[Rheumatology : what's new in 2022]. / Rhumatologie : ce qui a changé en 2022.

In rheumatology, this year has seen an expansion of knowledge about the treatment of rheumatoid arthritis, with the availability of results from randomized trials evaluating a new molecule targeting IL-6, and regarding the safety profile of tofacitinib compared to TNF-alpha inhibitors. Interesting data on the outcome of pregnancy in patients with spondylarthritis have also been published. New molecules and different treatment strategies have shown promising results in psoriatic arthritis and systemic lupus erythematosus. The utility of botulinum toxin A injections for Raynaud's phenomenon and the efficacy of transplantation of autologous adipose-derived regenerative cells for the treatment of hand dysfunctions have been questioned by 2 randomized controlled trials of patients with systemic sclerosis.

Cette année a vu un approfondissement des connaissances sur le traitement de la polyarthrite rhumatoïde, avec la publication de résultats d'essais randomisés évaluant une nouvelle molécule ciblant l'IL-6 et le profil de sécurité du tofacitinib par rapport aux inhibiteurs du TNF-alpha. Des données intéressantes sur l'issue de la grossesse chez les patientes atteintes de spondylarthrite ont également été publiées. De nouvelles stratégies de traitement ont donné des résultats prometteurs dans le rhumatisme psoriasique et le lupus érythémateux systémique. L'utilité des injections de toxine botulique A pour le phénomène de Raynaud et l'efficacité de la transplantation de cellules régénératrices adipeuses autologues pour le traitement de dysfonctions de la main ont été remises en question par deux études dans la sclérose systémique.

[Monitoring of antirheumatic drugs]. / Suivi biologique des traitements de fond en rhumatologie.

Regular blood monitoring allows for treatment adjustments and early detection or even prevention of some side effects of antirheumatic dugs. Guidelines may vary between national societies for rheumatology, but largely recommend baseline screening followed by regular blood tests depending on the specific drug and duration of treatment. In this article we discuss the monitoring of the major antirheumatic drugs and further develop on some significant and specific drug side effects.

Le suivi biologique des traitements de fond rhumatologiques permet non seulement de les adapter en fonction des cibles thérapeutiques, mais également de détecter précocement et parfois prévenir certains effets toxiques indésirables, liés aux médicaments. Les recommandations varient selon la société experte et le pays, mais s'accordent sur un bilan biologique préalable, puis des contrôles sanguins périodiques dont la fréquence dépend de la molécule et de sa durée d'utilisation. Dans cet article, nous discutons du suivi biologique des principaux traitements de fond et abordons quelques effets indésirables biologiques significatifs, spécifiques à certaines molécules.

[Rheumatology: 2021 update]. / Rhumatologie.

In rheumatology, this year has seen an expansion of knowledge about the effects of COVID and the vaccine response in patients with autoimmune diseases, but also a re-examination of the usual doses of glucocorticoids in vasculitides and new treatments strategies for diseases such as systemic lupus erythematosus, spondylarthritis and rheumatoid arthritis. New criteria for imaging assessment in spondylarthritis and new management guidelines for patients with low back pain have also been proposed.

En rhumatologie, dans les nouveautés que nous avons choisi de mettre en avant, cette année a vu l'élargissement des connaissances sur le Covid et la réponse vaccinale chez les patients avec maladies autoimmunes, la remise en question des doses habituelles des corticostéroïdes dans les vascularites et la possibilité de nouveaux traitements ou stratégies de prise en charge, dans le lupus érythémateux systémique, les spondylarthrites et la polyarthrite rhumatoïde. De nouveaux critères pour l'évaluation de l'imagerie des spondylarthrites ont aussi été proposés et des précisions quant au type de prise en charge nécessaire pour les patients lombalgiques ont également été apportées.

[Differential diagnosis and prognosis of inflammatory myopathies]. / Diagnostic différentiel et pronostic des myopathies inflammatoires.

Inflammatory myopathies are characterized by muscle weakness, occasionally pain, and an inflammatory infiltrate of the skeletal muscle. Despite the description of novel autoantibodies and advances in imaging, the lack of universal consensus on classification criteria and routine clinical use of validated outcome measures has direct implications on treatment trials and observational registries. In this article we discuss the differential diagnosis and prognosis of the idiopathic inflammatory myopathies.

