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© Copyright Clinical and Experimental Rheumatology 2022., Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Multiscale homogenization represents a powerful tool to treat certain fluid-structure interaction problems involving porous, elastic, fibrous media. This is shown here for the case of the interacti ...

International audience; The coupling between the flow through a fibrous porous medium and that in a free-fluid region is studied. The flow dynamics inside the porous medium are described using the volume averaging method applied to the incompressible Navier−Stokes equations in the laminar regime. The two different flow domains are coupled via a penalization method that consists of varying the porous medium properties (porosity and permeability) continuously across the interface. This approach permits the use of the same set of the equations throughout the whole domain. The averaging method is validated against simulations which fully account for the presence of cylindrical fibers positioned at the bottom wall of a square driven cavity. Numerical experiments are carried out for two different Reynolds numbers, large enough to ensure that inertial effects inside the porous domain are not negligible. Good agreement is found when comparing the two approaches.

Marco A Cimmino,1 Massimiliano Parodi,1 Francesca Barbieri,1 Stefano Bombardieri,2 Giuseppe Zampogna,1 Annamaria Iagnocco,3 Alberto Batticciotto,4 Luca Maria Sconfienza,5,6 Luigi Sinigaglia,7 Fabrizio De Benedetti,8 Fabiola Atzeni,9 Piercarlo Sarzi-Puttini10 1Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; 2Rheumatology Unit, Santa Chiara Hospital, University of Pisa, Pisa, Italy; 3Academic Rheumatology Centre, Università degli Studi di Torino, Turin, Italy; 4Rheumatology Unit ASST-Settelaghi, Ospedale di Circolo – Fondazione Macchi, Varese, Varese, Italy; 5IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 6Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy; 7Rheumatology Unit, G. Pini Hospital, Milan, Italy; 8Division of Rheumatology, IRCCS, Bambin Gesù Paediatric Hospital, Rome, Italy; 9Rheumatology Unit, University of Messina, Messina, Italy; 10Rheumatology Unit, L. Sacco University Hospital, Milan, ItalyCorrespondence: Piercarlo Sarzi-PuttiniReumatology Department, L. Sacco University Hospital, ASST Fatebenefratelli – Sacco, Via G.B. Grassi, 74, Milan 20157, ItalyTel +39 02 39042208Email piercarlo.sarziputtini@gmail.comObjective: This open-label study evaluated the effects of combined tocilizumab (TCZ) and disease-modifying antirheumatic drugs (DMARDs) on magnetic resonance imaging (MRI) changes in synovial membrane enhancement, bone marrow edema (BME), and erosions in the wrist and hand joints of rheumatoid arthritis (RA) patients inadequately responding to DMARDs alone.Methods: The efficacy of intravenous TCZ 8 mg/kg administered every four weeks for 48 weeks was evaluated on six occasions. The primary endpoints were the changes in the extent and degree of wrist synovitis as measured using the RA MRI Score (RAMRIS) and dynamic, gadolinium-enhanced 0.2T MRI (DCE-MRI). A number of different parameters of DCE-MRI were evaluated.Results: Fifty-eight patients were treated, eight of whom (13.8%) discontinued the study prematurely. The mean RAMRIS significantly decreased after two weeks and the decrease was maintained for up to 48 weeks. By week 4, the mean RAMRIS synovitis score had significantly decreased from baseline (− 0.804± 1.575; p=0.018), but not the mean early enhancement (REE) or relative enhancement (RE). However, there were significant decreases in RE at week 24, in REE and Ntotal (total number of enhancing voxels)*IRE (initial rate of enhancement) at weeks 12, 24 and 48, and in Ntotal*ME (maximal enhancement) at weeks 24 and 48. Mean BME decreased from baseline to week 48, and bone erosions did not progress. The patients’ clinical parameters significantly improved from baseline until week 48.Conclusion: TCZ in combination with DMARDs improved wrist synovitis, BME and clinical parameters, without any progression in bone erosions. The RAMRIS for synovitis rapidly improved from as early as two weeks after the first TCZ infusion. (Funded by F. Hoffmann–La Roche; ACTRACE EudraCT No. 2009 012185-32).Keywords: tocilizumab, rheumatoid arthritis, wrist, synovitis, low-field MRI, dedicated MRI

Small-scale, deformable riblets, embedded within the viscous sublayer of a turbulent boundary layer and capable to adapt to the overlying motion, are studied. The wall micro-grooves are made of a linearly elastic material and can undergo small deformations; their collective behavior is assumed to occur over a large, elastic wavelength. The presence of two length scales allows for the use of a multiscale homogenization approach yielding microscopic problems for convolution kernels and parameters, which must then be employed in macroscopic boundary conditions to be enforced at a virtual wall through the riblets. The results found suggest that, in analogy to the case of rigid riblets, compliant, blade-like wall corrugations are more effective than triangular riblets in reducing skin friction drag, provided the spanwise periodicity of the indentations is sufficiently small for the creeping flow approximation to be tenable. (C) 2019 Elsevier Ltd. All rights reserved.

A macroscopic boundary condition to be used when a fluid flows over a rough surface is derived. It provides the slip velocity $\boldsymbol{u}_{S}$ on an equivalent (smooth) surface in the form $\boldsymbol{u}_{S}=\unicode[STIX]{x1D716}{\mathcal{L}}\boldsymbol{ : }{\mathcal{E}}$, where the dimensionless parameter $\unicode[STIX]{x1D716}$ is a measure of the roughness amplitude, ${\mathcal{E}}$ denotes the strain-rate tensor associated with the outer flow in the vicinity of the surface and ${\mathcal{L}}$ is a third-order slip tensor arising from the microscopic geometry characterizing the rough surface. This boundary condition represents the tensorial generalization of the classical Navier slip condition. We derive this condition, in the limit of small microscopic Reynolds numbers, using a multi-scale technique that yields a closed system of equations, the solution of which allows the slip tensor to be univocally calculated, once the roughness geometry is specified. We validate this generalized slip condition by considering the flow about a rough sphere, the surface of which is covered with a hexagonal lattice of cylindrical protrusions. Comparisons with direct numerical simulations performed in both laminar and turbulent regimes allow us to assess the validity and limitations of this condition and of the mathematical model underlying the determination of the slip tensor ${\mathcal{L}}$.

In the context of the PELskin project, a homogenized model to study flows over and inside poroelastic media has been developed. It allows to simulate the fluid–structure interaction between a fluid and an extremely dense poroelastic medium, without limitations on physical and geometrical parameters such as the density of the elastic material, the porosity or the number of periodic microstructures which constitute the medium. The model is applied to the case of the flow in a channel driven by an oscillating pressure gradient, with half the channel covered by a carpet of flexible, densely packed fibers, connected to each other to allow for the propagation of the deformation field.

Honami and monami waves are caused by large-scale coherent vortex structures which form in shear layers generated by canopies. In order to reach new insights on the onset of such waves, the instability of these shear layers is studied. Two different approaches are used. In the first approach, the presence of the canopy is modeled via a drag coefficient, taken to vary along the canopy as by experimental indications. The second approach considers the canopy as a porous medium and different governing equations for the fluid flow are deduced. In this second case, the anisotropy of the canopy, composed by rigid cylindrical elements, is accounted for via an apparent permeability tensor. The results obtained with the latter approach approximate better experimental correlations for the synchronous oscillations of the canopy.

