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Objectives: We aimed to compare clinical spectrum and outcome between adults and children with Takayasu's arteritis (TAK) in a European population., Methods: We made a nationwide retrospective observational study between 1988 and 2019. All adult patients met the ACR diagnostic criteria for TAK and all children met the EULAR/PRINTO/PRES criteria for paediatric TAK., Results: We identified 46 children and 389 adults with TAK. The male to female ratio was 34/46 (0.74) in the paediatric group compared to 241/274 (0.88) in the adult group (P<0.05). Children presented with significantly more systemic symptoms; i.e., fever (P<0.05), fatigue (P<0.001), weight loss (P<0.001), abdominal pain (P<0.05), and myalgia (P<0.05) while adults had more upper limb claudication (P<0.01). Topography of the lesions differed significantly between the two groups: adults had more damage at the cerebral vasculature (P<0.01), upper and lower limbs (P<0.001) while children had more kidney lesions (P<0.05). Children TAK had more frequent (P<0.01) and higher (P<0.001) biological inflammation than adults. Children received higher dose-weight of corticosteroids (P=0.001) and less biotherapy (P<0.010) at diagnosis. Relapses (P<0.05) and death (8.6% vs 4.9%) were more frequent in children TAK than in adults., Conclusion: Paediatric TAK seems more severe than adult TAK. Therefore, paediatrics patients may require closer monitoring and systemic use of biological treatment., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Mind-body practices are complementary approaches recognized by the World Health Organization (WHO). While these practices are very diverse, they all focus on the interaction between mind and body. These include mindful meditation, yoga, Tai Chi, sophrology, hypnosis and various relaxation techniques. There is growing interest in incorporating these strategies in the management of chronic rheumatic diseases including rheumatoid arthritis. The aim of this review is to describe the main mind-body practices and analyze the existing evidence in chronic rheumatic diseases. In rheumatoid arthritis, the Mindfulness-Based Stress Reduction program, yoga, Tai Chi and relaxation may improve patient-reported outcomes, but the benefit on inflammation and structural progression is unclear. In spondyloarthritis, very few studies are available but similar evidence exist. Further evaluations of these practices in chronic rheumatic diseases are needed since their risk/benefit ratio appears excellent., (Copyright © 2023. Published by Elsevier Masson SAS.)

Skeletal muscle inflammation is the feature shared by all forms of myositis. However, the muscle damage ranges in severity from asymptomatic to responsible for severe weakness. In addition, myositis usually occurs as a systemic disease that affects multiple organs. More specifically myositis should be considered in patients with muscular, cutaneous, pulmonary, and articular manifestations. The definitive diagnosis and classification of myositis has benefited considerably in recent years from the identification of characteristic autoantibodies. Nonetheless, a muscle biopsy is often necessary to confirm the diagnosis, and the differential diagnoses may raise challenges that require evaluation at a myositis referral center. The management depends on the type of myositis. Treatments should be provided for both the systemic complications (involving the lungs, heart, gastrointestinal tract, and/or joints) and the comorbidities (cancer and risks factors for cardiovascular disease, thromboembolism, and fractures), which together determine the prognosis. Many drugs are available for treating myositis. Findings from randomized controlled trials will help to use them optimally., (Copyright © 2019. Published by Elsevier Masson SAS.)

There have been many advances in the diagnosis and therapeutic management of systemic lupus erythematosus (SLE) over the past decades. Following more than eleven centuries of therapeutic uncertainty, the discovery of the therapeutic properties of glucocorticoids is without any doubt one of the most significant advance in the field of autoimmune diseases. The many progresses made by rapidly growing chemical industry of the 19th century chemistry have allowed the identification of valuable therapeutic compounds such as anti-malarials, cyclophosphamide, azathioprine, cyclosporine and later mycophenolate mofetil, which have all profoundly changed the face of the disease. A very visible consequence of this is the profound improvement in the prognosis of the disease, with 10-year survival rates of more than 90% in most dedicated centres. Following the development of biotherapies in rheumatoid arthritis, the late 20th century has slowly opened a new era for the treatment of SLE, that of targeted therapies. With the approval of belimumab in 2011 and 74 targeted therapies in clinical development, we may expect great changes in the therapeutic management of SLE. Those molecules target inflammatory cytokines or chemokines and their receptors, B cells or plasma cells, intracellular signalling pathways, B/T cells co-stimulation molecules, interferons, plasmacytoid dendritic cells, as well as various other targets of interest. Current challenges are now slowly shifting from whether some new drugs will be available to how to select the most adequate drug (or drug combination) at the patient-level., (Copyright © 2018 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Relapsing polychondritis is a rare, multi-systemic and inflammatory condition of unknown origin. We currently lack a core set of measures to assess and follow damage in patients suffering from this condition. Our primary aim was to derive a disease-specific damage measuring tool for relapsing polychondritis, the Relapsing Polychondritis Damage Index (RPDAM)., Methods: We performed an international 4-round multicenter Delphi study during which experts were asked to rate the relevance of potential damage items for relapsing polychondritis (141 items were obtained from a literature review and 12 from expert suggestion), using a Likert Scale. The selection of items for each subsequent round was based on the median rating of each item., Results: Twenty-four experts from 11 nationalities participated in round 1 and 22 in rounds 2, 3 and 4. From the initial 153 potential damage items, 44 items were selected during round 1, 30 items during round 2 and 16 during round 3. During round 4, we refined the index to a total of 17 items referring to ear nose and throat, eye, respiratory, cardiovascular and hematological systems as well as to treatment-related specific damage items., Conclusion: We have developed by international consensus a scoring system to assess damage in patients with relapsing polychondritis. Following its validation, the RPDAM may contribute to improve the care of patients suffering from this rare condition as well as to standardize data collection for future clinical trials., (Copyright © 2018. Published by Elsevier Masson SAS.)

