Publications by authors named "Thomas Papo"

149 Publications

Hunting for the genetic basis of Susac syndrome.

Eur J Neurol 2021 Mar 27. Epub 2021 Mar 27.

Département de Médecine Interne, Assistance Publique Hôpitaux de Paris, Hôpital Bichat, Université de Paris, Paris, France.

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http://dx.doi.org/10.1111/ene.14836DOI Listing
March 2021

A 29-Year-Old Man With an Osteolytic Rib Lesion.

Chest 2021 Feb;159(2):e115-e117

Department of Médecine Interne, Université de Paris, Assistance Publique Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France. Electronic address:

Case Presentation: A 29-year-old man with no significant medical history presented to the ED with a 4-week history of chest pain. The pain was insidious, located on the right side of the chest, increased by deep breathing, and incompletely alleviated by acetaminophen. The patient had never smoked tobacco. He denied any recent fevers, chills, dyspnea, cough, night sweats, hemoptysis, or history of trauma but had lost at least 8 kg in the past 6 months. The patient was from Morocco and had lived in France for 1 year.
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http://dx.doi.org/10.1016/j.chest.2020.09.089DOI Listing
February 2021

Arterial Thrombotic Events in Adult Inpatients With COVID-19.

Mayo Clin Proc 2021 02 27;96(2):295-303. Epub 2020 Nov 27.

Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université de Paris, France; INSERM U1149, Paris, France. Electronic address:

Objective: To evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19).

Methods: All consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form.

Results: Overall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001).

Conclusion: A dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.
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http://dx.doi.org/10.1016/j.mayocp.2020.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691140PMC
February 2021

Acquired factor V inhibitor: a nation-wide study of 38 patients.

Br J Haematol 2021 Mar 20;192(5):892-899. Epub 2021 Jan 20.

Département de Médecine Interne, Hôpital Bichat, Université de Paris, Assistance Publique Hôpitaux de Paris, Paris, France.

Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency <50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty-eight (74 [36-100] years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow-up (7 [0·2-48.7] months). At diagnosis, FV was <10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) [0·36-0·80], P < 0·05}. Bleeding onset during follow-up was associated with a slow AFVI clearance (P < 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29-100) and a specificity of 86% (95% CI: 57-98, P = 0·02). Kaplan-Meier analysis showed that AFVI clearance >7 months increased the risk of bleeding by 8 (95% CI: [0·67-97], P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow-up are both associated with bleeding in patients with AFVI.
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http://dx.doi.org/10.1111/bjh.17308DOI Listing
March 2021

French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides).

Orphanet J Rare Dis 2020 12 29;15(Suppl 2):351. Epub 2020 Dec 29.

Internal Medicine, CHU Cochin, AP-HP, Paris, France.

Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3-6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12-48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.
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http://dx.doi.org/10.1186/s13023-020-01621-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771069PMC
December 2020

Primary antiphospholipid syndrome revealed by acute myocardial infarction in young adults: a prospective observational study.

Thromb Res 2021 Feb 11;198:151-153. Epub 2020 Dec 11.

Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France; INSERM U1149, Laboratoire d'excellence INFLAMEX, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2020.12.003DOI Listing
February 2021

Basophils and IgE contribute to mixed connective tissue disease development.

J Allergy Clin Immunol 2021 Apr 15;147(4):1478-1489.e11. Epub 2020 Dec 15.

Université de Paris, Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Faculté de Médecine site Bichat, Paris, France; Université de Paris, Laboratoire d'Excellence Inflamex, Paris, France. Electronic address:

Background: Mixed connective tissue disease (MCTD) is a rare and complex autoimmune disease that presents mixed features with other connective tissue diseases, such as systemic lupus erythematosus, systemic sclerosis, and myositis. It is characterized by high levels of anti-U1 small nuclear ribonucleoprotein 70k autoantibodies and a high incidence of life-threatening pulmonary involvement. The pathophysiology of MCTD is not well understood, and no specific treatment is yet available for the patients. Basophils and IgE play a role in the development of systemic lupus erythematosus and thus represent new therapeutic targets for systemic lupus erythematosus and other diseases involving basophils and IgE in their pathogenesis.

