Laurent Arnaud

UPMC, Pittsburgh, Pennsylvania, United States

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Publications (136)530.62 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months. © 2014 by American Society of Clinical Oncology.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 11/2014;
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    ABSTRACT: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients. Copyright © 2014. Published by Elsevier SAS.
    La Revue de medecine interne / fondee ... par la Societe nationale francaise de medecine interne. 11/2014;
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    ABSTRACT: This study aimed to estimate the responsiveness to change of a generic [the 36-item Short Form Health Survey (SF-36)] and a specific health-related quality of life questionnaire [the Lupus Quality if Life questionnaire (LupusQoL)] according to SLE patients' self-reported changes in health status.
    Rheumatology (Oxford, England) 10/2014; · 4.24 Impact Factor
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    ABSTRACT: We performed an individual patient meta-analysis to determine whether aspirin has a significant protective effect on the risk of first thrombosis among patients with antiphospholipid antibodies (aPL). Five international cohort studies with available individual patient-level data, reporting on primary prophylaxis with continuous treatment with low-dose aspirin in patients with aPL were included. The main outcome was the occurrence of a first thrombotic in patients with aPL treated with low-dose aspirin compared to those not treated with low-dose aspirin. Pooled Hazard Ratios (HRs) and 95%CIs were calculated using frailty models. We pooled data from 497 subjects and 79 first thrombotic events (3469 patient-years of follow-up). After adjustment on cardiovascular risk factors, aPL profiles, and treatment with hydroxychloroquine, the HR for the risk of a first thrombosis of any type in aPL carriers treated with low-dose aspirin versus those not treated with aspirin was 0.43 (95%CI 0.25–0.75). Subgroup analysis showed a protective effect of aspirin against arterial (HR: 0.43 [95%CI: 0.20–0.93]) but not venous (HR: 0.49 [95%CI: 0.22–1.11]) thrombosis. Subgroup analysis according to underlying disease revealed a protective effect of aspirin against arterial thrombosis for systemic lupus erythematosus (SLE) (HR: 0.43 [95%CI: 0.20–0.94]) and asymptomatic aPL carriers (HR: 0.43 [95%CI 0.20–0.93]). We found no independent protective effect of hydroxychloroquine. This individual patient data meta-analysis shows that the risk of first thrombotic event as well of first arterial thrombotic event is significantly decreased among SLE patients and asymptomatic aPL individuals treated by low-dose aspirin.
    Autoimmunity Reviews. 10/2014;
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    ABSTRACT: Multiple factors contribute to the increased cardiovascular risk observed in patients with systemic lupus erythematosus (SLE). Among these are the so-called classical cardiovascular risk factors, the disease itself through its activity, treatments, and complications, and the thrombotic risk due to antiphospholipid antibodies (aPL). Observational studies suggest that most classical cardiovascular risk factors are observed more frequently in SLE patients than in the general population, and that these are insufficient to explain the increased cardiovascular risk observed in most studies. Given this high risk, adequate management of cardiovascular risk factors should be recommended in SLE patients. Paradoxically, the benefit due to the anti-inflammatory properties of treatments such as corticosteroids may exceed, in certain cases, their pro-atherogenic effect. Importantly, the tools that were developed for the estimation of cardiovascular risk at the individual level among the general population cannot be used reliably in SLE patients, as these tools appear to underestimate the true cardiovascular risk. The adequate indications and targets of cardiovascular treatments are therefore not fully known in SLE. A better understanding of the determinants of the cardiovascular risk in SLE will allow the identification and more tailored management of these high-risk patients.
    La Revue de medecine interne / fondee ... par la Societe nationale francaise de medecine interne. 09/2014;
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    ABSTRACT: In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability.