Greater accuracy in clinical descriptions combined with advances in muscle histology and immunology have established that inflammatory myopathies (IMs), similarly to inflammatory rheumatic diseases, constitute a highly heterogeneous group of conditions. The topographic distribution, severity, and tempo of onset of the myopathy vary widely, and the histological findings distinguish at least five different profiles, which may reflect different pathophysiological processes. Most IMs are connective tissue diseases that can affect multiple organs, among which the most common targets are the skin, joints, and lungs. The extramuscular manifestations may antedate the muscular involvement and should therefore suggest a diagnosis of IM even in the absence of obvious muscle disease. About 20 different autoantibodies have been identified in patients with IM. Some are mutually exclusive and associated with specific combinations of clinical manifestations. Following the model of antisynthetase syndrome, about 10 syndromes associated with autoantibodies specific of IM have been identified. Thus, polymyositis is now emerging as a rare entity that is often mistaken for more recently described patterns of IM. No consensus exists to date about the classification of IMs. Nevertheless, the clinical manifestations, autoantibody profile, and muscle histology can be used to distinguish patient subgroups with fairly homogeneous patterns of complications, treatment responses, and outcomes. These subgroups are also characterized by specific genetic and environmental factors. The advances made in the nosology of IMs have benefited the diagnosis, personalization of treatment strategies, and understanding of pathophysiological mechanisms. They can be expected to assist in the development of specific treatments., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: Assess the frequency of paradoxical reactions encountered in daily practice under tocilizumab, using the REGATE (Registry-RoActemra) registry. The secondary objectives were to determine the type of paradoxical reaction and the consequences of these reactions., Methods: The REGATE registry is an independent prospective registry, promoted by the French Society of Rheumatology, consisting of patients treated with tocilizumab for rheumatoid arthritis. The paradoxical reaction was retained if it was a paradoxical precipitation of a condition for which tocilizumab was indicated, if tocilizumab was being used for an alternative indication, and if it appeared after at least one tocilizumab infusion., Results: Among the 1491 patients included with at least one follow-up visit (3429 patient-years), a paradoxical reaction occurred in 9 patients (0.60% of patients; 2.62/1000 patient-years). These were 7 de novo pathologies (3 vasculitis, 3 uveitis, 1 lupus) and 2 exacerbations of pre-existing conditions (1 vasculitis, 1 lupus). Permanent discontinuation of tocilizumab was chosen for 5 patients., Conclusions: In the REGATE registry, the occurrence of paradoxical reactions in patients treated with tocilizumab was rare., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: Describe the clinical significance of anti-SG2NA antibodies also called anti-pseudo-PCNA type 1 (proliferating cell nuclear antigen auto-antibodies) which are rare antinuclear antibodies (ANAs) staining distinctly S/G2 proliferative HEp-2 cells by indirect immunofluorescence. By analogy with anti-PCNA antibodies, they have been suspected to be associated with systemic lupus erythematosus (SLE), cancers or viral diseases., Methods: From May 2006 to February 2013, 16,827 patients were tested positive for ANAs in the Laboratory of Immunology, Strasbourg, France. We retrospectively analyzed clinical and biological data from 126 patients with anti-pseudo-PCNA type 1 antibodies., Results: There was a 0.75% prevalence of anti-pseudo-PCNA type 1 Abs among ANAs(+) patients. Median age was 56.9 years (standard deviation [SD] 13.4 years) with a sex ratio female/male of 1.9. Compared to ANAs(+) patients, many more patients have been hospitalized in the Oncology and Hematology Department (23% vs. 6.3%, P < 0.05). Indeed, anti-pseudo-PCNA type 1 Abs were detected in 33 patients suffering from solid and hematological cancers (26%). Another group of patients presented various auto-immune diseases but surprisingly none of our patients was affected with SLE when 5 out of 8 patients in anti-PCNAs(+) Abs group (P < 5.10(-6)) were. Finally, the presence of anti-pseudo-PCNA type 1 Abs was associated in 30 cases with other auto-Abs reflecting a more general breakdown of B cell tolerance against other self-antigens., Conclusion: Considering our results, explorations for tumors should be at least recommended for patients with anti-pseudo-PCNA type 1 Abs. Lupus disease is not associated with these autoAbs., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