Objective: We sought to investigate the role of basophils and IgE in the pathophysiology of MCTD.

Methods: Basophil activation status and the presence of autoreactive IgE were assessed in peripheral blood of a cohort of patients with MCTD and in an MCTD-like mouse model. Basophil depletion and IgE-deficient animals were used to investigate the contribution of basophils and IgE in the lung pathology development of this mouse model.

Results: Patients with MCTD have a peripheral basopenia and activated blood basophils overexpressing C-C chemokine receptor 3. Autoreactive IgE raised against the main MCTD autoantigen U1 small nuclear ribonucleoprotein 70k were found in nearly 80% of the patients from the cohort. Basophil activation and IgE anti-U1 small nuclear ribonucleoprotein 70k were also observed in the MCTD-like mouse model along with basophil accumulation in lymph nodes and lungs. Basophil depletion dampened lung pathology, and IgE deficiency prevented its development.

Conclusions: Basophils and IgE contribute to MCTD pathophysiology and represent new candidate therapeutic targets for patients with MCTD.
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http://dx.doi.org/10.1016/j.jaci.2020.12.622DOI Listing
April 2021

Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study.

PLoS One 2020 16;15(12):e0243961. Epub 2020 Dec 16.

Pulmonology and Thoracic Oncology Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France.

Background: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated.

Material And Methods: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3-5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects.

Results: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80-1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%).

Conclusion: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243961PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743937PMC
December 2020

Susac syndrome following COVID-19 infection.

Acta Neurol Belg 2020 Nov 24. Epub 2020 Nov 24.

Department of Neurology, Centre Hospitalo-Universitaire de Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), 78 Rue du Général Leclerc, 94275, Le Kremlin-Bicêtre, France.

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http://dx.doi.org/10.1007/s13760-020-01554-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685681PMC
November 2020

Management of patients with myocardial tuberculosis: A case series.

Int J Cardiol 2021 Mar 7;327:132-137. Epub 2020 Nov 7.

Département de Médecine Interne, Hôpital Bichat, Université de Paris, Assistance Publique Hôpitaux de Paris, Paris, France; INSERM U1149, Paris, France. Electronic address:

Background: Myocardial Tuberculosis (MT) is exceedingly rare. We aimed to report on myocardial involvement in tuberculosis (TB).

Methods: All adult patients admitted in a department of Internal Medicine over an 8-year period with microbiologically proven MT were retrospectively reviewed. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records.

Results: Six patients (4 women, 37.6 [21.3-62.1] years) with MT were identified. MT included cardiac mass (n = 1), coronaritis (n = 1), left ventricle spontaneous rupture (n = 1) and myocarditis (n = 3). Pericardial effusion was associated with myocardial involvement in 2 cases. Four patients presented with acute heart failure. CRP serum level was high in all cases. The mean delay between the first symptoms and TB diagnosis was of 6 [1-44] months. The time from admission to diagnosis was of 18 (9-28) days. No patient had human immunodeficiency virus infection. Fluorodeoxyglucose - positron emission tomography (FDG-PET) detected extra-cardiac asymptomatic Mycobacterium tuberculosis infection localization and guided biopsy in 5 cases. As compared to TB patients without cardiac involvement, patients with MT were younger and more frequently women. All patients received antituberculosis therapy for 7.5 to 12 months associated with steroids for at least 6 weeks. Cardiac surgery was required in all but one patient. No patient died over a median follow-up of 1.2 [0.2-4.4] years.

Conclusion: Our study emphasizes the clinical spectrum of life-threatening MT. Early diagnosis using FDG-PET imaging to target biopsy in extra-cardiac tissues and combined treatment strategy associating antituberculosis therapy, corticosteroids and surgery prevent complications and death.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.001DOI Listing
March 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.

AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, 27 rue du Faubourg Saint-Jacques, 75014, 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

Highly sensitive serum cardiac troponin T and cardiovascular events in patients with systemic lupus erythematosus (TROPOPLUS study).

Rheumatology (Oxford) 2021 Mar;60(3):1210-1215

Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris (APHP), Institut national de la santé et de la recherche médicale (INSERM) U1149, Université de Paris, France.

Objective: Identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. We aimed to determine whether serum cardiac troponin T (cTnT) levels measured with a highly sensitive assay [high sensitivity cTnT (HS-cTnT)] may predict cardiovascular events (CVEs) in SLE.

Method: All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicentre PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analysed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed.

Results: Overall, 442 SLE patients (of the 573 included in the PLUS study) were analysed for the primary outcome with a median follow up of 110 (interquartile range: 99-120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31-91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidaemia, age and HS-cTnT were associated with the occurrence of CVE. Kaplan-Meier analysis showed that a concentration of HS-cTnT > 4.27 ng/l at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.3, 5.6), P =0.0083] the risk of CVE in SLE.

Conclusion: HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients.
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http://dx.doi.org/10.1093/rheumatology/keaa434DOI Listing
March 2021

Serum IgG2 levels predict long-term protection following pneumococcal vaccination in systemic lupus erythematosus (SLE).

Vaccine 2020 10 4;38(44):6859-6863. Epub 2020 Sep 4.

Département de Médecine Interne, Université de Paris, Assistance Publique Hôpitaux de Paris, Paris, France; Centre de Recherche sur l'Inflammation, INSERM U1149, Paris, France. Electronic address:

Systemic lupus erythematosus (SLE) patients are at risk for pneumococcal infection. Twenty-one consecutive SLE patients (40[25-75] years) received the sequential PCV13/PPSV23 vaccine and factors associated with long-term protection were analyzed. Immune protection, defined by an antigen-specific IgG concentration ≥1.3 µg/mL for at least 70% of 7 pneumococcal serotypes was assessed at baseline, 2, 6, 12 and 36 months defining long-term protection. Only 10 patients showed pneumococcal immune protection 36 months after vaccination. Eleven (52.4%) patients had no long-term protection with a seroconversion that never or only transiently occurred. SLE disease features, treatment received and immunological characteristics did not differ between protected and unprotected patients except for the pre-vaccination IgG2 serum levels. Serum IgG2 level >2.125 µg/ml showed a sensitivity of 100% and a specificity of 90.9% for long-term protection. Sequential pneumococcal vaccination conferred poor immune protection in SLE. Baseline IgG2 serum level identified patients able to benefit from pneumococcal vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2020.08.065DOI Listing
October 2020

Effects of BAFF Neutralization on Atherosclerosis Associated With Systemic Lupus Erythematosus.

Arthritis Rheumatol 2021 02 15;73(2):255-264. Epub 2020 Dec 15.

Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Laboratoire d'Excellence Inflamex, Université de Paris, Hôpital Bichat-Claude-Bernard, AP-HP, Paris, France.

Objective: Cardiovascular disease (CVD) is the leading cause of death in systemic lupus erythematosus (SLE). B cells play a key role in the pathogenesis of lupus, and anti-BAFF therapy has been approved for use in SLE. Since mature B cells also promote atherosclerosis, we undertook this study to evaluate, in a mouse model and in SLE patients, whether BAFF neutralization has an atheroprotective effect in SLE.

Methods: The effect of BAFF on atherosclerosis associated with lupus was investigated in the atherosclerosis/lupus-prone apolipoprotein E-knockout D227K mouse model and in a cohort of SLE patients. Mice were treated with a blocking anti-BAFF monoclonal antibody (mAb), while fed a standard chow diet. Carotid plaque and carotid intima-media thickness were assessed by ultrasound at baseline and during follow-up in SLE patients who were asymptomatic for CVD.