Background Anti-MDA5 antibodies are a known set of antibodies observed mainly in dermatomyositis, typically associated with cutaneous involvement, presence and often rapid progression (RP) of interstitial lung disease (ILD) and amyopathic muscle involvement. Despite the increased attention, described cohorts involves only a limited number of cases Objectives to define clinical characteristics of a large cohort of anti-MDA5 antibodies positive patients Methods Retrospective assessment of anti-MDA5 positive patients from centres referring to our group Results 82 anti-MDA5 positive cases (56 females) were collected. In median: onset age was 44 Y (IQR 22.57), diagnostic delay 4 Mo (IQR 1–10), follow-up 13 Mo (IQR 3–43). Fifty-three patients had ILD, that was RP in 24 cases (15 at ILD onset, 9 after ILD onset). Fifthteen ILD patients were admitted in Intensive Care Unit (ICU): 4 were treated with Extracorporeal-Membrane-Oxygenation, 7 with mechanical-invasive and 2 with mechanical-non-invasive ventilation. Forthy-nine patients had muscle involvement (39 symptomatic), 42 arthritis, 54 cutaneous involvement, 9 history of malignancy. Twelve patients died (ILD=7, ILD and sepsis=3, neoplasia=1, not specified=1), 7 of those in ICU Conclusions In our cohort, ILD was the most frequent finding. A RP of ILD was common, occurring also in ILD with symptomatic/chronic onset. The low rate of survival in ICU raised the problem of follow up and early treatment of ILD. In our cohort arthritis was common and muscle involvement mainly symptomatic. Finally, the high percentage of observed malignancies suggests a careful neoplastic screening and follow up Reference [1] Labrador-Horrillo M, et al. J Immunol Res2014;2014:290797. Disclosure of Interest None declared

The aim of this study was to identify possible correlations between nailfold microangiopathy severity, finger dermal thickness (DT) and fingertip blood perfusion (FBP) in systemic sclerosis (SSc) patients.Fifty-seven SSc patients and 37 healthy subjects were enrolled. All patients were evaluated by nailfold videocapillaroscopy (NVC) to classify and score the severity of microangiopathy. Both modified Rodnan skin score (mRss) and skin high-frequency ultrasound were used to detect finger DT. Laser Doppler flowmetry (LDF) was employed to detect FBP.A positive correlation was found between nailfold microvascular damage severity and both ultrasound-DT (p=0.028) and mRss values (p0.0001). In particular, both ultrasound-DT and mRss were found progressively higher in patients with 'Early', 'Active' or 'Late' NVC pattern of microangiopathy. A negative correlation was observed between nailfold microvascular damage severity and FBP (p0.0001), showing the lowest FBP of the patients with more advanced NVC patterns. A negative correlation was observed between FBP, and both ultrasound-DT (p=0.007) and mRss values (p=0.0002). SSc patients showed a higher ultrasound-DT at the level of the fingers, as well as a lower FBP than healthy subjects (p0.0001).This study demonstrates a relationship between nailfold microangiopathy severity, DT and FBP in SSc patients.

A 46-year old man, affected by Darier’s disease (DD), was seen because of right hand pain, later extended to shoulders and ankles. Physical examination showed swelling and tenderness of the wrist, metacarpophalangeal and metatarsophalangeal joints, of the right Achilles tendon’s enthesis and of the left knee, with psoriatic-like lesions of the scalp. A diagnosis of seronegative spondyloarthritis, supported by HLA-B27 positivity and by the magnetic resonance imaging fi nding of hand synovitis and unilateral sacro-iliitis, was made. The correlation between DD, spondyloarthritis and psoriasis has been already anecdotally reported. Further observations may clarify if this association is more than casual.

The interaction between a fluid flow and a transversely isotropic porous medium is described. A homogenized model is used to treat the flow field in the porous region, and different interface conditions, needed to match solutions at the boundary between the pure fluid and the porous regions, are evaluated. Two problems in different flow regimes (laminar and turbulent) are considered to validate the system, which includes inertia in the leading-order equations for the permeability tensor through a Oseen approximation. The components of the permeability, which characterize microscopically the porous medium and determine the flow field at the macroscopic scale, are reasonably well estimated by the theory, both in the laminar and the turbulent case. This is demonstrated by comparing the model’s results to both experimental measurements and direct numerical simulations of the Navier–Stokes equations which resolve the flow also through the pores of the medium.

Objective.Systemic sclerosis (SSc) is characterized by microvascular injury, fibrosis, and hypoxia of involved tissues. The vasoactive peptide endothelin-1 (ET-1) seems to be implicated in these events. Using nailfold videocapillaroscopy (NVC), we evaluated longterm effects of ET-1 antagonist treatment on nailfold microvascular damage in patients with SSc, over a 3-year followup period.Methods.Thirty patients with SSc (mean age 64 ± 5 yrs, mean disease duration 8 ± 1 yrs) were recruited during their programmed standard treatment protocols. At baseline (T0), 15 patients with SSc (mean age 63 ± 15 yrs, mean disease duration 7 ± 3 yrs), already receiving cyclic intravenous infusion of iloprost (5 continuous days, average 80 μg/day, every 3 mo), continued the treatment for a further 3 years (ILO group). The remaining 15 patients with SSc (mean age 68 ± 13 yrs, mean disease duration 8 ± 4 yrs), although they continued the same cyclic intravenous iloprost treatment as the previous group, also received bosentan 125 mg twice a day for 3 years (ILO+BOS group). Qualitative analysis (scleroderma patterns) and semiquantitative scoring of the microvascular damage were performed by validated routine NVC methods.Results.During followup, a statistically significant increase of capillary number was observed in the ILO+BOS group (p < 0.02), with a significant and progressive increase of angiogenesis (p < 0.01). In contrast, the ILO group showed a statistically significant decrease of capillary number (p < 0.05). After 3 years the number of capillaries was significantly higher in the ILO+BOS group than in the ILO group (p < 0.05). The score for giant capillaries decreased significantly in both groups of patients with SSc (p < 0.05).Conclusion.In this open study, longterm treatment with ET-1 receptor antagonist in combination with iloprost was found to interfere with progression of nailfold microvascular damage in patients with SSc, as assessed by NVC over a 3-year followup period.

Objective To investigate the timing of transition through different patterns of nailfold microvascular damage in patients with systemic sclerosis (SSc). Methods In this medium-term longitudinal study, 38 SSc patients (median disease duration 12 months) with the early scleroderma pattern of microangiopathy seen on baseline nailfold videocapillaroscopy (NVC) were followed up by NVC for a median of 84 months. The evolution of the NVC pattern over time was monitored and recorded. Results At the end of followup, the NVC pattern was still that of early scleroderma in 47% of the patients. The active scleroderma pattern was seen in 34%, the late scleroderma pattern in 13%, and a normal pattern in 5%. The mean± SD time of progression from the early to the active pattern and from the early to the late pattern was of 28 ± 20 months and 36± 29 months, respectively. In the subgroup of patients whose microangiopathy progressed from the early to the late NVC pattern, the time of progression from the early to the active pattern was only 8± 1 months (P = 0.01), demonstrating that there is a subset of patients with rapid progression of microangiopathy. Clinical symptoms progressed in accordance with the nailfold morphologic changes in 60% of the SSc patients. Conclusion The results of this longitudinal study demonstrate dynamic transition of microvascular damage through different NVC patterns of microangiopathy in ∼50% of SSc patients. It is recommended that patients exhibiting rapid progression from the early to the active NVC pattern (

Objectives To study with MRI the hands of consecutive PMR patients, who were not selected on the basis of peripheral arthritis, with a correlation to clinical and laboratory findings. Methods Twenty-six hands of 15 PMR patients and 26 hands of 13 healthy controls were studied by extremity-dedicated MRI for the presence of synovitis, tenosynovitis, soft-tissue oedema, bone marrow oedema and erosions. Results Sixteen (61.6%) of the 26 PMR hands and 4 (15.4%) of the 26 control hands showed tenosynovitis (P = 0.001). Extensor tendon tenosynovitis was seen in 9 (34.6%) of the 26 PMR hands, but in only 1 (3.8%) control hand (P = 0.002) and flexor tenosynovitis was seen in 12 (46.1%) of the 26 PMR hands and in 4 (15.4%) of the 26 control hands (P = 0.03). All other features were similar in the two groups. Conclusions Our data support the view that tenosynovitis, especially of the extensor tendons, is a frequent event in PMR, unrelated to clinical involvement of the hand. This finding is in agreement with the concept of PMR as a disease of extra-articular structures.