The risk of infection associated with autoimmune diseases is further increased by the use of biotherapies. Recommendations to minimize this risk include administering the full complement of vaccines on the standard immunization schedule, as well as the pneumococcal and influenza vaccines. Adults with chronic inflammatory joint disease (IJD) may receive a 13-valent pneumococcal conjugate vaccine, as well as a live attenuated vaccine against recurrent herpes zoster, recently licensed by European regulatory authorities. Live attenuated vaccines can be given only after an interval without immunosuppressant and/or glucocorticoid therapy. The effectiveness of vaccines, as assessed based on titers of protective antibodies, varies across vaccine types and disease-modifying antirheumatic drugs (DMARDs). Thus, methotrexate and rituximab are usually associated with decreased vaccine responses. The risks associated with vaccines are often considerably exaggerated by the media, which serve lobbies opposed to immunizations and make some patients reluctant to accept immunizations. Increasing immunization coverage may diminish the risk of treatment-related infections. A physician visit dedicated specifically to detecting comorbidities in patients with chronic IJD may result in improved immunization coverage. In this review, we discuss immunizations for adults with chronic IJD based on the treatments used, as well as immunization coverage. Many questions remain unanswered and warrant investigation by studies coordinated by the French networks IREIVAC (Innovative clinical research network in vaccinology) and IMIDIATE (Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research)., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: Patient-reported outcomes (PROs) reflect treatment efficacy from the patients' perspective. The objective was to assess PROs improvement with rituximab in rheumatoid arthritis., Methods: Patients with long-standing rheumatoid arthritis received rituximab 1000mg twice at 2 weeks interval, and were assessed over 6 months. PROs including physical PROs (pain, functional assessment, physical quality of life) and mental or mixed aspects (fatigue, sleep and mental quality of life) were assessed. Standardized response means were calculated. Early improvement in PROs was used to predict EULAR response at 6 months., Results: For the 175 patients (mean age 54.6±10.6 years, mean disease duration 12.9±9.3 years), the plateau of efficacy of rituximab on PROs was reached at week 12, and the effect was more prominent on physical PROs (e.g., pain standardized response means -0.75 [95% confidence interval -0.91; -0.60]), than on sleep (-0.43; [-0.56; -0.29]). It was not possible to accurately predict 6-month EULAR response by early improvement in PROs., Conclusion: Rituximab was effective on PROs with an early effect. PROs reflecting physical aspects were more modulated by this biologic than other PROs (fatigue, sleep or mental quality of life). Links between sleep difficulties, fatigue and RA should be further studied., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: To compare retention rates of adalimumab, etanercept and infliximab as first-line biotherapy in rheumatoid arthritis (RA), to determine causes of discontinuation, retention-associated factors, and retention rates of possible second-line TNF-α inhibitors (TNFi)., Methods: In this retrolective, multicentric study, medical charts of RA patients starting TNFi between March 2005 and April 2009 were reviewed, with follow-up between two and six years. The retention rate was estimated using the Kaplan-Meier method. Comparison between TNFi was done after adjustment using a Cox model. Factors associated with better retention were identified by multivariate analysis., Results: Of the 706 patients included, the percentage continuing treatment after two years was 54.9, 61.9 and 48.7%, and the median retention was 31, 45 and 23 months for adalimumab, etanercept and infliximab, respectively. The hazard ratios (HRs) for discontinuation were greater with adalimumab and infliximab than etanercept (1.315, 95% CI [1.050-1.648] and 1.380, 95% CI [1.041-1.828], respectively). The HR for discontinuation due to inefficacy was significantly higher with adalimumab than etanercept. Adverse events were significantly higher with infliximab than etanercept. Past use of more DMARDs and higher baseline ESR were associated with better retention. The median retention of the second-line TNFi was 11, 43 and 19.1 months for adalimumab, etanercept, and infliximab, respectively. HRs for adalimumab discontinuation due to all causes were significantly greater than for etanercept., Conclusions: Etanercept had a better retention rate than adalimumab and infliximab as first-line biotherapy in RA, and than adalimumab as second-line biotherapy., (Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: To assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients., Methods: This work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions., Results: The AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14-3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68-6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94-18.69], p = 0.002) on the risk of erosions in ACPA+ patients., Conclusion: A haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA., (Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

