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ObjectiveThis literature review aimed to identify the most efficacious current interventions for dactylitis and provide up-to-date scientific evidence to support the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommendations on the management of psoriatic arthritis.MethodsOriginal articles published from 2013 to 2020, registered in MEDLINE, Embase, and Cochrane Library, describing interventional trials and reporting dactylitis-related outcomes were included. The 20 members of the GRAPPA dactylitis group were divided into 9 subgroups according to treatment, and members of each group independently extracted data from articles/abstracts corresponding to their group by using a standardized data extraction form.ResultsForty-nine publications were analyzed, representing 40 randomized clinical trials (RCTs) and including 16,752 patients. Dactylitis was assessed as a secondary outcome in 97.5% of these trials and more than 40% of RCTs did not employ a specific dactylitis measure or instrument.ConclusionThe emergence of agents with novel mechanisms of action in recent years, such as interleukin 17 (IL-17), IL-12/23, IL-23, and Janus kinase inhibitors, has significantly expanded the available treatment options for dactylitis. This article points out the lack of consensus regarding dactylitis assessment and the paucity of data concerning the effect of local steroid injections, nonsteroidal antiinflammatory drugs, and conventional disease-modifying antirheumatic drugs. Clinical trials evaluating the effect of these traditional and low-cost medications used to treat dactylitis should be encouraged.

Objective. To assess the performance of the new 2012 provisional European League Against Rheumatism (EULAR)/ American College of Rheumatology (ACR) polymyalgia rheumatica (PMR) clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous 5 diagnostic criteria in a multicenter prospective study. Methods. Patients older than 50 years, presenting with new-onset bilateral shoulder pain with elevated acute-phase reactants (APR), were assessed for the fulfillment of the new and old classification/diagnostic criteria sets for PMR. At the end of the 1-year followup, 133 patients were diagnosed with PMR (expert opinion) and 142 with non-PMR conditions [69 rheumatoid arthritis (RA)]. Discriminating capacity, sensitivity, and specificity of the criteria sets were estimated. Results. Discriminating capacity of the new clinical criteria for PMR from non-PMR conditions and RA as estimated by area under the curve (AUC) were good with AUC of 0.736 and 0.781, respectively. The new criteria had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. When tested against all RA, seropositive RA, seronegative RA, and non-RA control patients, specificity changed to 66.7%, 100%, 20.7%, and 49.3%, respectively. Except for the Bird criteria, the 4 previous criteria had lower sensitivity and higher specificity (ranging from 83%-93%) compared with the new clinical criteria in discriminating PMR from all other controls. Conclusion. The new 2012 EULAR/ ACR clinical classification criteria for PMR is highly sensitive; however, its ability to discriminate PMR from other inflammatory/noninflammatory shoulder conditions, especially from seronegative RA, is not adequate. Imaging and other modifications such as cutoff values for APR might increase the specificity of the criteria.

Objective. Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. Methods. Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results. We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 x 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 x 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 x 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 x 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 x 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Conclusion. Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped similar to 200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 x 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 x 10(-9); and rs189754752, OR = 2.47, p = 4.22 x 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 x 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 x 10(-8)).

Introduction: HLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Beh et's disease and HLA-B*52 in Takayasu's arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B* 52 as susceptibility and severity factors. Methods: TAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B* 51 or HLA-B* 52 was screened for by using PCR with sequence-specific primers. Results: We found a significant association of HLA-B* 52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B* 51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA-B* 52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B* 52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78). Conclusions: In this study, the previously reported association of TAK with HLA-B* 52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B* 52 in TAK pathogenesis needs to be explored further.

Background Genetic and environmental factors are known to play a role in the pathogenesis of spondyloarthropathies (SPA). Mannose binding lectin (MBL) which is a member of collectin family proteins, is an important component of innate immunity. Low levels of MBL is associated with susceptibility to infections. Several variants of MBL gene may result in MBL deficiency. MBL gene polymorphisms and MBL deficiency are shown to be related with several autoimmune and inflammatory diseases. Objectives The relationship between the MBL levels or MBL gene polymorphisms and SPA predisposition has previously been investigated in a few small studies with conflicting results. In this particular study, we aimed to assess the relationship of the MBL genes in the develepoment of SPA in a group of Turkish patients. Methods Study included 132 patients with SPA (75 female, 57 male, mean age: 43.0±12.4) and 87 healthy subjects (58 women, 29 men, mean age: 40.3±13.4) as control group. Eighty nine of the SPA patients had ankylosing spondylitis (AS) and 43 had non-AS SPA. MBL gene single nucleotide polymorphisms (SNP) in the codons 52, 54 and 57 of exon 1 were studied by sequencing method. Results G54D G>A polymorphism was not different between the patient and the healthy control groups (p=0.291). The frequencies of R52C C>T and G57E G>A polymorphisms were found to be significantly higher in the SPA patients than those of the healthy controls (p=0.019 and 0.001 respectively). While the non-AS subgroup showed significancy for both R52C C>T and G57E G>A polymorphisms (p=0.004 and 0.000 respectively), the AS subgroup showed significancy only for G57E G>A (p=0.113 and 0.014 respectively). Clinical characteristics of either AS or non-AS SPA patients were not associated with any of the MBL polymorphisms. In a previous study, haplotypes of MBL genetic polymorphisms were found to be associated with AS in Korean patients. Our study is the first one from Turkey indicating the relationship between SPA9s and MBL gene polymorphisms. Conclusions Even though we had rather small sample size, our results showed significantly higher R52C C>T and G57E G>A polymorphisms in Turkish patients with SPA. Therefore we may suggest that MBL gene polymorphisms could be related with the predisposition of the disease. References Churl Hyun Im et al.: Mannose-binding lectin 2 gene haplotype analysis in Korean patients with ankylosing spondylitis. Rheumatol Int (2012) 32:2251–5 Aydin SZ et al: Mannose binding lectin levels in spondyloarthropathies. J Rheumatol. (2007) Oct;34(10):2075–7 Aydin SZ et al: Mannose binding lectin levels are not related to radiographic damage in ankylosing spondylitis Rheumatol Int (2010) 30:415–7 Disclosure of Interest None declared

