Publications by authors named "Laurence Bouillet"

111 Publications

Apremilast in Refractory Behçet's Syndrome: A Multicenter Observational Study.

Front Immunol 2020 4;11:626792. Epub 2021 Feb 4.

Sorbonne Universités AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Médecine Interne et Immunologie Clinique, Paris, France.

Objective: Mucocutaneous and joint disorders are the most common manifestations in Behçet's syndrome (BS) and are frequently clustered in the so-called minor forms of BS. There remains a need for safe and effective treatment for joint lesions in BS. We report the long-term safety and effectiveness of apremilast in refractory joint and mucocutaneous manifestations of BS.

Methods: French nationwide multicenter study including 50 BS patients with either active joint and/or mucocutaneous manifestations resistant to colchicine and/or DMARDs. Patients received apremilast 30 mg twice a day. Primary effectiveness endpoint was the proportion of patients with complete response (CR) of articular symptoms at month 6 (M6), defined as resolution of inflammatory arthralgia and arthritis, with joint count equal to zero.

Results: At inclusion, the median tender and swollen joint count was of 4 [2-6] and 2 [1-2], respectively. The proportion of CR in joint disease at M6 was 65% (n = 15/23), and 17% (n = 4/23) were partial responders. CR of oral and genital ulcers, and pseudofolliculitis at M6 was 73% (n = 24/33), 94% (n = 16/17) and 71% (n = 10/14), respectively. The overall response at M6 was 74% for the entire cohort and 70% for the mucocutaneous-articular cluster (n = 27). The median Behçet's syndrome activity score significantly decreased during study period [50 (40-60) 20 (0-40); 0.0001]. After a median follow-up of 11 [6-13] months, 27 (54%) patients were still on apremilast. Reasons for apremilast withdrawal included adverse events (n = 15, 30%) and treatment failure (n = 8, 16%). Thirty-three (66%) patients experienced adverse events, mostly diarrhea (n = 19, 38%), nausea (n = 17, 34%) and headache (n = 16, 32%).

Conclusion: Apremilast seems effective in BS-related articular disease refractory to colchicine and DMARDs. Discontinuation rates were significantly higher than that reported in clinical trials.
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http://dx.doi.org/10.3389/fimmu.2020.626792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889954PMC
February 2021

Efficacy of lanadelumab in acquired angioedema with C1-inhibitor deficiency.

J Allergy Clin Immunol Pract 2021 Feb 6. Epub 2021 Feb 6.

Department of Internal Medicine, Grenoble University Hospital, Grenoble, France; National Reference Centre for Angioedema, CREAK, Grenoble, France.

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http://dx.doi.org/10.1016/j.jaip.2021.01.040DOI Listing
February 2021

Tolerance and efficacy of anti-TNF currently used for severe non-infectious uveitis.

Autoimmun Rev 2021 Mar 18;20(3):102752. Epub 2021 Jan 18.

Grenoble Alpes University, Grenoble, France; Department of Ophthalmology, Grenoble Alpes University Hospital, Grenoble, France; Hypoxia and Physiopathology Laboratory HP2, INSERM U1042, University Grenoble Alpes, Grenoble, France.

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http://dx.doi.org/10.1016/j.autrev.2021.102752DOI Listing
March 2021

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

Authors:
Emek Kocatürk Andaç Salman Ivan Cherrez-Ojeda Paulo Ricardo Criado Jonny Peter Elif Comert-Ozer Mohamed Abuzakouk Rosana Câmara Agondi Mona Al-Ahmad Sabine Altrichter Rand Arnaout Luisa Karla Arruda Riccardo Asero Andrea Bauer Moshe Ben-Shoshan Jonathan A Bernstein Mojca Bizjak Isabelle Boccon-Gibod Hanna Bonnekoh Laurence Bouillet Zenon Brzoza Paula Busse Regis A Campos Emily Carne Niall Conlon Roberta F Criado Eduardo M de Souza Lima Semra Demir Joachim Dissemond Sibel Doğan Günaydın Irina Dorofeeva Luis Felipe Ensina Ragıp Ertaş Silvia Mariel Ferrucci Ignasi Figueras-Nart Daria Fomina Sylvie M Franken Atsushi Fukunaga Ana M Giménez-Arnau Kiran Godse Margarida Gonçalo Maia Gotua Clive Grattan Carole Guillet Naoko Inomata Thilo Jakob Gul Karakaya Alicja Kasperska-Zając Constance H Katelaris Mitja Košnik Dorota Krasowska Kanokvalai Kulthanan M Sendhil Kumaran Claudia Lang José Ignacio Larco-Sousa Elisavet Lazaridou Tabi Anika Leslie Undine Lippert Oscar Calderón Llosa Michael Makris Alexander Marsland Iris V Medina Raisa Meshkova Esther Bastos Palitot Claudio A S Parisi Julia Pickert German D Ramon Mónica Rodríguez-Gonzalez Nelson Rosario Michael Rudenko Krzysztof Rutkowski Jorge Sánchez Sibylle Schliemann Bulent Enis Sekerel Faradiba S Serpa Esther Serra-Baldrich Zhiqiang Song Angèle Soria Maria Staevska Petra Staubach Anna Tagka Shunsuke Takahagi Simon Francis Thomsen Regina Treudler Zahava Vadasz Solange Oliveira Rodrigues Valle Martijn B A Van Doorn Christian Vestergaard Nicola Wagner Dahu Wang Liangchun Wang Bettina Wedi Paraskevi Xepapadaki Esra Yücel Anna Zalewska-Janowska Zuotao Zhao Torsten Zuberbier Marcus Maurer

