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Featured researches published by Arnaud Theulin.


Autoimmunity | 2015

Chronic histiocytic intervillositis: Outcome, associated diseases and treatment in a multicenter prospective study

A. Mekinian; Nathalie Costedoat-Chalumeau; Agathe Masseau; Angela Botta; Anastasia Chudzinski; Arnaud Theulin; Virginie Emmanuelli; E. Hachulla; Sara De Carolis; Aurélie Revaux; Pascale Nicaise; Françoise Cornelis; Damien Subtil; Francois Montestruc; Martine Bucourt; Sylvie Chollet-Martin; Lionel Carbillon; Olivier Fain

Abstract Introduction: In this prospective multicenter study, we aimed to describe (1) the outcome of pregnancy in the case of previous chronic histiocytic intervillositis (CHI), (2) the immunological findings and associated diseases, (3) the treatments, and (4) the factors associated with pregnancy loss. Methods: We prospectively included all patients with a prior CHI with ongoing pregnancy between 2011 and 2013. Results: Twenty-four women (age 34 ± 5 years) were included in this study. An autoimmune disease was present in seven (29%) cases. Twenty-one prospective pregnancies were treated. The number of live births was more frequent comparatively to the previous obstetrical issues (16/24 versus 24/76; p = 0.003). Most of the pregnancies were treated (88%), whereas only 13% of previous pregnancies were treated (p < 0.05). No difference was found with respect to the pregnancy outcome in the different treatment regimens. In univariate analyses, a prior history of intrauterine death and intrauterine growth restriction and the presence of CHI in prospective placentas were associated with failure to have a live birth. Discussion: In this multicenter study, we show the frequency of the associated autoimmune diseases in CHI, as well as the presence of autoantibodies without characterized autoimmune disease. The number of live births increased from 32% to 67% in the treated pregnancies. Despite the treatment intervention, the risk of preterm delivery remained at 30%. Last, we show that the recurrence rate of an adverse pregnancy outcome persisted at 30% despite treatment intervention. Conclusion: CHI is associated with high recurrence rate and the combined regimen seems to be necessary, in particular, in the presence of previous intrauterine death.


Expert Review of Clinical Immunology | 2014

Classification criteria and treatment modalities in primary Sjögren’s syndrome

Alia Fazaa; Tristan Bourcier; Emmanuel Chatelus; Christelle Sordet; Arnaud Theulin; Jean Sibilia; Jacques-Eric Gottenberg

Primary Sjögren’s syndrome is a systemic autoimmune disease, characterized by a lymphocytic exocrinopathy. Oral and ocular dryness, asthenia and pain represent hallmarks of the disease. Systemic manifestations concern a third of patients, including lymphoma in 5% of the patients. The American European Consensus Group classification criteria have been used in current practice and clinical trials since 2002. New classification criteria were recently proposed by the American Congress of Rheumatology. A group of international experts are currently working to reach a new consensus between the American European Consensus Group classification criteria and the American Congress of Rheumatology proposal for disease classification. In addition, international consensus disease activity scores were recently established. Regarding treatment modalities, symptomatic treatments remain the cornerstone of therapy in pSS, but new biologic treatments are currently evaluated.


Joint Bone Spine | 2014

An arthro-dermato-pulmonary syndrome associated with anti-MDA5 antibodies

Raphaëlle Goussot; Arnaud Theulin; Joëlle Goetz; Jean Sibilia; Jacques-Eric Gottenberg; Alain Meyer

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 1 mars 2014


Annals of the Rheumatic Diseases | 2012

Campylobacter fetus infection in three rheumatoid arthritis patients treated with rituximab

Alain Meyer; Arnaud Theulin; Emmanuel Chatelus; Xavier Argemi; Christelle Sordet; R.-M. Javier; Yves Hansmann; Jean Sibilia; Jacques-Eric Gottenberg