Psoriatic arthritis (PsA) is a chronic inflammatory disease with a wide and heterogeneous spectrum of pathologic conditions including intra-articular and peri-tendinous synovitis, enthesitis, psoriatic plaque and onycopathy (1). Since angiogenesis plays a key role in the pathogenesis of both synovial tissue and skin involvement, the term “psoriatic disease” has been introduced to underline that the disease has the potential to affect different tissues (2). Technological advances are constantly improving the diagnostic ability of the imaging modalities, especially of ultrasound and magnetic resonance imaging, opening new sceneries in the research field (3–11). The recent availability of an ultrasound probe with a B-mode frequency reaching 22 MHz allows for a detailed morpho-structural assessment together with a highly sensitive detection of blood flow in small vessels of superficial tissues. This is of particular interest, considering that most of the PsA targets are superficial tissues. The main aims of this presentation are to discuss the most relevant investigations aiming at assessing the role of histology and imaging in PsA, and to show the diagnostic ability of the last generation imaging modalities in the evaluation of the main PsA targets (i.e. joint, tendon, enthesis, skin, and nail). References Coates LC, Anderson RR, Fitzgerald O, Gottlieb AB, Kelly SG, Lubrano E, McGonagle DG, Olivieri I, Ritchlin CT, Tan AL, De Vlam K, Helliwell PS. Clues to the pathogenesis of psoriasis and psoriatic arthritis from imaging: a literature review. J Rheumatol 2008;35:1438–42 Gutierrez M, Filippucci E, De Angelis R, Filosa G, Kane D, Grassi W. A sonographic spectrum of psoriatic arthritis: “the five targets”. Clin Rheumatol 2010;29:133–42 Aydin SZ, Bas E, Basci O, Filippucci E, Wakefield RJ, Celikel C, Karahan M, Atagunduz P, Benjamin M, Direskeneli H, McGonagle D. Validation of ultrasound imaging for Achilles entheseal fibrocartilage in bovines and description of changes in humans with spondyloarthritis. Ann Rheum Dis 2010;69:2165–8. Filippucci E, De Angelis R, Salaffi F, Grassi W. Ultrasound, skin, and joints in psoriatic arthritis. J Rheumatol Suppl. 2009;83:35–8. McGonagle D, Ash Z, Dickie L, McDermott M, Aydin SZ. The early phase of psoriatic arthritis. Ann Rheum Dis 2011;70 Suppl 1:i71–6. McGonagle D, Aydin SZ, Tan AL. The synovio-entheseal complex and its role in tendon and capsular associated inflammation. J Rheumatol Suppl 2012;89:11–4. Terslev L, Naredo E, Iagnocco A, Balint PV, Wakefield RJ, Aegerter P, Aydin SZ, Bachta A, Hammer HB, Bruyn GA, Filippucci E, Gandjbakhch F, Mandl P, Pineda C, Schmidt WA, D9Agostino MA; Outcome Measures in Rheumatology Ultrasound Task Force. Defining enthesitis in spondyloarthritis by ultrasound: results of a Delphi process and of a reliability reading exercise. Arthritis Care Res (Hoboken) 2014;66:741–8. Gutierrez M, Filippucci E, Salaffi F, Di Geso L, Grassi W. Differential diagnosis between rheumatoid arthritis and psoriatic arthritis: the value of ultrasound findings at metacarpophalangeal joints level. Ann Rheum Dis 2011;70:1111–4. Gutierrez M, Di Geso L, Salaffi F, Bertolazzi C, Tardella M, Filosa G, Filippucci E, Grassi W. Development of a preliminary US power Doppler composite score for monitoring treatment in PsA. Rheumatology (Oxford). 2012;51:1261–8. Gutierrez M, De Angelis R, Bernardini ML, Filippucci E, Goteri G, Brandozzi G, Lemme G, Campanati A, Grassi W, Offidani A. Clinical, power Doppler sonography and histological assessment of the psoriatic plaque: short-term monitoring in patients treated with etanercept. Br J Dermatol. 2011 Jan;164(1):33–7. Grassi W, Gutierrez M, Filippucci E. The sound of enthesis. J Rheumatol 2010;37:1986–8. Disclosure of Interest None declared

The spondyloarthropathies (SpA) are characterized by asymmetrical arthritis especially affecting the lower limbs and inflammation at many other diverse locations, chief of which is axial skeleton involvement. Enthesitis, or inflammation of ligaments and tendons insertions to bone, is considered to be the unifying pathological hallmark of the disease but the link between enthesitis and how it may trigger a “secondary synovitis” was contentious. The microanatomical, functional biomechanics and immunopathogenic considerations pertaining to the enthesis led to the concept that the enthesis organ contained a unit termed a “synovio-entheseal complex” (SEC) [1]. The SEC work together to dissipate load over a wider area and at the same time the adjacent synoviocytes function to lubricate and nourish the fibrocartilage via synovial fluid which in health maintains joint homeostasis. On the other hand, the SEC structure brings the synovium, a tissue lined with macrophages with considerable pro-inflammatory potential into close juxtaposition with mechanically stressed or injured adjacent avascular fibrocartilage tissue. It was hypothesized that these joint specific injurious/mechanical factors acted as danger signals thus triggering innate immune responses in the adjacent synovium. What could not be demonstrated at that time was the order of the events- e.g. the enthesitis being the initial manifestation; the triggering factors and why the enthesis is a target tissue in spondyloarthropathies. Recent experimental studies supported the SEC concept. Jacques et al showed that biomechanical stress is a key component to trigger enthesitis, which subsequently spreads to the adjacent synovium with erosion and pannus formation, and that unloading by tail suspension suppresses the inflammation of the enthesis [2]. Sherlock et al, showed that type II-collagen-specific antibody transfer resulted with severe enthesitis that was prominent before progression to the destructive synovitis and osteitis [3]. This group also reported that disease was dependent on an enthesis resident population of RORΥt + CD3 + CD4 – CD8 – that were dependent on IL-23 stimulation with the elaboration of inflammatory mediators such as IL-17 that are mechanistically associated with synovitis. Prior work has also shown that TNF overexpression is also associated with arthritis that starts at the enthesis before spreading to the adjacent synovium [4]. The current evidence shows that the mechanical stress in mice that are prone to spondyloarthropathies may cause to enthesitis initially which is then followed by synovitis. With respect to the SEC in man, imaging studies in SpA have shown that findings indicative of inflammation may not be evident at the enthesis insertion per se but may manifest in the adjacent bursae in some cases supporting the idea of integrated SEC related disease rather than inflammation spreading from the more distal parts of the enthesis. Finally, the well-known association of psoriatic nail disease with adjacent distal interphalangeal arthritis has been carried one step further and it has been demonstrated that the inflammation can also distribute to the skin and the extensor tendon enthesis supporting the idea of an elaborate SEC organ around the DIP joint [5]. The recognition of increased vascularity in aymptomatic enthesis of patients with psoriatic arthritis compared to both psoriasis and healthy controls led to the hypothesis that a vascular phenotype at insertions may be an important step to switch from psoriasis to psoriatic arthritis [6]. In conclusion since the first introduction of SEC, evidence has accumulated from different approaches including animal models, molecular biology and imaging which are all supportive of SEC. References McGonagle D et al. The concept of a “synovio-entheseal complex” and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 2007; 56:2482-2491 Jacques P et al. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis 2014; 73:437-445 Sherlock JP, Joyce-Shaikh B, Turner SP, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med 2012; 18:1069-1076 Armaka M et al. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J Exp Med 2008; 205:331-337 Aydin SZ et al. Ultrasonographic assessment of nail in psoriatic disease shows a link between onychopathy and distal interphalangeal joint extensor tendon enthesopathy. Dermatology 2012; 225:231-235 Aydin SZ et al. The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development. Ann Rheum Dis 2012 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.6158

