Alessandra Magnani1, Pauline Brosselin2, Julien Beauté3, Nathalie de Vergnes2, Richard Mouy4, Marianne Debré4, Felipe Suarez5, Olivier Hermine5, Olivier Lortholary6, Stéphane Blanche1, Alain Fischer7, Nizar Mahlaoui8. 1. Assistance Publique-Hôpitaux de Paris, Service d'Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Paris, France; Assistance Publique-Hôpitaux de Paris, Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France. 2. Assistance Publique-Hôpitaux de Paris, Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France. 3. Assistance Publique-Hôpitaux de Paris, Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris, France. 4. Assistance Publique-Hôpitaux de Paris, Service d'Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Paris, France. 5. Assistance Publique-Hôpitaux de Paris, Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France; Assistance Publique-Hôpitaux de Paris, Service d'Hématologie Adultes, Hôpital Universitaire Necker-Enfants Malades, Paris, France. 6. Assistance Publique-Hôpitaux de Paris, Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France; Assistance Publique-Hôpitaux de Paris, Service de Maladies Infectieuses et Tropicales, Hôpital Universitaire Necker-Enfants Malades, Paris, France. 7. Assistance Publique-Hôpitaux de Paris, Service d'Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Paris, France; Assistance Publique-Hôpitaux de Paris, Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France; Collège de France, France. 8. Assistance Publique-Hôpitaux de Paris, Service d'Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Paris, France; Assistance Publique-Hôpitaux de Paris, Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France; Laboratoire de Génétique Humaine des Maladies Infectieuses, Hopital Universitaire Necker-Enfants Malades, Inserm U1163, Paris, France. Electronic address: nizar.mahlaoui@nck.aphp.fr.
Abstract
BACKGROUND: Chronic granulomatous disease (CGD) is a rare phagocytic disorder that results in not only infections but also potentially severe inflammatory manifestations that can be difficult to diagnose and treat. OBJECTIVE: To describe inflammatory manifestations in a single-center cohort of patients with CGD. METHODS: Medical records of patients treated at Necker-Enfants Malades Hospital (Paris, France) between 1968 and 2009 and registered at the French National Reference Center for Primary Immunodeficiencies (CEREDIH) were retrospectively reviewed. RESULTS: In a study population of 98 patients, a total of 221 inflammatory episodes were recorded in 68 individuals (69.4%). The incidence rate of inflammatory episodes was 0.15 per person-year (0.18 in patients with X-linked [XL] CGD and 0.08 in patients with autosomal-recessive [AR] CGD). The most commonly affected organs were the gastrointestinal tract (in 88.2% of the patients), lungs (26.4%), the urogenital tract (17.6%), and eyes (8.8%). Inflammation at other sites (the skin, central nervous system, and tympanum) and autoimmune manifestations (lupus, arthritis, etc) were recorded in 19.1% and 10.3% of the patients, respectively. Granuloma was found in 50% of the 44 histological analyses reviewed. The risk of inflammatory episodes was 2-fold higher in patients with XL-CGD than in patients with AR-CGD (relative risk, 2.22; 95% CI, 1.43-3.46). CONCLUSIONS: Patients with XL-CGD have a higher risk of developing inflammatory episodes than do patients with AR-CGD. Although the most commonly affected organ is the gastrointestinal tract, other sites can be involved, making the management of patients with CGD a complex, multidisciplinary task.
BACKGROUND:Chronic granulomatous disease (CGD) is a rare phagocytic disorder that results in not only infections but also potentially severe inflammatory manifestations that can be difficult to diagnose and treat. OBJECTIVE: To describe inflammatory manifestations in a single-center cohort of patients with CGD. METHODS: Medical records of patients treated at Necker-Enfants Malades Hospital (Paris, France) between 1968 and 2009 and registered at the French National Reference Center for Primary Immunodeficiencies (CEREDIH) were retrospectively reviewed. RESULTS: In a study population of 98 patients, a total of 221 inflammatory episodes were recorded in 68 individuals (69.4%). The incidence rate of inflammatory episodes was 0.15 per person-year (0.18 in patients with X-linked [XL] CGD and 0.08 in patients with autosomal-recessive [AR] CGD). The most commonly affected organs were the gastrointestinal tract (in 88.2% of the patients), lungs (26.4%), the urogenital tract (17.6%), and eyes (8.8%). Inflammation at other sites (the skin, central nervous system, and tympanum) and autoimmune manifestations (lupus, arthritis, etc) were recorded in 19.1% and 10.3% of the patients, respectively. Granuloma was found in 50% of the 44 histological analyses reviewed. The risk of inflammatory episodes was 2-fold higher in patients with XL-CGD than in patients with AR-CGD (relative risk, 2.22; 95% CI, 1.43-3.46). CONCLUSIONS:Patients with XL-CGD have a higher risk of developing inflammatory episodes than do patients with AR-CGD. Although the most commonly affected organ is the gastrointestinal tract, other sites can be involved, making the management of patients with CGD a complex, multidisciplinary task.
Authors: Sebastian Boeltz; Poorya Amini; Hans-Joachim Anders; Felipe Andrade; Rostyslav Bilyy; Simon Chatfield; Iwona Cichon; Danielle M Clancy; Jyaysi Desai; Tetiana Dumych; Nishant Dwivedi; Rachael Ann Gordon; Jonas Hahn; Andrés Hidalgo; Markus H Hoffmann; Mariana J Kaplan; Jason S Knight; Elzbieta Kolaczkowska; Paul Kubes; Moritz Leppkes; Angelo A Manfredi; Seamus J Martin; Christian Maueröder; Norma Maugeri; Ioannis Mitroulis; Luis E Munoz; Daigo Nakazawa; Indira Neeli; Victor Nizet; Elmar Pieterse; Marko Z Radic; Christiane Reinwald; Konstantinos Ritis; Patrizia Rovere-Querini; Michal Santocki; Christine Schauer; Georg Schett; Mark Jay Shlomchik; Hans-Uwe Simon; Panagiotis Skendros; Darko Stojkov; Peter Vandenabeele; Tom Vanden Berghe; Johan van der Vlag; Ljubomir Vitkov; Maren von Köckritz-Blickwede; Shida Yousefi; Alexander Zarbock; Martin Herrmann Journal: Cell Death Differ Date: 2019-01-08 Impact factor: 15.828