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Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to alleviate pain and inflammation in conditions like arthritis, migraines, and post-operative recovery. Their mechanism involves inhibiting prostaglandins that contribute to inflammation. NSAIDs are categorized based on their structure, selectivity for COX-1 and COX-2 enzymes, and plasma half-life. They are effective in treating osteoarthritis, spondyloarthritis, and rheumatoid arthritis but might carry an elevated risk of adverse events. Despite their effectiveness, NSAIDs have limitations and risks that warrant cautious consideration. Extensive research has investigated their side effects, and this review aims to examine the current limitations of oral NSAID therapy, including safety profiles, specific scenarios where their use may not be appropriate, and gaps in knowledge. By critically evaluating these aspects, healthcare practitioners can make informed decisions about prescribing NSAIDs, optimizing patient outcomes while minimizing potential risks. This narrative review summarizes existing knowledge and underscores the importance of risk-benefit assessments in NSAID prescribing. Ultimately, the goal is to enhance the rational use of NSAIDs, maximizing benefits while mitigating adverse effects., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients., Methods: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant., Results: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495)., Conclusion: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Background: Anti-Jo-1 autoantibodies represent essential markers in the diagnosis of antisynthetase syndrome (ASS). In this retrospective study, we aimed to investigate whether their concentrations and fluctuations could both respectively reflect the severity and evolution of ASS., Methods: Between 2015 and 2020, clinical and biological features of ASS patients with at least one positive measure of anti-Jo-1 autoantibody were collected. At each serum sampling, we assessed myositis activity by using the Myositis Intention to Treat Activities Index (MITAX) and compared anti-Jo-1 concentrations with ASS severity, anti-Jo-1 concentrations between patients with and without active disease, and changes in anti-Jo-1 concentrations with disease activity., Results: Forty-eight patients with ASS had at least one positive determination of anti-Jo-1 concentration. Among them, twenty-nine patients had at least two determinations of anti-Jo-1 autoantibody in their follow-up. We showed that these autoantibody concentrations were significantly correlated with MITAX (r = 0.4, p = 0.03) and creatine kinase concentration (r = 0.34, p = 0.002) and that they were significantly higher in patients with active disease than in those with inactive disease (91.7 IU/L vs 44.4 IU/L, p = 0.016). During follow-up, we found a significant correlation between fluctuations of anti-Jo-1 autoantibody concentrations and MITAX score (r = 0.7, p < 0.0001)., Conclusion: Our results suggest that anti-Jo-1 autoantibody concentration could be a predictive marker of the severity and evolution of ASS and show that their quantification could represent a precious tool for disease monitoring and for improving the therapeutic management of ASS patients., (© 2023. The Author(s).)

Objective: The prevalence of the musculoskeletal immune-related adverse events (irAEs) is probably underestimated, as most studies report only severe side effects. Our aim was to describe and characterize all musculoskeletal irAEs in a large cohort of patients treated with immune checkpoint inhibitors (ICI)., Methods: We conducted a retrospective study among patients who received ICI from 07/27/2014 to 05/08/2020 at the medical oncology department of the Institut Paoli-Calmettes, Marseille, France. All medical files were systemically reviewed by a rheumatologist who collected clinical features, time of occurrence, treatment regimen, irAEs management, course and outcomes. We also assessed tumor response 3 months after introduction of ICI, according to severity and treatments used to manage musculoskeletal irAEs., Results: Among 927 patients treated with ICI for a solid tumor, 118 patients (12.7%) presented a musculoskeletal irAE. Their median age was 66.5, 61% were male, and they mainly had a lung (57.6%) or urological cancer (27.1%). The most frequently involved ICI was an anti PD-1. Arthralgias and myalgias were the most frequent musculoskeletal irAEs (9.8%) and inflammatory rheumatic features were reported in 36 patients (3.9%) with elevated acute phase reactants and negative immunological markers. The median time of onset was 2 months (IC 95% 1.8; 2.7). Tumor response at 3 months did not differ according to musculoskeletal irAE severity, type of manifestation (arthralgias/myalgias versus inflammatory rheumatic features), pain patterns (mechanical versus inflammatory) or irAE treatments., Conclusion: Musculoskeletal irAEs in this large cohort of patients treated with ICI were frequent (12.7%), mostly mild and well tolerated., (Copyright © 2022 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs., Methods: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO., Results: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events., Conclusions: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs., Competing Interests: Declaration of Competing Interest L Guillo declares consulting fees for Abbvie. J Avouac has received consultancy relationship and/or received honoraria and/or participated to advisory boards from Galapagos, Lilly, Pfizer, Abbvie, Bristol-Myers Squibb, Sanofi, Roche-Chugai, Nordic Pharma, Medac, Novartis, Biogen, Fresenius Kabi, Janssen, and MSD. M Nachury received board membership, consultancy, or lecture fees from Abbvie, Adacyte, Amgen, Arena, Biogen, CTMA, Celltrion, Ferring, Fresenius-Kabi, Janssen, Mayoli-Spindler, MSD, Pfizer, Takeda. G Bouguen has served as a speaker, consultant or advisory board member abbvie, takeda, fresinus Kabin, Janssen, Vifor pharma, Sandoz, MSD, Biogen, TIllots, FErring, Amgen, Mylan. A Buisson declares consulting fees for Abbvie, Amgen, Arena, Biogen, CTMA, Janssen, MSD, Pfizer, Roche, Takeda and Tillots. Lecture fees for Abbvie, Amgen, Biogen, Janssen, Mayoly-Spindler, MSD, Norgine Pfizer, Roche, Takeda and Tillots. L Caillo declares lecture and consulting fees for Abbvie, Pfizer, Ferring, Janssen, Amgen, Biogen, Takeda and Tillotts. M Fumery has served as a speaker, consultant, advisory board member for Abbvie, Takeda, MSD, Pfizer, Janssen, Biogen, Amgen, Sandoz, Ferring, Tillots, Gilead, Galapagos, Boehringer, Celgene and Celltrion. X Hebuterne Hébuterne has served as a speaker, consultant and advisory board member for Abbvie, Abivax, Alphasigma, Amgen, Arena, Cellgen, Gilead, Eli Lilly, Ferring, Fresenius-Kabi, InDex Pharmaceuticals, Janssen, MSD, Mylan, Nestlé Health Science, Nutricia, Pfizer, Roche, Sanofi-Advantis, SAlix, Sangamo, Takeda, Theravance, Tillots. D Laharie declares counseling, boards, transports or fees from Abbvie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, Tillots. E Mahé has paid activities as a consultant, advisor, or speaker for AbbVie, Amgen, Janssen Cilag, Celgene, Leo Pharma, Lilly, Novartis, and Sanofi. H Marotte has served as a speaker, consultant, advisory board member for Abbvie, Amgen, Biogen, BMS, Celgene, Fresenius-Kabi, Janssen, Lilly, Pfizer, MSD, Nordic, Novartis, Pfizer, Sandoz, Sanofi, and UCB. S Nancey declares lecture and consulting fees for Abbvie, Celltrion, Amgen, Biogen, Janssen, Hospira/Pfizer, MSD, HAC, Fresenius, Takeda, Bristol Myers Squibb and Tillotts. S Ottaviani has received personal fees from Abbvie, Janssen, Lilly, MSD, BMS, Roche-Chugai, UCB. JH Salmon has served as a speaker, consultant or advisory board member for Abbvie, BMS, Galapagos, Lilly, Janssen, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sanofi and UCB. M Serrero declares lecture and consulting fees for Abbvie, Celltrion, Ferring, Janssen, MSD, Takeda and Tillotts. M Uzzan has received personal fees from Janssen and Abbvie. M Viguier has served as a speaker, consultant and advisory board member for Abbvie, Janssen, Boerhinger-Ingelheim, Lilly, Novartis, Medac, Leo Pharma, Almirall and UCB. C Richez has served as a speaker, consultant, advisory board member for Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, GSK, Lilly, Pfizer, MSD, Pfizer, Sandoz, Sanofi, and UCB. L Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance. P Seksik has received personal fees from Takeda, Merck MSD, Biocodex, Ferring, Mayoly Spindler, Astellas, Amgen, Pfizer, Pilege and Abbvie but has no conflict of interest linked to this work. T Pham reports speaker and consulting fees from Abbvie, Amgen, Biogen, BMS, Celgene, Fresenius-Kabi, Janssen, Lilly, MSD, Nordic, Novartis, Pfizer, Sandoz, Sanofi and UCB. The remaining authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Despite introduction of biological disease modifying anti-rheumatic drugs (DMARDs) for Rheumatoid arthritis (RA) treatment, therapeutic strategies do not always lead to disease control and remission. Hence, a more efficient patient stratification and monitoring biomarkers and tools are needed to enable a more personalized medicine. We used a whole blood based functional flow cytometry assay to characterize immune cells from RA patients (treated or not), healthy donors and psoriatic arthritis (PsA) patients according to their responses to LPS and/or anti-TNFα (infliximab, IFX). Activation marker expression was measured using a 10-color flow cytometry panel following a no-wash protocol. Naïve-to-treatment RA patients had a stronger inflammatory profile in comparison to healthy donors at basal level. Higher expression of activation markers (CD69 and/or CD11b) on NK, B cells and granulocytes and lower expression of the adhesion molecule CD62L were measured on monocytes, granulocytes and B cells. After LPS, naïve RA patients' cells were less capable of regulating CD69, CD11b, CD16 or CD62L showing impaired activation capabilities. Upon LPS and IFX co-incubation, hierarchical clustering analysis showed different profiles between cohorts. We believe that this whole blood-based approach should further be assessed for RA patient characterization as it provides new perspectives for stratification and/or monitoring., (© 2022. The Author(s).)