    Annals of the rheumatic diseases. 08/2014;
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    ABSTRACT: Background Autoimmune thrombotic thrombocytopenic purpura (AI-TTP) is characterized by an excess of circulating ultra-large von Willebrand Factor (vWF) due to anti-ADAMTS13 auto-antibodies. Animal studies however have shown that endothelial cell activation may also be an important trigger of AI-TTP.Objectives To prospectively study circulating biomarkers of endothelial lesion and activation such as circulating endothelial cells (CEC), soluble (s)P-selectin or vWF and of endothelial repair such as circulating progenitor cells (CPC) and endothelial progenitor cells (EPC) in AI-TTP, in correlation with disease severity and prognosis.Results22 patients were included in this study. CEC (p<0.01), vWF (p<0.05) and sP-selectin (p<0,01) were significantly increased during crisis and returned to baseline levels during remission. Both CEC (p<0.05) and sP-selectin (p<0.05) were significantly higher in patients who died or developed neurological sequelae. CPC counts were highly increased during the acute phase of the disease (p<0.001) and returned to baseline levels during remission. Among CPC, EPC were also increased during crisis (p<0.05) and significantly decreased during remission. Patients who received less than 16 plasma exchange (PE) therapy had significantly higher EPC counts (p<0.05) than those who needed more numerous PE to obtain remission, suggesting that initial EPC counts may be associated with faster endothelial repair.Conclusion The profile of circulating endothelial markers shows massive endothelial activation and repair/remodeling during AI-TTP, and suggests that CEC and EPC may be promising prognosis biomarkers of the disease.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 08/2014; · 6.08 Impact Factor
  • Source
    A. Mathian, L. Arnaud, Z. Amoura
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    ABSTRACT: Systemic lupus erythematous is a chronic autoimmune disease characterized by the inflammation of several tissues and the production of auto-antibodies directed against nuclear antigens. Complex genetic disorders and environmental factors are at the origin of the disease but the precise cause of the auto-immune process is still unknown. Both innate and adaptive immune systems are involved. Apoptosis seems to be the main source of auto-antigens. The interactions between apoptotic cells, dendritic cells and lymphocytes activate the production of pathogenic antibodies and T lymphocytes. Amplification loops sustain the auto-immune process and the chronic inflammation. Several data point out B-lymphocytes and several cytokines involved in their homeostasis as new promising therapeutic targets.
    La Revue de Médecine Interne. 08/2014; 35(8):503–511.
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    ABSTRACT: Distinction between infection and febrile disease flare in patients with systemic lupus erythematosus (SLE) is fundamental but often difficult to make, because clinical presentation can be similar. A systematic review of all articles indexed in PubMed through October 2013 was performed, in order to examine the potential role of procalcitonin (PCT) for the discrimination between SLE flare and infection. Among the 12 papers identified, 5 articles reported on PCT levels in SLE patients without infection, 6 compared PCT levels between SLE patients with flare versus those with infection, and 1 analyzed PCT levels in active patients with and without bacterial infection. These data suggest the absence of correlation between PCT levels and SLE disease activity. Furthermore, PCT levels detected during disease flares are lower than those observed during bacterial infections. PCT can therefore be used accurately in the early differentiation between bacterial infection and flare in febrile SLE patients. Raised PCT levels ≥0.5 μg/L should strongly suggest bacterial infection in the context of SLE, keeping in mind the limited data available in case of hemophagocytic syndrome. Elevated PCT levels in SLE patients should always prompt a thorough search for sources of potential infection.
    Clinical Rheumatology 07/2014; · 2.04 Impact Factor
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    ABSTRACT: Histiocytoses are a group of heterogeneous diseases that mostly comprise Langerhans cell histiocytosis (LCH) and non-LCH. The association of LCH with non-LCH is exceptional. We report 23 patients with biopsy proven LCH associated with Erdheim-Chester disease (ECD) (mixed histiocytosis) and discuss the significance of this association. We compare the clinical phenotype of these patients with that of 56 patients with isolated LCH and 53 patients with isolated ECD. The average age at diagnosis was 43. ECD followed (n=12), or was diagnosed simultaneously (n=11), but never preceded LCH. Although heterogeneous, the phenotype of patients with mixed histiocytosis was closer to that of isolated ECD than to that of isolated LCH (principal component analysis). LCH and ECD improved in response to interferon-α-2a treatment in only 50% (8/16) of cases. We found the BRAF(V600E) mutation in 11/16 LCH lesions (69%) and in 9/11 ECD lesions (82%). Eight patients were mutated in both ECD and LCH biopsies. Our findings indicate that the association of LCH and ECD is not fortuitous and suggest a link between these diseases involving the BRAF(V600E) mutation.
