Chronic granulomatous disease

Chronic granulomatous disease (CGD), also known as granulomatous disease, chronic, or Bridges-Good syndrome, is a rare primary immunodeficiency disorder caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex in phagocytic cells (neutrophils, monocytes, and macrophages). This enzyme complex is responsible for generating reactive oxygen species (the "respiratory burst") that are essential for killing certain bacteria and fungi. When this system is defective, patients become highly susceptible to severe, life-threatening, and recurrent infections caused by catalase-positive organisms such as Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia species, and Aspergillus species. The disease primarily affects the immune system but can involve virtually any organ. Common clinical features include recurrent pneumonia, liver abscesses, lymphadenitis (swollen and infected lymph nodes), skin infections and abscesses, osteomyelitis (bone infections), and perianal abscesses. A hallmark of the disease is the formation of granulomas — clusters of immune cells that form in response to chronic inflammation — which can obstruct the gastrointestinal or genitourinary tracts. Inflammatory bowel disease-like colitis is a frequent complication, and patients may also develop granulomatous inflammation in the lungs, liver, and spleen. Failure to thrive and growth delay may be seen in affected children. CGD can be caused by mutations in several genes. The most common form (approximately 65-70% of cases) is X-linked recessive, caused by mutations in the CYBB gene encoding the gp91-phox protein. Autosomal recessive forms are caused by mutations in CYBA (p22-phox), NCF1 (p47-phox), NCF2 (p67-phox), or NCF4 (p40-phox). Treatment includes lifelong antimicrobial prophylaxis with trimethoprim-sulfamethoxazole and itraconazole, as well as interferon-gamma (IFN-γ) therapy to reduce the frequency and severity of infections. Aggressive treatment of acute infections with appropriate antimicrobials is essential. Hematopoietic stem cell transplantation (HSCT) is the only established curative therapy and is increasingly offered to patients with a suitable donor, particularly those with severe disease. Gene therapy is under active investigation as a potential curative approach.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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