ObjectivesTo assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases.MethodsThe TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019.ResultsHundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued.ConclusionThese initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Douleur & Analgésie, première revue internationale francophone consacrée à la douleur, dont le champ de son expertise s'étend de la recherche fondamentale à la clinique tant sur le plan de l'évaluation de la douleur que de ses traitements.

Cette étude, menée dans une population de patients atteints de LES, avait pour objectifs (1) de décrire les atteintes articulaires échographiques (US), (2) d'estimer la corrélation du nombre d'articulations cliniquement gonflées (NAG-C) et du SLEDAI clinique (SLEDAI-C) avec le NAG échographique (NAG-US) et le SLEDAI échographique (SLEDAI-US), (3) de mettre en évidence les caractéristiques spécifiques des patients lupiques selon les observations en mode Doppler puissance (DP). Nous avons inclus dans cette étude transversale multicentrique 151 patients adultes consécutifs atteints de LES. L'évaluation comprenait un examen clinique standardisé des articulations, une échographie en mode B et en mode Doppler puissance (DP) sur 40 articulations et 26 tendons, en aveugle des résultats de l'examen clinique. La corrélation entre l'examen clinique et l'échographie en mode B a été calculée au moyen du coefficient de corrélation intra-classe (ICC [Intervalle de confiance à 95 %]). Un taux très élevé d'anomalies infracliniques échographiques a été observé chez les patients asymptomatiques : l'existence d'au moins une manifestation échographique a été retrouvée chez 85 % des patients qui ne présentaient aucun symptôme articulaire. Parmi eux, 46 patients (87 %) avaient un antécédent d'atteinte articulaire. L'épanchement articulaire (108 patients), l'hypertrophie synoviale (HS, 109 patients) et la synovite (61 patients) étaient les anomalies les plus fréquemment retrouvées. Un signal DP positif des articulations ou des tendons (grade > 1) a été retrouvé dans 44 % des cas (67/151). Des synovites ont été détectées principalement aux articulations MCP et des poignets. Malgré la faible corrélation de l'examen clinique au NAG-US en mode B, une bonne corrélation du SLEDAI clinique au SLEDAI échographique a été retrouvée. La comparaison des patients atteints de LES avec et sans signal DP n'a pas mis en évidence de caractéristiques spécifiques du LES. L'échographie est une méthode d'imagerie qui a prouvé son utilité pour l'évaluation des atteintes articulaires dans le LES mais qui ne modifiait pas de manière significative le score SLEDAI.

OBJECTIVES:The aims of this study in SLE population were (1) to describe ultrasonography (US) joint abnormalities, (2) to estimate the reliability of clinical swollen joint count (C-SJC) and SLEDAI (C-SLEDAI) versus US-SJC and US-SLEDAI scores, (3) to highlight specific patterns of lupus patients with Power Doppler (PD) abnormalities. METHOD:For this cross-sectional multicenter study, 151 consecutive adult SLE patients were recruited. Evaluation included a clinical standardized joint assessment, B-mode and PD US of 40 joints and 26 tendons blinded for clinical examination. Reliability and agreement between clinical and B-mode US were calculated using the intraclass correlation coefficients (ICC [95% Confidence Interval]). RESULTS:We found a very high frequency of subclinical US abnormalities in asymptomatic patients: 85% of patients without joint symptoms had at least 1 US abnormality. Among them 46 patients (87%) had a history of joint involvement. The most frequent abnormalities were joint effusmaions (108 patients), synovial hypertrophy (SH, 109 patients) and synovitis (61 patients). Joint or tendon PD signal (grade>1) was found in 44% of patients (67/151). Synovitis were mainly located especially on MCPs and wrists. Even if reliability between clinical and grey-scale US SJC assessments was poor, reliability between clinical and US SLEDAI was good. Comparison between SLE patients with and without PD signal did not show any specific SLE pattern. CONCLUSION:US may be useful to assess joint involvement in SLE patients but did not significantly change SLEDAI score.

