title: Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.
abstract: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients.
  
  
  
  Our objective was to assess the effect of mycobacterial disease in patients with CGD.
  
  
  
  We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria.
  
  
  
  Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients.
  
  
  
  Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; Department of Public Health and Cellular Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Conti
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; Immunodeficiencies Research Unit, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: Saul Oswaldo
authors.initials: SO
authors.lastname: Lugo-Reyes
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; Immunodeficiencies Research Unit, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Blancas Galicia
authors.affiliation: Xicheng District Nanlishilu Road 56 Beijing Children's Hospital, Beijing, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey.
authors.forename: Güzide
authors.initials: G
authors.lastname: Aksu
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Edgar
authors.initials: E
authors.lastname: Borges de Oliveira
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Deswarte
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Hubeau
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Karaca
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Maylis
authors.initials: M
authors.lastname: de Suremain
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Guérin
authors.affiliation: Laboratory of Biology and Health UARC34-Metabolic and Immunologic Pathology Research Team, Faculty of Science of Ben M'sik, King Hassan II University-Mohammedia, Casablanca, Morocco.
authors.forename: Laila Ait
authors.initials: LA
authors.lastname: Baba
authors.affiliation: Bioinformatics Laboratory, Pelé Pequeno Principe Research Institute, Curitiba, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Prando
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Gloria G
authors.initials: GG
authors.lastname: Guerrero
authors.affiliation: Department of Pediatric Infectious Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.
authors.forename: Melike
authors.initials: M
authors.lastname: Emiroglu
authors.affiliation: Pediatric Infectious Diseases Department, Dr Sami Ulus Maternity and Children's Research and Training Hospital, Ankara, Turkey.
authors.forename: Fatma Nur
authors.initials: FN
authors.lastname: Öz
authors.affiliation: Department of Immunology, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Yamazaki Nakashimada
authors.affiliation: Department of Immunology, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: Edith
authors.initials: E
authors.lastname: Gonzalez Serrano
authors.affiliation: Department of Immunology, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: Sara
authors.initials: S
authors.lastname: Espinosa
authors.affiliation: Department of Pediatrics, Allergy and Immunology, Marmara University, Istanbul, Turkey.
authors.forename: Isil
authors.initials: I
authors.lastname: Barlan
authors.affiliation: Immunology Unit, Children's Hospital "Superiora Sor María Ludovica", La Plata, Argentina.
authors.forename: Nestor
authors.initials: N
authors.lastname: Pérez
authors.affiliation: Immunology Unit, Children's Hospital "Superiora Sor María Ludovica", La Plata, Argentina.
authors.forename: Lorena
authors.initials: L
authors.lastname: Regairaz
authors.affiliation: Allergy and Immunology Unit, National Children's Hospital "Benjamín Bloom", San Salvador, El Salvador.
authors.forename: Héctor Eduardo
authors.initials: HE
authors.lastname: Guidos Morales
authors.affiliation: Immunology Unit, Children's Hospital "Ricardo Gutierrez", Buenos Aires, Argentina.
authors.forename: Liliana
authors.initials: L
authors.lastname: Bezrodnik
authors.affiliation: Immunology Unit, Children's Hospital "Ricardo Gutierrez", Buenos Aires, Argentina.
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Giovanni
authors.affiliation: Department of Pediatrics, American University of Beirut-Medical Center, Beirut, Lebanon.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Dbaibo
authors.affiliation: Clinical Immunology Unit, Casablanca Children's Hospital, Ibn Rochd Medical School, King Hassan II University, Casablanca, Morocco.
authors.forename: Fatima
authors.initials: F
authors.lastname: Ailal
authors.affiliation: Children's Hospital "Victor J. Vilela", Rosario, Argentina.
authors.forename: Miguel
authors.initials: M
authors.lastname: Galicchio
authors.affiliation: Department of Immunology, "Juan Pedro Garrahan" National Hospital of Pediatrics, Buenos Aires, Argentina.
authors.forename: Matias
authors.initials: M
authors.lastname: Oleastro
authors.affiliation: Department of Pediatrics, Sahloul Hospital, Sousse, Tunisia.
authors.forename: Jalel
authors.initials: J
authors.lastname: Chemli
authors.affiliation: Department of Immunology, "Juan Pedro Garrahan" National Hospital of Pediatrics, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Danielian
authors.affiliation: Department of Immunology, "Juan Pedro Garrahan" National Hospital of Pediatrics, Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Perez
authors.affiliation: Children's Hospital "San Jose" and Medical School, Bogota, Columbia.
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Ortega
authors.affiliation: Concepcion Regional Hospital, Concepción, Chile.
