Materiały źródłowe

• #1 Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

  https://www.mdpi.com/2077-0383/13/15/4435

  Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. […] Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. […] We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. […] Like many inborn errors of immunity (IEI), early diagnosis of CGD is important for several reasons, which together support optimal clinical outcomes: (1) early instigation of effective preventative care, (2) appropriate and tailored management of acute infections and complications, (3) early definitive treatment, and (4) early identification of affected family members.

• #2 Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/chronic-granulomatous-disease-pathogenesis-clinical-manifestations-and-diagnosis

  Chronic granulomatous disease (CGD) is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. […] The diagnosis is made by neutrophil function testing for superoxide production (nitroblue tetrazolium reduction or dihydrorhodamine [DHR] 123 flow cytometry assay). […] The exact molecular defect is determined by genotyping. […] Diagnosis may also be delayed because of newer, potent antimicrobials that inadvertently treat many CGD-associated infections, postponing diagnosis until more severe infections indicate CGD as the underlying cause.

• #3 Chronic Granulomatous Disease: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1116022-overview

  Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any of the five subunits of the NADPH oxidase complex responsible for the respiratory burst in phagocytic leukocytes. […] The implementation of routine antimicrobial prophylaxis and the advent of azole antifungals has considerably improved overall survival. […] The main defect in chronic granulomatous disease (CGD) is a failure of neutrophils, monocytes, macrophages, and eosinophils to mount a respiratory burst and, therefore, to generate superoxide anions and other reactive oxygen species derived from superoxide, such as hydrogen peroxide. […] This renders the patients susceptible to severe, recurrent bacterial and fungal infections. […] To prevent infections, chronic granulomatous disease (CGD) patients should receive lifelong antibiotics and antifungal prophylaxis. […] Diagnostic Testing for Chronic Granulomatous Disease.

• #4 Chronic Granulomatous Disease (CGD) | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/childhood-chronic-granulomatous-disease

  How is CGD diagnosed in children? […] Chronic granulomatous disease (CGD) is an inherited immune system disorder that occurs when a type of white blood cell that usually helps the body fight infection, called a phagocyte, does not work properly. […] Rarely, and in milder forms of the disease, the diagnosis doesn’t become clear for years or decades.

• #5

• #6 CGD Association of America – Cgd Testing, Diagnosing Cgd, How to Diagnose Chronic Granulomatous Disease

  https://cgdaa.org/diagnosing-cgd

  Diagnosing CGD usually occurs in childhood. If there is a family history of CGD or a child has symptoms, doctors will test for Chronic Granulomatous Disease. […] Most people will have symptoms by the time they are three years old. Additionally, many of those affected by CGD will be diagnosed by age five. […] When testing and diagnosing for CGD, a doctor studies a sample of blood, skin, hair or saliva to identify if the faulty gene that causes CGD is present. […] The results of this genetic test can confirm if CGD is present in addition to the type of CGD present (e.g. X-linked, autosomal recessive). […] During a physical exam, doctors can look for inflammation and granulomas in order to diagnose CGD. […] Dihydrorhodamine 123 (DHR) tests for Chronic Granulomatous Disease can determine how well a type of white blood cell (neutrophil) in your blood is functioning. The results of the DHR test can determine the risk of infection, carrier status, and the type of CGD (autosomal recessive or X-linked). Knowing the level of risk for serious infections can be useful for helping to guide a treatment plan.

• #7 Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

  https://www.mdpi.com/2077-0383/13/15/4435

  CGD testing is indicated where there is history of repeated invasive bacterial or fungal infections typical for this disorder, tissue granulomas, inflammatory manifestations or complications, especially in the context of a suggestive family history or characteristic histologic or radiologic findings. […] The main differential diagnoses for CGD are disorders of recurrent severe or atypical infection, granulomas and hyperinflammation, including cystic fibrosis, severe G6PD deficiency, glutathione synthetase deficiency, protein kinase C delta deficiency, leukocyte adhesion deficiency, combined or common variable immunodeficiency, MyD88/IRAK4 deficiency, hyper-IgE syndrome, allergic bronchopulmonary aspergillosis, sarcoidosis, IBD, MPO deficiency and SAPHO syndrome. […] Defective ROS production mediates the effect of genotype on phenotype in CGD, and diagnosis requires demonstration of a significantly impaired respiratory burst.

