Amélie Duréault1, Colas Tcherakian2, Sylvain Poiree3, Emilie Catherinot4, François Danion1, Grégory Jouvion5, Marie Elisabeth Bougnoux6, Nizar Mahlaoui7, Claire Givel4, Martin Castelle8, Capucine Picard7, Marie Olivia Chansdesris8, Olivier Lortholary9, Fanny Lanternier10. 1. Service de Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP), Université Paris Descartes, Paris, France. 2. Service de Pneumologie, Hôpital Foch, Suresnes, France; Faculté des Sciences de la Santé Simone Veil, Université Versailles-Saint-Quentin-en-Yvelines, Versailles, France; National Referral Center for Hypereosinophilic (CEREO). 3. Service de Radiologie, Hôpital Necker-Enfants Malades, APHP, Paris, France. 4. Service de Pneumologie, Hôpital Foch, Suresnes, France; Faculté des Sciences de la Santé Simone Veil, Université Versailles-Saint-Quentin-en-Yvelines, Versailles, France. 5. Unité de Neuropathologie Expérimentale, Institut Pasteur, Paris, France; Département de Génétique Médicale, Hôpital Trousseau, Sorbonne Université, APHP, Paris, France. 6. Service de Microbiologie, Hôpital Necker-Enfants Malades, APHP, Paris, France. 7. Centre d'Etude des Déficits Immunitaires (CEDI), Hôpital Necker-Enfants Malades, APHP, Paris, France; CEREDIH, Centre de Référence des Déficits Immunitaires Héréditaires, Hôpital Universitaire Necker-Enfants Malades, APHP, Paris, France; Service Immunologie-Hématologie Pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris, France; Imagine Institut INSERM UMR1163, Université Paris Descartes, Paris, France. 8. Service d'Hématologie, Hôpital Necker-Enfants Malades, APHP, Paris, France. 9. Service de Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP), Université Paris Descartes, Paris, France; Institut Pasteur, CNRS, Centre National de Référence Mycoses Invasives et Antifongiques, Unité de Mycologie Moléculaire, Paris, France. 10. Service de Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP), Université Paris Descartes, Paris, France; Institut Pasteur, CNRS, Centre National de Référence Mycoses Invasives et Antifongiques, Unité de Mycologie Moléculaire, Paris, France. Electronic address: fanny.lanternier@aphp.fr.
Abstract
BACKGROUND: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging. OBJECTIVE: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort. METHODS: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized. RESULTS: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse. CONCLUSIONS: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.
BACKGROUND: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging. OBJECTIVE: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficientpatients of the National French cohort. METHODS: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficientpatients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized. RESULTS: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficientpatients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse. CONCLUSIONS: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficientpatients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.