Violeta Vlad

The role of Doppler ultrasound in rheumatic diseases

The use of Doppler techniques, including power, colour and spectral Doppler, has greatly increased in rheumatology in recent years. This is due to the ability of Doppler US (DUS) to detect pathological vascularization within joints and periarticular soft tissues, thereby demonstrating the presence of active inflammation, which has been reported to be correlated with the local neo-angiogenesis. In synovitis, DUS showed a high correlation with histological and MRI findings, thus it is considered a valid tool to detect pathological synovial vascularization. Moreover, it is more sensitive than clinical examination in detecting active joint inflammation and in the evaluation of response to treatment. In addition, DUS may be considered as a reference imaging modality in the assessment of enthesitis, MRI being not sensitive and histology not feasible. Moreover, it has been demonstrated to be able to detect changes in asymptomatic enthesis. In conclusion, DUS is a useful and sensitive tool in the evaluation and monitoring of active inflammation. Its widespread use in clinical rheumatological practice is recommended. The aim of this article is to review the current literature about the role of DUS in rheumatic diseases, analysing its validity, reliability and feasibility.

Dysregulation of anergy-related factors involved in regulatory T cells defects in Systemic Lupus Erythematosus patients: Rapamycin and Vitamin D efficacy in restoring regulatory T cells.

Systemic Lupus Erythematosus (SLE) patients display dysfunctions in T cell activation and anergy. Therefore the aims of our study were to explore the expression of anergy‐related factors in CD4+ T cells in relationship with regulatory T cells (Tregs) frequency in SLE patients and to identify strategies to redress these defects.

Definition and Reliability Assessment of Elementary Ultrasonographic Findings in Calcium Pyrophosphate Deposition Disease: A Study by the OMERACT Calcium Pyrophosphate Deposition Disease Ultrasound Subtask Force

Objective. To define the ultrasonographic characteristics of calcium pyrophosphate crystal (CPP) deposits in joints and periarticular tissues and to evaluate the intra- and interobserver reliability of expert ultrasonographers in the assessment of CPP deposition disease (CPPD) according to the new definitions. Methods. After a systematic literature review, a Delphi survey was circulated among a group of expert ultrasonographers, who were members of the CPPD Ultrasound (US) Outcome Measures in Rheumatology (OMERACT) subtask force, to obtain definitions of the US characteristics of CPPD at the level of fibrocartilage (FC), hyaline cartilage (HC), tendon, and synovial fluid (SF). Subsequently, the reliability of US in assessing CPPD at knee and wrist levels according to the agreed definitions was tested in static images and in patients with CPPD. Cohen’s κ was used for statistical analysis. Results. HC and FC of the knee yielded the highest interobserver κ values among all the structures examined, in both the Web-based (0.73 for HC and 0.58 for FC) and patient-based exercises (0.55 for the HC and 0.64 for the FC). Kappa values for the other structures were lower, ranging from 0.28 in tendons to 0.50 in SF in the static exercise and from 0.09 (proximal patellar tendon) to 0.27 (triangular FC of the wrist) in the patient-based exercise. Conclusion. The new OMERACT definitions for the US identification of CPPD proved to be reliable at the level of the HC and FC of the knee. Further studies are needed to better define the US characteristics of CPPD and optimize the scanning technique in other anatomical sites.

Tenosynovitis US scoring systems follow synovitis and clinical scoring systems in RA and are responsive to change after biologic therapy.

AIMS To investigate by ultrasonography (US) in a cohort of active RA patients starting biologic therapy the responsiveness of tenosynovitis of wrist and hands compared to the responsiveness of synovitis in a 6 month period follow-up, to compare the responsiveness of finger flexor tenosynovitis with the responsiveness of wrist extensor tenosynovitis and to describe the subclinical synovitis and tenosynovitis in RA patients in clinical remission. MATERIAL AND METHODS Fifty seven patients with active RA starting biologic therapy were included. Clinical, laboratory, and US evaluations were performed at baseline, 1, and 6 months. US evaluation included wrist and MCPs 2-5 joints, bilaterally for synovitis and extensor tendons compartments 2, 4, and 6 and finger flexors 2-5 for tenosynovitis. Eighteen US scores based on semiquantitative or binary grades were calculated at each visit. Responsiveness of synovitis and tenosynovitis scores was calculated using the standardized response mean (SRM). RESULTS The responsiveness of US tenosynovitis was lower comparing with the responsiveness of US synovitis but both showed large effect of therapy. Furthermore, tenosynovitis responsiveness was similar to CRP responsiveness (SRM -0.90). Finger flexors tenosynovitis showed a higher responsiveness than extensor tenosynovitis on GS (-0.94 compared to -0.63) and a lower SRM on PD (-0.56 compared to -0.85). Tenosynovitis scores remission was overlapping clinical remission according to CDAI and SDAI in 100% of cases. Overall there was less subclinical tenosynovitis than subclinical synovitis at final visit according to clinical activity indices. CONCLUSION Tenosynovitis US scoring in RA may be as good as synovitis scoring for characterization of disease activity and responsiveness.