Bone erosions, considered the hallmark of rheumatoid arthritis (RA), are shown more accurately by MRI than by conventional radiography (CR). Erosions healing is exceptional when studied by CR. This study is concerned with an extremity-dedicated MRI evaluation of erosion changes in patients with RA followed over time. Wrist and metacarpo-phalangeal (MCP) joints of 57 RA patients were imaged with a dedicated-extremity, 0.2 T MRI at baseline and follow up. A decrease of the RAMRIS erosion score indicating erosion healing, calculated both by conventional visual judgement and by a semi-automated method, was seen in 7 (12.3%) patients at the wrist and in 3 (5.3%) at the MCPs. In the same locations, RAMRIS was unchanged in 17 (29.8%) and 31 (54.4%) patients, and worsened in 33 (57.9%) and 17 (29.8%), respectively. Healing of erosions occurs, although rarely, in patients with RA when studied with sensitive imaging techniques, such as MRI.

Despite the ubiquity of fluid flows interacting with porous and elastic materials, we lack a validated non-empirical macroscale method for characterizing the flow over and through a poroelastic medium. We propose a computational tool to describe such configurations by deriving and validating a continuum model for the poroelastic bed and its interface with the above free fluid. We show that, using stress continuity condition and slip velocity condition at the interface, the effective model captures the effects of small changes in the microstructure anisotropy correctly and predicts the overall behaviour in a physically consistent and controllable manner. Moreover, we show that the performance of the effective model is accurate by validating with fully microscopic resolved simulations. The proposed computational tool can be used in investigations in a wide range of fields, including mechanical engineering, bio-engineering and geophysics., Main paper: 28 pages, 14 figures; Supplementary appendicies: 7 pages; under consideration for publication in Roy. Soc. Proc. A

Objective.To evaluate the longterm effects of endothelin-1 (ET-1) antagonism on peripheral blood perfusion (PBP) in patients with systemic sclerosis (SSc).Methods.Twenty-six patients with SSc already receiving cyclic intravenous iloprost (ILO) for severe Raynaud phenomenon were enrolled. Thirteen patients continued the treatment for a further 3 years (ILO group) and 13 patients, because of the appearance of digital ulcers, received in addition bosentan (BOS; 125 mg twice/day) for 3 years (ILO + BOS group). Both PBP at fingertips and nailfold microangiopathy were evaluated yearly by laser Doppler flowmetry and nailfold videocapillaroscopy, respectively.Results.A progressive significant increase of PBP was observed in the ILO + BOS group during the 3 followup years (p = 0.0007, p = 0.0002, p = 0.01, respectively). In contrast, an insignificant progressive decrease of PBP was observed in the ILO group. Difference of perfusion between the PBP evaluations at basal temperature and at 36°C (to test capillary dilation capacity), was found progressively decreased during the 3-year followup only in the ILO group (p = 0.05, p = 0.26, p = 0.09, respectively). A progressive increase of nailfold capillary number was observed only in the ILO + BOS group after 2 and 3 years of followup (p = 0.05).Conclusion.Longterm treatment of SSc patients with ET-1 antagonism, in combination with ILO, seems to increase fingertip blood perfusion, as well as both capillary dilation capacity and number.

Finite amplitude coherent structures with a reflection symmetry in the spanwise direction of a parallel boundary layer flow are reported together with a preliminary analysis of their stability. The search for the solutions is based on the self-sustaining process originally described by Waleffe (Phys. Fluids 9, 883 (1997)). This requires adding a body force to the Navier-Stokes equations; to locate a relevant nonlinear solution it is necessary to perform a continuation in the nonlinear regime and parameter space in order to render the body force of vanishing amplitude. Some states computed display a spanwise spacing between streaks of the same length scale as turbulence flow structures observed in experiments (S.K. Robinson, Ann. Rev. Fluid Mech. 23, 601 (1991)), and are found to be situated within the buffer layer. The exact coherent structures are unstable to small amplitude perturbations and thus may be part of a set of unstable nonlinear states of possible use to describe the turbulent transition. The nonlinear solutions survive down to a displacement thickness Reynolds number Re * = 496 , displaying a 4-vortex structure and an amplitude of the streamwise root-mean-square velocity of 6% scaled with the free-stream velocity. At this Re* the exact coherent structure bifurcates supercritically and this is the point where the laminar Blasius flow starts to cohabit the phase space with alternative simple exact solutions of the Navier-Stokes equations.

The objective of this prospective study was to investigate the transition from primary (PRP) to secondary (SRP) Raynaud’s phenomenon (RP), in a large cohort of patients affected by isolated RP. A total of 2065 patients with RP were investigated by clinical interview, laboratory examinations, and nailfold videocapillaroscopy (NVC). Patients with negative NVC at first visit were yearly followed to monitor either the appearance of specific morphological alterations at NVC, or clinical manifestations of an underlying disease. Capillary abnormalities at NVC were scored, as well as the qualitative patterns of microangiopathy (Early, Active and Late). NVC was found negative at first visit in 1500 subjects; among them, 412 patients were evaluable and they were followed for a mean time of 5±4 years (range 2-13 years). Sixty-eight patients (16%) achieved a diagnosis of SRP during follow-up, showing normal or not specific capillary alterations at NVC 4% of patients (the diagnosis was undifferentiated connective tissue diseases), Early scleroderma-pattern 57%, Active scleroderma-pattern 7%, Late scleroderma-pattern 12%, and scleroderma-like pattern 18% of patients. The time of transition from normal/not specific capillary alterations to Early scleroderma-pattern was 4.4±3.8 years. Enlarged capillaries (diameter between 20 and 50 microns) and mild reduction of capillary density were found the more frequent markers at first NVC visit in patients who progressed to a scleroderma pattern (P=0.01). This study demonstrates in a large cohort, that almost 16% of patients initially diagnosed as affected by RP with negative NVC may transit to SRP during a mean follow-up of 4.4 years. PRP patients showing major notspecific alterations of nailfold capillaries at first NVC should be strictly monitored at least once a year since at higher risk of transition to SRP.

Objective.This study evaluates possible correlations between the pattern of antinuclear antibodies (ANA) on indirect immunofluorescence (IIF) testing and nailfold microangiopathy stage (early, active, and late stage) in systemic sclerosis (SSc). Patients with SSc were followed prospectively to monitor progression of microvascular damage.Methods.The ANA pattern on IIF was searched in 42 patients with SSc showing an early pattern of nailfold microangiopathy at baseline, and was followed using nailfold videocapillaroscopy (NVC) for a median time of 91 months.Results.Among patients whose microangiopathy showed a rapid progression from early to late pattern on NVC, the IIF pattern was fine-speckled + nucleolar (Scl-70+) in 44%, centromeric in 33%, nucleolar in 11%, and homogeneous in 11% of patients with SSc. Antitopoisomerase I antibodies were significantly more frequent (57%) in patients with late pattern of microangiopathy on NVC. The median time of progression from early to active disease was significantly lower in patients with both fine-speckled + nucleolar and nucleolar ANA positivity. The severity of microangiopathy was higher in patients with the nucleolar pattern on IIF. Patients already showing a slight reduction of capillary number at baseline were likely to have either the nucleolar or the fine-speckled + nucleolar pattern on IIF. Of note, 37% of patients still showing the early microangiopathy pattern on NVC at the end of the followup were ANA-negative.Conclusion.ANA-negative patients with SSc display a slower progression of nailfold microangiopathy characterized by the early pattern on NVC. Progression to the late NVC pattern (more advanced stage of microvascular damage) seems to be associated with a different autoantibody pattern on IIF (fine-speckled + nucleolar pattern being the most prevalent).

Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, evaluates synovitis and bone marrow edema in psoriatic arthritis (PsA). In this pilot study, we looked at possible differences between joint synovitis and tenosynovitis in PsA as compared with rheumatoid arthritis (RA).Seven patients with PsA and 10 with RA were studied. After DCE-MRI was performed on 3 axial slices of the wrist, the enhancement ratio was calculated on 6 different regions of interest (ROI) of the synovial membrane outlined by the operator: the wrist compartment, 3 extensor tendon compartments, and 2 flexor compartments. DCE-MRI results were quantitatively analyzed using the Dynamika software, a computer-aided semiautomated method.In PsA, the area of the ROI outlined around the first and second extensor compartments was larger than in RA; the opposite was true for the extensor carpi ulnaris region. The volume of inflammation was significantly higher in RA than in PsA for all the extensor compartments except the second, and in the joint synovial membrane. The DCE-MRI indicators of the degree of inflammation were higher for PsA in the joint synovial membrane (p = 0.002 and p0.001, respectively). There was a significant correlation between volume of inflammation but not its degree and 28-joint Disease Activity Score at the level of the wrist joint (r = 0.6; p = 0.01).DCE-MRI can reveal useful and potentially clinically important information on the characteristics of different types of arthritis.

Objectives: MRI has been proposed as the imaging method of choice to evaluate the long-term outcome in patients with early arthritis. The role of dynamic MRI, performed at presentation, in predicting the outcome of patients with early arthritis has been addressed in the present study. Methods: 39 patients with early arthritis, involving at least one wrist, were studied with clinical visits and laboratory investigations, every 3 months. Dynamic MRI was performed with a low-field (0.2T), extremity-dedicated machine (Artoscan, Esaote, Genova, Italy) equipped with a permanent magnet and with a dedicated hand and wrist coil. During the intravenous injection of Gd-DTPA, twenty consecutive fast images of 3 slices of the wrist were acquired. The synovial contrast enhancement ratio was calculated both as rate of early enhancement (REE) per second during the first 55” and as relative enhancement (RE) at t seconds. Results: In our cohort of patients, REE and RE were significantly lower than those observed in a historical cohort of 36 patients with active rheumatoid arthritis. In univariate analysis, low RE predicted complete remission of arthritis. In multivariate analysis, fulfillment of RA criteria during follow-up was predicted by high RE. The need for immunosuppressive treatment at the end of follow-up was predicted by both low RE and high REE. Conclusions: Dynamic MRI may be used to predict several outcomes of early arthritis involving the wrist

BACKGROUND AND PURPOSE: A growing body of evidence suggests the involvement of the brain in FM. The purpose of this proton MRS study was to test the hypothesis that there are metabolic alterations in some brain regions processing pain (VLPFC and thalamus) in patients with FM compared with HC. MATERIALS AND METHODS: Twelve patients with FM (30–54 years of age; mean age, 43.2 years), and 12 HC, matched for age and sex, underwent 1 session of single-voxel MRS performed on a 3T MR imaging scanner. MRS spectra were acquired with a PRESS for localization. The raw data from each spectrum was evaluated with an LCModel. T tests were used to evaluate differences of brain metabolites between groups. The Pearson correlation tested the relationship of metabolite ratios and clinical symptoms. RESULTS: Glx/Cr and Glu/Cr ratios within the VLPFC of both sides were significantly higher in patients than in HC (P < .01). No significant differences of metabolites between groups were found in the thalami. Positive correlations were found between Glu/Cr in the left thalamus and the VAS for pain (r = 0.730, P = .007) and between mIns/Cr in the right VLPFC and the VAS for pain (r = 0.607, P = .037) and the FIQ (r = 0.719, P = .008). CONCLUSIONS: The presence of elevated Glu/Cr levels in VLPFC strengthens the opinion that a complex neurophysiologic imbalance of different brain areas involved in pain processing underlies FM. These data may be useful in the diagnosis and development of more effective pharmacologic treatments.

Gouty arthritis (GA), a recurrent arthritis induced by precipitation of monosodium urate (MSU) crystals, has a 1.4% prevalence.1 2 The hands are affected in 24.7% of patients3 often with long-standing and diuretic-induced disease. Imaging can help in the differential diagnosis of GA and in understanding its pathogenic mechanisms. MRI has been mainly used to evaluate tophi4; information on synovitis, bone marrow oedema (BME) and erosions is scanty. Eight patients affected by acute GA involving the wrist were considered. Gout was diagnosed using the American College of Rheumatology (ACR) criteria5 and confirmed by the identification of MSU crystals in tophi or synovial fluid. Immunoglobulin M rheumatoid factor (RF), anticyclic citrullinated protein (anti-CCP) antibodies, psoriasis or family history of psoriasis were absent. Gout patients were compared with eight patients with active (mean Disease Activity Score 28-CRP 5.78±0.95), RF and anti CCP antibodies positive, RA diagnosed according to the ACR criteria.6 All patients signed an informed consent. The study was approved by the local ethical committee. MRI was performed during the …

Objective: To assess the clinical characteristics of gout and its diagnostic approach in a group of Italian patients. Methods: In a retrospective analysis, we evaluated 72 consecutive gouty patients examined in the years 2000-2007.We recorded demographic data, family history, comorbidities and disease characteristics (seasonality of the attacks, joints affected, serum uric acid concentration, and treatment). Result: 63/72 (87.5%) patients were men and 9 women, with mean age 61.9±13.7 years. 8/72 (11.1%) patients reported a familial history of gout. The first attack occurred mainly in the months of June, July and December. The first metatarsophalangeal joint was affected in 59.7% of patients and the hand in 25%. Treatment changed over the follow- up period, with a decreased use of NSAIDs (p

Background Polymyalgia rheumatica (PMR) is an inflammatory disease of the elderly characterized by girdle pain and systemic symptoms. Imaging techniques, such as 18F-fluorodesoxyglucose (FDG)-PET/CT, have demonstrated that inflammation is localized mainly in the joint capsule and in bursae, with occasional large vessel vasculitis. However, the correspondence between FDG uptake and subjective symptoms is unclear. We have recently demonstrated that interspinous bursitis is typical of PMR, although it does not associate with pain. Objectives To test if FDG uptake, which is frequently seen in the girdles of PMR patients, is associated with the clinical experience of pain in the individual patients. Methods Eighty-four patients affected by PMR according to the ACR/EULAR criteria were studied. A standardized clinical examination, including pain at pressure of the long head of the biceps (LHB), the subacromial area (SA), the ischiatic (IB) and trochanteric (TB) bursae, and at mobilization of the shoulder and hip girdles, was performed immediately before PET/CT. After a minimum of six hours fasting, a dose of 4.8-5.2 MBq of FDG per kilogram body weight was injected through a peripheral vein catheter. Data acquisition started between 60 and 90 minutes after tracer administration. Patients underwent simultaneous FDG-PET and CT imaging from the skull base to the knee using an integrated PET/CT scanner (Hirez; Siemens Medical Solutions, Knoxville TN, USA). PET raw data were reconstructed by means of ordered subset expectation maximization and attenuation correction was performed using the CT raw data. The entire CT dataset was fused with the 3-dimensional PET images using an integrated software interface (Syngo Image Fusion; Siemens Erlangen, Germany) to create superimposed anatomical images. Joint uptake was scored relative to liver uptake as 0=no uptake present, 1=lower than liver uptake, 2=similar to liver uptake, 3=higher than liver uptake. Results A history of shoulder pain was present in all patients, whereas that of the pelvic girdle was present in 42/84 (50%). The concordance between pain elicited in the different areas and FDG uptake is shown in the table for the right (R) and left (L) sides. At clinical examination, 11/84 (13.1%) patients reported spontaneous pain or pain on passive motion which was clearly more intense in one shoulder. In these cases, tracer uptake was more intense in the symptomatic side in only 2, whereas in the remaining ones it was symmetrically distributed (bilaterally absent in 1 and bilaterally present in 8). Pelvic pain side was discordant in only 1 patient. The TB and IB were involved more often at PET than clinically. Conclusions The concordance between pain and FDG uptake in the girdles of PMR patients is only modest, except for shoulder capsulitis/synovitis, suggesting that factors other than inflammation visible at PET could contribute to clinical presentation. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3011

