Chronic Granulomatous Disease h1 >
What is Chronic Granulomatous Disease (CGD)?
Chronic Granulomatous Disease (CGD) is an inherited condition characterized by a defect of specific white blood cells called neutrophils. Neutrophils are important for the killing of bacterial and fungal infections. In CGD, the neutrophils are unable to make the hydrogen peroxide needed to kill bacteria and fungi. Patient with CGD are, therefore, highly susceptible to infections from certain bacterial and fungal organisms. Patients with CGD have normal immunity to other microbes, including viruses. As a result, patients with CGD have normal immunity against common infections like the common cold or stomach flu (the majority of which are caused by viruses).
Children with CGD are usually healthy at birth; however, they typically develop serious bacterial and fungal infections in early childhood that are difficult to treat. Patients may have severe or frequent infections including:
- Bacterial ear infections, pneumonia, or blood infections
- Bone infections
- Skin or liver abscesses
- Fungal pneumonia
Individuals with CGD can also develop a number of complications that are related to the immune system trying (ineffectively) to deal with bacterial and fungal infections. Large numbers of inflammatory cells (neutrophils and macrophages that do not work) can “clump” together into larger masses known as granulomas. This is why the condition is known as Chronic Granulomatous Disease. These granulomas are not effective at killing bacteria and fungi, become long-standing and can last for months to years, and can cause problems for patients with CGD. These complications are often known as the “inflammatory” complications of CGD. Problems can include:
- Persistent vomiting from granulomas obstructing the ability of the stomach to empty.
- Difficulty voiding (peeing), often with pain, because of granulomas obstructing the outflow from the bladder. Sometimes, granulomas develop in the ureters. Both of these situations can lead to a backflow of urine into the kidneys (hydronephrosis) which over time can lead to kidney problems if not dealt with.
- Mouth sores from small granulomas in the mouth.
- Severe diarrhea and weight loss due to granulomatous colitis. This can look very similar to a patient with Crohn’s disease (a type of inflammatory bowel disease).
Who gets CGD?
CGD can affect either boys or girls of any race or ethnicity. Defects in each of five distinct genes have been reported to result in CGD. The most common form (about 80% of cases) occurs in boys and is inherited as an X-linked disease, meaning that females may carry the abnormal gene for the disorder but don’t develop symptoms, whereas boys develop the clinical problems associated with the disease. The other four forms of CGD are inherited as an autosomal recessive disorder, meaning that the patient has one defective gene inherited from each parent. CGD is estimated to occur in approximately 1 out of every 250,000 live births. The average age at diagnosis is 3 years for boys and 7 years for girls.
How is CGD Diagnosed?
Frequent respiratory and skin infections suggest the possibility of CGD, especially if the infections are caused by certain bacteria or fungi, such as Serratia and Aspergillus. Definitive diagnosis of CGD is made by testing the production of hydrogen peroxide by neutrophils, and is confirmed by gene sequencing analysis to identify disease-causing mutations in any of the genes that are responsible for this condition.
What is the treatment for CGD?
Treatment for CGD may include the following:
- Medications: Medications should be prescribed to both prevent and treat bacterial and fungal infections. Standard of care includes the use of an antibiotic known as trimethoprim-sulfamethoxazole (also known as co-trimoxazole, Septra) and an anti-fungal medication (common ones used include itraconazole, voriconazole, and posaconazole). These medications should be taken every day to prevent bacterial and fungal infections. Note that fluconazole, a common anti-fungal used to treat yeast infections, is not sufficient for anti-fungal prevention in patients with CGD.
- Despite the use of preventative medications, infections can still occur. Signs such as fevers, skin redness, cough, difficulty breathing, and extreme tiredness may signify an underlying infection and medical attention should be sought. Additional antibiotics and antifungals may be needed.
- Corticosteroids (steroids such as prednisone, methylprednisolone and dexamethasone) may be needed to treat the inflammatory / granulomatous complications of CGD, most notably the gastrointestinal disease (colitis).
- In addition, your doctor may recommend a medication known as interferon-gamma, although its use is not universal and some doctors will wait to prescribe this only in certain situations.
