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Objective An annual assessment of cardiovascular (CV) risk factors in rheumatoid arthritis (RA) is recommended, but its practical modalities have not been determined. The objective was to assess the feasibility and usefulness of a standardized CV risk assessment in RA, performed by rheumatologists during outpatient clinics. Methods We used a cross-sectional design within a network of rheumatologists. Each rheumatologist included 5 consecutive unselected patients with definite RA. Data collection included standardized assessment of CV risk factors: blood pressure, interpretation of glycemia and of lipid levels, and calculation of the Framingham CV risk score. Outcome criteria included feasibility (missing data and time taken to assess the patients) and usefulness (the CV risk assessment was considered useful if at least 1 modifiable and previously unknown CV risk factor was evidenced). Results Twenty-two rheumatologists (77% in office-based practice) assessed 110 RA patients. The mean ± SD age was 57 ± 10 years, and the mean ± SD RA duration was 11 ± 9 years; 50 patients (45%) were treated with biologic agents, and 76% were women. Regarding feasibility, missing data were most frequent for glycemia (27% of patients) and cholesterolemia (14% of patients). The mean ± SD duration of the CV risk assessment was 15 ± 5 minutes. The CV risk assessment was considered useful in 33 patients (30%), evidencing dyslipidemia (15% of patients) or high blood pressure (9% of patients) as the most frequently previously unknown CV risk factor. Conclusion The assessment of CV risk factors is feasible, but labor intensive, during an outpatient rheumatology clinic. This assessment identified modifiable CV risk factors in 30% of the patients. These results suggest that RA patients are not sufficiently assessed and treated for CV risk factors. [ABSTRACT FROM AUTHOR]

Background: Despite guidelines, poor access to appropriate care for juvenile idiopathic arthritis (JIA) patients remains a global issue. Prompt referral to a pediatric rheumatology (PR) center and effective care is known to be critical for changing the natural history of the disease and improving long-term prognosis. This project assesses socio-economic factors of delayed referral to a pediatric rheumatologist (PRst) for JIA patients in France and Switzerland within the Juvenile Inflammatory Rheumatism (JIR) Cohort., Methods: All patients diagnosed with JIA, presenting at one center of the JIRcohort in France or Switzerland with additional data on referral pathway were included. Patient characteristics at first visit to the PR center, dates of visits to healthcare providers during referral, and parent characteristics were extracted from the JIRcohort database., Results: Two hundred fifty children were included. The overall median time to first PR assessment was 2.4 months [1.3; 6.9] and ranged widely across the JIA subtypes, from 1.4 months [0.6; 3.8] for children with systemic juvenile idiopathic arthritis (sJIA) to 5.3 months [2.0; 19.1] for children with enthesitis-related arthritis (ERA). A diagnosis of ERA and an appointment with an orthopedist during the referral pathway were significantly associated with a longer time before the first PR visit (hazard ratio HR 0.50 [95% CI: 0.29; 0.84]) and HR 0.68 [95% CI: 0.49; 0.93], respectively) in multivariable analysis. Having a mother with a post-graduate educational attainment level was tendentially associated with a shorter time before the first PR visit, (HR 1.32 [95% CI: 0.99; 1.78])., Conclusions: Time to first PRst visit was most often short compared to other studies and close to the British recommendations. However, this time remained too long for many patients. We observed no social inequities in access to a PRst, but we show the need to improve effective pathway and access to a PR center for JIA patients., (© 2023. The Author(s).)

