Publications by authors named "Laurent Sailler"

77 Publications

Characteristic vacuolization of myeloid precursors and UBA1 mutation in a woman with monosomy X.

Int J Lab Hematol 2021 Jun 10. Epub 2021 Jun 10.

Laboratoire d'Hématologie, Centre Hospitalo-universitaire (CHU) de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-O), Toulouse, France.

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http://dx.doi.org/10.1111/ijlh.13617DOI Listing
June 2021

Epidemiology of autoimmune hemolytic anemia: A nationwide population-based study in France.

Am J Hematol 2021 Apr 30. Epub 2021 Apr 30.

Department of Internal Medicine, Toulouse University Hospital, Toulouse, France.

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http://dx.doi.org/10.1002/ajh.26213DOI Listing
April 2021

Real-world Risk of Relapse of Giant Cell Arteritis Treated With Tocilizumab: A Retrospective Analysis of 43 Patients.

J Rheumatol 2021 Feb 15. Epub 2021 Feb 15.

J. Cl é ment, MD, Bordeaux University Hospital, Department of Internal Medicine and Infectious Diseases, Bordeaux; P. Duffau, MD, PhD, Bordeaux University Hospital, Internal Medicine Department, Bordeaux; J. Constans, MD, PhD, Bordeaux University Hospital, Vascular Medicine Department, Saint-Andr Hospital, Bordeaux; T. Schaeverbeke, MD, PhD, Bordeaux University Hospital, Department of Rheumatology, Bordeaux; JF Viallard, MD, PhD, CHU de Bordeaux, Department of Internal Medicine and Infectious Diseases, H ô pital Haut-L é v ê que, Pessac; D. Barcat, MD, CH de Libourne, Department of Internal Medicine, Libourne; JP Vernhes, MD, CH of Libourne, Department of Rheumatology, Libourne; L. Sailler, MD, PhD, Toulouse University Hospital, Department of Internal Medicine, Toulouse; F. Bonnet, MD, PhD, CHU de Bordeaux, Department of Internal Medicine and Infectious Diseases, H ô pital Saint-Andr é, Bordeaux, and Universit é de Bordeaux, INSERM U1219, Bordeaux Population Health Research Center, Bordeaux, France. The authors declare no conflicts of interest. Address correspondence to Dr. F. Bonnet, Service de M é decine Interne and Infectious Diseases, H ô pital Saint-Andr é, CHU de Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux, France. Email: Accepted for publication January 26, 2021. break /> The authors declare no conflicts of interest. Address correspondence to Dr. F. Bonnet, Department of Internal Medicine and Infectious Diseases, H ô pital Saint-Andr é, CHU de Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux, France. Email: Accepted for publication January 26, 2021. break /> The authors declare no conflicts of interest. Address correspondence to Dr. F. Bonnet, Department of Internal Medicine and Infectious Diseases, H ô pital Saint-Andr é, CHU de Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux, France. Email: Accepted for publication January 26, 2021.

Objective: Tocilizumab (TCZ), an interleukin 6 (IL-6) receptor antagonist, is approved for giant cell arteritis (GCA) as a cortisone-sparing strategy and in refractory patients. This study assessed the real-world efficacy, safety, and long-term outcomes of patients with GCA treated with TCZ.

Methods: We conducted a multicenter retrospective observational study at 3 French centers. All patients aged ≥ 50 years who met the American College of Rheumatology (ACR) criteria, and had received at least 1 dose of TCZ were included. Relapse was defined by therapeutic escalation, such as increased doses of corticosteroids (CS), resumption of CS after weaning, or introduction or intensification of adjuvant therapy.

Results: Between 2013 and 2019, 43 patients were included. Patients were followed up for a median 511 days between GCA diagnosis and inclusion, with 34/43 (79%) patients experiencing relapses. At inclusion, median age was 77 years, and median dose of CS was 15 mg/day. After inclusion, the mean cumulative dose of CS was 2.1 g/year vs 9.4 g/year before inclusion ( < 2 × 10), with 12/43 (28%) patients experiencing relapses on TCZ. Among 29 patients undergoing TCZ discontinuation, 18 (62%) experienced relapses. Factors associated with relapse after inclusion were introduction of TCZ > 6 months after diagnosis ( = 0.005), absence of ischemic signs at diagnosis ( = 0.006), relapse rate > 0.8/year ( = 0.03), and absence of CS tapering ≤ 5 mg/day ( = 0.03) before inclusion. Serious adverse events occurred in 18/43 patients (42%), including 4 deaths.

Conclusion: Our results confirm the effectiveness of TCZ for CS sparing, but after discontinuation of treatment, TCZ allows for a prolonged remission in < 50% of patients. Attention must be paid to the tolerance of this long-term treatment in this elderly, heavily treated refractory population.
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http://dx.doi.org/10.3899/jrheum.200952DOI Listing
February 2021

Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age: A Retrospective Monocentric Cohort Study.

Drugs Aging 2021 Jan 4;38(1):43-52. Epub 2020 Nov 4.

Department of Infectious and Tropical Diseases, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France.

