From the Guidelines
Chronic granulomatous disease (CGD) is a rare inherited immune disorder that requires prompt and aggressive management with prophylactic antimicrobials, interferon-gamma, and prompt treatment of acute infections to reduce morbidity and mortality. The disease is characterized by the inability of neutrophils and other phagocytes to kill certain bacteria and fungi due to defects in the NADPH oxidase enzyme complex, resulting in recurrent severe infections and formation of granulomas in various tissues 1. According to the practice parameter for the diagnosis and management of primary immunodeficiency, CGD occurs in approximately 1 in 200,000 live births, with a higher incidence in consanguinous communities 1.
Key Management Strategies
- Prophylactic antimicrobials, such as trimethoprim-sulfamethoxazole (5-10 mg/kg/day of the trimethoprim component) and itraconazole (100-200 mg daily for adults, 5-10 mg/kg/day for children), to prevent bacterial and fungal infections
- Interferon-gamma (50 μg/m² subcutaneously three times weekly) to reduce infection frequency
- Prompt and aggressive treatment of acute infections with appropriate antibiotics or antifungals, often requiring longer courses than in immunocompetent patients
- Hematopoietic stem cell transplantation for severe or refractory cases, offering potential cure
- Gene therapy, emerging as a promising treatment option
- Avoidance of activities with high exposure to environmental fungi, such as gardening or construction sites
- Regular follow-up with immunologists for monitoring and adjusting treatment
Disease Characteristics
- Results from mutations in genes encoding components of the NADPH oxidase complex, leading to defective production of reactive oxygen species necessary for pathogen killing
- Characterized by recurrent severe infections and formation of granulomas in various tissues
- Patients are at increased risk of autoimmune diseases and malignancies, such as autoimmune cytopenias, inflammatory arthropathies, and vasculitides, as well as hematologic malignancies like lymphoma and leukemia 1.
From the Research
Definition and Causes of Chronic Granulomatous Disease
- Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide phosphatase (NADPH) oxidase enzyme complex 2.
- This defect leads to recurrent life-threatening infections and may develop infectious or inflammatory complications.
Commonly Associated Pathogens
- The most common microorganisms observed in patients with CGD are:
- Staphylococcus aureus
- Aspergillus spp.
- Candida spp.
- Nocardia spp.
- Burkholderia spp.
- Serratia spp.
- Salmonella spp. 2
Diagnosis and Treatment
- Antibacterial prophylaxis with trimethoprim-sulfamethoxazole, antifungal prophylaxis usually with itraconazole, and interferon gamma immunotherapy have been successfully used in reducing infection in CGD 2.
- Haematopoietic stem cell transplantation (HCT) has been successfully proven to be the treatment of choice in patients with CGD 2, 3.
- Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis is indicated for the management of patients with CGD and decreases the incidence of non-fungal infections without increasing the incidence of fungal infections 4.
Management and Prevention of Infections
- The long-term use of trimethoprim-sulfamethoxazole and ketoconazole as a preventive therapy for infections has been evaluated, with TMP-SMX being effective against bacterial infections 5.
- Current prophylaxis with trimethoprim-sulfamethoxazole, itraconazole, and in selected cases additional interferon gamma is efficient, but imperfect 3.
- Allogeneic haematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD and can be offered to selected patients 3.