Publications by authors named "Jean-Charles Piette"

220 Publications

Evaluation of the severe preeclampsia classification criterion for antiphospholipid syndrome in a study of 40 patients.

Arthritis Res Ther 2021 05 4;23(1):134. Epub 2021 May 4.

AP-HP, Cochin Hospital, Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares d'Ile de France, Paris, France.

Background: The criteria for antiphospholipid syndrome (APS) include severe preeclampsia and/or placental insufficiency leading to preterm delivery before 34 weeks of gestation, but this APS manifestation has been rarely studied. Thus, we report a series of severe preeclampsia occurred in patients with APS.

Methods: We retrospectively analysed data of women with APS (Sydney criteria) who experienced severe preeclampsia with delivery before 34 weeks' gestation between 2000 and 2017 at five French internal medicine departments and one Italian rheumatology unit.

Results: The 40 women had a mean age of 30.5 ± 4.6 years at their first episode of preeclampsia; 21 were nulligravid (52.5%), 12 (30%) had already been diagnosed with APS, and 21 (52.5%) had a triple-positive antiphospholipid (aPL) antibody test. Preeclampsia occurred at a median gestational age of 25.5 weeks (IQR 23-29). It was associated with HELLP in 18 cases (45%), eclampsia in 6 (15%), placental abruption in 3 (7.5%), catastrophic APS in 3 (7.5%), and foetal and neonatal death in 11 and 15 cases. Overall, 14 (35%) children survived, born at a median gestational age of 31 weeks. Among other APS criteria, 16 women (40%) experienced at least one thrombosis, 17 (42.5%) an intrauterine foetal death, and 19 (47.5%) at least one episode of HELLP during follow-up (median 5 years, IQR = 2-8). None had three or more consecutive miscarriages. Notably, 12 women (30%) had systemic lupus erythematosus.

Conclusions: Severe preeclampsia led to high mortality in the offspring. Almost half of these women experienced other APS features, but not three consecutive miscarriages.
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http://dx.doi.org/10.1186/s13075-021-02518-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094564PMC
May 2021

Catastrophic antiphospholipid syndrome and posterior ocular involvement: case series of 11 patients and literature review.

Retina 2021 Apr 2. Epub 2021 Apr 2.

AP-HP, Cochin Hospital, Internal Medicine department, Centre de référence maladies auto-immunes et systémiques rares de l'Ile de France, Paris, France. Université Paris-Descartes, Paris, France. AP-HP, Cochin Hospital, Ophthalmology Department, Paris, France. Centre Hospitalier Saint Joseph Saint Luc, Internal medicine department, Lyon, France. Foch Hospital, Internal Medicine department, Suresnes, France. AP-HP, Henri Mondor Hospital, Internal Medicine department, Creteil, France. AP-HP, La Pitié-Salpêtrière Hospital, Internal Medicine department, Centre de référence maladies auto-immunes et systémiques rares de l'Ile de France, Paris, France. Normandie Université, UNIROUEN, Inserm U1096, Rouen university hospital, department of internal medicine, vascular and thrombosis unit, 76000 Rouen, France. Univ. Lille ; INSERM U1167 ; CHU Lille, Internal Medicine department, Centre National de Référence Maladies Systémiques et Auto-Immunes Rares, European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases (ReCONNECT), F-59000 Lille, France Department of Internal Medicine, CHU de Saint-Etienne, France. Université Paris Descartes-Sorbonne Paris Cité, Paris, France ; INSERM U 1153, Center for Epidemiology and Statistics, Sorbonne Paris Cité (CRESS), Paris, France.

Purpose: To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome (CAPS).

Methods: Retrospective case series of patients presenting with CAPS and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at CAPS diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best corrected visual acuity (BCVA).

Results: This study included 23 patients (11 cases treated by the authors and 12 published case reports), 21 (91%) of them female. Their median age at diagnosis was 28 years (range 16-79). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n=11, 48%), and/or retinal vasculitis (n = 1, 4%). Final BCVA was not significantly worse than BCVA at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months [2-132], nearly half the patients (n = 11, 48%) had permanent vision loss including BCVA < 20/400 for 4 patients.

Conclusion: Posterior ophthalmic manifestations of CAPS were mainly bilateral retinal vascular occlusion, which had the worst visual prognosis, followed by choroidopathy and retinal vasculitis. Permanent visual loss was common.
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http://dx.doi.org/10.1097/IAE.0000000000003185DOI Listing
April 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

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186841PMC
December 2020

Catastrophic antiphospholipid syndrome following the introduction of rivaroxaban.

Lupus 2020 Jun 29;29(7):787-790. Epub 2020 Mar 29.

Internal Medicine Department, Cochin Hospital, Paris, France.