Objectives: Pyrazinamide (PZA) has a controversial safety profile in older patients. We aimed to assess the frequency and risk factors for adverse drug reactions (ADRs) in patients over 75 years of age treated for tuberculosis with or without PZA.

Methods: We conducted a retrospective monocentric study including patients aged over 75 years treated for active tuberculosis between 2008 and 2018. The frequency, type, seriousness, and causality assessment of ADRs to anti-tuberculosis treatment were compared between patients receiving PZA or not. Risk factors for ADRs were investigated using univariable and multivariable analyses by logistic regression.

Results: Among the 110 patients included, 54 (49.1%) received PZA (group 1) and 56 (50.9%) did not (group 2). ADRs to anti-tuberculosis drugs occurred in 31 patients (57.4%) in groups 1 and 15 (26.8%) in group 2 (p = 0.003). PZA-related ADRs occurred in 40.7% of exposed patients. Frequency of renal ADRs was higher in group 1 (9.3% vs 0%; p = 0.026). Rates of hepatic (18.5% vs 12.5%; p = 0.38), digestive (22.2% vs 8.9%; p = 0.054), and allergic (14.8% vs 5.4%; p = 0.12) ADRs were numerically higher in group 1 although the differences were not statistically significant. Serious ADRs occurred more frequently in group 1 (24.1% vs 8.9%; p = 0.03). The use of PZA was the only independent risk factor for ADRs to anti-tuberculosis drugs (odds ratio 3.75, 95% CI 1.5-9.6; p = 0.0056). No risk factors for PZA-related ADRs were identified.

Conclusion: In older French patients, the use of PZA was associated with more frequent ADRs to anti-tuberculosis drugs.
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http://dx.doi.org/10.1007/s40266-020-00811-9DOI Listing
January 2021

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence.

Arthritis Res Ther 2020 09 25;22(1):223. Epub 2020 Sep 25.

UPMC, Université Paris 6, Paris, France.

Background: Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients.

Methods: HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL.

Results: The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76-0.94) and specificity of 0.89 (95% CI 0.72-0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL).

Conclusions: These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.
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http://dx.doi.org/10.1186/s13075-020-02291-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517694PMC
September 2020

Pulmonary mucormycosis following autologous hematopoietic stem cell transplantation for rapidly progressive diffuse cutaneous systemic sclerosis: A case report.

Medicine (Baltimore) 2020 Jul;99(31):e21431

Department of Internal Medicine.

Rationale: The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc).

Patient Concerns: A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT.

Diagnoses: The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample.

Interventions And Outcomes: Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up.

Lessons: With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.
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http://dx.doi.org/10.1097/MD.0000000000021431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402716PMC
July 2020

Validation of hemolytic anemia discharge diagnosis codes in the French hospital database.

Eur J Intern Med 2020 09 24;79:136-138. Epub 2020 Apr 24.

Service de Médecine Interne, CHU de Toulouse, hôpital Purpan, place du Dr Baylac, 31059 Toulouse, France; CIC 1436, CHU de Toulouse, hôpital Purpan, place du Dr Baylac, 31059 Toulouse, France; UMR 1027 INSERM-Université de Toulouse, Faculté de Médecine, 37 allées Jules Guesde, 31000 Toulouse, France. Electronic address:

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http://dx.doi.org/10.1016/j.ejim.2020.04.030DOI Listing
September 2020

Antithrombotic therapy management in patients with inherited bleeding disorders and coronary artery disease: A single-centre experience.

Haemophilia 2020 Mar 17;26(2):e34-e37. Epub 2019 Dec 17.

Service de Médecine Interne, salle Le Tallec, Centre Hospitalier Universitaire de Toulouse-Purpan, Toulouse, France.

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http://dx.doi.org/10.1111/hae.13904DOI Listing
March 2020

[Giant cell arteritis: Ischemic complications].

Presse Med 2019 Sep 26;48(9):948-955. Epub 2019 Sep 26.

CHU de Toulouse, Hôpital Purpan, université de Toulouse, service de médecine interne, Pavillon URM, UMR Inserm 1027, 31059 Toulouse cedex 9, France.

GCA ischemic complications occur generally in patients with a yet undiagnosed or uncontrolled disease. When disease control is fair, ischemic complications may be due mostly to atheromatosis. Ophtalmic complications are most frequent and are dominated by anterior ischemic optic neuropathy. Vasculitic strokes occur essentially in the vertebrobasilar arterial territory. Overt vasculitic coronary disease is exceptional. The diagnosis of upper and lower limbs ischemic complications benefit from advances in echography (halo sign) and positron emission tomography imaging. Treatment relies on corticosteroids (initially 1mg/kg prednisone or more, preceded by intravenous methylprednisolone gigadoses if necessary), the control of cardiovascular risk factors and antiplatelet drugs; heparin may be indicated for threatening limbs ischemia.
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http://dx.doi.org/10.1016/j.lpm.2019.09.013DOI Listing
September 2019

High rate of indeterminate results of the QuantiFERON-TB Gold in-tube test, third generation, in patients with systemic vasculitis.

Rheumatology (Oxford) 2020 05;59(5):1006-1010

Department of Internal Medicine.

