Seger Reinhard A
University Children's Hospital, Zürich, Switzerland.
Curr Opin Hematol. 2011 Jan;18(1):36-41. doi: 10.1097/MOH.0b013e32834115e7.
Chronic granulomatous disease (CGD), characterized 50 years ago as a primary immunodeficiency disorder of phagocytic cells (resulting in failure to kill a defined spectrum of bacteria and fungi and in concomitant chronic granulomatous inflammation) now comprises five genetic defects impairing one of the five subunits of phagocyte NADPH oxidase (Phox). Phox normally generates reactive oxygen species (ROS) engaged in intracellular and extracellular host defence and resolving accompanying inflammatory processes. 'Fatal' granulomatous disease has now changed into a chronic inflammatory condition with a median survival of 35 years and is now of interest to both paediatricians and internists. Clinical vigilance and expert knowledge are needed for early recognition and tailored treatment of this relatively rare genetic disorder.
Infections by unanticipated pathogens and noncirrhotic portal hypertension need to be recognized as new CGD manifestations. Adult-onset CGD too is increasingly observed even in the elderly. Conservative treatment of fungal infections needs close monitoring due to the spread of azole resistance following extensive use of azoles in agriculture. Curative haematopoietic stem cell transplantation (HSCT) in early childhood has expanded with impressive results following use of matched, unrelated or cord blood donors and of a reduced intensity conditioning (RIC) regimen. Gene therapy, however, still has major limitations, remaining experimental.
CGD is more prevalent than initially believed with a birth prevalence of 1: 120 000. As patients are increasingly diagnosed around the world and grow older, further manifestations of CGD are expected. While fungal infections have lost some threat, therapeutic research focuses on two other important aims: pharmacologic cure of chronic inflammation and long-term cure of CGD by gene therapy.
慢性肉芽肿病（CGD）在50年前被定义为吞噬细胞的原发性免疫缺陷疾病（导致无法杀灭特定种类的细菌和真菌，并伴有慢性肉芽肿性炎症），如今已知其包含五种基因缺陷，这些缺陷影响吞噬细胞NADPH氧化酶（Phox）五个亚基中的一个。Phox通常产生参与细胞内和细胞外宿主防御以及解决伴随炎症过程的活性氧（ROS）。“致命”的肉芽肿病现已转变为一种慢性炎症性疾病，中位生存期为35年，目前受到儿科医生和内科医生的关注。对于这种相对罕见的遗传性疾病，早期识别和针对性治疗需要临床警惕性和专业知识。
由意外病原体引起的感染和非肝硬化性门静脉高压需要被视为CGD的新表现形式。成人期CGD甚至在老年人中也越来越多地被观察到。由于农业中广泛使用唑类药物后唑类耐药性的传播，真菌感染的保守治疗需要密切监测。儿童早期进行的根治性造血干细胞移植（HSCT）随着使用匹配的、无关供体或脐血供体以及降低强度预处理（RIC）方案而取得了令人瞩目的扩展成果。然而，基因治疗仍然存在重大局限性，仍处于实验阶段。
CGD比最初认为的更为普遍，出生患病率为1:120000。随着世界各地越来越多的患者被诊断出来且年龄增长，预计CGD会出现更多表现形式。虽然真菌感染的威胁有所降低，但治疗研究集中在另外两个重要目标上：慢性炎症的药物治愈以及通过基因治疗实现CGD的长期治愈。