Background Rituximab (RTX), a chimeric monoclonal antibody targeting CD20 B cell antigens, is a safe and effective treatment for rheumatoid arthritis (RA) [1]. It has been approved for RA patients who have inadequately responded to one or more anti-TNF agent and has recently been demonstrated to be significantly more effective after a first anti-TNF than switching to a second [2]. Long-term extensions of randomised controlled trials have demonstrated that prolonged RTX exposure of up to 9.5 years does not affect its safety, but there are no data concerning real-life clinical experience. Objectives The aim of this multicentre clinical study was to evaluate the retention of RTX treatment in patients with RA. Methods The clinical records of 472 RA patients treated with RTX from August 2006 to December 2013 in ten Italian rheumatology centres were reviewed, and treatment survival and the impact of selected variables were evaluated using Kaplan-Meier and Cox survival analyses. Results Four hundred and seventy-two patients with a diagnosis of RA based on the 1987 ACR classification criteria (81.6% female; mean age 56.2±12.8 years; mean disease duration 10.5±8 years; 76.3% RF positive; 75% anti-CCP positive) were treated with RTX for a mean of 40.1±26.37 months (range 0-122). Seventy-six percent were co-treated with MTX, and 24% had previously received two or more anti-TNF agents. Their median DAS28 score at baseline was 5.07±1.3. For patients completing at least 12, 24, 36, 48 and 60 months of follow-up, the retention rates were respectively 87.9%, 78.8%, 72.5%, 67.6% and 63.8% (Fig. I) Treatment discontinuations because of adverse events and inefficacy had a similar temporal trend. Multivariate analysis (Cox regression) showed that none of the considered predictive variables was significantly associated with treatment survival: gender p=0.399; age p=0.486; disease duration p=0.999, baseline DAS28 p=0.412; number of previous anti-TNFα failures p=0.975; the presence of RF p=0.513; MTX treatment p=0.340. Conclusions Our findings show that 63.8% of RA patients continued treatment with RTX for 60 months. References Chi Chiu Mok. Rituximab for the treatment of rheumatoid arthritis: an update. Drug Des Devel Ther. 2013;8:87-100 Emery P, et al. Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study. Ann Rheum Dis. 2014. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3994

To the Editor: Olech, et al 1 recently used extremity-dedicated magnetic resonance imaging (MRI) to highlight hand lesions in patients with rheumatoid arthritis (RA) in comparison with controls. They noted that the second and third metacarpal heads were more often eroded in RA. Bone lesions, morphologically identical with erosions, were also common in controls at the same locations. A similar observation was made by Tan, et al , who linked it to anatomical causes2. The term “lesion” in MRI studies of the joints encompasses bone edema, erosions, and cysts3. According to the OMERACT definition4, an erosion is a sharply marginated bone lesion, of typical juxtaarticular localization and specific signal characteristics, which is … Address correspondence to Prof. M.A. Cimmino; E-mail: cimmino{at}unige.it

Background Bone erosions have been always considered the hallmark of rheumatoid arthritis (RA). Advanced imaging techniques, such as computed tomography, MRI, and, at least in several joint areas, ultrasonography have shown increased sensitivity for demonstration of erosions in comparison with conventional radiography. In addition, modern follow-up of erosions requires high sensitivity to change in view of the increased capability of new therapeutic strategies to promote their improvement. Erosions healing in patients with RA is considered exceptional when studied by conventional radiology. Modern and sensitive imaging techniques can appreciate more subtle changes of bone morphology due to their multiplanar capacity. Objectives This study is concerned with an extremity-dedicated MRI evaluation of erosion changes in patients with RA followed over time. Methods 57 patients affected by RA (42 women, median age 52 years, range 20-73 years, median disease duration 22 months, range 1-420 months) diagnosed according to the 1987 revised ACR criteria were studied. Wrist and metacarpophalangeal (MCP) joints were imaged with a dedicated-extremity, 0.2 T MRI (Artoscan, Esaote, Genova, Italy) at baseline and after a median of 15 months (range 6-121 months). A turbo T1-weighted three dimensional sequence (T3-D T1) in the coronal plane, with subsequent multiplanar reconstructions on the axial and sagittal planes was used; slice thickness was 0,3 mm, TR 860 ms, TE 26 ms, and number of excitations (NEX) 1. Bone studied included the 2 nd to 5 th MCPs, the 1 st to 5 th metacarpal bases, the 8 wrist bones, and the distal radius and ulna. Erosions were scored according to the RAMRIS. Results 30/57 (52.6%) patients were RF positive and 34/57 (59.6%) anti CCP positive. Median ESR was 40 mm/h (range 7-120 mm/h) and median CRP was 6.9 mg/dL (range 0.6-128 mg/dL). A decrease of the RAMRIS erosion score, indicating erosion healing, was seen in 7 (12.3%) patients at the wrist and in 3 (5.3%) at the MCPs. The same figures in patients with unchanged and worsened RAMRIS were 17 (29.8%) and 31 (54.4%), and 33 (57.9%) and 17 (29.8%), respectively. Altogether 1311 bones were evaluated (855 wrist and 456 MCP bones). A decrease of at least one point in the RAMRIS for erosions was observed in 27 (3.2%) wrist bones and in 7 (1.5%) MCPs. The bones with more frequent healing were 2 nd metacarpal basis (0.7%), triquetrum (0.6%), 2 nd (0.5%) and 5 th (0.74%) metacarpal heads. 3 patients with improved global RAMRIS had, however, worsening of the erosions in at least one wrist bone. 3 patients with unchanged RAMRIS and 7 with worsening RAMRIS had erosion healing in at least one wrist bone. The same finding was observed at the MCPs level in 2 and 1 patients, respectively. Finally 5 patients with unchanged RAMRIS had worsening of the erosions at the wrist and 2 patients at the MCPs. Conclusions Healing of erosions occurs, although rarely, in patients with RA when studied with sensitive imaging techniques, such as MRI. The coexistence of erosion’s healing and deterioration in the same hand or even in the same bone was frequent, supporting the view that not only general disease activity but also localized inflammatory and mechanical mechanisms are important. Disclosure of Interest None Declared

