Andrea Delle Sedie

Limits and perspectives of ultrasound in the diagnosis and management of rheumatic diseases

Musculoskeletal sonography (MSUS) has played a growing role in the diagnosis and management of rheumatic diseases, enabling the imaging of synovitis, bone erosion, and cartilage damage in the early phase of arthritis. “Dynamic” evaluation of tendons and help in guiding needle positioning in interventional manoeuvres are some of the other reasons for its success. MSUS, particularly when coupled with power Doppler (PD) examination, has recently been shown to be an efficient tool for monitoring disease activity and progression in rheumatoid arthritis, spondyloarthritis, crystal-related arthropathy, and osteoarthritis, with general consensus on its interesting results. More specifically, the PD signal has proved to be a simple and promising tool for short-term monitoring of synovial vascularity changes induced by steroids or biological agents in RA patients. MSUS has some limits, because of the physical properties of US and the quality of the equipment; it is, moreover, an operator-related imaging technique, with few standardized protocols. Future goals should be standardization of the examining approach in grey scale and Doppler ultrasound (US), including use of new equipment (3D US), extensive use in other fields (i.e. connective tissue diseases and vasculitis), and possible new applications (e.g. thoracic US).

International Consensus for ultrasound lesions in gout: results of Delphi process and web-reliability exercise

OBJECTIVEnTo produce consensus-based definitions of the US elementary lesions in gout and to test their reliability in a web-based exercise.nnnMETHODSnThe process consisted of two steps. In the first step a written Delphi questionnaire was developed from a systematic literature review and expert international consensus. This collated information resulted in four statements defining US elementary lesions: double contour (DC), tophus, aggregates and erosion. The Delphi questionnaire was sent to 35 rheumatology experts in US, asking them to rate their level of agreement or disagreement with each statement. The second step tested the reliability by a web-exercise. US images of both normal and gouty elementary lesions were collected by the participants. A facilitator then constructed an electronic database of 110 images. The database was sent to the participants, who evaluated the presence/absence of US elementary lesions. A group of 20 images was displayed twice to evaluate intra-reader reliability.nnnRESULTSnA total of 32 participants responded to the questionnaires. Good agreement (>80%) was obtained for US definitions on DC, tophus, aggregates and erosion in the Delphi exercise after three rounds. The reliability on images showed inter-reader κ values for DC, tophus, aggregates, erosion findings of 0.98, 0.71, 0.54 and 0.85, respectively. The mean intra-reader κ values were also acceptable: 0.93, 0.78, 0.65 and 0.78, respectively.nnnCONCLUSIONnThis, the first consensus-based US definition of elementary lesions in gout, demonstrated good reliability overall. It constitutes an essential step in developing a core outcome measurement that permits a higher degree of homogeneity and comparability between multicentre studies.

Responsiveness in rheumatoid arthritis. a report from the OMERACT 11 ultrasound workshop.

Objective. To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Task Force on the validity of different US measures in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) presented during the OMERACT 11 Workshop. Methods. The Task Force is an international group aiming to iteratively improve the role of US in arthritis clinical trials. Recently a major focus of the group has been the assessment of responsiveness of a person-level US synovitis score in RA: the US Global Synovitis Score (US-GLOSS) combines synovial hypertrophy and power Doppler signal in a composite score detected at joint level. Work has also commenced examining assessment of tenosynovitis in RA and the role of US in JIA. Results. The US-GLOSS was tested in a large RA cohort treated with biologic therapy. It showed early signs of improvement in synovitis starting at Day 7 and increasing to Month 6, and demonstrated sensitivity to change of the proposed grading. Subsequent voting questions concerning the application of the US-GLOSS were endorsed by > 80% of OMERACT delegates. A standardized US scoring system for detecting and grading severity of RA tenosynovitis and tendon damage has been developed, and acceptable reliability data were presented from a series of exercises. A preliminary consensus definition of US synovitis in pediatric arthritis has been developed and requires further testing. Conclusion. At OMERACT 11, consensus was achieved on the application of the US-GLOSS for evaluating synovitis in RA; and work continues on development of RA tenosynovitis scales as well as in JIA synovitis.

Is GRP78/BiP a potential salivary biomarker in patients with rheumatoid arthritis?

Purpose: In the last few years, serum and joint synovial fluid have been extensively analyzed for the proteomic research of rheumatoid arthritis (RA) biomarkers. Nonetheless, to date, there have been no studies investigating salivary biomarkers in this condition. Therefore, aim of this study is to investigate the presence of potential biomarkers of RA in human whole saliva.