Les myopathies inflammatoires sont caractérisées par une faiblesse musculaire, parfois douloureuse, et un infiltrat inflammatoire du muscle strié squelettique. Malgré la description de nouveaux anticorps et les techniques d'imagerie, de nombreux défis persistent, notamment en ce qui concerne les critères de classification et l'utilisation de mesures d'activité validées en pratique clinique, avec des conséquences directes sur les essais thérapeutiques et les registres observationnels. Dans cet article, nous discutons du diagnostic différentiel des myopathies inflammatoires auto-immunes et de leur pronostic.

[Rheumatological complications of immune checkpoint inhibitor therapy]. / Complications rhumatologiques des inhibiteurs de points de contrôle immunitaires.

Cancer management has been revolutionised by immune checkpoint inhibitors. Their use and indications increase in parallel with the recognition of their various side effects. Arthritis, myositis, and vasculitis are among the most common rheumatologic immune-related adverse events (irAE) of immunotherapy. Rheumatological irAEs can be of late onset, occur even after the cessation of the culprit drug and persist into time. In this article we discuss the principles of cancer immunotherapy, clinical manifestations and management of the most common rheumatologic irAEs, and aspects of immune checkpoint inhibitors therapy in patients with pre-existing autoimmune disease.

La prise en charge de certains cancers a été révolutionnée par l'arrivée des inhibiteurs de points de contrôle immunitaires. Leurs utilisation et indications augmentent en parallèle de la reconnaissance de leurs effets secondaires. Parmi les effets indésirables immunomédiés (immune-related adverse events ­ irAE) rhumatologiques, arthrites, myosites et vasculites sont les plus fréquents. Les irAE rhumatologiques peuvent survenir tardivement ­ même après l'arrêt de l'immunothérapie ­ et se chroniciser. Dans cet article, nous reprenons les principes de l'immunothérapie, les manifestations ainsi que la prise en charge des irAE rhumatologiques les plus fréquents et discutons brièvement le sujet de l'immunothérapie chez le patient avec maladie autoimmune préexistante.

Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients.

OBJECTIVES: To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally. METHODS: 144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression. RESULTS: Cellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) diffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression. CONCLUSIONS: We demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.

[Inflammatory arthritides pathotypes]. / Pathotypes des rhumatismes ­inflammatoires.

The pathophysiology of the inflammatory arthritides (IA) is complex and the result of interactions between genetic and environmental factors, leading to -in the case of seropositive rheumatoid arthritis-a breach of immune tolerance and subsequent development of joint and systemic manifestations. Regardless of the exact site of the initial immune dysregulation, the synovial membrane is the main target of IA. The heterogeneity of the clinical phenotypes is even more evident on the histological level (pathotypes), which in turn renders research on disease mechanisms more complicated. This article focusses on the various pathotypes of IA.

La physiopathologie des rhumatismes inflammatoires est complexe et résulte de l'interaction entre facteurs génétiques et environnementaux, qui aboutissent, dans le cas de la polyarthrite rhumatoïde séropositive, à une perte de tolérance immunitaire puis au développement d'atteintes articulaires et systémiques. Indépendamment du lieu de naissance du conflit immunologique initial, la membrane synoviale est la cible principale des rhumatismes inflammatoires. L'hétérogénéité des phénotypes des patients est encore plus prononcée au niveau histologique (pathotypes), ce qui rend l'étude des mécanismes pathogéniques impliqués plus compliquée. Dans cet article, nous nous sommes donc intéressés aux différents pathotypes des arthrites inflammatoires.

[Management of septic arthritis]. / Prise en charge médico-chirurgicale de l'arthrite septique.

Native joint septic arthritis is a medical emergency requiring urgent joint drainage and antibiotic therapy. In the absence of an artificial joint or a foreign body, the « rheumatological approach ¼ with repetitive arthrocentesis yields similar outcomes in the literature when compared to surgical drainage. Arthrocentesis could therefore be viewed as the preferential method of joint drainage as it is associated both with reduced morbidity for patients and decreased costs for the healthcare system. In case of failure with arthrocentesis, surgical arthroscopic drainage becomes necessary. In addition, the prescription of systemic steroids is promising but requires further studies, especially in adult patient populations.