Results: Anti-BAFF mAb in ApoE D227K mice induced B cell depletion, efficiently treated lupus, and improved atherosclerosis lesions (21% decrease; P = 0.007) in mice with low plasma cholesterol levels but worsened the lesions (17% increase; P = 0.06) in mice with high cholesterol levels. The atheroprotective effect of the BAFF-BAFF receptor signaling inhibition on B cells was counterbalanced by the proatherogenic effect of the BAFF-TACI signaling inhibition on macrophages. In SLE patients, blood BAFF levels were associated with subclinical atherosclerosis (r = 0.26, P = 0.03). Anti-BAFF mAb treatment had a differential effect on the intima-media thickness progression in SLE patients depending on body mass index.

Conclusion: Depending on the balance between lipid-induced and B cell-induced proatherogenic conditions, anti-BAFF could be detrimental or beneficial, respectively, to atherosclerosis development in SLE.
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http://dx.doi.org/10.1002/art.41485DOI Listing
February 2021

Infliximab use for corticosteroid-resistant tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in an immunocompetent patient.

Infection 2020 Oct 26;48(5):799-802. Epub 2020 Jun 26.

Assistance Publique Hôpitaux de Paris, Département de Médecine Interne, Hôpital Bichat-Claude Bernard, Université de Paris, 46 rue Henri Huchard, 75018, Paris, France.

In non-human immunodeficiency virus (HIV)-infected patients, tuberculosis (TB) immune reconstitution inflammatory syndrome (IRIS) is unusual. The management of corticosteroids-refractory IRIS is unclear. We report on infliximab efficacy for treatment of corticosteroid-resistant TB-IRIS occurring in an immunocompetent patient.
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http://dx.doi.org/10.1007/s15010-020-01470-zDOI Listing
October 2020

Risk factors for hydroxychloroquine retinopathy in systemic lupus erythematosus: a case-control study with hydroxychloroquine blood-level analysis.

Rheumatology (Oxford) 2020 12;59(12):3807-3816

Department of Internal Medicine, Centre de Référence Maladies Auto-Immunes et Systémiques Rares d'Ile de France, Cochin Hospital, APHP.

Objective: HCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels.

Methods: This case-control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy.

Results: The study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P < 0.001), height (P = 0.045), creatinine clearance (P < 0.001), haemoglobin concentration (P = 0.01), duration of HCQ intake, (P < 0.001), higher cumulative HCQ dose (P < 0.001) and geographical origin (West Indies and sub-Saharan Africa) (P = 0.007) were associated with the risk of retinopathy, while HCQ blood levels were not. In the multivariate analysis, only cumulative dose (P = 0.016), duration of intake (P = 0.039), creatinine clearance (P = 0.002) and geographical origin (P < 0.0001, odds ratio 8.7) remained significantly associated with retinopathy.

Conclusion: SLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.
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http://dx.doi.org/10.1093/rheumatology/keaa157DOI Listing
December 2020

Women's representation in French Internal Medicine meetings: gender distribution among speakers, moderators and organisers, 2013-2018.

Intern Med J 2020 04;50(4):477-480

Sorbonne Université, Assistance Publique Hôpitaux de Paris, Hôpital de la Pitié Salpêtrière, Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares et Histiocytoses, Paris, France.

Medical meetings are a time for increasing scientific visibility and leadership. We aimed to examine women's representation in French National Internal Medicine meetings (2013-2018). Women represented 25% of congress presidents, 22% of plenary session speakers, 19% of plenary session moderators and 25% oral session moderators, but 45% of anonymously selected oral communication speakers. Women are under-represented among invited speakers in French Internal Medicine meetings.
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http://dx.doi.org/10.1111/imj.14791DOI Listing
April 2020

Cognitive dysfunction and brain atrophy in Susac syndrome.

