E. Hachulla

Université du Droit et de la Santé Lille 2, Lille, Nord-Pas-de-Calais, France

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Publications (886)1762.07 Total impact

  • P-Y Hatron · E Hachulla
    La Revue de Médecine Interne 09/2015; DOI:10.1016/j.revmed.2015.08.003 · 1.07 Impact Factor
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    ABSTRACT: To assess the relation between Takayasu's arteritis (TA) and pregnancy outcome. This study included 240 pregnancies in 96 patients fulfilling ACR and/or Ishikawa criteria. Obstetrical and maternal outcomes in pregnant women before or concomitant with or after TA diagnosis were analyzed. Factors associated with complicated pregnancy were assessed. One hundred and forty two pregnancies occurred in 52 patients before TA diagnosis [median age at pregnancy 26 [23-30] years] and 98 pregnancies occurred in 52 patients concomitantly or after TA diagnosis [median age at pregnancy 28 [26-31] years]. Pregnancies concomitant with or after TA diagnosis had 13 times higher rates of obstetrical complications compared to pregnancies before TA diagnosis (OR=13, 95% CI [5-33], p<0.0001). TA was associated with 40% obstetrical complications and include preeclampsia/eclampsia [n=24, (24%)], prematurity [n=8 (8%)] and intrauterine fetal growth restriction or death [n=5 (5%)]. Specific TA complications during pregnancy occurred in 39% and include mainly new onset or worsening hypertension [n=26, (26%)]. In multivariate analysis, smoker (OR=6.15 [1.31-28.8]) and disease activity of TA (i.e. NIH score >1) (OR=28.7 [7.89-104.7]) were independently associated with obstetrical and maternal complications. TA negatively impacts pregnancy outcomes. Disease activity increases the risk of obstetrical and maternal complications mainly due to arterial hypertension. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    Arthritis and Rheumatology 08/2015; DOI:10.1002/art.39335
  • La Revue de Médecine Interne 08/2015; DOI:10.1016/j.revmed.2015.07.010 · 1.07 Impact Factor
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    ABSTRACT: To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. 695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan-Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors. The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies. Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the Rheumatic Diseases 07/2015; DOI:10.1136/annrheumdis-2015-207271 · 10.38 Impact Factor
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    ABSTRACT: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab). Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Autoimmunity 07/2015; 62. DOI:10.1016/j.jaut.2015.06.005 · 8.41 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):88.1-88. DOI:10.1136/annrheumdis-2015-eular.1728 · 10.38 Impact Factor
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    ABSTRACT: Background Systemic sclerosis (SSc) is classically dichotomized in limited or diffuse cutaneous subsets associated with different prognosis. However, it appears that SSc is a highly heterogeneous disease, with probably more subtle clinical phenotypes. Objectives The primary objective of our study was to identify and characterize homogeneous phenotypes in the EUSTAR SSc population using a cluster analysis. The secondary objective is to assess the survival in the different clusters. Methods The participants were SSc patients of the EUSTAR prospective cohort. Inclusion criteria were: age ≥18 years, fulfilled American College of Rheumatology criteria for SSc, and had a calculable follow up. Hierarchical clustering based on the Ward method was performed using 25 clinically meaningful variables. The clinical relevance of the clusters was analysed by their characteristics and survival outcomes. Survival curves were plotted by the Kaplan-Meier method. Crud and adjusted (on the age at diagnosis and gender) Cox models were performed. Results A total of 6.927 patients were analyzed. Cluster analysis identified 5 clusters (Table 1). The first cluster C1 (n=1,963) was mainly characterized by a low Rodnan skin score contrasting with a relatively similar percentage of anti topoisomerase 1 and anti-centromere Ab (28% and 40%) and a high percentage of lung fibrosis (48%); the second cluster C2 (n=1,186) by a large majority of limited SSc (89%) and anti-centromere (79%) and the lowest percentage of lung fibrosis (22%); the third cluster C3 (n=1,249) and the fourth cluster C4 (n=856) by a high percentage of diffuse SSc/anti topoisomerase 1 (72%/50% and 92%/77% respectively) and the highest proportion of male patients. Digital ulcers, renal crisis/anti RNA polymerase III antibodies, joint involvement were