Background: Anterior uveitis (AU) is the most frequent extra-articular feature of axial spondyloarthritis (axSpA). We aimed to assess and compare the incidence of AU in axSpA patients treated with anti-TNF or anti-IL17A., Methods: We systematically reviewed PubMed, EMBase, and Cochrane from inception to May 3, 2020, and searched for placebo-controlled and head-to-head randomized controlled trials (RCTs) assessing anti-TNF monoclonal antibodies (mAb) or soluble receptor fusion protein or anti-IL17A in patients with axSpA according to ASAS criteria and reporting safety data on AU. Data were extracted following a predefined protocol. We did pairwise and network meta-analyses for the primary outcome of AU flares (relapse or de novo) incidence and estimated summary odds ratios (ORs). We assessed the quality of evidence using the Cochrane risk-of-bias 2.0 tool. We ranked treatments according to their effectiveness in preventing AU flare using the P-score., Results: We identified 752 citations and included 33 RCTs, comprising 4544 treated patients (anti-TNF mAb 2101, etanercept [ETN] 699, anti-IL17A 1744) and 2497 placebo-receiving patients. Incidence of uveitis was lower with anti-TNF mAb versus placebo (OR = 0.46; CI 95% [0.24; 0.90]) and versus anti-IL17A (OR = 0.34; CI 95% [0.12; 0.92]. According to the P-score, the ranking from the most to the least preventive treatment of uveitis flare was as follows: anti-TNF mAb, ETN, placebo, and anti-IL17A., Conclusion: In RCTs assessing anti-TNF and anti-IL17A in axSpA, incident uveitis are rare events. However, this network meta-analysis demonstrates that anti-TNF mAb are associated with a lower incidence of uveitis compared to placebo and anti-IL17A., (© 2021. The Author(s).)

Objectives: Rheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36-50cit, α171-185cit, α501-515cit, α621-635cit, and β60-74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides., Methods: 184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA., Results: Anti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 - 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 - 7.16], p= 0.044)., Conclusion: Immune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Larid, Pancarte, Offer, Clavel, Martin, Pradel, Auger, Lafforgue, Roudier, Serre and Balandraud.)