Background: The treatment of children with juvenile idiopathic arthritis (JIA) to prevent disability is a major challenge in paediatric rheumatology. The presence of synovitis, which is difficult to detect in children, is associated with structural damage. Musculoskeletal ultrasonography (MSUS) can be used in patients with JIA to reveal subclinical synovitis., Objective: The primary aim was to determine whether the use of MSUS was associated with therapeutic modification in patients with JIA. The secondary aim was to identify other factors associated with therapeutic decisions., Methods: We conducted an observational study based on the JIRECHO multi-centre cohort, which was developed to provide a systematic MSUS follow-up for patients with JIA. Follow-up occurred every 6 months and included clinical and MSUS examinations. We included children who underwent MSUS of the elbows, wrists, second metacarpophalangeal joints, knees and ankles, which was performed by expert sonographers. Clinical and biological data, disease activity scores and information on therapeutics were collected., Results: A total of 185 visits concerning 112 patients were recorded. Three groups were defined according to the therapeutic decision: escalation (22%, n = 40), de-escalation (14%, n = 26) or stable (64%, n = 119). In the "therapeutic escalation" group: the presence of ultrasonographic synovitis in B-mode and the presence of grade 2 or 3 synovitis in B-mode were not significantly more frequent than in the "stable therapeutic or de-escalation" group (80% versus 65%, p = 0.06; 33% versus 19%, p = 0.06), and the patient's and physician's visual analogue scale (VAS) scores, the clinical JADAS and the C-reactive protein level were significantly higher, but only physician's VAS score remained in the model of logistic regression. In the "therapeutic de-escalation" group: there was no difference in the presence of US synovitis compared with the "stable therapeutic or escalation" group (62% versus 69%, p = 0.48)., Conclusion: Even though US synovitis tended to be more frequent in patients with therapeutic escalation, the study did not show that the presence of synovitis in MSUS was statistically associated with therapeutic modifications in patients with JIA. Treatment remained stable despite the presence of US synovitis., (© 2022. The Author(s).)

Objectives: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC)., Methods: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive., Interventions: (1) TC/T2T : visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion., Main Outcome: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed., Statistical Analysis: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC., Results: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC., Conclusion: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective., Trial Registration Number: NCT03043846., Competing Interests: Competing interests: Dr van Tubergen reports grants and personal fees from Novartis, grants from Pfizer, grants from UCB, grants from Biogen, grants from AbbVie, outside the submitted work. Dr van der Heijde reports personal fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, outside the submitted work; and Director of Imaging Rheumatology bv. Dr van Gaalen reports grants from Stichting vrienden van Sole Mio, grants from Stichting ASAS, grants and personal fees from Novartis, grants from UCB, personal fees from MSD, personal fees from AbbVie, personal fees from Bristol Myers Squibb, outside the submitted work. AB received a research grant to her department from AbbVie, consultation fees from Eli Lilly and Galapagos and a speakers fee from UCB, all paid to her department. Dr Van den Bosch reports personal fees from AbbVie, personal fees from Celgene, personal fees from Eli Lilly, personal fees from Galapagos, personal fees from Janssen, personal fees from Novartis, personal fees from Pfizer, personal fees from UCB, outside the submitted work. Dr Claudepierre reports personal fees from Roche Chugai, Novartis, Pfizer, MSD, grants from Roche Chugai, Novartis, Pfizer, UCB, MSD, AbbVie, Lilly, Celgene, Janssen, BMS, outside the submitted work. Dr Molto reports grants from UCB during the conduct of the study; personal fees from AbbVie, grants and personal fees from UCB, personal fees from BMS, grants and personal fees from Pfizer, grants and personal fees from MSD, personal fees from Novartis, personal fees from Gilead, personal fees from Lilly, outside the submitted work. Dr Gossec reports grants from Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, Galapagos, personal fees from AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, outside the submitted work. Dr Dougados reports grants from UCB, during the conduct of the study; grants and personal fees from AbbVie, grants and personal fees from Pfizer, grants and personal fees from Lilly, grants and personal fees from Novartis, grants and personal fees from Roche, grants and personal fees from BMS, grants and personal fees from Merck, outside the submitted work. Dr Dernis, Dr Ruyssen-Witrand, Dr Lenaerts, Dr Lopez-Medina, Dr Sparsa, Dr Starmans-Kool, Dr C Webers, Dr Pouplin, Dr Soubrier and Dr Joos have nothing to declare., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the reliability of the OMERACT paediatric ultrasound (US) synovitis definitions and scoring system in JIA., Methods: Thirteen sonographers analysed 75 images for the presence/absence of elementary lesions (binary scoring) and for grading synovitis, synovial hypertrophy, effusion and Doppler signals. Static US images of the second metacarpophalangeal joint (MCP-II), wrist, elbow, knee and ankle in JIA patients at different ages and different disease stages were collected with standardized scanning by two experienced sonographers. Intra- and inter-reader reliability were analysed with kappa coefficients., Results: Intra-reader reliability was good for binary scoring (Cohen's kappa 0.62, range 0.47-0.75), synovitis and synovial hypertrophy; excellent for Doppler signals (quadratic weighted kappa 0.77, 0.66-0.86; 0.76, 0.61-0.84; and 0.87, 0.77-0.94, respectively); and moderate for effusion (0.55, 0.24-0.76). Inter-reader reliability was good for synovitis and synovial hypertrophy (Light's kappa 0.68, 95% CI: 0.61, 0.75 and 0.63, 0.54-0.71, respectively), excellent for Doppler signals (0.85, 95% CI: 0.77, 0.90), and moderate for binary scoring and effusion (0.48, 95% CI: 0.36, 0.64 and 0.49, 0.40-0.60, respectively). We obtained the best scores for the knee (0.71, 0.54-0.85) except for Doppler signals, with reliability higher for MCP-II. We found a trend toward better results in older children., Conclusions: This is the first study establishing the reliability of the OMERACT paediatric US synovitis definitions and scoring system in the five most commonly affected joints in JIA. The reliability was good among a large group of sonographers. These results support the applicability of these definitions and scoring system in clinical practice and multicentre studies., (© 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.)

