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Summary Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. Findings Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66–6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46–0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55–3·19, p=0·53). Interpretation Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. Funding None.

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.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 (CARQPARQ). 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.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; P0.001) PARQ (r=0.37; P0.001). In univariate analysis, disease activity (P0.05), place of residence (P0.01) and family status (P0.01) were associated with child's TA. In multivariate analysis, only the place of residence (P0.001) and the family status (P0.05) remained associated with TA.TA strongly influences therapeutic adherence and therefore may be important for treatment effectiveness.

ObjectivesThere is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.MethodsIndividuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate–severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.ResultsOf 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05–1.10), female gender (OR=0.45, 95% CI: 0.25–0.80), body mass index (OR=1.07, 95% CI: 1.02–1.12), hypertension (OR=1.86, 95% CI: 1.01–3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09–3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47–29.62) and rituximab (OR=4.21, 95% CI: 1.61–10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87–2.42) (n=175 each group).ConclusionsIn the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD.Trial registration numberClinicalTrials.gov Registry (NCT04353609).

ObjectiveTo 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.DesignProspective observational study with two visits 3 months apart.PatientsAdult patients with AxSpa initiating a TNFb.Study groupsFM 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 analysisPrevalence 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.ResultsAmong 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.ConclusionThis 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.

Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and quality of life in SSc patients receiving bosentan.ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores [Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI)], pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up.Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 (p0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 (p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 (p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 (p0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI (p = 0.04), CHFS (p = 0.04), and pain score (p = 0.046).In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability.

Objective To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc). Methods In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Results Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756). Conclusion This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs.

Background Patients treated with biologic DMARDs have to be aware of the specific adverse events and have to be able to manage their treatments in case of infectious disease. Therapeutic Patient Education aims to enable patient to acquire these safety skills. Objectives To assess the impact of Therapeutic Patient Education on safety skills and management of infectious events in patients treated with biologic DMARDs in rheumatology. Methods Bi-centric analytical study comparing safety skills and infectious events between two cohorts of patients (TPE and TPE-naive). Safety skills were assessed by an auto-assessment called “Biosecure”, rated on a scale from 0 to 100. This assessment explores several dimensions of treatment management and was validated for assessment of safety skills in patients treated with biologic DMARDs in rheumatology in a preliminary study. Infectious events and their management were self-reported by patients. A cluster analysis aimed to separate patients into working group based on their shortcomings (on the basis of their answers to the Biosecure Assessment). Results 414 patients answered the assessment. The median Biosecure Score was 70.98/100 (Q1Q3: 60.97–84.63) 47% attended Therapeutic Patient Education. The median Biosecure Score was significantly higher in the TPE group than in the TPE-naive group (74.88 versus 67.20/100; p Cluster analysis based on Biosecure assessment separated patients into 3 level groups but failed to identify specific patient profiles. Conclusions Therapeutic Patient Education could provide better safety skills and better treatment management in patients treated with biologic DMARDs in rheumatology. Prospective studies may confirm the impact of TPE on treatment management during infectious events. Further studies may assess the impact of TPE on incidence of serious infectious events. References [1] Orefice D, Beauvais C, Gossec L, Flipon E, Fautrel B, Marguerie L, et al. Cross-sectional study of self-care safety skills in 677 patients on biodrugs for inflammatory joint disease. Jt Bone Spine Rev Rhum. dec 2014;81(6):502. [2] Rat A-C, Fautrel B, Flipon E, Gossec L, Marguerie L, Nataf H, et al. Factors associated with knowledge and safety skills of arthritis patients receiving biologics: A survey of 677 patients. Joint Bone Spine. Disclosure of Interest None declared

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. journal article 2017 2017 12 29 imported

Background Coexisting fibromyalgia (FM) in axial spondyloarthritis (axSpA) can represent therapeutic challenges, particularly when evaluating the treatment effect of biologics (i.e. TNF alpha blockers (TNFb)). Indeed, since FM patients often report high levels of pain and disability there is the risk of classifying such patients as refractory to TNFb (ie, as not reaching a significant improvement in disease activity). Objectives To evaluate the impact of concomitant FM on the TNFb treatment effect in axSpA. Methods Design: Prospective observational national study with 2 visits 3 months apart (baseline and 12 weeks after TNFb initiation) (Predict-SpA study ClinicalTrials.gov: NCT03039088). Patients: axSpA patients (diagnosis according to treating rheumatologist) initiating a TNFb. Data collection: the FiRST questionnaire (Fibromyalgia Rapid Screen Test) which screens for FM, patients and disease characteristics and effectiveness measures (e.g. ASAS response components). Statistical analysis: FM positive screening was defined by a FIRST score ≥5/6; the primary efficacy outcome was the ASAS 40. Non-responder imputation and baseline observation carried forward imputation (for binary and continuous outcome variables, respectively) was performed. Impact of FM on the TNFb treatment effect was evaluated by multivariable logistic regression, with ASAS 40 as the dependent variable and FM as the independent variable; were also included in the model other factors previously reported in the literature as associated with treatment efficacy (i.e. X-ray and MRI sacroiliitis, abnormal CRP (>6mg/L), HLA B-27, smoking status, previous TNFb exposure, age Results Among the 527 patients enrolled in the study, 508 patients were analysed. Mean age was 41.4 (±11.6), 237 (46.7%) were women, with a 6.1±8.5 mean disease duration. Among them, 192 (37.8%) were screened as FM by the FiRST questionnaire. Overall efficacy of the TNFb was good (ASAS40, 201/508 (39.6%)) though 50 patients (9.8%) patients discontinued the TNFb before the follow-up visit and were considered as non-responders. Patients with FM presented less frequently an ASAS 40 response (87/192 (45.3%) vs 171/316 (54.1%), for the FM vs non-FM groups according to the FIRST definition. Presence of FM was independently associated with poorer ASAS40 response (adjusted odds ratio, OR =0.5 [95% CI 0.3 – 0.8]) while X-ray sacroiliitis (1.8 [1.2 – 2.8]), abnormal CRP (1.6 [1.0 - 2.4]) and absence of previous exposure to TNFb (1.7 [1.1 – 2.6]) were found to be associated with an ASAS40 response. Conclusions This study 1) confirms the “conventional” predisposing factors of TNFb treatment response such as X-ray sacroiliitis, abnormal CRP and absence of previous exposure to TNFb; and 2) suggests that concomitant FM influences treatment response. FM deserves to be screened in axSpA, in particular in case of a decision to initiate a TNFb therapy. References Perrot S, Bouhassira D, Fermanian J; Cercle d9Etude de la Douleur en Rhumatologie. Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain. 2010;150:250–6. Acknowledgements The PredicSpA study was supported by MSD thanks to an unrestricted grant. Disclosure of Interest None declared