The use of TNFα antagonists must follow specific guidelines to ensure optimal effectiveness and safety. The French Society for Rheumatology (SFR) and Task Force on Inflammatory Joint Diseases (CRI), in partnership with several French learned societies, asked the French National Authority for Health (HAS) to develop and endorse good practice guidelines for the prescription and monitoring of TNFα antagonist therapy by physicians belonging to various specialties. These guidelines were developed, then, validated by two multidisciplinary panels of experts based on an exhaustive review of the recent literature and in compliance with the methodological rules set forth by the HAS. They pertain to the initial prescription of TNFα antagonists and to a variety of clinical situations that can arise during the follow-up of patients receiving TNFα antagonists (infections, malignancies, pregnancy, vaccination, paradoxical adverse events, surgery, use in older patients, and vasculitides)., (Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: Calcium pyrophosphate (CPP) crystal-induced arthritis occurs particularly in elderly people. This population has frequently associated comorbidities and treatments, which could limit the use of conventional therapies (colchicine, non-steroidal anti-inflammatory drugs and corticosteroids). The aim of the study was to evaluate the efficacy and tolerance of anakinra in patients with CPP crystal-induced arthritis., Methods: We performed a multicentric retrospective chart review of patients who received anakinra for CPP crystal-induced arthritis. Demographic information, comorbidities, co-prescription, short-term treatment outcomes, adverse event, complication and subsequent flares were reviewed., Results: A total of 16 patients (12 females, mean age: 80.2±11.1 years) received anakinra (100 mg subcutaneously per day). The mean number of anakinra injection was 15.5±42.9 per patient (median: 3). All patients had contraindication and/or failure to conventional therapies. The majority (14 [87.5%]) of patients with CPP crystal-induced arthritis demonstrated a beneficial response to anakinra therapy: 10 good responses and four partial responses. A relapse occurred in six (37.5%) patients (mean time to relapse: 3.4±4.9 months). One patient had an acute bacterial pneumonitis., Conclusion: Our results suggest that anakinra is relatively well tolerated and could be a good option in the treatment of CPP crystal-induced arthritis, illustrating that IL-1β blockade may be helpful to control flares in patients having CPP crystal-induced arthritis for which conventional therapies are ineffective or contra-indicated., (Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Hepatitis E is a rare and usually asymptomatic infection. However, its incidence is rising in France, and it can cause severe or chronic manifestations in immunocompromised patients. Here, we report a case of hepatitis E in a patient with rheumatoid arthritis who had immunosuppression due to treatment with a biological agent., (Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: To develop and/or update fact sheets about abatacept treatment, in order to assist physicians in the management of patients with inflammatory joint disease., Methods: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable 2. identification and review of publications relevant to each topic 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields (dermatologist, cardiologist, pediatric rheumatologist, endocrinologist, hematologist, immunologist, infectiologist), and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid arthritis (RA). They were members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society (Societe Francaise de Rhumatologie). Each fact sheet was revised by several experts and the overall process was coordinated by three experts., Results: Several topics of major interest were selected: contraindications of abatacept treatment; management of adverse effects and concomitant diseases that may develop during abatacept treatment; and management of common situations such as pregnancy, surgery, patient older than 75 years of age, and patients with co-morbidities (such as dialysis, hemoglobinopathy, or splenectomy). After a review of the literature and discussion among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of the abatacept treatment, management of patients with specific past histories, and specific clinical situations such as pregnancy 2. diseases other than RA, such as juvenile idiopathic arthritis, spondylarthropathies, or autoimmune diseases (systemic lupus erythematosus and other systemic autoimmune diseases) 3. models of letters for informing the rheumatologist and general practitioner 4. patient information about the use of abatacept in RA 5. and data on the new abatacept formulation for subcutaneous administration (approved by the FDA in August 2011 for patients with moderate-to-severe RA)., Conclusion: These fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on abatacept. They will be available continuously on www.cri-net.com and will be updated at appropriate intervals., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Hepatitis C-associated osteosclerosis (HCAO) is characterized by increased bone mass following hepatitis C infection. We report here a case of HCAO that lasted 8 years before the patient received antiviral hepatitis treatment. Seven years after the antiviral treatment, the evolution of radiographs and densitometry showed skeletal recovery of osteosclerosis. This case strengthens the relationship between viral infection and osteosclerosis., (Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: To develop and/or update fact sheets about TNFα antagonists treatments, in order to assist physicians in the management of patients with inflammatory joint disease., Methods: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several experts and the overall process was coordinated by three experts., Results: Several topics of major interest were selected: contraindications of TNFα antagonists treatments, the management of adverse effects and concomitant diseases that may develop during these therapies, and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA and SpA, initiation and monitoring of TNFα antagonists treatments, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information., Conclusion: These TNFα antagonists treatments fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on these therapies. They will be available continuously at www.cri-net.com and updated at appropriate intervals., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Aim: To investigate potential predictors of response to conventional DMARDs in RA., Methods: Study design - 6-month follow-up prospective study., Participants: RA patients with active disease. INTERVENTION AND FOLLOW-UP: Introduction of one DMARD. Response to treatment evaluated at 6 months (ACR20 criteria)., Analysis: Potential predictors of response, patients' demographics, disease activity, percentages of PBMC subsets expressing P-gp, serum IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α levels, were evaluated using univariate and multivariate logistic regression analysis. ROC curve analyses were performed in order to obtain thresholds allowing the prediction of response., Results: Forty-two patients (mean age = 57 ± 13 years, mean disease duration = 5.4 ± 7.2 years) were included. MTX was given to 30. The response to therapy was predicted by the baseline serum level of TNF-α (mean = 30.2 pg/ml ± 18 in non-responders vs. 11.9 pg/ml ± 11.2 in responders). The threshold, which predicted with the best accuracy the response to treatment, was 20.1 pg/ml (sensitivity, specificity, positive and negative predictive values of 75, 78.9, 83.3, and 69.2%, respectively; AUC = 80.3%, 95% CI = 62.8-97.7%). Similar results were obtained in the subgroups of patients treated with MTX and patients with early RA of less than 3 years duration., Conclusion: In the present work, the serum concentration of TNF-α was related to further response to DMARDs. Other works are needed for confirmation and to assess whether such biomarker could be used to predict the response to DMARDs at the individual level., (Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: To develop fact sheets about tocilizumab, in order to assist physicians in the management of patients with inflammatory joint disease., Methods: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The 20 experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of RA. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several. experts and the overall process was coordinated by three experts., Results: Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of tocilizumab therapy, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information., Conclusion: These tocilizumab fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on tocilizumab therapy. They will be available continuously at www.cri-net.com and updated at appropriate intervals., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