BackgroundPsoriatic arthritis (PsA) can present with peripheral (i.e. arthritis, enthesitis, dactylitis) and/or axial (spondyloarthritis) manifestations. Positron Emission Tomography (PET) may be a promising imaging technique for detection of whole body disease activity since it combines quantification and picomolar sensitivity for accurate depiction of pathologic processes with anatomical low dose CT imaging as a reference (3, 4). It was recently demonstrated that [18F]Fluoride PET-CT scans can successfully visualize and monitor ankylosing spondylitis disease activity by imaging of bone formation in the axial skeleton (5). Since bone formation is associated with enthesitis and synovitis in PsA, [18F]Fluoride may enable sensitive, whole body detection of disease activity in PsA.ObjectivesTo investigate the feasibility of [18F]Fluoride PET-CT to visualize disease activity of PsA by imaging of bone formation at axial and peripheral sites in PsA patients.MethodsSixteen patients (female 10/16, age 50.6 ±8.9 years) with PsA fulfilling CASPAR criteria and clinically active disease including ≥1 clinically active enthesitis site were included. Clinical disease activity was assessed by swollen joint count/tender joint count 44, MASES and SPARCC. Of each patient, a whole body [18F]Fluoride PET-CT scan at 45 minutes post injection was performed. All scans were dichotomously scored by two board certified readers (blinded for clinical data) for PET-positive lesions in the joints, peripheral enthesis sites and spine. Low dose CT was used for anatomical reference.ResultsOut of 1088 evaluated joints, 109 joints showed PET enhancement, most frequently in the interphalangeal- and metatarsal joints of the feet (14/109, 12,9%) (Figure 1A) and the distal interphalangeal joints of the hands (14/109, 12,9%). Out of 416 evaluated entheseal sites, PET positivity was found at 44 sites, mainly located at the patella tendon insertion (11/44, 25%) (Figure 1B) and the quadriceps tendon insertion (10/44, 22.7%). Of the PET positive joints and entheses sites, respectively 81.1% and 70.5% were not associated with tender or swollen joints and clinical enthesitis, respectively. In 11 out of the 16 patients ≥1 axial PET positive lesion was observed (Figure 1C), most frequently located in the cervical spine (19/49 observed axial lesions, 38.8%). Two patients showed PET enhancement in one sacro-iliac joint (SIJ) without any inflammatory back pain (IBP). Only four out of 15 patients reported IBP and missing data for 1 patient. In two patients clinical dactylitis was observed which was also depicted on PET-CT.Figure 1.[18F]Fluoride uptake in the metatarsal and IP-joints of the feet (A), in the patella tendon (B) and in the spine (C)Conclusion[18F]Fluoride PET-CT scans can visualize disease activity at whole body musculoskeletal manifestations of PsA by demonstrating local bone formation in joints, entheses and the axial skeleton. By sensitive imaging of bone formation at active sites, [18F]Fluoride PET-CT adds information to clinical disease activity, reflected by a high number of clinically negative, PET positive sites on top of concordant findings.References[1]Kaeley GS, Eder L, Aydin SZ, Gutierrez M, Bakewell C. Enthesitis: A hallmark of psoriatic arthritis. Semin Arthritis Rheum. 2018;48(1):35-43.[2]Ogdie A, Coates LC, Gladman DD. Treatment guidelines in psoriatic arthritis. Rheumatology (Oxford). 2020;59(Suppl 1):i37-i46.[3]von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and future directions. Radiology. 2006;238(2):405-22.[4]Jones T. The role of positron emission tomography within the spectrum of medical imaging. Eur J Nucl Med. 1996;23(2):207-11.[5]Bruijnen STG, Verweij NJF, van Duivenvoorde LM, Bravenboer N, Baeten DLP, van Denderen CJ, et al. Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography. Rheumatology (Oxford). 2018;57(4):770.AcknowledgementsWe thank Pfizer and Novartis for financial support of this investigator initiated study.Disclosure of InterestsJerney de Jongh: None declared, Robert Hemke: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer, MSD, Consultant of: AbbVie, UCB, MSD, Novartis, Eli Lilly, Grant/research support from: Unrestricted Grants received for investigator initiated studies from MSD, Pfizer, AbbVie, UCB, Marleen G.H. van de Sande Speakers bureau: UCB, Consultant of: Advisory board AbbVie, Eli Lilly, Novartis, UCB, Grant/research support from: Novartis, Janssen, UCB, Eli Lilly, Arno Van Kuijk Speakers bureau: Novartis, Consultant of: Novartis, AbbVie, Janssen, Irene Bultink Speakers bureau: Eli Lilly, MSD, Amgen, UCB, GSK, Roche, Sanofi Genzyme (outsite the submitted work), Consultant of: Sanofi Genzyme, Astrazeneca (outside the submitted work), Lot Burgemeister Consultant of: Advisory board Novartis, Galapagos, Nancy M.A. van Dillen: None declared, Alexandre Voskuyl: None declared, Conny J. van der Laken: None declared

Background Obtaining remission is the ultimate and now attainable goal of treatment in rheumatoid arthritis (RA). However, the definition of remission kept changing over the last decade. Several composite scores and indices are now validated to assess remitting RA such as the Disease Activity Index 28 joints (DAS28), and more recently, the Simplified Disease Index (SDAI) and the Clinical Disease Index (CDAI). Despite more stringent definition criteria, progressive radiographic damages still occur in RA patients who reached remission. Defining other criteria for remission including ultrasound (US) might help preventing such evolution. Objectives The aim of this study was to compare US findings and composite score results in RA patients that achieved a status of remission according to DAS28. Methods Thirty Tunisian patients followed up for RA with DAS28 ≤2,6 for at least three months were enrolled. Among them, we identified patients in remission according to the SDAI (≤3,3) and the CDAI (≤2,8).US (Esaote MyLab 60 machine and a 13-18 MHz linear array transducer) was performed by an experienced rheumatologist blinded to clinical and laboratory data. For each patient, 22 joints were scanned (wrists, metacarpo-phalangeal, and proximal interphalangeal joints) using a semi-quantitative score. Results Over the 26 patients in CDAI remission, ultrasonographic synovitis in B-mode were noted in 81% of patients. The average ultrasound score per patient was 4.58. In PD mode, US abnormalities were noted in 58% of patients. The average PD score per patient was 2.6. Neither correlation between CDAI and B-mode US score (r = 0.104; p = 0.319) nor between CDAI and DP US score (r = 0.251; p = 0.217) was noted. B-mode examination of the 19 patients in SDAI remission detected synovitis in 79% of patients. The average ultrasound score per patient was 3.95. PD signal was positive in 53% of patients. The average PD-US score per patient was 2.3. Likewise, no correlation with SDAI was found neither with B-mode US score (r = 0.99; p = 0.687) nor with DP US score (r=-0,036; p=0,884). Conclusion Thanks to the therapeutic armory we dispose of and the treat-to-target approach, remission is now a reachable goal. However, defining this goal is no easy task. Including US parameters in definition criteria of remission might help to detect subclinical evolving RA and adjust treatment in such cases. References [1] Olmez MO, Gunal EK, Ureyen SB, Keskin H, Ozturk AB, Yeter G, Cobanoglu E, Aydin SZ. Comparison of composite indices with global synovitis score on ultrasound for detecting remission. Clin Rheumatol. 2018 Apr;37(4):1111-1114. [2] E Naredo,L Valor,I De la Torre,J Martinez-Barrio, M Hinojosa F Aramburu et al,Ultrasound Joint Inflammation in Rheumatoid Arthritis in Clinical Remission: How Many and Which Joints Should Be Assessed?.Rheumatoid Arthritis Vol65, Issue4 Apr 2013: 512-517 Disclosure of Interests None declared