• #8 Chronic granulomatous disease

  https://dermnetnz.org/topics/chronic-granulomatous-disease

  Diagnosis of chronic granulomatous disease is based on patients signs and symptoms and history of specific recurrent infections. […] Tests used to diagnose chronic granulomatous disease include: Dihydrorhodamine reduction (DHR) […] Nitroblue tetrazolium. […] DHR is also known as the Neutrophil Oxidative Burst Measurement test. It assesses phagocyte production of hydrogen peroxide and other important chemicals. Nitroblue tetrazolium is not considered as accurate as DHR. After diagnosis, further testing is done to establish the genetic subtype.

• #9 Chronic Granulomatous Disease (CGD) – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/chronic-granulomatous-disease-cgd

  Chronic granulomatous disease is characterized by white blood cells that cannot produce activated oxygen compounds and by defects in phagocytic cell microbicidal function. […] Diagnosis is by assessing oxygen radical production in white blood cells via a flow cytometric oxidative burst assay. […] Diagnosis of chronic granulomatous disease is by a flow cytometric oxidative (respiratory) burst assay to detect oxygen radical production using dihydrorhodamine 123 (DHR) or nitroblue tetrazolium (NBT). This test can also identify female carriers of the X-linked form and recessive forms. […] Use the flow cytometric oxidative burst assay to diagnose CGD and identify carriers.

• #10 Diagnostic Testing for Chronic Granulomatous Disease – PubMed

  https://pubmed.ncbi.nlm.nih.gov/31172495/

  Chronic granulomatous disease (CGD) is a rare genetic immunodeficiency associated with recurrent bacterial infections, granulomas, and increased mortality. […] Diagnosis of patients with CGD is commonly based on the assessment of ROS production by neutrophils. […] Multiple assays to assess ROS production are described-a flow cytometric dihydrorhodamine assay and a histochemical nitroblue tetrazolium assay, both of which can be used to visualize ROS production in individual cells, and two quantitative assays-O2- reduction of ferricytochrome c and a ROS-dependent, luminol-enhanced chemiluminescence assay that will quantitate the response of a population of cells. […] When determining the status of a patient, several assays should be used to assess ROS production and identify the protein defect. […] The results of these assays should agree and can be used to develop a comprehensive package, which includes confirmation of a diagnosis of CGD, identification of the specific protein target for genetic sequencing, and an indication of the prognosis for the patient.

• #11 DHR Test for CGD: Efficient Testing in CGD Diagnosis – For HCPs

  https://www.cgdpathways.com/testing/test-for-chronic-granulomatous-disease

  Previously, the nitroblue tetrazolium (NBT) test was the recognized diagnostic test for CGD. Relying on light microscopy, the NBT test relies on a subjective analysis of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. […] The dihydrorhodamine (DHR) test is the most common test for identifying CGD. While some physicians still use the NBT test, it has been largely replaced by the flow cytometric DHR test. […] The DHR test has largely replaced the NBT test to diagnose CGD. […] Testing may help identify patients before a serious infection occurs. […] X-linked carriers, who are often diagnosed after a diagnosis of a relative with X-linked CGD, must be identified early to prevent disease progression and poor outcomes. […] An X-linked carrier with a DHR level under 20% is at increased risk of infection. […] An X-linked carrier with a DHR level under 10% is highly associated with infection. […] Symptomatic autoimmunity does not correlate with DHR levels, but is associated with the carrier state.

