Chronic Granulomatous Disease – How to Live Well: A Comprehensive Guide [Causes, 4 Symptoms, and Treatment]

Chronic granulomatous disease, also known as Bridges – Good syndrome and Quie syndrome is a hereditary disease that occurs when certain cells of the immune system encounter difficulties in forming reactive oxygen compounds (especially radical superoxide) due to damage to phagocytes, when such reactive compounds are needed to kill pathogens. Consequently, Granulomatous is formed in many organs.

Chronic granulomatous disease (CGD) is a rare genetic disorder that affects the immune system and makes it harder to fight off infections. People with CGD are more prone to getting serious and recurrent infections from bacteria and fungi that are usually harmless to others.

These infections can affect various parts of the body, such as the lungs, skin, lymph nodes, liver, and digestive tract.

CGD can also cause inflammation and granulomas, which are clumps of immune cells that form in response to infection. CGD can be diagnosed at any age, but most cases are detected in childhood. CGD has no cure, but with proper treatment and care, people with CGD can live long and fulfilling lives.

People with chronic granulomatous disease are often infected with pneumonia, lung infections, dermatitis, infection of the lymph nodes, liver infections, gastrointestinal inflammation or other infections. They are more at risk of developing a group of white blood cells (masses) in infected areas (granulomas).

Most people are diagnosed with CGD in childhood, but in some people this condition may not be diagnosed until adulthood

The disease affects approximately 1 in 200,000 people in the United States, with about 20 cases recorded annually. 

The disease was first discovered in 1950 on the four sons of Minnesota. The mechanism that resulted in the disease was discovered in 1967. Bernard Babior had contributed to the efforts to discover the cause of the disease with damage to the superoxide production process in white blood cells.

Harmful infections can lead to premature death. The frequent causes of death in this disease are recurrent lung infections. Preventive and treatment can reduce the risk of infection and control temporary infections.

Chronic Granulomatous Disease in children

Chronic Granulomatous disease is a type of primary immune deficiency disease, in which a group of white blood cells called neutrophils, fails to form hydrogen peroxide which is required to fight bacterial and fungal infections in the body

This disease is classified as not contagious and caused by hereditary or genetic factors. Those who are affected by this disease will experience repeated infection attacks due to decreased immune system capacity to resist disease-causing organisms.

What causes CGD and how is it inherited?

More than 50% of cases of chronic granulomatous disease are inherited and are mostly in males. In chronic granulomatous disease, white blood cells do not produce an active substance that makes it unable to kill bacteria and fungi as it should.

CGD is caused by mutations in one of five genes that code for proteins that make up an enzyme called phagocyte NADPH oxidase. This enzyme is essential for the function of phagocytes, which are white blood cells that engulf and kill microbes.

When the enzyme is defective, phagocytes cannot produce enough reactive oxygen species, which are chemicals that destroy the microbes. As a result, phagocytes cannot clear the infection effectively and may release inflammatory substances that cause tissue damage and granuloma formation.

Depending on which gene is mutated, CGD can be inherited in two ways: X-linked or autosomal recessive. X-linked CGD is the most common form, affecting about 70% of cases. It is caused by mutations in the CYBB gene, which is located on the X chromosome.

Males have only one X chromosome, so if they inherit a mutated CYBB gene from their mother, they will have X-linked CGD. Females have two X chromosomes, so if they inherit one mutated CYBB gene from either parent, they will be carriers of X-linked CGD. Carriers usually do not have symptoms, but they can pass on the mutation to their children.

Autosomal recessive CGD is caused by mutations in any of the other four genes: NCF1, NCF2, NCF4, or CYBA. These genes are located on the autosomes, which are the non-sex chromosomes. Both males and females have two copies of each autosomal gene, one from each parent.

If they inherit two mutated copies of the same gene, they will have autosomal recessive CGD. If they inherit one mutated copy and one normal copy, they will be carriers of autosomal recessive CGD. Carriers usually do not have symptoms, but they can pass on the mutation to their children.

Chronic Granulomatous Disease Symptoms & Complications

Chronic granulomatous disease usually begins with the emergence of recurrent abscesses during children, but symptoms can also occur during adolescence. Infection by certain organisms can even lead to death.