Background Both genetic and environmental factors may have roles in the pathogenesis of Behcet’s Syndrome (BS). Likewise, occurrence of different clinical cluster of BS may be also influenced by the combination of these two factors. But we do not know the weight of the factors during the emergence of the disease and clinical clusters. Objectives We conducted a study for evaluating the frequency of family history for BS in different clinical BS clusters. Furthermore, we assessed the hypothesis that “BS patients in the same family generally accumulate in the similar clinical cluster.” Methods Eighty-five patients and their relatives in our BS cohort were participated to the study. We used international Study Group Criteria for Behcet Disease (ISBD) criteria (1) for classifying our index patients and their first and second degree relatives as BS. We sub-classified BS patient to mucocutenous, vascular, acne-arthritis-enthesis, eye, neurologic, intestinal and undetermined clusters (2). Firstly, we re-evaluated the family history of our BS patients. Then, the relatives of the patients with already known BS or with having symptoms related with BS were interviewed with phone. All participants have been informed about the study and we have taken consent from them. Results Twenty-two (25.9%) of the patients had first or second degree relatives with BS. Furthermore, 27 (31.8%) of our patient were classified to mucocutenaous cluster. In our study, the BS patient with enthesis-arthritis-acne cluster had highest frequency (44.4%) of family history. However, there was no apparent accumulation of similar findings in index BS cases and their close relatives (Table). Conclusion According to result of these studies, there was no finding that supports the hypothesis“BS patients in the same family generally accumulate in the similar clinical cluster”. Still genetic may have major role in the emerging of the BS, such as it is accepted as a member of a group of diseases called MHC-I –opathy (3). However, like most of the diseases, genetic background is not enough for the expression of full-blown disease. Briefly, even in the similar genetic background, multiple and separate hits of environmental or non-genetic factors may take role in the pathogenesis. References [1] Criteria for diagnosis of Behcet’s disease. International Study Group for Behcet’s Disease. Lancet. 1990;335(8697):1078-80. [2] Tunc R, Keyman E, Melikoglu M, Fresko I, Yazici H. Target organ associations in Turkish patients with Behcet’s disease: a cross sectional study by exploratory factor analysis. J Rheumatol. 2002;29(11):2393-6. [3] McGonagle D, aydin SZ, Gul a, Mahr a, Direskeneli H. ‘MHC-I-opathy’-unified concept for spondyloarthritis and Behcet disease. Nature reviews Rheumatology. 2015;11(12):731-40. Acknowledgement None Disclosure of interests None declared

Background:Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are two forms of chronic progressive large-vessel vasculitis (LVV) of unknown etiology. In 2016, the OMERACT Vasculitis Working Group proposed the development of a Core Domain Set of outcome measures for LVV including organ and arterial function, fatigue, pain, biomarkers, and death (1). Understanding the psychometric properties of outcome measurement instruments is essential when selecting among instruments to use in research; a summary of such properties for measures of LVV has not been developed.Objectives:To systematically review and summarize the psychometric properties of outcome measurement instruments used to measure the domains of the OMERACT core domain set for LVV.Methods:A comprehensive search of several databases (Medline, EMBASE, Cochrane, among others) from inception to July 14, 2020 was conducted. Articles were included if they covered psychometric properties of instruments used in LVV. Following the COSMIN and OMERACT frameworks, different psychometric properties (validity, inter- and intra-observer reliability, sensitivity to change, and feasibility) of outcome measurement instruments used in LVV (GCA and TAK) were assessed. Risk of bias was assessed according to the COSMIN checklist.Results:Among the 3534 articles identified, 15 studies focusing on the development or validation of psychometric properties on LVV met the predefined criteria. Two were development studies and 13 were validation studies. These studies provided information on 13 instruments: 5 instruments specific to TAK, 2 specific to systemic vasculitides, and 6 general, non-disease-specific instruments. No instruments specific to GCA were identified.Of the main psychometric properties assessed in the included studies, 40% had a low, 47% had moderate, and 13% had high risk of bias. Construct validity was the property most frequently assessed (in 93% of the tools) (Figure 1).In TAK, the Indian Takayasu Clinical Activity Score 2010 (ITAS2010) showed good consistency (r=0.97), reliability (intra-observer, ICC=0.60; inter-observer, ICC=0.92) and validity (correlation with Physician Global Assessment (PGA) (r=0.73)) for disease activity. Regarding disease damage, the Disease Extent Index-Takayasu (DEI-Tak) showed good validity (correlation with NIH score 94%, k=0.85). Non-specific vasculitis instruments such as the Vasculitis Damage Index (VDI) and the Birmingham Vasculitis Activity Score (BVAS) showed moderate validity in the assessment of disease damage in GCA (cumulative glucocorticoid dose and disease duration, r=0.30 and r=0.29) and TAK (cumulative glucocorticoid dose and disease duration, r=0.29 and r=0.25) in the former and disease activity in GCA in the later (PGA, r=0.50).Six non-vasculitis-specific patient-reported outcomes (PROs) instruments were identified, all showing low to moderate validity in GCA/TAK.Conclusion:The psychometric properties of 13 outcome measures to study LVV covering the OMERACT domains of disease activity, damage, and patient-reported outcomes were assessed. ITAS2010, DEI-Tak, VDI, and BVAS were the instruments with better psychometric properties for disease activity and/or damage. Disease activity and/or damage instruments specific for GCA, and validated PROs for both GCA and TAK are needed.References:[1]Sreih GA, Alibaz-Oner F, Kermani TA, Aydin SZ, Cronholm PF, Davis T, et al. Development of a Core Set of Outcome Measures for Large-vessel Vasculitis: Report from OMERACT 2016 | The Journal of Rheumatology [Internet]. [cité 26 avr 2020]. Disponible sur: http://www.jrheum.org/content/44/12/1933.longDisclosure of Interests:None declared