Multicentric reticulohistiocytosis is a rare, systemic, reactive histiocytic disease of unknown aetiology. Autoimmune diseases have previously been reported in association with multicentric reticulohistiocytosis, but whether this is a true association or mere coincidence is not known. Here, we report the case of a 50-year-old woman who had been diagnosed as suffering from rheumatoid arthritis (RA), four years ago with positive rheumatoid serology was evaluated for multiple asymptotic papulonodules eruption. Histopathologic examination was suggestive of multicentric reticulohistiocytosis. She developed concomitantly Sjogren syndrome with systemic manifestations. Multicentric reticulohistiocytosis may be misdiagnosed as RA, but evaluation of the time course of specific symptoms can greatly help in the correct diagnosis. The possibility of commune etiopathogeny of these affections is discussed., (Copyright 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Bone metastases are usually seen on imaging studies as lytic lesions and less often as sclerotic or mixed lesions. We report an exceedingly unusual case of breast cancer identified after magnetic resonance imaging showed bone metastases with fluid-fluid levels in the spine and sacrum. Bone images containing fluid-fluid levels are usually solitary abnormalities produced by aneurismal bone cysts. The fluid-fluid level is due to bleeding within the tumor followed by layering of the blood components based on density differences. Only two other cases of bone metastases with multiple fluid-fluid levels have been reported. Although fluid-fluid levels are exceedingly rare, clinicians should be aware that they might indicate a malignancy, particularly when they are multiple., (Copyright 2010. Published by Elsevier SAS.)

Objectives: To elaborate a how-to-use abatacept material intended to help physicians in the management of patients with inflammatory diseases treated with this drug in routine practice., Methods: 1) Selection of the relevant domains by a rheumatologists' panel; 2) Search for published evidence in each domain; 3) Elaboration of the clinical tool guide with a 3-level gradation of evidence (evidence-based medicine EBM, official recommendations and expert's opinion). The experts were 11 academic rheumatologists with a large experience in prescribing abatacept and in managing rheumatoid arthritis. They were all members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society dedicated to the inflammatory rheumatic diseases. Each fact sheet was reviewed by two other experts; 4) Regular updating based on medical literature and postmarketing surveillance data., Results: Four domains were considered relevant: abatacept contraindications, management of side effects or associated diseases appearing during abatacept treatment, management of "practical situations" such as surgery or pregnancy, physician and patient information. After the literature analysis and discussion during an experts' meeting, a consensus was reached on: a pre-treatment checklist aimed at searching abatacept contraindications; a what-to-do document when facing side effects or associated diseases (autoimmune pathology, bacterial or viral infections, cardiovascular diseases, intolerance to abatacept, solid or haematological malignancy) or "practical situations" (surgery, pregnancy, vaccination, travel, drug-drug interactions); an example of standard information letter to be addressed to the attending physician (rheumatologist and general practitioner); an example of standard information letter to be addressed to the patient., Conclusion: Based on both an EBM approach and an expert's opinion approach, this abatacept clinical tool guide should provide assistance to all physicians attending patients treated with abatacept. For a better implementation in clinical practice, this tool guide will be available online at www.cri-net.com and regularly updated.

Rituximab is a chimeric anti-CD20 monoclonal antibody targeting B cells, which play numerous pathogenic roles in rheumatoid arthritis (RA). This review summarises the results of three controlled studies using rituximab in RA and the data regarding tolerance and repeated treatment in 1053 patients included in the clinical studies. These studies demonstrated the efficacy of rituximab in patients with RA, including those who had been unresponsive or intolerant to one or more TNF inhibitor therapies. Rituximab was globally well-tolerated. The current informations on the efficacy and the tolerance of rituximab led us to propose recommendations for the screening of patients, the use of rituximab, and the follow-up of patients. A longer follow-up duration and data from off-trial patients, included in registries, are now required.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose main complication is accelerated atheroma responsible for high rates of cardiovascular morbidity and mortality. Hyperhomocysteinemia is among the factors incriminated in RA-associated atheroma. We managed a 46-year-old patient with RA who required admission to evaluate severe arterial and venous disease with involvement of the coronary, renal, and peripheral arteries. She had no laboratory evidence of rheumatoid vasculitis or conventional cardiovascular risk factors (diabetes and hypercholesterolemia) and had never smoked. Her serum homocysteine level was elevated to 20.9 micromol/L as a result of a homozygous C667T mutation in the methylenetetrahydrofolate (MTHFR) gene. Folate and vitamin B12 levels were normal. A circulating anticoagulant was identified. Hyperhomocysteinemia, which is defined as a homocysteine level greater than 15 micromol/L, is a risk factor for arterial and venous disease. Hyperhomocysteinemia is found in 20%-42% of patients with RA. Methotrexate therapy is the most common causative factor. Other causes include MTHFR deficiency, vitamin B12 deficiency, renal failure, old age, and smoking. Whatever the underlying cause, folic acid supplementation returns the homocysteine level to normal.