• #12 Diagnosis of Chronic Granulomatous Disease (CGD)

  https://www.medindia.net/health/conditions/chronic-granulomatous-disease-diagnosis.htm

  Dihydro rhodamine (DHR) test is perhaps the most accurate diagnostic test for Chronic Granulomatous Disease (CGD). […] Nitroblue tetrazolium (NBT) test – is the most widely-known test for chronic granulomatous disease. Normal white blood cells turn blue when NBT is added as they make special oxygen compounds that kills bacteria. […] In CGD, as we already discussed in previous section, production of oxidants is scarce, hence the colour change does not occur. In short NBT is negative (no colour change) in CGD patients. It is a visual test and is prone to errors (subjective ones). […] Dihydro rhodamine (DHR) Test – is perhaps the most accurate diagnostic test for chronic granulomatous disease. Though similar to NBT test, it is associated with fewer errors and is more reliable. […] Genetic testing – is of great value in identifying genetic mutations, establishing genetic inheritance patterns. It also aids family counselling.

• #13 Diagnosis – CGDSociety

  https://cgdsociety.org/about-cgd/diagnosis/

  Doctors usually diagnose CGD in childhood. […] If a child has a family history of CGD, doctors will use a blood test to check for the condition. […] The DHR (dihydrorhodamine) (flow cytometry test) and NBT (nitroblue tetrazolium) tests are used to diagnose CGD. […] Once CGD is diagnosed, doctors may need to do further x-rays, blood and urine tests, depending on the persons symptoms. […] The faulty gene can also be defined by using a genetic test that analyses a persons DNA and looks for changes in the genes coding for the enzyme NADPH oxidase. […] Its vital that people with CGD have regular blood tests so any problems can be found and treated early.

• #14 Chronic Granulomatous Disease Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1116022-workup

  Laboratory diagnosis of chronic granulomatous disease (CGD) can be made using the NBT test, stimulated with substances such as phorbol myristate acetate or Escherichia coli lipopolysaccharide, which promote an oxidative response in 90-100% of normal neutrophils. […] Neutrophils in patients with chronic granulomatous disease are unable to reduce oxidized NBT to insoluble blue formazan; this principle forms the basis of the standard diagnostic screening test for chronic granulomatous disease. […] This test is best used to identify gene carriers, and it has been used for the prenatal diagnosis of chronic granulomatous disease. […] This test can also be used to diagnose chronic granulomatous disease. The principles are the same as for the NBT dye test, but a different dye is used. Additionally, X-linked carrier status can also be detected.

• #15 CGD Association of America – Cgd Testing, Diagnosing Cgd, How to Diagnose Chronic Granulomatous Disease

  https://cgdaa.org/diagnosing-cgd

  Nitroblue tetrazolium tests (NBT) can determine if immune cells are making substances that the body uses to fight infections. Normally, the white blood cells turn blue when NBT is added. This means that the cells should be able to kill bacteria and protect the person from infections. Please note that NBT tests can show an incorrect result and may miss mild cases of CGD.

• #16 Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/11/9/2233

  Initial diagnostic tests for CGD often rely on the various measurements of neutrophil superoxide production. […] The oldest laboratory test for CGD is the NBT test, often the primary screening test for CGD. […] Dihydrorhodamine (DHR) assay testing is often the test of choice in diagnosing CGD. […] The diagnosis of CGD based on positive abnormal neutrophil function testing should be followed by genetic testing for confirmation.

• #17 Diagnostic Testing for Chronic Granulomatous Disease – PubMed

  https://pubmed.ncbi.nlm.nih.gov/31172495/

  Chronic granulomatous disease (CGD) is a rare genetic immunodeficiency associated with recurrent bacterial infections, granulomas, and increased mortality. […] Diagnosis of patients with CGD is commonly based on the assessment of ROS production by neutrophils. […] Multiple assays to assess ROS production are described-a flow cytometric dihydrorhodamine assay and a histochemical nitroblue tetrazolium assay, both of which can be used to visualize ROS production in individual cells, and two quantitative assays-O2- reduction of ferricytochrome c and a ROS-dependent, luminol-enhanced chemiluminescence assay that will quantitate the response of a population of cells. […] When determining the status of a patient, several assays should be used to assess ROS production and identify the protein defect. […] The results of these assays should agree and can be used to develop a comprehensive package, which includes confirmation of a diagnosis of CGD, identification of the specific protein target for genetic sequencing, and an indication of the prognosis for the patient.