Objectives: Therapeutic alliance (TA) is the agreement between caregiver and patient during the care process. Therapeutic adherence is a major issue for the management of Juvenile Idiopathic Arthritis (JIA) requiring child's strong ability to follow treatments. The aim of this study was to evaluate the relationship between TA and adherence in patients with JIA., Methods: Observational, cross-sectional, multicenter study. Children, with JIA, aged 8-16, were included. Children, parents and physicians completed the Helping Alliance Questionnaire (HAQ-CP) for assessing TA. Adherence was measured using the Child/Parent Adherence Report Questionnaire (CARQ & PARQ). Demographic data, disease characteristics, current treatments and social environment were collected. The univariate relationship between TA and adherence, was studied by Pearson correlation coefficient. The multivariate analysis used a multiple linear regression model., Results: A total of 119 patients were included: 68.9% girls, mean age (SD) 12.4 (2.9) years, disease duration 73.1 (48.2) months. JIA was in remission (52%), in low activity (32%) and active (16%). TA scores were high (≥80/100) for children, parents and physicians. HAQCP was highly correlated with CARQ (r=0.31; P<0.001) PARQ (r=0.37; P<0.001). In univariate analysis, disease activity (P<0.05), place of residence (P<0.01) and family status (P<0.01) were associated with child's TA. In multivariate analysis, only the place of residence (P<0.001) and the family status (P<0.05) remained associated with TA., Conclusion: TA strongly influences therapeutic adherence and therefore may be important for treatment effectiveness., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objective: To describe the prevalence of fibromyalgia (FM) in an axial spondyloarthritis (axSpA) population and to confirm that concomitant FM had a negative impact on tumour necrosis factor blockers' (TNFb) response., Design: Prospective observational study with two visits 3 months apart., Patients: Adult patients with AxSpa initiating a TNFb., Study Groups: FM was defined by the Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained positive FiRST (both visits) and by a fulfilment of the 1990 American College of Rheumatology criteria for FM., Statistical Analysis: Prevalence of FM; evaluation of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors known to have an impact on TNFb response., Results: Among the 508 patients included in the main analysis, 192 (37.8%) were screened at baseline as FM. Percentage of success after 12 weeks of treatment was lower in the FM group for most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not FM groups according to the FiRST), except for the C reactive protein change endpoints which were not different across groups., Conclusion: This study confirms that FM coexists in patients with axSpA and that its presence seems to have a negative impact on TNFb response, which seems more related to the self-reported instruments used in its evaluation, rather than a different treatment effect of the molecule in this subgroup of patients., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The efficacy of antitumour necrosis factor alpha (anti-TNF-α) treatment is well recognised in rheumatoid arthritis (RA) but remains controversial in systemic lupus erythematosus (SLE). Therefore, the role of anti-TNF-α treatment in 'Rhupus', a disease sharing features of RA and SLE, is still debated., Objective: To evaluate the efficacy and tolerance of anti-TNF-α in patients with rhupus., Methods: Fifteen patients with rhupus with Disease Activity Score 28 (DAS 28) >3.2 despite conventional disease-modifying anti-rheumatic drugs were included in an open-label study. Patients were monitored at months (M) 3, 6, 12, 24 and 60 with SLE Disease Activity Index (SLEDAI) and DAS 28. Statistical analyses were performed using Bayesian methods and Prob >97.5% was considered significant., Results: Twelve patients were treated with etanercept for a median duration of 62.5 (range: 6-112) months and three patients by adalimumab during 36.0 (range: 4-52) months. At baseline, median DAS 28 and SLEDAI were 5.94 (4.83-8.09) and 6 (4-8), respectively. DAS 28 and SLEDAI decreased significantly after 3 months, respectively, to 3.70 (1.80-6.42) and 4 (0-6) (Prob >99.9%, for both). These changes persisted at M6, M12, M24 and M60 (Prob >99.9%, for all). Median prednisone dose decreased significantly from 15 (5-35) mg/day to 5 (0-20) mg/day after 6 months and over the follow-up (Prob >99.9%, for all). Tolerance was acceptable, with a severe infection rate of 3.0 per 100 patient-years., Conclusion: This pilot study suggests that anti-TNF-α is effective in patients with rhupus with refractive arthritis and has an acceptable safety profile., Competing Interests: Competing interests: FD reports personal fees from Gilead outside the submitted work. LS reports personal fees from AbbVie, Pfizer, Roche and Roche Chugai, outside the submitted work. LA reports consulting fees from Amgen, GSK, Lilly and AstraZeneca. TM reports personal fees from GSK and Merck, during the conduct of the study. J-EG reports research grants and consulting fees from AbbVie, BMS, MSD, UCB, Pfizer and Roche. JS reports personal fees from AbbVie, BMS, MSD, UCB, Pfizer, Roche, Novartis, GSK, Actelion, Amgen and Hospira, during the conduct of the study, and consultancies and speaking fees from AbbVie, Roche, Pfizer, Merck, UCB, Novartis, BMS and Actelion. CS reports personal fees from AbbVie and Pfizer, outside the submitted work.