J Neurol 2020 Apr 11;267(4):994-1003. Epub 2019 Dec 11.

Department of Internal Medicine, APHP, Bichat Hospital, Paris, France.

Background: Susac syndrome is a very rare cerebral small vessel disease, which can leave patients with cognitive impairment. We aimed at evaluating processing speed slowing, executive dysfunction and apathy and their relationships with whole brain and callosal atrophy.

Methods: Patients with Susac syndrome included in a prospective observational cohort study were evaluated, while clinically steady-state, with standardized brain MRI and a neuropsychological battery specifically designed to capture minimal cognitive alterations in non-disabled young patients. Brain volume and corpus callosum area were measured using 3D-T1 sequences, repeatedly overtime. Relationships between neuropsychological data and brain volumetric measures obtained the same day were tested with linear regression while controlling for sex, age, level of education, scores of depression and of apathy.

Results: Nineteen patients aged 37.5 ± 10.5 years were included. Mean follow-up time was 2.6 ± 1.3 years (5.8 ± 2.2 evaluations). While Montreal Cognitive Assessment scores were 25.1 ± 3.6, processing speed slowing was obvious (Trail Making Test version A: 43.1 ± 16.2 s; version B: 95.5 ± 67.9 s; reaction time: 314.6 ± 79.6 ms). Brain and corpus callosum atrophy was striking. No relationship was found between cognitive performances and brain volume or corpus callosum area.

Conclusion: Patients with Susac syndrome show largely preserved global cognitive functions but important processing speed alterations. Although brain and corpus callosum area atrophy is prominent and evolving, we did not find any relationship with cognitive alterations, questioning the mechanisms underlying cognitive alterations in these patients.

Trial Registration: Clinical Trial Registration-URL: https://www.clinicaltrials.gov Unique Identifier: NCT01481662.
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http://dx.doi.org/10.1007/s00415-019-09664-8DOI Listing
April 2020

A 22-Year-Old Woman With Fever, Palpitations, and a Cardiac Mass.

Chest 2019 08;156(2):e51-e55

Département de Médecine Interne, Université Paris-Diderot, Assistance Publique Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France. Electronic address:

Case Presentation: A 22-year-old woman was admitted to our department for fever of unknown origin. The patient reported intermittent fever and nonspecific abdominal pain for several years. Six months before admission she started complaining of palpitations and exertional dyspnea. She had no weight loss, chest pain, headache, or joint complaints. Medical history was unremarkable. She did not consume tobacco, alcohol, or illicit drugs. The patient was from Malia. She had lived in France for 4 years and did not report recent travel.
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http://dx.doi.org/10.1016/j.chest.2019.03.023DOI Listing
August 2019

Critical role of neutrophil extracellular traps (NETs) in patients with Behcet's disease.

Ann Rheum Dis 2019 09 30;78(9):1274-1282. Epub 2019 May 30.

LVTS, INSERM 1148, Paris, France

Objectives: Behçet's disease (BD) is a chronic systemic vasculitis. Thrombosis is a frequent and life-threatening complication. The pathogenesis of BD is poorly understood and evidence supporting a role for primed neutrophils in BD-associated thrombotic risk is scant. To respond to inflammatory insults, neutrophils release web-like structures, known as neutrophil extracellular traps (NETs), which are prothrombotic. We evaluated the role of NETs and markers of NETs in BD.

Methods: Blood samples were collected from patients with BD, according to the International Study Group Criteria for Behçet's disease, and healthy donors (HD). NET components, including cell-free DNA (CfDNA) and neutrophil enzymes myeloperoxidase (MPO), were assessed in serum or in purified neutrophils from patients with BD and HD.