L'arthrite septique nécessite une prise en charge urgente, incluant le drainage articulaire et une antibiothérapie. En l'absence de prothèse ou de corps étrangers, les différents modes de drainage articulaire ont une efficacité similaire sur l'évolution clinique. L'approche rhumatologique avec arthrocentèse est la méthode la plus simple de drainage, associée à une morbidité et des coûts inférieurs aux techniques chirurgicales. Par conséquent, elle devrait être utilisée en premier lieu. En cas d'échec, l'arthroscopie, la méthode chirurgicale la moins invasive, pourra être considérée. La prescription d'une corticothérapie adjuvante semble prometteuse ; néanmoins, de plus amples études sont nécessaires chez l'adulte.

Drug-induced myopathies. / Myopathies médicamenteuses.

Drug myopathies are frequent and their identification important because of their potential morbidity. Apart from statins, the drugs most often involved are glucocorticoids, antimalarials, colchicine, and antiretrovirals. These myopathies are largely preventable, particularly those that occur in combinations of treatments or in the presence of comorbidities. Their relatively specific presentation often makes it possible to approach the diagnosis and to target the possible molecule to be interrupted. In general, they are spontaneously and rapidly reversible upon discontinuation of the drug, with the exception of statin-induced autoimmune necrotizing myopathy ; however, the latter is reversible under immunosuppressants, when initiated early enough.

Les myopathies médicamenteuses sont fréquentes et leur identification importante en raison de leur morbidité potentielle. En dehors des statines, les médicaments les plus souvent impliqués sont les glucocorticoïdes, les antimalariques, la colchicine et les antirétroviraux. Ces myopathies sont largement évitables, particulièrement celles qui surviennent lors de combinaisons de traitements ou en présence de comorbidités. Leur présentation relativement spécifique permet souvent d'approcher le diagnostic et de cibler l'éventuelle molécule à interrompre. D'une manière générale, elles sont spontanément et rapidement réversibles à l'arrêt du médicament, à l'exception de la myopathie autoimmune nécrosante aux statines ; cette dernière est cependant réversible sous immunosuppresseurs, quand ils sont initiés suffisamment tôt.

Ultrasound-guided synovial biopsy of the wrist does not alter subsequent clinical or ultrasound disease activity assessments: a prospective study for incorporation of imaging in clinical trials.

OBJECTIVES: Ultrasound-guided synovial biopsy (UGSB) is a minimally-invasive procedure capable of retrieving good quality tissue from small and large joints. The use of UGSB in prospective clinical trials poses a dilemma as to whether biopsied joints may be later included in core data sets for clinical or imagining response, as the procedure itself may alter disease activity assessment. In this study, we examine the impact of UGSB of the wrist on subsequent clinical and ultrasound (US) assessments in a cohort of rheumatoid arthritis (RA) patients prior to initiation of anti-TNF-alpha therapy. METHODS: Patients had active disease (DAS>5.1) involving their wrist. Both wrists were scanned and the most inflamed one underwent an UGSB. Ultrasonographic and clinical assessments were repeated at the patients' subsequent visit, without any changes in disease-modifying treatment between visits. US images were scored semi-quantitatively and quantitatively for synovial thickness (ST) and power Doppler (PD). Mixed-effects model and paired-Wilcoxon signed rank test were used to assess the effect of UGSB on these scores. RESULTS: Twenty-nine patients were enrolled. No significant difference in mean ST (p=0.32) or PD (p=0.21) was demonstrated pre- and post-biopsy (mean time 14.7 days). Similar results were obtained using quantitative measures. The DAS-28 and its components did not change significantly post-biopsy. CONCLUSIONS: In this population, UGSB of the wrist did not significantly alter subsequent clinical or US assessments, indicating that a wrist joint, which has undergone UGSB, may be incorporated into an US dataset or clinical outcome assessment tools, such as the DAS-28, without prejudice.

Ultrasound-guided synovial biopsy: a systematic review according to the OMERACT filter and recommendations for minimal reporting standards in clinical studies.

