Chronic granulomatous disease: the European experience.
CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH oxidase complex in phagosomes of certain phagocytic cells leads to a "respiratory burst", essential for the clearance of phagocytosed micro-organisms. CGD patients lack this mechanism, which leads to life-threatening infections and granuloma formation. However, a clear picture of the clinical course of CGD is hampered by its low prevalence (approximately 1:250,000). Therefore, extensive clinical data from 429 European patients were collected and analyzed. Of these patients 351 were males and 78 were females. X-linked (XL) CGD (gp91(phox) deficient) accounted for 67% of the cases, autosomal recessive (AR) inheritance for 33%. AR-CGD was diagnosed later in life, and the mean survival time was significantly better in AR patients (49.6 years) than in XL CGD (37.8 years), suggesting a milder disease course in AR patients. The disease manifested itself most frequently in the lungs (66% of patients), skin (53%), lymph nodes (50%), gastrointestinal tract (48%) and liver (32%). The most frequently cultured micro-organisms per episode were Staphylococcus aureus (30%), Aspergillus spp. (26%), and Salmonella spp. (16%). Surprisingly, Pseudomonas spp. (2%) and Burkholderia cepacia (<1%) were found only sporadically. Lesions induced by inoculation with BCG occurred in 8% of the patients. Only 71% of the patients received antibiotic maintenance therapy, and 53% antifungal prophylaxis. 33% were treated with gamma-interferon. 24 patients (6%) had received a stem cell transplantation. The most prominent reason of death was pneumonia and pulmonary abscess (18/84 cases), septicemia (16/84) and brain abscess (4/84). These data provide further insight in the clinical course of CGD in Europe and hopefully can help to increase awareness and optimize the treatment of these patients.
van den Berg
J Merlijn
JM
Sanquin Research, and Landsteiner Laboratory, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. j.m.vandenberg@amc.nl
van Koppen
Elsbeth
E
Ahlin
Anders
A
Belohradsky
Bernd H
BH
Bernatowska
Ewa
E
Corbeel
Lucien
L
Español
Teresa
T
Fischer
Alain
A
Kurenko-Deptuch
Magdalena
M
Mouy
Richard
R
Petropoulou
Theoni
T
Roesler
Joachim
J
Seger
Reinhard
R
Stasia
Marie-José
MJ
Valerius
Niels H
NH
Weening
Ron S
RS
Wolach
Baruch
B
Roos
Dirk
D
Kuijpers
Taco W
TW
D005060:Europe / Q000453:epidemiology; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male