Ultrasound as an Outcome Measure in Gout. A Validation Process by the OMERACT Ultrasound Working Group

Objective. To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Working Group on the validation of US as a potential outcome measure in gout. Methods. Based on the lack of definitions, highlighted in a recent literature review on US as an outcome tool in gout, a series of iterative exercises were carried out to obtain consensus-based definitions on US elementary components in gout using a Delphi exercise and subsequently testing these definitions in static images and in patients with proven gout. Cohen’s κ was used to test agreement, and values of 0–0.20 were considered poor, 0.20–0.40 fair, 0.40–0.60 moderate, 0.60–0.80 good, and 0.80–1 excellent. Results. With an agreement of > 80%, consensus-based definitions were obtained for the 4 elementary lesions highlighted in the literature review: tophi, aggregates, erosions, and double contour (DC). In static images interobserver reliability ranged from moderate to almost perfect, and similar results were found for the intrareader reliability. In patients the intraobserver agreement was good for all lesions except DC (moderate). The interobserver agreement was poor for aggregates and DC but moderate for the other components. Conclusion. These first steps in evaluating the validity of US as an outcome measure for gout show that the reliability of the definitions ranged from moderate to excellent in static images and somewhat lower in patients, indicating that a standardized scanning technique may be needed, before testing the responsiveness of those definitions in a composite US score.

High values of alpha (CXCL10) and beta (CCL2) circulating chemokines in patients with psoriatic arthritis, in presence or absence of autoimmune thyroiditis.

The possible role of circulating alpha and beta chemokines in psoriatic arthritis is not extensively studied. The aim of the study is to evaluate serum levels of CXCL10, CXCL9 (alpha) and CCL2 (beta) chemokines in a large series of psoriatic arthritis patients, with or without autoimmune thyroid (AT) disorders, and to relate chemokines levels to the clinical phenotype of these patients. Serum levels of CXCL10 and CCL2 were measured in 37 patients with psoriatic arthritis without AT (PsA) and 28 with AT (PsA+AT), and in gender- and age-matched (1:1) controls without (control 1) or with AT (control 2). Serum CXCL10 levels were significantly higher in control 2 than in control 1 (p < 0.001) and in PsA than control 1 or 2 (p < 0.0001). PsA+AT patients have CXCL10 higher than controls 1 and 2 (p < 0.0001, for both) and than PsA (p < 0.001). By defining a high CXCL10 level as a value at least 2 SD above the mean value of the control group (>192 pg/ml), 5% of control 1, 19% of control 2, 42% of PsA and 63% of PsA+AT, had high CXCL10 (p < 0.0001; χ2). Serum CCL2 levels were similar in controls 1 and 2. PsA or PsA+AT patients have serum CCL2 levels significantly (p < 0.01, for both) higher than controls 1 and 2. Serum CXCL9 was not significantly different in the study groups. In conclusion, our study demonstrates higher serum levels of CXCL10 and CCL2 chemokines in patients with PsA than in controls. Serum CXCL10 (alpha chemokine) levels in psoriatic arthritis patients are significantly higher in presence of AT.

Assessing Elementary Lesions in Gout by Ultrasound: Results of an OMERACT Patient-based Agreement and Reliability Exercise

Objective. To test the reliability of the consensus-based ultrasound (US) definitions of elementary gout lesions in patients. Methods. Eight patients with microscopically proven gout were evaluated by 16 sonographers for signs of double contour (DC), aggregates, erosions, and tophi in the first metatarsophalangeal joint and the knee bilaterally. The patients were examined twice using B-mode US to test agreement and inter- and intraobserver reliability of the elementary components. Results. The prevalence of the lesions were DC 52.8%, tophus 61.1%, aggregates 29.8%, and erosions 32.4%. The intraobserver reliability was good for all lesions except DC, where it was moderate. The best reliability per lesion was seen for tophus (κ 0.73, 95% CI 0.61–0.85) and lowest for DC (κ 0.53, 95% CI 0.38–0.67). The interobserver reliability was good for tophus and erosions, but fair to moderate for aggregates and DC, respectively. The best reliability was seen for erosions (κ 0.74, 95% CI 0.65–0.81) and lowest for aggregates (κ 0.21, 95% CI 0.04–0.37). Conclusion. This is the first step to test consensus-based US definitions on elementary lesions in patients with gout. High intraobserver reliability was found when applying the definition in patients on all elementary lesions while interobserver reliability was moderate to low. Further studies are needed to improve the interobserver reliability, particularly for DC and aggregates.