more frequently found in C4 than in the other clusters. Patients in the cluster C5 (n=1,673) were mainly female patients, older than in the other clusters, had a rather low mean Rodnan skin score, a high percentage of anti-topoisomerase 1 antibodies (46%) and a high percentage of lung fibrosis. Concerning survival, C2 had the best survival and C4 the worst. When compared to C1, C2 to C5 clusters had a significantly different prognosis (C2: adjusted hazard ratio [95% CI]: 0.70 [0.51-0.96]; C3: 2.27 [1.76-2.94]; C4: 4.52 [3.57-5.72]; and C5: 1.94 [1.51-2.44]. Conclusions This cluster analysis on the largest ever worldwide database of SSc patients showed 5 different clusters characterized by different sex ratio, maximum Rodnan skin scores, autoantibodies status, joint and organ involvement as well as by a different prognosis. Autoantibodies status seemed to play an important role for association with organ involvement. Although systemic sclerosis is a heterogeneous disease, this study shows that homogeneous groups beyond the classical limited/diffuse dichotomy can be delineated in this disease. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):90.1-90. DOI:10.1136/annrheumdis-2015-eular.1915 · 10.38 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):78.2-79. DOI:10.1136/annrheumdis-2015-eular.3807 · 10.38 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):143.2-143. DOI:10.1136/annrheumdis-2015-eular.4156 · 10.38 Impact Factor
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    ABSTRACT: Background Refractory and corticodependent Systemic Lupus Erythematous (SLE) often represents a therapeutic challenge. Only one biologic, belimumab, has been approved to date, but others are used off-label. However, the strategy of use remains a “grey area” in the available recommendations (1-3), because of the lack of evidence-based data and the wide range of situations encountered in real-life practice. We decided to set-up recommendations, following the French High Authority for Health (HAS) guidelines. Objectives To establish Recommendations of Good Practice (RGP) for the use of biologics in SLE, in 5 domains: Which patient might benefit from biologics?; Which biologic might be used?; Which information and co-medication(s) should be given to patients?; How should the effectiveness of a biologic be evaluated?; When does the biologic have to be discontinued? Methods We used the “Experts Formalized Consensus” methodology, as recommended by HAS. In brief, the degree of agreement on each recommendation is formalized, and a recommendation is validated only after a consensus has been reached. In case of controversy, proposed recommendations are modified and submitted again to the panel of experts until a consensus is reached. This process highlights extremes and not only median opinion. Transparency requires publishing all comments that are not retained. If the degree of agreement is not strong enough, proposals may be rejected. Results Three strictly independent SLE experts groups were established: a steering group SG (n=9), an evaluation group EG (n=28) and a reading group RG (n=40). Cf Fig. 1. A systematic literature review was conducted by SG in Pubmed-MeSH. The search terms were “SLE” AND [biological] – [mode of action] – [study design]. Until June 2014, 444 references matched. According to the state of art, 20 initial recommendations were drafted by the SG and then submitted to the EG. Each individual expert of the EG scored his degree of agreement from 1 to 9 (1: lowest agreement; 9: strongest agreement). The 1st evaluation round showed 4 recommendations with strong agreement (median ≥7; values ≥7), 5 with relative agreement (median ≥7; some values <7); and 11 recommendations without sufficient consensus. These latter recommendations are currently being reformulated before a 2nd round scoring. The SG will then formulate a last version. Then the RG will score and comment each recommendation. At last, the recommendations will be finalized and published by the SG. Conclusions After the 1st evaluation round, the large number of uncertainties is due to some extreme values in score distribution, which illustrates the wide range of practice among experts. The methodology provides several rounds to try to reach a consensus, by taking into account punctual disagreement. We report our experience of using the Experts Formalized Consensus methodology in the establishment of international recommendations for the use of biologics in SLE. 2nd round results and/or final recommandations will be prepared and presented at EULAR. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):343.1-343. DOI:10.1136/annrheumdis-2015-eular.3693 · 10.38 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):99.1-99. DOI:10.1136/annrheumdis-2015-eular.5149 · 10.38 Impact Factor