Background:Enthesis anatomy and biomechanics have a key role in Spondyloarthritis (SpA) pathogenesis (1) but few data are available about the influence of structural and biomechanical changes of Achilles tendon (AT) on persisting pain in longstanding SpA patients.Objectives:To correlate AT pain in longstanding SpA patients with ultrasonographic detectable disorders and biomechanical abnormalities.Methods:We performed a monocentric cross-sectional analysis including 35 consecutive patients affected by SpA (13 with Psoriatic Arthritis, 9 with Enteropathic SpA, 6 with Ankylosing Spondylitis and 7 with Undifferentiated SpA) under treatment with anti- TNF agents. A rheumatologic clinical and clinimetric evaluation (AT VAS pain, BASDAI, BASFI, HAQ), an ultrasound study of AT according to the Madrid Sonographic Enthesis Index (MASEI) score and a podiatrist biomechanical evaluation [Foot posture index (FPI), degree of ankle dorsiflexion with the knee extended and flexed] were performed.Results:Study population (13 F; 22 M; mean age 54.9 ±13.9 years; mean disease duration 9.5 ± 5.0 years; mean BMI 25.8 ±4.4) showed a mean AT VAS pain of 3.4 ± 2.2, a mean HAQ of 0.6 ± 0.6, a mean BASDAI of 3.3 ±2.1 and a mean BASFI of 2.2 ±1.9. At the ultrasonographic evaluation 47% (33/70) of the AT entheses analysed presented a dishomogeneous echostructure, 31% (22/70) structural thickness, 53% (37/70) calcifications, 10% (7/70) erosions, 44% (31/70) a retrocalcanear bursitis. A power Doppler positivity was found only in 0.07% (5/70) of the AT.At the biomechanical evaluation 50% (35/70) of the feet showed a FPI score between 0 and + 5 (neutral foot), 46% (32/70) a FPI score between +6 and +9 (slight foot pronation) and 6% (4/70) a FPI score between -1 and -4 (slight foot supination).The mean degree of ankle dorsiflexion with extended knee was 8.4 ± 3.9 with the 61% (43/70) of the patients with a maximum dorsiflexion < 10° of whom 46% (20/43) do not recover after the knee flexion.We found a between the mean degree of left ankle dorsiflexion with extended/flexed knee both with ultrasound-revealed left AT enthesis calcifications (p=0.014/0.037) and with left AT enthesis thickness (p=0.049/0.035), and a significant association between the mean degree of right ankle dorsiflexion and extended/flexed knee and ultrasound-revealed right AT calcifications (p=0.008/0.012). Moreover, we noticed an inverse correlation between the mean overall degree of ankle dorsiflexion with extended/flexed knee and the BASFI values (p=0.007/0.004). AT VAS pain was statistically related with Achilles PDUS signal persistence (p=0.048) but not with US signs of chronic entesopathy or biomechanical alterations [calcification (p=0.39), erosions (p=0.74)]. The limits of the study were the low number of patients recruited and the lack of a control group.Conclusion:In this monocentric study on a cohort of SpA patients, we demonstrated a statistically significant correlation between ankle–subtalar joint complex biomechanics alterations, ultrasonographic signs of chronic enthesopathy and clinimetric index of functional disability. Residual Achilles pain seems to be related to US signs of active enthesitis.References:[1]The enthesis organ concept and its relevance to the spondyloarthropathies. Benjamin, M and McGonagle, D. s.l.: Adv Exp Med Biol, 2009, Vol. 649.[2]The Synovio-entheseal Complex and Its Role in Tendon and Capsular Associated Inflammation. McGonagle, E D, Aydin, SZ and Tan, AL. 0, s.l.: J Rheumatol Suppl, 2012, Vol. 89Disclosure of Interests:None declared

Background:Overweight/obesity has increased exponentially in the last decades, becoming a huge Public Health problem. Moreover, an increase in adipose tissue is associated with an increased production of several proinflammatory cytokines and acute phase reactants. Higher BMI has been related with new bone formation including syndesmophytes and enthesophytes. In fact, besides rheumatologic conditions including Psoriatic Arthritis (PsA), enthesopathy can be a consequence of several clinical conditions including metabolic syndrome, mechanical injuries and degeneration.Objectives:To evaluate the effect of body mass index (BMI) on disease activity scores and enthesitis scores in Psoriatic Arthritis.Methods:Retrospective study including all the patients with PsA meeting the CASPAR criteria, beginning first-line biologic therapy at our centre. Demographic and clinical data were collected from the Portuguese database Reumapt. Statistical analysis was performed with SPSS. Continuous variables were compared through Spearman/Pearson correlations.Results:The mean BMI was 26.8 (SD 0.5). In our sample of 119 PsA patients, 21.5% were overweight and 8.3% were obese. The mean age of patients was 46.3 ± 1.03 years; 60 female and 59 male. The median disease duration was 6.8 (0.3-33.8) years. At baseline mean (SD) disease activity variables were: DAS 28 4vESR 4.9 (0.2), ESR 33.2 (2.3) mm/h; CRP 2.35 (0.3) mg/dL, BASDAI 6.6 (0.2), ASDAS 3.9 (0.1), BASMI 3.7 (0.2), BASFI 5.8 (0.3), MASES 1.9 (0.3), SPARCC 2.3 (0.3). There were statistically significant positive correlations between BMI and MASES at baseline (p=0.024, r=0.411) but there weren’t with SPARCC, DAS 28 4vESR, ESR, CRP, BASDAI, ASDAS, BASMI and BASFI.Conclusion:The data showed that patients with higher BMI values had higher enthesitis scores suggesting that overweight/obesity may have a negative impact on enthesopathy. Further studies are still needed to further understand that possible relationship.References:[1]Bakirci S, Dabague J, Eder L, McGonagle D, Aydin SZ. The role of obesity on inflammation and damage in spondyloarthritis: a systematic literature review on body mass index and imaging. Clin Exp Rheumatol. 2019 Apr 29.Disclosure of Interests:Sara Ganhão: None declared, Bruno Miguel Fernandes: None declared, Salomé Garcia: None declared, Filipe Pinheiro: None declared, Maria Rato: None declared, Eva Mariz: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Lúcia Costa: None declared

