2023 EULAR recommendations on imaging in diagnosis and management of crystal-induced arthropathies in clinical practice.

OBJECTIVE: To formulate evidence-based recommendations and overarching principles on the use of imaging in the clinical management of crystal-induced arthropathies (CiAs). METHODS: An international task force of 25 rheumatologists, radiologists, methodologists, healthcare professionals and patient research partners from 11 countries was formed according to the EULAR standard operating procedures. Fourteen key questions on the role of imaging in the most common forms of CiA were generated. The CiA assessed included gout, calcium pyrophosphate deposition disease and basic calcium phosphate deposition disease. Imaging modalities included conventional radiography, ultrasound, CT and MRI. Experts applied research evidence obtained from four systematic literature reviews using MEDLINE, EMBASE and CENTRAL. Task force members provided level of agreement (LoA) anonymously by using a Numerical Rating Scale from 0 to 10. RESULTS: Five overarching principles and 10 recommendations were developed encompassing the role of imaging in various aspects of patient management: making a diagnosis of CiA, monitoring inflammation and damage, predicting outcome, response to treatment, guided interventions and patient education. Overall, the LoA for the recommendations was high (8.46-9.92). CONCLUSIONS: These are the first recommendations that encompass the major forms of CiA and guide the use of common imaging modalities in this disease group in clinical practice.

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

OBJECTIVE: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard. METHODS: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings. RESULTS: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation. CONCLUSION: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

Effectiveness of secukinumab versus an alternative TNF inhibitor in patients with axial spondyloarthritis previously exposed to TNF inhibitors in the Swiss Clinical Quality Management cohort.

OBJECTIVE: To compare effectiveness of treatment with secukinumab (SEC) with that of alternative tumour necrosis factor inhibitors (TNFis) in patients with axial spondyloarthritis (axSpA) after withdrawal from one or more TNFis. METHODS: Patients diagnosed as having axSpA in the Swiss Clinical Quality Management cohort were included if they had initiated SEC (n=106) or an alternative TNFi (n=284) after experiencing TNFi failure. Drug retention was investigated with matching weights propensity score (PS) analyses and multiple adjusted Cox proportional hazards models. Matching weights PS-based analyses and multiple-adjusted logistic regression analyses were used to assess the proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year. RESULTS: SEC was more often used as third-line or later-line biological drug (76% vs 40% for TNFi). Patients starting SEC had higher BASDAI, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and C reactive protein levels. A comparable risk of drug discontinuation was found for SEC versus TNFi (HR 1.14, 95% CI 0.78 to 1.68 in the PS-based analysis and HR 1.16, 95% CI 0.79 to 1.71 in the multiple-adjusted analysis). No significant difference in BASDAI50 responses at 1 year was demonstrated between the two modes of biological drug action, with CI of estimates being, however, wide (OR for SEC vs TNFi 0.76, 95% CI 0.26 to 2.18 and 0.78, 95% CI 0.24 to 2.48 in the PS-based and the covariate-adjusted model, respectively). CONCLUSION: Our data suggest a comparable effectiveness of SEC versus an alternative TNFi after prior TNFi exposure.

Synovitis in rheumatoid arthritis detected by grey scale ultrasound predicts the development of erosions over the next three years.

OBJECTIVES: To evaluate grey scale US (GSUS) and power Doppler US synovitis (PDUS), separately or in combination (CombUS), to predict joint damage progression in RA. METHODS: In this cohort study nested in the Swiss RA register, all patients with sequential hand radiographs at their first US assessment were included. We analysed the summations of semi-quantitative GSUS, PDUS and CombUS assessments of both wrists and 16 finger joints (maximum 54 points) at their upper limit of normal, their 50th, 75th or 87.5th percentiles for the progression of joint damage (ΔXray). We adjusted for clinical disease activity measures at baseline, the use of biological DMARDs and other confounders. RESULTS: After a median of 35 months, 69 of 250 patients with CombUS (28%), 73 of 259 patients with PDUS (28%) and 75 of 287 patients with available GSUS data (26%) demonstrated joint damage progression. PDUS beyond upper limit of normal (1/54), GSUS and CombUS each at their 50th (9/54 and 10/54) and their 75th percentiles (14/54 and 15/54) were significantly associated with ΔXray in crude and adjusted models. In subgroup analyses, GSUS beyond 14/54 and CombUS higher than 15/54 remained significantly associated with ΔXray in patients on biological DMARDs, while clinical disease activity measures had no significant prognostic power in this subgroup. CONCLUSION: Higher levels of GSUS and CombUS are associated with the development of erosions. GSUS appears to be an essential component of synovitis assessment and an independent predictor of joint damage progression in patients on biological DMARDs.

[Rheumatoid arthritis†: imagery what is new†?] / Polyarthrite rhumatoïde†: apport de l'imagerie, quoi de neuf†?