Introduction: In chronic inflammatory rheumatic diseases (CIRDs), comorbidities such as cardiovascular disease and infections are sub-optimally managed. EULAR recently developed points to consider to collect and report comorbidities. The objective of this present study was to develop a pragmatic guide to collect, report and propose management recommendations for comorbidities, from a rheumatologist perspective., Methods: The collection and reporting of comorbidities and risk factors was adapted from the EULAR points to consider. To develop management recommendations, the process comprised (1) systematic literature reviews by 3 fellows and (2) a 2-day consensus process involving 110 experts (rheumatologists and health professionals). Votes of agreement (Likert 1-5 where 5 indicates full agreement) were obtained., Results: The six selected comorbidities were ischemic cardiovascular diseases, malignancies, infections, diverticulitis, osteoporosis and depression. The literature review retrieved 97 articles or websites, mostly developed for the general population. The consensus process led to reporting presence of comorbidities, current treatment, risk factors (e.g. hypertension), screening (e.g. mammography) and prevention (e.g. vaccination). Management recommendations include physical examination (e.g. blood pressure or lymph node examination), prescribing screening procedures, and interpreting results to refer in a timely manner to appropriate other health professionals. Agreement was high (mean±standard deviation, 4.37±0.33)., Conclusions: Using an evidence-based approach followed by expert consensus, this initiative furthers the dissemination in France of the EULAR points to consider, and clearly defines what part of the management of comorbidities is potentially within the remit of rheumatologists. This initiative should facilitate systematic management of patients with CIRDs., (Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: Few studies have assessed Health-Related Quality of Life (HR-QoL) in adults following juvenile idiopathic arthritis, and none since the advent of biotherapies. The aim of our study is to assess the impact of juvenile idiopathic arthritis on quality of life in a large transitional cohort, evaluate which factors influence quality of life in juvenile idiopathic arthritis, and determine which questionnaire should be used in practice., Methods: All consecutive juvenile idiopathic arthritis patients followed during adulthood in a transitional care program were included. Demographical, clinical and biological data were collected. The following quality of life questionnaires were administered: SF36 and EuroQoL. Age- and sex-matched controls (without rheumatic disease) were included., Results: One hundred and sixty-one juvenile idiopathic arthritis (120 women and 41 men) and 76 (51/25) controls were included. Out of 161, sixty-five (40%) were considered to be in remission. Juvenile idiopathic arthritis had a large impact on the physical scales of quality of life. Pain seemed to be the most important factor affecting quality of life in cases of juvenile idiopathic arthritis. No significant difference was found between sub-types of juvenile idiopathic arthritis., Conclusion: In this large transitional cohort of patients at the era of biotherapies, juvenile idiopathic arthritis has a larger effect on physical than mental scale of quality of life measures. Pain was the main factor influencing quality of life. Sub-types of juvenile idiopathic arthritis do not seem to influence quality of life., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Introduction: Tocilizumab (TCZ) is a humanized antihuman interleukin (IL)-6 receptor antibody recommended for the treatment of moderate to severe active rheumatoid arthritis, adult-onset Still disease, Castleman disease and more recently, systemic juvenile idiopathic arthritis. Like anti-TNFα, rituximab and less frequently abatacept, TCZ can induce paradoxical cutaneous eruption like psoriasis with predominantly palmoplantar presentation., Case Report: We report a 47-year-old woman with psoriastic arthritis who developed under anti-TNFα therapy and later under tocilizumab a paradoxical palmoplantar