- Avoiding infection-causing substances - Since severe infections in CGD can be caused by organisms present in the environment, patients with CGD are often encouraged to avoid areas with visible mold, including places containing woods and mulch.
- Blood and Marrow Transplantation (BMT) - provides patients with CGD with a functioning immune system capable of protecting them from infections. BMT replaces the defective cells with normally functioning cells from a healthy donor. BMT has been effective in many patients, especially if done before major organ damage occurs and in the absence of active infection.
- Gene therapy to correct the genetic mutation in CGD is still in experimental stages and is still considered an investigational treatment option.
Frequently Asked Questions h2 >
Can patients with CGD have children?
Women with CGD can become pregnant and have babies without adverse effects to their health. Some of the drugs used to treat the infections common in patients with CGD can be passed from a pregnant woman to her baby, and may cause birth defects or miscarriage. However, there are alternatives that are safe to use in pregnancy. Women with CGD should discuss plans for alternative medication with her doctor prior to becoming pregnant.
How likely are patients with CGD to have children with CGD?
The chance a parent who is affected by CGD will transmit CGD to their own children varies considerably with the type of CGD involved (X linked or autosomal recessive) as well as the sex of the parent.
Men with x-linked CGD have a 100% chance of having a baby girl who is a carrier of CGD (i.e. not affected by CGD, but the baby girl could pass the gene on to her sons or daughters with the next generation). A man with x-linked CGD will not have a girl affected by CGD, unless in the rare situation that the mother is also a carrier for x-linked CGD. Since CGD is a rare condition, it would be unusual for a mother to be a carrier and a father to have x-linked CGD. A man with x-linked CGD will not transmit the gene to any of his baby boys.
Men and women with autosomal recessive CGD have a 100% chance of their baby boys and girls being at least carriers. As long as the other parent (1) is not affected by CGD and (2) is not a carrier for the same genetic mutation, the children will not be affected by CGD (although all will be carriers). If the other partner is also a carrier for autosomal recessive CGD, there is a 50% chance the child (regardless of whether a boy or a girl) will be affected by CGD and a 50% chance the child will be a carrier. If the other partner also has two genetic mutations resulting in autosomal recessive CGD, then 100% of the offspring will be affected by CGD.
For women who are carriers of x-linked CGD (often this is tested for in a woman because a brother or uncle was affected by x-linked CGD), 50% of her girls will be carriers and 50% of her girls will not be carriers. None of the mother’s baby girls will be affected by CGD. However, 50% of her boys will be affected with CGD.
Autosomal recessive CGD is more common in populations where partnerships between men and women are more closely related from a genetic perspective, such as in cultures where marriage between close relatives is customary. Sometimes children can also be born with CGD where it is not apparent that a family history was present. In these situations, new mutations have arisen and these children will have the same risks of transmitting the gene to their own offspring in the future.
Do carriers of CGD experience any medical problems?
Mothers of males with CGD may be carriers of the X-linked form of CGD. Carrier status can be determined by a blood test. Often carrier mothers are healthy, although in some cases they may be prone to recurrent mouth ulcers or skin disorders.
What types of infections are common in CGD?
- Frequent and difficult-to-clear skin infections, such as abscesses, chronic nasal infection, boils, eczema, and impetigo
- Joint infections
How often do these infections occur?
These infections occur often, and may be difficult to heal.
How does CGD affect a person’s quality of life?
Many people with CGD can carry on normal daily activities. Patients and their families should expect, and be prepared for, frequent and sometimes long stays in the hospital that may interfere with school or work.
Can CGD affect the growth and development of children?
Some children with CGD may grow and develop more slowly than peers. There is, also, the possibility that children who have received prolonged courses of steroids or who have been very ill for a long time, may not reach the their full height when they get older. Consulting an endocrinologist (doctor who specializes in growth and the way hormones work) may be appropriate.
What about the emotional strain that CGD places on patients and their families?
Frequent episodes of being ill, serious infections, and prolonged hospital admissions may be stressful for patients and their families. Patients with CGD and their families may benefit from working with a social worker or a clinical psychologist for support.