Allergy 2021 Mar 29;76(3):816-830. Epub 2020 Dec 29.

Urticaria Center of Reference and Excellence (UCARE), Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin, Berlin, Germany.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.

Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19.

Materials And Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.

Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19.

Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
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http://dx.doi.org/10.1111/all.14687DOI Listing
March 2021

Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women.

J Clin Immunol 2021 Jan 31;41(1):163-170. Epub 2020 Oct 31.

AP-HP, HUPC, Unité de Gynécologie Endocrinienne, Centre de Référence sur les angiœdèmes à kinines (CRéAk), Hôpital Port Royal, Université de Paris, Paris, France.

Purpose: Most types of hereditary angioedema (HAE) are worsened by endogenous or exogenous estrogens. Conversely, androgens can improve HAE with abnormal C1-Inhibitor (C1-INH) by increasing C1-INH concentrations. Menopause is associated with an extinction of ovarian estrogenic and androgenic secretion. There is currently insufficient information on postmenopausal women with HAE. The objective of this study was to describe the activity of HAE in postmenopausal women.

Methods: This was a French retrospective, multicenter study in postmenopausal women with HAE with or without C1-INH deficiency/dysfunction. The patients were classified before and after menopause with a previously validated HAE disease severity score.

Results: We included 65 women from 13 centers in France. The mean age was 62.7± 9.2 years, and the mean time between menopause and inclusion was 12.5± 9.1 years. HAE was associated with C1-INH deficiencyin 88% (n = 57) of the patients, a mutation of factor 12 in 8% (n = 5), a mutation in plasminogen gene in one, and unknown HAE for two. The HAE course was not different after menopause in 46.1% (n = 30), improved in 38.5% (n = 25), and worsened in 15.4% (n = 10). Improvement was correlated with estrogen sensitivity of angioedema before menopause (p = 0.06 for improvement vs no effect or worsening). In addition, we observed that only ten women received treatment (transdermal or oral estradiol+ progestogen) for their menopause symptoms. Among them, only 3 experienced worsening of symptoms (2 on transdermal and 1 on oral estradiol).

Conclusion: Following menopause, most women with HAE remain stable but some worsen. Improvement was mainly observed in patients with previous estrogen sensitivity. More research is required in menopausal women with HAE to better understand how to manage climacteric symptoms.
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http://dx.doi.org/10.1007/s10875-020-00902-7DOI Listing
January 2021

Description of an influenza outbreak in a French university hospital and risk factors of nosocomial influenza.

Eur J Clin Microbiol Infect Dis 2020 Oct 15. Epub 2020 Oct 15.

Infection control unit, CHU Grenoble Alpes, Grenoble, France.

Our objective was to evaluate risk factors of nosocomial influenza (NI) in an university hospital during the 2015/2016 influenza season. All hospitalized patients with influenza-like illness associated with laboratory confirmation by polymerase chain reaction were included in a prospective observational study. We identified 44 cases (19%) of NI among the 233 cases of influenza: 38/178 (21%) in adults and 6/55 (11%) in children. Among adults, hospitalization in a double or multi-occupancy room was independently associated with NI (adjusted Odds Ratio, 3.42; 95% CI, 1.29-9.08; p = 0.013). The results of the study underline the importance of single room to prevent NI.
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http://dx.doi.org/10.1007/s10096-020-04070-9DOI Listing
October 2020

Measurement of Bradykinin Formation and Degradation in Blood Plasma: Relevance for Acquired Angioedema Associated With Angiotensin Converting Enzyme Inhibition and for Hereditary Angioedema Due to Factor XII or Plasminogen Gene Variants.

Front Med (Lausanne) 2020 17;7:358. Epub 2020 Jul 17.

Department of Dermatology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.

