Publications by authors named "Romain Paule"

19 Publications

  • Page 1 of 1

The Clinical Spectrum and Outcome of Uveomeningitis: A Comprehensive Analysis of 110 Cases.

Ocul Immunol Inflamm 2021 May 11:1-6. Epub 2021 May 11.

Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, APHP-Centre Université de Paris (CUP), Paris, France.

Uveitis can be associated with meningitis (uveomeningitis) and the inflammation shared with the central nervous system. We aimed to describe the characteristics and outcome of uveomeningitis. We retrospectively analyzed 110 consecutive adult patients with uveomeningitis. The main causes of uveomeningitis were Vogt-Koyanagi-Harada (31%), syphilis (16%), sarcoidosis (12%), Behçet's disease (7%), and multiple sclerosis (5%). Sixteen percent of uveomeningitis remained of undetermined origin. Compared to etiology-matched uveitis without meningitis, patients with uveomeningitis were younger, had more frequent neurological manifestations, and had more frequent abnormal cerebral magnetic resonance imaging findings. In contrast, no ocular feature upon examination was significantly associated with the presence of meningitis. Patients with uveomeningitis were more frequently treated with immunosuppressants but uveitis relapse and systemic complications did not differ between groups. Uveomeningitis is associated with a limited spectrum of diseases. Meningitis does not seem to impact ocular and extraocular outcomes. Therefore, lumbar puncture should be performed on an individual basis during the diagnostic workup of uveitis.
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http://dx.doi.org/10.1080/09273948.2021.1898000DOI Listing
May 2021

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

A French cohort of patients with giant cell arteritis: glucocorticoid treatment and its associated side effects.

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):155-160. Epub 2021 Apr 30.

Department of Internal Medicine, Hôpital Cochin, Université de Paris, Sorbonne Paris Cité, INSERM Unité 1016, Centre de Référence pour les Maladies Auto-immunes Rares, Paris, and Institut Cochin, INSERM U1016, CNRS UMR 8104, Paris, France.

Objectives: Giant cell arteritis (GCA) is the most common primary large-vessel vasculitis. Glucocorticoids (GC) therapy remains the standard of care for GCA despite frequent side effects (SEs). However, treatment modality changes, prophylactic treatment of osteoporosis, or vaccinations might have decreased the frequency of GC-related SEs. This study aims to describe GCA treatment and GC-related SEs in a recent cohort.

Methods: Patients with a diagnosis of GCA between May 2009 and March 2018 were included in this multicentric retrospective study. Characteristics of patients, treatment modalities and GC-related SEs were collected and analysed. Risk factors associated with the occurrence of SE were studied.

Results: We analysed the files from 206 patients (153 women, 53 men; median age 74 years). Median follow-up was 34 months. Patients received GC for a median of 25 months, starting at 0.7 mg/kg/day, with tapering to 5 mg/day after 11 months follow-up. Flares occurred in 83/201 (41%) patients. Among the 132 patients who stopped GC, 29 (22%) experienced a relapse. SEs occurred in 129 (64%) patients: bone fractures and infections in 13% each and hypertension onset in 9%. Age >75 years, treatment duration >2 years, past medical history of diabetes were risk factors associated with GC-related SEs.

Conclusions: Flares occur in 41% of patients during GC withdrawal. As much as 64% of patients had treatment related SEs. An age> 75 year and a past medical history of diabetes were predictive of SEs during follow-up.
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May 2021

Characteristics and risk factors for poor outcome in patients with systemic vasculitis involving the gastrointestinal tract.

Semin Arthritis Rheum 2021 04 3;51(2):436-441. Epub 2021 Mar 3.

Department of Internal Medicine and Clinical Immunology, CHRU Tours, Tours, France.

Background: Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype.

Aims: This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis.

Methods: Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death.