Objectives: To describe the frequency of QuantiFERON-TB Gold in-tube test® (QFT-GIT) indeterminate results due to no response to phytohaemagglutinin A stimulation in the control tube in vasculitis patients prior to immunosuppressant therapy; and to compare it with other groups of patients.

Methods: This was a single-centre, retrospective study. Patients and controls were included between 1 January 2008 and 31 December 2015. We assessed the rate of indeterminate results of the QFT-GIT in 38 patients with systemic vasculitis prior to any corticosteroid or immunosuppressant therapy, compared with 40 non-vasculitis patients with biological inflammatory syndrome, and 310 non-immunosuppressed patients matched for gender and age.

Results: Indeterminate results due to no response to phytohaemagglutinin A were more frequent in vasculitis patients (21.1%) compared with non-vasculitis patients with biological inflammatory syndrome (7.5%) (Fisher's exact test: P = 0.11) and to anonymized controls (7%) (P = 0.009). Responses to phytohaemagglutinin A were significantly lower in vasculitis patients compared with other groups (Kruskal-Wallis test: P < 0.0001) and compared with non-vasculitis patients with biological inflammatory syndrome (P = 0.0015). The multivariable analysis identified as independent predictors of an indeterminate result of the QFT-GIT: the presence of systemic vasculitis (odds ratio 9.64 [1.14-81.3], P = 0.037) and a high neutrophil-to-lymphocyte ratio (odds ratio 1.70 [1.21-2.37], P = 0.002). One patient with an indeterminate result of QFT-GIT developed active tuberculosis after one year of corticosteroid therapy for giant cell arteritis.

Conclusion: Our results question the reliability of QFT-GIT to rule out latent tuberculosis in vasculitis patients at diagnosis, prior to immunosuppressant therapy.
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http://dx.doi.org/10.1093/rheumatology/kez390DOI Listing
May 2020

The factor VIII:C/VWF:Ag ratio as a useful tool to predict relapse in patients with acquired haemophilia A: A retrospective cohort study.

Haemophilia 2019 May 2;25(3):527-534. Epub 2019 May 2.

Laboratoire d'Hématologie, CHU de Toulouse, France.

Introduction: Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of autoantibodies against coagulation factor VIII (FVIII). The mortality rate remains high. International recommendations define complete remission as undetectable inhibitor (<0.6 Bethesda Units [BU]) and normal FVIII activity (FVIII:C) that persists after immunosuppressive therapy stopped. For patients achieving remission, the risk of relapse reaches 20%. The risk factors for this relapse are not well known.

Aim: In this study, we examined the accuracy of the FVIII/W ratio (FVIII:C/von Willebrand Factor Antigen (VWF:Ag) ratio) to predict relapse in 64 consecutive patients with AHA.

Results: In this cohort, all patients had a very low FVIII/W ratio at the time of diagnosis, and this value progressively increased in the first weeks of immunosuppressive treatment. In our study, 9/55 (14%) did not achieve complete remission. Twenty-seven patients were followed long enough (more than a year) to show that in the 22 patients who did not relapse, the FVIII/W ratio remained durably normalized. By contrast, in the five patients who relapsed during follow-up, we noted either no normalization of the FVIII/W ratio, or a secondary decrease to an abnormal value of <0.7 after initial normalization. In all patients who relapsed, the ratio was the first abnormal biological result to be observed, always preceding changes in the activated partial thromboplastin time (aPTT), FVIII:C and anti-FVIII reappearance.

Conclusion: These data suggest that the FVIII/W ratio could be considered a sensitive biological marker to predict recovery and/or relapse in AHA.
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http://dx.doi.org/10.1111/hae.13752DOI Listing
May 2019

Impact of risk factors on the occurrence of arterial thrombosis and venous thromboembolism in adults with primary immune thrombocytopenia - Results from two nationwide cohorts.

Thromb Res 2019 Jun 17;178:124-131. Epub 2019 Apr 17.

Centre for Pharmacoepidemiology, Department of Medicine, Solna, Karolinska Institutet, Sweden.

Background: Previous studies have found that patients with Immune thrombocytopenia (ITP) have an increased risk of arterial thrombosis (AT) and venous thromboembolism (VTE). However, risk factors for thrombosis in adults with primary ITP remain unassessed in large cohorts. Aim To assess the occurrence and impact of risk factors for AT and VTE in patients with primary ITP in France and Sweden.

Methods: Both countries have national health databases, including hospital diagnoses and drug dispensing data. Adults with incident primary ITP identified using algorithms between the years 2009-2015 in France, and 2009-2016 in Sweden were included. Cumulative incidence rates (IR) of AT and VTE were calculated by risk factors and multivariable Cox models were used to estimate associations.

Results: The study included 7225 patients from France and 2490 from Sweden. The IR of AT were 15.0 (95% CI: 13.4-16.7) and 14.7 (95% CI: 12.4-17.5) per 1000 person-years, respectively. The incidences of VTE were 6.9 (95% CI: 5.9-8.1) and 6.5 (95% CI: 5.1-8.4), respectively. Increasing age, male sex and a previous AT were associated with AT in both countries and so were exposure to antiplatelet drugs in France and a history of VTE and chronic kidney disease in Sweden. Increasing age and a history of VTE were associated with VTE in both countries, in France also cancer.