Objectives: To update French Society for Rheumatology guidelines regarding the use of TNFalpha antagonists for treating patients with rheumatoid arthritis (RA)., Methods: Existing guidelines were updated using the AGREE instrument. Items that required updating were selected by a task force, the relevant literature was critically appraised, and new wording was suggested by a limited committee of experts then validated by the task force and subsequently by a panel of external reviewers. The three-topic structure of the recommendations (indication, initiation, and adjustment) and the final algorithm format were maintained., Results: Of the 12 items, five were selected for updating; one pertained to the indication for treatment with TNFalpha antagonists, two to treatment initiation, and two to treatment adjustment. Of the four initially recommended criteria for determining that TNFalpha antagonist therapy is indicated, the first three were left unchanged (confirmed diagnosis of RA; active disease for more than 1month with objective evidence of inflammation or progressive structural damage, or dependency on glucocorticoid therapy, or progressive radiographic damage; and failure to respond adequately to methotrexate - or another agent when methotrexate is contraindicated - in the optimal tolerated dosage). The fourth and last criterion was modified as follows: co-morbidities should be evaluated in order to distinguish absolute contraindications from relative contraindications that require referral to a specialist. Of the four initial recommendations about TNFalpha antagonist initiation, the first and fourth were left unchanged (a workup should be performed prior to treatment initiation, and the patient should receive regular standardized follow-up); the second and third recommendations were modified as follows: there is no evidence that one TNFalpha antagonist is more effective than the others, and concomitant methotrexate therapy is generally advisable, regardless of the TNFalpha antagonist used. Of the four recommendations about treatment adjustment, the first two were modified as follows: the goal of treatment is to achieve the EULAR response criteria or better; and in non-responders, the dosage or dosing interval can be modified when infliximab is used, methotrexate should be added when the TNFalpha antagonist is used alone, and in all other situations the patient should be switched to a different TNFalpha antagonist. The other two recommendations about treatment adjustment were left unchanged (patients who fail to tolerate one TNFalpha antagonist can be switched to another TNFalpha antagonist if allowed by the nature of the adverse event; and when a remission is achieved, reduction or discontinuation of symptomatic drugs - most notably glucocorticoids - is appropriate, followed in the event of a prolonged remission by changes in the dosage and/or dosing interval of the TNFalpha antagonist or concomitant disease-modifying drug)., Conclusion: These recommendations are designed to help practitioners optimize the use of TNFalpha antagonists in patients with RA seen in everyday practice. They do not constitute regulations.

Objectives: The French Society of Rheumatology initiated a large national multicenter, longitudinal and prospective cohort, the so-called "ESPOIR cohort study" in order to set up databases to allow various investigations on diagnosis, prognostic markers, epidemiology, pathogenesis and medico-economic factors in the field of early arthritis and rheumatoid arthritis., Methods: Patients were recruited if they had undifferentiated arthritis or rheumatoid arthritis, of less than 6 months disease duration and if they were DMARD and steroids naïve. Patients have then to be followed every 6 months during the first 2 years then every year during at least 10 years. Clinical, biological, radiographic and medico-economic databases have been constituted to fit in the different objectives of the project and more than 20 scientific studies have already been accepted by the scientific committee., Results: 813 patients were included (76.75% were female). The mean age was 48.07+/-12.55 years. The mean delay from the onset of symptoms to referral to the rheumatologist was 74.8+/-76.6 days. Baseline swollen and tender joint counts were 7.19+/-5.37 and 8.43+/-7.01; DAS28 score was 5.11+/-1.31. CRP was abnormal in 38.9% of the patients; 44.2%, 45.8% and 38.8% had respectively IgM rheumatoid factor (RF), IgA RF and anti-CCP antibodies. HLA DRB1*01 or 04 genes were found in 56.7% of them. Finally, 22% of these patients had erosions on hand or feet at baseline.

After many barren years, conceptual advances and the introduction of new biotherapies are yielding improvements in the management of systemic lupus erythematosus (SLE). The result is a radical change in the management strategy. The main therapeutic advances rest on new discoveries (or rediscoveries), some of which are original. They can be summarized under 12 headlines. Smoking is inadvisable, as it promotes not only atheroma but also lupus flares. Hydroxychloroquine and conventional drugs (cyclophosphamide) are helpful provided they are used appropriately. Combined oral contraception and hormone replacement therapy may be less hazardous than previously thought, although caution remains in order. Drugs used in transplant recipients, such as mycophenolic acid, are generating optimism as treatments for SLE. Rituximab and new anti-B-cell drugs hold promise for the treatment of severe SLE. Efforts to develop an "etiologic" treatment for SLE based on type 1 (alpha/beta) interferon blockade still face a number of obstacles. Peptide vaccines, whose main effect is stimulation of regulator T cells, hold promise-but confirmation is needed. Whether TNF antagonists can be used in lupus with skin and joint manifestations or in SLE is generating debate. Complement blockade for treating SLE and antiphospholipid syndrome is an attractive avenue of research. Numerous new immunotherapy modalities based on modulating intracellular signaling are being evaluated. In the most severe forms of SLE, autologous peripheral stem cell transplantation deserves consideration. A key component of the treatment of SLE is control of atheroma, which is among the most severe complications. This rich harvest of new treatment possibilities can be expected to radically modify the prognosis of SLE, whose more aggressive forms remain severe.