Bradykinin (BK)-mediated angioedema (AE) states are rare acquired or hereditary conditions involving localized edema of the subcutaneous and submucosal tissues. Citrated plasma from healthy volunteers or patients with hereditary angioedema (HAE) with normal level of C1-inhibitor (C1-INH) was used to investigate pathways of BK formation and breakdown relevant to AE physiopathology. The half-life of BK (100 nM) added to normal plasma was 34 s, a value that was increased ~12-fold when the angiotensin converting enzyme (ACE) inhibitor enalaprilat (130 nM) was added (enzyme immunoassay measurements). The BK half-life was similarly increased ~5-fold following 2 daily oral doses of enalapril maleate in healthy volunteers, finding of possible relevance for the most common form of drug-associated AE. We also addressed the kinetics of immunoreactive BK (iBK) formation and decline, spontaneous or under three standardized stimuli: tissue kallikrein (KLK-1), the particulate material Kontact-APTT™ and tissue plasminogen activator (tPA). Relative to controls, iBK production was rapid (10-20 min) and very intense in response to tPA in plasma of female heterozygotes for variants in gene coding for factor XII (FXII) (p.Thr328Lys, 9 patients; p.Thr328Arg, one). An increased response to Kontact-APTT™ and an early tPA-induced cleavage of anomalous FXII (immunoblots) were also observed. Biotechnological inhibitors showed that the early response to tPA was dependent on plasmin, FXIIa and plasma kallikrein. Results from post-menopausal and pre-menopausal women with HAE-FXII were indistinguishable. The iBK production profiles in seven patients with the plasminogen p.Lys330Glu variant (HAE-PLG) did not significantly differ from those of controls, except for an unexpected, rapid and lanadelumab-resistant potentiation of KLK-1 effect. This enzyme did not cleave plasminogen or factor XII, suggesting a possible idiosyncratic interaction of the plasminogen pathogenic variant with KLK-1 activity. KLK-1 abounds in salivary glands and human saliva, hypothetically correlating with the clinical presentation of HAE-PLG that includes the swelling of the tongue, lips and contiguous throat tissues. Samples from HAE patients with normal C1-INH levels and gene did not produce excessive iBK in response to stimuli. The approach provides physiopathological insight into AE states and supports the heterogeneous physiopathology of HAE with normal C1-INH.
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http://dx.doi.org/10.3389/fmed.2020.00358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380097PMC
July 2020

Prospective study of serum and aqueous humour anti-Hsp70.1 IgG antibody levels in ocular toxoplasmosis.

Parasite Immunol 2020 10 7;42(10):e12771. Epub 2020 Aug 7.

CNRS, INSERM, CEA, Institute of Interdisciplinary Research of Grenoble (IRIG), Laboratory of Biology of Cancer and Infection, Univ. Grenoble Alpes, Grenoble, France.

Aims: We evaluate whether the serum and aqueous humour (AH) level of IgG anti-Hsp70.1 antibodies improved the biological diagnosis of ocular toxoplasmosis.

Methods And Results: In this prospective cross-sectional and multicentre study, serum and AH were collected at the time of active uveitis. Anti-Hsp70.1-antibody levels were determined by ELISA. Patients with confirmed (Group A1, n = 21) or suspected ocular toxoplasmosis (group A2, n = 30) were enrolled, as well as a control group of patients with cataract (group B, n = 42). Serum IgG anti-Hsp70.1 antibody levels were not significantly different within the group of uveitis patients (A1, n = 21 vs A2, n = 30, P = .8) and were significantly associated with the affected retinal zone (P = .006) and with the size of the retinal lesion (P = .03). Serum anti-Hsp70.1 antibody level was positive in 10 out of the 18 patients of group A2. Significant anti-Hsp-70.1 antibody level in AH was reported in only three patients (3 eyes) with confirmed ocular toxoplasmosis.

Conclusion: While the level of IgG anti-Hsp-70.1 antibody in AH did not improve the laboratory diagnosis of ocular toxoplasmosis, its level in serum was of major significance for retinal damage diagnosis.
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http://dx.doi.org/10.1111/pim.12771DOI Listing
October 2020

Idiopathic Angioedema: Current Challenges.

J Asthma Allergy 2020 17;13:137-144. Epub 2020 Apr 17.

National Reference Center for Angioedema (CREAK), Department of Internal Medicine/Clinical Immunology, Grenoble Alpes University Hospital, Grenoble, France.

The etiological diagnosis of isolated recurrent angioedema poses problems because it must often be done urgently. Angioedema secondary to nonspecific mast cell activation (MC-AE) is the most frequent form and is usually mild. Bradykinin mediated angioedema (BK-AE) is rarer but potentially fatal in the absence of the correct treatment. Few biological markers exist. The C1-inhibitor (C1-inh) functional assay can exclude AE due to C1-inh deficiency. Genetic diagnoses of hereditary AE due to abnormal C1-inh AE have progressed with four currently known mutations. However, determining the physiopathological mechanism leading to some isolated AE cases is sometimes very difficult. In such cases, therapeutic tests are then the only solution: antihistamines at high doses and omalizumab for suspected MC-AE, icatibant for suspected AE-BK. Identifying new markers would be a great help.
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http://dx.doi.org/10.2147/JAA.S205709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173836PMC
April 2020

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

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

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

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

Definition, aims, and implementation of GA LEN/HAEi Angioedema Centers of Reference and Excellence.