Rapporter les résultats de notre expérience monocentrique de la prise en charge par mycophénolate mofétil (MMF) de 4 enfants atteints d’angéite primaire du système nerveux central (PACNS).De décembre 2011 à août 2015, quatres patients (dont 3 garçons; âgés de 9 mois à 13 ans) atteints de PACNS ont été suivis. Les enfants inclus dans l’étude ont reçu le protocole thérapeutique suivant : acide acétylsalicylique et/ou traitement anticoagulant utilisant l’héparine de bas poids moléculaire (HBPM) à une dose de 100 U/k BID remplacée par l’acénocoumarol ; méthyl-prednisolone (30 mg/kg/jour pendant 3–5 jours) suivi de la prednisone (2 mg/kg/jour) avec un schéma de décroissance progressive puis une interruption après un délai de 7–8 mois ; MMF en traitement d’induction puis d’entretien (750–1 000 mg/m2 BID, demi-dose pour les 10–15 premiers jours suivie d’une dose complète).Il n’a été rapporté aucune récidive de vascularite cérébrale pendant toute la durée du suivi avec une amélioration observée chez tous les enfants dès lors qu’ils étaient sous traitement MMF. L’imagerie par résonance magnétique (IRM) et l’angiographie par résonance magnétique (ARM) réalisées à 6, 9 ou 12 mois d’intervalle n’ont mis en évidence aucune progression des lésions radiologiques typiques. La durée moyenne du traitement par MMF était de 29 mois (extrêmes, 10–42 mois). Aucun évènement indésirable lié au traitement n’a été observé.Nous rapportons pour la première fois les données d’efficacité et de tolérance du MMF en traitement d’induction et pour le maintien de la rémission clinique de la PACNS chez l’enfant. D’après notre expérience monocentrique, le MMF dans le traitement de la PACNS pédiatrique apparaît comme étant une option thérapeutique encourageante et fiable à long terme.

Radioisotope synovectomy has been extensively used to treat patients with chronic inflammatory joint disease but has moved to a less prominent position since the introduction of new and highly effective drugs. Remaining indications are refractory synovitis, pigmented villonodular synovitis as an adjunct to surgery, and hemophilic arthropathy. The three main radioisotopes used are yttrium-90, rhenium-186, and erbium-189. Radioisotope synovectomy should be performed only by highly experienced professionals, to minimize the risk of injection-related complications. The available safety data, in particular regarding the risk of malignancy, are reassuring. The efficacy of yttrium-90 in chronic inflammatory joint disease remains controversial.

To analyse and report the incidence of side effects of biological agents in paediatric patients with inflammatory diseases using of real-life follow-up cohort.In this international, observational, retrospective, multicentre study of children treated by biological agents and followed in the Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan–Meier method was used to estimate the occurrence of adverse events. A Cox model was constructed to identify independent predictors of adverse events.Overall 813 patients totalling 3439 patients–year (PY) of biological agents were included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of 222 patients (27.3%) had 419 adverse events, representing an incidence rate of 12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab were significantly associated with adverse events and canakinumab with serious adverse events. Univariate and multivariable analysis of adverse events and serious adverse events indicated that patients under biological agents with concomitant immunosuppressive drugs (excluding methotrexate) suffered from more of these events.This study suggests an overall an acceptable safety of biologic agents in children with inflammatory rheumatic diseases treated with biological agents. However, the concomitant prescription of immunosuppressive drugs with biological agents represents a substantial risk of adverse events.

Les synoviorthèses isotopiques ont été très utilisées en rhumatologie dans le cadre des rhumatismes inflammatoires chroniques. L’arrivée de nouveaux traitements plus efficaces a rendu leur utilisation plus rare. Elles sont encore utiles dans le traitement de synovites rebelles, de synovites villonodulaires en complément de la chirurgie et dans l’arthropathie hémophilique. L’yttrium 90, le rhénium 186 et l’erbium 169 sont les trois principaux isotopes utilisés. Leur utilisation doit faire appel à une équipe entraînée afin d’éviter les complications en lien avec l’infiltration. Les données de tolérance notamment de risque néoplasique sont rassurantes. L’efficacité de l’yttrium 90 dans les rhumatismes inflammatoires chroniques est débattue.