Campylobacter fetus osteoarticular or prosthetic material infection or cellulitis has been rarely described, mainly in immunocompromised patients. Among these cases, only two patients had inflammatory systemic diseases treated with rituximab (RTX).1 We report three patients with rheumatoid arthritis (RA) treated with RTX who developed osteoarticular or cutaneous infection due to C fetus . The patients were aged 71, 53 and 80 years with disease durations of 24, 13 and 19 years, respectively. All patients had a history of diabetes. Patients 1 and 3 had hypertensive cardiomyopathy, while patient 2 suffered from chronic obstructive pulmonary disease (COPD) and patient 3 from bronchiolitis obliterans organising pneumonia. All patients were co-treated with corticosteroids (10 mg/day) and disease-modifying antirheumatic …


Presse Medicale | 2014

When biologics should be used in systemic lupus erythematosus

Jacques-Eric Gottenberg; Noël Lorenzo; Christelle Sordet; Arnaud Theulin; Emmanuel Chatelus; Jean Sibilia

Recently, the use and evaluation of biologics increased in systemic lupus erythematosus (SLE). However, no international recommendation is available concerning the use of biologics with regards to the subset of patients who should be treated, the optimal time to treat, the objective of treatment and the manner to discontinue it. To address these complex questions, we focused on biologics already evaluated in at least two published randomized controlled trials. We summarized the results of these trials and available observational data in registries. Taking into account the clinical evidence, we proposed some guidance on the way biologics could be used in SLE. Many areas of uncertainty persist and require intensifying efforts from the academic world to set up new trials, and develop international recommendations.


International Journal of Cardiology | 2017

Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus

Nathalie Morel; Kateri Levesque; Alice Maltret; Gabriel Baron; Mohamed Hamidou; P. Orquevaux; Jean-Charles Piette; François Barriere; Jérôme Le Bidois; Laurent Fermont; Olivier Fain; Arnaud Theulin; François Sassolas; Quentin Hauet; G. Guettrot-Imbert; Sophie Georgin-Lavialle; Christophe Deligny; E. Hachulla; Luc Mouthon; Claire Le Jeunne; Philippe Ravaud; Delphine Le Mercier; B. Romefort; Elisabeth Villain; Damien Bonnet; Nathalie Costedoat-Chalumeau

BACKGROUND Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. METHODS We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. RESULTS Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth-36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20-8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81-9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94-15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth-4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months-22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63-4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. CONCLUSION Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB.


Annals of the Rheumatic Diseases | 2015

OP0090 Determinants of Survival of Fetuses with Autoimmune Congenital Heart Block and Factors Associated with Neonatal and Late-Onset Dilated Cardiomyopathy: 214 Cases from the French Registry of Neonatal Lupus

Kateri Levesque; Nathalie Morel; Alice Maltret; Gabriel Baron; Mohamed Hamidou; P. Orquevaux; J.-C. Piette; F. Barriere; J. Lebidois; Laurent Fermont; Olivier Fain; Arnaud Theulin; F. Sassolas; P. Pezard; Zahir Amoura; G. Guettrot-Imbert; D. Lemercier; S. Georgin-Lavialle; Christophe Deligny; E. Hachulla; Luc Mouthon; Philippe Ravaud; Elisabeth Villain; Damien Bonnet; Nathalie Costedoat-Chalumeau

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 | 2013

THU0412 Reactive hyperemia index (RHI) is associated with macrovascular disease and lung disease in systemic sclerosis

Alain Meyer; Arnaud Theulin; Emmanuel Chatelus; Christelle Sordet; R.-M. Javier; Bernard Geny; Jacques-Eric Gottenberg; Jean Sibilia