Authors:
Marcus Maurer Werner Aberer Rosana Agondi Mona Al-Ahmad Maryam Ali Al-Nesf Ignacio Ansotegui Rand Arnaout Luisa Karla Arruda Riccardo Asero Emel Aygören-Pürsün Aleena Banerji Andrea Bauer Moshe Ben-Shoshan Alejandro Berardi Jonathan A Bernstein Stephen Betschel Carsten Bindslev-Jensen Mojca Bizjak Isabelle Boccon-Gibod Konrad Bork Laurence Bouillet Henrik Balle Boysen Nicholas Brodszki Sigurd Broesby-Olsen Paula Busse Thomas Buttgereit Anette Bygum Teresa Caballero Régis A Campos Mauro Cancian Ivan Cherrez-Ojeda Danny M Cohn Célia Costa Timothy Craig Paulo Ricardo Criado Roberta F Criado Dorottya Csuka Joachim Dissemond Aurélie Du-Thanh Luis Felipe Ensina Ragıp Ertaş José E Fabiani Claudio Fantini Henriette Farkas Silvia Mariel Ferrucci Ignasi Figueras-Nart Natalia L Fili Daria Fomina Atsushi Fukunaga Asli Gelincik Ana Giménez-Arnau Kiran Godse Mark Gompels Margarida Gonçalo Maia Gotua Richard Gower Anete S Grumach Guillermo Guidos-Fogelbach Michihiro Hide Natalia Ilina Naoko Inomata Thilo Jakob Dario O Josviack Hye-Ryun Kang Allen Kaplan Alicja Kasperska-Zając Constance Katelaris Aharon Kessel Andreas Kleinheinz Emek Kocatürk Mitja Košnik Dorota Krasowska Kanokvalai Kulthanan M Sendhil Kumaran José Ignacio Larco Sousa Hilary J Longhurst William Lumry Andrew MacGinnitie Markus Magerl Michael P Makris Alejandro Malbrán Alexander Marsland Inmaculada Martinez-Saguer Iris V Medina Raisa Meshkova Martin Metz Iman Nasr Jan Nicolay Chikako Nishigori Isao Ohsawa Kemal Özyurt Nikolaos G Papadopoulos Claudio A S Parisi Jonathan Grant Peter Wolfgang Pfützner Todor Popov Nieves Prior German D Ramon Adam Reich Avner Reshef Marc A Riedl Bruce Ritchie Heike Röckmann-Helmbach Michael Rudenko Andaç Salman Mario Sanchez-Borges Peter Schmid-Grendelmeier Faradiba S Serpa Esther Serra-Baldrich Farrukh R Sheikh William Smith Angèle Soria Petra Staubach Urs C Steiner Marcin Stobiecki Gordon Sussman Anna Tagka Simon Francis Thomsen Regina Treudler Solange Valle Martijn van Doorn Lilian Varga Daniel O Vázquez Nicola Wagner Liangchun Wang Christina Weber-Chrysochoou Young-Min Ye Anna Zalewska-Janowska Andrea Zanichelli Zuotao Zhao Yuxiang Zhi Torsten Zuberbier Ricardo D Zwiener Anthony Castaldo

Allergy 2020 08 27;75(8):2115-2123. Epub 2020 Apr 27.

HAE International (HAEi), Fairfax City, VA, USA.

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http://dx.doi.org/10.1111/all.14293DOI Listing
August 2020

Angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibitor-induced angioedema: A disproportionality analysis of the WHO pharmacovigilance database.

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2406-2408.e1. Epub 2020 Mar 31.

Médecine interne, Centre national de référence des angioedèmes bradykiniques, CHU Grenoble-Alpes, Grenoble, France.

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http://dx.doi.org/10.1016/j.jaip.2020.03.015DOI Listing
March 2020

Screening of hepatitis E in patients presenting for acute neurological disorders.

J Infect Public Health 2020 Jul 26;13(7):1047-1050. Epub 2020 Mar 26.

Department of Internal Medicine, Grenoble University Hospital, Grenoble, France; Univ. Grenoble Alpes, Department of Internal Medicine CHU Grenoble, Inserm (U1036), CEA, BIG-BCI, France.

Introduction: Hepatitis E virus (HEV) infection has been reported to be associated with neurological disorders. However, the real prevalence of acute hepatitis E in those diseases is still unknown. We determined the prevalence of anti-HEV IgM antibody in a population with acute non-traumatic, non-metabolic, non-vascular neurological injury.