Conclusion: The IR of AT and VTE were similar in France. Age and male sex remained the most important risk factors for AT, age for VTE.
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http://dx.doi.org/10.1016/j.thromres.2019.04.016DOI Listing
June 2019

Diagnostic biologique des angioedèmes bradykiniques : les recommandations du CREAK.

Presse Med 2019 Jan 8;48(1 Pt 1):55-62. Epub 2018 Nov 8.

Centre de référence national des angioedèmes (CREAK), 38043 Grenoble, France; Service d'immunologie, CHUGA, 38043 Grenoble, France.

Bradykinin mediated angioedema (BK-AE) can be associated either with C1Inhibitor deficiency (hereditary and acquired forms), either with normal C1Inh (hereditary form and drug induced AE as angiotensin converting enzyme inhibitors…). In case of high clinical suspicion of BK-AE, C1Inh exploration must be done at first: C1Inh function and antigenemy as well as C4 concentration. C1Inh deficiency is significant if the tests are below 50 % of the normal values and controlled a second time. In case of C1Inh deficiency, you have to identify hereditary from acquired forms. C1q and anti-C1Inh antibody tests are useful for acquired BK-AE. SERPING1 gene screening must be done if a hereditary angioedema is suspected, even if there is no family context (de novo mutation 15 %). If a hereditary BK-AE with normal C1Inh is suspected, F12 and PLG gene screening is suitable.
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http://dx.doi.org/10.1016/j.lpm.2018.06.015DOI Listing
January 2019

Impact of micronutrient deficiency & malnutrition in systemic sclerosis: Cohort study and literature review.

Autoimmun Rev 2018 Nov 10;17(11):1081-1089. Epub 2018 Sep 10.

Service de Médecine interne, URM, CHU de Toulouse, France; UMR 1027 Inserm-Université de Toulouse, France.

Objectives: The purpose of our study was to determine the prevalence and risk factors associated with malnutrition, and selenium (Se) and vitamin C (vitC) deficiencies in systemic sclerosis (SSc) patients.

Methods: We included adult SSc patients fulfilling the 2013 ACR/EULAR criteria from the Toulouse University Hospital cohort who underwent a micronutrient workup (including vitC, Se or thiamine levels) between 2011 and 2016.

Results: 82 patients were included, mostly women (76%), with a median age of 60 years. SSc was limited in 76% of the cases, with Scl-70 and centromere antibodies in 32% and 44%, respectively. Median disease duration was 7.4 years. Cardiac involvement was noticed in 19% and gastrointestinal tract in and 95%; 9% had pulmonary artery hypertension (PAH) and 63% had interstitial lung disease. Overt malnutrition was present in 14 (17%) patients. Micronutrient deficiencies included Se (35%), vitC (31%) and/or thiamine (6%). Malnourished patients had significantly a higher summed Medsger disease severity scales (7.5 vs. 5, P = .003), lower hemoglobin (10.6 vs. 12.9 g/dL, P < .0001) and vitC levels (3.6 vs. 10.6 mg/L, P = .003). Cardiac involvement was significantly associated with Se deficiency (OR 6.2, IC 95%[1.48-32.70], P = .05). The factors associated with vitC deficiency were malnutrition (OR 8.57, IC 95%[2.16-43.39], P = .003), modified Rodnan skin score ≤ 14 (OR 0.33, IC95[0.11-1], P = .05), PAH (27% in deficient vs. none in non-deficient patients, P = .0006) and esophagitis or Barrett's mucosa (OR 4.05, IC95[1.27-13.54], P = .02).

Conclusions: Se testing should be considered as soon as cardiac involvement is suspected. VitC testing should be considered in malnourished SSc patients, especially if skin involvement is extensive.
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http://dx.doi.org/10.1016/j.autrev.2018.05.010DOI Listing
November 2018

Cross-national health care database utilization between Spain and France: results from the EPICHRONIC study assessing the prevalence of type 2 diabetes mellitus.

Clin Epidemiol 2018 27;10:863-874. Epub 2018 Jul 27.

IdiSNA, Pamplona, Spain.

Aim: The EPICHRONIC (EPIdemiology of CHRONIC diseases) project investigated the possibility of developing common procedures for French and Spanish electronic health care databases to enable large-scale pharmacoepidemiological studies on chronic diseases. A feasibility study assessed the prevalence of type 2 diabetes mellitus (T2DM) in Navarre and the Basque Country (Spain) and the Midi-Pyrénées region (France).

Patients And Methods: We described and compared database structures and the availability of hospital, outpatient, and drug-dispensing data from 5.9 million inhabitants. Due to differences in database structures and recorded data, we could not develop a common procedure to estimate T2DM prevalence, but identified an algorithm specific to each database. Patients were identified using primary care diagnosis codes previously validated in Spanish databases and a combination of primary care diagnosis codes, hospital diagnosis codes, and data on exposure to oral antidiabetic drugs from the French database.