The myositides are systemic autoimmune conditions of which the most important are polymyositis, dermatomyositis, and inclusion body myositis. In addition to the classic clinical diagnostic criteria, myositis-specific autoantibodies were identified about 15 years ago. Among the dozen or so myositis-specific autoantibodies reported to date, the most characteristic are directed against cytoplasmic antigens, such as tRNA synthetase (Jo-1 or PL-1, PL-7, PL-12, EJ, OJ, JS, and KS), signal-recognition particle (SRP), Mas, KJ, Fer (eEF1), and Wa. Antibodies to nuclear antigens include anti-Mi-2, anti-PMS (PMS1, and PMS2), and related antibodies (MLH1, DNA protein kinase catalytic subunit (DNA PKCS)...), and anti-56 kDa. Myositis-associated antibodies are not specific but may be found in patients with myositis. They are directed to nuclear or nucleolar antigens such as PM-Scl, Ku, RNP (U1-RNP and U2-RNP, U4/U6-RNP, and U5-RNP), Ro 52 kDa and, more rarely, Ro 60 kDa and La. Myositis-specific antibodies have proved useful on two fronts. They have improved the diagnosis of myositis by leading to the identification of characteristic clinical patterns, such as anti-synthetase syndrome. The place of autoantibodies alongside classic clinical and laboratory criteria remains to be determined, however. First, standardized assays will have to be developed to replace current detection methods, which use widely variable techniques and antigen preparations. Myositis-specific antibodies have also shed light on the pathogenesis of myositis. For instance, the development of antibodies to tRNA synthetases constitutes an original autoimmunity model that shows how muscle damage, probably of a nonspecific nature, can lead to the production of autoantibodies that perpetuate and aggravate the muscle lesions.

Objective: To develop clinical practice guidelines for the evaluation and management of cardiovascular risk in patients with rheumatoid arthritis (RA), using the evidence-based approach and expert opinion., Methods: Recommendations were developed using the evidence-based approach and expert opinion: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; Evidence providing answers to the five questions was sought in the literature; Based on this evidence, recommendations were developed by a panel of experts., Results: The recommendations were as follows: 1) In patients with RA, attention should be given to the risk of cardiovascular disease, which is responsible for an excess burden of morbidity and mortality; 2) It must be recognized that RA may be an independent cardiovascular risk factor. Persistent inflammation is an additional risk factor; 3) The cardiovascular risk should be evaluated, and modifiable risk factors should be corrected; 4) In patients with RA requiring glucocorticoid therapy, the need for cardiovascular risk minimization is among the reasons that mandate the use of the minimal effective dose; 5) It should be recognized that methotrexate may protect against cardiovascular mortality in patients with RA; 6) It should be recognized that TNFalpha antagonists remain contraindicated in patients with RA and severe heart failure. TNFalpha antagonists do not seem to worsen moderate heart failure and may protect against cardiovascular mortality; 7) AFSSAPS recommendations about LDL-cholesterol objectives should be followed, with active RA being counted as a cardiovascular risk factor; 8) In patients with RA, statin therapy should be considered only when cholesterol levels are elevated despite appropriate dietary treatment; 9) RA per se does not indicate aspirin for primary prevention. When aspirin is used for secondary prevention, it should be recognized that concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the antiplatelet effects and increase the gastrointestinal side effects of aspirin therapy.

Objectives: To develop recommendations for TNFalpha-antagonist therapy in patients with rheumatoid arthritis (RA) seen in everyday practice, under the aegis of the French Society for Rheumatology., Method: We used the methods recommended by the French Agency for Healthcare Accreditation and Evaluation, the AGREE collaboration, and the European League against Rheumatism (EULAR). The recommendations focus on patient selection, monitoring, and treatment adjustments., Results: Criteria for selecting patients eligible for TNFalpha-antagonist treatment of RA include: 1) a definitive diagnosis of RA; 2) disease activity for longer than 1 month, including presence of objective signs of inflammation; or radiographic progression; 3) previous failure of methotrexate in the highest tolerated dosage or of another disease-modifying antirheumatic drug in patients with contraindications to methotrexate; 4) absence of contraindications to TNFalpha-antagonist therapy. When starting TNFalpha-antagonist therapy 1) a thorough baseline evaluation should be conducted; 2) any of the three available agents can be used, as no differences in efficacy have been identified in patient populations; 3) concomitant methotrexate therapy is recommended regardless of the TNFalpha antagonist used; and 4) patients should receive standardized follow-up at regular intervals. Treatment adjustments should be based on the following: 1) the treatment objective is achievement of a EULAR response; 2) when such a response is not achieved, the dosage or dosing interval can be changed, or the patient can be switched to another TNFalpha antagonist; 3) in patients who experience intolerance to a TNFalpha antagonist, another TNFalpha antagonist may be tried, depending on the nature of the adverse event; 4) occurrence of a remission should lead to a reduction in symptomatic medications, most notably glucocorticoids where used; in the event of a prolonged remission, either the TNFalpha antagonist or the concomitant disease-modifying antirheumatic drug may be reduced., Conclusion: These recommendations are intended to help physicians use TNFalpha antagonists in their everyday practice with RA patients. They do not constitute regulations.