In 2013, EULAR made a number of recommendations regarding the contribution of modern imaging : MRI and ultrasound as an aid to the diagnosis and for the monitoring of rheumatoid arthritis. This article aims to review if these recommendations are still relevant and if some questions have been resolved since then by new studies.

En 2013, l'EULAR avait émis un certain nombre de recommandations quant à l'apport de l'imagerie moderne : IRM et échographie comme aide au diagnostic et pour le suivi de la polyarthrite rhumatoïde. Cet article a pour but de revoir si ces recommandations sont toujours d'actualité et si certaines interrogations ont été résolues depuis par de nouvelles études.

TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

OBJECTIVES: To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). METHODS: Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. RESULTS: A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). CONCLUSION: TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.

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.

[Rheumatic manifestations of Lyme disease : questions and controversies]. / Manifestations rhumatologiques de la maladie de Lyme : questions et controverses.

Osteoarticular manifestations of Lyme disease are well known features, although a number of controversies persist. These concern both the diagnosis, in particular the interpretation of serology results and the management, notably the role of antibiotics. In the article, we review a number of issues, and strive to shed light on the current evidence based Swiss and international data.

Bien que les manifestations ostéoarticulaires de la maladie de Lyme soient connues depuis de nombreuses années, un certain nombre de questions et de controverses persistent. Elles concernent aussi bien le diagnostic, en particulier l'interprétation de la sérologie, que la thérapeutique, notamment les régimes antibiotiques. Dans cet article, nous passons en revue un certain nombre de ces questions et controverses avec des tentatives de réponse au vu des données récentes de la littérature internationale et des données propres à la situation suisse.

Female hormonal factors and the development of anti-citrullinated protein antibodies in women at risk of rheumatoid arthritis.

Objectives: To analyse the association between female hormonal factors and the development of systemic autoimmunity associated with RA in women at increased risk for RA, namely first-degree relatives of patients with RA (RA-FDRs). Methods: In an ongoing cohort study of RA-FDRs, we analysed all women with available ACPA status. The primary outcome was ACPA positivity. The predictors of interest were female hormonal factors, such as oral contraceptives, breastfeeding, post-menopausal status, early post-menopausal period and total number of ovulatory years. Results: A total of 768 female RA-FDRs were analysed, of which 42 (5%) had developed ACPA positivity. ACPA-positive women were older (52 vs 44 years, P = 0.001). Hormonal factors significantly and independently associated with the presence of ACPA were the post-menopausal (P < 0.001) and the early post-menopausal periods (P = 0.040). Conclusions: In women at increased risk of RA, characteristic systemic autoimmunity was associated with menopause, suggesting that the acute decline in ovarian function might contribute to the development of autoimmunity associated with RA and potentially to the increased risk of RA in women.

[Drug-induced iatrogenic arthropathies]. / Arthropathies iatrogènes induites par les médicaments.

Arthropathies induced by drugs, especially arthralgias, are very frequently reported in pharmacology. The major difficulty often consists in confirming the accountability of the drug in the occurrence of the symptoms. Stopping the drug when it really responsible of the arthralgia is then likely to lead to the disappearance of the symptoms. The aim of this article is to review some of classical known induced arthropathies and some innovations by describing the clinical characteristics as well as the mechanisms linking the drug to the arthropathies when these have been clarified.

Les arthropathies induites par les médicaments, en particulier les arthralgies, sont très fréquemment rapportées en pharmacologie. La difficulté majeure consiste souvent à confirmer l'imputabilité du médicament dans la survenue des symptômes. L'arrêt du médicament suspect permet lorsqu'il est véritablement responsable de l'arthropathie d'entraîner alors la disparition des symptômes. Le but de cet article est de revoir les arthropathies classiques induites, ainsi que quelques nouveautés en décrivant les caractéristiques cliniques, ainsi que les mécanismes reliant le médicament à l'arthropathie quand ceux-ci ont été élucidés.

[Anti-IL-6 : new therapeutic trends]. / Rhumatologie. Anti-IL-6 : nouvelles perspectives thérapeutiques.

The anti-IL-6 tocilizumab is a recognized treatment in rheumatoid arthritis and in systemic juvenile idiopathic arthritis. Almost ten years after its first use, there is more information about its security profile and its indication should be extended to other systemic inflammatory diseases, such as the giant cell arteritis. New molecules targetting the IL-6 pathway are under validation : sarilumab, sirukumab and olokizumab. Here is a brief state of the future outlook and trends of this therapeutic class.