The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology

Background In 2001, the European League Against Rheumatism developed and disseminated the first guidelines for musculoskeletal (MS) ultrasound (US) in rheumatology. Fifteen years later, the dramatic expansion of new data on MSUS in the literature coupled with technological developments in US imaging has necessitated an update of these guidelines. Objectives To update the existing MSUS guidelines in rheumatology as well as to extend their scope to other anatomic structures relevant for rheumatology. Methods The project consisted of the following steps: (1) a systematic literature review of MSUS evaluable structures; (2) a Delphi survey among rheumatologist and radiologist experts in MSUS to select MS and non-MS anatomic structures evaluable by US that are relevant to rheumatology, to select abnormalities evaluable by US and to prioritise these pathologies for rheumatology and (3) a nominal group technique to achieve consensus on the US scanning procedures and to produce an electronic illustrated manual (ie, App of these procedures). Results Structures from nine MS and non-MS areas (ie, shoulder, elbow, wrist and hand, hip, knee, ankle and foot, peripheral nerves, salivary glands and vessels) were selected for MSUS in rheumatic and musculoskeletal diseases (RMD) and their detailed scanning procedures (ie, patient position, probe placement, scanning method and bony/other landmarks) were used to produce the App. In addition, US evaluable abnormalities present in RMD for each anatomic structure and their relevance for rheumatology were agreed on by the MSUS experts. Conclusions This task force has produced a consensus-based comprehensive and practical framework on standardised procedures for MSUS imaging in rheumatology.

A10.06 Detecting adalimumab serum level and anti-drug antibodies – future tool in monitoring spondyloarthritis patients?

Background and objectives Anti-TNF agents have highly proved their efficacy in spondylarthritis (SpA) patients, with a good rate of response of approximately 70%. However a third of patients lose response to treatment. Measuring the drug serum level and anti-drug antibodies might lead to identifying the cause of non-response, followed by adjusting the therapeutic scheme. The aim was to determine the utility of determining drug serum adalimumab (ADL) and anti-ADL antibodies in assessing disease activity in SpA patients. Methods Over a period of 11 months we included 54 SpA patients on ADL, with further exclusion of those who had delayed drug administration or suffered a concomitant infection. Demographic, clinical (disease activity scores) and laboratory (ESR, CRP) data were collected. We measured the determination of interest using Promonitor kits, using the ELISA technique and the statistical analysis was performed with SPSS 20.0. Results Out of the total 35 patients, 74% were males, the mean age was 40 years old with a mean disease duration of 102 months. HLA B27 was positive in 91% of patients and 28% required sacroiliac joint MRI at diagnosis, being a non-radiographic form. 28% of patients tested positive for Quantiferon and underwent chemoprophylaxis. 22% had history of uveitis before diagnosis and 9% had recurrences while on ADL. 82% of patients had detectable ADL levels. The BASDAI score was significantly higher in patients with undetectable ADL (P < 0.001), with a mean value of 6.3 indicating an inadequate disease control. Furthermore, both ASDAS-ESR and ASDAS-CRP were higher in these patients (P < 0.001). 25% had positive anti-ADL antibodies. Patients with no identified antibodies had lower disease activity scores (BASDAI, ASDAS-VSH and ASDAS-CRP, P < 0.001). Acute phase reactants (ESR, CRP) had a higher value in patients with positive anti-ADL antibodies (P = 0.015 and P < 0.001, respectively). Serum level ADL negatively correlated to the presence of anti-ADL antibodies (r = -0.360, P = 0.034) and to disease activity scores. Conclusions Undetectable serum drug level together with the presence of anti-drug antibodies and the increase of SpA activity scores indicate the impact of immunogenicity throughout secondary non-responder patients. Prompt identification of these patients might lead to a better adapted therapeutic scheme.