• #18

  https://step1.medbullets.com/immunology/105009/chronic-granulomatous-disease

  Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of phagocytes. […] Evaluation includes flow cytometry reduction of dihydrorhodamine, which is abnormal and can detect X-linked carrier status, but cannot differentiate oxidase-positive from oxidase-negative phagocyte subpopulations in CGD carriers. […] Nitroblue tetrazolium dye reduction test shows a negative finding if incubated leukocytes do not turn the plate blue. […] Cytochrome c reduction assay measures production of reactive oxygen species.

• #19 Orphanet: Diagnosis of Chronic Granulomatous Disease (Phagoburst test)

  https://www.orpha.net/en/diagnostic-tests/diagnostic/319198?country=&name=&mode=

  Diagnosis of Chronic Granulomatous Disease (Phagoburst test) […] Post-natal diagnosis […] List of diseases tested (1) Chronic granulomatous disease

• #20 Chronic granulomatous disease – Wikipedia

  https://en.wikipedia.org/wiki/Chronic_granulomatous_disease

  When chronic granulomatous disease (CGD) is suspected, neutrophil-function testing should be carried out, and positive findings should be confirmed by genotyping. […] Infections caused by the pathogens commonly associated with CGD should prompt functional or genetic screening; neonatal or early postnatal screening of potentially affected children is essential with a family history of CGD. […] Neutrophil function tests: These include nitroblue tetrazolium (NBT) reduction test, dihydrorhodamine (DHR) 123 test, direct measurement of superoxide production, cytochrome c reduction assay, and chemiluminescence. […] Genetic testing: Once CGD has been diagnosed based on abnormal neutrophil function tests, genetic testing should go next. […] Prenatal testing: It is particularly useful when a family member has already been diagnosed with CGD. This test may be performed by analysis of NADPH oxidase activity of neutrophils from fetal blood.

• #21 CGD Testing for Genetic Carriers | ACTIMMUNE® (Interferon gamma-1b) HCP

  https://www.actimmunehcp.com/chronic-granulomatous-disease/about-cgd/cgd-carrier-testing

  Genetic testing can confirm CGD and identify CGD type when CGD is suspected. Patients and their families may also benefit from genetic counseling to better understand CGD and genetic testing options. […] CGD is most commonly inherited in an X-linked mode, with the subunit gp91phox of NADPH oxidase being affected; all other CGD-related subunit deficiencies are inherited in an autosomal recessive mode. […] The data in the above table is from the 1980s and 1990s, which may not fully reflect current distributions based on improved diagnostic tests. […] ACTIMMUNE (Interferon gamma-1b) is indicated for reducing the frequency and severity of serious infections associated with chronic granulomatous disease.

• #22 Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

  https://www.mdpi.com/2077-0383/13/15/4435

  Most CGD cases exhibit a total lack of NADPH oxidase activity. […] However, functional assays, which provide quantitative information on residual enzymatic activity, are important for guiding prognosis, because of the well-recognised survival benefit conferred by residual oxidase function. […] Confirmation of a CGD diagnosis following positive functional testing is established by identifying a pathogenic variant in one of the CGD-related genes that encode or permit assembly or function of NADPH oxidase. […] Genetic testing methods generally include: (1) gene-targeted testing in single- or multi-gene panels performed by Sanger or next-generation sequencing (NGS) techniques; (2) comprehensive genomic testing, including whole exome (WES) and whole genome sequencing (WGS); (3) copy number variant (CNV) analysis, e.g., by multiplex ligation-dependent probe amplification (MLPA) or comparative genomic hybridisation (CGH) arrays; and (4) ancillary methods, e.g., single nucleotide variant (SNV) arrays, mRNA size and sequence analysis, deep amplicon sequencing, and optical gene mapping.