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    ABSTRACT: Background Little is known about the pathogenesis of fatigue, a hallmark of primary Sjögren's syndrome. The respective contribution of depression, disease activity, or auto-immunity itself has never been studied ever since international disease activity scores were established. We therefore investigated the association between fatigue and other characteristics of the disease in a large multi-center prospective cohort. Methods ASSESS is a multi-center prospective cohort which included 395 patients. At baseline and every year of the follow-up, systemic disease activity and patient-related outcome are evaluated by the ESSDAI and ESSPRI (the average of patient's visual analogic scales (VAS) for fatigue, pain and dryness), respectively, and patients fill questionnaires including the Hospital Anxiety and Depression (HAD) scale. Serum markers of B-cell activation, BAFF, interferon (IFN)-inducible chemokines, and IL-21 were assessed. Results Median (25th-75th) fatigue VAS was 6 (4-8). Fatigue VAS was correlated with dryness VAS (r=0.46, p<0.0001) and pain VAS (r=0.54, p<0.0001). Fatigue VAS was not correlated with age or disease duration, the ESSDAI, unstimulated salivary flow or Schirmer's test. Fatigue VAS was significantly higher in patients with depression (defined by a HAD subscale for depression (HAD-D) ≥8 (median fatigue VAS of 7 (6-9) in patients with depression and of 6 (4-8) in patients without depression, p<0.0001). In patients without depression, fatigue VAS remained not associated with anti-SSA, the ESSDAI, unstimulated salivary flow and Schirmer's test. Among patients without depression, a high fatigue VAS (≥5, the median of fatigue VAS in these patients) was not associated with a higher level of serum IFN-inducible chemokines (CCL2, CXCL10, CCL19), B-cell activating cytokines such as BAFF or IL-21, markers of B-cell activation (total Ig levels, free light chains of immunoglobulins, rheumatoid factor levels). Conclusions These results confirm the diversity of factors associated with fatigue in primary Sjögren's syndrome, including depression and the two other main symptoms, dryness and pain. Even when focusing on patients without depression, no association was observed between fatigue and systemic disease activity, autoantibody profile, serum surrogate markers of the IFN signature and of B-cell activation. Further work is necessary to determine the existence of potential other immunological drivers. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):796.2-796. DOI:10.1136/annrheumdis-2015-eular.3949 · 10.38 Impact Factor
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    ABSTRACT: Background Patients with a history of cancer were excluded from pivotal clinical trials evaluating biologics. Therefore, only registries can inform us on the incidence of cancers in such patients treated with a biologic. Methods Registries of the French Society of Rheumatology AIR and ORA included 1985 and 1024 patients to study tolerance and efficacy of rituximab and abatacept in common practice, respectively. Cancers and serious infections were validated by analysis of the charts of patients. Results 258 patients had a history of cancer and 1552 patients did not have a history of cancer before rituximab (175 missing data). Among the 1552 patients without a history of cancer, 1549 patients had at last one follow-up visit (5344 patient-years) and 42 cancers occurred (0.8 cancers/100 patient-years). Among the 258 patients with a history of cancer, 257 had at least 1 follow-up visit (867 patient-years) and 26 incident cancers (2.9 cancers/100 patient-years), including 12 new cancers (1.3 cancers/100 patient-years) and 14 relapses of past cancers (1.6 cancers/100 patient-years). 54 patients had a history of cancer and 958 patients did not have a history of cancer before abatacept (12 missing data). Among the 958 patients without a history of cancer, 930 patients had at least 1 follow-up visit (2705 patient-years) and 36 cancers occurred (1.3 cancers/100 patient-years). Among the 54 patients with a history of cancer, 53 patients had at least 1 follow-up visit (152 patient-years). Four incident cancers occurred (2.6 cancers/100 patient-years) including 2 new cancers (1.3 cancers/100 patient-years) and 2 relapses of past cancers (1.3 cancers/100 patient-years). Conclusions The incidence of cancers in the French national registries of patients with a history of cancer treated with rituximab or abatacept, approximately two-fold that of patients without a history of cancer, is comparable to that observed in the German RABBIT registry in patients with a history of cancer and rheumatoid arthritis treated with synthetic DMARDs or rituximab. Thus, until now, the risk of recurrence of cancer in patients with a history of cancer treated with rituximab or abatacept is in the range of what is expected in these patients at higher risk of cancer. Given the relatively short follow-up, it is necessary to continue to monitor patients with a history of cancer and to keep on evaluating the benefit/risk ratio before initiating a biologic, even a non anti-TNF biologic, in such patients. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):478.2-479. DOI:10.1136/annrheumdis-2015-eular.3822 · 10.38 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1087.2-1087. DOI:10.1136/annrheumdis-2015-eular.3282 · 10.38 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):803.2-804. DOI:10.1136/annrheumdis-2015-eular.6116 · 10.38 Impact Factor
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    La Revue de Médecine Interne 06/2015; 36:A54. DOI:10.1016/j.revmed.2015.03.289 · 1.07 Impact Factor
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    ABSTRACT: Background The long-term efficacy of canakinumab and changes in the daily lives of patients (and their caregivers) have not been thoroughly evaluated since its first use in France in 2007 and its approval for CAPS in 2010. Objectives A multicentre retrospective, observational study set up to assess the “real life” use of canakinumab in all French CAPS patients ever treated since 2007, to describe their clinical course on a long-term, and to analyse changes in their (and their caregiver's) quality of lives. Methods We targeted the 70-80 patients ever treated for CAPS in France, at least once and even during a clinical trial. Investigators were known experts in the field of CAPS in France who accepted to take part in the study. Data were collected through questionnaires by phone interviews and medical chart reviews, at treatment initiation, 6 months, 12 months and at the last medical visit. They included: clinical data, canakinumab use in real life conditions, impact on patients' (and caregivers') quality of life, and care consumption. The significance limit was set at 5% for all of the statistical tests. Results 68 CAPS patients, >90% of the target number, were enrolled (23 children, 45 adults). Sixteen patients (24%) had FCAS, 43 (63%) had MWS and 9 (13%) had NOMID-CINCA. The median duration of treatment was 5 years (from July 2007 to July 2014). >95% of patients remained on treatment. Doses were not modified in nearly half cases (31/68). For 37 patients, dosage adjustments (more often increase) were required (102 in total), especially in younger patients and those with the most severe phenotypes. The global activity of the disease, skin disorders and most of the symptoms were significantly better after canakinumab treatment (p<0.001) at the different study timepoints. The quality of life score also showed a significant improvement as median was 8 before canakinumab versus 2 (p<0.0001). Canakinumab treatment allowed also improvement in patient's daily activities, mood, and social life. Patients reported less school absences (79% versus 36%), and less sick leaves (48% versus 6%) after the initiation of canakinumab. The effect was weaker in CINCA patients; due in part to the late initiation of anti -IL1β treatment. Caregivers (49) were mostly family members and 35% of them had CAPS. They dedicated a mean of 7 hours/week to the CAPS patients before treatment and 4 hours during the last year. They spent on average 11.1 days per year of their job before canakinumab treatment versus 3 days after. The trend was less pronounced for caregivers of NOMID-CINCA patients. Conclusions ENVOL study showed real-life results similar to those obtained during the phase III clinical trials with canakinumab, reinforcing its sustained activity. The maintenance of more than 95% of patients on therapy confirmed its major benefit to CAPS patients, which was demonstrated herein by the positive impact of canakinumab in patients (and their caregivers) social, emotional, educational and professional lives. Disclosure of Interest I. Kone-Paut Grant/research support from: SOBI, Novartis, Roche, Consultant for: SOBI, Novartis, Pfizer, Abbvie, Chugai, Speakers bureau: Novartis, SOBI, P. Quartier Grant/research support from: Abbvie, Novartis, Pfizer, Consultant for: Abbvie, Novartis, Servier, SOBI, Speakers bureau: Abbvie, Chugai Roche, Medimmune, Novartis, Sobi, O. Fain Consultant for: Shire et CSL Behring, G. Grateau Grant/research support from: Abbvie, Novartis, Pfizer, Consultant for: Abbvie, Novartis, Servier, SOBI, Speakers bureau: Abbvie, Chugai Roche, Medimmune, Novartis, Sobi, P. Pillet: None declared, V. Despert: None declared, K. STANKOVIC STOJANOVIC: None declared, S. quere Employee of: Novartis employee, L. willemins Employee of: Novartis employee, O. Reigneau Employee of: novartis employee, E. Hachulla Consultant for: Novartis, SOBI