Background Fibromyalgia (FM) can be a comorbid condition in axial spondyloarthritis (axSpA). FM screening questionnaires and classification criteria fulfillment may demonstrate different prevalence and patients9 characteristics may differ. Objectives To evaluate frequency of comorbid FM, and the differences between axSpA patients with/without comorbid FM according to screening (FiRST) and classification tools (ACR1990 FM criteria). Methods A multicenter national study involving 39 rheumatology centers in France included 519 patients with axSpA starting an anti-TNF treatment (PredictSpA study; ClinicalTrials.gov: NCT03039088). Patients (pts) were screened for FM with the FiRST questionnaire and classified as FM by ACR 1990 criteria. Demographic characteristics, comorbidities, axSpA characteristics, CRP and imaging were recorded in all patients. Kappa coefficient (and its 95% CI) was calculated to compare FiRST and ACR1990 criteria. Baseline characteristics associated with FM were evaluated by univariable and multivariable logistic regression (including the variables with a p value Results In the 519 pts (females: 46%, age: 42±12 years, mean BASDAI 5.7±2.0, mean ASDAS-CRP 3.3±0.9), a comorbid FM was screened in 38% and diagnosed in 16% of pts. Agreement between FiRST and ACR1990 was poor, with a Kappa coefficient of 0.2 [0.2–0.3]. In the multivariable analysis, comorbid FM (by the FiRST questionnaire) in axSpA patients was independently associated with a lower education level, more sick leave, more heel pain, more frequent second line anti-TNF. Comorbid FM defined by the ACR1990 classification criteria was independently associated with heel pain and inversely associated with B27 haplotype. (Table) Conclusions FM is frequently associated with active axSpA, with poor correlation between screening (FiRST) and diagnosis (ACR1990) test. Several characteristics are associated with comorbid FM, depending on FM classification and screening tools. References Perrot S et al. Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain. 2010;150:250–6. Acknowledgements This study was conducted thanks to an unrestricted grant from MSD. Disclosure of Interest None declared

Background Five different sub-cutaneous TNF alpha blockers (TNFb) are available for the treatment of NSAID-refractory and active axial spondyloarthritis (axSpA). The efficacy of these drugs in axSpA has been well reported in several RCT and real-life studies separately or as a group, but only very few head-to-head studies have compared each molecule9s treatment effect in axSpA. Also, some data suggest that TNFb treatment effect in patients failing to a first TNFb is poorer than in TNFb-naive patients, but some other suggest that response to a second TNFb might be comparable. Objectives to describe TNFb prescription and treatment response of each TNFb, and to compare treatment response in TNFb- naive/not naive axSpA patients in a real-life setting. Methods Prospective, multicenter, usual care study with 2 visits (baseline and 12 weeks after TNFb initiation, Predict-SpA study, ClinicalTrials.gov: NCT03039088)). Patients: axSpA patients (diagnosis according to treating rheumatologist) initiating a TNFb. Data collection: Patients and disease characteristics at baseline. Previous exposure to TNFb was collected. Disease activity and function measures were collected at both visits. The choice of the TNFb to be started during the trial was at the treating rheumatologist9s discretion. Statistical analysis: effectiveness was defined by the BASDAI50 response. Non-responder imputation and baseline observation carried forward imputation (for binary and continuous outcome variables, respectively) were performed for patients who discontinued the TNFb treatment between baseline and the follow-up visit. Results Among the 527 patients enrolled in the study, 508 patients were included in the analysis (1 patients was excluded due to missing data on all disease activity measures at baseline, and 18 patients were excluded due loss of follow-up between baseline and the follow-up visit). Mean age was 41.4 (±11.6), 237 (47%) were women, with a 6.1±8.5 mean disease duration. 377/508 (74%) were TNFb-naive while 66 (13%), 35 (7%),19 (3.7%),8 (2%) and 3 (1%) had previously received, 1,2, 3, 4 and >4 TNFb, respectively. In the whole study population the most frequently prescribed TNFb was etanercept (197 (39%)), followed by adalimumab (131 (26%)), golimumab (88 (17%)), infliximab 53 (10%) and certolizumab (39 (8%)); the same order was observed in TNFb naive patients; however, in patients previously exposed to TNFb, the most frequently prescribed TNFb was infliximab (31 (24%)) followed by golimumab (29 (22%)), adalimumab (29 (22%)), certolizumab (22 (17%)) and etanercept (20 (15%)). BASDAI50 responses were comparable for all TNFb molecules: 52%, 52%, 48%, 53% and 49% for etanercept, adalimumab, golimumab, infliximab and certolizumab, respectively. BASDAI 50 response was comparable in patients TNFb-naive and patients previously exposed to only 1 previous TNFb (53% vs. 52%, for naive vs. non-naive patients) but significantly decreased after (i.e. 37% and 36.% for patients previously exposed to 2 and to 3 or more TNFb) Conclusions this study suggests that the TNFb treatment response is similar across the different available molecules but this treatment response decreased in case of a previous use of two TNFb. Acknowledgements This study was conducted thanks to an unrestricted grant from MSD Disclosure of Interest None declared

Background In axSpA, treatment decisions are mainly based on patient-reported symptoms: recommendations are to initiate TNFi in patients with active disease and with physician conviction that treatment is needed (ref). However, the attribution of symptoms to inflammation is difficult to establish in axSpA. Objectives The objective of the present analysis was to explore the link between physician-attributed causality for symptoms and treatment response to TNFi. Methods The PredictSpA study (ClinicalTrials.gov: NCT03039088) was a longitudinal observational multicenter study in France in 2015. Patients with physician-defined definite axSpA and starting a TNFi treatment were included, a TNFi was prescribed according to usual practice and efficacy was assessed at 12 weeks by BASDAI50 response. At baseline, symptoms levels including BASDAI and ASDAS were collected and the physician evaluated the causality of symptoms by answering the following 3 questions: how convinced are you that the symptoms of this patient are due to (A) inflammatory axSpA activity (B) to axSpA severity (eg syndesmophytes, kyphosis) and NOT to disease activity and (C) to other diseases and NOT axSpA. Each question was assessed 0–10 (not convinced at all to absolutely convinced). The link between a score ≥4/10 on each of the 3 questions and BASDAI50 response was assessed by univariate logistic regression. Patients interrupting the TNFi before 3 months were considered as non-responders and missing data were imputed using non-responder imputation. Results In all, 519 patients were included and 508 had data over 3 months: mean age 41.3 (SD 11.6) years, mean disease duration 6.1 (SD 8.4) years, 237 (46.7%) were women, 424 (83.5%) satisfied the ASAS criteria for axSpA of whom 379 (74.6%) were in the imaging arm and 45 (8.9%) in the clinical arm. Symptom levels were high: mean BASDAI was 5.7 (SD 1.8) and mean ASDAS-CRP was 3.3 (SD 0.9) with only 6 (1.2%) patients in inactive disease state according to ASDAS. The physician-attributed causality of symptoms was mostly related to inflammatory activity: mean scores for (A), (B) and (C) were respectively, 7.4 (SD 2.0), 2.3 (SD 2.5) and 2.1 (SD 2.2). When physicians attributed causality to non-axSpA (score (C) ≥4/10), BASDAI50 response was less frequent: 45/118 (38.4%) vs 213/390 (54.6%), odds ratio 0.5 [95% CI 0.3, 0.8]. Conclusions In axSpA patients starting a TNFi with high symptom levels, physician-attributed causality of symptoms was mainly related to inflammatory activity of the axSpA. When physician-attributed causality was more oriented towards non-axSpA causes, BASDAI50 response after 3 months of a TNFi was lower. This confirms the validity of the ASAS-EULAR recommendations for starting a TNFi which rest on a level of symptoms but associated to physician conviction of the indication. References van der Heijde D, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017 [Epub ahead of print]. Acknowledgements This study was conducted thanks to an unrestricted grant from MSD. Disclosure of Interest None declared