Results: Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29-7.34), performance status (OR 1.40, 1.05-1.87), use of morphine (OR 2.51, 0.87-7.24), abdominal guarding (OR 3.08, 1.01-9.37), ileus (OR 2.29, 0.98-5.32), melena (OR 2.74, 1.17-6.42), increased leukocytes (per G/L, OR 1.05, 1.00-1.10), low hemoglobin (per g/dL, OR 0.80, 0.71-0.91) and increased CRP (log mg/L, OR 1.21, 0.94-1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well.

Conclusions: Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death.
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http://dx.doi.org/10.1016/j.semarthrit.2021.03.002DOI Listing
April 2021

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis.

J Clin Immunol 2021 02 14;41(2):303-314. Epub 2020 Nov 14.

Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France.

Background: High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters.

Methods: The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology.

Results: Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25-0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36-0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31-1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17-2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22-2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group.

Conclusion: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.
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http://dx.doi.org/10.1007/s10875-020-00911-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666405PMC
February 2021

IgA monoclonal gammopathy associated with refractory IgA vasculitis successfully treated with clone-targeted therapy.

Autoimmun Rev 2020 Sep 11;19(9):102611. Epub 2020 Jul 11.

Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases of Ile de France, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Paris Descartes University, Paris University, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2020.102611DOI Listing
September 2020

Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data.

BMJ 2020 May 14;369:m1844. Epub 2020 May 14.

Clinical Epidemiology and Aging Team, Mondor Institute for Biomedical Research (INSERM U955), Public Health Services, Henri-Mondor Hosptial, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France.

Objective: To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen.

Design: Comparative observational study using data collected from routine care.

Setting: Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020.

Participants: 181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care.

Interventions: Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group).

Main Outcome Measures: The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting.

Results: In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment.

Conclusions: Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.
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http://dx.doi.org/10.1136/bmj.m1844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221472PMC
May 2020

Lymphocyte Immunophenotyping and CD4/CD8 Ratio in Cerebrospinal Fluid for the Diagnosis of Sarcoidosis-related Uveitis.

Ocul Immunol Inflamm 2021 Feb 31;29(2):290-298. Epub 2019 Oct 31.

Department of Internal Medicine, Cochin Hospital, Paris, France.

: This study aimed to assess the diagnostic relevance of CD4/CD8 ratio in cerebrospinal fluid (CSF) for the etiological diagnosis work-up of uveitis.: We consecutively included patients who were referred to our department for the diagnostic workup of intermediate and/or posterior uveitis. Etiological diagnoses were established in a blind manner regarding CD4/CD8 ratio.: Fifty-two patients were included. A diagnosis of ocular sarcoidosis was made in 15 (29%) patients, 21% had another determined diagnosis while 50% remained of undetermined origin. Median CD4/CD8 ratio in CSF was 4.57 (IQR 3.39-5.47) in ocular sarcoidosis, 1.74 (1.60-3.18) in uveitis due to other determined cause ( = .008), and 2.83 (2.34-3.54) in those with uveitis of undetermined origin ( = .007). CD4/CD8 ratio >3.23 was associated with a diagnosis of ocular sarcoidosis.: Determination of CD4/CD8 ratio in CSF can be useful for diagnosis work-up since a CD4/CD8 ratio >3.23 in CSF is associated with ocular sarcoidosis.
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http://dx.doi.org/10.1080/09273948.2019.1678647DOI Listing
February 2021

Distal ischemia as the initial presentation of hypereosinophilic syndrome-related arterial involvement: A case study and literature review.

Autoimmun Rev 2019 Aug 7;18(8):828-830. Epub 2019 Jun 7.

Service de Médecine Interne, Centre de Référence Maladies Autoimmunes et Systémiques Rares d'Ile de France, Hôpital Cochin, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2019.06.004DOI Listing
August 2019

P-selectin drives complement attack on endothelium during intravascular hemolysis in TLR-4/heme-dependent manner.

Proc Natl Acad Sci U S A 2019 03 8;116(13):6280-6285. Epub 2019 Mar 8.