Catastrophic antiphospholipid syndrome is the most severe complication of antiphospholipid syndrome. Vitamin K antagonists are the reference treatment for preventing relapsing thrombotic complications in patients with antiphospholipid syndrome. Direct oral anticoagulants are nonetheless sometimes used in this setting. We report two cases of women who were triple-positive for antiphospholipid antibodies and developed catastrophic antiphospholipid syndrome in the week after the introduction of rivaroxaban. The first patient, who had had a previous thrombotic event, had multiorgan failure 3 days after vitamin K antagonists was replaced by rivaroxaban, and the second developed a similar clinical presentation 7 days after introduction of the same treatment. Both catastrophic antiphospholipid syndrome episodes were successfully treated with heparin followed by vitamin K antagonists, corticosteroids, and plasmapheresis. These two cases highlight for the inefficacy of rivaroxaban preventing severe thrombotic events such as catastrophic antiphospholipid syndrome and thus provide further support for recommendations that vitamin K antagonists must remain the reference anticoagulant in patients with triple-positive antiphospholipid antibodies.
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http://dx.doi.org/10.1177/0961203320914363DOI Listing
June 2020

Rituximab-associated Vasculitis Flare: Incidence, Predictors, and Outcome.

J Rheumatol 2020 06 1;47(6):896-902. Epub 2019 Aug 1.

From the Départements Hospitalo-Universitaires (DHU) Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Department of Pathology, Laboratory of Immunology, and Pharmacy Department; Département de Biostatistiques, Hôpital Saint-Louis; AP-HP, Groupe Hospitalier Lariboisière, Department of Internal Medicine, Paris; Hôpital Bretonneau, Centre Hospitalier de Tours, Department of Internal Medicine, Tours; Hôpital Necker, Laboratory of Immunology, Paris; Centre Hospitalier de Valence, Department of Internal Medicine, Valence, France.

Objective: To report the incidence, predictors, and outcome of rituximab (RTX)-associated autoimmune disease flare.

Methods: We conducted a retrospective study in a tertiary referral center from 2005 to 2015. Disease flare was defined as the onset of a new organ involvement or worsening of autoimmune disease within 4 weeks following RTX.

Results: Among the 185 patients, we identified 7 disease flares (3.4%). All were due to type II mixed cryoglobulinemia vasculitis. Vasculitis flare occurred after a median time of 8 days (range 2-16) following RTX infusion and included acute kidney insufficiency (n = 7), purpura with cutaneous (n = 7), gastrointestinal (GI) tract involvement (n = 4), and myocarditis (n = 1). Patients with RTX-associated cryoglobulinemia vasculitis flare had these conditions more frequently: renal involvement (p = 0.0008), B cell lymphoproliferation (p = 0.015), higher level of cryoglobulin (2.1 vs 0.4 g/l, p = 0.0004), and lower level of C4 (0.02 vs 0.05, p = 0.023) compared to patients without flare after RTX (n = 43). Four patients (57%) died after a median time of 3.3 months. The 1-year survival rate was poorer in patients with vasculitis flare after RTX compared to their negative counterpart [43% (95% CI 18-100) vs 97% (95% CI 92-100), p < 0.001]. Immunofluorescence analysis of kidney biopsy in patients with worsening RTX-associated vasculitis highlighted the presence of RTX-, IgM-, and IgG1-positive staining of endomembranous deposits and thrombi within kidney lesions.

Conclusion: RTX-associated cryoglobulinemia vasculitis flare is associated with high mortality rate. We provided evidence that kidney lesions are due to immune complex deposition and to glomerular obstruction by cryoglobulinemia and RTX.
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http://dx.doi.org/10.3899/jrheum.190076DOI Listing
June 2020

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

Intrauterine fetal deaths related to antiphospholipid syndrome: a descriptive study of 65 women.

Arthritis Res Ther 2018 Nov 6;20(1):249. Epub 2018 Nov 6.

AP-HP, Cochin Hospital, Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares d'île de France, 27 Rue du Faubourg Saint Jacques, 75014, Paris, France.

Objective: Although one of the three obstetric manifestations of antiphospholipid syndrome (APS) is intrauterine fetal death (IUFD), little is known about it in this context. We report the first large series of patients with APS and IUFD.

Methods: We retrospectively analyzed the history and clinical data of women at four French hospitals. All had (1) APS diagnosis (Sydney criteria) and (2) IUFD at or after 10 weeks of gestation (weeks) between 2000 and 2016.

Results: The study included 65 women. Their median age at the index IUFD was 29 years (IQR 26-33); 38 (58%) were primigravidas. The index IUFD was the first APS clinical manifestation in 48 women (74%). Overall, 35% had a triple-positive antibody profile. IUFD occurred at a median gestational age of 24 weeks (IQR 18-27) and was associated with maternal obstetric complications in 16 women (25%), namely, preeclampsia (n = 12), hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP) (n = 6), and/or placental abruption (n = 5). Half of the 50 women with available data had a small-for-gestational-age fetus. Overall, including during the follow-up period of 4 years (IQR 2-9), 28 women (43%) had at least one thrombosis, and 29% were diagnosed with systemic lupus erythematosus (SLE). Ultimately, 54 women (83%) had at least one live birth. Only one woman had three consecutive early miscarriages.