    Blood 06/2014; · 9.78 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A43–A44. · 0.90 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A44. · 0.90 Impact Factor
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    ABSTRACT: Erdheim-Chester disease is a rare and orphan disease. Despite having been overlooked previously, numerous new cases have been diagnosed more recently. The number of Erdheim-Chester disease cases reported has increased substantially: more than 300 new cases have been published in the past 10 years. This situation is mainly a result of the generally better awareness among pathologists, radiologists, and clinicians of various aspects of this rare disease. The field has been particularly active in the last few years, with evidence of the efficacy of interferon-α, the description of a systemic pro-inflammatory cytokine signature, and most recently, reports of the dramatic efficacy of BRAF inhibition in severe, BRAF(V600E) mutation-associated cases of Erdheim-Chester disease. Also, BRAF mutations have been found in more than half of the patients with Erdheim-Chester disease who were tested. Detailed elucidation of the pathogenesis of the disease is likely to lead to the development of better targeted and more effective therapies.
    La Revue de Médecine Interne 05/2014; · 0.90 Impact Factor
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    ABSTRACT: Erdheim-Chester Disease (ECD) is a rare non-Langerhans histiocytosis. Recent findings suggest that ECD is a clonal disorder, marked by recurrent BRAFV600E mutations in more than 50% of patients, in which chronic uncontrolled inflammation is an important mediator of disease pathogenesis. Although approximately 500-550 cases have been described in the literature to date, increased physician awareness has driven a dramatic increase in ECD diagnoses over the last decade. ECD frequently involves multiple organ systems and has historically lacked effective therapies. Given the protean clinical manifestations and the lack of a consensus-derived approach for the management of ECD, we provide here the first multidisciplinary consensus guidelines for the clinical management of ECD. These recommendations were outlined at the First International Medical Symposium for ECD, comprised of a comprehensive group of international academicians with expertise in the pathophysiology and therapy of ECD. Detailed recommendations on the initial clinical, laboratory, and radiographic assessment of ECD patients are presented in addition to treatment recommendations based on critical appraisal of the literature and clinical experience. These formalized consensus descriptions will hopefully facilitate ongoing and future research efforts in this disorder.
    Blood 05/2014; · 9.78 Impact Factor
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    ABSTRACT: Necrotizing autoimmune myopathy (NAM) is a group of acquired myopathies characterized by prominent myofiber necrosis with little or no muscle inflammation. Recently, researchers identified autoantibodies (aAb) against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with NAM, especially in statin-exposed patients. Here we report what is to our knowledge the first European cohort of patients with NAM.The serum of 206 patients with suspicion of NAM was tested for detection of anti-HMGCR aAb using an addressable laser bead immunoassay. Forty-five patients were found to be anti-HMGCR positive. Their mean age was 48.9 ± 21.9 years and the group was predominantly female (73.3%). Statin exposure was recorded in 44.4% of patients. Almost all patients had a muscular deficit (97.7%), frequently severe (Medical Research Council [MRC] 5 ≤3 in 75.5%). Subacute onset (<6 mo) was noted for most of them (64.4%). Nevertheless, 3 patients (6.6%) had a slowly progressive course over more than 10 years. Except for weight loss (20%), no extramuscular sign was observed. The mean CK level was high (6941 ± 8802 IU/L) and correlated with muscle strength evaluated by manual muscle testing (r = -0.37, p = 0.03). Similarly, anti-HMGCR aAb titers were correlated with muscular strength (r = -0.31; p = 0.03) and CK level (r = 0.45; p = 0.01). Mean duration of treatment was 34.1 ± 40.8 months, and by the end of the study no patient had been able to stop treatment.This study confirms the observation and description of anti-HMGCR aAb associated with NAM. The majority of patients were statin naive and needed prolonged treatments. Some patients had a dystrophic-like presentation. Anti-HMGR aAb titers correlated with CK levels and muscle strength, suggesting their pathogenic role.