Method: A registry was created in Grenoble Hospital University from 2014 to 2018 to collect data on patients with acute (<3 months) non-traumatic, non-metabolic, non-vascular neurological injuries. Acute hepatitis E was defined as anti-HEV IgM-positive serum in immunocompetent patient, and as anti-HEV IgM-positive serum or HEV RNA-positive serum in immunocompromised patients.

Results: One hundred fifty-nine patients were included. Anti-HEV IgM seroprevalence in our cohort of non-traumatic, non-metabolic, non-vascular neurological injuries was 6.9% (eleven patients, including 4 Parsonage-Turner syndrome (PTS) and 2 Guillain-Barré syndrome (GBS)). Elevated transaminases were observed in only 64% of hepatitis E patients and cholestasis in 64%.

Conclusion: In this study, 6·9% of patients with acute non-traumatic, non-metabolic, non-vascular neurological injuries had a probable recent HEV infection. HEV serology should be systematically performed in this population, even in patients with normal transaminase level.
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http://dx.doi.org/10.1016/j.jiph.2019.12.012DOI Listing
July 2020

Update on bradykinin-mediated angioedema in 2020.

Therapie 2020 Apr 13;75(2):195-205. Epub 2020 Feb 13.

Centre de référence national des angioedèmes (CREAK), centre hospitalier universitaire Grenoble-Alpes, 38000 Grenoble, France.

Bradykinin-mediated angioedema is a rare disease, due to vasodilation and increased vascular permeability resulting from bradykinin. This kind of angioedema affects abdominal and/or upper airways. It differs clinically from histamine-mediated angioedema by the absence of urticaria or skin rash. Antihistamines and corticosteroids are not effective. Delayed diagnosis can lead to inadequate and potentially fatal management by asphyxiation. Bradykinin-mediated angioedema results from either overproduction of bradykinin or inhibition of its degradation. Etiology can be hereditary or acquired. Deficiency of C1 inhibitor and drug induced are the main causes of bradykinin-mediated angioedema. Its diagnosis is clinical (presentation, family history, seriousness, frequency, etc.) and biological (dosage of C1-INH level, C1-INH activity, and complement protein 4 level). Acute attack treatment is based on C1-inhibitor concentrates and icatibant, a bradykinin receptor antagonist. Long-term prophylaxis can be necessary, especially before surgical and dental procedures. New drugs, including gene therapy, are being tested.
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http://dx.doi.org/10.1016/j.therap.2020.02.011DOI Listing
April 2020

Exogenous hormones and hereditary angioedema.

Int Immunopharmacol 2020 Jan 16;78:106080. Epub 2019 Dec 16.

Université de Grenoble, Service de Médecine Interne, CHU de Grenoble 38043 Cedex 09, France; National Reference Centre for Angioedema (CREAK), France.

Gonadal hormones, estrogen and androgen are strongly involved in the control of the bradykinin production. Estrogen may worsen whereas androgen can be part of the long-term prophylactic treatment. In this review, we will describe the potential impact of estrogen in the pathophysiology of hereditary angioedema (HAE). Then we will review the different hormone treatments and their implication on the course of HAE in women and men: contraception, Assisted Reproductive Technology (ART), menopause, hormone dependent cancers in women and men, treatment of hyperandrogenism in women.
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http://dx.doi.org/10.1016/j.intimp.2019.106080DOI Listing
January 2020

Serum amyloid A as a marker of disease activity in Giant cell arteritis.

Autoimmun Rev 2020 Jan 15;19(1):102428. Epub 2019 Nov 15.

Internal Medicine/clinical immunology department, CHU Grenoble Alpes, France; Univ. Grenoble Alpes, Inserm U1036, CEA, BIG-BCI, Grenoble, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2019.102428DOI Listing
January 2020

[Prevalence and characteristics of serum autoantibodies in patients followed for infertility at Grenoble University Hospital].

Presse Med 2019 Nov 11;48(11 Pt 1):e307-e315. Epub 2019 Nov 11.

Centre hospitalier universitaire de Grenoble, service de médecine interne, 38000 Grenoble, France; Laboratoire de Biologie du Cancer et de l'Infection CEA-Grenoble, 38000 Grenoble, France.

Introduction: Fertility disorders in autoimmune diseases are well described. However, little is known about the presence of a humoral serum autoimmunity in case of infertility (antinuclear antibodies, ACAN or antiphospholipid, APL) without criteria of autoimmune disease.

Methods: We studied the prevalence, associated factors, and efficacy of immunomodulatory therapy in patients with unexplained infertility. Two groups were created retrospectively among patients followed in medically assisted procreation (PMA) for infertility: a group with serum autoimmunity (AI+) (ACAN, APL or anti-thyroperoxidase antibodies) and a group without serum autoimmunity (HAVE-). Clinical, biological, and therapeutic data were collected.