Background:In the last few years annular pulleys inflammation has been highlighted as a possible key pathogenetic factor in psoriatic dactylitis, first with magnetic resonance imaging (MRI)1, then, in a very recent paper2, with power Doppler (PD) ultrasound (US). However, the prevalence of PD US inflammation of annular pulleys in psoriatic arthritis (PsA) patients compared to rheumatoid arthritis (RA) patients has not been investigated yet.Objectives:To determine the prevalence of PD US findings indicative of A1 pulley inflammation in PsA patients and in controls with RA and to preliminarily investigate the correlation between A1 pulley inflammation and disease activity (DAPSA).Methods:Consecutive patients with PsA and RA were included in this cross-sectional single-centre study. A rheumatologist recorded demographic and clinical data and in the same day another rheumatologist performed the US examination using a MyLab ClassC (Esaote, Genova, Italy) equipped with a 10-22 MHz linear probe. A1 pulleys of fingers 2ndto 5thwere assessed bilaterally adopting longitudinal and transverse scans. The following pathological US findings were recorded: inflammation of the pulley (defined as the presence of PD signal within a thickened pulley) and tenosynovitis of the digital flexor tendons at finger level according to OMERACT definition.Results:Sixty patients were enrolled: 30 with PsA and 30 with RA. Inflammation of A1 pulley was found in 15 out 240 fingers (6.3%) of 8 (26.7%) PsA patients and in 1 out of 240 fingers (0.4%) of 1 (3.3%) RA patients (pConclusion:This pilot study demonstrated that ultrasound A1 pulley inflammation, defined as the presence of power Doppler signal within a thickened pulley, is relatively common at patient level in psoriatic arthritis and seems to be characteristic of PsA compared to RA. In psoriatic arthritis patients, a positive significant correlation was found between ultrasound A1 pulley inflammation and disease activity.References:[1]Tan AL, Fukuba E, Halliday NA, Tanner SF, Emery P, McGonagle D. High-resolution MRI assessment of dactylitis in psoriatic arthritis shows flexor tendon pulley and sheath-related enthesitis. Ann Rheum Dis 2015; 74: 185-9.[2]Tinazzi I, McGonagle D, Macchioni P, Aydin SZ. Power Doppler enhancement of accessory pulleys confirming disease localization in psoriatic dactylitis. Rheumatology (Oxford) 2019 [Epub ahead of print].Disclosure of Interests:Gianluca Smerilli: None declared, Edoardo Cipolletta: None declared, Marco Di Carlo: None declared, Andrea Di Matteo Grant/research support from: the publication was conducted while Dr. Di Matteo was an ARTICULUM fellow, Walter Grassi Speakers bureau: Prof. Grassi reports personal fees from AbbVie, personal fees from Celgene, personal fees from Grünenthal, personal fees from Pfizer, personal fees from Union Chimique Belge Pharma, outside the submitted work., Emilio Filippucci Speakers bureau: Dr. Filippucci reports personal fees from AbbVie, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Roche, personal fees from Union Chimique Belge Pharma, personal fees from Pfizer, outside the submitted work.

Background:The association between PsA and cardiovascular disease is generally thought to be greater than the risk between psoriasis and cardiovascular disease. Vascular calcifications (VC) are considered an early marker of atherogenesis and accurate VC scores including Carotid, Aortic and Lower limbs vascular Calcifications (CALC) were published2. PsA localises to entheses that are sites of high physical stressing, analogous to artery bifurcations which are sites of high vascular stress. Entheseal calcification is a feature of the post-inflammatory changes. We hypothesised that there may be common “deep koebernisation” responses in the entheses and vessels in PsA as a common biomechanical response specifically linking PsA with cardiovascular diseaseObjectives:To quantify non-coronary VC in a consecutive series of PsA patients using CALC score (CALCs) and compare PsA patients with CV risk factors to the group without. To independently evaluate sonographic entheseal changes including new bone formation and to determine if the magnitude of vascular and entheseal lesions was linkedMethods:122 adult PsA patients diagnosed according to the CASPAR criteria underwent US assessment for the presence of VC according to CALCs. Carotids arteries intima-media thickness (IMT) was also measured. Blinded to this US assessment, further US imaging of 12 large entheseal sites was performed. The presence of enthesophytes was scored dichotomously for each site and summed up to generate the ARES score. Enthesophytes were scored semiquantitatively in a 0-3 scale according to previous studies3to generate RESS score. Enthesal inflammatory changes were identified according with OMERACT definitionsResults:Overall, 83 patients were female (68%), mean age 58.6±10.3 y and mean PsA duration 9.5±7.0 y. PsA with obesity, metabolic syndrome and hypertension presented higher IMT values. The IMT scores correlated significantly with entheseal thickness (p< 0.001). A statistical significant correlation was found between CALCs with enthesophytes scores ARES and RESS (spearman rho = 0.665, p < 0.001 and 0.634, p < 0.001 respectively). CALCs, ARES and RESS were significantly increased in patients with CV risk factors or an history of CV events, compared with patients without (table 1). No significant correlation was found between CALCs and PsA duration (Spearman rho = 0.132, p = 0.135)PATIENTS, N. (%)CALCsARESRESSHypertension50 (41%)8.18 ± 6.20 **6.55 ± 2.59 **12.06 ± 5.91 **No hypertension72 (59%)3.82 ± 4.24 **4.79 ± 2.61 **8.05 ± 5.40 **Positive history of CV events16 (13%)11.5 ± 5.34 **7.56 ± 2.50 *13.56 ± 4.97 *No CV events106 (87%)4.70 ± 5.02 **5.16 ±2.64 *9.06 ± 5.86 *Obesity31 (25%)6.55 ± 5.036.63 ± 1.86 *12.03 ± 4.96 *No obesity91 (75%)5.48 ± 5.775.32 ± 2.85 *9.17 ± 6.07 *Hyperuricemia14 (11%)11.86 ± 8.15 *7.43 ± 2.56 *15.00 ± 5.33 **No hyperuricemia108 (89%)4.65 ± 4.55 *5.23 ± 2.68 *8.97 ± 5.69 **Dyslipidemia54 (44%)7.47 ± 6.43 **5.90 ± 2.7010.84 ± 6.13 *No Dyslipidemia68 (56%)3.92 ± 4.03 **5.11 ± 2.738.59 ± 5.58 *Diabetes11 (9%)10.09 ± 7.29 *7.18 ± 2.14 *14.55 ± 5.20 *No diabetes111 (91%)5.08 ± 5.16 *5.31 ± 2.73 *9.14 ± 5.79 ** = pConclusion:In PsA patients vascular and entheseal calcifications are significantly correlated. Patients with CV risk factors and/or history of CV events have higher values of CALCs, ARES and RESS. This suggests possible commonalites between entheses and vessels that might represent a deep Koebnerisation response in arteries and entheses. This raises the possibilities that the primary joint inflammatory responses and what is viewed as a comorbidity are closely linkedReferences:[1]Eder L, et al. J Rheumatol Suppl. 2019;95:20-27.[2]Flore R, et al. Eur Rev Med Pharmacol Sci. 2018;22(3):736-742.[3]Aydin SZ, et al. Rheumatol Int. 2016;36(3):397-404.Disclosure of Interests:Ilaria Tinazzi: None declared, Giorgia Citriniti: None declared, Nicolò Girolimetto: None declared, Federica Martinis: None declared, Carlo Salvarani: None declared, Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC, Pierluigi Macchioni: None declared