Conclusion: IUFD was most often the inaugural sign of APS. Of the APS classification criteria, IUFD, preeclampsia, and thromboses were common in this cohort, while the "3 consecutive early miscarriages" criterion was met only once. With treatment, most of the women successfully had at least one live birth.
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http://dx.doi.org/10.1186/s13075-018-1745-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235231PMC
November 2018

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires.

Clin Pharmacol Ther 2019 08 2;106(2):374-382. Epub 2018 Sep 2.

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ < 200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI < 80%). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 23.4% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).
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http://dx.doi.org/10.1002/cpt.1194DOI Listing
August 2019

Characteristics, outcome and treatments with cranial pachymeningitis: A multicenter French retrospective study of 60 patients.

Medicine (Baltimore) 2018 07;97(30):e11413

AP-HP, Hôpital Saint Antoine, Service de Médecine Interne et Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris AP-HP, Hôpital Jean Verdier, Service de Médecine Interne, Bondy Département de Médecine Interne, CHU de la Timone, Aix-Marseille Université, AP-HM, Marseille Université Paris Descartes, Paris AP-HP, Hôpital Cochin, Centre de Référence des Maladies Auto-immunes et Systémiques Rares, Service de Médecine Interne, Paris Département de Neurologie, Hôpital Gui de Chauliac, CHU de Montpellier Département de Médecine Interne, GH Saint-Louis Lariboisière Fernand Widal Université Paris Diderot, Paris Service de Médecine Interne, CHU Hôtel-Dieu, Nantes Service de Médecine Interne et Vasculaire, CHU Montpellier, Montpellier Service de Médecine Interne, Hôpital Pierre Oudot, Bourgoin Jailleu Service de Médecine Interne, Clinique Sainte Anne, rue Philippe Thyss, Strasbourg Service de Neurologie, Centre Hospitalier Compiègne, Compiègne Service de Médecine Interne, Hôpital Pitié Salpetrière, Université Paris, APHP, Paris Université Pierre et Marie Curie, Paris, UPMC Centre National de Référence des Maladies Auto-immunes et Systémiques Rares Service de Médecine Interne, Hôpital Delafontaine, Saint Denis Service de Médecine Interne, Université Paris, AP-HP, Avicenne, Bobigny Service de Médecine Interne, CHU Jean Minjoz, Besançon Service de Médecine Interne, Hôpital Pitié Salpetrière, Université Paris, APHP, Paris, France.

The aim of this study was to determine the characteristics, treatment, and outcome according to each etiology of pachymeningitis.We conducted a retrospective multicenter French nationwide study between 2000 and 2016 to describe the characteristics, outcome, and treatment of pachymeningitis.We included 60 patients (median age 55.5 years; interquartile range [IQR] 30-80, female/male ratio 0.43). Neurologic signs were present in 59 patients (98%) and consisted of headache in 43 (72%), cranial nerve palsy in 33 (55%), confusion in 10 (17%), seizures in 7 (12%), and focal neurologic signs in 9 (15%). Fever and weight loss were present in 8 (13%) and 13 cases (22%), respectively. Cerebral venous thrombosis was present in 8 cases (13%). Analysis of cerebrospinal fluid showed moderate hyperproteinorachia (median 0.68 g/L; IQR 0.46-3.2) with or without pleiocytosis. Diagnosis included idiopathic pachymeningitis (n = 18; 30%); granulomatosis with polyangiitis (n = 13; 17%); Erdheim-Chester disease (n = 10; 17%); IgG4-related disease and tuberculosis (n = 3; 5% each); Rosai-Dofman disease, microscopic polyangiitis, and sarcoidosis (n = 2, 3% each); cryptococcal meningitis, Lyme disease, ear-nose-throat infection, postlumbar puncture, low spinal-fluid pressure syndrome, and lymphoma (n = 1 each). We found no difference in demographics and neurologic presentation among idiopathic pachymeningitis, Erdheim-Chester disease, and granulomatosis with polyangiitis. In contrast, frequencies were lower with idiopathic pachymeningitis than Erdheim-Chester disease for general signs (6% and 40%, respectively, P = .041) and complete neurologic response (0% vs 39%, P = .045).The detection of extraneurologic signs and routine screening are needed to classify the pachymeningitis origin. Prospective studies are warranted to determine the best treatment in each case.
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http://dx.doi.org/10.1097/MD.0000000000011413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078725PMC
July 2018

Classification of primary antiphospholipid syndrome as systemic lupus erythematosus: Analysis of a cohort of 214 patients.

Autoimmun Rev 2018 Sep 10;17(9):866-872. Epub 2018 Jul 10.

