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Epidemiology and Outcome of Invasive Fungal Diseases in Patients With Chronic Granulomatous Disease: A Multicenter Study in France

Beauté, Julien MD*; Obenga, Gaëlle MD*; Le Mignot, Loïc MSc*; Mahlaoui, Nizar MD*†; Bougnoux, Marie-Elisabeth MD; Mouy, Richard MD; Gougerot-Pocidalo, Marie-Anne MD§¶; Barlogis, Vincent MD; Suarez, Felipe MD, PhD**; Lanternier, Fanny MD††‡‡; Hermine, Olivier MD, PhD**‡‡; Lecuit, Marc MD, PhD††‡‡; Blanche, Stéphane MD, PhD†‡‡; Fischer, Alain MD, PhD*†‡‡; Lortholary, Olivier MD, PhD***††‡‡¶¶the French PID Study Group CEREDIH

The Pediatric Infectious Disease Journal: January 2011 - Volume 30 - Issue 1 - p 57-62
doi: 10.1097/INF.0b013e3181f13b23
Original Studies

Background: Chronic granulomatous disease (CGD) is a rare inherited phagocytic disorder resulting in an increased susceptibility to infections including invasive fungal diseases (IFDs) and inflammatory complications. This study is aimed at assessing the incidence, prevalence, and outcome of IFDs among CGD patients followed in France.

Methods: CGD patients were identified through the French national registry for primary immunodeficiencies (PID) held by the French national reference Centre of PID (Centre de Référence Déficits Immunitaires Héréditaires), which comprises a total of 3083 patients including 155 with CGD followed between 1976 and 2008. A questionnaire was filled out for each episode of IFD. Information retrieved included a description of the IFD using the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group IFD definition criteria.

Results: Of CGD patients, 42.6% (66/155) developed at least 1 episode of IFD. Overall incidence of IFD was 0.040/patient-years (1862 patient-years of total follow-up). IFD incidence was found to be significant while receiving itraconazole prophylaxis compared with no prophylaxis (0.027 vs. 0.053 IFD/patient-years; P < 0.01). Median age at IFD diagnosis was 6.5 years (3.3–11.3). The most common fungal genus was Aspergillus sp. accounting for 40% of all IFDs. Of the IFDs, 42.5% were proven, 30.0% probable, and 27.5% possible. Of all IFD episodes, 52.5% were treated by antifungal monotherapy, mostly by amphotericin B. Survival was reduced in IFD patients compared with those without it (log-rank = 0.04).

Conclusions: IFDs are a frequent and life-threatening complication in CGD patients. Itraconazole significantly reduces its incidence and should be recommended in absence of better alternatives.

From the *Centre de Référence Déficits Immunitaires Héréditaires, Hôpital Necker-Enfants Malades, AP-HP, Paris, France; †Unité d'Immuno-Hématologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France; ‡Service de Bactériologie-Virologie-Parasitologie et Hygiène, Hôpital Necker-Enfants Malades, AP-HP, Paris, France; §Département d'Hémato-Immunologie, Hôpital Bichat-Claude Bernard, CIB Phenogen, AP-HP, Paris, France; ¶INSERM U773, Paris, France; ∥Service d'Hématologie, Hôpital de la Timone, AP-HM, Marseille, France; **Service d'Hématologie Adulte, Hôpital Necker-Enfants Malades, AP-HP, Paris, France; ††Service de Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, AP-HP, Centre d'Infectiologie Necker-Pasteur, Paris, France; ‡‡Faculté de Médecine, Université Paris Descartes, Paris, France; §§Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, Institut Pasteur, Paris, France; and ¶¶CNRS URA3012, Paris, France.

Accepted for publication July 8, 2010.

Supported by a grant of the French Ministry of Health and the French association of patients with PID (IRIS). The CEREDIH received support and educational grants from Pfizer, LFB Biomédicaments, Baxter Biosciences, CSL Behring, and Octapharma.

Address for correspondence: Olivier Lortholary, MD, PhD, Service de Maladies Infectieuses et Tropicales, Groupe Hospitalier Necker-Enfants Malades, Centre d'Infectiologie Necker Pasteur, 149 rue de Sèvres, 75015 Paris, France. E-mail:

© 2011 Lippincott Williams & Wilkins, Inc.