Multiple granulomatous lesions may appear in the lungs, liver, lymph nodes, gastrointestinal tract, and urinary tract. Patients with the chronic granulomatous disease can experience obstacles in their growth.

The symptoms and complications of CGD vary depending on the type and location of the infection, the severity of the immune defect, and the age of the person. Some people with CGD may have mild or no symptoms, while others may have frequent and severe infections that require hospitalization. The most common symptoms and complications of CGD are:

Pneumonia

Pneumonia: an infection of the lungs that causes fever, cough, chest pain, and difficulty breathing. Pneumonia can be caused by bacteria such as Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia, or Nocardia, or fungi such as Aspergillus or Candida.

Skin and soft tissue infections

Infections of the skin, muscles, or connective tissues that cause redness, swelling, pain, and pus. Skin and soft tissue infections can be caused by bacteria such as Staphylococcus aureus, Serratia marcescens, or Nocardia, or fungi such as Aspergillus or Candida.

Lymphadenitis

Lymphadenitis: inflammation of the lymph nodes that causes swelling, tenderness, and fever. Lymphadenitis can be caused by bacteria such as Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia, or Nocardia, or fungi such as Aspergillus or Candida.

Liver abscess

Liver abscess: a collection of pus in the liver that causes fever, abdominal pain, jaundice, and weight loss. Liver abscess can be caused by bacteria such as Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia, or Nocardia, or fungi such as Aspergillus or Candida.

Gastrointestinal infections

Gastrointestinal infections: infections of the stomach, intestines, or colon that cause vomiting, diarrhea, abdominal pain, and blood in the stool. Gastrointestinal infections can be caused by bacteria such as Salmonella, Shigella, Campylobacter, or Listeria, or fungi such as Aspergillus or Candida.

Granulomas

Granulomas: clumps of immune cells that form in response to infection and cause inflammation and obstruction of the affected organ. Granulomas can occur in various parts of the body, such as the lungs, skin, lymph nodes, liver, spleen, kidneys, bladder, or genitals.

Granulomas can cause symptoms such as cough, chest pain, difficulty breathing, skin ulcers, urinary problems, or infertility.

Other infections

CGD can also increase the risk of other infections, such as meningitis, osteomyelitis, septic arthritis, endocarditis, or sepsis. These infections can be life-threatening and require prompt medical attention.

Some other symptoms that can be found in chronic granulomatous disease:

• Infections of the bones and joints
• Skin infections that are often occurring and difficult to heal, e.g. Abscesses
• Sedentary diarrhea.

Diagnosis of chronic Granulomatous disease

The doctor will ask about the symptoms and medical history, and perform a physical exam. Tests may include the following:

Studies of liquids and tissues, with use:

• Biopsy
• General blood analysis;
• The flow of cytometry using dihydrorhodamine blood test, where the presence of determining chemical phagocytes, which can kill bacteria;
• Levels of erythrocyte sedimentation (ESR) to determine the presence of inflammation;

Images can form within the body structure, where the following methods:

• Chest X-ray;
• Bone scan;
• Scanning the liver.

Life expectancy and prognosis

The individual life expectancy with CGD is slightly reduced due to repeated episodes of infection and inflammation. However, if people with CGD have the right treatment, most will live until the mid to late adulthood.

Treatment options

The treatment of CGD aims to prevent and treat infections, reduce inflammation and granuloma formation, and improve the quality of life of the person. The main components of the treatment are:

Antibiotics and antifungals

These medications are used to prevent and treat bacterial and fungal infections. People with CGD may need to take them daily or intermittently, depending on their risk of infection and their doctor’s advice. Some of the common antibiotics and antifungals used for CGD are penicillin, sulfamethoxazole, itraconazole, and voriconazole.

Interferon gamma

This is a type of protein that enhances the function of the immune system and helps fight infections. People with CGD may need to inject themselves with interferon gamma three times a week, under the supervision of their doctor.

Interferon gamma can reduce the frequency and severity of infections and granulomas, but it can also cause side effects such as fever, headache, fatigue, and bone pain.

Stem cell transplantation

This is a procedure that replaces the defective immune cells with healthy ones from a donor. Stem cell transplantation can cure CGD, but it is a risky and complex procedure that requires a compatible donor and a specialized center.