eruption., Conclusion: The specific underlying mechanisms of this side effect are unclear but relapse of these lesions seems to be observed with certain biological agents., (Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Objective: Fractal bone analysis (Hmean) is a texture parameter reflecting bone microarchitecture. The BMA device (D3A™ Medical Systems, Orléans, France) is a high-resolution X-ray device that allows assessment of bone texture analysis. We aimed to measure Hmean in rheumatoid arthritis patients at the second and third metacarpal bones, at baseline and after 1 year of follow-up, and to assess the relationship of Hmean and rheumatoid arthritis disease parameters., Methods: Patients with rheumatoid arthritis according to ACR criteria were included. They were assessed over 1 year, in the context of a prospective study conducted in Maastricht. For this substudy, activity of the disease was assessed by erythrocyte sedimentation rate, C-reactive protein and Disease Activity Score 28 performed at each visit. Radiographic bone damage was assessed using hand and feet radiographs at baseline and on a 1-year basis. The bone texture parameters were evaluated on the second and third metacarpal heads of the left hand using BMA device., Results: One hundred and sixty-five rheumatoid arthritis patients were included in this study. At baseline, Hmean was negatively correlated with age [r=-0.22 (P=0.013)] and erythrocyte sedimentation rate [r=-0.16 (P=0.039)]. No significant correlation was found between Hmean and Disease Activity Score, disease activity Visual Analog Scale, daily corticosteroid dose and C-reactive protein. There was a significant increase in Hmean of second and third metacarpal bones over 1 year (1.6% and 1.3%, P<0.01) except in patients with local second and third metacarpal bones erosion., Conclusion: The bone texture parameter Hmean is influenced by age, inflammation and local erosions in rheumatoid arthritis., (Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

The use of biological therapies for treating autoimmune diseases is increasing. These therapies are sometimes administered to pregnant women as part of a planned therapeutic regimen or to women with unexpected or unplanned pregnancies. The safety of biological therapies in this setting is a major issue. Here, we describe three young pregnant patients with autoimmune disorders: two patients with rheumatoid arthritis and one with idiopathic thrombotic thrombocytopenic purpura. These patients were exposed to rituximab (anti-CD20 monoclonal antibody) or abatacept (fusion protein CTLA4Ig) during the first trimester of their pregnancies. No significant adverse effects or complications were observed during the pregnancies, and all three patients delivered healthy newborns. In the rituximab cases, this result might be explained in part by the very low transplacental maternofetal transfer of rituximab during the first trimester of pregnancy. Despite these favorable outcomes, the use of these two biological agents must follow international recommendations. Their use is not currently allowed during pregnancy except in cases where the potential benefit to the mother justifies the potential risk to the fetus. In the case of exposure to the single agent rituximab during the first trimester, current data suggest that the low risk to the fetus may be outweighed by the potential benefit to the mother.

The type I cryoglobulins (CGs) account for 10-15% of all cryoglobulins and are found in patients with hematological disorders. We here describe the largest series of seven cases of type I cryoglobulinemia associated with multiple myeloma (MM) and provide a detailed review of the literature associated with this disorder, with the aim of improving the future diagnosis and therapeutic management of this rare disease. Six of the cases in our series were men aged 28-69 years, and most of the subject patients had an immunoglobulin G (IgG) monoclonal component and stage I indolent MM that manifested as cryoglobulin-related symptoms. The patients were all karyotypically normal. Clinical manifestations in this group were: skin lesions (five cases, 71.4%), rheumatologic failure (four cases, 57.1%), neurological abnormalities (two cases, 28.6%), mixed cutaneous/rheumatologic/renal defects (one case, 14.3%) and one case in which the cryoglobulinemia was asymptomatic. Two patients experienced acute renal failure but underwent a full recovery following treatment for MM. We conclude from our analysis that treatment approaches for severe type I cryoglobulinemia should involve plasmapheresis at the onset to achieve a rapid control of the CG-related symptoms, and that specific MM treatments should be introduced also at an early stage to avoid cryoglobulinemia relapse. In this context, bortezomib and lenalidomide are potentially the most effective therapeutic agents.