Le diagnostic de syndrome de Sjögren primaire repose sur un faisceau d’arguments cliniques et biologiques. L’apport de l’échographie des glandes salivaires a été récemment reconnu pour le diagnostic et l’évaluation thérapeutique au cours de celui-ci. Notre objectif était d’estimer par la technique échographique du mode ARFI, les valeurs d’élasticité des glandes salivaires de patients souffrant d’une maladie de Sjögren et de les comparer aux valeurs de témoins sains.Dix patients souffrant de ce syndrome et 15 témoins sains ont subi un examen échographique couplé au mode Acoustic radiation force impulse (ARFI). Dix tirs impulsionnels par glande ont été réalisés sur leurs parotides et submandibulaires afin de déterminer s’il existait des différences entre les valeurs moyennes de shear waves velocity (SWV) en m/s entre malades et témoins. La significativité a été appréciée par le test U de Mann-Whitney.Les valeurs moyennes en m/s de SWV parotidiennes du groupe « Sjögren » (2,335 ± 0,315) apparaissent significativement plus élevées que celles des témoins (1,785 ± 0,384) ; (p = 0,001). Il n’existe pas de différence significative des valeurs submandibulaires entre malades et témoins, respectivement 1,812 ± 0,308 et 1,766 ± 0,187 ; (p = 0,892).L’élastométrie en mode ARFI semble pouvoir constituer une aide diagnostic au syndrome de Sjögren en décelant, par une technique non invasive, rapide et peu coûteuse, les remaniements architecturaux pathologiques des glandes parotides.

Diminuer l’irradiation des patients lors des gestes de rhumatologie interventionnelle, sans diminuer la qualité du geste. La dose d’irradiation reçue (produit dose surface [PDS]) a d’abord été quantifiée lors de 283 infiltrations réalisées sous scopie, avant optimisation, entre mai et juillet 2013. Elle a été à nouveau mesurée en 2014, lors de 158 nouvelles infiltrations réalisées cette fois après optimisation des procédures : (1) interposition d’un filtre cuivre ; (2) retrait de la grille antidiffusante ; (3) réglage de la sensibilité de la cellule d’exposition en mode élevé. Avant optimisation, l’irradiation moyenne était de 175 μgray/m2 pour les infiltrations de quatre articulations zygapophysaires et de 43 μgray/m2 pour celles des hanches, mais elle restait inférieure à 20 μgray/m2 pour celles des épaules (15,7), chevilles (7,7), poignets (3,7) et doigts (3,3). Une très nette diminution des PDS a été observée pour chaque site d’infiltration après optimisation des procédures, la baisse de la PDS allant de 52 % (pour l’épaule) à 87 % (pour les articulations zygapophysaires, désormais à 22,7 μgray/m2 seulement). Ceci étant vrai pour les 3 étapes : installation du patient, geste médical et cliché final. Les PDS des infiltrations des articulations zygapophysaires étaient de 84 (54,5–108,5) μgray/m2 pour les indices de masse corporelle (IMC) < 25, versus 228,9 (161,3–340,4) μgray/m2 pour les IMC > 30. Des procédures techniques simples permettent une diminution majeure de l’irradiation des patients lors des infiltrations réalisées sous scopie, en particulier pour les articulations zygapophysaires et chez des personnes à IMC élevé.

To analyze the prevalence, characteristics and outcome of cystic lung disease associated with Sjögren's syndrome (SS).From June 2010 to February 2015, 90 consecutive SS patients [60.1 ± 14.8 years; 88 (97.8%) female, 75 (83.3%) primary SS] had a systematic chest CT-scan. The presence of thin-walled cysts was analyzed by one experienced radiologist. Demographic data, clinical history, laboratory findings, and pulmonary function tests were extracted retrospectively from medical records.Twenty-one (23.3%) patients had cysts on CT scan performed 40.5 ± 54.5 months after SS diagnosis. Cysts number ranged from 1 to 25 were often bilateral (52.4%) and mostly located in the middle lung zone (76.2%). Cysts were isolated (n = 6, 28.6%) or associated with other lesions, including bronchiectasis (n = 5, 23.8%), micronodules (n = 5, 23.8%), ground-glass opacity (n = 4, 19%) and/or air trapping (n = 3, 14.3%). Most patients with cysts (57.1%) had no respiratory symptoms. When comparing SS patients with and without cysts, patients with cysts tended to be older (65.3 ± 15.3 versus 58.5 ± 14.4 years, P = 0.06). Smoking habits were similar in both groups. Anti-SSB antibodies were more frequently detected in patients with cysts (57.1% vs. 26.1%, P = 0.02). Pulmonary function tests were normal or displayed only mild small airways obstruction and reduced diffusion capacity to carbon monoxide. Four (19%) patients with cysts had a past history of associated pulmonary disease, including interstitial lung disease. During follow-up (25.1 ± 17.7 months), no patient developed specific lung disease or lymphoproliferative disorders.Cystic lung disease is frequent, benign, associated with anti-SSB/La antibodies and has no impact on outcome in SS.