Results: Spanish and French databases (the latter termed Système National d'Information Inter-Régimes de l'Assurance Maladie [SNIIRAM]) included demographic, primary care diagnoses, hospital diagnoses, and outpatient drug-dispensing data. Diagnoses were encoded using the International Classification of Primary Care (version 2) and the International Classification of Diseases, version 9 and version 10 (ICD-9 and ICD-10) in the Spanish databases, whereas the SNIIRAM contained ICD-10 codes. All data were anonymized before transferring to researchers. T2DM prevalence in the population over 20 years was estimated to be 6.6-7.0% in the Spanish regions and 6.3% in the Midi-Pyrénées region with ~2% higher estimates for males in the three regions.

Conclusion: Tailored procedures can be designed to estimate the prevalence of T2DM in population-based studies from Spanish and French electronic health care records.
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http://dx.doi.org/10.2147/CLEP.S151890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067780PMC
July 2018

Zoster after Cyclophosphamide for Systemic Lupus Erythematosus or Vasculitis: Incidence, Risk Factors, and Effect of Antiviral Prophylaxis.

J Rheumatol 2018 11 15;45(11):1541-1548. Epub 2018 Jul 15.

From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.

Objective: To assess the incidence and the risk factors for zoster in patients exposed to intravenous cyclophosphamide (CYC) for systemic vasculitis or systemic lupus erythematosus (SLE), as well as the protective effect of prophylaxis by valacyclovir (VCV).

Methods: This retrospective study included all adults treated by intravenous CYC for SLE or systemic vasculitis between 2011 and 2015 at Toulouse University Hospital, France. Zoster occurrence was recorded using medical chart review, laboratory data, and patient interviews. Univariate Cox models were computed to assess the risk factors for zoster and the protective effect of prophylaxis by VCV.

Results: The cohort consisted of 110 patients (81 systemic vasculitis and 29 SLE). During a mean followup of 3.4 years after CYC initiation, 10 cases of zoster occurred, leading to an overall incidence of 27.9/1000 patient-years (95% CI 15.2-50.6); it was 59.4/1000 patients (95% CI 27.5-123.6) during the year after CYC initiation. Four patients experienced persistent postherpetic neuralgia. Probable risk factors were lymphopenia < 500/l at CYC initiation (HR 5.11, 95% CI 0.94-27.93) and female sex (HR 4.36, 95% CI 0.51-37.31). The incidence was higher in patients with SLE (HR as compared with systemic vasculitis patients = 2.68, 95% CI 0.54-13.26). None of the 19 patients exposed to VCV during the followup developed zoster.

Conclusion: The incidence of zoster is high in systemic vasculitis and in patients with SLE exposed to intravenous CYC. CYC may favor postherpetic neuralgia. Prophylaxis by VCV should be considered, particularly in cases of lymphopenia < 500/l at CYC initiation and during the year after.
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http://dx.doi.org/10.3899/jrheum.180310DOI Listing
November 2018

Catastrophic multiple arterial dissections revealing concomitant polyarteritis nodosa and vascular Elhers-Danlos syndrome.

Clin Exp Rheumatol 2018 Mar-Apr;36 Suppl 111(2):174-175. Epub 2018 May 3.

Internal Medicine Department, CHU Toulouse, France.

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July 2018

Camptocormia with trigeminal involvement revealing myositis with anti-Ku antibodies.

Joint Bone Spine 2019 01 10;86(1):111-112. Epub 2018 Apr 10.

CHU Purpan Toulouse, place du Docteur-Baylac, 31059 Toulouse, France.

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http://dx.doi.org/10.1016/j.jbspin.2018.03.013DOI Listing
January 2019

Efficacy and safety of biologics in relapsing polychondritis: a French national multicentre study.

Ann Rheum Dis 2018 08 13;77(8):1172-1178. Epub 2018 Mar 13.

UMR 1027, INSERM, University of Toulouse, Toulouse, France.

Objectives: To assess the efficacy and the safety of biologics in a cohort of patients with relapsing polychondritis (RP).

Methods: We conducted a French multicentre retrospective cohort study including patients treated with biologics for RP. Efficacy outcomes were clinical response (partial or complete) and complete response during the first 6 months of exposure, plus daily corticosteroid dose at 6 months. Other outcomes were adverse drug reactions (ADRs), persistence of biologics and factors associated with a response.

Results: This study included 41 patients exposed to 105 biologics (tumour-necrosis factor (TNF) inhibitors, n=60; tocilizumab, n=17; anakinra, n=15; rituximab, n=7; abatacept, n=6). Overall response rate during the first 6 months of exposure was 62.9%. Complete response rate was 19.0%. Reduced corticosteroid doses were highly variable among patients. ADRs were mostly infections (n=42). Reasons for biologic withdrawal (73.3%) were insufficient efficacy (34.3%; ranging from 23.5% for tocilizumab to 72.7% for etanercept), loss of efficacy (18.1%) and ADRs (20.9%; mostly for anakinra: 46.7%). Persistence was comparable among biologic classes. Among TNF inhibitors, the highest persistence was observed with adalimumab. Differences in clinical response rates were observed depending on biologics and organ involvement. There were trends towards a lower response rate in cases with associated myelodysplastic syndrome and for a higher response rate for nasal/auricular chondritis, sternal chondritis and concomitant exposure to non-biologic disease-modifying antirheumatic drugs.