Introduction: Whipple disease is a rare infectious disease with protean clinical manifestations. This infection may mimic chronic inflammatory rheumatisms such as rheumatoid arthritis or spondylarthritis. In this context, introduction of a biotherapy after a diagnostic hesitation does not always lead to early complications. Sometimes, the clinical degradation follows an initial improvement, encouraging continuation of the immunosuppressive treatment and leading consequently to a greater diagnostic delay., Case Reports: We report two cases of Whipple disease diagnosed in the context of an inflammatory disease with anti-TNFα failure. The first patient was a 53-year-old man who presented with an axial and peripheral spondylarthritis who was treated with etanercept and adalimumab. The second was a 42-year-old man who received adalimumab and then etanercept for a peripheral spondylarthritis., Conclusion: Whipple disease should be suspected in all patients who present with a chronic inflammatory rheumatism that is partially or not controlled with anti-TNFα therapy and who had persisting elevated acute phase reactants., (Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Leflunomide can have adverse effects, but cases of subacute cutaneous lupus have more rarely been described. This drug, through its immunomodulatory effect, can favor the appearance of a Th2 lymphocyte immune response inducing lupus. A recent study has suggested that Jessner-Kanof disease (JKD) could be a dermal form of lupus. We report a case of subacute cutaneous lupus induced by leflunomide with anti-Ro/SSA Ab and unusual histological presentation, identical to that of JKD. Leflunomide can induce cutaneous lupus characterized by exclusively dermal involvement and histologically comparable to JKD. This observation therefore suggests that JKD could be a dermal variant of lupus. This prompted a revision of the classification of cutaneous lupus, which has until now been divided into acute, subacute and chronic forms but could equally be classed as epidermal, dermal and hypodermal. The last point of interest in our observation is the efficacy of a combination of chloroquine and anakinra, which led to complete remission of the articular and cutaneous symptoms after the failure of corticotherapy.

Intra-articular osteoid osteoma is rare and difficult to diagnose. We report a 38-year-old woman who presented with an inflammatory monoarticular arthritis in the right ankle in the context of a spondylarthropathy, otherwise well-controlled by leflunomide. This monoarthritis was resistant to all types of treatment. Investigations led to the diagnosis of an intra-articular osteoid osteoma. This original observation is the first description of an osteoid osteoma developing in a patient already known to have inflammatory rheumatism. All previous reported cases were monoarthritis consecutive to the osteoid osteoma itself and interpreted as incipient inflammatory rheumatism., (Copyright 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Introduction: Interleukin-32 (IL-32) is a recently described cytokine that is a strong inducer of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8. The expression of this cytokine is highly increased in the rheumatoid synovium and correlated with the severity of joint inflammation. Little is known regarding the innate immune-related regulation of IL-32 by fibroblast-like synoviocytes (FLSs). We therefore investigated the effect of innate immune stimulation by ligands of Toll-like receptor (TLR)2, TLR3, and TLR4, and cytokines such as TNF-α and interferon (IFN)-γ, on IL-32 expression by FLSs., Methods: FLSs were isolated from patients with rheumatoid arthritis (RA) according to the ACR criteria. Quantitative RT-PCR, confocal analysis, and ELISA were performed to evaluate IL-32 mRNA induction and IL-32 release by FLSs stimulated with TLR2 (BLP), TLR3 (poly I:C), and TLR4 (lipopolysaccharide) ligands, TNF-α and IFN-γ., Results: TLR2, -3, and -4 ligands as well as IFN-γ and TNF-α induced IL-32 β, γ and δ mRNA expression by RA FLSs. Mature IL-32 was expressed intracellularly and released by cells stimulated with the various activators. The IL-32α isoform was expressed intracellularly in response to TNF-α and poly I:C and not released in culture supernatants. Stimulation of FLS with TNF-α, BLP, lipopolysaccharide, or poly I:C concomitant with IFN-γ increased IL-32 expression compared with stimulation with IFN-γ alone., Conclusions: IL-32 synthesis by FLSs is tightly regulated by innate immunity in rheumatoid arthritis. Thus TNF-α, IFN-γ, double-strand RNA, hyaluronic acid, or other damage-associated molecular patterns (DAMPs), highly secreted in synovial tissues of RA patients, might trigger IL-32 secretion by FLSs. IL-32 might therefore represent a relevant therapeutic target in RA.