Marciano Beatriz E, Spalding Christine, Fitzgerald Alan, Mann Daphne, Brown Thomas, Osgood Sharon, Yockey Lynne, Darnell Dirk N, Barnhart Lisa, Daub Janine, Boris Lisa, Rump Amy P, Anderson Victoria L, Haney Carissa, Kuhns Douglas B, Rosenzweig Sergio D, Kelly Corin, Zelazny Adrian, Mason Tamika, DeRavin Suk See, Kang Elizabeth, Gallin John I, Malech Harry L, Olivier Kenneth N, Uzel Gulbu, Freeman Alexandra F, Heller Theo, Zerbe Christa S, Holland Steven M
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
Clinical Research Directorate/Clinical Monitoring Research Program.
Clin Infect Dis. 2015 Apr 15;60(8):1176-83. doi: 10.1093/cid/ciu1154. Epub 2014 Dec 23.
Chronic granulomatous disease (CGD) is due to defective nicotinamide adenine dinucleotide phosphate oxidase activity and characterized by recurrent infections with a limited spectrum of bacteria and fungi as well as inflammatory complications. To understand the impact of common severe infections in CGD, we examined the records of 268 patients followed at a single center over 4 decades.
All patients had confirmed diagnoses of CGD, and genotype was determined where possible. Medical records were excerpted into a standard format. Microbiologic analyses were restricted to Staphylococcus, Burkholderia, Serratia, Nocardia, and Aspergillus.
Aspergillus incidence was estimated at 2.6 cases per 100 patient-years; Burkholderia, 1.06 per 100 patient-years; Nocardia, 0.81 per 100 patient-years; Serratia, 0.98 per 100 patient-years, and severe Staphylococcus infection, 1.44 per 100 patient-years. Lung infection occurred in 87% of patients, whereas liver abscess occurred in 32%. Aspergillus incidence was 55% in the lower superoxide-producing quartiles (quartiles 1 and 2) but only 41% in the higher quartiles (rate ratio, <0.0001). Aspergillus and Serratia were somewhat more common in lower superoxide producing gp91phox deficiency. The median age at death has increased from 15.53 years before 1990 to 28.12 years in the last decade. Fungal infection carried a higher risk of mortality than bacterial infection and was the most common cause of death (55%). Gastrointestinal complications were not associated with either infection or mortality.
Fungal infections remain a major determinant of survival in CGD. X-linked patients generally had more severe disease, and this was generally in those with lower residual superoxide production. Survival in CGD has increased over the years, but infections are still major causes of morbidity and mortality.
慢性肉芽肿病（CGD）是由于烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性缺陷所致，其特征为反复感染，感染的细菌和真菌种类有限，并伴有炎症并发症。为了解常见严重感染对CGD的影响，我们查阅了在一个中心随访40多年的268例患者的记录。
所有患者均确诊为CGD，并尽可能确定其基因型。将病历摘录为标准格式。微生物学分析仅限于葡萄球菌、伯克霍尔德菌、沙雷菌、诺卡菌和曲霉菌。
曲霉菌发病率估计为每100患者年2.6例；伯克霍尔德菌为每100患者年1.06例；诺卡菌为每100患者年0.81例；沙雷菌为每100患者年0.98例，严重葡萄球菌感染为每100患者年1.44例。87%的患者发生肺部感染，32%的患者发生肝脓肿。在超氧化物产生较低的四分位数（第1和第2四分位数）中，曲霉菌发病率为55%，而在较高四分位数中仅为41%（率比，<0.0001）。在超氧化物产生较低的gp91phox缺陷患者中，曲霉菌和沙雷菌感染更为常见。死亡年龄中位数已从1990年前的15.53岁增加到过去十年的28.12岁。真菌感染的死亡风险高于细菌感染，是最常见的死亡原因（55%）。胃肠道并发症与感染或死亡率均无关。
真菌感染仍然是CGD患者生存的主要决定因素。X连锁患者的疾病通常更严重，这通常发生在超氧化物产生残留较低的患者中。多年来，CGD患者的生存率有所提高，但感染仍然是发病和死亡的主要原因。