Results: The prevalence of autoimmunity was 33% among consultant patients. One hundred patients were seen in internal medicine consultation, 70 were included in the AI+ group and 30 in the AI- group. In the AI+ group, 76% had ACANs, 29% had anti-TPOs and 23% had APLs. There was a significant correlation between ACAN level and the presence of endometriosis (P=0.048). Immunomodulatory therapy was introduced for 68 of the 70 women in the AI+ group; pregnancy occurred in 28 patients (40%) during the treatment period, compared with 7 in the "AI-" group (23%), with a tendency to significance (P=0.09). In conclusion, there is an increased prevalence of serum autoimmunity in patients with fertility disorders, possibly with the efficacy of an immunomodulatory treatment to confront prospective therapeutic studies.
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http://dx.doi.org/10.1016/j.lpm.2019.10.002DOI Listing
November 2019

Mast cell activation diseases and chronic spontaneous urticaria: Common points and differences.

J Allergy Clin Immunol Pract 2020 Mar 27;8(3):1121-1123.e1. Epub 2019 Sep 27.

Internal Medicine and Clinical Immunology Department, CREAK, Grenoble Alpes University Hospital, Grenoble, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2019.09.016DOI Listing
March 2020

Guillain-Barré syndrome in AIDS patient secondary to an acute and confirmed hepatitis C virus.

Presse Med 2019 Sep 19;48(9):981-982. Epub 2019 Sep 19.

Grenoble university hospital, department of internal medicine, 38043 Grenoble cedex 09, France.

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http://dx.doi.org/10.1016/j.lpm.2019.08.004DOI Listing
September 2019

Glucocorticoids for acute urticaria: study protocol for a double-blind non-inferiority randomised controlled trial.

BMJ Open 2019 08 21;9(8):e027431. Epub 2019 Aug 21.

Urgences-SAMU 93-Unité Recherche-Enseignement-Qualité, APHP, Hôpital Avicenne, Bobigny, France.

Introduction: This study protocol describes a trial designed to investigate whether antihistamine alone in patients with acute urticaria does not increase the 7-day Urticaria Activity Score (UAS7) in comparison with an association of antihistamine and glucocorticoids and reduces short-term relapses and chronic-induced urticaria.

Methods And Analysis: This is a prospective, double-blind, parallel-group, multicentre non-inferiority randomised controlled trial. Two-hundred and forty patients with acute urticaria admitted to emergency department will be randomised in a 1:1 ratio to receive levocetirizine or an association of levocetirizine and prednisone. Randomisation will be stratified by centre. The primary outcome will be the UAS7 at day 7. The secondary outcomes will encompass recurrence of hives and/or itch at day 7; occurrence of spontaneous hives or itch for >6 weeks; patients with angioedema at day 7, and 2, 6, 12 and 24 weeks; new emergency visits for acute urticaria recurrences at days 7 and 14, and 3 months; Dermatology Life Quality Index at days 7 and 14, and 3 and 6 months; and Chronic Urticaria Quality of Life Questionnaire at 6 weeks.

Ethics And Dissemination: The protocol has been approved by the and will be carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. A steering committee will oversee the progress of the study. Findings will be disseminated through national and international scientific conferences and publication in peer-reviewed journals.

Trial Registration Number: NCT03545464.
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http://dx.doi.org/10.1136/bmjopen-2018-027431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707704PMC
August 2019

Elderly versus younger patients with hereditary angioedema type I/II: patient characteristics and safety analysis from the Icatibant Outcome Survey.

Clin Transl Allergy 2019 19;9:37. Epub 2019 Jul 19.

10Department of Dermatology and Allergy, Dermatological Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling in subcutaneous or submucosal tissues. Symptoms often begin by age 5-11 years and worsen during puberty, but attacks can occur at any age and recur throughout life. Disease course in elderly patients is rarely reported.

Methods: The Icatibant Outcome Survey (IOS) is an observational study evaluating the safety, tolerability, and efficacy of icatibant. We conducted descriptive analyses in younger (age < 65 years) versus elderly patients (age ≥ 65 years). Here, we report patient characteristics and safety-related findings.

Results: As of February 2018, 872 patients with C1-INH-HAE type I/II were enrolled, of whom 100 (11.5%) were ≥ 65 years old. Significant differences between elderly versus younger patients, respectively, were noted for median age at symptom onset (17.0 vs 12.0 years), age at diagnosis (41.0 vs 19.4 years), and delay between symptom onset and diagnosis (23.9 vs 4.8 years) (P ≤ 0.0001 for all). Median age at diagnosis was significantly higher in elderly patients regardless of family history (P < 0.0001). Throughout the study, icatibant was used to treat 6798 attacks in 574 patients, with 63 elderly patients reporting 715 (10.5%) of the icatibant-treated attacks. No serious adverse events (SAEs) in elderly patients were judged to be possibly related to icatibant, whereas two younger patients reported three possibly related SAEs. Excluding off-label use and pregnancy (evaluated for regulatory purposes), the percentage of patients with at least one possibly/probably related AE was similar for elderly (2.0%) versus younger patients (2.7%). No deaths linked to icatibant treatment were identified. All related events in elderly patients were attributed to general disorders/administration site conditions, whereas related events in younger patients occurred across various system organ class designations.