Objectives: To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA., Methods: In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected., Results: A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts., Conclusion: In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The presence of autoantibodies to citrullinated proteins (ACPAs) often precedes the development of rheumatoid arthritis (RA). Citrullines are arginine residues that have been modified by peptidylarginine deiminases (PADs). PAD4 is the target of autoantibodies in RA. ACPAs could arise because PAD4 is recognized by T cells, which facilitate the production of autoantibodies to proteins bound by PAD4. We previously found evidence for this hapten-carrier model in mice. This study was undertaken to investigate whether there is evidence for this model in humans., Methods: We analyzed antibody response to PAD4 and T cell proliferation in response to PAD4 in 41 RA patients and 36 controls. We tested binding of 65 PAD4 peptides to 5 HLA-DR alleles (DRB1*04:01, *04:02, *04:04, *01:01, and *07:01) and selected 11 PAD4 peptides for proliferation studies using samples from 22 RA patients and 27 controls. Peripheral blood lymphocytes from an additional 10 RA patients and 7 healthy controls were analyzed by flow cytometry for CD3, CD4, CD154, and tumor necrosis factor expression after PAD4 stimulation., Results: Only patients with RA had both antibodies and T cell responses to PAD4. T cell response to peptide 8, a PAD4 peptide, was associated with RA (P = 0.02), anti-PAD4 antibodies (P = 0.057), and the shared epitope (P = 0.05)., Conclusion: ACPA immunity is associated with antibodies to PAD4 and T cell responses to PAD4 and PAD4 peptides. These findings are consistent with a hapten-carrier model in which PAD4 is the carrier and citrullinated proteins are the haptens., (© 2019 INSERM. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Background: There is very little epidemiologic data available in the literature concerning long-term corticosteroid prescriptions in France., Methods: The information was collected from a national public health-insurance database in our geographic area of Provence-Alpes-Côte-d'Azur and Corsica. We included in the analysis, patients using a daily glucocorticoid above 7,5 milligrams for a period exceeding 90 days., Results: Among the patients, 4,1 million were included in the analysis. The prevalence of glucocorticoids was around 0.8% and the incidence was 2.3/1000 inhabitants/year. The mean age of the patients was 57.6±18.8 years old. The median prednisone-equivalent dose was 11.9mg/day (Interquartile range: 8.6-20.0). The average treatment duration was 206 days (CI 95% 202-210). Most prescriptions (72,0%) were started by general practitioners., Conclusion: Long-term corticosteroid therapy is frequent in France. Its description is close to what is already known in Europe., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Recent reports described possible mechanical factors in the development and aggravation of osteonecrosis of the femoral head (OFH), but these have yet to be confirmed on dedicated mechanical study. We therefore developed a 3D finite element model based on in-vivo data from patients with incipient OFH, with a view to determining whether the necrosis area was superimposed on the maximal stress area on the femoral head., Hypothesis: The location of the necrosis area is determined by stress on the femoral head., Material and Method: All patients from the rheumatology department with early stage OFH in our center were investigated. Analysis of CT scans showed stress distribution on the head by 3D finite elements models, enabling determination of necrosis volume within the maximal stress area and of the percentage intersection of necrosis within the stress area (%I n/s: necrosis volume in stress area divided by total stress area volume and multiplied by 100) and of stress within the necrosis area (%I s/n: stress volume in necrosis area divided by total necrosis area volume and multiplied by 100)., Results: Nineteen of the 161 patients assessed retrospectively for the period between 2006 and 2015 had incipient unilateral OFH, 10 of whom (4 right, 6 left) had CT scans of sufficient quality for inclusion. Mean age was 52 years (range, 37-81 years). Mean maximal stress was 1.63MPa, mean maximal exported stress volume was 2,236.9 mm 3 and mean necrosis volume 6,291.1 mm 3 . Mean %I n/s was 83% and mean %I s/n 35%, with no significant differences according to gender, age, side or stress volume. There was a strong inverse correlation between necrosis volume and %I s/n (R 2 =-0.92) and a strong direct correlation between exported stress volume and %I s/n (R 2 =0.55). %I s/n was greater in small necrosis (<7,000mm 3 )., Conclusion: OFH seems to develop within the maximal stress area on the femoral head. The present results need confirmation by larger-scale studies. We consider it essential to take account of these mechanical parameters to reduce failure rates in conservative treatment of OFH., Level of Evidence: IV., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: Enthesitis is the spondyloarthritis (SpA) landmark, but can also be seen after entheses overuse, such as during intensive sport., Methods: We aimed to compare entheses ultrasound (US) findings in a prospective cross-sectional study of 30 axial SpA cases, 30 athletes, and 29 controls., Results: Mean (SD) MAdrid Sonographic Enthesis Index (MASEI) score was 26.3 (13), 12.2 (7), and 10.4 (6) in patients with SpA, athletes, and non-athlete control groups, respectively (p < 0.0001)., Conclusion: The MASEI score was significantly higher in patients with SpA compared with healthy controls, athletes, and non-athletes, and can be of value to distinguish SpA from healthy subjects, whatever their physical activity.

Objective: To investigate the frequency and risk factors of postoperative complications in RA patients treated with abatacept (ABA)., Methods: The Orencia RA registry recruited 1012 patients receiving ABA for RA in routine care. Data from patients treated with ABA who underwent surgery were reviewed to describe the frequency of postoperative complications. Characteristics of patients and surgeries with and without complications were compared to identify factors associated with complications., Results: We identified 205 (20.3%) patients who underwent 263 surgeries, including 176 (66.9%) orthopaedic surgeries. Nineteen (7.2%) surgeries, in 19 patients (9.3%), entailed complications, including 7 delayed wound healing (2.7% of surgeries) and 6 surgical site infections (2.3% of surgeries). The median time between the last infusion of ABA and surgery was 5.9 weeks (range: 0.3-12.0 weeks), with no significant difference between patients with and without complications. The median corticosteroids daily dosage was higher in the group with complications [10.0 (6.25-15.0) vs 6.0 (5.0-10.0) mg/day, P = 0.042]. In multivariate analysis, only the duration of ABA treatment was significantly associated with postoperative complications [adjusted odds ratio (aOR) = 0.94 (95% CI: 0.89, 0.99) for each month of treatment], as were orthopaedic surgeries compared with other kinds of surgery [aOR = 4.45 (95% CI: 1.01, 20.2)]., Conclusion: In RA patients treated with ABA, the rate of surgical complications was low: 7.2% and higher in case of orthopaedic procedure and a more recent initiation of ABA. The median time between surgery and the last infusion of ABA was short and did not influence the rate of postoperative complications., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Meningococcal infection is a multifaceted disease including acute polyarthritis. This presentation should be known by clinicians in order to prevent delay in treatment. We report what we believe to be the first case of an association of parvovirus B19 and meningococcal polyarthritis in a young adult., Case Presentation: A 19-year-old Caucasian woman presented to our hospital with fever, intense leg pain, and a transient rash. A physical examination showed asymmetric polyarthritis and no neurological abnormalities. A parvovirus B19 polymerase chain reaction performed using a blood sample and knee fluid aspirate came back positive, but serology was negative for immunoglobulin M and positive for immunoglobulin G. A blood culture was positive for serotype C meningococcus; a polymerase chain reaction performed for Neisseria meningitidis was positive in joint fluid but negative in blood samples (performed after antibiotic treatment had begun). Our patient was treated with ceftriaxone for 15 days, associated with analgesic therapy. Hydroxychloroquine treatment was introduced 5 months after the onset of polyarthritis because of persisting inflammatory arthralgia., Conclusions: To the best of our knowledge, this is the first case report of polyarthritis caused by concomitant meningococcal and parvovirus B19 infections. This unusual presentation of meningococcal disease may have resulted from the persistent parvovirus B19 infection. Our experience with this case illustrates the need for a systematic approach to the diagnosis of febrile acute polyarthritis. Only long-term follow-up will reveal if this infectious polyarthritis will evolve towards an autoimmune rheumatism.