Background Decreased peripheral blood perfusion is a typical clinical aspect of systemic sclerosis (SSc) (1,2). Laser speckle contrast analysis (LASCA) is a new technique to assess and quantify blood perfusion (BP) in different skin areas of the body (3). Objectives The aim of the study was to assess by LASCA the BP in different areas of the hand and face, in SSc patients and healthy subjects. Methods Twenty-one SSc patients (mean disease duration 7±6 years) and twenty-five healthy subjects (matched for sex and age with SSc patients) were enrolled, after informed consent. BP was analysed by LASCA technique at level of face and dorsal and palmar regions of the hands in both SSc patients and healthy subjects. Different regions of interest (ROIs) were created at fingertips, periungual areas, palm and dorsum of both hands, as well as at the level of the face (forehead, tip of nose, zygomas and perioral region). The average BP was scored as perfusion units (PU). Concerning LASCA technique, when an object is illuminated by laser light, the backscattered light will form a random interference pattern consisting of dark and bright areas (speckle pattern). If the illuminated object is static, the speckle pattern is stationary; when there is movement in the object, such as red blood cells in a tissue, the speckle pattern will change over time. The machine records these changes in the speckle pattern. Non-parametric tests were used to carry out the statistical analysis. Results SSc patients showed a statistically significant lower median BP than healthy subjects at the level of fingertips (112 and 164 PU, respectively, p=0.02) and periungual areas (93 and 147 PU, respectively, p=0.003). A statistically significant positive correlation was observed between BP of the fingertips and BP of the periungual areas in both SSc patients (r=0.94, p Conclusions This study shows that LASCA technique detect significant differences of BP at the level of fingertips and periungual areas in SSc patients versus healthy subjects. However, at the level of palm/dorsum of hands and face, no significant BP difference have been detected between SSc patients and healthy subjects. References Cutolo M, et al. J Rheumatol 2010; 37:1174-80. Rosato E, et al. Rheumatology 2011;50:1654-8. Draijer M et al. Laser Med Sci 2009; Disclosure of Interest : None Declared

Background Systemic sclerosis (SSc) is characterized by early impairment of the microvascular system and decrease in peripheral blood perfusion (PBP) (1,2). Objectives The aim of this study was to asses PBP by new technique laser speckle contrast analysis (LASCA) in SSc patients with different patterns of nailfold microangiopathy, checking for any correlations between LASCA and laser Doppler flowmetry (LDF) techniques (1-3). Methods Sixty-one SSc patients and 61 sex and age-matched healthy subjects were enrolled, after informed consent was signed. PBP was analysed by LASCA in both SSc patients and healthy subjects, by creating eight regions of interest (ROI) at the fingertips of the 2nd-5th finger bilaterally, after a 30 second recording of whole hand: the average perfusion was scored as perfusion units (PU). PBP was measured also by LDF at the central area of the fingertips, through a 30 second recording for each fingertip (2). Peripheral microangiopathy was detected and scored by nailfold videocapillaroscopy (NVC), assessing the proper pattern of microvascular damage (Early, Active, or Late), calculating the microangiopathy evolution score (MES) (4-6). Patients enrolled into the study were not taking vasoactive drugs. Non-parametric tests were used for the statistical analysis. Results PBP was significantly lower in SSc patients than in healthy subjects, as evaluated by both LASCA (median 85 and 187 PU, respectively; p Conclusions As evaluated by LASCA, PBP was found lower in SSc patients than in healthy subjects, and was found progressively lower in SSc patients with worsening pattern of nailfold microangiopathy. There was a significant positive correlation between LASCA and LDF in the assessment of PBP. However, LASCA is less time consuming than LDF and shows lower intra-operator variability. References Cutolo M, et al. Nat Rev Rheumatol 2010; 6, 578-87. Cutolo M, et al. J Rheumatol 2010; 37:1174-80. Draijer M et al. Laser Med Sci 2009; 24: 639-51. Sulli A, et al Arthritis Rheum. 2012; 64: 821-5. Sulli A, et al. Ann Rheum Dis 2008; 67:885-7. Smith V, et al. Ann Rheum Dis 2010; 69:1092-6. Disclosure of Interest: None Declared

Background Three different and progressive patterns of nailfold microvascular damage are evident in systemic sclerosis (SSc) (1). The dynamic transition from “Early” to “Active” or to “Late” pattern was described in about half of SSc patients during a 7 year follow-up, but the precise factors or events influencing a slower or faster progression of the SSc microangiopathy are still not yet identified (2). Objectives To detect serum autoantibodies in SSc patients showing the progression of nailfold microangiopathy, to look at possible correlations between autoantibody patterns and microangiopathy stages. Methods Forty-two SSc patients (median age 47 years; median disease duration 1 year) with the “Early” pattern of nailfold microangiopathy at baseline were prospectively followed-up by nailfold videocapillaroscopy (NVC) for an average time of 91 months. SSc patients were classified according to their pattern of microangiopathy, as previously described (1,3). Anti-nuclear (ANA), anti-topoisomerase I (Scl70), and anti-centromere (ACA) antibodies were evaluated in all patients. Results At the end of follow-up, the NVC pattern of microangiopathy changed in 55% of the SSc patients: 14 patients (33%) were showing the “Active” NVC pattern, 9 patients (21%) the “Late” pattern, while 19 patients (45%) were still showing the “Early” scleroderma-pattern. Concerning serological markers in nine patients whose microangiopathy showed a progression to “Late” NVC pattern through the “Active” pattern, four patients were found positive for Scl70 (44%), three patients were ACA positive (33%), and two patients were ANA positive (with nucleolar (11%) and homogeneous (11%) fluorescence pattern, respectively). Prevalence of ACA (positive in 40% of all patients) was found significantly higher in SSc patients showing either the “Early” (41%) or the “Active” (41%) NVCpatterns of microangiopathy at the end of follow-up, confirming previous observations that ACA are likely to be associated with a slower disease progression. Opposite results were obtained for the Scl70 autoantibodies (positive in 17% of patients), which were found more frequent in patients with “Late” (44%)NVC patterns of microangiopathy (p=0.05). Interestingly, 37% of patients showing the “Early” pattern of microangiopathy at the end of the follow-up were found ANA negative. Conclusions The results of the study confirm the progressive transition of the SSc microvascular damage through different NVC patterns. Both ANA-negative and ACA positive SSc patients might display a slower progression rate of the nailfold microangiopathy. The progression to the “Late” NVC pattern (more advanced stage of microvascular damage) is associated with different autoantibody presence, and needs investigation through larger longitudinal studies. References Cutolo M, et al. Rheumatology 2004; 43: 719-26. Sulli A, et al. Arthritis Rheum 2012; 62: 000-000. In press. Cutolo M, et al. Nat Rev Rheumatol 2010; 6: 578-87. Disclosure of Interest None Declared

Background Nailfold videocapillaroscopy (NVC) analysis can definitely distinguish between primary (PRP) and secondary (SRP) Raynaud’s phenomenon by identifying the “early” scleroderma-pattern of microangiopathy (giant capillaries and microhaemorrhages) (1). Objectives The aim of the study was to evaluate, in recent SRP patients, who developed the “early” pattern of nailfold microangiopathy (and SRP) the evolution of very early non-specific morphological capillary alterations by a follow up of their previous NVC microvascular status. Methods After informed consent and Ethical Committee approval, fifty patients with early diagnosis of SRP (mean age 47±16 years; mean SRP duration 7±8 years) based on the new finding of “early” NVC scleroderma-pattern of microangiopathy were evaluated (one year retrospective follow-up), to study the evolution of not specific capillary abnormalities possibly present at previous NVC examinations, in particular capillary ectasias (diameter between 20-50 microns). Two fields per finger (from the 2nd to the 5th finger) of both hands were analyzed and the average semiquantitative scores for the capillaroscopic parameters (i.e. capillary number, ectasias, giant capillaries, microhaemorrhages, ramified capillaries), as previously reported (2-3). The statistical examination was performed by non-parametric tests. Results All the SRP patients showed two or more giant capillaries, identifying the “early” scleroderma-pattern of microangiopathy at the moment of inclusion. In 74% of patients the “ectasia score” remained the same during one-year follow-up, despite the appearance of giant capillaries, while in 26% of patients the “ectasia score” increased from 1 to 2 (p=0.005). 42% of patients showed a one-point increment of the microhaemorrhage score (from 0 to 1 or from 1 to 2) (p=0.005). At first NVC examination, 9% of patients showed a mild capillary number reduction, which did not change during the subsequent follow-up (score 1); in 16% of cases a not statistically significant reduction of capillary number (score from 0 to 1) was observed at last NVC visit. Capillaries ramifications were not observed at follow-up. Conclusions The results confirm that the transition from PRP to SRP is characterised by the appearance of giant capillaries, at NVC. However, the very early identification of nailfold capillary ectasias in a subgroup of PRP patients suggests the need for close NVC monitoring of these patients, in order to early detect the onset of giant capillaries and related diseases, such as systemic sclerosis, especially when other clinical features of the disease are not evident. References Cutolo, M. et al. Nature Rev Rheumatol 2010; 6, 578–587. Cutolo M, et al. Rheumatology 2004; 43: 719-26. 3. Sulli A, et al. Ann Rheum Dis 2008; 67:885-7. Disclosure of Interest None Declared