Conclusions: This study describes the efficacy of biologics for refractory RP. However, the number of complete responses was low and there were concerns about the risk of ADRs, particularly infections.
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http://dx.doi.org/10.1136/annrheumdis-2017-212705DOI Listing
August 2018

Pretreatment with standard-dose intravenous methylprednisolone does not improve outcomes in newly diagnosed immune thrombocytopenia (ITP).

Eur J Haematol 2018 May 12;100(5):412-418. Epub 2018 Mar 12.

CIC 1436, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Objective: To assess the benefits and harms to initiate corticosteroids with intravenous methylprednisolone at a conventional dose (1 mg/kg/d) to treat adults with immune thrombocytopenia (ITP).

Methods: Population stemmed from the prospective multicenter CARMEN registry and included newly diagnosed hospitalized ITP adults with platelet counts<30 × 10 /L. We compared the patients treated with conventional-dose methylprednisolone (CDMP) before continuing with oral prednisone to patients treated with just conventional-dose oral prednisone (CDOP). The primary outcome was the time until response. Secondary outcomes were time until complete response, response rate, complete response rate, duration of hospital stay, and occurrence of adverse drug reactions. Analyzes were adjusted for propensity score and for exposure to intravenous immunoglobulin.

Results: Among the included 87 patients, the median time to response was 3 days in the CDMP group vs 4 in the CDOP group (adjusted hazard ratio [aHR]: 1.35; 95%CI: 0.76-2.41). The CDMP group had an earlier complete response (aHR: 2.29; 95%CI: 1.20-4.36). There was no difference between the groups regarding other secondary outcomes.

Conclusions: Initiating methylprednisolone at a conventional dose provided no significant benefit compared to giving oral prednisone only to adults with ITP.
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http://dx.doi.org/10.1111/ejh.13032DOI Listing
May 2018

Positive predictive values of peripheral arterial and venous thrombosis codes in French hospital database.

Fundam Clin Pharmacol 2018 Feb 15;32(1):108-113. Epub 2017 Nov 15.

UMR 1027, INSERM, Faculté de Médecine, Université de Toulouse III, 37 allées Jules Guesde, 31000, Toulouse, France.

French hospital database, called Programme de Médicalisation des Systèmes d'Information (PMSI), covers all hospital stays in France (>66 million inhabitants). The aim of this study was to estimate the positive predictive values (PPVs) of primary diagnosis codes of peripheral arterial and venous thrombosis codes in the PMSI, encoded with the International Classification of Diseases, 10th revision. Data were extracted from the PMSI database of Toulouse University Hospital, south of France. We identified all the hospital stays in 2015 with a code of peripheral arterial or venous thrombosis as primary diagnosis. We randomly selected 100 stays for each category of thrombosis and reviewed the corresponding medical charts. The PPV of peripheral arterial thrombosis codes was 83.0%, 95% confidence interval (CI): 73.9-89.1, and the PPV of correct location of thrombosis was 81.0%, 95% CI: 72.2-87.5. The PPV of pulmonary embolism was 99.0%, 95% CI: 93.8-99.9. The PPV of peripheral venous thrombosis was 95.0%, 95% CI: 88.2-98.1, and the PPV of correct location of thrombosis was 85.0%, 95% CI: 76.7-90.7. Primary diagnoses of peripheral arterial and venous thrombosis demonstrated good PPVs in the PMSI.
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http://dx.doi.org/10.1111/fcp.12326DOI Listing
February 2018

Incremental Costs in Giant Cell Arteritis.

Arthritis Care Res (Hoboken) 2018 07 23;70(7):1074-1081. Epub 2018 Apr 23.

UMR 1027 INSERM, Université de Toulouse, and Service de Médecine Interne, CHU Toulouse, Toulouse, France.

Objective: To assess and compare direct costs between giant cell arteritis (GCA) patients and matched controls and to identify incremental cost drivers.

Methods: We carried out a population-based, retrospective cohort study using the French National Health Insurance System database. Cost analysis was performed from the French health insurance perspective and took into account direct medical and nonmedical costs (2014, €). Costs were evaluated according to different cost components and divided into periods of 6 months for the accurate assessment of care consumption. Longitudinal multivariate regression analyses using generalized estimating equations were used to adjust the effect of GCA on the mean cost over time.

Results: Analyses were performed on 96 incident GCA patients and 563 matched controls. The cumulative incremental cost due to GCA was €6,406 and €7,236 for 3 and 5 years, respectively. Total incremental costs were significant for the first 18 months, amounting to €1,342 for the first 6 months, €1,498 between 6 and 12 months, and €1,165 between 12 and 18 months (P = 0.012, P = 0.065, and P = 0.029, respectively). The most important cost drivers were paramedical procedures, inpatient stays, medication, and medical procedures. Multivariate analysis shows the significant effect of GCA on mean cost during the first 3 years of followup (relative risk [RR] 1.72 [95% confidence interval (95% CI) 1.31-2.27], P < 0.001) with significant cost reductions (RR 0.70 [95% CI 0.49-0.99], P = 0.05) at the end of followup.

