From the Research
Chronic granulomatous disease (CGD) should be managed with prophylactic antimicrobials, including trimethoprim-sulfamethoxazole and itraconazole, as well as interferon-gamma, and considered for hematopoietic stem cell transplantation as the only curative option, especially for patients with severe disease or frequent life-threatening infections, as supported by the most recent and highest quality study 1. The primary treatment for CGD includes:
- Prophylactic antimicrobials, specifically trimethoprim-sulfamethoxazole (5-10 mg/kg/day of the trimethoprim component, divided twice daily) to prevent bacterial infections
- Itraconazole (100-200 mg daily for adults, 5-10 mg/kg/day for children) to prevent fungal infections
- Interferon-gamma (50 μg/m² subcutaneously three times weekly) to reduce the frequency of serious infections For active infections, aggressive treatment with appropriate antibiotics or antifungals is necessary, often requiring longer courses than in immunocompetent patients. CGD results from mutations in genes encoding components of the NADPH oxidase complex, which prevents the production of reactive oxygen species needed to kill pathogens, leading to recurrent infections and formation of granulomas in various tissues, causing inflammatory complications, as described in 2, 3, 1. The implementation of antimicrobial, anti-fungal, and interferon-γ prophylaxis has greatly improved overall survival, and new therapeutic approaches using immunomodulators for CGD-related inflammatory manifestations are under investigation, including pioglitazone, tamoxifen, and rapamycin, as mentioned in 1. Hematopoietic stem cell transplantation (HSCT) is the curative treatment, with outcomes improved substantially over the last decade, and gene therapy using genome-editing technology such as CRISPR/Cas9 nucleases is a promising approach for patients with CGD in the future, as discussed in 1.