Background Fibromyalgia (FM) is a frequent comorbid condition in axial spondyloarthritis (axSpA). It is not known how FM comorbidity may respond to the management of SpA, and especially to anti-TNF agents. Objectives To evaluate the change of comorbid FM status of axSpA patients starting an anti-TNF treatment. Methods A prospective multicenter national study involving 39 rheumatology centers in France, analyzing 519 patients with axSpA requiring anti-TNF therapy (ClinicalTrials.gov: NCT03039088). Patients were screened for FM with the FiRST questionnaire before and after 3 months of anti-TNF. Kappa coefficient was calculated to determine the agreement of the FiRST at M0 and M3. Response to anti-TNF (BASDAI50 response was compared according to positive screening for FM or not, at both time-points using chi2 tests. Results Of the 519 enrolled pts, 504 (with complete data on the FiRST questionnaire) were analyzed at M3. A positive screening for comorbid FM was found in 192 pts (38%) at M0 and in 127 (25%) pts at M3. Correlation between FiRST at M0 and M3 was weak with a Kappa coefficient correlation of 0.4 [0,3 - 0,5]. Four groups were identified: group [+/+] with comorbid FM at M0 and M3: N=93 (18%; group [+/-] with comorbid FM at M0 but not at M3: N=99 (20%); group [-/-] without comorbid FM at M0 and M3: N=278 (55%); group [-/+] without comorbid FM at M0 but at M3: N=34 (7%) Changes in the status of comorbid FM (disappearance or appearance) was observed in 134 pts (26%). In the 193 pts with baseline comorbid FM, after 3 months of anti-TNF treatment, comorbid FM was no longer found in 99 (51%)%.Efficacy at M3 was significantly better, according to BASDAI 50, in patients without comorbid FM at M3 (Table). Conclusions There is a high frequency of comorbid FM screened by the FiRST in active axSpA, decreased by 51%f after 3 months of anti-TNF treatments. Persistence of FM after 3 months of anti-TNF treatment is associated with lower anti-TNF response. Further studies are required to analyze the impact of screening FM before starting anti-TNF therapy in axSpA. References Perrot S, et al. Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain. 2010;150:250–6. Acknowledgements This study was conducted thanks to an unrestricted grant from MSD. Disclosure of Interest None declared

Background Currently, the European Medicine Agency (EMA) is recommending the use of anti-TNF in case of active NSAID refractory axial (ax) spondyloarthritis (SpA) only in the presence of either structural radiographic damage of the sacroiliac Joints (SIJ) or objective signs of inflammation (either elevated CRP or inflammation at MRI-SIJ) probably mainly because of the fear of a concomitant fibromyalgia (FM). Objectives To evaluate the interaction of a concomitant FM on the anti-TNF response with regard to the application of the EMA recommendation Methods Study design: Prospective, multicenter, longitudinal (12 weeks) open trial (Predict-SpA, ClinicalTrials.gov: NCT03039088). Patients (pts): axSpA requiring an anti-TNF. Data collected: At baseline, 1/Radiographic SIJ damage 2/ MRI-SIJ inflammation 3/ Elevated CRP 4/ FM according to the FiRST (Fibromyalgia Rapid Screen Test) questionnaire. At baseline and after 12 weeks of therapy: BASDAI. Statistical analysis: Non Responder Imputation (NRI), Baseline Carried Forward Technic (BOCF) in case of missing data. Interaction test between the presence of FM and the fulfillment of the EMA recommendation (defined by the presence of either structural radiographic damage of the SIJ or objective signs of inflammation (either elevated CRP or inflammation at MRI-SIJ)) on the anti TNF treatment response (BASDAI50) Results Of the 508 enrolled pts (females: 46.7%, age: 41.4+11.6 years old, HLA B27 positive: 57.5%, X-Ray sacroiliitis: 53.2%, inflammation at MRI-SIJ: 52.0%), only 59 had no structural damage at SIJ-X-Rays and no inflammation at MRI-SIJ (12%). A concomitant FM was noticed in 42% vs 37% of pts treated in accordance vs not with the EMA recommendation, respectively (p=0.44). The anti-TNF treatment effect was higher in the groups of pts treated in accordance (vs not) with the EMA recommendation (BASDAI 50: 52% vs 39%, respectively; p=0.054). There was a trend (but not statistically significant) suggesting an interaction of the concomitant FM on the anti TNF treatment response with regard to the application of the EMA recommendation (interaction p value=0.140). In the 59 pts not treated in accordance with the EMA recommendation, the treatment effect in the sub-groups of pts without ( vs with) concomitant FM was 38% vs 40% respectively, p=0.891. In the 449 pts treated in accordance with the EMA recommendation, the treatment effect in the sub-groups of pts without ( vs with) concomitant FM was 56% vs 46%, p=0.042). Conclusions This study suggests that 1/ French rheumatologists are applying the EMA recommendation in daily practice 2/ these recommendations result in a better outcome in terms of short term symptomatic treatment effect. In this study, concomitant FM was not more frequently observed in patients without ( vs with) objective sign of structural damage or inflammation and the impact of a concomitant FM was not more pronounced (or even lower) in pts without (vs with) objective sign of structural damage or inflammation. References Perrot S, et al. Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain.2010;150:250–6. Acknowledgements This study was conducted thanks to an unrestricted grant from MSD. Disclosure of Interest None declared

Resume Introduction Le tocilizumab (TCZ) est un anticorps anti-recepteur de l’IL-6 humanise, indique dans le traitement de la polyarthrite rhumatoide (PR) active, moderee a severe, la maladie de Still de l’adulte, la maladie de Castleman et, de facon plus recente, l’arthrite juvenile idiopathique dans sa forme systemique. De meme que les anti-TNFα, le rituximab et plus rarement l’abatacept, le TCZ est capable d’induire des reactions cutanees paradoxales de type psoriasique essentiellement a type de pustulose palmo-plantaire. Observation Nous rapportons l’observation d’une patiente suivie pour un rhumatisme psoriasique qui developpait sous anti-TNFα puis sous tocilizumab une eruption psoriasiforme palmo-plantaire. Conclusion Le mecanisme de ces reactions reste imparfaitement compris, mais des reactions croisees avec d’autres biotherapies sont observees.

Objective.Ischemic digital ulcers (DU) are frequent and severe complications of systemic sclerosis (SSc). The purpose of our study was to assess the effect of DU on hand disability and pain in patients with SSc.Methods.The Evaluation of the Impact of Recurrent Ischemic DU on Hand Disability in Patients with SSc (ECLIPSE) is a prospective, multicenter, noninterventional study with a 2-year followup. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan therapy were included between October 2009 and March 2011. This cohort is described at the time of inclusion.Results.There were 190 patients (132 females) from 53 centers. Mean age ± SD was 43 ± 15 years at SSc diagnosis and 53 ± 15 years at inclusion. In 105 patients (56.2%), DU were the first non-Raynaud symptoms of SSc. The mean time interval between the occurrence of Raynaud phenomenon and the first DU episode was 6.6 ± 9.1 years. The mean numbers of active DU and fingers affected per patient for both hands were 2.3 ± 1.8 and 2.2 ± 1.6, respectively. Presence of active DU at inclusion was significantly associated with pain and impaired hand function: Visual Analog Scale for pain (0 to 10) was 6.2 ± 2.6 versus 2.5 ± 2.4 (p < 0.0001) and Cochin Hand Function Scale for hand disability (0 to 90) was 38 ± 20 versus 25 ± 19 (p < 0.0001), respectively.Conclusion.DU represent a major sign of SSc, often affecting multiple fingers and both hands. They are significantly associated with pain and hand disability.

