Summary about Disease
Chronic Granulomatous Disease (CGD) is a rare genetic disorder that affects the immune system's ability to fight off bacterial and fungal infections. Individuals with CGD have phagocytes (a type of white blood cell) that can ingest but not kill certain microorganisms. This leads to the formation of granulomas (masses of immune cells) in various parts of the body and makes individuals susceptible to recurrent and severe infections.
Symptoms
Symptoms of CGD can vary in severity and can affect different parts of the body. Common symptoms include:
Recurrent bacterial and fungal infections, especially in the lungs, skin, lymph nodes, liver, and bones.
Granuloma formation, which can cause inflammation and tissue damage.
Abscesses.
Pneumonia.
Lymphadenitis (inflammation of the lymph nodes).
Skin rashes or lesions.
Gastrointestinal problems, such as diarrhea and abdominal pain.
Delayed growth.
Fever of unknown origin.
Causes
CGD is caused by genetic mutations that affect the function of NADPH oxidase, an enzyme complex critical for the production of reactive oxygen species (ROS) within phagocytes. ROS are essential for killing ingested microorganisms. Most cases are caused by mutations in the CYBB gene on the X chromosome (X-linked recessive inheritance), which primarily affects males. Other mutations can occur in autosomal recessive genes (*CYBA*, *NCF1*, *NCF2*, *NCF4*), affecting both males and females.
Medicine Used
Treatment for CGD typically involves a combination of preventative and therapeutic measures:
Antibiotics: To treat and prevent bacterial infections. Common antibiotics include trimethoprim-sulfamethoxazole (Bactrim) or other broad-spectrum antibiotics.
Antifungals: To treat and prevent fungal infections. Common antifungals include itraconazole, voriconazole, or posaconazole.
Interferon Gamma: This medication helps to boost the immune system's function and reduce the frequency and severity of infections.
Granulocyte Colony-Stimulating Factor (G-CSF): In some cases, G-CSF may be used to increase the number of neutrophils.
Stem Cell Transplant (Hematopoietic Stem Cell Transplantation): This is the only curative treatment for CGD. It involves replacing the patient's defective immune system with healthy stem cells from a donor.
Gene Therapy: Experimental treatments are being researched.
Is Communicable
CGD is not communicable. It is a genetic disorder and cannot be spread from person to person. Infections that individuals with CGD acquire can be communicable, but CGD itself is not.
Precautions
Individuals with CGD need to take several precautions to minimize their risk of infection:
Maintain Good Hygiene: Frequent hand washing, proper wound care, and good dental hygiene are essential.
Avoid Exposure to Mold and Fungi: Stay away from environments with high mold or fungal counts, such as decaying vegetation, construction sites, and damp areas.
Vaccinations: Follow recommended vaccination schedules, but live vaccines may be contraindicated. Consult with a physician.
Prophylactic Medications: Take prescribed antibiotics and antifungals as directed to prevent infections.
Avoid Cat Litter Boxes and Compost: These can harbor fungi and other pathogens.
Water source: Consider distilled water for susceptible individuals.
How long does an outbreak last?
The duration of an infection or inflammatory outbreak in a person with CGD can vary widely depending on the specific infection, its severity, the location of the infection, and how quickly treatment is initiated and effective. Infections can last for several weeks or even months if not treated promptly or if resistant organisms are involved. Granulomas can persist for extended periods and may require ongoing management.
How is it diagnosed?
CGD is typically diagnosed through a combination of clinical evaluation and laboratory tests:
Nitroblue Tetrazolium (NBT) Test: A traditional test that measures the ability of neutrophils to produce superoxide. Reduced NBT reduction indicates CGD.
Dihydrorhodamine (DHR) Assay: A more sensitive and specific flow cytometry-based test that measures NADPH oxidase activity in neutrophils. This is the preferred diagnostic test.
Genetic Testing: Can identify the specific gene mutation responsible for CGD.
Complete Blood Count (CBC): May show elevated white blood cell counts, particularly neutrophils, during an infection.
Imaging Studies: X-rays, CT scans, or MRI may be used to identify infections or granulomas in various organs.
Timeline of Symptoms
The timeline of symptoms in CGD can vary significantly from person to person. Some individuals may present with symptoms in early infancy, while others may not be diagnosed until later in childhood or even adulthood.
Early Infancy/Childhood: Recurrent skin infections (abscesses, cellulitis), pneumonia, lymph node infections, failure to thrive.
Later Childhood/Adolescence/Adulthood: Liver abscesses, osteomyelitis, colitis, granuloma formation, fungal infections.
Throughout Life: Increased susceptibility to specific bacterial (e.g., Staphylococcus aureus, *Burkholderia cepacia* complex, *Serratia marcescens*) and fungal (e.g., *Aspergillus*) infections.
Important Considerations
Early Diagnosis is Crucial: Prompt diagnosis and treatment are essential to prevent severe infections and improve long-term outcomes.
Lifelong Management: CGD requires lifelong monitoring and management by a healthcare team experienced in immunodeficiency disorders.
Genetic Counseling: Genetic counseling is recommended for families with a history of CGD to assess the risk of recurrence in future pregnancies.
Psychosocial Support: Living with a chronic illness like CGD can be challenging. Psychosocial support and resources are important for both the individual and their family.
Infection Prevention: Strict adherence to infection prevention measures is crucial to minimize the risk of infections.
Awareness: Patients should wear a medical alert bracelet/necklace to indicate their condition to healthcare providers in emergency situations.
Consult specialists: Regular consultations with immunologists and other specialists are vital.