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2. Musculoskeletal Symptoms in Patients With Cryopyrin-Associated Periodic Syndromes: A Large Database Study

Author

Houx , Laetitia, Hachulla , Eric, Kone-Paut , Isabelle, Quartier , Pierre, Touitou , Isabelle, Guennoc , Xavier, Grateau , Gilles, Hamidou , Mohamed, Neven , Bénédicte, Berthelot , Jean-Marie, Lequerré , Thierry, Pillet , Pascal, Lemelle , Irène, Fischbach , Michel, Duquesne , Agnès, Le Blay , Pierre, Le Jeunne , Claire, Stirnemann , Jérome, Bonnet , Christine, Gaillard , Dominique, Alix , Lilian, Touraine , Renaud, Garcier , François, Bedane , Christophe, Jurquet , Anne-Laure, Duffau , Pierre, Smail , Amar, Frances , Camille, Grall-Lerosey , Martine, Cathebras , Pascal, Tran , Tu Anh, Morell-Dubois , Sandrine, Pagnier , Anne, Richez , Christophe, Cuisset , Laurence, Devauchelle-Pensec , Valérie, Service de médecine physique et de réadaptation, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Médecine Interne (DMP - LILLE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service Pédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Rhumatologie (Rhumato - HD - NANTES), Hôtel-Dieu de Nantes, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire Aimé Cotton (LAC), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-École normale supérieure - Cachan (ENS Cachan), Service de Pédiatrie [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Néphrologie Pédiatrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1), CHU Necker - Enfants Malades [AP-HP], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne-Hôpital Nord - Saint-Etienne, Service de Dermatologie [CHU Limoges], CHU Limoges, Service de Biochimie et Génétique Moléculaire [CHU Limoges], Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-hôpital Sud, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], Service de Médecine Interne, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Marseille, CHU Amiens-Picardie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Cochin [AP-HP], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Département de Médecine Interne ( DMP - LILLE ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé ( LIMICS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris 13 ( UP13 ), Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Département de Rhumatologie ( Rhumato - HD - NANTES ), Service de rhumatologie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Laboratoire Aimé Cotton ( LAC ), École normale supérieure - Cachan ( ENS Cachan ) -Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'environnement et du Travail ( ANSES ), ANSES - Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail ( ANSES ), CHU Amiens-Picardie-Hôpital Sud, Unité fonctionnelle de dermatologie, CHU Pitié-Salpêtrière [APHP], Immunologie et Pathologie ( EA2216 ), and Université de Brest ( UBO ) -IFR148

Subjects
Adult, Male, musculoskeletal diseases, Adolescent, Databases, Factual, Arthropathy, Young Adult, Genetic heterogeneity, Open label, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Child, Cold autoinflammatory syndrome, CIAS1 mutations, Musculoskeletal System, ComputingMilieux_MISCELLANEOUS, Aged, Multisystem inflammatory disease, Arthritis, Infant, Newborn, Long term efficacy, Infant, Myalgia, Middle Aged, Arthralgia, Cryopyrin-Associated Periodic Syndromes, Phenotype, Anakinra, Child, Preschool, Mutation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Muckle wells syndrome, Articular syndrome
Abstract

International audience; Objective: To determine the type and frequency of musculoskeletal symptoms at onset and during followup of cryopyrin-associated periodic syndromes (CAPS).Methods: We retrospectively recorded the articular and muscular symptoms of patients with CAPS followed up in French hospitals. Data were presented as frequencies or the median (range), and patient groups were compared using chi-square test, Fisher's exact test, and Mann-Whitney test.Results: The study included 133 patients (33 children), 20 with familial cold autoinflammatory syndrome, 88 with Muckle-Wells syndrome, 22 with chronic infantile neurologic, cutaneous, articular syndrome, and 3 with unclassified CAPS. The median age was 35 years (range 0-78 years) at the time of the study, 1 year (range 0-41 years) at symptom onset, and 23 years (range 0-58 years) at diagnosis. The disease was sporadic in 17% of the patients. Cutaneous symptoms predominated at onset (77%), followed by articular symptoms (30%). The p.Thr348Met and p.Arg260Trp NLRP3 mutations were significantly associated with the presence and absence of articular symptoms at onset, respectively. During followup, 86% of the patients had musculoskeletal symptoms, 88% had arthralgia, and 58% had arthritis, but only 9% had joint destruction. Tendinopathies occurred in 21.5% of the patients, tender points in 16.5%, and myalgia in 33%. Only 3 patients had typical knee deformities. Radiographs were rarely obtained. Except for bone deformities, osteoarticular symptoms occurred at similar frequencies in the different CAPS phenotypes.Conclusion: Joint manifestations were frequent in all CAPS phenotypes. Bone deformities were rare. Musculoskeletal manifestations varied within given families but tended to worsen over time.

Published
2015
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3. International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients.

Author

Hofer, Michaël, Pillet, Pascal, Cochard, Marie-Madeleine, Berg, Stefan, Krol, Petra, Kone-Paut, Isabelle, Rigante, Donato, Hentgen, Véronique, Anton, Jordi, Brik, Riva, Neven, Bénédicte, Touitou, Isabelle, Kaiser, Daniela, Duquesne, Agnès, Wouters, Carine, and Gattorno, Marco

Subjects
*ACADEMIC medical centers, *CONFIDENCE intervals, *FEVER, *GASTROINTESTINAL diseases, *LYMPHADENITIS, *MEDICAL cooperation, *HISTORY of medicine, *MYALGIA, *PHARYNGITIS, *RESEARCH, *PHENOTYPES, *GENOMICS, *RELATIVE medical risk, *CANKER sores, *JOINT pain, *MEVALONATE kinase deficiency, *SYMPTOMS
Abstract

Objectives. The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries.Methods. We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes.Results. Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever.Conclusion. We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed. [ABSTRACT FROM PUBLISHER]

Published
2014
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4. PFAPA syndrome is not a sporadic disease.

Author

Cochard, Marie, Clet, Johanna, Pillet, Pascal, Onrubia, Xavier, Guéron, Thierry, Faouzi, Mohammed, Hofer, Michaë l, and Lan Le

Subjects
FEVER, STOMATITIS, CANKER sores, PHARYNGITIS, LYMPHADENITIS, CERVIX uteri diseases
Abstract

Objectives. To determine whether PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) patients have a positive family history (FH) for recurrent fever syndromes. [ABSTRACT FROM PUBLISHER]

Published
2010
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