Resume Introduction La maladie de Whipple (MW) est une maladie infectieuse rare responsable de signes cliniques variables tant dans leur localisation que dans leur severite. Elle peut mimer un rhumatisme inflammatoire chronique de type polyarthrite rhumatoide ou spondyloarthrite. L’instauration d’une biotherapie a la suite d’une erreur diagnostique dans ce contexte n’entraine pas toujours des complications immediates. Parfois, l’aggravation fait suite a une amelioration initiale encourageant la poursuite du traitement immunosuppresseur et conduisant par consequent a un retard diagnostique. Observations Nous rapportons deux nouvelles observations de MW diagnostiquees en raison de l’echec de traitement anti-TNFα mis en route pour rhumatisme inflammatoire actif. Dans la premiere observation, il s’agissait d’un homme de 53 ans traite par etanercept puis adalimumab pour une spondylarthropathie axiale et peripherique et dans la seconde d’un homme de 42 ans traite par adalimumab et etanercept pour une spondylarthropathie peripherique. Conclusion Une MW doit etre evoquee devant tout patient suspect de rhumatisme inflammatoire chronique non repondeur ou partiellement repondeur aux anti-TNFα et dont le syndrome inflammatoire biologique persiste sous traitement.

Summary Background Imatinib mesylate is a potent inhibitor of platelet-derived growth factor and transforming growth factor-β signalling pathways which may play a role in systemic sclerosis (SSc)-associated skin changes. Objectives We aimed primarily at assessing the efficacy of imatinib mesylate in scleroderma skin fibrosis. Methods We performed a phase II double-blinded trial on patients with scleroderma with either morphoea involving > 20% of body surface area or SSc with extensive skin involvement: modified Rodnan Skin Score (mRSS) ≥ 20/51. Each patient was randomized to receive either imatinib mesylate 400 mg or placebo daily for a total of 6 months, and then was followed up 6 months after therapy discontinuation. Skin fibrosis was assessed by mRSS and measurement of the dermal thickness using skin biopsies performed at inclusion and at 6 months of treatment. In addition, quality of life (Dermatology Life Quality Index and modified Health Assessment Questionnaire for Scleroderma) was recorded at each visit, and pulmonary function before and after intervention. Results Twenty-eight patients were included in the study with a mean age of 48·9 years (range 30–71): 25 had a diagnosis of a SSc and three of diffuse cutaneous scleroderma. Demographic data, frequency of organ involvement of SSc and mRSS were comparable between groups. At 6 months, the proportion of variation of mRSS from inclusion was not statistically significantly different between the two groups (median +0·10 in imatinib group vs. −0·16 in placebo group, P = 0·098). Similarly, changes in dermal thickness, quality of life and diffusion capacity for carbon monoxide were not significantly different between groups. Conclusions This study failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis of diffuse scleroderma after 6 months of treatment based on validated outcome measurements.

A rise in the incidence of bullous pemphigoid (BP) was documented recently in Europe, and the main risk factors for BP remain unknown. We conducted a multicenter case-control study to evaluate risk factors for BP. We identified 201 incident BP cases and 345 controls individually matched for age, gender, center, and place of residence (home, nursing home, or extended-care facility). We used univariate and multivariate logistic regression analyses to compare drugs used for over 3 months, comorbidities, and physical and cognitive impairments between cases and controls. Mean age of BP patients was 84.2 (±8.7) years. Factors independently associated with BP by multivariate analysis were major cognitive impairment (odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.24-3.87), bedridden condition (OR, 2.19; 95% CI, 1.23-3.89), Parkinson's disease (OR, 2.16; 95% CI, 1.09-4.27), unipolar or bipolar disorder (OR, 5.25; 95% CI, 1.21-22.86), and chronic use of spironolactone (OR, 2.30; 95% CI, 1.20-4.46) or phenothiazines with aliphatic side chains (OR, 3.70; 95% CI, 1.21-11.34). Chronic analgesic use was associated with a lower risk of BP (OR, 0.49; 95% CI, 0.30-0.81). Thus, risk factors for BP include neurological disorders, particularly dementia and Parkinson's disease, psychiatric disorders (unipolar and bipolar disorders), bedridden condition, and chronic use of several drugs.

Introduction Les lupus actifs et corticodependants malgre un traitement immunosuppresseur conventionnel, representent un defi therapeutique. Aujourd’hui, si seul le belimumab a ete autorise par une AMM, d’autres biomedicaments sont parfois utilises au lieu a titre derogatoire dans des lupus refractaires. Etant donne le manque de donnees prouvant l’efficacite de ces biomedicaments dans certaines situations rencontrees en clinique, nous avons decide d’etablir des recommandations d’experts pour l’utilisation de biomedicaments dans le lupus erythemateux systemique. Materiels et methodes Nous avons developpe ces recommandations par « consensus formalise d’experts ». Le but de cette methode est de formaliser le degre d’accord entre experts en identifiant, par une cotation iterative avec retour d’information, les points de convergence, de divergence ou d’indecision entre experts. Cette methode comporte plusieurs etapes chronologiques consecutives (phase de pilotage, de cotation, de lecture, de finalisation et diffusion) realisees par des groupes de travail independants. Au travers de 3 reseaux dedies aux maladies auto-immunes systemiques (FLEUR, IMIDIATE, FAI2R) et sous l’egide du CRI, nous avons recueilli les opinions de 59 experts francophones du lupus exercant en Algerie, Belgique, France, Italie, Maroc, Suisse et Tunisie. Les specialites medicales representees etaient la medecine interne (49 %), rhumatologie (34 %), nephrologie (7 %), dermatologie (5 %), pediatrie (3 %) et medecine vasculaire (2 %). Deux methodologistes et 3 groupes d’experts strictement independants ont contribues a ces recommandations : un groupe de pilotage (GP) (n = 9), un groupe de cotation (GC) (n = 28) et un groupe de lecture (GL) (n = 23). Les propositions de recommandations ont ete redigees par le GP et soumises au GC. Chaque membre du GC a indique son degre d’accord de 1 a 9 (1 : totalement inapproprie ; 9 : totalement approprie ; 5 : indecision) et ses commentaires pour chaque recommandation. Apres 2 tours de cotations, le GP a reformule une version initiale des recommandations qui a ete soumise au GL. La distribution des scores et les commentaires du GL ont permis au GP de rediger une version finale des recommandations ( Tableau 1 , Tableau 2 , Tableau 3 , Tableau 4 ). Resultats Dix-sept recommandations finales ont ete elaborees par le GP, en tenant compte de tous les scores et commentaires faits par chaque membre du GC, du GL et des 2 methodologistes de l’etude. Ces recommandations definissent notamment 4 domaines : – le type de patients necessitant un biomedicament ; – le type de biomedicament (belimumab, rituximab, etc.) et de co-traitement a utiliser en fonction de l’atteinte d’organe ; – l’information a donner aux patients ; – la facon d’evaluer l’efficacite du traitement. Un algorithme de choix de biomedicament a ete realise a partir des recommandations finales du domaine 2. Conclusion Dix-sept recommandations pour l’utilisation de biomedicaments dans le lupus erythemateux systemique ont ete formulees par un large panel d’experts pour donner des conseils aux cliniciens dans la pratique quotidienne. Ces recommandations seront regulierement mises a jour en fonction des resultats de nouveaux essais cliniques randomises et de l’experience clinique croissante.