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1277.2-1278. DOI:10.1136/annrheumdis-2015-eular.2997 · 10.38 Impact Factor
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    ABSTRACT: Background High throughput study of metabolic pathways might help identify new biomarkers and therapeutic targets in autoimmune diseases. Primary Sjögren's syndrome (pSS) currently lacks prognostic biomarkers and efficacious and specific treatments. We therefore assessed serum levels of 35 metabolites in pSS using high-resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy. Methods The blood samples of 194 patients with pSS enrolled in the prospective multicenter ASSESS cohort and 41 blood donors were analysed in this study. After cryopreservation at -80°C, the samples were studied with HRMAS proton magnetic resonance spectroscopy (1H-MRS). Spectra were recorded on a Bruker Avance III 500 spectrometer operating at a proton frequency of 500 MHz. All the 1D NMR spectra were acquired during 76 min. Supervised clustering was performed on the spectral region between 0.5 and 4.7 ppm using partial least square discriminant analysis (PLS-DA). Results Supervised clustering of the 194 samples allowed to discriminate all patients with pSS from healthy controls (R2Y=0.88 and Q2=0.86 (figure 1)). Interestingly, 4 serum metabolites were significantly increased in pSS compared to healthy controls: threonine, lactate, glutamine and acetate. 6 metabolites were significantly decreased in pSS compared to healthy controls: myo-inositol, creatine, lysine, aspartate, glutamate and alanine Conclusions This first high-throughput analysis of metabolic pathways disclosed a specific metabolomic signature of pSS allowing discriminating all patients with pSS from controls. This new and very potent means of metabolic analysis may help to increase our knowledge on the pathogenesis of pSS, identify biomarkers, and new therapeutic targets. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):948.2-948. DOI:10.1136/annrheumdis-2015-eular.3978 · 10.38 Impact Factor
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    ABSTRACT: Background Primary Sjögren syndrome (pSS) is an autoimmune disease which may be associated to several systemic manifestations. Neurological manifestations seem to be frequent but prevalence is inconstant in literature (1). Objectives To assess neurological involvement prevalence in a national multi-center prospective cohort and to study epidemiological aspects of neurological involvement. Methods The ASSESS (Assessment of Systemic Signs and Evolution in Sjögren's Syndrome) cohort is a French, multi-centre, prospective cohort, set up in 2006, including 395 pSS patients fulfilling American- European Consensus Criteria (AECG). Demographic and clinical data were compared between patients with and without neurological manifestations, and between patients with peripheral nervous system (PNS) manifestations, central nervous system manifestations (CNS) and no manifestations. Medical records of 26 patients with CNS manifestations and/or cranial nerve involvement were reviewed by both local investigator and our group to confirm or invalidate the association between pSS and the neurological manifestations. Results Data at inclusion were available for 392 patients. Mean follow-up was 33.8 months. Mean age at inclusion was 58 (±12) years. Mean age at diagnosis was 51 (±12) years. Seventy-four of 392 patients (65 females and 9 males) presented neurological manifestations (18.9%). Sixty-three had PNS manifestations (16%) and 14 had CNS manifestations (3.6%). Most frequent peripheral manifestations were pure sensitive neuropathy (9.2%) and sensory-motor neuropathy (5.3%). Only 2 patients (0.6%) had isolated ganglionopathy. Most frequent central manifestations were cerebral vasculitis (5 patients, 1.3%) and myelitis (4 patients, 1.0%) Patients with neurological involvement had more severe disease according to the ESSDAI scoring system, 8.9 (±6.6) versus 3.9 (±4.8). They had more frequently immunomodulatory/immunosuppressive drugs, 32.4% (24/74) versus 13.8% (44/318) (p=0003). Vasculitis was seen in 21 of 73 patients with neurological manifestations (28.8%) and in 30 of 318 patients without (9.4%) (p<0.0001). During follow up, appearance of new neurological symptoms was seen more frequently in patients with neurological manifestations at inclusion, 30.2% (16/53) versus 7.0% (19/270), than in those without neurological manifestations (p<0.0001). Symptoms improvement was seen in 19/76 patients (25%). Conclusions The prevalence of neurological manifestations in the ASSESS cohort was about 20% and is comparable to data in the literature. Isolated ganglionopathy, which is frequently considered as the most specific neurological manifestation in pSS, was rare (<1%). Neurological manifestations was associated with more general systemic activity and more frequent use of immunosuppressors. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):804.1-804. DOI:10.1136/annrheumdis-2015-eular.4357 · 10.38 Impact Factor