Objectives: To decrease radiation exposure of patients undergoing interventional rheumatology procedures, without adversely affecting quality of care.Methods: The radiation dose received, assessed by the dose-area product (DAP), was measured during 283 intraarticular injections performed under fluoroscopic guidance between May and July 2013. Then, three steps were taken to decrease patients' radiation exposure: a copper filter was added, the anti-scatter grid was removed, and exposure cell sensitivity was set at the highest value. DAP was measured during 158 intraarticular injections performed in 2014 with these measures in place.Results: Mean DAP before optimization was 175 mu Gray.m(2) during facet joint injections (n = 4) and 43 mu Gray.m(2) during hip injections but was less than 20 mu Gray m(2) for injections into the shoulders (15.7 mu Gray.m(2)), ankles (7.7 mu Gray m(2)), wrists (3.7 mu Gray m(2)), and fingers (3.3 mu Gray m(2)). After optimization, DAP decreased markedly for all injection sites, by 52% (shoulders) to 87% (facet joints, 22.7 mu Gray m(2)). Decreases occurred at all three steps of the procedure, i.e., patient installation, injection, and last image hold. Exposure during facet joint injections varied from 84 (54.5-108.5) mu Gray m(2) when body mass index (BMI) was < 25 kg/m(2) to 228.9 (161.3-340.4) mu Gray m(2) when BMI was > 30 kg/m(2).Conclusion: Simple technical changes translate into large decreases in patient radiation exposure during fluoroscopically-guided injections, particularly at the facet joints and in obese patients. (C) 2016 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

Objective. - Septic arthritis of the facet joint is a rare clinical entity. We report 11 cases of facet joint infections diagnosed in our institution. Patients and method. Patients were identified via the computerized patients record (PMSI). Their features were collected and compared with published data.Results. - The clinical symptoms are similar to those of infectious spondylodiscitis: back pain with stiffness (11/11), fever (9/11), radicular pain (5/11), and asthenia. Ten patients presented with lumbar infection and 1 with dorsal infection. An inflammatory syndrome was observed in every case. A rapid access to spine MRI allowed making the diagnosis in every case, and assessing a potential extension of infection (epidural extension 5/11, paraspinal extension 5/11). Blood culture (8/11) or culture of spinal samples allowed identifying the causative bacterium in every case and adapting the antibiotic treatment. The bacteria identified in our series were different from previously reported ones, with less staphylococci. The origin of the infection was found in 4 cases. Another localization of infection was observed in 4 cases. The outcome was favorable with medical treatment in 10 cases. An abscess was surgically drained in 1 case. None of our patients presented with neurological complications, probably because of the rapid diagnosis.Conclusion. - Assessing the facet joint is essential in case of inflammatory back pain, and the radiologist must be asked to perform this examination. (C) 2015 Published by Elsevier Masson SAS.

Objectives: To characterize the interstitial cystitis (IC) associated with Sjogren's syndrome (SS).Methods: Report of three new cases. Only cases fulfilling the American-European consensus criteria for SS and the European Society for the Study of Interstitial Cystitis criteria with positive histological findings for IC were included.Results: Thirteen cases of SS and IC have been reported in women, including the three reported here, with a mean age of 54 years. SS appeared first in 77% (n = 10) of cases, a mean of 6.6 years before IC. The symptoms of IC included pollakiuria (n = 11), lower abdominal pain (n = 8), urinary urgency (n = 5), painful micturition (n = 6), hematuria (n = 3) and dysuria (n = 3). Urinary dilatation occurred in three cases, leading to acute renal failure in two patients. The diagnosis of IC was confirmed by anatomical evidence of cystitis inflammation on bladder biopsy in all (n = 13) patients. Treatment was reported for nine patients, seven of whom (78%) received corticosteroid treatment, which was partially or completely effective in six cases. Immunosuppressive treatment was added in three cases (cyclosporine, n = 2; azathioprine, n = 1; cyclophosphamide, n = 1). Local bladder treatments were performed, with hydraulic distension in five cases and DMSO instillation in one patient. A urinary catheter was inserted in the two cases of acute obstructive renal failure.Conclusions: Urinary symptoms without infection should lead the physician to consider a diagnosis of IC in SS patients. Urinary dilatation may occur, leading to acute obstructive renal failure. Corticosteroid treatment may be effective and local treatments have been tried. (C) 2015 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