Centre de Recherche des Cordeliers, UMR_S 1138, INSERM, F-75006 Paris, France;

Hemolytic diseases are frequently linked to multiorgan failure subsequent to vascular damage. Deciphering the mechanisms leading to organ injury upon hemolytic event could bring out therapeutic approaches. Complement system activation occurs in hemolytic disorders, such as sickle cell disease, but the pathological relevance and the acquisition of a complement-activating phenotype during hemolysis remain unclear. Here we found that intravascular hemolysis, induced by injection of phenylhydrazine, resulted in increased alanine aminotransferase plasma levels and NGAL expression. This liver damage was at least in part complement-dependent, since it was attenuated in complement C3 mice and by injection of C5-blocking antibody. We evidenced C3 activation fragments' deposits on liver endothelium in mice with intravascular hemolysis or injected with heme as well as on cultured human endothelial cells (EC) exposed to heme. This process was mediated by TLR4 signaling, as revealed by pharmacological blockade and TLR4 deficiency in mice. Mechanistically, TLR4-dependent surface expression of P-selectin triggered an unconventional mechanism of complement activation by noncovalent anchoring of C3 activation fragments, including the typical fluid-phase C3(HO), measured by surface plasmon resonance and flow cytometry. P-selectin blockade by an antibody prevented complement deposits and attenuated the liver stress response, measured by NGAL expression, in the hemolytic mice. In conclusion, these results revealed the critical impact of the triad TLR4/P-selectin/complement in the liver damage and its relevance for hemolytic diseases. We anticipate that blockade of TLR4, P-selectin, or the complement system could prevent liver injury in hemolytic diseases like sickle cell disease.
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http://dx.doi.org/10.1073/pnas.1814797116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442544PMC
March 2019

Heme Drives Susceptibility of Glomerular Endothelium to Complement Overactivation Due to Inefficient Upregulation of Heme Oxygenase-1.

Front Immunol 2018 20;9:3008. Epub 2018 Dec 20.

INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.

Atypical hemolytic uremic syndrome (aHUS) is a severe disease characterized by microvascular endothelial cell (EC) lesions leading to thrombi formation, mechanical hemolysis and organ failure, predominantly renal. Complement system overactivation is a hallmark of aHUS. To investigate this selective susceptibility of the microvascular renal endothelium to complement attack and thrombotic microangiopathic lesions, we compared complement and cyto-protection markers on EC, from different vascular beds, in and models as well as in patients. No difference was observed for complement deposits or expression of complement and coagulation regulators between macrovascular and microvascular EC, either at resting state or after inflammatory challenge. After prolonged exposure to hemolysis-derived heme, higher C3 deposits were found on glomerular EC, and , compared with other EC in culture and in mice organs (liver, skin, brain, lungs and heart). This could be explained by a reduced complement regulation capacity due to weaker binding of Factor H and inefficient upregulation of thrombomodulin (TM). Microvascular EC also failed to upregulate the cytoprotective heme-degrading enzyme heme-oxygenase 1 (HO-1), normally induced by hemolysis products. Only HUVEC (Human Umbilical Vein EC) developed adaptation to heme, which was lost after inhibition of HO-1 activity. Interestingly, the expression of KLF2 and KLF4-known transcription factors of TM, also described as possible transcription modulators of HO-1- was weaker in micro than macrovascular EC under hemolytic conditions. Our results show that the microvascular EC, and especially glomerular EC, fail to adapt to the stress imposed by hemolysis and acquire a pro-coagulant and complement-activating phenotype. Together, these findings indicate that the vulnerability of glomerular EC to hemolysis is a key factor in aHUS, amplifying complement overactivation and thrombotic microangiopathic lesions.
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http://dx.doi.org/10.3389/fimmu.2018.03008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306430PMC
November 2019

Acute paraplegia due to schistosomiasis: an uncommon cause in developed countries.

J Neurovirol 2019 06 4;25(3):434-437. Epub 2019 Jan 4.

Department of internal medicine, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, University Paris-Descartes, Paris, France.

We present a case of a young African migrant from Guinea-Conakry presented to a French emergency department with burning pain in both feet for 2 days. The symptoms progressed to limb paraparesis with sphincter disorders. A magnetic resonance imaging (MRI) scan showed a hyperintense spinal cord lesion without contrast enhancement extending from the T6 vertebrae to the conus medullaris. Cerebrospinal fluid exam (CFE) showed an isolated hyperproteinorachia (0.61 g/l). Schistosomiasiss serology was positive and a rectal biopsy showed a schistosoma egg surrounded by an inflammatory reaction with granulomatosis. After steroid and antihelminthic therapy, accompanied by intensive physical therapy, the patient had an improved neurological neurological outcome.
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http://dx.doi.org/10.1007/s13365-018-0713-6DOI 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

Serum 1,25(OH) Vitamin D and 25(OH) Vitamin D Ratio for the Diagnosis of Sarcoidosis-Related Uveitis.

Ocul Immunol Inflamm 2020 Apr 5;28(3):341-347. Epub 2018 Nov 5.

Department of Internal Medicine, Cochin Hospital, Paris, France.

: The diagnostic workup of uveitis is challenging, with 30 to 50% of cases remaining of undetermined etiology despite multiple investigations. Sarcoid granuloma-related increase of 1,25(OH)D levels could be helpful for the diagnosis of ocular sarcoidosis.: Monocentric retrospective cohort study of patients for whom serum 25(OH)D and 1,25(OH)D levels were measured during the etiologic workup of unexplained uveitis in a tertiary referral center. The diagnoses of uveitis' underlying diseases were established according to international diagnostic criteria.: Fifty-nine patients were included. The diagnosis of defined, presumed or probable sarcoidosis was made in 37% of patients while 41% of cases remained of undetermined origin. The median serum levels of 25(OH)D in patients with ocular sarcoidosis and in those with uveitis due to another cause were 34.50 [21.2-40.8] and 43.20 [32.2-58.3] nmol/L (P=0.02), respectively. In the same subgroups of patients, the median serum levels of 1,25(OH)D were 132.4 [107.4-163.9] and 108.0 [84.30-130.5] pmol/l (P=0.02), and the median 1,25(OH)D/25(OH)D ratio was 4.17 [3.11-5.09] and 2.56 [1.54-3.37] (P=0.0007) respectively. A 1,25(OH)D/25(OH)D ratio >3.5 was associated with the diagnosis of sarcoidosis with a 68 % sensitivity and a 78% specificity and, in univariate analysis, was associated with an abnormal chest CT-scan (OR=5.7, P=0.003), granulomas on bronchial biopsy (OR=14.7, P=0.007) and bronchoalveolar lavage fluid lymphocytosis (OR=12.4, P=0.0006).: The measurement of serum 25(OH)D and 1,25(OH)D levels is a useful tool in the etiological workup of patients with unexplained uveitis, since a high 1,25(OH)D/25(OH)D ratio is suggestive of ocular sarcoidosis.
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http://dx.doi.org/10.1080/09273948.2018.1537399DOI Listing
April 2020

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

A Severe But Easily Treatable Dysphagia.

Gastroenterology 2017 Oct 4;153(4):e9-e10. Epub 2017 Sep 4.

Department of Internal Medicine, National Reference Center for Rare Autoimmune and Systemic Diseases, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University (Paris 5), Paris, France.

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http://dx.doi.org/10.1053/j.gastro.2017.02.049DOI Listing
October 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

A nationwide study of acquired C1-inhibitor deficiency in France: Characteristics and treatment responses in 92 patients.

Medicine (Baltimore) 2016 Aug;95(33):e4363

Internal Medicine Department, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, DHU i2B, Paris 6 University, Paris Hematology Department, Pitié Salpétrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris 6 University, Paris Immunology Laboratory, University Hospital, Grenoble Centre de Référence et d'Etude des Angioedèmes à Kinine (CREAK) , Grenoble Public Health Department, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Paris 6 University Immunology Laboratory, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris 5 University, Paris Joint Unit 1036 CNRS-CEA-INSERM, University Grenoble Alpes Internal Medicine Department, University Hospital, Grenoble Université Joseph Fourier Grenoble, GREPI/AGIM CNRS FRE 3405, Grenoble Internal Medicine Department, La Conception Hospital, AP-HM, Marseille Internal Medicine and Clinical Immunology Department, Lille University Hospital LIRIC, INSERM UMR 995, EA2686, Lille Dermatology Department, L'UNAM Université, University Hospital, Angers, France.

Acquired angioedema (AAE) due to C1-inhibitor (C1INH) deficiency is rare. Treatment options for acute attacks are variable and used off-label. Successful treatment of the associated lymphoma with rituximab seems to prevent acute attacks in subjects with AAE. The aim of this study was to describe AAE manifestations, its associated diseases, and patients' responses to treatments in a representative cohort.A retrospective nationwide study was conducted in France. The inclusion criteria were recurrent angioedema attacks and an acquired decrease in functional C1INH <50% of the reference value.A total of 92 cases were included, with a median age at onset of 62 years. Facial edema and abdominal pain were the most frequent symptoms. Fifteen patients were hospitalized in the intensive care unit because of laryngeal edema, and 1 patient died. Anti-C1INH antibodies were present in 43 patients. The associated diseases were primarily non-Hodgkin lymphoma (n = 44, with 24 splenic marginal zone lymphomas) and monoclonal gammopathy of undetermined significance (n = 24). Three patients had myeloma, 1 had amyloid light-chain (of immunoglobulin) (AL) amyloidosis, 1 patient had a bronchial adenocarcinoma, and 19 patients had no associated disease. Icatibant relieved the symptoms in all treated patients (n = 26), and plasma-derived C1INH concentrate in 19 of 21 treated patients. Six patients experienced thromboembolic events under tranexamic acid prophylaxis. Rituximab prevented angioedema in 27 of 34 patients as a monotherapy or in association with chemotherapy. Splenectomy controlled AAE in 7 patients treated for splenic marginal zone lymphoma. After a median follow-up of 4.2 years, angioedema was on remission in 52 patients.AAE cases are primarily associated with indolent lymphoma-especially splenic marginal zone lymphoma-and monoclonal gammopathy of undetermined significance but not with autoimmune diseases or other conditions. Icatibant and plasma-derived C1INH concentrate control attacks; splenectomy and immunochemotherapy prevent angioedema in lymphoma setting.
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http://dx.doi.org/10.1097/MD.0000000000004363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370791PMC
August 2016

[Kidney and thyroid dysfunction].

Nephrol Ther 2013 Feb 28;9(1):13-20. Epub 2012 Sep 28.

Service de néphrologie, hôpital de Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75013 Paris, France. Electronic address:

Thyroid hormones influence renal development, kidney structure, renal hemodynamics, glomerular filtration rate, the function of many transport systems along the nephron, and sodium and water homeostasis. Effects of hypothyroidism and hyperthyroidism on kidney function are the result of direct renal effects, as well as systemic hemodynamic, metabolic, and cardiovascular effects. Most of the renal manifestations of thyroid disorders, which are clinically most significant with hypothyroidism, are reversible with treatment. Patients with hypothyroidism can have clinically important reductions in GFR, so screening for hypothyroidism should be considered in patients with unexplained elevations in serum creatinine. Patients with thyroid disorders are also at risk for immune-mediated glomerular diseases. Finally, patients with nephrotic syndrome, as well as acute and chronic kidney injury, have alterations in thyroid gland physiology that can impact thyroid function and the testing of thyroid function status. Dialysis patients have frequently hypothyroidism whose biological diagnosis must be careful.
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http://dx.doi.org/10.1016/j.nephro.2012.06.005DOI Listing
February 2013