Université Paris Descartes-Sorbonne Paris Cité, France; AP-HP, Centre de référence maladies auto-immunes et systémiques rares de l'île de France, Service de médecine interne Pôle médecine, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75679 Paris cedex 14, France; INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France. Electronic address:

Objectives: To assess the limitations of the SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for systemic lupus erythematosus (SLE), in patients with primary antiphospholipid syndrome (PAPS).

Methods: Retrospective study of a cohort of APS patients (Sydney criteria). We successively excluded patients with (1) at least one "SLE-specific" manifestation (biopsy-proven SLE nephropathy, arthritis, cutaneous, or neurologic SLE manifestations, pericarditis, autoimmune haemolytic anaemia, oral and nasal ulcers, non-scarring alopecia, anti-dsDNA, and anti-Sm antibodies), (2) any other autoimmune connective tissue disease, and/or (3) antinuclear antibodies >1/320. Careful file review confirmed PAPS among the remaining patients. We then assessed the number of SLICC criteria each patient met.

Results: Among these 214 APS patients, we excluded 85 with at least one SLE-specific manifestation, 8 with another connective tissue disease, and 21 with antinuclear antibodies >1/320, leaving 100 patients with primary APS. Among them, 28% met at least 4 SLICC classification criteria including one clinical and one immunological criterion (antiphospholipid antibodies, aPL, by definition) and could thus theoretically be classified with SLE. Fourteen had an arterial phenotype (50%), 9 a history of catastrophic APS (32%), and 18 a triple-positive profile for aPL (64%). None had developed SLE during a median follow-up of 12 [6.5-17] years.

Conclusion: Because 28% of our patients with longstanding and strictly defined PAPS could be mistakenly classified as SLE, they were at risk of deleterious therapeutic management. We therefore suggest that any future classification for SLE should specifically require at least one SLE-specific criterion for patients with aPL.
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http://dx.doi.org/10.1016/j.autrev.2018.03.011DOI Listing
September 2018

Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies.

Front Immunol 2018 7;9:864. Epub 2018 May 7.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili di Brescia, Brescia, Italy.

Objective: Antiphospholipid antibodies positivity (aPL) is considered as a risk factor for adverse pregnancy outcome (APO). The aim of this study was to determine the risk factors for APO in patients with confirmed aPL positivity, isolated (aPL carriers) or associated with a definite primary antiphospholipid syndrome (PAPS).

Methods: The clinical and laboratory features of 283 pregnancies occurring between 2000 and 2014 in 200 women were collected in three institutions.

Results: The rate of live birth was 87.9% and APO was observed in 50 cases (17.7%). Multivariate analysis showed that the independent variables related to APO were the concomitant diagnosis of an organ-specific autoimmune disease ( = 0.012, odds ratio (OR) 3.29, confidence interval (CI) 95% 1.29-8.38) and the presence of low complement levels during the first trimester ( = 0.02, OR 2.3, CI 95% 1.17-9.15). No statistical differences were found in APO occurrence among patients treated with low-dose aspirin (LDA) versus those treated with LDA plus heparin (LMWH), but LDA + LMWH was more frequently administered in patients with triple aPL positivity ( = 0.001, OR 3.21, CI 95% 1.48-7.11) and with PAPS ( < 0.001, OR 8.08, CI 95% 4.3-15.4). Based on clinical history, the patients were divided into four groups: obstetric, thrombotic, non-criteria antiphospholipid syndrome (clinical non-criteria), and aPL carriers. APOs were more frequent in the thrombotic group (24%). Seven patients had a thrombotic event during pregnancy or puerperium (2.4%).

Conclusion: Maternal and fetal complications were observed in some aPL-positive patients despite their efficient management according to the current recommendations. A higher risk of APO was observed in patients with a previous thrombosis and/or more complex autoimmune phenotype.
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http://dx.doi.org/10.3389/fimmu.2018.00864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949611PMC
July 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

News on Relapsing Polychondritis: The Patient's Experience.

Arthritis Care Res (Hoboken) 2018 08;70(8):1121-1123

AP-HP, Cochin Hospital, Université Paris Descartes-Sorbonne Paris Cité, and INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité, Paris, France.

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http://dx.doi.org/10.1002/acr.23490DOI Listing
August 2018

Treatment adherence in systemic lupus erythematosus and rheumatoid arthritis: time to focus on this important issue.

Rheumatology (Oxford) 2018 Sep;57(9):1507-1509

AP-HP, Service de Médecine Interne, Centre de Référence des Maladies Auto-immunes Systémiques Rares d'Ile de France, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France, France.

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http://dx.doi.org/10.1093/rheumatology/kex337DOI Listing
September 2018

Reply.

Arthritis Rheumatol 2018 01 28;70(1):149. Epub 2017 Nov 28.

Université Pierre et Marie Curie Paris VI , Paris, France.