Staphylococcus caprae est un staphylocoque coagulase négaive mis en évidence pour la première fois chez l’homme en 1991 1]. Il est associé à des infections ostéoarticulaires [2,3], des bacériémies [4,5], des infections urinaires [4], une endocardite [4] t une méningite [6]. Nous rapportons deux cas d’infection articulaire à S. caprae : ne sacro-iliite et une arthrite de genou sur prothèse totale.

Objective: In rheumatoid arthritis (RA), nurses are now increasingly involved in joint count assessment but training is not standardized. The aim was to evaluate and describe the learning curve of nurses for the assessment of swollen and tender joints in RA.Method: Twenty nurses from university rheumatology centres inexperienced with joint counts were allocated to a rheumatologist from their centre (teacher). Acquisition of skills consisted of Phase 1: (training), a centralized 4 hour training session, with (a) lecture and demonstration, and (b) practical sessions on patients with their teachers, followed by Phase 2: (practice) involving further practice on 20 patients in their own hospitals. Primary outcome was achievement of adequate swollen joint agreement between nurse and their teacher ("gold standard") at the "joint" level defined by prevalence adjusted biased adjusted kappa (PABAK) > 0.60. Agreement at the "patient" level of swollen joint count (SJC), tender joint count (TJC) as well as DAS28 between nurse and their teacher were assessed with intra-class correlation coefficients (ICC).Results: During the training phase, 75% of nurses achieved a swollen joint PABAK > 0.60 when compared with their teachers, which further improved to 89% after the 20 practice patients (Phase 2). Median swollen joint PABAK improved from 0.64 (Q1 :Q3 0.55,0.86) to 0.83 (Q1 :Q3 0.77,1) by the end of Phase 2. At the "patient" level, SJC agreement remained globally stable (ICC, 0.52 to 0.66), while TJC and DAS28 agreement remained excellent throughout.Conclusion: Nurses inexperienced in joint counts were able to achieve excellent agreement with their teachers in assessment of tender and swollen joints through a short training session; practice further enhanced this agreement. Larger longitudinal studies are required to assess skills retention. (C) 2013 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

Hemophagocytic syndromes (hemophagocytic lymphohistiocytosis, HLH) are characterized by a wide range of etiologies, symptoms, and outcomes, but have a common etiopathogenic pathway leading to organ damage: an excessive inflammatory response. Biological therapies have been proposed as a therapeutic option for refractory HLH, but have also been related to the development of HLH in severe immunosuppressed patients.The purpose of this study was to analyze the clinical characteristics and outcomes of adult patients who developed HLH after receiving biological therapies.We identified 30 patients (29 from the PubMed search and one unpublished case), including 19 women and 11 men, with a mean age of 46.5 years. Underlying diseases consisted of rheumatologic/autoimmune diseases in 24 patients and hematological neoplasia in the remaining 6. Biological agents received before the development of HLH were mainly anti-TNF agents (n = 19). Search for microorganisms confirmed systemic infection in 20 (67%) patients, including Mycobacterium tuberculosis (n = 5), cytomegalovirus (CMV) (n = 4), Epstein–Barr virus (EBV) (n = 3), Histoplasma capsulatum (n = 3), Escherichia coli (n = 2), Staphylococcus aureus, Leishmania amastigotes and Brucella melitensis (n = 1, respectively); viral infections were mainly reported in inflammatory bowel disease (IBD) patients. Patients with infections had more frequently received previous immunosuppressive therapies (p = 0.036) and had lower leukocyte counts (p = 0.020) in comparison with patients without associated infections. The outcome was described in 29 patients. After a mean follow-up of 6.3 months, 8 patients died (28%) and 6 had received anti-TNF agents. There was a high mortality rate in patients aged >65 years and those with tuberculosis (62% and 60%, respectively).In patients receiving biological therapies who develop HLH, searching for a concomitant infectious process is mandatory, and specific surveillance for EBV/CMV infections (in patients with IBD) and for bacteria, including mycobacteria (in elderly patients receiving anti-TNF therapy), is recommended.