The role of imaging in the evaluation of joint involvement in 102 consecutive patients with systemic lupus erythematosus

OBJECTIVEnTo assess the prevalence of joint involvement in consecutive patients with systemic lupus erythematosus (SLE) by means of clinical assessment, joint US and MRI and to evaluate the sensitivity and specificity of physician evaluation of joint involvement.nnnMETHODSnAt enrollment, patients underwent a complete physical examination including a 44-joint count, and hand deformities were scored. On the day of enrollment, each patient underwent a non-dominant hand-wrist ultrasound (US) examination and a non-dominant hand-wrist MRI study without contrast injection.nnnRESULTSnOne hundred and two patients (F 95, M 7) were enrolled. By physician examination hand or wrist involvement was diagnosed in 23.5%. At least one pathological finding was revealed by US examination at wrist and/or hand joints in 55%. We found a low sensitivity (46.5%) with high specificity (93.2%) of the physician assessment for the evaluation of joint involvement. The MRI imaging showed at least one erosion in 47.3% patients at the hand and in 98.9% at the wrist; in healthy subjects erosions were found in 19.6% and 97.8% at the hand and wrist, respectively.nnnCONCLUSIONSnIn conclusion, (i) physicians tend to underestimate the severity of joint involvement in SLE; (ii) US assessment shows a high prevalence of joint and tendon involvement; and (iii) the MRI evaluation shows a high prevalence of damage, suggesting that joint involvement in SLE could be more severe than expected.

Vitamin D in “early” primary Sjögren’s syndrome: does it play a role in influencing disease phenotypes?

Beyond its well-established role in the maintenance of mineral homeostasis, 25-OH-vitamin D deficiency seems to be involved in the development and severity of several autoimmune diseases. To date, contrasting data have been reported regarding the presence of hypovitaminosis D in primary Sjögren’s syndrome (pSS). To assess the prevalence of hypovitaminosis D in pSS at an early stage of the disease and to evaluate its impact on pSS clinical manifestations and disease activity, unselected consecutive subjects with recent onset dry mouth and/or dry eyes who underwent a comprehensive diagnostic algorithm for pSS (AECG criteria) were prospectively included in the study. The levels of 25[OH]-D3 were measured by monoclonal antibody immunoradiometric assay. Conditions of 25[OH]-D3 severe deficiency, deficiency, and insufficiency were defined as levels <10, <20, and 20–30xa0ng/ml, respectively, and their frequencies were investigated in pSS patients and controls. The levels of 25[OH]-D3 were also correlated with patients’ demographic, clinical, and serologic features. Seventy-six consecutive females were included: 30/76 patients fulfilled the AECG criteria for pSS. The remaining 46/76 patients represented the control group. No statistical differences were found in the serum levels of 25[OH]-D3 between pSS patients [median levelsxa0=xa020xa0ng/ml (IQR 9.3–26)] and controls [median levelsxa0=xa022.5xa0ng/ml (IQR 15.6–33)]. In particular, the frequency of 25[OH]-D3 severe deficiency was not significantly different in patients with pSS when compared to controls (23 vs. 17.4xa0%, p valuexa0=xa00.24). We found a significant correlation between serum 25[OH]-D3 levels and white blood cells count (rxa0=xa00.29, pxa0=xa00.01). More specifically, leukocytopenia was significantly associated with 25[OH]-D3 severe deficiency, being documented in 40xa0% of the subjects with a 25[OH]-D3 severe deficiency and in 11xa0% of the subjects without a severe vitamin D deficiency (pxa0=xa00.02). We did not observe any further association or correlation between hypovitaminosis D and pSS glandular and extra-glandular features. Although the role of hypovitaminosis D in pSS pathogenesis remains controversial, the results of this study encourage the assessment of vitamin D in specific pSS subsets that could mostly benefit from a supplementation.

TNF-alpha inhibitors in Systemic Lupus Erythematosus. A case report and a systematic literature review

Abstract Joint involvement is a common manifestation of systemic lupus erythematosus (SLE) and is described as a non-erosive mild synovitis. However some SLE patients may present a more severe joint involvement requiring aggressive therapy. We describe the case of a SLE patient with a severe arthritis unresponsive to methotrexate, successfully treated with anti-TNF-alpha drug as induction therapy and we report the results of a systematic literature review on the use of TNF-alpha inhibitors in SLE.