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http://dx.doi.org/10.1002/art.40329DOI Listing
January 2018

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires.

Clin Pharmacol Ther 2018 06 9;103(6):1074-1082. Epub 2017 Nov 9.

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ <200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI <80% or MMAS-8 <6). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 39.9% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).
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http://dx.doi.org/10.1002/cpt.885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858989PMC
June 2018

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

Int J Cardiol 2017 Dec 7;248:263-269. Epub 2017 Aug 7.

AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, Paris, France. Electronic address:

Background: Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear.

Methods: We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies.

Results: Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth-36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20-8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81-9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94-15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth-4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months-22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63-4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM.

Conclusion: Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB.
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http://dx.doi.org/10.1016/j.ijcard.2017.07.100DOI Listing
December 2017

Catastrophic antiphospholipid syndrome (CAPS)-induced ischemic pancreatic ducts injury mimicking intraductal papillary mucinous neoplasm (IPMN).

Semin Arthritis Rheum 2018 02 10;47(4):565-568. Epub 2017 Jul 10.

Université Paris-Descartes, Paris, France; AP-HP, Hôpital Cochin, Centre de référence des maladies auto-immunes et systémiques rares, Service de Médecine Interne, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; INSERM U 1153, Center for Epidemiology and Statistics, Sorbonne Paris Cité (CRESS) Paris, France. Electronic address:

Objectives: Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening disease characterized by multiple small-vessel occlusions of rapid onset. Ischemic pancreatic duct lesions secondary to CAPS have never been reported.

Methods: We describe 4 patients who presented lesions suspected to be intraductal papillary mucinous neoplasm (IPMN) of the pancreas following a CAPS.

Results: All patients had a history of CAPS months or years before the IPMN diagnosis. They had abdominal pain or abnormal liver test results and had undergone radiography. In a 36-year-old man, endoscopic ultrasonography and magnetic resonance cholangiopancreatography demonstrated parietal thickening, stenoses and dilatations of the main pancreatic duct, which suggested IPMN. A pancreatic resection was performed because of presumed risk of malignancy. Histology revealed pancreatitis and thrombosis of small pancreatic vessels but no IPMN. The 3 other cases had lesions consistent with IPMN disclosed on MRI. From the first case experience, regular radiography surveillance was decided for the 3 other patients. After more than 4 years of follow-up, lesions remained unchanged.

Conclusion: Physicians must be aware that these lesions may be encountered in CAPS and may closely mimic IPMN, with subsequent risk of performing unnecessary pancreatectomy.
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http://dx.doi.org/10.1016/j.semarthrit.2017.07.001DOI Listing
February 2018

Biologics in myelodysplastic syndrome-related systemic inflammatory and autoimmune diseases: French multicenter retrospective study of 29 patients.

Autoimmun Rev 2017 Sep 10;16(9):903-910. Epub 2017 Jul 10.

Service de Médecine Interne, Hôpital Saint Antoine, APHP, Université Paris 6, 75012 Paris, France; Service de médecine interne, CHU Bretagnes Atlantique, Vannes, France.

Background: Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified.

Methods: In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α [TNF-α] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics.

Results: We included 29 patients (median age 67years [interquartile range 62-76], 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis (n=6; 20%), relapsing polychondritis (n=8; 30%) and vasculitis (n=10; 34%). During a 3-year median follow-up (IQR 1.3-4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-α antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) (p<0.05). Rituximab had better response in vasculitis and TNF-α antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection.

Conclusion: This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising.
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http://dx.doi.org/10.1016/j.autrev.2017.07.003DOI Listing
September 2017

Longterm Outcome of Patients with Primary Antiphospholipid Syndrome: A Retrospective Multicenter Study.

J Rheumatol 2017 08 1;44(8):1165-1172. Epub 2017 Jun 1.

From the Rheumatology and Clinical Immunology Department, Spedali Civili and University of Brescia, Brescia; Division of Rheumatology, Department of Clinical Sciences and Community Health, Ospedale Gaetano Pini, University of Milan, Milan; Rheumatology Unit, Department of Medicine - DIMED, University of Padua, Padua; Internal Medicine and Medical Specialties Department, Policlinico Umberto I, La Sapienza University of Rome, Rome, Italy; AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, Service de Médecine Interne; AP-HP, Hospital Pitié-Salpêtrière, Centre de référence maladies auto-immunes et systémiques rares, Service de Médecine Interne, Pierre et Marie Curie Paris VI University, Paris, France; University of the West Indies, Kingston, Jamaica.

Objective: To assess the longterm frequency of thrombotic recurrences, obstetrical complications, organ damage, severe comorbidities, and evolution toward connective tissue disease (CTD) in primary antiphospholipid syndrome (PAPS).

Methods: Medical records of patients with PAPS followed in 6 centers for ≥ 15 years were retrospectively reviewed.

Results: One hundred fifteen patients were studied: 88% women, followed between 1983 and 2014 with a mean (± SD) age at diagnosis of 33 (± 10) years. During a median followup of 18 years (range 15-30), 50 patients (44%) had at least a thrombotic event for a total of 75 events and an annual incidence of 3.5%. Thromboses were more frequent in patients with previous thrombotic history (p = 0.002). A catastrophic antiphospholipid syndrome occurred in 6 patients (5%). The use of oral anticoagulants in patients with thrombotic onset did not appear to be protective against recurrences (p = 0.26). Fifty-two women had 87 pregnancies, successful in 78%. Twenty-nine percent of patients accrued functional damage. Damage was significantly associated with a thrombotic history (p = 0.004) and with arterial events (p < 0.001), especially stroke, but not with demographics, serology, or treatment. Twenty-four major bleeding episodes were recorded in 18 patients, all receiving anticoagulants. Severe infections affected 6 patients (5%), with 1 fatality. A solid cancer was diagnosed in 8 patients (7%). Altogether, 16 patients (14%) developed an autoimmune disease and 13 (11%) a full-blown picture of CTD.

Conclusion: Despite therapy, a high proportion of patients experienced new thrombotic events and organ damage, while evolution toward CTD was infrequent.
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http://dx.doi.org/10.3899/jrheum.161364DOI Listing
August 2017

Fertilization in 37 Women with Systemic Lupus Erythematosus or Antiphospholipid Syndrome: A Series of 97 Procedures.

J Rheumatol 2017 05 15;44(5):613-618. Epub 2017 Jan 15.

From the Centre de compétence de maladies auto-immunes et systémiques rares, Service de médecine interne, Hôpital Robert Debré, Centre Hospitalier Universitaire (CHU), Reims Cedex; Service de médecine interne, CHU, Nantes; Université René Descartes Paris V, Centre de référence maladies auto-immunes et systémiques rares, Service de médecine interne, Hôpital Cochin, AP-HP; Service de gynécologie-obstétrique, Hôpital Cochin, AP-HP; Service de gynécologie-obstétrique, Groupe Hospitalier Pitié Salpêtrière, AP-HP; Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B); INSERM, UMR_S 959, F-75013; CNRS, FRE3632, F-75005; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.

Objective: To compile and assess data about complication and success rates for fertilization (IVF) of women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). To date, such data are sparse.

Methods: This retrospective study described women with SLE and/or APS who have had at least 1 IVF cycle.

Results: Thirty-seven women with SLE (n = 23, including 8 with antiphospholipid antibodies), SLE with APS (n = 4), or primary APS (n = 10) underwent 97 IVF procedures. For 43% of cases, the infertility was female in origin, for 19% male, 14% mixed, and 24% unexplained. No women had premature ovarian insufficiency because of cyclophosphamide. Median age at IVF was 34 years (range 26-46). The median number of IVF cycles was 2.6 (1-8). Patients were treated with hydroxychloroquine (72%), steroids (70%), azathioprine (3%), aspirin (92%), and/or low molecular weight heparin (62%). There were 27 (28%) pregnancies, 23 live births among 26 neonates (3 twin pregnancies), 2 miscarriages, and 2 terminations for trisomy 13 and 21. Six spontaneous pregnancies occurred during the followup. Finally, 26 women (70%) delivered at least 1 healthy child. Complications occurred in or after 8 IVF cycles (8%): SLE flares in 4 (polyarthritis in 3 and lupus enteritis in 1) and thromboembolic events in 4 others. One SLE flare was the first sign of previously undiagnosed SLE. Poor treatment adherence was obvious in 2 other flares and 2 thromboses. No ovarian hyperstimulation syndrome was reported.

Conclusion: These preliminary results confirm that IVF can be safely and successfully performed in women with SLE and/or APS.
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http://dx.doi.org/10.3899/jrheum.160462DOI Listing
May 2017

Lupus Myocarditis: Initial Presentation and Longterm Outcomes in a Multicentric Series of 29 Patients.

J Rheumatol 2017 01 15;44(1):24-32. Epub 2016 Nov 15.

From the APHP, Service de Médecine Interne, Institut E3M, Hôpital de la Pitié-Salpêtrière and Sorbonnes Universités, UPMC Université Paris VI, Paris; Service de Réanimation, and Service de Médecine Interne, Hôpital Européen, Marseille; Centre National de Référence pour les Maladies systémiques rares, Lupus et Syndrome des Anticorps antiphospholipides, Hôpital de la Pitié-Salpêtrière, Paris; APHP, Service de Médecine Interne, Centre de référence maladies auto-immunes et systémiques rares, Paris; Université Paris Descartes-Sorbonne Paris Cité, Paris; Assistance Publique-Hôpitaux de Marseille (APHM), Service de Médecine interne, Hôpital de la Conception, Marseille; APHM, Service de Médecine interne, Hôpital de la Timone, Marseille; APHP, Service de Radiologie, Pitié-Salpêtrière, Paris; Unité de Dermatologie-Médecine Interne, EA4546, CHU Pointe à Pitre, Guadeloupe; Département de Néphrologie et Transplantation, CHU de Toulouse, Toulouse; APHP, Service de Réanimation, INSERM, UMRS-1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.