Results: Patients with active BD had elevated serum cfDNA levels and MPO-DNA complexes compared with patients with inactive BD and to HD. In addition, levels of cfDNA and MPO-DNA complexes were significantly higher in patients with BD with vascular involvement compared with those without vascular symptoms. Purified neutrophils from patients with BD exhibited spontaneous NETosis compared with HD. Thrombin generation in BD plasma was significantly increased and positively correlated with the levels of MPO-DNA complexes and cfDNA. Importantly, DNAse treatment significantly decreased thrombin generation in BD plasma but not in HD plasma. In addition, biopsy materials obtained from patients with BD showed NETs production in areas of vasculitic inflammation and thrombosis.

Conclusions: Our data show that NETs and markers of NETS levels are elevated in patients with BD and contribute to the procoagulant state. Targeting NETs may represent a potential therapeutic target for the reduction or prevention of BD-associated thrombotic risk.
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http://dx.doi.org/10.1136/annrheumdis-2018-214335DOI Listing
September 2019

The burden of chronic kidney disease in systemic lupus erythematosus: A nationwide epidemiologic study.

Autoimmun Rev 2019 Jul 4;18(7):733-737. Epub 2019 May 4.

Département de Médecine Interne, Hôpital Bichat, Université Paris Diderot, PRES Sorbonne Paris Cité, Assistance Publique Hôpitaux de Paris, Paris, France; INSERM U1149, Université Paris-Diderot, Paris, France. Electronic address:

Objective: To analyze the impact of chronic kidney disease (CKD) on major clinical outcome in SLE by using a nationwide database.

Patients And Methods: Characteristics of all admitted SLE patients experiencing CKD (eGFR <60 mL/min/1.73 m2) in France from 2009 to 2015 were analyzed through the French medico- administrative database. Factors associated with CKD and major clinical outcomes such as end-stage renal disease (ESRD), cardiovascular event (CVE), septic shock and death were assessed. We used a multivariate Cox proportional hazard model and subdistribution hazard models to analyze survival without major clinical events according to the presence of CKD.

Results: From 2009 to 2015, 26,320 SLE patients were hospitalized in France. Among them, 6439 (86.5% women; mean age 45.7 [16.5] years old) had a baseline stay in 2009 during which CKD was reported in 428 (6.7%) cases. Multivariate analysis showed that lupus nephritis (OR 6.6 [5.2-8.4]), high blood pressure (OR 3.5 [2.8-4.5]), septic shock (OR 3.2 [1.7-6.0]) and past cardiovascular history (OR 1.4 [1.0-2.0]) were associated with CKD status. From 2009 to 2015, ESRD, CVE, septic shock, and death occurred in 4.0%, 14.4%, 6.3% and 9.6% of the 6439 SLE patients. CKD at baseline was independently and strongly associated with the occurrence of ESRD (sdHR 15.9 [11.6-21.9]), CVE (sdHR 1.7 [1.4-2.2]), septic shock (sdHR 2.1 [1.5-2.8]) and death (HR 1.7 [1.3-2.2]) during the follow up.

Conclusion: CKD is a major risk factor for overall morbidity and mortality in SLE patients, highlighting the need for early pre-CKD lupus nephritis diagnosis and treatment.
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http://dx.doi.org/10.1016/j.autrev.2019.05.011DOI Listing
July 2019

Women in internal medicine academic positions in France.

Eur J Intern Med 2019 Jun 10;64:e18-e20. Epub 2019 Apr 10.

Sorbonne Université, Assistance Publique Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Médecine Interne 1, 75013 Paris, France.

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http://dx.doi.org/10.1016/j.ejim.2019.04.002DOI Listing
June 2019

Septic shock among patients with systemic lupus erythematosus: Short and long-term outcome. Analysis of a French nationwide database.

J Infect 2019 06 8;78(6):432-438. Epub 2019 Apr 8.

APHP Medical and infectious diseases ICU Bichat hospital, F75018 Paris, France; IAME UMR 1137, Université Paris-Diderot Equipe 5 DeScID, France.

Objectives: We aimed to assess the characteristics, outcomes and costs of septic shock complicating Systemic Lupus Erythematosus (SLE).