Conclusion: This study provides an accurate assessment of GCA costs during a 5-year period and gives useful information for future cost-effectiveness studies based on new expensive biotherapies.
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http://dx.doi.org/10.1002/acr.23429DOI Listing
July 2018

Validation of an algorithm identifying incident primary immune thrombocytopenia in the French national health insurance database.

Eur J Haematol 2017 Oct 22;99(4):344-349. Epub 2017 Aug 22.

UMR 1027 INSERM-University of Toulouse, Toulouse, France.

Objectives: To evaluate the accuracy of an algorithm identifying newly diagnosed immune thrombocytopenia (ITP) patients in the French national health insurance database (SNIIRAM).

Methods: The source of data was the SNIIRAM of Midi-Pyrenees region (southwest of France, three million inhabitants). Data of patients with at least one ITP code (D69.3 code of the International Classification of Disease, version 10) were extracted between January 1, 2012, and December 31, 2014. We used an algorithm that identifies newly diagnosed primary ITPs. Medical charts of incident ITPs were reviewed. Positive predictive values (PPVs) of identification of true, incident, and primary ITP cases were estimated.

Results: Of the 168 patients selected, 161 were true ITP cases yielding a PPV of 95.8% (95% confidence interval-95% CI: 92.8-98.8). Among them, 128 were truly incident according to symptom onset date and 134 according to the diagnosis date yielding PPVs of 79.5% (95% CI: 73.2-85.7) and 83.2% (95% CI: 77.4-89.0), respectively. Median time between estimated diagnosis date by the algorithm and true diagnosis date was 0 days (interquartile range: 0 to 15).

Conclusions: This study showed a very good PPV of this algorithm identifying incident primary ITP patients in the SNIIRAM.
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http://dx.doi.org/10.1111/ejh.12926DOI Listing
October 2017

Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial.

Arthritis Rheumatol 2017 11 15;69(11):2175-2186. Epub 2017 Oct 15.

National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France.

Objective: In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN).

Methods: All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24.

Results: Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms.

Conclusion: Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.
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http://dx.doi.org/10.1002/art.40205DOI Listing
November 2017

International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus.

Autoimmun Rev 2017 Jun 18;16(6):650-657. Epub 2017 Apr 18.

Internal Medicine Department, Lille University Hospital, University of Lille, Lille, France.

Background/purpose: Despite conventional immunosuppressants, active and steroid-dependent systemic lupus erythematosus (SLE) represents a therapeutic challenge. Only one biologic, belimumab, has been approved, but other biologics are sometimes used off-label. Given the lack of evidence-based data in some clinical situations encountered in real life, we developed expert recommendations for the use of biologics for SLE.

Methods: The recommendations were developed by a formal consensus method. This method aims to formalize the degree of agreement among experts by identifying, through iterative ratings with feedback, the points on which experts agree, disagree or are undecided. Hence, the recommendations are based on the agreed-upon points. We gathered the opinion of 59 French-speaking SLE experts from 3 clinical networks dedicated to systemic autoimmune diseases (FLEUR, IMIDIATE, FAI2R) from Algeria, Belgium, France, Italy, Morocco, Switzerland and Tunisia. Represented medical specialities were internal medicine (49%), rheumatology (34%), nephrology (7%), dermatology (5%), pediatrics (3%) and cardiology (2%). Two methodologists and 3 strictly independent SLE expert groups contributed to developing these recommendations: a steering group (SG) (n=9), an evaluation group (EG) (n=28) and a reading group (RG) (n=22). Preliminary recommendations were drafted by the SG, then proposed to the EG. Each EG member rated the degree of agreement from 1 to 9 (1: lowest; 9: strongest) for each recommendation. After 2 rating rounds, the SG submitted a new version of the recommendations to the RG. With comments from the RG, the SG finalised the recommendations.

Results: A total of 17 final recommendations were formulated by the SG, considering all agreement scores and comments by the EG and RG members and the two methodologists. These recommendations define the subset of patients who require a biologic; the type of biologics to use (belimumab, rituximab, etc.) depending on the organ involvement and associated co-treatments; what information should be given to patients; and how to evaluate treatment efficacy and when to consider discontinuation.

Conclusion: Overall, 17 recommendations for the good use of biologics in SLE were formulated by a large panel of SLE experts to provide guidance for clinicians in daily practice. These recommendations will be regularly updated according to the results of new randomized trials and increasing real life experience.
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http://dx.doi.org/10.1016/j.autrev.2017.04.011DOI Listing
June 2017

Newly diagnosed immune thrombocytopenia adults: Clinical epidemiology, exposure to treatments, and evolution. Results of the CARMEN multicenter prospective cohort.

Am J Hematol 2017 Jun 20;92(6):493-500. Epub 2017 Mar 20.

Service de Médecine Interne, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, F-31100, France.