Le tocilizumab (Actemra) est un anticorps monoclonal anti-IL-6 reconnu comme traitement de la polyarthrite rhumatoïde et de l'arthrite juvénile idiopathique systémique après échec du méthotrexate. Presque dix ans après sa mise sur le marché, on dispose davantage d'informations quant à son profil de sécurité et son indication devrait s'étendre à d'autres maladies systémiques inflammatoires, telles que l'artérite gigantocellulaire. De nouvelles molécules inhibant la voie de l'IL-6, le sarilumab, le sirukumab et l'olokizumab sont également en cours de validation. Voici une revue des perspectives à venir pour cette classe thérapeutique.

[New synthetic and biologic treatments for spondylarthritis]. / Nouveaux traitements biologiques et synthétiques de fond pour les spondylarthropathies.

The only biological treatments recognized and reimbursed for spondylarthritis in Switzerland are anti TNF. Other effective agents in rheumatoid arthritis were found to be of little use in this indication. Fortunately, in recent years appeared biological molecules blocking cytokines involved in new pathways of inflammation in particular that of IL7. They have been very effective against psoriasis and have a high potential in psoriatic arthritis and spondylarthritis. In parallel, synthetic small molecules capable of modulating the production of intracellular cytokines begin to be marketed. They also are potentially active in the same rheumatic diseases. The purpose of this article is to review these new drugs, in particular to review the progress of their development and commercialization status.

[Intra-articular infiltrations in rheumatology: update]. / Rhumatologie. Infiltrations intra-articulaires en rhumatologie: mise au point.

Intra-articular treatments are very useful in the daily practice of rheumatology, although their survival in the joint cavity is short and their mode of action still widely misunderstood. Corticosteroids were first used in fifty's, and are still the most widely used, despite potential local and systemic side effects. In recentyears, other molecules have been developed, especially in the treatment of osteoarthritis, but their effectiveness is controversial. Therapeutic trials were conducted with biological treatments in inflammatory arthritis, without success so far In the area of biotechnology, molecules to increase the survival of drugs into the joint are in preparation.

[MRI of axial spondyloarthritis: diagnostic role and pitfalls]. / IRM dans le diagnostic des spondyloarthrites axiales: utilité et pièges diagnostiques.

MRI has become a major tool for the diagnosis of axial spondyloarthritis and provides objective signs based on which therapy can be initiated. In clinical practice, ASAS classification criteria are often applied for the diagnosis of spondyloarthritis at a pre-radiographic stage. However, MRI signs of spondyloarthritis as stated in ASAS criteria lack specificity, and can be encountered in a wide array of diagnoses, in particular degenerative and mechanical conditions. In this article, we will review the role of MRI in the diagnosis and classification of spondyloarthritis, general technical considerations, the elementary MRI signs of axial spondyloarthritis, as well as diagnostic pitfalls. We also provide a practical approach on how to avoid overdiagnosis of spondyloarthritis and to improve the diagnostic value of MRI.

The importance of sonographer experience and machine quality with regards to the role of musculoskeletal ultrasound in routine care of rheumatoid arthritis patients.

OBJECTIVES: Regarding recent progress, musculoskeletal ultrasound (US) will probably soon be integrated in standard care of patient with rheumatoid arthritis (RA). However, in daily care, quality of US machines and level of experience of sonographers are varied. We conducted a study to assess reproducibility and feasibility of an US scoring for RA, including US devices of different quality and rheumatologist with various levels of expertise in US as it would be in daily care. METHODS: The Swiss Sonography in Arthritis and Rheumatism (SONAR) group has developed a semi-quantitative score using OMERACT criteria for synovitis and erosion in RA. The score was taught to 108 rheumatologists trained in US. One year after the last workshop, 19 rheumatologists participated in the study. Scans were performed on 6 US machines ranging from low to high quality, each with a different patient. Weighted kappa was calculated for each pair of readers. RESULTS: Overall, the agreement was fair to moderate. Quality of device, experience of the sonographers and practice of the score before the study improved substantially the agreement. Agreement assessed on higher quality machine, among sonographers with good experience in US increased to substantial (median kappa for B-mode and Doppler: 0.64 and 0.41 for erosion). CONCLUSIONS: This study demonstrated feasibility and reproducibility of the Swiss US SONAR score for RA. Our results confirmed importance of the quality of US machine and the training of sonographers for the implementation of US scoring in the routine daily care of RA.

Anti-tumor necrosis factor drug survival in axial spondyloarthritis is independent of the classification criteria.