Background Aromatases increase estrogen synthesis in inflammatory tissues whereas vitamin D (calcitriol, 1,25-dihydroxyvitamin D3, 1,25(OH) 2 D 3 ) seems to decrease the aromatase expression at least in human cancer cells (BCa cells) (1). Interestingly, the aromatase activity is increased together with the estrogen synthesis in the synovial tissue of rheumatoid arthritis (RA) patients, especially at the level of macrophages (2-4). Objectives To evaluate in cultures of human activated macrophages the influence exerted by calcitriol on aromatase expression, as a new target for 1,25(OH) 2 D 3 cell modulation of proinflammatory cytokine production (5). Methods Cultures of human monocytic THP-1 were activated to macrophages and treated for 24 hours with 1,25(OH) 2 D 3 (10 -8 M), alone or in combination with 17b-estradiol (E 2 , 10 -8 M), in order to evaluate the effects on the intracrine estrogen metabolism (aromatase-driven) and cytokine synthesis. Untreated human macrophages were used as controls (basal condition). P450-aromatase synthesis was evaluated by immunocytochemistry (ICC) and western blot analysis (WB). The expression of P450-aromatase gene (CYP19A1) was investigated by real-time PCR (RT-PCR). Macrophage proinflammatory cytokines IL1-β, IL-6 and TNF-α were evaluated by ELISA and WB. Results Interestingly, 1,25(OH) 2 D 3 downregulated P450-aromatase synthesis, CYP19A1-gene expression, and proinflammatory cytokine production (IL1-β, IL-6 and TNF-α) in basal conditions when compared to 1,25(OH) 2 D 3 -untreated macrophages. However and interestingly, the treatment with 1,25(OH) 2 D 3 significantly reduced the increase in P450-aromatase (p 2 D 3 -untreated) macrophages. Conclusions Our data suggest that 1,25(OH) 2 D 3 may downregulate the proinflammatory cytokine production in human activated macrophages by significantly decreasing the aromatase activity, especially in presence of an enhancing estrogenic milieu. Interestingly, this latter hormonal metabolic condition is observed in the synovial tissue and fluid of RA patients of both sexes (2,3). References Krishnan AV et al. Endocrinology 2010;151:32-42. Cutolo M et al. Autoimmun Rev. 2011;2 [Epub ahead of print]. Cutolo M. Rheumatology (Oxford) 2009;48:210-12. Le Bail J et al. Steroids. 2001;66:749-57. Zwerina K et al. Ann Rheum Dis. 2011;70:1122-9. Disclosure of Interest None Declared

Background Modified Rodnan skin score (mRss) and high frequency ultrasound (US) are employed to evaluate dermal thickness (DT) in systemic sclerosis (SSc) patients (1-3). Laser Doppler flowmetry (LDF) is used to assess and measure the peripheral blood perfusion (4). Objectives The aim of this study was to identify possible correlations between finger dermal thickness (DT) using both US and mRss, and fingertip blood perfusion (FBP) in SSc patients. Methods Forty-nine consecutive SSc patients and 37 healthy subjects (CNT) were enrolled, after informed consent. US was performed in both SSc patients and CNT to evaluate DT (ultrasound-DT) at the level of the dorsum of the middle phalanx of the third finger on both right and left hand, and the average value was recorded in millimetres. After double blind evaluation of US pictures, the intra-operator reproducibility in measuring DT was found of 95%. DT was also assessed by mRss in SSc patients at the level of the dorsum of the fingers bilaterally, and the average score of the fingers was calculated. LDF was performed in both SSc patients and CNT. FBP was detected at the level of the fingertips bilaterally, and the results were expressed as perfusion units (PU). The same operator (BR) performed the examination, and there was a 88% reproducibility of the LDF assessment. Statistical analysis was carried out by non parametric tests. Results SSc patients showed higher ultrasound-DT as well as lower FBP at the level of the fingers, than healthy subjects (p Conclusions A significant negative correlation between finger DT, evaluated by either US or mRss, and FBP, evaluated by LDF, is detectable with reliability in SSc patients. References Clements PJ, et al. J Rheumatol 1993; 20: 1892-6. Moore TL, et al. Rheumatology 2003; 42: 1559-63. Kaloudi O et al. Ann Rheum Dis. 2010; 69:1140-3. Cutolo M, et al. J Rheumatol 2010; 37:1174-80. Disclosure of Interest None Declared

Background Systemic sclerosis (SSc) is characterized by microvascular injury, fibrosis and hypoxia of involved tissues causing progressive organ damage (i.e.digital ulcers-DU). The endothelin1 receptor antagonism (bosentan-BOS) is actually used to prevent DU in SSc patients. Nailfold videocapillaroscopy (NVC) allows to characterize (SSc patterns), quantify and monitor the nailfold microvascular damage progression in SSc. Objectives To evaluate by NVC the effects of BOS treatment on nailfold microvascular damage evolution in SSc patients already under symptomatic treatment with prostacyclin (iloprost-ILO). Methods 26 SSc patients (pts- mean age 64±5 yrs, disease duration 7.4±1yrs) according to the LeRoy and Medsger’s criteria, entered an open study after informed consent and Etical Committee approval. Subsequently, 13 SSc pts of them (mean age 61±16, disease duration 6.6±2.8) already receiving ILO from an average of 5.5±1.4 yrs, continued their treatment for at least 2 yrs (cycles of 5 day ILO iv-infusion-24 hours, 80 microgr/day every 4 months); the remaining 13 SSc pts (mean age 68±14, disease duration 8.1±3.8) were under treatment with ILO from an average of 7.3±2.8 yrs and at the first appearance of DU combined treatment with ILO+BOS (125mg twice a day). All SSc pts were followed for at least 2 yrs. NVC was yearly performed from basal analysis, in order to detect the SSc patterns and to score the markers of damage (namely number of normal and giant capillaries, microhaemorrhages and angiogenesis). Statistical analysis was carried out by non-parametric tests. Results At baseline, no statistically significant differences were present between the two groups concerning NVC SSc patterns. Interestingly, at 2 yrs, NVC showed a statistically significant increase of capillary number limited to the ILO+BOS SSc group (p=0.05). At the same time, both giant capillaries and microhaemorrhage scores significantly decreased only in ILO+BOS SSc pts (p=0.05 and p=0.02, respectively). On the contrary, the microangiopathy score (MES), evaluating the capillary markers of microvascular damage progression, significantly increased only in ILO-treated pts at 2 yrs (p=0.05). No side effects and appearance of further DU was observed during the survey in all SSc pts. Conclusions In SSc patients affected by DU, bosentan addiction significantly reduces the progression of the microvascuar damage as assessed by NVC over a period of 2 years. In particular, the number of normal capillaries significantly increases, whereas the number of giant capillaries and related microhaemorrhages significantly decreases, in comparison to SSc pts treated only with ILO. For the first time the microvascular effects induced by the long term endothelin1 receptor antagonism in SSc are detected by NVC. References Herrick AL. Curr Opin Rheumatol 2011;23:555-61. Sulli A, et al. Arthritis Rheum 2011;29. doi: 10.1002/art.33463. Smith V et al. Ann Rheum Dis. 2010;69:1092-6. Cutolo, M. et al. Nature Rev Rheumatol 2010;6:578–587. LeRoy EC et al.J Rheumatol 2001;28:1573-6. Disclosure of Interest None Declared