OBJECTIVES: To describe existing techniques of US-guided synovial biopsy (USG-SB) and critically appraise the literature on this technology through the OMERACT filter. METHODS: USG-SB techniques are described and compared. A systematic literature search of PubMed and Embase was performed for original research reports including US and SB. The subjects, procedure protocols and reported results were analysed. A future research agenda is proposed. RESULTS: USG-SB can be performed using a portal-and-forceps or a dedicated semi-automatic guillotine-type biopsy needle approach. Of 50 reports identified, 7 were included in the review. Large, intermediate and small joints were all amenable to USG-SB. We found great heterogeneity with regard to indications for and definition of a successful procedure and of synovitis. Adverse events were assessed in most papers with an overall major complication rate of 0.4%. However, there was a lack of construct validity using a histological comparator. Relatively few papers reported details on the technique used, tissue processing, synovitis scoring and blinding for tissue analysis. CONCLUSION: USG-SB can be regarded as a valuable tool for large-scale synovial tissue sampling. Standardization of the techniques of USG-SB and tissue processing is needed. Future research should focus on the reliability, responsiveness and feasibility of this procedure in prospective studies.

Felty's syndrome and hypofibrinogenemia: an unusual target for anti-cyclic citrullinated peptide antibodies?

BACKGROUND: Rheumatoid arthritis (RA) is a risk factor for the development of Felty's syndrome and large granular lymphocyte (LGL) leukemia. Anti-cyclic citrullinated peptide (CCP) antibodies are considered highly specific for RA and are directed against various citrullinated antigens, including citrullinated fibrinogen. Anti-CCP antibodies may interfere with the detection of citrullinated proteins and their function. In this article, we describe the possible inhibition of fibrinogen by anti-CCP antibodies with clinical consequences which have never been reported in the literature to our best knowledge. CASE REPORT: We present the case of a 79-year-old Caucasian woman with a longstanding history of untreated seropositive RA and who had been investigated for severe neutropenia since several months. The association of splenomegaly led to suspicion of Felty's syndrome. Flux cytometry was compatible with T-cell LGL leukemia. In addition, severe hypofibrinogenemia was detected. The later finding has not been consistently associated with the former clinical entities. Further investigations demonstrated that the anti-CCP antibodies of the patient also recognized the P41 peptide of citrullinated fibrinogen. The patient deceased of intracranial hemorrhage. CONCLUSION: It is likely, yet not definite, that high anti-citrullinated fibrinogen titers may contribute to low fibrinogen levels and could have contributed to the fatal hemorrhagic event.

Left main coronary artery perforation during percutaneous coronary intervention in a patient with noninfectious aortitis.

Noninfectious aortitis is increasingly recognized as an important cause of aortic aneurysms and dissection. Coronary involvement in noninfectious aortitis has been reported in several case reports and is marked by a high mortality. Here, we describe the case of a 72-year-old patient suffering from aortitis with involvement of the left main coronary artery trunk, who underwent percutaneous coronary intervention (PCI), which was complicated by left coronary artery perforation. Active inflammatory disease of the vessel wall may cause excessive tissue frailty and therefore has to be considered as a risk factor for perforation during PCI.

[Use of glucocorticoids in low back pain due to disc herniation with radicular involvement]. / Utilisation de corticostéroïdes lors de lomboradiculalgies par hernie discale.

Although systemic glucocorticoids are frequently used for the treatment of radicular pain due to disc herniation, there are only few studies available. No trial has successfully demonstrated the superiority of systemic glucocorticoids compared to placebo. Therefore their use is not recommended. Spinal injection using radiographic guidance appears to provide some beneficial short-term effect on pain. It might be offered when pain treatments according to the WHO steps have failed. Because rare but serious adverse events have been reported, transforaminal periradicular injections should only be used after thorough analysis of risks and benefits with the patient.

Treatment-resistant synovitis and radiographic progression are increased in elderly-onset rheumatoid arthritis patients: findings from a prospective observational longitudinal early arthritis cohort study.