Background Although skin lesion is the most typical findings in patients with psoriasis (PsO), nail psoriasis is also one of the clinical manifestation. Moreover, nail disorders in PsO are known as a risk factor for psoriatic arthritis (PsA). However, pathological feature and the relationship with inflammation of the soft tissue around the nail is unknown.1–2 Objectives The aim of this study was to compare the soft tissue thickness around the nail in patients with PsO, PsA and other rheumatic diseases by using ultrasonography. Methods Twenty-five PsO · 35 PsA · 23 rheumatoid arthritis (RA) · 28 ulcerative colitis (UC) and 13 Crohn’s disease (CD) patients performed ultrasonographic assessment in nail were included in this analysis. Ultrasonographic examination was performed by using HI VISION Ascendus (Hitachi Medical Corporation, Japan) with a multifrequency linear transducer (18–6 MHz) and the grey scale (GS) and power Doppler (PD) findings were assessed. The distance between the proximal nail fold on the dorsal side of the nail matrix and the nail bed on the volar side of the nail matrix was measured by electric calliper Results The distance between the proximal nail fold and the nail bed was 2.58±0.56 mm in PsA and 2.55±0.58 mm in PsO patients (p=0.603). Among the 60 patients who combined PsO and PsA patients, 41 patients with nail psoriasis and 19 patients without nail psoriasis was compared. The distance was 2.68±0.62 mm in patients with nail psoriasis and 2.30±0.41 mm in without nail psoriasis (p Conclusions Soft tissue thickness around the nail in patients with PsO and PsA was compared with other rheumatic diseases by ultrasonographic assessment. In patients with PsO and PsA with nail psoriasis, soft tissue swelling around nail was observed. References [1] Sandobal C, Carbo E, Iribas J, et al. Ultrasound nail imaging on patients with psoriasis and psoriatic arthritis compared with rheumatoid arthritis and control subjects. J Clin Rheumatol. 2014;20:21–4. [2] Aydin SZ, Castillo-Gallego C, Ash ZR, et al. Ultrasonographic assessment of nail in psoriatic disease shows a link between onychopathy and distal interphalangeal joint extensor tendon enthesopathy. Dermatology. 2012;225:231–5. Acknowledgements We wish to thank Tomoko Nakatsuka for clinical assistant, Setsuko Takeda, Emi Yamashita and Yuko Yoshida for their special efforts as a sonographer and collecting data. Disclosure of Interest None declared

Objective: Higher subclinical enthesitis on US has been reported in IBD and celiac disease, separately. The objective of this study was to compare IBD and celiac disease for enthesitis on US. Higher enthesitis scores in IBD compared with celiac disease would support a shared pathogenic mechanism between IBD and spondyloarthritis, whereas similar scores may suggest a general impact of gut inflammation on the enthesis. Methods: Patients with IBD, celiac disease and healthy controls (HCs) were recruited and 12 entheses were scanned by US, blind to the diagnosis and clinical assessment. Elementary lesions for enthesitis were scored on a scale between 0 and 3, for inflammation, damage and total US scores. Results: A total of 1260 entheses were scanned in 44 patients with celiac disease, 43 patients with IBD and 18 HCs. The three groups were matched for age and BMI. Patients with celiac disease and IBD had higher inflammation scores than HCs [10.4 (6.5), 9.6 (5.4) and 5.6 (5.2), respectively, P = 0.007) whereas damage scores were similar. Both age and BMI had significant effects on the entheseal scores, mostly for inflammation scores but when controlling for these the US enthesopathy scores were still higher in celiac disease and IBD. Conclusion: The magnitude of subclinical enthesopathy scores is similar between celiac disease and IBD in comparison with HCs. These findings suggest that the common factor between both diseases and enthesopathy is abnormal gut permeability, which may be modified by the genetic architecture of IBD leading to clinical arthropathy.

Spinal new bone formation is a major but incompletely understood manifestation of ankylosing spondylitis (AS). We explored the relationship between spinal new bone formation and ultrasound (US)-determined Achilles enthesophytes to test the hypothesis that spinal new bone formation is part of a generalized enthesis bone-forming phenotype. A multicenter, case control study of 225 consecutive AS patients and 95 age/body mass index (BMI) matched healthy controls (HC) was performed. US scans of Achilles tendons and cervical and lumbar spine radiographs were obtained. All images were centrally scored by one investigator for US and one for radiographs, blinded to medical data. The relation between syndesmophytes (by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and the number of syndesmophytes) and enthesophytes (with a semi-quantitative scoring of the US findings) was investigated. AS patients had significantly higher US enthesophyte scores than HCs (2.1(1.6) vs. 1.6(1.6); p = 0.004). The difference was significant in males (p = 0.001) but not in females (p = 0.5). The enthesophyte scores significantly correlated with mSASSS scores (rho = 0.274, p < 0.0001) with the association even stronger in males (enthesophyte scores vs. mSASSS rho = 0.337, p < 0.0001). In multiple regression analysis, age, BMI, enthesophyte scores and disease duration were significantly associated with syndesmophytes in males, and keeping all other variables constant, increasing US enthesophyte scores increased the odds of having syndesmophytes by 67 %. Male AS patients that have more severe US-determined Achilles enthesophyte also associated spinal syndesmophytes suggesting a bone-forming gender-specific phenotype that could be a useful marker predicting of new bone formation.

Evaluation of: Aydin SZ, Bas E, Basci O et al.: Validation of ultrasound imaging for Achilles entheseal fibrocartilage in bovines and description of changes in humans with spondyloarthritis. Ann. Rheum. Dis. 69(12), 2165–2168 (2010). Enthesitis, the hallmark of spondyloarthritis is underestimated in clinical practice and improving the knowledge of structural damage and inflammation in enthesis is challenging. The results of a study by Aydin et al.are put into the context of the recent advances and definitions in the field of enthesis ultrasound and the new contributions of this original paper in the visualization of the enthesis fibrocartilage and its relationship with the histology are discussed.

Skin involvement is of major prognostic value in systemic sclerosis (SSc) and often the primary outcome in clinical trials. Nevertheless, an objective, validated biomarker of skin fibrosis is lacking. Optical coherence tomography (OCT) is an imaging technology providing high-contrast images with 4 μm resolution, comparable with microscopy ('virtual biopsy'). The present study evaluated OCT to detect and quantify skin fibrosis in SSc.We performed 458 OCT scans of hands and forearms on 21 SSc patients and 22 healthy controls. We compared the findings with histology from three skin biopsies and by correlation with clinical assessment of the skin. We calculated the optical density (OD) of the OCT images employing Matlab software and performed statistical analysis of the results, including intraobserver/interobserver reliability, employing SPSS software.Comparison of OCT images with skin histology indicated a progressive loss of visualisation of the dermal-epidermal junction associated with dermal fibrosis. Furthermore, SSc affected skin showed a consistent decrease of OD in the papillary dermis, progressively worse in patients with worse modified Rodnan skin score (p0.0001). Additionally, clinically unaffected skin was also distinguishable from healthy skin for its specific pattern of OD decrease in the reticular dermis (p0.001). The technique showed an excellent intraobserver and interobserver reliability (intraclass correlation coefficient0.8).OCT of the skin could offer a feasible and reliable quantitative outcome measure in SSc. Studies determining OCT sensitivity to change over time and its role in defining skin vasculopathy may pave the way to defining OCT as a valuable imaging biomarker in SSc.

