Chronic granulomatous disease: recent advances in pathophysiology and treatment.
Chronic granulomatous disease (CGD) was characterised half a century ago as a primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a specific spectrum of bacteria and fungi and in concomitant hyperinflammation with widespread tissue granuloma formation. CGD now comprises five genetic defects, each impairing one of five essential subunits of the phagocyte NADPH oxidase generating reactive oxygen species. In the past few years CGD has lead to a new understanding of the importance of phagocyte oxygen metabolism for intra- and extracellular host defence and for resolution of the concomitant inflammatory process. In a not too distant future, this may help to tailor novel pharmacological and cellular interventions to the requirements of individual patients. This review covers recent advances in the pathophysiology of CGD and outlines today's clinical presentation as well as the basic principles for treatment of this relatively rare genetic disease. 'Fatal' granulomatous disease 50 years later has become a chronic inflammatory disorder with a median survival of 30 years and is of interest to both paediatricians and internists.
Division of Immunology/Haematology/BMT, University Children's Hospital of Zurich, Zurich, Switzerland. reinhard.seger@kispi.uzh.ch
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D005817:Genetic Counseling; D015316:Genetic Therapy / Q000379:methods; D006105:Granulomatous Disease, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000517:prevention & control; D019255:NADPH Oxidases / Q000172:deficiency / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism / Q000473:pathology*; D010588:Phagosomes; D017382:Reactive Oxygen Species / Q000378:metabolism; D012008:Recurrence
D017382:Reactive Oxygen Species; D019255:NADPH Oxidases