Conclusions: Elderly patients with C1-INH-HAE were significantly older at diagnosis and had greater delay in diagnosis than younger patients. Elderly patients contributed to approximately 10% of the icatibant-treated attacks. Our analysis found similar AE rates (overall and possibly/probably related) in icatibant-treated elderly versus younger patients, despite the fact that elderly patients had significantly more comorbidities and were receiving a greater number of concomitant medications. Our analysis did not identify any new or unexpected safety concerns.
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http://dx.doi.org/10.1186/s13601-019-0272-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639901PMC
July 2019

Hereditary angioedema, emergency management of attacks by a call center.

Eur J Intern Med 2019 Sep 18;67:42-46. Epub 2019 May 18.

AP-HP, Urgences - Samu 93, Hôpital Avicenne, Université Paris 13, Inserm U942, 93000 Bobigny, France. Electronic address:

Objective: Hereditary angiœdema (HAE) is a rare autosomal dominant disease characterized by recurrent, unpredictable, potentially life-threatening swelling. Objective is to assess the management of the acute HAE attacks in the real life setting through a call center in France.

Methods: A pre-specified ancillary study of SOS-HAE, a cluster-randomized prospective multicenter trial, was conducted. HAE patients were recruited from 8 participating reference centers. The outcome of interest was the rate of hospitalization.

Results: onerhundred patients were included. The median (quartile) age was 38 (29-53) years, and 66 (66%) were female. Eighty (80%) patients had HAE type I, 8 (8%) had HAE type II and 12 (12%) patients had FXII-HAE. Fifty-one (51%) patients had experienced at least one time the call center during the follow-up. Nine over 166 (5%) attacks for 9 different patients resulted in hospital admission to the hospital (in the short-stay unit, ie, <24 h) during the follow-up period. During 2 years, there were 166 calls to call center for 166 attacks. All attacks were treated at home after call center contact.

Conclusions: Use of emergency departments and hospitalizations are reduced by the use of a coordinated national call center in HAE after therapeutic education program that promoted self-administration of specific treatment and use of call to call center.

Trial Registration: clinicalTrials.gov identifier: NCT01679912.
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http://dx.doi.org/10.1016/j.ejim.2019.05.007DOI Listing
September 2019

Paroxysmal Permeability Disorders: Development of a Microfluidic Device to Assess Endothelial Barrier Function.

Front Med (Lausanne) 2019 24;6:89. Epub 2019 Apr 24.

IRCCS-Istituti Clinici Scientifici Maugeri, University of Milan, Milan, Italy.

Paroxysmal Permeability Disorders (PPDs) are pathological conditions caused by periodic short lasting increase of endothelial permeability, in the absence of inflammatory, degenerative, ischemic vascular injury. PPDs include primary angioedema, idiopathic systemic capillary leak syndrome and some rare forms of localized retroperitoneal-mediastinal edema. to validate a microfluidic device to study endothelial permeability in flow conditions. we designed a microchannel network (the smallest channel is 30μm square section). Human Umbilical Vein Endothelial Cells (HUVECs) were cultured under constant shear stress in the networks. Endothelial permeability assessment was based on interaction of biotinylated fibronectin used as a matrix for HUVECs and FITC-conjugated avidin. The increase in endothelial permeability was identified as changes in fluorescence intensity detected by confocal fluorescent microscopy. The microchannels were constantly perfused with a steady flow of culture medium, ensuring a physiologically relevant level of shear stress at the wall of ~0.2 Pa. Our preliminary results demonstrated that circulation of culture medium or plasma from healthy volunteers was associated with low fluorescence of fibronectin matrix. When bradykinin diluted in culture medium was perfused, an increase in average fluorescence was detected. Our microvasculature model is suitable to study endothelial functions in physiological flow conditions and in the presence of factors like bradykinin known as mediator of several PPDs. Therefore, it can be a promising tool to better understand the mechanisms underlying disorders of endothelial permeability.
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http://dx.doi.org/10.3389/fmed.2019.00089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491734PMC
April 2019

Letter to the Editor: Protein phosphatase 1 subunit Ppp1r15a/GADD34 is overexpressed in systemic lupus erythematosus and related to the expression of type I interferon response genes.

Autoimmun Rev 2019 02 19;18(2):211-213. Epub 2018 Dec 19.