Introduction Quelques etudes ouvertes suggerent une efficacite du rituximab, sur l’amelioration de la sclerose cutanee et des capacites pulmonaires dans le sclerodermie systemique [1] . Nous presentons trois patients ayant beneficie au cours de leur suivi, de cures de rituximab en raison de 1 g a j0 et j14 pour une sclerodermie systemique refractaire ou intolerante au traitement habituel. Observation Cas no 1. Il s’agissait d’une femme de 68 ans, aux antecedents de cancer du sein gauche traite par radio-chimiotherapie et hormonotherapie et d’un emphyseme centrolobulaire post-tabagique, pour qui un diagnostic de sclerodermie systemique diffuse de forme rapidement progressive a ete pose en 2014 avec anticorps anti-ARN polymerase III positif. Elle presentait une atteinte digestive (œsophagite et estomac en pasteque), cutanee et cardiaque (sclerose aortique). Apres 4 cures de cyclophosphamide (CYC) entre juin et septembre 2015, on notait une aggravation de la sclerose cutanee distale engendrant un handicap fonctionnel et une erythrodermie apres la derniere cure de CYC. Apres 3 cures de rituximab entre decembre 2015 et decembre 2017 avec une bonne tolerance clinique, on notait une amelioration du score de Rodnan modifie (passant de 42 a 31) et de certains parametres fonctionnels respiratoires (capacite vitale forcee [CVF] passant de 62 a 84 %, capacite de diffusion [DLCO] passant de 32 a 52 %). Cas no 2. Un homme de 51 ans presentait une sclerodermie systemique seronegative avec atteinte cutanee, digestive (gastrite, prolapsus rectal, diarrhees chroniques), pulmonaire (HTAP et syndrome interstitiel) et cardiaque (fibrose endomyocardique). Il avait beneficie de 10 cures de CYC entre 2012 et 2013, avec un relais par mycophenolate mofetil (MMF) entre 2013 et 2016 en entretien. Devant la majoration de l’atteinte cutanee, cardiaque et digestive, un traitement par rituximab est entrepris en association a des immunoglobulines intraveineuses. Apres 2 cures de rituximab entre juillet 2016 et aout 2017, on notait une amelioration du score de Rodnan modifie (passant de 30 a 8) et une stabilite des explorations fonctionnelles respiratoires. Cas no 3. Une femme de 64 ans, presentant une sclerodermie systemique seronegative diagnostiquee en 1996 avec atteinte digestive (gastroparesie et reflux gastro-œsophagien), cutanee, pulmonaire (syndrome interstitiel), recevait des cures de CYC entre 1998 et 2002 avec efficacite initiale sur l’atteinte pulmonaire, puis d’un traitement par MMF en 2013 sur apparition d’une fibrose endomyocardique. Devant une aggravation de l’atteinte interstitielle pulmonaire et de l’atteinte cutanee, le rituximab est introduit. Apres 4 cures de rituximab entre decembre 2013 et septembre 2017, on notait une amelioration du score de Rodnan modifie (passant de 31 a 13) et un ralentissement de l’atteinte pulmonaire. Conclusion Plusieurs etudes, dont l’etude cas-temoin EUSTAR en 2014 portant sur 63 patients sclerodermiques, montraient une tendance a l’amelioration de la sclerose cutanee evaluee par le score modifie de Rodnan et du syndrome restrictif par l’amelioration de la CVF, voire de la DLCO au cours de l’utilisation du rituximab dans les sclerodermies systemiques diffuses, associee a une bonne tolerance clinique et biologique [2] . Or, l’etude randomisee et controlee portant sur des formes precoces de sclerodermie systemique de Boonstra et al. ne retrouve pas d’efficacite significative sur le plan cutane et pulmonaire entre rituximab et placebo [3] . Chez nos patients, l’introduction de l’anticorps monoclonal anti-CD20 semble ameliorer la sclerose cutanee avec une tendance a la diminution du score de Rodnan modifie et d’une amelioration des capacites pulmonaires ou du moins de leurs stabilisations dans les deux derniers cas. Bien que l’amelioration du score de Rodnan dans ce contexte puisse etre expliquee par l’histoire naturelle de la forme systemique diffuse et par son evaluation operateur-dependant, le rituximab pourrait etre une alternative therapeutique interessante et bien toleree dans la sclerodermie systemique. D’autres etudes randomisees sont cependant necessaires pour evaluer son efficacite ainsi que la posologie optimale.

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.

Calciphylaxis is a rare necrotizing calcifying arteriolopathy, with a poor prognosis, for which there is currently no effective treatment. One of the major challenges of the therapy is normalizing the calcium-phosphate balance. Therefore, cinacalcet, which inhibit the production of parathormone by negative feedback, was considered a treatment option to control the evolution of calciphylaxis in a dialysed patient suffering from cholangiocarcinoma.

Resume Introduction L'efflorescence brutale de lesions papuleuses evoluant vers la necrose ou l'ulceration renvoie a de nombreux diagnostics dermatologiques, en premier lieu infectieux ou immunoallergiques. La presentation febrile ulceronecrotique ou dermatose de Mucha-Habermann est une forme severe de pityriasis aigue lichenoide et varioliforme (PLEVA) pouvant avoir une evolution multisystemique initiale gravissime parfois mortelle. La papulose lymphomatoide se caracterise par une eruption papulonodulaire de presentation clinique voisine. Si l'evolution est en general benigne, 10 % des patients developpent a long terme un lymphome. Exegese Les auteurs rapportent une forme aigue de PLEVA survenue chez un jeune homme hospitalise en medecine interne pour eruption varioliforme febrile, d'evolution favorable sous cyclines ainsi qu'un cas de papulose lymphomatoide de presentation clinique identique survenue chez une femme de 34 ans, dont le diagnostic a ete fait devant l'infiltration CD30 caracteristique a la biopsie cutanee. Conclusion Ces deux dermatoses exceptionnelles et de presentation clinique identique doivent etre connues de l'interniste du fait des risques evolutifs particuliers de ces deux affections.

Resume Introduction La dermatomyosite est une myopathie inflammatoire connue pour ses atteintes viscerales potentiellement graves. Bien que ne mettant pas en jeu le risque vital, l'atteinte cutanee parfois invalidante et souvent resistante aux traitements classiques necessite de nouvelles alternatives therapeutiques. Nous rapportons trois cas de patients presentant une atteinte cutanee de dermatomyosite resistante, traites avec succes par tacrolimus topique. Exegese Ce traitement a permis chez nos trois patients atteints de dermatomyosite une disparition totale des lesions invalidantes siegeant sur le visage et le dos des mains, et une amelioration partielle des lesions ayant une autre topographie, sans effet secondaire notable. Conclusion Le tacrolimus est un immunosuppresseur dont la forme locale est utilisee dans le traitement de la dermatite atopique. Cette molecule est utilisee de maniere anecdotique dans les atteintes cutanees de certaines pathologies systemiques tels le lupus, la sclerodermie ou la polyarthrite rhumatoide par exemple. Le tacrolimus topique pourrait etre non seulement une alternative therapeutique efficace de l'atteinte cutanee de la dermatomyosite resistante, mais pourrait aussi etre propose en premiere intention du fait de sa tolerance.