Background Vasomotor endothelial function is an emerging data in functional exploration. Its meaning is well established in cardiology, where it independently predicted the occurrence of cardiovascular events. It interest has been poorly assess in rheumatology. Recently it was shown that patients with rheumatoid arthritis (RA) and systemic sclerosis (SS) have impaired endothelial function compared to controls. In the SS, endothelial function was correlated with the microvascular disease observed in capillaroscopy (1,2). Methods Reactive hyperhemia index (RHI), a simple, reliable and non invasive method for endothelial function exploration (3), taken at the estimated maximal vasodilatation (1 min 30 s after release of occlusion) using digital pulse amplitude tonometry was performed on 21 patients with SSc, 14 patients with IR and 15 healthy subjects. In IR and SSc patients, DAS 28, Rodnan score, cardiac echography, spirometry, DLCO and 6 minute walk test were also performed. Results Characteristics of the 3 groups: Mean age of SSc was 57 years (28-75), sex ratio (SR) was 5/1 and mean disease duration was 4.5 years (0-22). 11 patients had limited form and 7 had diffuse form. The mean Rodnan score in 13 of 18 SSc patients was 10.2 (4-28). IA patients had a mean age of 60 years (38-73) and SR was 6/1. 11 patients had RA, 1 spondylarthropathy, one antisynthetase syndrome and one myositis with SRP antibody. Mean IR duration was 16 years (0-31). Mean DAS 28 in 11 of 14 IR patients was 4.45 (2.03-6.66) and 8 patients were treated with biologic treatments. Controls were 57 years old (53-64) and SR was 6/1. Patients mean weight was comparable: 67 kg (45-106), 67 kg (54-79) and 64 kg (54-91) in SSc, PR and controls respectively. Mean blood pressure was also similar (SSc: 127/73mmHg, PR: 128/76mmHg and controls: 130/75mmHg in SSc). One IR patient suffered of diabetes mellitus and had history of heart infarct. Results: Median RHI was significantly lower in SSc patients (median 1.45, range 1.00-3.18) compared with IA patients (median 2.01, range 1.35-3.02) (p=0.03) and was significantly lower in both SSc and IA patients compared with controls (median 2.60, range 1.40-3.05) (p=0.001 and p=0.049 respectively). In SSc patient but not in IA patients, RHI value significantly correlated with echocardiograhic PAPs (r: -0.75; p=0.037), DLCO (r: 0.53; p=0.017), total pulmonary capacity (r: 0.46; p=0.032), functional and maximal vital capacity (r: 0.48; p=0.032 and r: 0.48; p=0.033 respectively). Conclusions RHI, an easy and non invasive test, is associated with macroangiopathy and lung involvement in SSc. Further studies are necessary to determine whether RHI may represent disease activity and therapeutic response marker. References Rollando et al. J Rheumatol. 2010;37:1168-73. Hannawi et al. Arthritis Res Ther. 2009;11:R51. Hamburg et al. Trends Cardiovasc Med. 2009;19:6-11. Disclosure of Interest None Declared


Annals of the Rheumatic Diseases | 2013

AB0779 Eosinophilic myositis and rheumatoid arthritis as first manifestation in a patient carrying myotonic dystrophy type 2 (CCTG)n expenssion of ZNF9 gene

Alain Meyer; Arnaud Theulin; Emmanuel Chatelus; Christelle Sordet; R.-M. Javier; B. Lannes; A. Echaniz; Bernard Geny; Jacques-Eric Gottenberg; Jean Sibilia