Methods: Characteristics of SLE patients experiencing a septic shock in France from 2010 to 2015 were analyzed through the French medico-administrative database. Factors associated with the 1-year post-admission mortality were analyzed, the crude 1-year survival of SLE patients experiencing septic shock was compared to those admitted for another reason, and we compared the 1-year outcome associated with SLE septic shock survival to a matched SLE ICU control population.

Results: Among 28,522 SLE patients, 1068 experienced septic shock. The 1-year mortality rate was 43.4%. Independently of the severity, an associated Sjögren syndrome was the only specific SLE phenotype associated with mortality (HR 1.392[1.021-1.899]). Within one year, post-septic shock survivors (n = 738) were re-admitted 6.42[17.3] times with total cost of € 14,431[20,444]. Unmatched analysis showed that the outcome of patients admitted in ICU for septic shock was poorer than that of patients admitted in ICU or hospital for another disease. However, 1-year healthcare use of septic shock survivors was not different from the other ICU survivors when matched on severity.

Conclusions: Septic shock is a frequent and severe complication among SLE patients even if it is not associated with more healthcare use than another episode of same severity.
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http://dx.doi.org/10.1016/j.jinf.2019.04.005DOI Listing
June 2019

Orbital mass in ANCA-associated vasculitides: data on clinical, biological, radiological and histological presentation, therapeutic management, and outcome from 59 patients.

Rheumatology (Oxford) 2019 09;58(9):1565-1573

Department of Internal Medicine, National Referral Center for Systemic and Autoimmune Diseases, Hôpital de la Pitié-Salpêtrière, Paris.

Objective: Orbital mass is a rare and sight-threatening manifestation of ANCA-associated vasculitides, which remains a therapeutic challenge. We aimed to describe the presentation, therapeutic management and outcome of ANCA-associated vasculitides-related orbital mass.

Methods: We conducted a French nationwide retrospective study of patients with orbital mass in the setting of ANCA-associated vasculitides according to ACR criteria and/or Chapel Hill Consensus Conference definitions.

Results: Fifty-nine patients [33 women, median age 46 (range 7-90) years] were included. Fifty-six (95%) patients had granulomatosis with polyangiitis, two eosinophilic granulomatosis with polyangiitis and one microscopic polyangiitis. Orbital mass was unilateral in 47 (80%) cases, and seemed to develop from ENT involvement in most cases. Orbital mass biopsy was available in 32 (54%) patients, showing lymphoplasmacytic infiltration in 65%, fibrosis in 55%, granulomas in 48% and vasculitis in 36%. All patients but one received glucocorticoids as first-line therapy associated with immunosuppressive agents in 82%, mainly cyclophosphamide. Response to therapy was noted in 52% of patients treated with cyclophosphamide compared with 91% of those treated with rituximab. Twenty-seven (46%) patients required a second-line therapy because of relapse (59%) or refractory course (41%). Sequelae included visual impairment in 28%, with definitive blindness in 17%. Refractory course was associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis.

Conclusion: Orbital mass is associated with refractory course and high frequency of sequelae, especially blindness. Refractory course is associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis.
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http://dx.doi.org/10.1093/rheumatology/kez071DOI Listing
September 2019

Persistent FDG/PET CT uptake in idiopathic retroperitoneal fibrosis helps identifying patients at a higher risk for relapse.

Eur J Intern Med 2019 04 31;62:67-71. Epub 2019 Jan 31.

Département de Médecine Interne, Hôpital Bichat, PRES Sorbonne Paris Cité, Assistance Publique Hôpitaux de Paris, Université Paris Diderot, Paris, France; Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodelling in Renal and Respiratory Diseases), Paris, France; INSERM U1149, Paris, France. Electronic address:

Background: The aim of this study was to evaluate the prognostic value of persistent retroperitoneal fibrosis FDG uptake using FDG/PET CT in patients with idiopathic retroperitoneal fibrosis (IRF).