International audience; OBJECTIVES:Ischaemic digital ulcers (DUs) are a common complication of systemic sclerosis (SSc). This study aimed to characterize patients with SSc and ongoing DUs treated with the endothelin receptor antagonist bosentan in clinical practice in France.METHOD:An observational, retrospective, longitudinal study was conducted in 10 French expert centres. Medical records from randomly selected adult SSc patients who received treatment with bosentan for DU prevention from March 2007 to December 2010 were analysed. The primary objective was to determine the profile of patients at treatment initiation. Secondary objectives were to monitor bosentan dosing, treatment schedule, and reasons for treatment termination.RESULTS:The study included 89 patients (mean age 52 years, 69% female, 44% diffuse cutaneous SSc). At bosentan treatment initiation, the mean duration of Raynaud's phenomenon was 15 ± 12 years, and the mean time since first episode with DU was 6.5 ± 7 years. Most patients had a history of at least two episodes with DUs, separated by < 12 months (61%), and had received intravenous iloprost (63%). Previous DU complications included auto-amputation (8%), surgical amputation (6%), osteitis (6%), and gangrene (4.5%). Active smokers (25%) had a history of significantly more surgical amputation (p = 0.004) and osteitis (p = 0.004) than non-smokers. At least one active DU at bosentan initiation was detected in 82% of patients. Bosentan was used according to prescription guidelines and was well tolerated; six patients (7%) withdrew from treatment because of raised liver enzymes.CONCLUSIONS:Patients treated with bosentan for DU prevention in France have severe, refractory, ongoing ulcerative disease. Active smoking was correlated to a history of DU complications. Tolerance of bosentan was comparable to previous studies.

Background Drug-induced aphthous ulcers have been the subject of several isolated and heterogeneous case reports for the last three decades. Objectives To perform a case–control study to evaluate the risks linked to drug exposure in aphthous ulcers. Methods Eighty patients with typical clinical patterns of aphthous ulcers and 152 control patients who had had consultations for skin tumours were studied. A standardized questionnaire, concerning clinical features, life-style and medications taken during the last month, was completed for each patient. Results Case patients had a much higher intake of medications than control patients, respectively, 5·1 and 2·8 medications per patient (P

Resume Propos. – Le syndrome d’hypersensibilite medicamenteuse est une reaction medicamenteuse aigue et severe associant un exantheme, une hyperthermie, des polyadenopathies, une eosinophilie sanguine et des atteintes viscerales. Les syndromes d’hypersensibilite medicamenteuse avec des manifestations systemiques graves sont responsables d’une mortalite de 10 %, et nous ont fait discuter un traitement corticoide. Methodes. – Nous rapportons une serie retrospective de huit cas de syndrome d’hypersensibilite medicamenteuse colliges a partir du programme de medicalisation des systemes d’information, de novembre 1991 a novembre 1998. Resultats. – Notre serie etait constituee de cinq hommes et trois femmes d’un âge moyen de 52,6 ans (extremes : 23 a 83 ans). Les delais entre la prise medicamenteuse et l’apparition des premiers symptomes variaient de deux a huit semaines. Trois patients ont eu un traitement par corticoides du fait d’une atteinte systemique grave. La guerison a ete obtenue en moyenne en 4,4 semaines (une a 56 semaines). Conclusion. – Le syndrome d’hypersensibilite medicamenteuse peut etre un piege diagnostique. Les criteres diagnostiques manquent et seul un faisceau d’argument permet de l’evoquer : le delai d’apparition des symptomes, les atteintes systemiques mimant un sepsis severe, l’hypereosinophilie, la lymphocytose activee... Le syndrome d’hypersensibilite medicamenteuse peut etre un piege therapeutique : il faut penser a arreter le medicament responsable. Les atteintes systemiques severes font discuter la corticotherapie bien que son utilisation soit controversee dans la litterature. Les tests epicutanes peuvent etre d’une aide precieuse pour determiner le medicament responsable, mais ils n’ont de valeur que positifs.

Resume Propos. – Les interferons alpha, beta ou gamma, cytokines produites par les fibroblastes en reponse a des stimulations antigeniques, sont utilises pour le traitement de maladies hepatiques, hematologiques, oncologiques et neurologiques. Les reactions cutanees representent 5 a 12 % des effets secondaires observes avec les interferons : rash, alopecie, herpes labial, erytheme et infiltration au site d’injection, necroses cutanees rarement. Nous rapportons six cas de reactions cutanees locales a l’interferon alpha dont cinq necroses et posons la question de la reintroduction du produit. Methodes. – Il s’agissait de cinq hommes et une femme d’âge moyen 59,1 ans (extremes : 42–74 ans). Trois patients etaient porteurs du virus de l’hepatite C et trois atteints de maladies hematologiques. Resultats. – Les delais d’apparition des necroses variaient de 1 a 10 mois. La guerison a ete obtenue en moyenne en 16,2 semaines avec reintroduction de l’interferon dans cinq cas sur six, sans recidive. Conclusion. – Les necroses cutanees a l’interferon surviennent quel que soit le type d’interferon, le lieu et la dose d’injection avec des delais de 2 mois a 9 ans. Les mecanismes physiopathologiques demeurent inconnus. La morbidite est liee aux longues durees de cicatrisation (4 a 6 mois), cette derniere necessitant parfois une chirurgie. Il faut etre vigilant devant un erytheme, premier signe avant la necrose, et changer le lieu d’injection. S’il existe une necrose, il convient de rechercher un facteur de thrombophilie, d’eliminer tout facteur diminuant la microcirculation (DHE, betabloquants, tabac...) et de reprendre les injections prudemment en d’autres sites, les injections etant alors realisees par une infirmiere lorsque le patient les faisaient lui-meme auparavant. Il faut insister sur un bon apprentissage de l’auto-injection.

Upper limb lymphangitis often complicates varied wounds on the hand or forearm and improvement is obtained in a few days with adapted antibiotic therapy. A 28-year-old woman presented since few years episodes of lymphangitis of the arm associated with vesicles on an erythematous base, on the palmar face of the first phalanx of the index finger, spontaneous relief within 10 days, without antibiotic therapy. Herpetic origin was confirmed on viral culture. No primary infection neither recurrence was noted. Because of the recurrences, a prophylactic treatment with valaciclovir was instituted. There was no reported recurrence at two years follow-up. Upper limb lymphangitis rarely complicates herpetic whitlow in immunocompetent patient. Clinicians should be aware of viral lymphangitis, which is often overlooked and associated with diagnostic errors and treatment delay.