Background Eosinophilia myopathies (EM) are a heterogeneous group of disease characterized by eosinophlic infiltration muscles associated with peripheral blood and/or bone marrow hypereosinophilia. The diagnosis of idiopathic EM is usually retained after the exclusion of accepted EM aetiologies. Recently, mutations in the CAPN3 and SGCG genes, encoding calapain-3 and γ-sarcoglycan proteins, were identified in some patients with idiopathic EM. Objectives We report the first case of a patient with idiopathic EM and rheumatoid arthritis (RA) who carried CCTG expansion in intron 1 of the ZNF9 gene, a mutation characteristic of myotonic dystrophy type 2 (DM2). Results A 40 years old woman presented with arthromyalgia for 4 months. She had a 18 months history of hypereosinophilia. Physical examination showed a symmetrical oedematous polyarthritis. Proximal muscles were painful but there was no muscle weakness. Eosinophilic polynuclear count was 8,210/mm3. CRP amount was 11mg/L. Serum creatine kinase level was 406 IU/L. Serum tested positive for anti-citrullinated protein antibodiesand rheumatoid factor. There was no anti nuclear antibody nor ANCA. Fecal examination didn’t found any parasite. Serological tests for T spiralis, T canis, A lubricoides, E histolytica, A fumigatus, E granulosus, and VIH were negative. Osteomedular biopsy showed hypereosinophilc infiltration (30%). Karyotype on myelogram was normal. Molecular analysis didn’t detected Philadelphia chromosome, mutation in JAK2, KIT, PDGFRs genes nor clonal TCR rearrangement. Foots and hands radiographs, tomography of chest abdomen and pelvis, electrocardiogram and cardiac echography found no abnormality. Electromyography showed myogenic features. Muscle biopsy is presented on figure n°1. The diagnosis of idiopathic ME associated with RA was retained. The patient was successfully treated with non steroidal anti inflammatory drugs and methotrexate Ten years after, a patient’s sister was diagnosed with DM2. Quadruplet repeat primed-PCR performed on the patient’s blood sample found CCTG expansion in intron 1 of the ZNF9 gene. Expansion size measured with southern blot was 8 kb. At this time, there was no muscular symptom but a diabetes had appeared. Conclusions DM2 is typically characterized by muscle weakness, myotonia, cataract and diabetes but increasingly, incomplete or atypical phenotypes are encountered. A strong incidence of autoimmune diseases, including RA, was reported in DM2 patients. In this observation, EM symptoms disappeared with immunomodulatory therapy, that argue for an authentic immunologic driven process. One explanation might be that, contrary to calpainopathies and sarcoglycanopathies, genetic lesion in DM2 does not eliminate an essential muscle protein. Instead, it induces a defect of RNA processing that may impact many different pathways including inflammation. EM with RA might be inaugural manifestations of DM2. Disclosure of Interest None Declared


Amyloid | 2012

In antisynthetase syndrome, amyloidosis is rare and might not be related to the disease

Alain Meyer; Arnaud Theulin; Emmanuel Chatelus; Christelle Sordet; Rose-Marie Javier; Luc Marcelin; Joëlle Goetz; Bernard Geny; Jean Sibilia; Jaques-Eric Gottenberg

Antisynthetase syndrome (ASS) is a rare systemic inflammatory disease associated with myositis, polyarthritis, interstitial lung disease, Raynaud’s phenomenon and the presence of auto-antibodies targeting aminoacyl-tRNA-synthetase enzymes [1]. We recently diagnosed amyloidosis in one patient with ASS. To better characterize this unusual association, we retrospectively assessed amyloidosis frequency in a monocentric cohort of 30 patients with ASS and performed a systematic review of the literature. The charts of the patients followed at Strasbourg University Hospital who serum tested positive for aminoacyltRNA-synthetase antibody using immunodot (Euroimmun, Germany and/or D-Tek, Belgium) between 1994 and 2011 were systematically reviewed. Patients were diagnosed with ASS if they had myositis according to Bohan and Peter criteria [2] and/or interstitial lung disease (ILD) diagnosed on chest computed tomography (CT). Diagnosis of amyloidosis was made if extracellular deposit stained with Congo Red was demonstrated in a biopsy. Monoclonal mouse antibodies against human AA protein, polyclonal rabbit antibodies against κ and λ light chains used for amyloidosis typing were purchased from Dako, Denmark. Thirty-three patients tested positive for aminoacyl-tRNAsynthetase antibodies. Charts were available for 30 patients who all had ASS. Patients tested positive for PL-7 (n = 4), PL-12 (n = 4), Jo-1 (n = 22) antibodies. Median follow-up was 6 years (range 1 month–16 years). Amyloidosis occurred in two patients with ASS.

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Jean Sibilia

University of Strasbourg

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Alain Meyer

University of Strasbourg

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Bernard Geny

University of Strasbourg

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R.-M. Javier

University of Strasbourg

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Joëlle Goetz

Louis Pasteur University

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