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    ABSTRACT: Background Neonatal lupus syndrome (NLS) includes congenital heart block (CHB) and cardiomyopathies. Its optimal management is debated. Objectives We analyzed the mortality and morbidity of CHB, with special focus on risk factors. Methods This was a retrospective study of the French national registry of NLS. Inclusion criteria were high-degree CHB associated with maternal anti-SSA/SSB antibodies. Results 214 CHB were included (202 in utero cases and 12 neonatal cases). These 214 fetuses or children were born to 195 mothers anti-SSA (99.5%) and/or anti-SSB antibodies (60%) positive. 51 mothers (26.2%) fulfilled the classification criteria for an autoimmune disease: systemic lupus erythematosus (n=23), Sjögren syndrome (n=14), undifferentiated connective tissue disease (n=7), or other autoimmune disease (n=7). The factors associated with feto-neonatal deaths (15.7%) were hydrops (p<0.001; HR: 12.4 [95%CI: 4.7-32.7]) and prematurity (p=0.002; HR: 17.1 [95%CI: 2.8-103.1]). During a median follow-up of 7 years [birth to 36.1 years], 148 of 187 surviving children (79.1%) had a pacemaker, 35 (18.8%, one missing data) had dilated cardiomyopathy (DCM), and 22 (11.8%) died. DCM was neonatal (n=13) or late-onset (n=22, diagnosed at a median age of 15.2 months [3.6 months-22.8 years]). Factors associated with neonatal DCM were maternal treatment with hydroxychloroquine, in utero cardiomegaly, in utero DCM, and hydrops. By contrast, only non-white race origin and significant in utero valvulopathy were associated with late-onset DCM. On multivariate analysis, only in utero DCM was associated with neonatal DCM (p=0.0001; HR 15.99 [95%CI: 3.93-65.01]), whereas non-white race origin was associated with late-onset DCM (p=0.0147; HR 3.65 [95%CI: 1.28-10.0]). For children who survived the neonatal period (n=179), the risk of death during follow-up was 7.8%. On multivariate analysis, the only factor associated with late mortality was postnatal DCM (neonatal and late-onset DCM) (p<0.0001; HR 36.48 [95% CI 8.11-164.13]). The probability of survival at 10 years of age for a child with CHB born alive was 87.1%: 23.1% in the presence of neonatal DCM, 53.9% for those who developed a late-onset DCM requiring treatment versus 98.6% in those without DCM. Fluorinated steroid in utero treatment was not associated with CHB regression, survival or absence of late-onset DCM. Conclusions The factors associated with late-onset DCM differ completely from those associated with neonatal DCM. Our findings do not support the use of fluorinated steroids for CHB. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):102.3-103. DOI:10.1136/annrheumdis-2015-eular.2641 · 10.38 Impact Factor

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6k Citations
1,762.07 Total Impact Points


  • 2000–2015
    • Université du Droit et de la Santé Lille 2
      • • Laboratorie d'Immunologie
      • • Faculty of Medicine
      Lille, Nord-Pas-de-Calais, France
    • Faculté des Sciences Ain Chock - Casablanca
      Anfa, Grand Casablanca, Morocco
    • Centre Oscar Lambret
      Lille, Nord-Pas-de-Calais, France
  • 1993–2015
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 1992–2013
    • Centre Hospitalier Régional Universitaire de Lille
      • Division of Internal Medicine
      Lille, Nord-Pas-de-Calais, France
  • 2009
    • University of Florence
      Florens, Tuscany, Italy
  • 1993–2009
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 2005
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
  • 2002–2004
    • Centre Hospitalier Régional et Universitaire de Besançon
      Becoinson, Franche-Comté, France
    • Centre Hospitalier Universitaire de Brest
      Brest, Brittany, France
  • 1997
    • Hôpital Saint-Vincent-de-Paul – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 1996
    • Université Paris 13 Nord
      Île-de-France, France
  • 1990–1992
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1989–1991
    • Unité Inserm U1077
      Caen, Lower Normandy, France