International audience; Objective: Fractal bone analysis (Hmean) is a texture parameter ă reflecting bone microarchitecture. The BMA device (D3ATM Medical ă Systems, Orleans, France) is a high-resolution X-ray device that allows ă assessment of bone texture analysis. We aimed to measure Hmean in ă rheumatoid arthritis patients at the second and third metacarpal bones, ă at baseline and after 1 year of follow-up, and to assess the ă relationship of Hmean and rheumatoid arthritis disease parameters. ă Methods: Patients with rheumatoid arthritis according to ACR criteria ă were included. They were assessed over 1 year, in the context of a ă prospective study conducted in Maastricht. For this substudy, activity ă of the disease was assessed by erythrocyte sedimentation rate, ă C-reactive protein and Disease Activity Score 28 performed at each ă visit. Radiographic bone damage was assessed using hand and feet ă radiographs at baseline and on a 1-year basis. The bone texture ă parameters were evaluated on the second and third metacarpal heads of ă the left hand using BMA device. ă Results: One hundred and sixty-five rheumatoid arthritis patients were ă included in this study. At baseline, Hmean was negatively correlated ă with age [r= 0.22 (13= 0.013)] and erythrocyte sedimentation rate ă [r= 0.16 (13= 0.039)]. No significant correlation was found between ă Hmean and Disease Activity Score, disease activity Visual Analog Scale, ă daily corticosteroid dose and C-reactive protein. There was a ă significant increase in Hmean of second and third metacarpal bones over ă 1 year (1.6% and 1.3%, P< 0.01) except in patients with local second ă and third metacarpal bones erosion. ă Conclusion: The bone texture parameter Hmean is influenced by age, ă inflammation and local erosions in rheumatoid arthritis. (C) 2013 ă Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All ă rights reserved.

BackgroundNeurotrophins play a central role in the development and maintenance of the nervous system. However, neurotrophins can also modulate B and T cell proliferation and activation, especially via autocrine loops. We hypothesized that both serum and lymphocytic neurotrophin levels may be deregulated in systemic Lupus erythematosus (SLE) and may reflect clinical symptoms of the disease.MethodsNeurotrophins in the serum (ELISA tests) and lymphocytes (flow cytometry) were measured in 26 SLE patients and 26 control subjects. Th1 (interferon-γ) and Th2 (IL-10) profiles and serum concentration of BAFF were assessed by ELISA in the SLE and control subjects.FindingsWe have demonstrated that both NGF and BDNF serum levels are higher in SLE patients than healthy controls (p=0.003 and pConclusionThis study demonstrates that serum and B cell levels of both NGF and BDNF are increased in SLE, suggesting that the neurotrophin production pathway is deregulated in this disease. These results must be confirmed in a larger study with naive SLE patients, in order to avoid the potential confounding influence of prior immune-modulating treatments on neurotrophin levels.

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.

Introduction La sclerodermie systemique (ScS) est responsable d’un handicap fonctionnel. L’objectif de ce travail est d’evaluer l’interet d’une prise en charge pluridisciplinaire dans l’evaluation et la prise en charge de ce handicap. Patients et methodes Il s’agit d’une etude retrospective unicentrique. Les patients vus en consultation pluridisciplinaire de la main sclerodermique (medecin interniste, dermatologue, rhumatologue et reeducateur fonctionnel, IDE d’education therapeutique) avec un diagnostic de ScS selon les criteres de Leroy et Medsger ou de l’ACR/EULAR ou de syndrome de chevauchement (SC) ont ete inclus. Le fonctionnement de la consultation est le suivant : pres une phase de diagnostic, tous les patients beneficient d’un programme de soins et de reeducation personnalise. Resultats Soixante-quinze patients d’âge moyen 57,9 ans ont ete inclus (80 % de ScS, 20 % de SC). Cinquante-huit pour cent des patients presentaient une atteinte fonctionnelle de la main caracterisee par une distance pulpe paume non nulle pour 39 %, une alteration des pinces chez 10 %, une limitation des amplitudes articulaires chez 43 %. Cinquante-cinq pour cent des patients avaient une histoire d’ulceres digitaux (UD). L’atteinte de la main est correlee a la duree d’evolution de la maladie et au score de Rodnan. Cinquante et un pour cent des patients avaient des douleurs articulaires. Le score moyen de la main de Cochin etait de 22,99 et le score moyen sHAQ de 1,090. Ils sont correles a l’atteinte de la main, aux UD et aux limitations articulaires des membres. Le score sHAQ est lie a l’atteinte diffuse, a l’HTAP. A 23 mois de suivi, on note une amelioration de 43 % des patients pour le score de la main de Cochin et de 50 % des patients concernant le score sHAQ. Conclusion Une evaluation systematique du handicap doit etre realisee aupres des patients sclerodermiques. Une prise en charge pluridisciplinaire et la mise en place d’un programme de reeducation permettent une amelioration de ce handicap.

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.

Superpotent topical corticosteroids (CS) have been demonstrated to improve bullous pemphigoid (BP) patients’survival. We assessed whether a mild regimen using lower doses of topical CS and a shorter duration could improve the outcome of BP patients even more. Three-hundred and twelve BP patients were included in a multicenter randomized controlled trial and stratified depending on the extent of BP as moderate (n ¼134) or extensive (n ¼178). Patients were randomly assigned to the standard regimen (clobetasol propionate cream, 40g per day initially, with CS tapering over 12 months) or the mild regimen (10–30g per day), with CS tapering over 4 months. A noninferior rate of BP control was obtained with the mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%; P ¼0.005). Event-free survival, that is, the combined outcome of deaths and life-threatening adverse events did not differ between the two treatment groups (P ¼0.77). However, upon adjusting through the Cox model for age and Karnofsky score, a strong beneficial effect of the m ild regimen was observed in patients with moderate BP, with an almost twofold decrease in the riskof death or life-threatening adverse events relative to the standard regimen (hazard ratio ¼0.54; 95% confidence interval, 0.30–0.97; P ¼0.039). This mild regimen allows a 70% reduction of the cumulative doses of CS and improves BP patients’ outcome.

Background Monoclonal gammapathy of undetermined significance (MGUS) is premalignant plasma-cell disorder. Its prevalence is about 3.2% of the general population older than 50 years. In patients with rheumatoid Arthritis (RA), little is known about the prevalence of MGUS and its evolution under biologics. Objectives To assess the prevalence of MGUS in longstanding RA, the characteristics of patients with MGUS, and the evolution of MGUS under abatacept. Methods ORA (Orencia and Rheumatoid arthritis) is a French prospective 7-year registry which included 1017 RA patients at abatacept initiation. Data on disease characteristics, biologic abnormalities including the presence of a monoclonal gammapathy, and the occurrence of severe adverse events, including cancers such as lymphomas, myelomas are collected at enrollment and every 6 months. Results Among the 1017 RA patients included in ORA registry, 38 had a MGUS (3.7%). Baseline disease characteristics (gender, age, RA duration, positivity for anti-CCP and rheumatoid factors, DAS28ESR) were not significantly different between patients with or without MGUS. In RA patients with MGUS, mean age and RA duration were 58.2±13.6 and 13.8±9.5 years, respectively. 76.3% were women 52.6% and 55.2% had anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RF), respectively. 92.1% of patients previously received biological treatments (with a mean of 2.5±1.3 biologics): 89.5% previously received anti-TNFs and 42.1% receive rituximab As concomitant treatment, 47.3% received methotrexate and 84.2% corticosteroids. During the follow-up of 1.50±1.10 years, no significant change in the blood level of the monoclonal component was observed. Two patients developed a multiple myeloma;. For the first patient, Immunoglobulin G Kappa stade 3 myeloma was diagnosed only 83 days after abatacept initiation. For the second patient, immunoglobuline G myeloma stade 1 was diagnosed 1 year after abatacept initiation. No lymphoma nor amyloidosis occurred. Conclusions The prevalence of MGUS in this population with longstanding RA was similar to that observed in the general population (∼3%). No significant effect of abatacept on the blood level of the monoclonal component was observed after 2 years of prospective follow-up. Although no signal has been observed, a longer follow-up is needed to evaluate the effect of abatacept on the risk of malignant transformation of MGUS. References Kyle RA et al. Prevalence of MGUS, N Engl J Med 2006;354:1362-9. Smale SW et al. Scand J Rheumatol. 2007;36: 405-6. Disclosure of Interest None declared