Objectives: To explore the relationship between clinical findings, biologic biomarkers, conventional radiography and MRI in patients with painful hand OA., Methods: The following patient baseline data from the DORA study (evaluating anti-TNF-α agents against painful hand OA) were used: clinical assessment (pain, swelling, stiffness and function: Dreiser functional hand index [FIHOA] and Cochin hand functional scale [CHFS]); measurement of biomarkers (cartilage oligomeric matrix protein (COMP), type IIA collagen N-propeptid (PIINP), hyaluronic acid (HA), ultrasensitive C-reactive protein (usCRP), tumour necrosis factor (TNF), interleukin (IL)-6, IL-1β and urinary CTXII); radiological staging (Verbruggen, Kallman, Kellgren-Lawrence); anatomical evaluation by contrast-enhanced MRI of proximal and distal interphalangeal joints of dominant hand. Associations between clinical, biomarker and imaging findings were assessed using the Spearman correlation coefficient and test., Results: 18 patients were recruited, and 144 joints studied. A correlation was found between clinical features (pain, FIHOA, CHFS) and the Verbruggen score (respectively: p=0.05, r=0.47; p=0.05, r=0.48; p=0.05, r=0.48). Serum IL-1 level was strongly associated with loss of function (FIHOA: p=0.02, r=-0.73; CHFS: p=0.01, r=-0.76) and radiological erosions (p=0.03, r=0.7) as with urinary CTX2. A significant association was found between MRI osteophytes and usCRP (p=0.0026). MRI and radiological features were significantly correlated except for synovitis and bone marrow lesions., Conclusions: MRI synovitis was not correlated with radiological scores, clinical or biologic markers of inflammation. There was a strong correlation between other MRI features and radiological scores. Serum IL-1 level was associated with structural damage and function.

There is agreement to label as bone infarcts avascular necrosis (AVN) occurring in the metaphyses or diaphyses of long bones, the terms AVN or osteonecrosis being used at the epiphyses. One might expect bone infarction to hold no mysteries. Oddly enough, however, scientific evidence about bone infarcts is extraordinarily scant. The prevalence of bone infarcts is unknown. The main sites of involvement are the distal femur, proximal tibia, and distal tibia. In patients without sickle cell disease or Gaucher's disease, involvement of the upper limbs and lesions confined to the diaphysis are so rare as to warrant a reappraisal of the diagnosis. Although widely viewed as a generally silent event, bone infarcts causes symptoms in half the cases. Standard radiographs are normal initially then show typical high-density lesions in the center of the marrow cavity. A periosteal reaction is common and may be the first and only radiographic change. Magnetic resonance imaging consistently shows typical features and therefore, in principle, obviates the need for other investigations. Bone infarcts are multifocal in over half the cases and, when multifocal, are usually accompanied with multiple foci of epiphyseal avascular necrosis. Thus, bone infarcts, whose prognosis is good per se (with the exception of the very low risk of malignant transformation), are usually a marker for systemic avascular necrosis. Consequently, patients with bone infarcts must be investigated both for known risk factors and for other foci of avascular necrosis, which may, in contrast, have function-threatening effects., (Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Introduction: Long-term glucocorticoid therapy is the leading cause of secondary osteoporosis. The management of glucocorticoid-induced osteoporosis (GIOP) seems to be inadequate in many European countries., Objective: To evaluate the rate of screening and treatment of GIOP., Design: Information was collected from a national public health-insurance database in our geographic area of Provence-Alpes-Côte-d'Azur and in Corsica, from September 2009 through August 2011., Patients: We identified participants aged 15 years and over starting glucocorticoid therapy (≥7.5 mg of prednisone equivalent per day during at least 90 days consecutive). This cohort was compared with an age-matched and sex-matched population that did not receive glucocorticoids., Main Outcome Measures: Bone mass, prescription of bone antiresorptive medication and use of calcium and/or vitamin D treatment., Results: We identified 32 812 patients who were prescribed glucocorticoid therapy, yielding 1% prevalence. Incidence of glucocorticoid therapy was 2.8/1000 inhabitants/year. Males represented 44%, the mean age was 58 years. The median prednisone-equivalent dose was 11 mg/day (IQR 9-18 mg/day). 8% underwent bone mass measurement. Calcium and/or vitamin D, and bisphosphonates were prescribed in 18% and 12%, respectively. Results were lower for the control population: 3% underwent bone mass measurement and 3% received bisphosphonate therapy. The rates of osteodensitometry and treatments were higher in women over 55 years of age than in men and women 55 years of age and younger, and also when glucocorticoid therapy was initiated by a rheumatologist versus other physician specialty., Conclusions: The management of GIOP remains very inadequate, despite the availability of a statutory health insurance system. Targeted interventions are needed to improve the management of GIOP.

