ConditionBlood & immune system
Chronic Granulomatous Disease (CGD)
Chronic granulomatous disease (CGD) is a rare inherited immune deficiency in which phagocytes, the white blood cells that swallow germs, cannot produce the chemicals needed to kill certain bacteria and fungi. People with CGD get repeated, serious infections of the lungs, skin, lymph nodes, liver and bones, and develop clumps of immune cells called granulomas. It usually shows in early childhood. Daily preventive antibiotics and antifungals greatly reduce infections, and a stem cell transplant can cure it.
Also called: CGD, phagocyte oxidase deficiency, NADPH oxidase deficiency, Bridges-Good syndrome
At a glance
- What it is
- An inherited defect in the NADPH oxidase enzyme of phagocytes.
- Inheritance
- About two-thirds X-linked (mostly boys); the rest autosomal recessive.
- Typical infections
- Staphylococcus aureus, Aspergillus, Burkholderia, Serratia, Nocardia; pneumonia, abscesses, lymphadenitis.
- Diagnosis
- DHR flow cytometry blood test, confirmed by genetic testing.
- Treatment
- Lifelong trimethoprim-sulfamethoxazole and itraconazole, interferon-gamma in some, stem cell transplant for cure.
When to get help
Call 911 or go to the ER
- Fever with breathing difficulty, confusion, or low blood pressure in someone with CGD. Call 911 or your local emergency number
See a doctor within a day or two
- Any fever in a person with CGD; infections can become severe quickly
- A new cough, chest pain, swollen painful lymph node, skin abscess, or bone pain
- Abdominal pain with fever (possible liver abscess)
Book a routine appointment
- A child with repeated pneumonia, abscesses or unusual infections
- Chronic diarrhea, weight loss or mouth ulcers in someone with CGD (possible CGD colitis)
- Family planning in families affected by CGD
How CGD affects the immune system
CGD is one of the primary immunodeficiencies, conditions present from birth in which part of the immune system does not work.
Neutrophils and other phagocytes engulf bacteria and fungi, then kill them using a "respiratory burst", producing reactive oxygen compounds through an enzyme complex called NADPH oxidase. In CGD, a gene defect disables one part of this enzyme, so phagocytes can swallow germs but cannot kill certain types.
The surviving germs and persistent inflammation lead to granulomas, collections of immune cells that can block the stomach outlet, bladder or bowel.
Organisms that people with CGD are particularly susceptible to make an enzyme called catalase. They include Staphylococcus aureus, Aspergillus species, which cause aspergillosis and are the leading cause of death, Burkholderia cepacia, Serratia marcescens and Nocardia.
Inheritance
| Type | Gene | Who is affected |
|---|---|---|
| X-linked | CYBB | Mostly boys; mothers may be carriers and some carriers have mild symptoms or lupus-like problems |
| Autosomal recessive | CYBA, NCF1, NCF2, NCF4, CYBC1 | Boys and girls; both parents are carriers; often milder |
CGD affects roughly 1 in 200,000 to 250,000 people.
Symptoms
Most people develop symptoms before age 5, though milder forms may appear in adolescence or adulthood.
- recurrent pneumonia, often fungal, and lung abscesses
- skin infections and abscesses, especially around the nose, mouth and anus
- swollen, infected lymph nodes that may need draining
- liver abscesses
- bone infections (osteomyelitis), often in the hands and feet
- chronic fevers and fatigue
- CGD colitis: diarrhea, abdominal pain and weight loss resembling Crohn's disease
- granulomas causing blockage of the stomach outlet or urinary tract
- poor growth in children
- mouth ulcers and gum inflammation
Diagnosis
Suspicion is raised by repeated or unusual infections, especially with the organisms above.
- Dihydrorhodamine (DHR) flow cytometry: the main screening test. It measures whether neutrophils produce reactive oxygen. The pattern helps distinguish X-linked from autosomal recessive forms and detects carrier mothers.
- Genetic testing confirms the specific gene variant.
- Older tests, such as the nitroblue tetrazolium (NBT) test, are rarely used now.
- Imaging (CT, ultrasound) and biopsies help find infections and granulomas.
Treatment
Lifelong prevention
- Trimethoprim-sulfamethoxazole daily to prevent bacterial infections
- Itraconazole (or another antifungal) daily to prevent fungal infections
- Interferon-gamma injections three times a week, used in many US centers to further reduce serious infections
- Avoiding exposure to fungal spores: no gardening, mulch, compost, hay, or cleaning out barns and leaf piles; caution with construction sites
Treating infections
Infections are treated early and aggressively, often with prolonged courses of antibiotics or antifungals, sometimes with surgical drainage. Fever should never be ignored.
Treating inflammation
Steroids and other immune-modifying medicines treat granulomas and colitis, balanced carefully against infection risk.
Cure
- Hematopoietic stem cell transplantation from a matched donor can cure CGD. Outcomes have improved substantially and transplant is increasingly offered in childhood.
- Gene therapy is being studied in clinical trials.
Outlook
With preventive medicines, most people with CGD survive into adulthood, and many live into their 40s and beyond. Life expectancy varies with the gene type and residual enzyme activity. Stem cell transplant offers the potential for normal life expectancy.
Frequently asked questions
What causes chronic granulomatous disease?
CGD is caused by inherited changes in genes that build the NADPH oxidase enzyme in white blood cells. Without it, these cells cannot kill certain bacteria and fungi. About two-thirds of cases are X-linked and mainly affect boys.
How is CGD diagnosed?
The main test is a dihydrorhodamine (DHR) flow cytometry blood test, which shows whether white blood cells can produce the chemicals that kill germs. Genetic testing then confirms the exact gene change.
Can chronic granulomatous disease be cured?
Yes. A stem cell transplant from a matched donor can cure CGD by replacing the faulty immune cells. Gene therapy is being studied. Without transplant, daily preventive antibiotics and antifungals keep many people well.
Why should people with CGD avoid gardening?
Garden soil, mulch, compost, hay and decaying leaves contain Aspergillus and other fungal spores. Inhaling them can cause life-threatening fungal pneumonia in people with CGD, so these activities are best avoided.
Sources
This guide was written from current patient and clinical guidance, including:
- NIAID: Chronic granulomatous disease
- Immune Deficiency Foundation: Chronic granulomatous disease
- NIH Genetic and Rare Diseases Information Center: Chronic granulomatous disease
- MedlinePlus Genetics: Chronic granulomatous disease
- American Academy of Allergy, Asthma & Immunology: Primary immunodeficiency