Identification of calcium pyrophosphate deposition disease (CPPD) by ultrasound: reliability of the OMERACT definitions in an extended set of joints—an international multiobserver study by the OMERACT Calcium Pyrophosphate Deposition Disease Ultrasound Subtask Force

Objectives To assess the reliability of the OMERACT ultrasound (US) definitions for the identification of calcium pyrophosphate deposition disease (CPPD) at the metacarpal-phalangeal, triangular fibrocartilage of the wrist (TFC), acromioclavicular (AC) and hip joints. Methods A web-based exercise and subsequent patient-based exercise were carried out. A panel of 30 OMERACT members, participated at the web-based exercise by evaluating twice a set of US images for the presence/absence of CPPD. Afterwards, 19 members of the panel met in Siena, Italy, for the patient-based exercise. During the exercise, all sonographers examined twice eight patients for the presence/absence of CPPD at the same joints. Intraoberserver and interobserver kappa values were calculated for both exercises. Results The web-based exercise yielded high kappa values both in intraobserver and interobserver evaluation for all sites, while in the patient-based exercise, inter-reader agreement was acceptable for the TFC and the AC. TFC reached high interobserver and intraobserver k values in both exercises, ranging from 0.75 to 0.87 (good to excellent agreement). AC reached moderate kappa values, from 0.51 to 0.85 (moderate to excellent agreement) and can readily be used for US CPPD identification. Conclusions Based on the results of our exercise, the OMERACT US definitions for the identification of CPPD demonstrated to be reliable when applied to the TFC and AC. Other sites reached good kappa values in the web-based exercise but failed to achieve good reproducibility at the patient-based exercise, meaning the scanning method must be further refined.

SAT0631 Inter-observer and intra-observer reliability of the omeract ultrasonographic (US) criteria for the diagnosis of calcium pyrophosphate deposition disease (CPPD) at the metacarpal-phalangeal (MCP), wrist, acromion-clavicular (AC) and hip joints

Background The OMERACT US subtask force “US in CPPD” recently created the definitions for US identification of crystal deposits in joints and tested the reliability at the knee [1]. Objectives To assess the inter/intra-observer reliability of US on detecting CPPD at triangular fibrocartilage complex (TFCC) of the wrists, fibrocartilage of the AC joint, hip labrum (HL), hyaline cartilage (HC) of the metacarpal (MC) and femoral head. Methods The OMERACT criteria for CPPD were used for the exercise [1] using a 2 steps approach. First, the panel of experts gave a dichotomous score (presence/absence of CPPD) of 120 images of the sites included, using a web platform. The images were evaluated twice to assess the inter/intra-observer reliability. Then, the experts met in Siena for a patient based exercise. Bilateral evaluation of TFCC, AC, HL /HC of the hip and HC of the II-III MCP of 8 patients was carried out twice in a day, using a dichotomous score for CPPD. 8 US machines (3 GE, 1 Samsung and 4 Esaote) equipped with high resolution linear probes were used. Results Reliability values of static exercise were high for all sites, demonstrating that definitions were clear. The results of the second step are presented in table 1. On live scanning, the TFCC resulted the most reliable site for CPPD assessment, followed by AC. Other sites demonstrated lower kappa values and thus are not reliable for CPPD assessment. Conclusions TFCC of the wrist is the most reliable site for CPPD. By adding these results to the previous [2], we confirm that the OMERACT definitions for CPPD can be applied reliably at the knee (meniscus and HC), TFCC and AC, usually the most involved sites in CPPD. The next step of the OMERACT subtask force will be to test these findings in a longitudinal observational study. References Filippou G, Scirè CA, Damjanov N et al. Definition and reliability assessment of elementary US findings in CPPD. Results of an international multi-observer study by the OMERACT sub-task force “US in CPPD”. J Rheumatol, in press. Disclosure of Interest None declared

SAT0664 Is there an early ultrasonographic pattern in salivary glands in both primary and secondary sjogren syndrome