    Medicine 05/2014; 93(3):150-7. · 4.35 Impact Factor
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    ABSTRACT: Conflicting data have been published regarding the risk of cervical lesions among women with systemic lupus erythematosus (SLE). We systematically reviewed the evidence for an association of SLE with cervical precancerous lesions (High-grade Squamous Intraepithelial lesions, HSIL), and performed a meta-analysis to determine the risk of HSIL in SLE patients. Observational studies identified up to February 2013 from the Medline, Embase and Cochrane databases were selected if they assessed the prevalence of HSIL in female SLE patients versus healthy female controls and included in a meta-analysis with pooled effect estimates obtained using a random-effects model. Of 235 citations retrieved, 7 studies met inclusion criteria. The pooled odds ratio for the risk of HSIL in SLE patients (n=416) versus female controls (n=11,408) was 8.66 (95% CI: 3.75-20.00), without significant heterogeneity across studies. Cumulative meta-analysis according to year of study publication revealed a slight increase in the risk of HSIL in the 2001-2011 period and then a stabilization afterwards. This meta-analysis shows that the risk of HSIL is significantly increased in SLE patients, compared to healthy female controls. This suggests that women with SLE may benefit from HPV vaccines and specific cervical cancer screening.
    Autoimmunity reviews 03/2014; · 6.37 Impact Factor
  • Laurent Arnaud, Herve Devilliers, Zahir Amoura
    Annals of the rheumatic diseases 03/2014; · 8.11 Impact Factor
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    ABSTRACT: Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA). We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy.
    PLoS ONE 01/2014; 9(2):e88548. · 3.53 Impact Factor
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    ABSTRACT: To date, only a small number of studies have examined the epidemiology of systemic lupus erythematosus (SLE) on a nation-wide basis. We used French national administrative databases to analyze the nation-wide prevalence and incidence rates of SLE within the largest French health insurance scheme, which covers 86% of the population (almost 58,200,000 individuals). Patients with SLE were identified if they had full coverage for a chronic disease with a code (ICD-10th M32) in the health insurance information system, or if they had a SLE code in the hospital discharge database as a primary or secondary diagnosis in 2010. We defined incident cases as patients who had a new long-term disease diagnosis of SLE in 2010. Overall, 27,369 individuals were identified as having SLE, 88% were female. The crude 2010 prevalence of identified SLE was 47.0/100,000, and the WHO age-standardized rate 40.8/100,000. The crude 2010 annual incidence of SLE was 3.32 cases per 100,000 with peaks in females aged 30-39yo (9.11/100,000) and in males aged 50-59yo (1.78/100,000). Major differences in regional age-standardized prevalence rates were observed, with highest rates in the Caribbean overseas areas (up to 126.7/100,000), and lowest rates in north-western metropolitan territories (down to 29.6/100,000). This is the largest nation-wide population-based study of SLE patients to date, based on more than 58 million beneficiaries of the French health insurance system. These data and subsequent analyses provide guidance to both clinicians and policymakers for improving care of SLE.
    Autoimmunity Reviews. 01/2014;
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    ABSTRACT: Multiple factors contribute to the increased cardiovascular risk observed in patients with systemic lupus erythematosus (SLE). Among these are the so-called classical cardiovascular risk factors, the disease itself through its activity, treatments, and complications, and the thrombotic risk due to antiphospholipid antibodies (aPL). Observational studies suggest that most classical cardiovascular risk factors are observed more frequently in SLE patients than in the general population, and that these are insufficient to explain the increased cardiovascular risk observed in most studies. Given this high risk, adequate management of cardiovascular risk factors should be recommended in SLE patients. Paradoxically, the benefit due to the anti-inflammatory properties of treatments such as corticosteroids may exceed, in certain cases, their pro-atherogenic effect. Importantly, the tools that were developed for the estimation of cardiovascular risk at the individual level among the general population cannot be used reliably in SLE patients, as these tools appear to underestimate the true cardiovascular risk. The adequate indications and targets of cardiovascular treatments are therefore not fully known in SLE. A better understanding of the determinants of the cardiovascular risk in SLE will allow the identification and more tailored management of these high-risk patients.
    La Revue de Médecine Interne. 01/2014;

Publication Stats

765 Citations
530.62 Total Impact Points

Institutions

  • 2014
    • UPMC
      Pittsburgh, Pennsylvania, United States
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2011–2014
    • Aix-Marseille Université
      • Département de biologie
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2008–2014
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • • Service de Médecine Interne 2
      • • Service de Médecine Interne 1
      Lutetia Parisorum, Île-de-France, France
  • 2010–2013
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • University of Burgundy
      Dijon, Bourgogne, France
  • 2008–2011
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2009
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2006–2007
    • Hôpital Foch
      Lutetia Parisorum, Île-de-France, France