BACKGROUND: Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naïve early arthritis cohort, the relationship between synovial pathobiology of elderly- (EORA) and younger-onset rheumatoid arthritis (YORA) patients through clinical, imaging and treatment response outcome-measures. METHODS: Patients (n = 140) with early RA (<12months) starting before (YORA, n = 99) or after (EORA, n = 41) age 60 had an ultrasound-guided synovial biopsy prior to conventional immunosuppressive therapy and after 6 months. Clinical, ultrasound and radiographic data were collected prospectively and compared between groups and against immunohistological features. Using multivariate logistic regression, we determined predictors of clinical response (disease activity score-28-erythrocyte sedimentation rate [DAS28-ESR]<3.2) at 6 months and radiographic progression (≥1-unit-increase in Sharp van der Heijde [SvdH] score) at 12 months. RESULTS: EORA patients were more frequently male and presented most commonly with an abrupt, polymyalgia rheumatica-like onset and extra-articular features. Both before and after treatment, DAS28-ESR was similar but ultrasound synovial-thickening (p<0.05) and power-Doppler (p<0.01) synovitis and SvdH (p<0.001) scores were higher in EORA patients. EORA was independently associated with poor treatment response at 6 months (OR=0.28, p = 0.047) and radiographic progression at 12 months (OR=4.08, p = 0.029). Synovial pathotype, synovitis scores and cellular infiltration were similar before treatment, but a pauci-immune-fibroid pathotype tended to be more common in YORA at 6 months (p = 0.093). Moreover, YORA patients had a marked improvement of all synovitis parameters (p<0.001), whereas EORA presented only mild decreases in synovitis (p<0.05), sublining macrophage (p<0.05) and T cell scores (p<0.05), with no significant changes in lining macrophages, B cells or plasma cells. CONCLUSION: Early EORA presents differently and has a worse overall prognosis than YORA, with poorer clinical, histological, ultrasonographic and radiographic outcomes.

US-Guided Biopsies: Overarching Principles.

Gathering synovial tissue from any swollen joint especially in early arthritis patients is critical for good quality research and to obtain further insight into the pathophysiology of inflammatory joint diseases. Multiplying biopsy sites is a challenge in terms of the techniques needed for each different joint but also in terms of safety and tolerability. It is important to provide the best care especially in very early arthritis patients who have only had the disease for a few months. This review discusses the minimal requirements applying to antiseptic techniques for the operator's hands, patient preparation, local anesthesia, and post-procedure care.

Ultrasound-Guided Synovial Biopsies of Wrists, Metacarpophalangeal, Metatarsophalangeal, Interphalangeal Joints, and Tendon Sheaths.

Ultrasound-guided synovial biopsy (UGSB) is a minimally-invasive procedure which allows quality synovial tissue retrieval. In this article, we will discuss overarching principles of the procedure performed in wrists, metacarpophalangeal (MCP), metatarsophalangeal (MTP), interphalangeal joints (IP), and tendon sheaths, including basic sonoanatomy, entry site and biopsy technique, as well as special considerations for each structure whenever relevant.

Ultrasound is not associated with the presence of systemic autoimmunity or symptoms in individuals at risk for rheumatoid arthritis.

Objective: To identify whether musculoskeletal ultrasound (MSUS) abnormalities are associated with specific phases of rheumatoid arthritis (RA) development in individuals at risk of RA. Methods: This is a prospective cohort study of individuals at risk of developing RA, namely first-degree relatives of patients with RA (RA-FDRs) without evidence of established rheumatic disease at inclusion. The inflammatory activity on MSUS was assessed according to a validated score (SONAR). Active MSUS was defined as a total B-mode score greater than 8, including at least one joint with significant synovitis (grade 2 or 3) or significant synovial hyperaemia (Doppler score greater than 1). We used logistic regression to analyse associations between MSUS findings and recognised preclinical phases of RA development, adjusting for other demographic and biological characteristics. Results: A total of 273 RA-FDRs were analysed, of whom 23 (8%) were anticitrullinated protein autoantibodies-positive, 58 (21%) had unclassified arthritis and 96 (35%) had an active MSUS, which was only associated with unclassified arthritis (OR: 1.8, 95% CI 1.0 to 3.3). Conclusion: In individuals at risk of RA, active MSUS was associated with the presence of unclassified arthritis, but not with any of the earlier described phases of RA development. These findings do not support an indiscriminate use of ultrasound in a screening strategy for preclinical RA.