Stem cell transplantation can cause complications such as graft-versus-host disease, infection, bleeding, and organ damage. Stem cell transplantation is usually reserved for people with severe or life-threatening CGD who do not respond to other treatments.

Bone marrow transplantation

Bone marrow transplantation is another treatment option for some people with severe CGD symptoms. Bone marrow transplantation can cure CGD. However, the therapy is very complex, and the transplant candidates and donors should be carefully selected.

How can you prevent and manage infections with CGD?

People with CGD can take some measures to prevent and manage infections and reduce their impact on their health and well-being. Some of the preventive and management strategies are:

Follow the prescribed medication regimen

Taking antibiotics, antifungals, and interferon gamma as prescribed can help prevent and treat infections and reduce the risk of complications. It is important to follow the instructions of the doctor and pharmacist, and to report any side effects or concerns.

Avoid exposure to infection sources

People with CGD should avoid contact with people who are sick or have symptoms of infection, such as fever, cough, or rash.

They should also avoid exposure to environments or substances that may contain harmful microbes, such as soil, dust, mold, hay, mulch, compost, animal feces, or raw or undercooked food. They should wash their hands frequently and practice good hygiene and sanitation.

• Avoid using mulch while gardening. Exposed mulch gardens can cause a life-threatening form of pneumonia Aspergillus infection.
• Avoid swimming in water other than ponds containing chlorine. Freshwater or salted water can contain organisms that, although safe for healthy people, it can cause infections in people with CGD.
• Changing piles of compost, repotting plants, and clearing warehouses are another activity that should be avoided by people with CGD.

Seek medical attention promptly

People with CGD should seek medical attention as soon as they notice any signs or symptoms of infection, such as fever, pain, swelling, redness, pus, or difficulty breathing. They should inform their doctor that they have CGD and what medications they are taking. They should also carry a medical alert card or bracelet that identifies their condition and their treatment.

Get vaccinated

People with CGD should get vaccinated against common infectious diseases, such as influenza, pneumococcal, meningococcal, and hepatitis B.

However, they should avoid live vaccines, such as measles, mumps, rubella, varicella, and oral polio, as they may cause serious infections in people with CGD. They should consult their doctor before getting any vaccine and follow the recommended immunization schedule.

How can you cope with the emotional and social aspects of CGD?

CGD can affect not only the physical health, but also the emotional and social well-being of the person and their family. People with CGD may experience feelings of fear, anxiety, anger, sadness, guilt, or isolation due to their condition and its impact on their daily life.

They may also face challenges in their relationships, education, work, or hobbies due to their frequent infections and hospitalizations. Therefore, it is important to cope with the emotional and social aspects of CGD and seek support when needed. Some of the coping and support strategies are:

Seek professional help

People with CGD may benefit from counseling or therapy to help them deal with their emotions and stress. They may also need medication to treat depression, anxiety, or other mental health issues. They should consult their doctor or a mental health professional for advice and referral.

Join a support group

People with CGD may find comfort and encouragement from joining a support group of people who have the same or similar condition. They can share their experiences, feelings, tips, and resources with each other. They can also learn from the experts and advocates who may visit the support group.

They can find a support group online or in their local area through organizations such as the Immune Deficiency Foundation or the Chronic Granulomatous Disease Association.

Educate yourself and others

People with CGD may feel more empowered and confident if they educate themselves and others about their condition and its management.

They can learn more about CGD from reliable sources, such as their doctor, their genetic counselor, or reputable websites and books. They can also educate their family, friends, teachers, employers, or others who are involved in their life about CGD and how they can support them.

Maintain a positive outlook

People with CGD may cope better if they maintain a positive outlook and focus on their strengths and achievements. They can practice gratitude, optimism, and resilience, and celebrate their milestones and successes. They can also find joy and meaning in their hobbies, interests, and passions, and pursue their goals and dreams.

Seek social support

People with CGD may cope better if they seek social support from their family, friends, or others who care about them. They can communicate their needs and feelings, and ask for help when they need it.

They can also spend quality time with their loved ones, and enjoy their company and activities. They can also make new friends or join new communities that share their interests or values.

FAQ

Here are some frequently asked questions and answers about CGD: