E. Hachulla

University of Lille Nord de France, Lille, Nord-Pas-de-Calais, France

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Publications (926)1817.41 Total impact

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    ABSTRACT: Evaluating lymphocytic infiltration of minor salivary gland biopsy in primary Sjögren’s syndrome is challenging. We developed and evaluated a digital method for quantifying B and T lymphocytes in whole minor salivary gland biopsy slides. Minor salivary gland biopsies were immunostained with anti-CD20/anti-CD3 antibodies using red/brown chromogens. Slides were digitised and spliced into mosaics of smaller JPEG format images in which red and brown pixels were counted. ImageJ Cell counter was used for validation. Agreement between the digital and manual methods was evaluated using Bland-Altman plots and the interclass correlation coefficient. External validation relied on the Chisholm-Mason, Tarpley, and focus-score methods. Of 62 minor salivary gland biopsy slides, 61.3 % had a Chisholm-Mason grade ≥ III or a focus score ≥1. The number of pixels correlated well with manual cell counts (r = 0.95 for red pixels vs. B cell count and r = 0.91 for brown pixels vs. T cell count). Interclass correlation coefficients between digital and manual counts were excellent (0.92 for B/T cells). B-cell proportion showed a significant positive correlation with the focus score (Spearman’s coefficient 0.463, p < 0.0001). Median B-cell proportion was lower in minor salivary gland biopsies with Chisholm grades I–II (2.5 % (0.2–13.9)) than III–IV (30.0 % (15.5–45.2)) and increased with Tarpley’s class (1, 2.2 % (0.2–6.6); 2, 27.2 % (13.0–38.9); and 3–4, 48.5 % (29.4–56.4); p < 0.001 for all comparisons). Minor salivary gland biopsy B-cell proportion was also significantly correlated with several markers of clinical and biological activity of the disease, especially with markers of systemic B-cell hyperactivation. The digital procedure proved accurate compared to the reference standard, producing reliable results for whole tissue sections. Trial registration ClinicalTrials.gov [NCT00740948]. Registered 22 August 2008.
    Full-text · Article · Dec 2016 · Arthritis research & therapy
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    ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased mortality and significant personal, psychological and socioeconomic consequences. An agreed definition of remission is needed and lacking. We sought to visualize 'remission in SLE' in European patients considered by their physicians to be 'in remission' by comparing the reported symptom burden as reported by treating physicians for patients considered to be 'in remission' and those not considered to be 'in remission'. Data for 1227 patients drawn from a multinational, real-world survey of patients with SLE consulting practising rheumatologists and nephrologists in France, Germany, Italy, Spain, and the UK show that physicians classed their patients as 'in remission' despite a considerable ongoing symptom burden and intensive immunosuppressive medication. Patients considered to be 'in remission' still had a mean of 2.68 current symptoms vs 5.48 for those considered to be not 'in remission' (p < 0.0001). The most common symptoms among those seen to be 'in remission' were joint symptoms, fatigue, pain, mucocutaneous involvement, haematological manifestations and kidney abnormalities. The current analysis highlights important ongoing disease activity, symptom burden and immunosuppressive medication in European patients with SLE considered by their treating physician to be 'in remission'. For a further improvement of outcome, there is an urgent need for an international consensus on the definitions for remission among patients with SLE.
    No preview · Article · Dec 2015 · Lupus

  • No preview · Article · Dec 2015

  • No preview · Article · Dec 2015

  • No preview · Article · Dec 2015 · La Revue de Médecine Interne
  • C.M. Yelnik · M. Lambert · E. Hachulla
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    ABSTRACT: Le cerveau est l’un des principaux organes touchés au cours du syndrome des anticorps antiphospholipides. Le neurologue est donc un acteur important de la prise en charge de ces patients. L’accident vasculaire cérébral ischémique ou l’accident ischémique transitoire sont les manifestations neurologiques les mieux documentées du syndrome des anticorps antiphospholipides, qui en font donc une étiologie classique d’ischémie cérébrale chez le sujet jeune. Poser un diagnostic est un enjeu majeur pour ces patients car ceux-ci sont exposés à risque immédiat et prolongé de récidive thrombotique. Ce risque est cependant hétérogène et étroitement lié au profil de positivité des anticorps antiphospholipides. De nombreuses autres manifestations neurologiques sont également rencontrées chez ces patients, telles que migraine, crises d’épilepsie, troubles cognitifs, troubles psychiatriques, chorée, myélite transverse et sclérose en plaques-like syndrome. L’objectif de cet article est de faire un état des lieux des connaissances actuelles sur les manifestations neurologiques centrales du syndrome des anticorps antiphospholipides, accompagnée d’une mise au point sur la prise en charge de ces patients après un événement neurologique, afin de guider le neurologue dans sa pratique quotidienne.
    No preview · Article · Dec 2015 · Pratique Neurologique - FMC

  • No preview · Article · Dec 2015

  • No preview · Article · Dec 2015
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    ABSTRACT: Subcutaneous immunoglobulin (SCIg) therapy is indicated in primary and secondary immunodeficiency diseases. Its use in practice is being extended to autoimmune diseases. Few studies investigated the feasibility and safety of SCIg in these rare conditions. The aim was to describe the use of SCIg in inflammatory myopathies including polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM), in real-life settings. This case series was based upon a retrospective data collection. The primary objective was to assess the feasibility of the SCIg injections for the treatment of autoimmune diseases and adherence to high doses. Secondary objectives included safety and efficacy. Nineteen cases were identified: 7 patients were diagnosed with PM, 7 with IBM, 2 with DM, and 3 with myositis associated with connective tissue disease. Patients were treated and followed-up for a mean duration of 18.8months (range 4.5-42). They received a median of 64 SCIg infusions and a total of 1215 infusions. Out of 14 patients, 10 showed an improvement in muscle strength, and 7 out of 11 showed an improvement in muscle disability scale. Two patients were lost to follow-up. Few slight adverse reactions were reported including mainly mild headaches and local skin reactions. Any serious adverse event was reported. These results suggest that the use of high-dose SCIg is feasible, beneficial and safe in patients with inflammatory myopathies. SCIg could be an alternative of IVIg in patients with difficult venous access or with insufficient response, and in patients preferring home care setting.
    No preview · Article · Dec 2015 · Autoimmunity reviews
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    ABSTRACT: Objective: To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (pSS). Methods: A multicenter case-controls survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after pSS diagnosis. They were mainly recruited through the "Club Rhumatismes et Inflammation" network. For each case, 2 controls (matched on disease duration and age) were randomly selected among patients without lymphoma. Cases and controls were compared with univariate then multivariate analysis to identify independent predictors of lymphoma. Results: One hundred and one pSS patients with lymphoma were included; 87 were women (86.1%) with a mean age ± SD of 57.4 ±12.6 years. Histologic type was B cell non Hodgkin lymphoma (B-NHL) in 99/101 with 76 (76.8%) marginal zone including 58 (58.6%) developed from the Mucosa associated lymphoid tissue (MALT). The most frequent localization was salivary glands (43 cases). A specific treatment was initiated at diagnosis in 87/99 patients with B-NHL and remission was obtained in 61 patients (61.6%). In the multivariate analysis salivary gland enlargement, rheumatoid factor, low C4, cryoglobulinemia, lymphopenia and disease activity (excluding the lymphoma domain) were found predictors of lymphoma. We did not find any role of previous treatments of pSS for preventing or favoring lymphoma occurrence. Conclusion: In addition to previous known predictive factors of lymphoma occurrence, this case-control study of pSS-associated lymphoma demonstrated the independent role of rheumatoid factor and of disease activity. It highlights the role of chronic antigenic stimulation and disease activity in the development of this severe complication. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Arthritis and Rheumatology
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    ABSTRACT: Introduction: Multicentric Castleman's disease can mimic adult-onset Still disease. It is exceptionally associated with anasarca, thrombotic microangiopathy and dysautonomia. Case report: We report a 32-year-old woman with an association of oligoanuria, anasarca, thrombotic microangiopathy with features compatible with adult-onset Still disease. The outcome was initially favorable with corticosteroids, immunoglobulins and plasmapheresis but with the persistence of relapses marked by severe autonomic syndrome and necessity of high dose corticosteroids. The diagnosis of mixed type Castleman's disease, HHV8 and HIV negative, was obtained four years after the onset of symptoms by a lymph node biopsy. The outcome was favorable after tocilizumab and corticosteroids but tocilizumab had to be switched to anakinra to ensure a proper and long-lasting control of the disease. Conclusion: Our patient partially fits the description of TAFRO syndrome (Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly), a MCM rare variant, recently described in Japanese patients.
    No preview · Article · Sep 2015 · La Revue de Médecine Interne
  • P-Y Hatron · E Hachulla

    No preview · Article · Sep 2015 · La Revue de Médecine Interne
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    Full-text · Article · Sep 2015 · Pediatric Rheumatology
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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.
    No preview · Article · Aug 2015 · Arthritis and Rheumatology

  • No preview · Article · Aug 2015 · La Revue de Médecine Interne
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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.
    No preview · Article · Jul 2015 · Annals of the Rheumatic Diseases
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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.
    Full-text · Article · Jul 2015 · Journal of Autoimmunity

  • No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background IgG4-related disease (IgG4-RD) is a recently recognized systemic condition characterized by unique pathological features that affect a wide variety of organs. Most available data come from descriptive series of patients with a unique organ involvement. Objectives To describe clinical and biological characteristics of IgG4-RD patients from a large multicentric national registry. Methods Cases were collected through a multicentric and multidisciplinary national registry between 2009 and 2014. Data were collected using a standardized form including clinical, biological, pathological and therapeutic findings. Results From 120 collected cases, 90 cases fulfilled comprehensive diagnostic criteria for IgG4-RD [1]. Patients presented with definite (44.5%), probable (24.4%) and possible (31.1%) IgG4-RD diagnosis. They were 64 males and 26 females (sex ratio 2.5:1) with a median age at onset of 56 years. Ninety-three percent of patients presented with symptoms at diagnosis, including constitutional symptoms (45%), abdominal pain (26%), cough or dyspnea (17%) and sicca syndrome (15%). Median number of organs involved was 3 and 80% of patients had multi-organ involvement, defined by ≥3 organs involved. Lymph nodes (58.9%), pancreas (44.4%), kidney (32.2%), salivary glands (32.2%), retroperitoneum (28.9%) and biliary ducts (27.8%) were the most frequent tissues involved. Inflammatory pseudotumors (IPT) were observed in 30% of patients (pulmonary, orbital, hepatic, meningeal or breast IPT). IgG4 serum concentration was >135 mg/dl in 84% of patients, with a mean of 989 mg/dl (ranging from 30 to 5380). Polyclonal hypergammaglobulinemia was noted in 79% of cases, and low complement in 34%. Elevated C reactive protein level was observed in 48% of patients. Mean follow-up was 17.6 months (ranging from 0 to 94). Only ten patients (11%) did not require systemic therapy. Seventy-seven patients (86%) received steroids in first line therapy. A second line therapy was required in 36 patients (40%), with 20 patients treated with 3 lines of treatment or more. Indications of second line treatments were essentially represented by relapse or corticodependance. Second line treatments were azathioprine in 14 patients, rituximab in 10, mycophenolate mofetil in 3, cyclophosphamide in 3 and methotrexate in 2. Six patients underwent surgery, essentially for histological diagnosis because cancer was suspected. Conclusions As described in Asiatic populations, most IgG4-RD patients from our national registry present with multiple organ involvement. Localized disease is less frequent. Normal IgG4 levels are observed in 16% of patients. Steroids are usually effective, but almost half of patients require second line immunosuppressive therapy as steroid sparing agent or for relapse. References Disclosure of Interest None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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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
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases

Publication Stats

7k Citations
1,817.41 Total Impact Points

Institutions

  • 1994-2016
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2015
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
    • Lille Catholic University
      Lille, Nord-Pas-de-Calais, France
    • Centre Hospitalier Universitaire de Nancy
      Laxou, Lorraine, France
  • 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
  • 1992-2015
    • Centre Hospitalier Régional Universitaire de Lille
      • Division of Internal Medicine
      Lille, Nord-Pas-de-Calais, France
  • 1993-2007
    • 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
  • 1991
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1989-1991
    • Unité Inserm U1077
      Caen, Lower Normandy, France