Aim: To test the efficiency of tumour necrosis factor blockers (adalimumab) in patients with painful refractory (non-responders to analgesics and non-steroidal anti-inflammatory drugs (NSAIDs)) hand osteoarthritis (OA)., Methods: We performed a randomised, double-blind, placebo-controlled, parallel group, multicentre study. Patients were randomised to: 1/1 adalimumab 40 mg for two subcutaneous injections at a 15-day interval or placebo and monitored for 6 months. The primary outcome was the percentage of patients with an improvement of more than 50% in global pain (Visual Analogue Scale) between week 0 (W0) and week 6 (W6). Secondary outcomes included the number of painful joints, swollen joints, morning stiffness duration, patient and practitioner global assessments, functional indexes for hand OA, and consumption of analgesics. Analysis on the mean primary outcome measure was done on patients who received at least one injection., Results: 99 patients were recruited and 85 patients were randomised. Among them, 37 patients in the placebo group and 41 in the adalimumab group received at least one injection and were evaluated at W6 (n=78) on the main efficacy outcome. Mean age was 62 years, 85% were women, and mean level of pain was 62 mm at W0. At W6, 35.1% in the adalimumab group versus 27.3% in the placebo group had a pain reduction ≥50% (RR 1.12 (95% CI 0.82 to 1.54; p=0.48). There were no statistical differences for all secondary end points. The rate of adverse events was similar in the two groups., Conclusions: Adalimumab was not superior to placebo to alleviate pain in patients with hand OA not responding to analgesics and NSAIDs., Trials Registration Number: NCT00597623., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Osteoarticular infection is an uncommon presentation of Q fever. Positron emission tomography (PET) scanning is a valuable tool for the diagnosis of Coxiella burnetii graft prosthesis infection and endocarditis. Our objective was to test a series of culture-negative osteoarticular samples using molecular assays for Coxiella burnetii. We tested for C. burnetii by molecular assays targeting the IS1111 and the IS30A spacer regions, using culture-negative osteoarticular samples obtained in our laboratory between January 2011 and December 2012. We examine a total of 1,410 osteoarticular samples, and we observed two cases of arthritis and subacromial bursitis caused by C. burnetii. The infections were localized using PET scanning, and the diagnosis was confirmed through serology. For one, a C. burnetii strain with a multispacer sequence type 8 genotype was isolated from synovial fluid culture. Q fever articular infections could be undiagnosed because of the long evolution of articular attack, and patients with high antibody titers against C. burnetii should be tested using PET scanning to localize the site of infection.

In Europe, autochthonous hepatitis E is caused by genotype 3 hepatitis E virus (HEV) in almost all cases. A total of 15 infections with genotype 4 HEV were diagnosed in France from May 2009 to April 2012, and all but one of the HEV-4 strains implicated in these infections were genetically related and highly similar to HEV-4 sequences isolated from swine in Belgium. In addition, 5 autochthonous HEV-4 infections have been described in the region of Lazio, Italy, during March and April 2011, and these HEV sequences were 100% identical to one another but showed relatively low similarity (74-85%) to HEV-4 RNA samples collected in France. We report 6 additional HEV-4 infections that were diagnosed from May to July 2012 which represented 50% of the HEV infections diagnosed during this period in our clinical microbiology laboratory. Five of these HEV-4 strains were associated with autochthonous infections and were clustered together and with the majority of HEV-4 previously described in France, whereas the sixth strain was genetically divergent. Taken together with reports from other teams, these observations indicate that autochthonous infections with HEV-4 are emerging in Europe and have been transmitted by at least two distinct sources., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To evaluate the efficacy and safety of rituximab (RTX) in several subsets of spondyloarthritis (SpA) using the data of the AIR (Autoimmunity and Rituximab) registry., Methods: All patients receiving RTX for SpA, and prospectively included in the AIR registry from September 2005 to September 2010, were retrospectively analyzed. The response to treatment was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index for axial disease, joint count for peripheral disease, and C-reactive protein reduction., Results: Among the 595 patients included in the AIR registry, 26 patients with SpA from 13 centers were reported: ankylosing spondylitis (10), undifferentiated SpA (7), and psoriatic arthritis (9). Mean disease duration was 8.8 years (range 1-40). The extraarticular features found were psoriasis, 12 cases; uveitis, 4 cases; and Crohn's disease, 3 cases. The mean number of disease-modifying antirheumatic drugs before RTX was 2.4; previous anti-tumor necrosis factor (TNF) agents were taken in 23 cases. The mean number of RTX courses was 1.5 (range 1-5), with a total of 35.6 patient-years. Efficacy was noted in 11/23 cases: 3 out of 3 anti-TNF-naive patients and 8 out of 20 anti-TNF nonresponder patients. No predictive factors of response could be identified, particularly in diagnosis subsets or clinical presentation (axial or peripheral)., Conclusion: In this nationwide study of several subsets of SpA, RTX had only a moderate efficacy that was more marked in patients who were anti-TNF-naive.

The monitoring of immunosuppressive therapy may involve the cardiologist in various settings. TNF inhibitors are contra-indicated in patients with NYHA III-IV cardiac failure. This contra-indication is not absolute for etanercept. In patients with milder forms of cardiac failure, TNF inhibitors can be prescribed in the absence of alternative therapy. A cardiac follow-up is necessary in this situation. Cyclosporine and tacrolimus are both nephrotoxic and hypertensive drugs. For the treatment of arterial hypertension induced by the immunosuppressive therapy, first-line recommended drugs are calcium-blockers and renin-angiotensin inhibitors. Other antihypertensive classes may also be used in these patients. Calcium-blockers may cause frequent oedema and plasma calcineurin-inhibitor concentration elevations. Moreover, cyclosporine+calcium-blocker association may induce gingival hypertrophy and gynecomastia., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objectives: To correlate magnetic resonance imaging (MRI) aspects of the femoral head with histological findings in advanced hip osteoarthritis (OA), with special emphasis on bone marrow edema (BME)., Methods: MRI was performed in patients with advanced hip OA scheduled for hip arthroplasty. Coronal T1-, fat-suppressed T2-, T1 with gadolinium intravenous injection sequences were obtained on a 1.5 T MR-scanner within 1 month before surgery. Coronal MR images corresponding to the ligamentum teres plane were analyzed by two independent readers blinded to histological data. Normal bone marrow, subchondral cyst, subchondral fracture, edema-like, necrosis-like, and necrosis MR patterns were reported on a synthesis scheme. After surgery, the femoral heads specimens were cut through the ligamentum teres plane and histologically analyzed for correlations., Results: Twenty-three femoral heads were analyzed (female 56.5%, mean age 64.5 years). Edema-like MR pattern was correlated with histological (H) edema (Kappa (K): 0.77). Necrosis-like MR pattern was correlated with H fibrosis (K: 0.49) and with H necrosis (K: 0.24). Cyst MR pattern was correlated with H bone cysts (K: 0.58). Necrosis MR pattern corresponded to a mixture of histological lesions. Sensitivity and specificity of MRI varied from 26% to 80% and from 86% to 95% respectively., Conclusion: In advanced hip OA, the so-called "BME" MR lesion corresponds to a combination of edema, fibrosis, and necrosis at histopathology. When the classical "BME" is more specifically separated into edema-like and necrosis-like MR patterns, MR Imaging and histological findings show substantial agreement, with edema-like MR pattern mainly corresponding to histological edema., (Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

We describe a recent case of presumed redback spider (Latrodectus hasselti) envenomation observed near Noumea in New Caledonia. This is the first local reported case in this archipelago, where L. hasselti is currently considered a native species. We highlight the challenge of providing appropriate analgesia in this situation and believe that the use of specific redback spider antivenom should be considered in New Caledonia.