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Background Optical coherence tomography (OCT) has been recently shown to be a novel quantitative reliable tool to assess skin involvement in Systemic Sclerosis (SSc) (1). However the sensitivity to change over-time has not been evaluated. Objectives The present study aimed to compare skin assessment by OCT over-time in patients with SSc. Methods We performed 52 OCT scans of dorsal forearms on 26 sites of analysis from 17 SSc patients (9 with diffuse, 8 with limited subset according to Le Roy et al; F/M =15:2; mean disease duration at baseline ± SD =6±4.5 years) at 0 and 24 months. Clinical skin involvement was assessed using the modified Rodnan skin score (mRss). Minimum and Maximum Optical Density (Min and Max OD) of the mean-A scans were calculated employing Matlab software as previously described (1). Comparison of the mRss at the site of analysis and Min and Max OD at the 2 time-points was performed by two-tailed paired t-test employing GraphPrism software. Results Fourteen sites of analysis with local mRss=0 did not change over 24 months. Accordingly, both Min and Max OD showed only an average +2.98% and -0.05% change, respectively (p>0.05). By contrast, at 6 sites of analysis mRss improved by 2 points (three sites with local score “2” improved to “0”, three sites with local score of “3” improved to “1”). At these sites Min OD showed an average increase of 23.92% (p=0.0084) and Max OD of 25.13% (p=0.008). At 4 sites of analysis mRss improved by 1 point (two sites with local score “3” improved to “2”, one site with local score of “2” improved to “1”, one site with local score of “1” improved to “0”). At these sites Min OD and Max OD showed no significant improvement (Min OD of 1.93% and Max OD of 8.15%; p>0.05 for both). Furthermore, both Min and Max OD showed a trend towards a decrease (-3.54%, -5.41% respectively) at the 2 sites of analysis with worsening mRSS (one point increase). Conclusions Although a low number of observations, this preliminary study provides the first evidence suggesting that OCT of the skin is sensitive to change over time and is consistent with mRss. The lack of improvement of OCT findings at sites with a mRSS of 1 deserves further evaluation to determine whether this is associated with poor accuracy of mRSS or room for improvement in OCT analysis. Studies including a larger number of patients and sites of analysis with different grades of skin involvement and improvement/deterioration of clinical score are needed for more definitive validation. References Abignano G, Aydin SZ, Castillo-Gallego C et al. Virtual Skin biopsy by Optical Coherence Tomography: the first quantitative imaging biomarker for Scleroderma. Ann Rheum Dis 2013;72:1845-51. Disclosure of Interest G. Abignano: None declared, L.-A. Bissell: None declared, J. Britton: None declared, G. Lettieri: None declared, D. Woods Employee of: Michelson Diagnostics, M. Buch: None declared, D. McGonagle: None declared, P. Emery: None declared, F. Del Galdo: None declared DOI 10.1136/annrheumdis-2014-eular.4697

Background The use of ultrasonography (US) can be of interest in the diagnosis and the follow-up of enthesitis, notably in SA. In recent studies asymptomatic US enthesitis were more frequently observed in psoriasis patients (pts) than in controls. Objectives 1/ To estimate the prevalence of US enthesitis in psoriasis pts with or without musculoskeletal symptoms 2/ To assess by US imaging the evolution of enthesitis with systemic treatment (TT). Methods Prospective bi-centre (rheumatology & dermatology) study over 6 months including Psoriasis pts requiring systemic TT, with or without musculoskeletal symptoms and psoriatic arthritis (PsA, according to CASPAR criteria). Clinical assessment (M0 M3 M6) included: BASDAI, HAQ, SPARCC, PASI, nail disease and comorbidities. US assessment (M0 M6) Grey Scale (GS) Power Doppler (PD) of 10 entheses, by a trained rheumatologist blinded to other data, scoring (absent/present) morphology (thickening and hypoechogenicity), structure and PD signal. Statistical analysis : test of Chi ² (data at baseline) ; test for series matched by Wilcoxon and Chi ² of Mc Nemar (analysis M0 M6). Results 340 entheses were studied in 34 pts, 22 asymptomatic and 12 PsA (fulfilling CASPAR criteria), mean age 43.5 years, mean psoriasis duration 15.9 years, mean BASDAI=48.1, mean PASI=15.9, mean CRP=4.2 mg/l. 23 patients received acitretin or methotrexate (MTX) or ciclosporin and 11 pts received anti TNF. At baseline: US abnormalities in 97.1% total population and in 86.4% psoriasis pts. 95/340 enthesitis, 57/220 in asymptomatic pts vs 38/120 in PsA (p = 0,258). Neither group had PD signal. 24/90 enthesitis in pts with nail disease (n=9) vs 33/130 without (n=13) (p = 0,831). 23 pts were assessed at M6, receiving MTX (n=12) and anti TNF (n=11). Improving US morphological abnormalities both in asymptomatic pts (n=13) (p=0,021) and PsA (n=10) (p= 0,164). Significant decrease of BASDAI, HAQ, SPARCC. Conclusions Discussion : According to the series, asymptomatic US enthesitis was reported in 11% to 32 % of psoriasis pts compared with the control (1, 2). In our study, US enthesitis were observed in 86.4 % of the psoriasis pats, possibly due to a severe psoriasis in our population, all requiring systemic TT (inclusion criteria). In patients with nail disease, we did not observe the previously reported higher frequencies of US enthesitis (3, 4), because only a few had nail disease. Previous studies of US-detected enthesitis have demonstrated a good response to change under SA TT, with a decrease in PD signal. To our knowledge, our study is the first to show an improvement of US entheseal morphological abnormalities in psoriasis pts after systemic TT. Conclusion : We observed a high frequency of US enthesitis in pts with severe psoriasis requiring systemic TT with or without musculoskeletal symptoms. These US morphological abnormalities are likely to improve after 6months of systemic TT. Further studies would be interesting to validate data and to estimate the predictive value of asymptomatic US enthesitis in psoriasis pts. References Naredo E. et al. Rheumatology (Oxford). 2011 ; Gutierrez M. et al. Semin Arthritis Rheum. 2011 ; Ash ZR et al.Ann Rheum Dis. 2012 ; Aydin SZ et al. Ann Rheum Dis. 2012. Disclosure of Interest None Declared