The clinical epidemiology of immune thrombocytopenia (ITP) is not well known in adults. This study was aimed at assessing the clinical epidemiology of incident ITP adults, the factors associated with chronicity and exposure to treatments. This study was conducted in the CARMEN registry, a multicentric prospective cohort aimed at including all newly diagnosed ITP adults in the French Midi-Pyrénées region, South of France (3 million inhabitants) from June 2013. Descriptive analyses and multivariate logistic regression models were conducted. Out of 121 newly diagnosed ITP until December 2014, 113 patients were followed in the region and gave informed consent. Median age was 65 years. Half of the patients were female, 20.3% had a secondary ITP, 50.4% had a Charlson's score ≥1, median platelet count was 17 × 10 /L; 50.9% had bleeding symptoms, including 2 severe gastrointestinal tract and 1 intracranial bleedings; 21.4% had another autoimmune disease and 20.3% experienced an infection within the six weeks before ITP onset. Persistency and chronicity rates were 68.2% and 58.7%, respectively. Antinuclear antibodies were associated with chronicity (OR: 2.89, 95% CI: 1.08-7.74). Sixty-eight (60.2%) patients were treated during the week following the diagnosis. Factors associated with the use of intravenous corticosteroids were secondary ITP and high bleeding score. Those associated with the use of intravenous immunoglobulin (IVIg) were a high bleeding score and low platelet count. In conclusion, severe bleeding is rare at ITP onset. Associated autoimmune diseases and recent infections were frequent. Antinuclear antibodies seem predictors of chronicity. Intravenous corticosteroids and IVIg were frequently used.
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http://dx.doi.org/10.1002/ajh.24702DOI Listing
June 2017

Diagnosis and treatment of upper airway oedema caused by acute angio-oedema in the emergency department: a French consensus statement.

Eur J Emerg Med 2017 Oct;24(5):318-325

aDepartment of Anaesthesiology and Intensive care, Edouard Herriot University Hospital bDepartment of Clinical Research and Innovation, Hospices Civils de Lyon, Lyon cEmergency Department, Louis Mourier University Hospital, Paris 7 University dDepartment of Internal Medicine, Saint Antoine University Hospital, Paris 6 University, Assistance Publique-Hôpitaux de Paris, Paris eDepartment of Internal Medicine, Grenoble University Hospital, Grenoble-Alpes University, Grenoble fDepartment of Dermatology, Gabriel-Montpied University Hospital, Clermont-Ferrand gDepartment of Internal Medicine, Niort Hospital, Niort hDepartment of Internal Medicine, Archet 1 University Hospital, Nice Sophia-Antipolis University, Nice iDepartment of Medicine, Saint Louis University Hospital, Saint Pierre, Réunion jDepartment of Internal Medicine, Caen University Hospital, Caen kDepartment of Dermatology and Allergology, Grenoble University Hospital, Grenoble lDepartment of Internal Medicine, Timone University Hospital, Assistance Publique-Hôpitaux de Marseille, Marseille mDepartment of Dermatology, Saint Eloi University Hospital, Montpellier nDepartment of Dermatology, Besançon University Hospital, Franche-Comté University, INSERM UMR 1098, Besançon oDepartment of Internal Medicine Toulouse University Hospital, Toulouse University, Toulouse pDepartment of Internal Medicine, Lille University Hospital, Lille University, INSERM U995 Lille, Lille, France.

Angio-oedema is a transitory, localized, noninflammatory oedema of subcutaneous tissue or mucous. When the oedema affects the mouth, lips, tongue or larynx, it can result in fatal asphyxiation in the absence of specific treatment. Oedema secondary to plasma extravasation is usually mediated by either histamine or bradykinin. As laboratory tests are not available in an emergency setting, the implicated mediator cannot be readily determined. The challenge for the emergency physician is to determine the aetiological type, evaluate severity and initiate adapted treatment by means of a structured approach. A team of experts from the French Reference Centre for Angio-oedema reached a consensus for recommendations for the diagnostic and therapeutic strategy to be adopted by emergency departments faced with angio-oedema of the upper airways in adults. The experts defined 11 important questions. Responses were rated using a two-round Delphi methodology. The 11 recommendations were related to triage on admission, a step-by-step diagnostic protocol, definition of attack severity, discouragement of instrumental examination, prioritization of treatment for severe attacks according to clinical signs and anticipation of access to specific treatments by the hospital. Angio-oedema of the upper airways can be fatal and requires anticipation by the emergency department. A search for the aetiology, an evaluation of clinical symptoms and the availability of the treatments are challenges justifying these recommendations.
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http://dx.doi.org/10.1097/MEJ.0000000000000446DOI Listing
October 2017

A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

Am J Hum Genet 2017 Jan 29;100(1):64-74. Epub 2016 Dec 29.

Department of Internal Medicine, Hospital Saint-Louis ECSTRA Team, Epidemiology and Biostatistics, Sorbonne Paris Cité Research Center UMR 1153, Inserm, University Paris Diderot, Paris 75010, France.

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10, per-allele OR = 1.79; and rs9275592, p = 1.14 × 10, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10, OR = 1.28; and rs128738, p = 4.60 × 10, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.
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http://dx.doi.org/10.1016/j.ajhg.2016.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223025PMC
January 2017