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🌱 來自: hematology

chronic granulomatous disease

• Definition and age at diagnosis : Chronic granulomatous disease (CGD) is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. Most patients are diagnosed before the age of five years. (See ‘Introduction’ above and ‘Epidemiology’ above.)

• Pathogenesis : CGD is caused by defects in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which comprises the phagocyte oxidase (phox). This enzyme complex is responsible for the phagocyte respiratory burst. (See ‘Pathogenesis’ above.)

• Genetic defects : Pathogenic variants in the genes for all six proteins (gp91phox, p47phox, p22phox, p67phox, p40phox, and essential for reactive oxygen species [EROS]) that make up the NADPH oxidase complex account for all of the known cases of CGD. Most pathogenic variants in North America are X linked (gp91phox deficiency). (See ‘Genetic defects’ above.)

• Types and sites of infections : Patients with CGD typically experience recurrent infections caused by bacterial and fungal pathogens. The overwhelming majority of infections in patients with CGD living in North America are due to five organisms: Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia, and Aspergillus. The frequent sites of infection are lung, skin, lymph nodes, and liver. (See ‘Infections’ above.)

• Inflammatory manifestations : Patients with CGD are prone to the formation of granulomata that are especially problematic in the gastrointestinal and genitourinary tracts. Colitis is a common gastrointestinal manifestation. (See ‘Inflammatory and other manifestations’ above.)

• Carriers : Female carriers generally do not have an increased rate of infections, but they are more predisposed to certain inflammatory manifestations associated with CGD. However, females can develop typical CGD infections when oxidase activity drops to <20 percent of normal due to skewed X-chromosome lyonization. (See ‘X-linked carriers’ above.)

• Diagnosis : A neutrophil function test, dihydrorhodamine (DHR) 123, is the initial diagnostic test performed. A significantly abnormal finding should be confirmed by genotyping. (See ‘Diagnosis’ above.)