Chronic granulomatous disease, often abbreviated CGD, is a rare inherited primary immunodeficiency that affects how certain white blood cells (phagocytes such as neutrophils and macrophages) destroy invading microbes. In CGD, an enzyme complex called NADPH oxidase does not function properly, so phagocytes engulf bacteria and fungi normally but cannot generate the reactive oxygen burst needed to kill them efficiently. The result is heightened susceptibility to severe, recurrent bacterial and fungal infections, along with the formation of granulomas (clusters of immune cells) and dysregulated inflammation that can affect multiple organ systems. CGD is rare, with an estimated prevalence of fewer than nine cases per million. Several genetically defined subtypes have been described, including an X-linked form that primarily affects males and several autosomal recessive forms that can affect any sex. With modern infection prevention, antimicrobial prophylaxis, and access to allogeneic stem cell transplantation, long-term outcomes have improved substantially compared with earlier decades. This summary reflects clinical data available as of 2026-05-10.

CGD typically presents in early childhood, with most affected individuals diagnosed before age five, although milder forms are increasingly recognized in adolescence or adulthood. The clinical picture is dominated by infections and inflammatory complications across several organ systems. Respiratory involvement is common and can include pneumonia, sinusitis, otitis media, mediastinal lymphadenopathy, and chronic pulmonary obstruction; pulmonary granulomas or progressive lung scarring may develop over time. The skin and soft tissues are frequently affected, with abscesses, cellulitis, slow-healing wounds, hyperpigmented skin patches (macules), and increased sensitivity to sunlight. Lymph nodes and the liver are common sites for deep abscesses, and bone infection (osteomyelitis) can occur. Gastrointestinal involvement may take the form of inflammatory colitis with frequent stooling, perirectal abscesses, or tracheoesophageal and other gut narrowings caused by granulomas. Persistent fever, growth restriction in childhood, and abnormalities of neutrophil function are characteristic findings. Catalase-positive bacteria and certain molds are particularly problematic pathogens. Not all individuals experience all features, and severity varies considerably depending on the underlying genetic subtype and on how much residual oxidase activity remains.

CGD is caused by inherited changes in genes that encode or assemble the subunits of the phagocyte NADPH oxidase complex. When this enzyme system is missing or impaired, phagocytes cannot mount the oxidative burst that normally kills ingested microbes, and unresolved organisms drive both recurrent infection and chronic granulomatous inflammation. In this packet the specific causative gene set is not enumerated, so individual genes are not named here; molecular genetic testing is the most reliable way to establish the precise cause in any given person. Inheritance is heterogeneous and depends on which oxidase subunit is affected. The X-linked form is the most common subtype and typically affects males, with female relatives sometimes showing partial features as carriers. Autosomal recessive forms also exist, in which both copies of a gene must carry pathogenic variants for the disease to manifest; recessive forms are relatively more common in regions where consanguineous marriages are frequent. Some individuals carry hypomorphic variants that allow partial protein function and a measurable degree of residual superoxide production, and this residual activity tends to correlate with milder disease and later age at diagnosis.

Symptoms can overlap with other primary immunodeficiencies and with chronic infectious or inflammatory disorders, so confirming the diagnosis requires specific testing. Evaluation generally begins with a careful clinical assessment when a child or adult presents with severe, recurrent, or unusual bacterial or fungal infections, deep tissue abscesses, granulomas, or unexplained colitis. The cornerstone diagnostic test is a functional assay of the phagocyte oxidative burst, most commonly the dihydrorhodamine (DHR) flow cytometry test, which measures whether neutrophils can generate reactive oxygen species after stimulation. An abnormal DHR result strongly supports CGD and can also suggest the inheritance pattern, though it cannot identify the precise genetic cause. Molecular genetic testing then confirms the diagnosis, defines the specific subtype, and informs genetic counseling for the family. Supporting laboratory studies may include markers of inflammation such as C-reactive protein and erythrocyte sedimentation rate, complete blood counts, liver chemistries, and microbiologic cultures or biopsies of infected tissue. Imaging is used to characterize abscesses, granulomas, and organ involvement, and endoscopy is helpful when colitis is suspected. Because the differential diagnosis includes other immune deficiencies, cystic fibrosis, mycobacterial disease, and inflammatory bowel disease, evaluation is best coordinated by clinicians experienced in primary immunodeficiency.

There is no single curative medication for CGD, and management combines daily preventive measures, prompt treatment of infections, attention to inflammatory complications, and consideration of definitive cellular therapy. Foundational care centers on long-term antimicrobial prophylaxis. Trimethoprim-sulfamethoxazole is widely used to reduce bacterial infections, and an antifungal agent such as itraconazole or posaconazole is typically added to lower the risk of mold infections including invasive aspergillosis. Interferon gamma-1b (brand name Actimmune) is FDA-approved for reducing the frequency and severity of serious infections in CGD and is sometimes added to the prophylaxis regimen at the discretion of the immunology team. Acute infections are treated aggressively with prolonged courses of targeted antibiotics or antifungals after a specific microbiologic diagnosis is established, and surgical drainage of abscesses may be required. Inflammatory complications such as colitis or obstructive granulomas are managed with anti-inflammatory therapy individualized to the situation. Vaccination is generally encouraged, but live bacterial vaccines such as BCG and Salmonella typhi vaccines are avoided. Exposure to environments rich in fungal spores, such as gardening, mulching, leaf raking, and stagnant water, is also avoided. Allogeneic hematopoietic stem cell transplantation is currently the only established curative therapy and is increasingly considered earlier in the disease course for selected patients with a suitable donor. Regular surveillance is an essential part of long-term care, with periodic monitoring of inflammation markers, blood counts, liver function, and pulmonary and gastrointestinal status to detect complications early.

Outcomes in CGD have improved substantially over the past several decades and continue to evolve. Long-term prognosis depends on the genetic subtype, the level of residual oxidase activity, the burden of prior infections and granulomatous complications, access to specialized immunology care, and whether and when curative cellular therapy is undertaken. Many individuals on consistent antimicrobial prophylaxis and close surveillance live well into adulthood, while severe complications such as invasive fungal pneumonia, deep-tissue abscesses, hepatic involvement, refractory colitis, and progressive pulmonary fibrosis can shorten survival when they occur. Hypomorphic variants that preserve some oxidase activity are generally associated with a milder disease course. Allogeneic hematopoietic stem cell transplantation has shifted the outlook for selected patients, offering the possibility of long-term cure when a suitable donor is available, although transplant itself carries risks that must be weighed individually. Care delivered by a team experienced in primary immunodeficiency, paired with attention to mental health and family support, contributes meaningfully to overall well-being.

Research in CGD is active, with several clinical trials underway across hematopoietic stem cell transplantation, gene-directed therapies for both X-linked and autosomal recessive forms, refined conditioning regimens to make transplantation safer, and improved approaches to managing inflammation and fungal disease. Investigational gene therapy and gene editing strategies aim to correct the defective oxidase component in a patient's own blood-forming stem cells, while other studies focus on natural history, infection prevention, and supportive care. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team to discuss whether participation is appropriate.