Background Sjogren Syndrome (SS) affects mainly exocrine glands. Ultrasonography (US) demonstrates specificity and sensibility in major salivary glands (SG) evaluation. Recent data confirm US might be used as primary evaluation technique for its ability to show structural alterations of parenchyma [1]. Objectives To assess the gray scale (GS) parenchymal inhomogeneity of major SG in patients with established primary and secondary SS and correlate with clinical and biological data. Methods Consecutive patients with SS were recruited and SG US was performed. Inhomogeneity of glandular parenchyma was quantified binary on each gland. ESSDAI and ESSPRI scores were calculated. Statistics was performed with SPSS. Results Twenty one (42.85% primary SS, 90.47% female) consecutive patients were included. Mean age was 53.66+/-12.99 years and disease duration 5.33+/-3.74 years. Antibody SSA/SSB presence was found in 85.7% (18/21). ESSDAI mean was 8.67+/-8.9 (0–29), ESSPRI 10.13+/-5.59 (0–20). There were no differences regarding ESSDAI and ESSPRI in the two groups (primary and secondary SS). Right parotid gland showed alterations in 71.4% patients (77% with primary SS, 66% with secondary SS). Frequently inhomogeneity was found in all major SG (33%, 22% left and right submandibular, 77%, 44.4% left and right parotid glands) in primary SS. Both submandibular glands were symmetrically involved (p<0.02). Duration of disease was negatively correlated to inhomogeneity of right parotid gland (p<0.02). Conclusions Inhomogeneity in major SG in GS US was found in the majority of patients with primary and secondary SS. The symmetrical involvement of submandibular glands was significant. The inhomogeneity appears in the early period of diagnosis. No major differences were found between two groups. References Damjanov N, Milic V, Nieto-González JC, Janta I, Naredo E. Multiobserver Reliability of Ultrasound Assessment of Salivary Glands in Patients with Established Primary Sjögren Syndrome. J Rheumatol. 2016 Oct;43(10):1858–1863. Disclosure of Interest None declared

AB1068 Ultrasound of salivary glands in sjogren's syndrome- which semi-quantitative scoring system is the best?

Background Sjogren Syndrome (SS) affects mainly exocrine glands. The latest diagnostic criteria designed for clinical studies are also used as guidance in clinical practice [1]. Ultrasonography (US) demonstrates specificity and sensibility in parotid and submandibular gland evaluation (SG). Parameters considered are echogenicity, homogeneity and margins regularity [1,2,3]. To standardize the assessment of B mode US of SG, different semi-quantitative scores were proposed. Objectives To apply and compare 9 US semi-quatitative scoring systems in B mode scanning of salivary glands in Sjogren Syndrome. Methods A research using keywords “salivary glands”, “ultrasonograpy”, “Sjogren Syndrome”, “semi-quantitative score” in Medline/Pubmed was performed. There was a selection of most relevant articles. There were not considered relevant publications with impact factor <1. We performed the examination on SG in B mode US and applied these scores (De Vita, Niemela, Hocevar, Salaffi, Yukinori, Cornec,Theander) to our patients (primary and secondary SS). Results Eighty four SG in patients diagnosed with primary and secondary (57.15%) SS were assessed. In the group of patients with SSA/SSB presence (85.7%), mean score was De Vita 1.78+/-1.21, Niemela 2.56+/-2.17, Hocevar and Wernicke 2.39+/-2.14, Salaffi 2.83+/-2.52, Yukinori 2.39+/-2.14, Milic 3.39+/-2.14, Cornec 1.78+/-1.215, Theander 1.28+/-0.752. Schirmer test and the need for using the artificial tears was correlated to SG alterations in scoring systems proposed by Niemela (r 0.465, p<0.05) and Salaffi ( r 0.496, p<0.02). All scoring systems were strongly correlated between them (r>0.8, p<0.01). Conclusions Inhomogeneity of parenchyma was considered in all scoring systems. Others considered relevant glandular dimension and margins regularity [2,3.4]. There was no difference between the scoring systems. Xeroftalmia valided through Schirmer test is correlated to SG parenchymal alterations. Our data is an update about semi-quantitative scoring systems in US of SG in SS. References Vitali C, Bombardieri S, Jonsson R et al. Classification criteria for Sjögrens Syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. AnnRheum Dis 2002;61:554–8. Makula E, Pokorny G, Palkό A.The place of magnetic resonance and ultrasonographic examinations of the parotid gland in the diagnosis and follow-up of primary Sjögrens syndrome. Rheumatology (Oxford). 2000;39(1):97–104. Niemelä RK, Takalo R, Hakala M. Ultrasonography of salivary glands in primary Sjogrens syndrome. A comparison with magnetic resonance imaging and magnetic resonance sialography of parotid glands. Rheumatology (Oxford). 2004 Jul;43(7):875–9. El Miedany YM, Ahmed I, El Gafaary M. Quantitative ultrasonography and magnetic resonance imaging of the parotid gland: can they replace the histopathologic studies in patients with Sjogrens syndrome? Joint Bone Spine.2004;71(1):29–38. Disclosure of Interest None declared