Chronic Granulomatous Disease (CGD): Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management

Chronic granulomatous disease (CGD) is a relatively rare inborn error of immune system caused by some defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, which leads to the impaired production of reactive oxygen species (ROS) and ineffective function of phagocyte. Moreover, genetic defects of any one of proteinaceous components of NADPH oxidase complex results in CGD. The most common type of CGD (65-70%) is caused by X-linked mutations in the CYBB gene encoding gp91phox, followed by autosomal recessive mutations in the NCF1, NCF2, CYBA and NCF4 genes, which encode p47phox, p67phox, p22phox, and p40phox, respectively. In this regard, Dihydrorhodamine (DHR) 123 oxidation and nitroblue tetrazolium (NBT) tests are both used for the diagnosis of CGD that should be confirmed by genetic testing at first. CGD patients generally present with recurrent infections caused by uncommon pathogens such as aspergillus, staphylococcus aureus, burkholderia cepacia, serratia marcescens, Aspergillus species, and nocardia. They usually manifest with deep seated abscess formation, genitourinary and gastrointestinal granuloma development, autoimmunity, and malignancy. Apart from comprehensive treatment of acute infections, the management of CGD is performed based on reducing bacterial and fungal infections as well as minimizing the inflammatory symptoms. Also, antibiotics, anti-fungal, and IFN-γ are used for prophylaxis. Allogeneic hematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently considered as the only proven curative treatment for CGD. Accordingly, gene therapy is known as an alternative novel therapeutic approach in near future.