Mixed warm and cold autoimmune anaemia is a rare haemolytic anaemia that is commonly associated with lymphoproliferative disorders and autoimmune diseases. Although steroid therapy is the first-line treatment, rituximab represents a good alternative. The present study reports on a successful treatment with rituximab in a young woman suffering from a mixed warm and cold autoimmune haemolytic anaemia associated with a mixed connective tissue disease.

Objective: To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV)., Methods: 1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids., Results: We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other., Conclusions: This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients.

Brucellosis is uncommon in humans and only rarely manifests as osteomyelitis. We report the case of a 57-year-old patient with chronic Brucella osteomyelitis of both humeri. The diagnosis was established upon evaluation of a spontaneous fracture of the right humerus. The organism was recovered in fluid draining to the skin from an abscess located in the bone and soft tissues.

Background: Pregnancy-related hip diseases epidemiology has been poorly evaluated. We report our experience of gestational and postpartum hip diseases and evaluate their incidence., Methods: (1) Prospective survey: all pregnant or early postpartum women suspected to have hip involvement during their follow-up in an Obstetric unit were referred to a rheumatologist. If clinically confirmed, magnetic resonance imaging (MRI) and additional investigations as needed were performed. This survey had 2 years duration. (2) Retrospective study: all cases of definite (with MRI confirmation) pregnancy-related hip disease referred to our Rheumatology unit during the past 15 years were analyzed., Results: During the 2-year prospective survey, 3 patients (4 hips) of pregnancy-related hip disease were observed over 4900 pregnancies (1 case of transient osteoporosis of the hip (TOH) and 2 cases of occult fracture of the femoral head). During the 15-year retrospective study, 12 patients (17 hips) with hip diseases during pregnancy or early postpartum were identified. There were 6 patients (9 hips) with TOH, 4 patients (6 hips) with occult fracture of the femoral head, 1 patient with osteonecrosis of the femoral head, and 1 coxitis in a patient with ankylosing spondylitis. Differentiating diagnosis between TOH and occult fractures could only be made by MRI. Five of the 6 women with TOH had osteopenia at the lumbar spine at dual energy X-ray absorptiometry (DEXA). The 4 women with occult fractures had either osteopenia or osteoporosis at the lumbar spine., Conclusion: Hip diseases are infrequent during pregnancy and early postpartum. Transient osteoporosis of the hip and occult stress fractures of the femoral head appear the main causes and those diagnoses justify evaluation for an underlying bone fragility. Osteonecrosis is very rare in this setting.

Avascular necrosis of bone (AVN) occurs as two main variants, local and systemic. Local AVN is usually caused by trauma or microtrauma; examples include primary osteonecrosis of the medial condyle, vertebral osteonecrosis, necrosis after meniscectomy, and osteonecrosis of the mandible or small bones. Systemic AVN manifests as epiphyseal necrosis or bone infarction, which is often multifocal. Little is known about the factors that trigger AVN. One possible mechanism is intraluminal obliteration of blood vessels by microscopic fat emboli, sickle cells, nitrogen bubbles (caisson disease), or focal clotting due to procoagulant abnormalities. Extraluminal obliteration may result from elevated marrow pressure or increased marrow fat. Cytotoxicity and genetic factors may be involved also. Many factors are probably capable of inducing AVN, and combinations of factors may be required, although the final mechanism is always critical ischemia. The natural history of AVN is better understood than the early triggering factors. AVN becomes detectable 1-6 months after exposure to an easily identifiable risk factor such as high-dose glucocorticoid therapy or femoral neck fracture. Later on, AVN is uncommon even when the patient remains exposed to the risk factor. The turning point in the natural history of AVN is subchondral plate fracture, which leads to collapse of the necrotic segment of the epiphysis, usually within the first 2 years. The risk of collapse depends chiefly on the initial size and location of the necrotic segment, which can be determined accurately by magnetic resonance imaging (MRI). This natural history has obvious clinical implications.

Introduction: The pathophysiology of intravertebral vacuum (IVV) remains unclear, although vertebral osteonecrosis is often incriminated. Gas may migrate from the disk to the vertebral body. The objective of this study was to investigate the relations between IVV and intradiscal vacuum (IDV)., Methods: We prospectively evaluated the presence of radiological findings suggestive of IVV in patients admitted to a rheumatology department for vertebral fracture, over a 6-year period. Suggestive radiological findings were defined as a radiolucent collection within a vertebral body, an increase in the anteroposterior diameter of the vertebral body, and/or evidence of horizontal dissection of a vertebral body. Patients with any of these findings underwent computed tomography; when this investigation showed IVV, the adjacent disks were examined for IDV, and when this was found a communication between the two cavities was looked for., Results: Of 278 patients admitted for vertebral fracture during the study period, 15 had IVV. IDV adjacent to the fractured endplate was visible in 13 of these 15 patients. All 15 patients had severe fractures (Genant semi-quantitative classification, grade 3 in 10 patients and grade 2 in five patients). A communication between the intradiscal and intravertebral collections was seen in five patients. Only two patients had evidence of IVV on plain radiographs., Conclusion: Our findings support migration of gas from the disk to a fracture in the adjacent vertebral body. The term "vertebral osteonecrosis" used to designate IVV may be inappropriate. IVV is rarely shown by plain radiographs, indicating a need for other morphological criteria.

Objective: To develop and to assess a simple, inexpensive method for ascertaining, without any imaging procedure, the intra-articular placement of the needle in the knee for intra-articular injections., Methods: Outpatients referred for intra-articular treatment with "dry" symptomatic knee osteoarthritis were included in this prospective study. "Dry" knee disease was defined as a knee without any clinically detectable effusion. Once intra-articular positioning of the needle considered adequate using the backflow technique, contrast solution was injected using the same needle without changing its position and immediately afterwards lateral and anterior-posterior X-rays were taken to assess the needle position., Results: Of the 32 of 33 cases with obtained backflow, the needle was correctly placed in all cases. In the remaining case, the needle was extra-articularly positioned. The concordance between the two techniques using the Cohen's Kappa was 1 [CI 95%: 0.22-1]., Conclusion: The backflow technique allows to accurate the intra-articular placement of the needle for "dry" knee joints injection. This technique can be proposed as a learning tool as well as a daily practice technique to ascertaining intra-articular knee injections without using fluoroscopy with injection of contrast material. Further studies are needed to assess the technique for other joint injections.