Laboratoire d'Immunologie, Pôle de Biologie, Centre Hospitalier Universitaire Grenoble Alpes, CS 10217, 38043 Grenoble, Cedex 9, France; BNI Team, TIMC-IMAG UMR5525, Université Grenoble Alpes, CNRS, BP170, 38042 Grenoble, Cedex 9, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2018.09.007DOI Listing
February 2019

Five-Year Trends in Multifocal Electroretinogram for Patients With Birdshot Chorioretinopathy.

Am J Ophthalmol 2019 04 15;200:138-149. Epub 2018 Dec 15.

Grenoble Alpes University, Grenoble, France; Department of Ophthalmology, Grenoble Alpes University Hospital, Grenoble, France. Electronic address:

Purpose: The aim of this study is to investigate temporal trends in multifocal ERG (mfERG) parameters and analyze their relationships with anatomic and functional markers in patients with birdshot chorioretinopathy (BSCR).

Design: Prospective observational case series.

Methods: Sixteen BSCR patients were include and underwent 2 standardized follow-up (FU) visits within 5 years following a baseline examination, including mfERG, visual acuity (VA), visual field (VF), Lanthony desaturated panel D-15 test for color vision, quality of life (QoL), fluorescein and indocyanine green angiography, and optical coherence tomography (OCT).

Results: A significant trend toward a decrease in absolute N1 amplitude values was observed over the follow-up period (P < .001) while N1 implicit time remained unchanged. In contrast, P1 amplitude decreased (P < .001) and P1 implicit time increased (P < .001) over the same period. No significant temporal change was found for VA, color vision score, foveal threshold, mean deviation of VF, and QoL. After adjusting for time to FU, increasing N1 and P1 IT were both associated with decreasing values of logMAR, foveal threshold, and QoL and with increasing color vision score and mean deviation of VF. A significant relationship was observed between decreasing P1 amplitude values and increasing mean deviation of VF. Lower absolute values of N1 amplitude were associated with venous vasculitis, whereas lower P1 amplitude values correlated with alteration of the outer retina in OCT.

Conclusions: Progressive deterioration in mfERG during a 5-year period is detected in BSCR, whereas classical functional test results were unchanged. This study suggests a better sensitivity of mfERG in monitoring the retinal function of BSCR patients.
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http://dx.doi.org/10.1016/j.ajo.2018.11.022DOI Listing
April 2019

Diagnostic biologique des angioedèmes bradykiniques : les recommandations du CREAK.

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

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

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

Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey.

Clin Transl Allergy 2018 12;8:42. Epub 2018 Oct 12.

2Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, Berlin, Germany.

The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time. Our findings demonstrate that some patients are still experiencing long delays to diagnosis, indicating an ongoing need for improved disease awareness.
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http://dx.doi.org/10.1186/s13601-018-0229-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182796PMC
October 2018

Bradykinin mechanism is the main responsible for death by isolated asphyxiating angioedema in France.

Clin Exp Allergy 2019 02 10;49(2):252-254. Epub 2018 Dec 10.

National Reference Center for Angioedema (CREAK), Grenoble Alpes University Hospital, Grenoble, France.

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http://dx.doi.org/10.1111/cea.13297DOI Listing
February 2019

Hypereosinophilia: Biological investigations and etiologies in a French metropolitan university hospital, and proposed approach for diagnostic evaluation.

PLoS One 2018 26;13(9):e0204468. Epub 2018 Sep 26.

Infectious Diseases Unit, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.

Objectives: We aimed to evaluate the usefulness of biological investigations in cases of eosinophilia in our area (French Alps).

Methods: We retrospectively included all adult patients attending the infectious disease and internal medicine units between 2009 and 2015 with eosinophilia ≥1 G/l.

Results: We identified 298 cases (129 women and 169 men). In 139 patients, eosinophilia had not been addressed. In the 159 others, the cause of eosinophilia was identified in 118 (74.2%). The main identified causes at the time were drug reactions (24.5%, mostly β-lactams and allopurinol), infectious diseases (17.0%), vasculitis (8.2%), autoimmune diseases (6.9%), and malignant diseases (6.2%). In patients with a skin rash, eosinophilia was significantly more often investigated, and a diagnosis significantly more often made. Helminthosis were mainly diagnosed in tropical travelers (18/24) excepting toxocariasis (3 non-travelers). Stool examination for helminthosis was positive in 5/76 patients (6.6%) (all tropical travelers); 391 helminth serologies were performed in 91 patients, with 7.9% being positive (all but 3 positive cases were travelers). Anti-neutrophil cytoplasmic antibodies (ANCA) were positive in 26/112 patients (23.2%), with 9 cases of vasculitis identified.

Conclusions: Drug-related eosinophilia is the main etiology. Search for helminthosis is not recommended among non-travelers (excepting toxocariasis). ANCA should be performed early so as not to overlook vasculitis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204468PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157892PMC
March 2019