To compare the impact of meeting specific classification criteria [modified New York (mNY), European Spondyloarthropathy Study Group (ESSG), and Assessment of SpondyloArthritis international Society (ASAS) criteria] on anti-tumor necrosis factor (anti-TNF) drug retention, and to determine predictive factors of better drug survival. All patients fulfilling the ESSG criteria for axial spondyloarthritis (SpA) with available data on the axial ASAS and mNY criteria, and who had received at least one anti-TNF treatment were retrospectively retrieved in a single academic institution in Switzerland. Drug retention was computed using survival analysis (Kaplan-Meier), adjusted for potential confounders. Of the 137 patients classified as having axial SpA using the ESSG criteria, 112 also met the ASAS axial SpA criteria, and 77 fulfilled the mNY criteria. Drug retention rates at 12 and 24 months for the first biologic therapy were not significantly different between the diagnostic groups. Only the small ASAS non-classified axial SpA group (25 patients) showed a nonsignificant trend toward shorter drug survival. Elevated CRP level, but not the presence of bone marrow edema on magnetic resonance imaging (MRI) scans, was associated with significantly better drug retention (OR 7.9, ICR 4-14). In this cohort, anti-TNF drug survival was independent of the classification criteria. Elevated CRP level, but not positive MRI, was associated with better drug retention.

[Update in psoriatic arthritis treatment]. / Rhumatologie. Rhumatisme psoriasique.

Psoriatic arthritis is a chronic inflammatory disease. It affects up to 40% of patients suffe- ring from skin psoriasis. Joint involvement is relatively heterogeneous. Some clinical manifestations are similar to those of rheumatoid arthritis, others are close to spondylarthritis manifestations and are therefore considered as part of this entity. Treatment depends on initial presentation (peripheral or axial) but often begins with non-steroidal anti-inflammatory drugs and methotrexate, followed by anti-TNFalpha if needed. New therapeutic op- tions are available or under evaluation, parti- cularly targeting cytokines involved in psoriatic arthritis (IL-12/IL-23 and IL-17).

[Knee pain in ambulatory practice]. / Gonalgies: que faire en médecine de premier recours?

Knee pain is a frequent complaint in ambulatory practice. Because of its complexity, the knee is prone to trauma, arthritis and the impact of aging. Septic arthritis is an emergency and has to be suspected when important knee pain is associated with fever, an alteration of the general condition, or in a particular social context. In most cases the clinical examination can identify the type of pathology. Conservative treatment is beneficial in most cases and physiotherapy a major component of the prognosis.

[Shoulder pain in ambulatory practice]. / Epaule douloureuse: prise en charge ambulatoire.

Scapulalgias or omalgias are a frequent complaint, with more than half of them being linked to an injury of the rotators cuff. As they often become chronic, omalgias result in higher rates of absenteeism and significant health care costs. Scapulalgias have three main causes: posttraumatic, intrinsic of the joint, or extrinsic. The extrinsic omalgias, either of neurologic, cardiovascular, pulmonary, or abdominal etiology, require swift identification, as their treatment is often an emergency. Most of the scapulalgias can be treated conservatively. Main factors of poor prognosis are old age, women gender and associated cervicalgias.

Real-life drug retention rate and safety of rituximab when treating rheumatic diseases: a single-centre Swiss retrospective cohort study.

BACKGROUND: In Switzerland, rituximab (RTX) is licenced for the treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) but is frequently used off-label to treat other auto-immune diseases (AID), especially connective tissue diseases (CTD). We aimed to characterise the use of RTX in AID in a real-life Swiss setting and compare RTX retention rates and safety outcomes between patients treated for RA, CTD and AAV. METHODS: A retrospective cohort study of patients who started RTX in the Rheumatology Department for RA or AID. The RTX retention rate was analysed using Kaplan-Meier survival curves. Occurrences of serious adverse events (SAE), low IgG levels and anti-drug antibodies (ADA) were reported. RESULTS: Two hundred three patients were treated with RTX: 51.7% had RA, 29.6% CTD, 9.9% vasculitis and 8.9% other AIDs. The total observation time was 665 patient-years. RTX retention probability at 2 years (95%CI) was similar for RA and CTD 0.65 (0.55 to 0.73), 0.60 (0.47 to 0.72) and lower for vasculitis 0.25 (0.09 to 0.45). Survival curves for RTX retention matched closely (p = 0.97) between RA and CTD patients but were lower for patients with vasculitis due to a higher percentage of induced remission. Patients with vasculitis (95%) and CTD (75%) had a higher rate of concomitant glucocorticoid use than RA (60%). Moderate to severe hypogammaglobulinaemia was observed more frequently in patients with vasculitis (35%) than with RA (13%) or CTD (9%) and was associated with an increased risk of presenting a first infectious SAE (HR 2.01, 95% CI 1.04 to 3.91). The incidence rate of SAE was 23.3 SAE/100 patient-years (36% were infectious). When searched, ADAs were observed in 18% of the patients and were detected in 63% of infusions-related SAE. 10 patients died during RTX treatment and up to 12 months after the last RTX infusion, 50% from infection. CONCLUSION: RTX retention rates are similar for patients with RA and CTD but lower for those with vasculitis due to more frequent remission. Patients treated with RTX for vasculitis present more SAE and infectious SAE than patients with RA and CTD, potentially due to a higher use of concomitant glucocorticoids and the occurrence of hypogammaglobulinaemia.