinary PGE2 titers and partly improving their symptoms, which clearly improved after treating the associated cause when possible.ConclusionIn the present series, all subjects with primary or secondary HOA and/or clubbing presented markedly increased PGE2values, particularly in urine, supporting the role of this agent in the etiopathogenesis of this disorder. Pulmonary disorders, including malignancy and liver diseases, constituted the most frequent associated conditions. The use of COX-2 seems to be an effective symptomatic therapeutic approach in this entity.Disclosure of InterestsNone declared

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