Methods: In this monocentric retrospective cohort study, all patients admitted for IRF from January 2009 to December 2017 underwent a FDG/PET CT at diagnosis and during follow up. Metabolic activity of IRF was assessed by retroperitoneal fibrosis FDG uptake measured as maximal standardized uptake value (SUVmax). The primary outcome was IRF relapse rate during follow-up.

Results: 23 consecutive patients (54.7 [36.9-89] years, 73.9% of men) diagnosed with IRF had FDG/PET CT imaging performed at diagnosis, 3.1 [1-8.7] months (i.e 1st evaluation) and 10.4 [4.9-17.5] months (i.e 2nd evaluation) after diagnosis. High FDG retroperitoneal fibrosis uptake was present in all patients at diagnosis (SUVmax 6.5 [3.8-11.9]) and persisted in 16 (69.6%; SUVmax 3.65 [2.1-5.4]) and 12 (52.2%; SUVmax 3.75 [2.7-7.8]) patients, at 1st and 2nd evaluation respectively. All but one patient had received steroids at IRF diagnosis and 21 (91.3%) were in complete remission at both 1st and 2nd evaluation. During a median follow-up period of 38.7 [3-106.9] months, 6 (26.1%) patients suffered IRF relapse that occurred 15.7 [9.2-42.8] months after diagnosis. Multivariate analysis showed that only persistent retroperitoneal fibrosis FDG uptake at 2nd evaluation was associated with IRF relapse (p = .046).

Conclusions: In IRF, persistent retroperitoneal fibrosis FDG uptake during follow up is associated with clinical outcome. FDG/PET CT may help to better stratify the risk of relapse and target therapy in IRF.
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http://dx.doi.org/10.1016/j.ejim.2019.01.019DOI Listing
April 2019

Clinical and immunological features of antiphospholipid syndrome in the elderly: a retrospective national multicentre study.

Rheumatology (Oxford) 2019 06;58(6):1006-1010

Département de Médecine Interne, Hôpital Bichat, Université Paris Diderot, PRES Sorbonne Paris Cité, Assistance Publique Hôpitaux de Paris, Paris, France.

Objective: APS mainly affects women who are of child-bearing age. We aimed to describe the clinical and immunological features of APS patients diagnosed after the age of 60.

Methods: The Elderly-Phospholipid study is a national, multicentre, retrospective study involving all APS (2006 Miyakis criteria) patients followed in five French tertiary university centres including four national referral lupus and APS centres. Clinical and serological data of patients in whom APS onset occurred after the age of 60 were analysed and compared with patients included in the Euro-Phospholipid cohort.

Results: Forty-four patients (30 women (68.2%); 68.7 (7) years at diagnosis; 72.7% of primary APS) were included in the Elderly-Phospholipid study. Stroke was the most common manifestation at diagnosis (38.6%) and during follow-up (11.4%). LA, aCL and anti-β2-glycoprotein I antibodies were detected in 70.4%, 72.7% and 65.9% of patients, respectively; 43.2% of patients were triple-positive for aPL antibodies. All patients were treated with antithrombotic treatment including antiplatelet agents (31.8%) and/or oral anticoagulants (77.3%). Over a 5.3 (3.8) years follow-up, nine (20.5%) patients displayed a new arterial (n = 8) or venous (n = 1) thrombotic event. Only three (6.8%) patients developed major bleeding. As compared with Euro-Phospholipid APS patients (mean age of 34 (13) years at disease onset), patients in the Elderly-Phospholipid study were more frequently male (P < 0.05) and had a higher frequency of primary APS (<0.05), stroke (<0.0001) and LA (P < 0.05).

Conclusion: APS patients with elderly onset share a distinct disease profile, with a higher frequency of LA, triple aPL positivity and arterial thrombosis.
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http://dx.doi.org/10.1093/rheumatology/key437DOI Listing
June 2019