Chronic Granulomatous Disease

Overview

Chronic granulomatous disease (CGD) is a rare inherited disorder of the immune system. Specialized white blood cells called phagocytes normally engulf bacteria and fungi and then destroy them using a burst of reactive oxygen chemicals. In CGD, a defect in the machinery that produces those chemicals means the cells can swallow certain germs but cannot kill them effectively. As a result, specific bacteria and fungi survive and cause repeated, sometimes severe, infections.

The body's attempt to wall off these persistent germs leads to clusters of inflammatory cells called granulomas, which give the disease its name. These can build up in organs such as the gut and urinary tract and cause problems of their own. Most cases are diagnosed in childhood, although milder forms may be recognized later.

Symptoms

The main feature is recurrent infections, often caused by a characteristic set of bacteria and fungi, together with granulomas that can affect different organs.

• Recurrent infections: Of the skin, lungs (pneumonia), lymph nodes, liver (abscesses), and bones.
• Abscesses: Collections of pus that may form in the skin or internal organs and can be slow to heal.
• Granulomas: Inflammatory masses that can block parts of the digestive or urinary tract, causing symptoms like cramping, difficulty passing urine, or bowel problems.
• General signs: Persistent or recurring fevers, poor growth in children, and prolonged tiredness during infections.

Infections in CGD can be caused by germs that rarely trouble people with normal immunity, which is an important clue.

Causes

CGD is caused by inherited mutations in genes that make the components of an enzyme complex (NADPH oxidase) used by white cells to generate germ-killing chemicals.

• X-linked form: The most common type results from a gene change on the X chromosome, so it mainly affects boys.
• Autosomal recessive forms: Caused by changes in other genes and affect boys and girls equally, requiring an altered copy from each parent.
• New mutations: Occasionally the gene change arises newly without a family history.

Whichever gene is involved, the end result is the same: phagocytes cannot produce the chemical burst needed to kill certain bacteria and fungi.

Risk Factors

• A family history of CGD, especially affected male relatives for the X-linked form
• Parents who both carry a recessive gene change
• Recurrent deep-seated infections or abscesses caused by unusual organisms in early childhood

As an inherited disorder, CGD is present from birth and is not caused by lifestyle or environment.

Diagnosis

Doctors suspect CGD in a child with recurrent serious infections from characteristic germs and confirm it with specialized tests of white cell function.

• Neutrophil function tests: Tests such as the dihydrorhodamine (DHR) assay measure whether white cells can produce the germ-killing chemical burst.
• Cultures and imaging: Identify the organisms causing infections and locate abscesses or granulomas.
• Genetic testing: Confirms the specific gene change and the form of the disease.
• Family testing and counseling: To identify carriers and inform future pregnancies.

Treatment

Treatment focuses on preventing and aggressively treating infections, controlling inflammation from granulomas, and, when possible, correcting the immune defect.

• Preventive antibiotics: Long-term antibiotics greatly reduce the rate of serious bacterial infections.
• Preventive antifungals: Used to guard against fungal infections, which are a particular danger in CGD.
• Interferon-gamma: An immune-boosting injection given in some patients to lower infection rates.
• Prompt, intensive treatment of infections: Often requiring intravenous antibiotics or antifungals and sometimes surgical drainage of abscesses.
• Anti-inflammatory treatment: Such as corticosteroids for symptomatic granulomas in the gut or urinary tract.
• Stem cell transplantation: Can cure the disease by replacing the faulty immune cells, and gene therapy is being studied.

Prevention

The disease itself cannot be prevented, but infections and complications often can.

• Take preventive antibiotics and antifungals consistently
• Avoid high-risk exposures such as decaying organic matter, mulch, and heavy dust, which can carry dangerous fungi
• Practice careful wound and skin care and treat injuries promptly
• Seek medical care early for fevers or new infections rather than waiting
• Attend regular specialist follow-up and consider genetic counseling for the family

When to See a Doctor

A child with recurrent deep infections, abscesses, or pneumonias caused by unusual germs should be evaluated for an immune disorder. Seek urgent or emergency care for:

• A high or persistent fever, especially with a known diagnosis of CGD
• Difficulty breathing, rapid breathing, or chest pain
• A rapidly enlarging or very painful abscess
• Severe abdominal pain, inability to pass urine, or signs of a serious bloodstream infection such as confusion

Because infections can escalate quickly, prompt treatment is essential.

Related Topics

Frequently Asked Questions

References

1. National Institute of Allergy and Infectious Diseases (NIAID).
2. MedlinePlus, U.S. National Library of Medicine. Chronic granulomatous disease.
3. Immune Deficiency Foundation.
4. National Organization for Rare Disorders (NORD).