Background Peripheral microangiopathy and increased dermal thickness (DT) are typical clinical aspects of systemic sclerosis (SSc) (1-3). Objectives The aim of this study was to identify and score possible correlations between nailfold microangiopathy severity and finger DT in systemic sclerosis (SSc) patients. Methods Fifty-five SSc patients (mean age 54±12SD years, disease duration 6±5 years) and 42 healthy subjects were enrolled, after informed consent. All patients were evaluated by nailfold videocapillaroscopy (NVC) to classify and score the severity of microangiopathy. The appropriate NVC pattern was assigned to the SSc patients (“early”, “active” and “late”), and the microangiopathy evolution score (MES) was also calculated (1,4-5). Both modified Rodnan skin score (mRss), and high frequency skin ultrasound (US), scored as PU, were employed to detect finger DT. US was performed at the level of the dorsum of the middle phalanx of the third finger on both right and left hand, and the average value of DT was recorded in millimetres. mRss was calculated at the level of the dorsum of the fingers bilaterally, as reported in the literature (6). Statistical analysis was carried out by non parametric tests. Results SSc patients showed a statistically significant higher ultrasound-DT than healthy subjects, at the level of the fingers (p Conclusions This study describes and scores for the first time the correlation existing between progressive impairement of microvasculature and amount of dermal tickness in SSc patients. References Sulli A et al Arthritis Rheum. 2012; 64: 821-5. Moore TL et al. Rheumatology 2003; 42: 1559-63. Kaloudi O et al. Ann Rheum Dis. 2010; 69:1140-3. Sulli A et al. Ann Rheum Dis 2008; 67:885-7. Smith V et al. Ann Rheum Dis 2010; 69:1092-6. Clements PJ et al. J Rheumatol 1993; 20: 1892-6. Disclosure of Interest None Declared

Background Novel treatment strategies of rheumatoid arthritis (RA) allow to reach remission in an increasing number of patients. However, follow-up studies often revealed progressive structural deterioration of the joints in patients in clinical remission. This apparent discordance has been clarified by advanced imaging techniques, such as ultrasonography (US) and magnetic resonance imaging (MRI), which showed persistence of subclinical synovitis in the majority of patients in clinical remission. Objectives This study is concerned with an evaluation of the frequency of MRI remission in patients with DAS 28 CRP lower than 2.6, according to different MRI measures of disease activity and clinical definitions of remission. Methods 35 consecutive RA patients (30 women, mean age 53,2±13,8 years) affected by RA diagnosed according to the 1987 ACR criteria who were in DAS 28 CRP remission were studied. Demographic data and clinical and laboratory findings necessary for the evaluation of DAS 28 CRP, DAS 28 ESR, SDAI, CDAI, the preliminary criteria by Pinals et al., and the Boolean-based definition of remission suggested by the ACR/EULAR study group, were recorded. MRI of the dominant hand was performed with a 0.2T extremity-dedicated machine (Artoscan C, Esaote, Genoa, Italy) using pre and post contrast T1 weighted turbo 3D and STIR sequences. MRI was analyzed using the OMERACT-RAMRIS score [synovitis, bone oedema (BME), erosions of distal radium and ulna, wrist and metacarpophalangeal joints] and the dynamic contrast-enhanced technique for wrist synovitis (DCE-MRI). The enhancement ratio was calculated both as the rate of early enhancement (REE) and the relative enhancement (RE). Results Median duration of remission was 5 months (1-62 months). Of the 35 patients in DAS 28 CRP remission, 22 (71%) were also in Pinals et al. criteria remission, 19 (54.3%) were in DAS 28 ESR remission, 17 (48.6%) in SDAI remission, 16 (45.7%) in CDAI remission and 13 (37.1%) in remission according to the recent ACR/EULAR definition. 31/35 patients could complete the post-contrast sequences. The mean RAMRIS score for wrist synovitis was 3.5±1.6 (range 0-8). Four patients (12.9%) showed no detectable synovitis by RAMRIS. By DCE-MRI no synovial membrane enhancement was seen for REE in 8 (25.8%) and for RE in 5 (16.1%) patients. BME was present in 33/35 patients (94.3%) with a median RAMRIS score of 7 (range 0-38). No difference between patients in remission or not according to the different criteria was observed for the RAMRIS synovitis score, REE and RE. The RAMRIS synovitis score and DAS 28 CRP at remission were inversely correlated with its duration (p=0.02 and p=0.01, respectively). Conclusions Our data suggest that nearly 13% of RA patients in DAS 28 CRP clinical remission do not show any MRI synovitis. This result is in keeping with the literature. Using DCE-MRI, the number of patients who can be considered in remission almost doubled. Follow-up studies are ongoing to evaluate if the clinical outcome will vary according to the different types of clinical and MRI remission. Disclosure of Interest None Declared

Background Rheumatoid arthritis (RA) is associated to an increased incidence of osteoporosis: more 15-20% at the standard measured sites. The main mechanisms leading to increased bone resorption in RA are the cytokines-induced osteoclastogenesis and parathyroid hormone (PTH) secretion impairment (1). Objectives The aim of our study is to investigate if there is a correlation between PTH secretion levels, the Disease Activity Score on 28 joints (DAS28) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) in a group of active RA patients. Furthermore it was investigated if the observed correlations vary according to the severity of the RA disease. Methods We subsequently enrolled 81 RA patients diagnosed according to the 2010 ACR/EULAR criteria (2) and treated with DMARDs and low-dose glucocorticoids, excluding subjets treated with biological agents or calcium metabolism modifying drugs. After collection of patient informed consent and local Ethic Committee approval, we performed two visits where we collected blood samples and performed clinical evaluation. The patients were divided into three subgroups according to the disease activity range. DAS28 was calculated with C-Reactive Protein (CRP): DAS-28 score >5.1 indicates high disease activity (26 subjects); DAS28 score ≤3.2 low disease activity (27) and DAS-28 between 3.2 and 5.1 moderate disease activity (28) (3). HAQ-DI scores varies from 0 (no disability) to 3 (total disability) (4). PTH was measured as 1-84 fraction by chemiluminescence (DiaSorin Liaison®) and CRP by immunoturbidimetry (BioGamma LT006®). Baseline comparisons between patients scores and laboratory findings were performed with Student’s t test for coupled data and Pearson χ2 test. Results Among high activity RA patients: DAS-28 vs PTH r=-0.40, p

Microvascular involvement is a key feature of systemic sclerosis (SSc). Nailfold capillaroscopy is widely used to evaluate capillary morphology. As well as laser Doppler flowmetry (LDF), it is a technique for measuring the peripheral microvascular perfusion.1 2 The aim of this study was to investigate possible correlations between fingertip blood perfusion (FBP) by LDF and different degrees of microvascular damage by nailfold videocapillaroscopy (NVC) in SSc patients. Forty-six SSc patients (mean±SD age 65±13 years) and 16 healthy subjects …