Chronic Granulomatous Disease

The genetic condition known as a chronic granulomatous disease (CGD) is brought on by malfunctions in the phagocyte, a kind of white blood cell that normally aids in the body's ability to fight infections. The phagocytes are unable to defend your body against bacterial and fungal infections as a result.

Infections in the lungs, skin, lymph nodes, liver, stomach, and intestines, among other places, can occur in people with a chronic granulomatous illness. Infected sites may also produce clumps of white blood cells. Most people with CGD receive their diagnosis while they are young, however, some people can wait until they are adults.

Chronic Granulomatous Disease: Causes

CGD can be brought on by a mutation in one of five genes. The gene mutation that causes CGD is inherited from a parent. The proteins that the genes typically make help build an enzyme that supports the healthy operation of your immune system. To defend you from infections, the enzyme is active in white blood cells called phagocytes that engulf and kill bacteria and fungi. Moreover, immunological cells that aid in your body's healing include the enzyme.

The protective proteins are either not created or are generated but fail to function correctly when one of these genes is mutated. Some CGD sufferers lack one of these gene alterations. Doctors are unsure of the reasons for the condition in these situations.

Chronic Granulomatous Disease: Symptoms

Every few years, people with chronic granulomatous illness will suffer a severe bacterial or fungal infection. Lung infections, such as pneumonia, are frequent. After being exposed to decaying leaves, mulch, or hay, people with CGD run the risk of developing a dangerous form of fungal pneumonia. Infections of the skin, liver, stomach, intestines, brain, and eyes are also frequent in those with CGD.

Infection-related symptoms and signs include −

  • Fever

  • Chest ache while breathing in or out

  • Enlarged and painful lymph nodes

  • An ongoing runny nose

  • Irritation of the skin that may result in a rash, edema, or redness.

  • Redness and swelling in your mouth

  • Digestive issues that may include nausea, vomiting, diarrhea, stomach discomfort, bloody stools, or a painful pus-filled pocket next to the anus.

Complications from CGD might include −

  • Less than 5% of all instances involve autoimmune illnesses, in which the body attacks its cells.

  • Gut abscesses and inflammation causing difficulty digesting meals

  • Growth slowdown

  • Colitis of the bowels (a disorder that involves bloody stool, diarrhea, stomach pain, and vomiting)

Chronic Granulomatous Disease: Risk Factors

A person is more likely to get CGD if they have a family member who does. It is often hereditary. It is less frequently caused by a spontaneous genetic mutation.

Chronic Granulomatous Disease: Diagnosis

Your doctor will examine you physically and go through your medical and family history to diagnose CGD. To identify CGD, your doctor may request several tests, such as −

  • Tests of neutrophil function. To determine how well a certain type of white blood cell (neutrophil) in your blood is operating, your doctor may use a dihydroergotamine 123 (DHR) test or another test. This test is typically used by doctors to identify CGD.

  • Genetic analysis. To establish the existence of a particular genetic mutation that causes chronic granulomatous disease, your doctor could ask for a genetic test.

  • Prenatal examination. If one of your children has already been diagnosed with CGD, doctors may use prenatal testing to make the diagnosis.

Chronic Granulomatous Disease: Treatment

The goal of CGD treatment is to manage your illness and assist you in preventing infections. Treatments might consist of −

  • Management of infections. To stop bacterial and fungal illnesses before they start, your doctor will take action. Itraconazole and trimethoprim and sulfamethoxazole are examples of continuous antibiotic treatment that may be used to treat fungal and bacterial infections, respectively. If an infection develops, further antibiotics or antifungal drugs may be required.

  • Interferon-gamma. Interferon-gamma injections may be given to you regularly, which might aid in boosting your immune system's ability to fight infections.

  • Transplanting of stem cells. A stem cell transplant may be able to cure CGD in some circumstances. The prognosis, the availability of donors, and the patient's personal preferences all play a role in the decision to use stem cell transplantation as a treatment.

Although corticosteroids have typically been avoided in individuals with CGD and active infection, several findings suggest that steroids may be utilized to treat hyperactive inflammation when combined with the proper antimicrobials.

Around one-third of CGD patients get liver abscesses, which are frequently recurring. Since they are thick, caseous, and challenging to drain, liver abscesses usually need to be surgically treated. Nevertheless, the use of corticosteroids resulted in the effective clearance of liver abscesses without the need for surgical intervention in a case series of nine patients at the NIH with Staphylococcal liver abscesses resistant to standard care.

The use of corticosteroids in the treatment of respiratory infections such as mulch pneumonitis and Nocardia pneumonia has also been demonstrated.

While infliximab therapy also produces quick improvements in CGD patients, it is also linked to higher rates of infection and mortality. TNF inhibitors should be rigorously avoided as a result. Salicylic acid derivatives, antimetabolites such as azathioprine, and 6-mercaptopurine are among the steroid-sparing medications used with varying degrees of efficacy.

Chronic Granulomatous Disease: Prevention

CGD cannot be avoided. The possibility of having a kid with the disorder should be discussed with a genetic counselor by anybody planning a family who has a history of the illness.


The emergence of azole antifungals, better awareness of CGD, and improved care of inflammatory and infectious consequences have all contributed to a more than threefold rise in the life expectancy of CGD patients over the past few decades. Nonetheless, triazole-resistant Aspergillus is becoming more common, and managing inflammatory side effects is still challenging.

Recent findings show that survival after HCT has grown from 85% before 2000 to more than 90%, and results have been positive independent of the donor source. Children who get HCT are healthier and have a higher quality of life than those who are treated conservatively. In light of this, HCT needs to be taken into account for all CGD patients, independent of sex, genetic mutation, or clinical symptoms. MAC seems to improve the chance of long-term myeloid engraftment and decrease the risk of graft failure.

While early HCT is preferred, patients who are adolescents or young adults, especially those with a history of severe infection and autoinflammation, may also be candidates for a definitive cure.

In the end, we anticipate a significant rise in overall life expectancy for individuals with CGD over the following few years as HCT becomes more widely accessible and better tolerated. Also, for patients without an HLA-matched donor, gene therapy may be a feasible option for allogeneic HCT with the development of novel SIN-lentiviral vectors and the improvement of conditioning regimens.

Dr. Durgesh Kumar Sinha
Dr. Durgesh Kumar Sinha


Updated on: 30-Mar-2023


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