authors.forename: Susana
authors.initials: S
authors.lastname: Soto Lavin
authors.affiliation: Department of Pediatrics, Tawam Hospital, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hertecant
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
authors.forename: Ozden
authors.initials: O
authors.lastname: Anal
authors.affiliation: Department of Immunology, Pasteur Institute of Algeria, Algiers, Algeria.
authors.forename: Nadia
authors.initials: N
authors.lastname: Kechout
authors.affiliation: Department of Pediatrics, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Eman
authors.initials: E
authors.lastname: Al-Idrissi
authors.affiliation: Department of Pediatrics, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Gehad
authors.initials: G
authors.lastname: ElGhazali
authors.affiliation: Department of Pediatrics Infectious Diseases and Clinical Immunology, Kiev, Ukraine.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Bondarenko
authors.affiliation: Department of Pediatrics Infectious Diseases and Clinical Immunology, Kiev, Ukraine.
authors.forename: Liudmyla
authors.initials: L
authors.lastname: Chernyshova
authors.affiliation: Department of Pediatrics, Comenius University Medical School, University Children's Hospital, Bratislava, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Ciznar
authors.affiliation: Hematology-Oncology Unit, Reunion CHU, Saint Denis Reunion, France.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Herbigneaux
authors.affiliation: Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France.
authors.forename: Aminata
authors.initials: A
authors.lastname: Diabate
authors.affiliation: Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ndaga
authors.affiliation: Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France.
authors.forename: Barik
authors.initials: B
authors.lastname: Konte
authors.affiliation: Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France.
authors.forename: Ambre
authors.initials: A
authors.lastname: Czarna
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Migaud
authors.affiliation: Unit of Biochemistry, National Institute for Medical Sciences and Nutrition Salvador Zubiran, Tlalpan, Mexico.
authors.forename: Sigifredo
authors.initials: S
authors.lastname: Pedraza-Sánchez
authors.affiliation: Microbiology Research Laboratory, Hospital General O'Horan and Infectious Diseases Research Unit, Hospital Regional de Alta Especialidad de la Peninsula de Yucatan, Merida, Mexico.
authors.forename: Mussaret Bano
authors.initials: MB
authors.lastname: Zaidi
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vogt
authors.affiliation: Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.affiliation: Laboratory of Cytoimmunology, Pasteur Institute of Tunis, Tunis-Belvèdère, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Benmustapha
authors.affiliation: Division of Infectious Diseases and Clinical Immunology, National Research Institute of Tuberculosis and Lung Diseases, Shahid Behesti University of Medical Sciences, Tehran, Iran.
authors.forename: Davood
authors.initials: D
authors.lastname: Mansouri
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New York, NY.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New York, NY.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.affiliation: Paris Descartes University, Imagine Institute, Paris, France; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France; French Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.affiliation: Clinical Immunology Unit, Casablanca Children's Hospital, Ibn Rochd Medical School, King Hassan II University, Casablanca, Morocco.
authors.forename: Ahmed Aziz
authors.initials: AA
authors.lastname: Bousfiha
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New York, NY; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.affiliation: Laboratory of Cytoimmunology, Pasteur Institute of Tunis, Tunis-Belvèdère, Tunisia.
authors.forename: Ridha
authors.initials: R
authors.lastname: Barbouche
authors.affiliation: Department of Pediatrics, Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.affiliation: Department of Immunology, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Espinosa-Rosales
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey.
authors.forename: Necil
authors.initials: N
authors.lastname: Kütükçüler
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Condino-Neto
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New York, NY; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France; Howard Hughes Medical Institute, New York, NY.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New York, NY. Electronic address: jacinta.bustamante@inserm.fr.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
mesh_terms: D001500:BCG Vaccine / Q000008:administration & dosage; D001424:Bacterial Infections / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications* / Q000453:epidemiology / Q000401:mortality / Q000628:therapy; D006801:Humans; D007223:Infant; D008297:Male; D009164:Mycobacterium Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D009181:Mycoses / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D063868:Patient Outcome Assessment; D012189:Retrospective Studies; D014376:Tuberculosis / Q000175:diagnosis / Q000209:etiology
chemical_list: D001500:BCG Vaccine
keywords: BCG; Mycobacteria; chronic granulomatous disease; primary immunodeficiency; tuberculosis