Objective: To conduct a practice survey of laboratory and imaging studies used by French rheumatologists to identify the cause of recent-onset arthritis., Methods: We selected a random sample of 210 rheumatologists, who were asked to recruit all patients with recent-onset arthritis (at least one joint involved, for less than one year) during a 2 week period, and to record laboratory and imaging studies performed. Results were analyzed in the overall group, in diagnostic subgroups, and in clinical presentation subgroups., Results: The 119 rheumatologists who participated recruited 104 patients. Investigations done in 50% to 75% of patients were blood cell counts; erythrocyte sedimentation rate; serum assays of C-reactive protein, rheumatoid factors, antinuclear antibodies; and hand radiographs. Investigations in 50% to 74% of patients were serum ASAT/ALAT, creatinine, and uric acid; and foot radiographs. Finally, 25% to 49% of patients were tested for proteinuria; antikeratin antibodies; hepatitis B, hepatitis C, and Lyme serologies; creatine phosphokinase; blood iron; HLA-B27; and radiographs of chest and pelvis. No differences were found between investigations in patients with suspected rheumatoid arthritis and/or undifferentiated arthritis and those in other patients. In contrast, suspected diagnoses and presence of extraarticular manifestations classically associated with specific diseases modified the selection of investigations., Conclusion: Although considerable variability occurred, our study suggests that a limited panel of laboratory and imaging studies is performed in at least 25% of patients with recent-onset arthritis, regardless of clues suggesting a specific diagnosis.

Avascular necrosis (AVN) most commonly affects the femoral head, but not exclusively. Besides post-traumatic avascular necrosis of the femoral head, other sites should also be screened, especially the other hip, the shoulders and the knees. AVN of the femoral head should systematically be considered in anyone suffering from hip pain with normal X-ray. The most useful complementary examinations are standard X-ray examination, to assess the stage of disease progression, and MRI, to establish the diagnosis when X-ray shows no abnormality and assess the prognosis. The spontaneous progression mainly depends on the lesion size and the amount of affected weight-bearing surface. Differentiating AVN from algodystrophy and especially stress fracture of the femoral head may be difficult, even with MRI. An etiology may be found in approximately &#95; of the cases. Medical treatment still exclusively addresses symptoms. Surgical treatment essentially consists of core decompression of the femoral head, the efficiency of which is still debated, and total hip arthroplasty, but new therapeutic options are likely to be developed. Above all, indications depend on the age, the stage of disease progression (prior to or following the subchondral fracture) and prognosis (lesion size and site on the MRI).

Introduction: We performed a randomized, double-blind, controlled clinical trial comparing intravenous pamidronate and placebo for pain relief in recent osteoporotic vertebral compression fractures (VCF)., Methods: Patients suffered from recent (<21 days), painful, osteoporosis-related VCF. They were randomized to receive daily intravenous infusions of either placebo or 30 mg pamidronate for three consecutive days (total pamidronate: 90 mg). The main criterion for efficacy was improvement in standing pain on a 100-mm visual analogical scale (VAS) at day 7. Secondary criteria were standing pain at days 3 and 30; supine pain at days 3, 7, and 30; patients' overall assessment of improvement; mobility index; and number of "20% responders" and "50% responders" (respectively, 20% and 50% improvement in standing pain at days 7 and 30). Statistical analysis with non-parametric tests was carried out on an intention to treat basis., Results: Thirty-two patients were enrolled in the study; 16 were given placebo and 16 pamidronate. Thirty-one patients were evaluated at day 7 and 26 patients at day 30. VAS pain decreased significantly in both groups at day 7 (placebo -23 mm, pamidronate -42 mm, p<0.01). The difference in pain scores between groups was -23.25 mm (confidence interval (CI) [-42.3; -4.2], p=0.018) at day 7 and -26 mm at day 30 (p=0.03), in favor of pamidronate. At day 7, there were 4 versus 12 "50% responders," respectively, in the placebo and in the pamidronate groups (likelihood ratio: 8.372; p=0.004) and 9 versus 14 "20% responders" (likelihood ratio: 4.038; p=0.044). At day 30, there were 5 versus 10 "50% responders," respectively, in the placebo and in the pamidronate groups, and 7 versus 11 "20% responders." Patients' overall assessment of improvement at day 7 was 37+/-26 mm in the placebo group and 59+/-30 mm in the pamidronate group (p=0.019), and 42+/-26 mm and 72+/-21 mm at day 30 (p=0.07). The two groups did not differ significantly at days 7 and 30 for supine pain, Schober index, or finger-ground distance. No significant adverse reaction related to treatment occurred., Conclusion: Pamidronate provides rapid and sustained pain relief in patients with acute painful osteoporotic VCF and is well tolerated. Further investigations are needed to better define the place of pamidronate in the management of painful recent osteoporotic collapse.

Study Design: Retrospective observational study., Objectives: We report our experience with patients who presented with osteoporotic vertebral fractures with no visible deformation of vertebral body., Summary of Background Data: The diagnosis of osteoporotic vertebral fractures largely relies on the observation of vertebral deformations on plain radiographs, termed vertebral collapses. There are no data on the characteristics, or indeed of the reality, of osteoporotic vertebral fractures with no significant deformation of the vertebral body., Methods: We retrospectively analyzed cases that presented with acute back pain with no initial deformation of the vertebral body on plain radiographs, and later proved to be fresh osteoporotic vertebral body fractures. All cases met each of the following criteria: 1) The incriminated vertebra appeared normal on initial radiographs (Genant's Grade 0 deformation). 2) The diagnosis of fresh vertebral body fracture was confirmed by MRI. 3) The diagnosis of osteoporosis was made by the combination of established osteoporosis, ruling out of underlying disease, and follow-up., Results: We observed 21 fractures in 16 patients (11 female/5 male; mean age, 72 years). Most of these fractures affected the lumbar spine (14 of 21 occurred at L2-L5). Osteoporosis was known beforehand in 9 patients and newly diagnosed in 7 patients. At follow-up, radiographs were obtained for 19 of 21 fractures: in 15 cases, the vertebral fracture developed a vertebral collapse (Genant's Grade > or = 0.5) in a mean of 12.5 weeks (range, 4-24 weeks); in the 4 remaining cases, the vertebra remained normal. All cases had a clinically favorable outcome., Conclusion: Osteoporotic vertebral fractures with no sign of vertebral collapse on initial radiographs do indeed exist. They are analogous to occult stress fractures well known in other skeletal sites. They must not be misdiagnosed as malignant lesions.