Objectives: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion., Methods: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified., Results: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately., Conclusion: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

Objective: To develop clinical practice guidelines for the use of nonpharmacological treatments in patients with early rheumatoid arthritis (RA), using the evidence-based approach and expert opinion., Methods: A scientific committee used a Delphi prioritization procedure to select five questions. Evidence providing answers to the five questions was sought in the literature and presented to a panel of rheumatologists. The panel developed five detailed recommendations, filling gaps in evidence with their expert opinion. The strength of each recommendation was determined., Results: Of the 565 publications retrieved by the literature review, 198 were included in the analysis. The five recommendations on nonpharmacological treatments for early RA were validated by a final vote among all participants. The recommendations are as follows: (1) physicians may decide to provide joint protection education to patients with potentially severe early RA, with the knowledge that structured joint protection programs have not been found effective; (2) physical exercise and sports can be recommended to patients with early RA; muscle strength exercises are advisable; (3) in patients with early RA, metatarsal pain and/or foot alignment abnormalities should be looked for regularly, and appropriate insoles should be prescribed if needed; (4) dietary measures and nutritional supplements are not indicated as part of the treatment of early RA; (5) elimination diets, particularly those with low intakes of dairy products, should be discouraged in patients with early RA., Conclusion: These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

Bone and joint infections due to Streptococcus pneumoniae are uncommon in adults in the absence of risk factors (e.g. alcohol abuse, immunodepression, or preexisting joint disease). We report two cases in previously healthy adults. The clinical picture was septic arthritis of the knee in one patient and discitis with an extensive epidural abscess in the other. The characteristics of S. pneumoniae bone and joint infections are reviewed, with emphasis on risk factors. The therapeutic strategy is discussed in the light of the recent upsurge in S. pneumoniae strains with reduced susceptibility to penicillin.

Primary immune deficiencies (PIDs) are characterized by functional and/or quantitative abnormalities of one or more immune system components. Several bone and joint abnormalities can occur in patients with PID, with arthritis being the most common. Joint manifestations, of which arthritis is the most common, occur chiefly in humoral PIDs (agammaglobulinemia, common variable immunodeficiency, hyper-IgM syndromes, and IgA deficiency) and occasionally in other PIDs (chronic granulomatous disease and Wiskott-Aldrich syndrome). Monoarthritis or oligoarthritis is the usual pattern, although polyarthritis may occur, occasionally with nodules suggesting rheumatoid arthritis. Arthritis in patients with PID is usually infectious in nature, the most common causative organism being Mycoplasma, followed by Staphylococcus, Streptococcus, and Haemophilus. These bacteria can induce not only synovial infections, but also aseptic arthritogenic inflammatory responses. Arthritis having no demonstrable relation to chronic infection has been reported also and ascribed to dysimmunity-driven mechanisms that exhibit a number of specific features. Bone lesions are far less common and usually due to infections complicating humoral PID. Distinctive bone manifestations occur in a number of rare PIDs (e.g., hyper-IgE syndrome and Di George syndrome) and in syndromes characterized by spondyloepiphyseal dysplasia. Familiarity with PID syndromes both enhances the diagnostic capabilities of physicians and provides insight into the pathophysiology of bone and joint abnormalities associated with immune dysfunction. In children and occasionally in adults, a combination of bone and/or joint manifestations and hypogammaglobulinemia may indicate PID. When there is no evidence of lymphoproliferative disease, infection, or iatrogenic complications, investigations for PID should be obtained. PID-related arthritis is a unique model for studying the pathogenesis of presumably postinfectious arthritis and of inflammatory joint diseases including rheumatoid arthritis.

Unlabelled: When the anti-TNFalpha drugs first came onto the market, their high price was the subject of much debate. Moreover, we must add the costs associated with their administration to the purchase price. Variations in medical practices may be the source of substantial variations in these costs., Objective: To compare the costs involved with the use of infliximab and etanercept in the treatment of rheumatoid arthritis (RA) and to study the impact of variations in medical practices on them., Methods: A pragmatic cost minimization analysis was conducted from the payer's perspective to compare the costs of administration, that is, the direct medical costs, of the first two available anti-TNFalpha agents: infliximab and etanercept. Records of 60 patients from three university hospital rheumatology departments were reviewed retrospectively for a 52-week period. This analysis considered the following costs: purchase costs for the drugs and for any co-prescribed disease-modifying drugs, inpatient or outpatient administration, medical follow-up and the transportation costs associated with treatment that were reimbursed by the French health insurance system. Costs that did not differ between the two products were excluded (work-up for inclusion, etc.)., Results: Data were collected for 58 patients, 30 treated with infliximab and 28 with etanercept. Patients' mean age was 52 years; 81% were women. RA had first developed on average 15 years earlier; the disease was positive for rheumatoid factors in 68% of cases and erosive in 93%. The total average annual cost of administration did not differ for infliximab and etanercept: 19,469 and 19,619 , respectively (P=0.56). The mean costs of administration nonetheless varied considerably between the three hospital centers: from 16,566 to 24,313 for infliximab (P<0.0001) and from 16,069 to 24,383 for etanercept (P<0.0001)., Conclusion: The financial burden of biological treatments for RA is strongly influenced by the substantial heterogeneity in medical practices.