Background According to the EULAR recommendations for the management of patients with rheumatoid arthritis (RA), the use of a biologic therapy should be done in combination with methotrexate (MTX) or another synthetic DMARD (csDMARD). However, in “real-life studies”, 30% of the patients are treated with biologic in monotherapy. Objectives Our objectives were to describe the characteristics of patients with RA receiving intravenous biologic therapy without csDMARD and the reasons for monotherapy. Methods We made an observational, retrospective and multicentric study in 3 rheumatology units in Alsace (France) between the 1/01/13 and the 31/01/14. Patients with a RA diagnosis according to the 2010 ACR criteria and treated with abatacept (ABA), infliximab (IXF), rituximab (RTX) or tocilizumab (TCZ) with no MTX, sulfazalazine, leflunomid or hydroxychloroquine for at least 3 months were included. Collected variables included patients9 characteristics (age, gender and comorbidities), RA characteristics, past and present antirheumatic therapies. Results 109 (27%) patients treated with an intravenous biologic were in monotherapy; 74% were women, mean (SD) age was 65 (12) years. Mean time (SD) since RA diagnosis was 15.2 years (9.4). 78% had rheumatoid factor and 72% anti-CCP antibodies, 80% had joint damage. Among the 109 patients, 20 (18.3%) were treated with ABA, 8 (7.3%) with IFX, 48 (44%) with RTX and 33 (30.3%) with TCZ. The mean (SD) DAS28 at the treatment initiation was 5 (1.4). The mean DAS28 (SD) at the last cure was 3.4 (1.4). The mean (SD) dose of oral corticosteroid at the last cure was 7.4 mg/d (5.5). The biologic was initiated in combination with 30% of patients and in monotherapy with 70% of patients. Patients had received a mean (SD) of 2.2 (1) synthetic DMARDs and 2.46 (1.3) biologics. 94% of patients previously received MTX, 58% MTX and LFN and 11% the 4 csDMARDs. About MTX, 43 patients were treated orally (57%), 25 subcutaneously (33%) and 7 had the 2 routes (9.3%). The mean dose before stopping MTX was 13.8mg ±4.4. Reasons for stopping MTX were: intolerance for 73% of patients, lack of effectiveness for 10% of patients, patient refusal (4%) and cancer (3%). Among withdrawals for intolerance, there was 35% of gastro-intestinal intolerance (abdominal pain, diarrhea, dyspepsia, nausea, loss of appetite), 30% of liver intolerance (ASAT and/or ALAT elevation superior to 2N), 11% of hematological intolerance and 8% of lung intolerance. 7 patients never had MTX: 6 because of medical contraindication and 1 refused. Conclusions Use of biologics in monotherapy is frequent though combination showed better control of disease progression and less immunogenicity. In our study, most patients previously received at least 2 csDMARDs. The most frequent reason for MTX withdrawal was gastrointestinal intolerance and only few patients received MTX in parenteral. In order to optimize the MTX, practitioners should give good information about side effects, try low dose of MTX, switch from oral to parenteral administration, assess the adherence to folic acid supplementation. Disclosure of Interest None declared

Erythema nodosum is a panniculitis occurring more frequently in young women. We report a 16-year-old woman who presented with erythema nodosum that occurred following Gardasil® administration (vaccine against HPV types 6, 11, 16 and 18) and that is proposed to young female. This adverse effect is not a contraindication to the HPV vaccination because its benefit against the oncogene risk of Papillomavirus is documented.

OBJECTIVE: To identify potential risk factors and the yield of routine screens for early detection of malignancy associated with dermatomyositis (DM) and polymyositis (PM). DESIGN: Retrospective study of malignancies in all patients with DM or PM followed up between the years 1981 and 2000 and a review of the relationship of DM and PM to malignancy, the usefulness of various tests or examinations for malignancy search, and the patients' course. SETTING: Departments of internal medicine and dermatology in a teaching hospital. PATIENTS: Forty consecutive adult patients with DM (33 cases) or PM (7 cases). MAIN OUTCOME MEASURES: (1) Rate of false-negative results of routine workup and yield (percentage of positive results) of blind malignancy search and (2) comparison of 16 characteristics in patients with malignancy vs those without. RESULTS: Malignancy occurred in 16 patients: 13 with DM and 3 with PM. In all cases, the diagnosis of malignancy was made concurrently with or shortly after the diagnosis of DM or PM. Factors associated with malignancy were recruitment in the internal medicine department (P =.02), constitutional symptoms (P

Background Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc) leading to hand disability. Objectives We investigated the impact of controlling the ulcerative disease on hand disability and quality of life in SSc patients following one year of bosentan treatment Methods ECLIPSE is a 2-year prospective, observational study. Patients with SSc who experienced at least one DU in previous year and received bosentan to prevent occurrence of new DU were included between October 2009 and March 2011.Demographical and clinical data were collected at inclusion and at 1 year, as well as disability scores (Cochin hand function scale (CHFS), health assessment questionnaire disability index (HAQ-DI)), pain score (Visual Analog Scale), and quality of life (SF-36). A controlled ulcerative disease was defined by healing of all DU present at inclusion and the absence of new ulcer between inclusion and one-year follow-up. Data are presented as means ± standard deviations. Results Follow-up data were available at one year for 120 patients out of the 190 included patients. Patients9 characteristics were similar to those of the overall cohort. Mean age at inclusion and at SSc diagnosis were 54±15 and 44±15 years, respectively. SSc was diffuse in 42% of the cases. At inclusion, patients had been receiving bosentan for 15.6±22.1 months. During the one-year follow-up, 46 (38%) patients experienced an episode of new DU and the incidence of the event was 0.6 event/patient-year [95% confidence interval: 0.44-0.81]. Nevertheless, the proportion of patients with at least one DU decreased from 61% to 22% and the number of DU per patient decreased from 1.4±1.8 to 0.6±1.6 (p Patients with a controlled ulcerative disease (n=58) significantly improved CHFS (p=0.04), HAQ-DI (p=0.04), and physical component of the SF-36 (p=0.05) compared with patients with an uncontrolled disease (n=62). During the one-year follow-up, 21 (17%) patients discontinued bosentan for an adverse event including 5 patients presenting elevated aminotransferases. Conclusions In patients with SSc receiving bosentan, a controlled ulcerative disease is associated with a significant attenuation of disability. Disclosure of Interest L. Mouthon Grant/research support: Actelion France, Pfizer, Consultant for: Actelion France, Pfizer, P. Carpentier Consultant for: Actelion France, C. Lok Consultant for: Actelion France, P. Clerson Consultant for: Actelion France, V. Gressin: None declared, E. Hachulla: None declared, A. Berezne: None declared, E. Diot: None declared, A. Khau Van Kien: None declared, P. Jego: None declared, C. Agard: None declared, A.-B. Modeste Duval: None declared, A. Sparsa: None declared, E. Puzenat: None declared, M.-A. Richard Consultant for: Actelion France DOI 10.1136/annrheumdis-2014-eular.5478