Thromboangiitis obliterans (or Buerger disease) is a rare vascular disease that selectively affects young males who are inveterate smokers. We report a case in a young female smoker who presented with recurrent episodes of polyarthralgia and distal extremity ischemia. The initial diagnosis was connective tissue disease, and the correct diagnosis was established only 7 years after symptom onset. Joint manifestations are common in thromboangiitis obliterans and usually antedate the diagnosis, which should be considered in patients with superficial venous thrombosis, upper limb ischemia, or Raynaud's phenomenon. This is true even in females, as shown by the case described here.

Background: Methotrexate and nonsteroidal antiinflammatory drugs are frequently coadministered in the treatment of rheumatoid arthritis (RA)., Objective: To evaluate the effect of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, on methotrexate pharmacokinetics and short-term safety in patients with RA., Methods: This multicenter, randomized, double-blind, placebo-controlled crossover study enrolled 18 patients (mean age 49.1 y) with stable RA. Patients were randomized to receive methotrexate 7.5-15 mg orally once weekly plus either lumiracoxib 400 mg/day or placebo for 7 days. Patients then received the other treatment combination for an additional 7 days. Serial blood and urine were collected for 24 hours after the methotrexate dose on day 1 (methotrexate alone) and days 8 and 15 (combination treatment)., Results: Plasma methotrexate pharmacokinetics (AUC(0-t), maximum concentration [C(max)], time to C(max)) and methotrexate protein binding were similar for methotrexate alone (108.0 ng.h/mL, 26.7 ng/mL, 1.5 h, and 57.1%, respectively), methotrexate/lumiracoxib (110.2 ng.h/mL, 27.5 ng/mL, 1.0 h, and 53.7%, respectively), and methotrexate/placebo (101.8 ng.h/mL, 22.6 ng/mL, 1.0 h, and 57.0%, respectively). Similarly, no clinically significant difference was found in the urinary excretion of methotrexate. Mean exposure to the 7-OH metabolite was lower when methotrexate was given with lumiracoxib compared with placebo, shown by a reduction in AUC and C(max), although similar amounts of the metabolite were recovered in urine following both lumiracoxib and placebo. Coadministration of methotrexate and lumiracoxib was well tolerated., Conclusions: Lumiracoxib had no significant effect on the pharmacokinetics, protein binding, or urinary excretion of coadministered methotrexate in patients with RA.

Objective: To evaluate the costs of workups to diagnose early arthritis., Methods: In 2000, the French Society for Rheumatology conducted a survey of a representative sample of French and Belgian rheumatologists (n = 239). The respondents were asked to consider 2 hypothetical scenarios, 1 describing undifferentiated arthritis and the other more suggestive of rheumatoid arthritis. They were then asked what diagnostic workup they would order. Costs for each study were determined in 2001 euros, according to the French public health system fee schedules., Results: In total, 151 rheumatologists participated in the study (63%). The mean +/- SD diagnostic costs were 406.5 +/- 194.3 euro for the case with no diagnostic clues, and 280.7 +/- 154.3 euro for the case suggestive of early RA. Responses were very heterogeneous. The 2 main sources of expenditure were immunology tests and imaging. Hospital staff physicians tended to order more expensive workups, and costs tended to vary inversely with physician experience. The most important predictor of cost was diagnostic doubt, as estimated by the number of diagnoses proposed by respondents in each case; each additional diagnosis cost an additional 19.1-26.1 euro., Conclusion: Diagnostic workups after a first medical visit for early polyarthritis result in substantial direct costs. This observation and the great variability observed in physicians' practices point out the need for consensus on the appropriate workups for these patients.

Objective: The purpose was to analyze magnetic resonance imaging (MRI) abnormalities in reflex sympathetic dystrophy syndrome (RSDS) of the foot, with the goal of helping to meet the difficult diagnostic challenges raised by this condition., Methods: Retrospective study of 20 patients with RSDS of the foot, 15 at the warm phase and five at the dystrophic phase., Results: Of the 15 patients at the warm phase, seven had evidence of bone edema (low signal on T1-weighted images and high signal on T2, T2 STIR, and fat saturation images) and five had occult fractures (linear band of low signal on T1 and T2 weighted images with no enhancement after contrast injection). Other abnormalities included soft tissue changes in three patients, joint effusion in five, and synovial hypertrophy in one. Of the five patients at the dystrophic phase, one had a fracture with a joint effusion, one had isolated joint edema, and three had normal MRI findings., Conclusion: Bone marrow edema is inconsistent at the warm phase of RSDS and is never present at the dystrophic phase. Thus, absence of bone edema does not rule out RSDS. Fractures may be visible by MRI in one-third of patients with RSDS and no clinical or plain radiography evidence of fracturing.

Concepts related to the pathophysiology of reflex sympathetic dystrophy syndrome (RSDS) are changing. Although sympathetic influences are still viewed as the most likely mechanism underlying the development and/or perpetuation of RSDS, these influences are no longer ascribed to an increase in sympathetic tone. Rather, the most likely mechanism may be increased sensitivity to catecholamines due to sympathetic denervation with an increase in the number and/or sensitivity of peripheral axonal adrenoceptors. Several other pathophysiological mechanisms have been suggested, including neurogenic inflammation with the release of neuropeptides by primary nociceptive afferents and sympathetic efferents. These neuromediators, particularly substance P, calcitonin gene-related peptide, and neuropeptide Y (NPY), may play a pivotal role in the genesis of pain in RSDS. They induce an inflammatory response (cutaneous erythema and edema) and lower the pain threshold. Neurogenic inflammation at the site of the lesion with neuromediator accumulation or depletion probably contributes to the pathophysiology of RSDS. However, no single neuromediator has been proved responsible, and other hypotheses continue to arouse interest.