Objective: Cardiac involvement during systemic lupus erythematosus (SLE) may include the pericardium, myocardium, valvular tissue, and coronary arteries. The aim of this study was to describe the clinical, biological, and radiological presentation of lupus myocarditis (LM) as well as the treatment response and longterm outcomes.

Methods: We conducted a multicentric retrospective study of LM from January 2000 to May 2014.

Results: Twenty-nine patients (3 men and 26 women) fulfilled the inclusion criteria (median age at the diagnosis of SLE: 30 yrs, range 16-57). Myocarditis was the first sign of SLE in 17/29 cases (58.6%). Troponin was elevated in 20/25 cases. Electrocardiogram results were abnormal in 25/28 cases. Echocardiography revealed low (≤ 45%) left ventricular ejection fraction (LVEF; 19/29, 66%) and pericardium effusion (20/29, 69%). Cardiac magnetic resonance imaging revealed delayed gadolinium enhancement in 9/13 patients (69%). Patients were treated with corticosteroids (n = 28), cyclophosphamide (CYC; n = 16), intravenous immunoglobulins (n = 8), and/or mycophenolate mofetil (n = 2). The median followup was 37 months. One month after the beginning of the treatment, 10/23 patients (43%) who had undergone echocardiography had an LVEF ≥ 55%. At the end of followup, 21/26 patients (81%) exhibited an LVEF ≥ 55%. Three patients died during followup, and 2 died from LM.

Conclusion: LM is a severe manifestation of SLE. It can be the first manifestation of the disease or it can occur during followup, in particular in untreated patients. However, the longterm prognosis is typically positive. Patients with less severe disease exhibited good LVEF recovery without CYC.
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http://dx.doi.org/10.3899/jrheum.160493DOI Listing
January 2017

Reply.

Arthritis Rheumatol 2017 03 2;69(3):683-684. Epub 2017 Feb 2.

Département de Médecine Interne 1, Centre de Référence Maladies Auto-immunes, et Systémiques Rares, Université Pierre et Marie Curie Paris VI, AP-HP, Paris, France.

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http://dx.doi.org/10.1002/art.39972DOI Listing
March 2017

[2016 review on catastrophic antiphospholipid syndrome].

Presse Med 2016 Dec 9;45(12 Pt 1):1084-1092. Epub 2016 Sep 9.

Assistance publique-Hôpitaux de Paris, université Pierre-et-Marie-Curie, hôpital Pitié-Salpêtrière, centre de référence national pour le lupus systémique et le syndrome des antiphospholipides, département de médecine interne et d'immunologie clinique, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France.

The catastrophic antiphospholipid syndrome (CAPS) develops in at least 1% of patients with antiphospholipid syndrome, either primary or associated with systemic lupus erythematosus. CAPS reveals the antiphospholipid syndrome in about 50% of cases. The CAPS is characterized by rapidly-progressive widespread thromboses mainly affecting the microvasculature in the presence of antiphospholipid antibodies. In a few days, the patients develop multiorgan failure with renal insufficiency with severe hypertension, pulmonary, cerebral, cardiac, digestive and/or cutaneous involvement. The vital prognosis is frequently engaged. CAPS is often precipitated by infectious diseases, surgical procedures and/or withdrawal or modification of the anticoagulation. CAPS overall mortality rate has decreased and is currently below 30%. The main differential diagnoses are other thrombotic microangiopathies, and heparin-induced thrombocytopenia. The treatment of CAPS consists of the association of anticoagulation and steroids, plus plasma exchange and/or intravenous immunoglobulins. Cyclophosphamide is added only in patients with active systemic lupus erythematosus. The potential contribution of some additional therapies (rituximab, eculizumab or sirolimus) needs to be assessed. The prevention of CAPS is essential and is based upon the adequate management of the perioperative period when surgery cannot be avoided, the prompt treatment and the prevention with immunization of infections and the education of patients with antiphospholipid syndrome, especially for the management of oral anticoagulants.
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http://dx.doi.org/10.1016/j.lpm.2016.07.023DOI Listing
December 2016

Pulmonary hyalinizing granuloma: a multicenter study of 5 new cases and review of the 135 cases of the literature.

Immunol Res 2017 02;65(1):375-385

Service de Médecine Interne 2, Centre National de Référence Maladies auto-immunes Systémiques Rares, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.

Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by single or multiple benign lung nodules mimicking lung neoplasma. Histologic analysis reveals homogenous hyaline lamellae, usually surrounded by collection of plasma cells, lymphocytes and histiocytes in a perivascular distribution. The clinical and radiological findings have been described in small series, but the long-term outcomes have rarely been reported. The objectives were to describe the clinical, radiological and outcomes of PHG in new cases and through a literature review. Patients with PHG were found by a multicenter search among French departments of internal medicine, pulmonology and anatomo-pathology. Review of the literature was made through the National Library of Medicine's MEDLINE database using keywords "hyalinizing granuloma." Five news cases and 135 cases of the literature were found. There were 82 men and 57 women, mean age at the diagnosis 44.6 years (15-83). Patients were frequently asymptomatic (n = 39, 27.4 %). The nodule was unique in 37 cases (28.9 %) and multiple in 91 cases (71.1 %). 18FDG PET scan revealed hypermetabolism of the nodule in 9/15 cases (60 %). A systemic disease was associated in 65 cases (mainly mediastinal and retroperitoneal fibrosis, autoimmune, tumoral or infectious disease or thromboembolism). The outcomes were evaluated in 73 patients when follow-up was available: 14 patients had a surgical resection of the nodule. Forty-five patients did not receive any immunosuppressive drug. Among these patients, 2 improved, 29 were stable and 14 worsened. Corticosteroids were used as a monotherapy in 19 patients and led to radiological improvement in 8 cases, stabilization in 8 cases and worsening in 3 cases. Five patients were treated with corticosteroids and at least one immunosuppressive drug and 4 patients improved. PHG is a rare benign disease, mimicking lung neoplasma, frequently associated with systemic diseases.
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http://dx.doi.org/10.1007/s12026-016-8852-4DOI Listing
February 2017

Relapsing Polychondritis Can Be Characterized by Three Different Clinical Phenotypes: Analysis of a Recent Series of 142 Patients.

Arthritis Rheumatol 2016 12;68(12):2992-3001

Université Pierre et Marie Curie Paris VI, AP-HP, and Centre de référence maladies auto-immunes et systémiques rares, Hôpital Pitié Salpêtrière, Paris, France.

Objective: Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on this disease remain scarce. This study was undertaken to describe patient characteristics and disease evolution, identify prognostic factors, and define different clinical phenotypes of RP.

Methods: We performed a retrospective study of 142 patients with RP who were seen between 2000 and 2012 in a single center.

Results: Of the 142 patients, 86 (61%) were women. The mean ± SD age at first symptoms was 43.5 ± 15 years. Patients had the following chondritis types: auricular (89%; n = 127), nasal (63%; n = 89), laryngeal (43%; n = 61), tracheobronchial (22%; n = 32), and/orcostochondritis (40%; n = 57). The main other manifestations were articular (69%; n = 98), ophthalmologic (56%; n = 80), audiovestibular (34%; n = 48), cardiac (27%; n = 38), and cutaneous (28%; n = 40). At a mean ± SD followup of 13 ± 9 years, the 5- and 10-year survival rates were 95 ± 2% and 91 ± 3%, respectively. Factors associated with death on multivariable analysis were male sex (P = 0.01), cardiac abnormalities (P = 0.03), and concomitant myelodysplastic syndrome (MDS) (P = 0.004) or another hematologic malignancy (P = 0.01). Cluster analysis revealed that separating patients into 3 groups was clinically relevant, thereby separating patients with associated MDS, those with tracheobronchial involvement, and those without the 2 features in terms of clinical characteristics, therapeutic management, and prognosis.

Conclusion: This large series of patients with definite RP revealed an improvement in survival as compared with previous studies. Factors associated with death were male sex, cardiac involvement, and concomitant hematologic malignancy. We identified 3 distinct phenotypes.
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http://dx.doi.org/10.1002/art.39790DOI Listing
December 2016

Routine Hydroxychloroquine Blood Concentration Measurement in Systemic Lupus Erythematosus Reaches Adulthood.

J Rheumatol 2015 Nov;42(11):1997-9

Hôpital Pitié-Salpêtrière, Centre de référence maladies auto-immunes et systémiques rares, Paris, France.

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http://dx.doi.org/10.3899/jrheum.151094DOI Listing
November 2015

Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study.

Rheumatology (Oxford) 2016 Feb 8;55(2):291-300. Epub 2015 Sep 8.

Service de rhumatologie, CH Croix Saint Simon.

Objective: We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study.

Methods: In this study, 123 patients with MDS and SIADs were analysed.

Results: Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P < 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P < 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5).

Conclusion: The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent.
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http://dx.doi.org/10.1093/rheumatology/kev294DOI Listing
February 2016

Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome.

Autoimmun Rev 2015 Dec 15;14(12):1154-60. Epub 2015 Aug 15.

AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Paris, France. Electronic address:

Background: Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB.

Methods: Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies.

Results: 214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p<0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p<0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB.

Conclusion: In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.
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http://dx.doi.org/10.1016/j.autrev.2015.08.005DOI Listing
December 2015