• #23 Chronic granulomatous disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/chronic-granulomatous-disease/

  Chronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. […] Individuals with chronic granulomatous disease may have recurrent bacterial and fungal infections. […] People with chronic granulomatous disease typically have at least one serious bacterial or fungal infection every 3 to 4 years. […] Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown. […] When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. […] When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. […] Genetic Testing Registry: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 […] Genetic Testing Registry: Granulomatous disease, chronic, X-linked […] Molecular diagnosis of chronic granulomatous disease.

• #24 Chronic Granulomatous Disease: The European Experience | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005234

  CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. […] The diagnosis of CGD was established in all 429 patients by means of several well-described diagnostic tests, such as the nitroblue tetrazolium assay (NBT) or the dihydrorhodamine-1,2,3 (DHR) test. […] In the majority of patients, the diagnosis was confirmed by Western blot, showing the absence of one of the NADPH oxidase components, and DNA analysis on blood samples of the patient or his relatives. […] Determination of the CGD subtype was also performed by means of Western blot and/or DNA analysis. […] Of female patients in which the diagnosis CGD had been established by adequate laboratory analysis, but the subtype had not been established by Western blot or DNA sequencing, it was assumed they were suffering from an autosomal recessive form of the disease (20 cases). […] In 17 male patients, the exact subtype of CGD was not established, but either the presence of gp91phox was shown by Western blot, or the family history strongly suggested an autosomal recessive mode of inheritance.

• #25 Chronic granulomatous disease – Wikipedia

  https://en.wikipedia.org/wiki/Chronic_granulomatous_disease

  When chronic granulomatous disease (CGD) is suspected, neutrophil-function testing should be carried out, and positive findings should be confirmed by genotyping. […] Infections caused by the pathogens commonly associated with CGD should prompt functional or genetic screening; neonatal or early postnatal screening of potentially affected children is essential with a family history of CGD. […] Neutrophil function tests: These include nitroblue tetrazolium (NBT) reduction test, dihydrorhodamine (DHR) 123 test, direct measurement of superoxide production, cytochrome c reduction assay, and chemiluminescence. […] Genetic testing: Once CGD has been diagnosed based on abnormal neutrophil function tests, genetic testing should go next. […] Prenatal testing: It is particularly useful when a family member has already been diagnosed with CGD. This test may be performed by analysis of NADPH oxidase activity of neutrophils from fetal blood.

• #26 Chronic granulomatous disease – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/chronic-granulomatous-disease/diagnosis-treatment/drc-20355818

  To diagnose CGD, a healthcare professional will review a family and medical history and do a physical exam. There are several tests used to diagnose CGD, including: […] A healthcare professional may do a dihydrorhodamine 123 (DHR) test or other tests to see how well a type of white blood cell, called a neutrophil, is functioning. This test is commonly used to diagnose CGD. […] A genetic test can confirm the presence of a specific genetic alteration that results in chronic granulomatous disease. […] A healthcare professional may do prenatal testing to diagnose CGD if one of your children already has been diagnosed with CGD.

• #27 Chronic Granulomatous Disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/chronic-granulomatous-disease

  Additional tests such as X-rays, blood and urine tests may be performed, depending on the child’s symptoms, to guide symptomatic treatment. […] We’ll also perform baseline blood tests while the child is feeling healthy so we can compare results when your child becomes ill. Regular blood tests are vitally important for children with chronic granulomatous disease because they often identify problems before symptoms arise and CGD can be treated early.

• #28 Chronic Granulomatous Disease Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1116022-workup

  Peripheral blood leukocytosis (8.5 X 103/L) is a characteristic finding that reflects increased numbers of circulating neutrophils. […] Culture and sensitivity studies may be helpful. Bacteria isolated from lesions in patients with chronic granulomatous disease are usually catalase positive. […] Levels of the three major classes of immunoglobulins, immunoglobulin G, immunoglobulin M, and immunoglobulin A, are increased. Immunoglobulin E levels are increased or in the reference range. […] Skin biopsy is important in correctly diagnosing chronic granulomatous disease. […] Chronic granulomatous disease (CGD) is histologically characterized by a mixed suppurative and granulomatous inflammation. A typical feature of visceral granulomas is the presence of golden-brown pigmented histiocytes.

• #29 Chronic Granulomatous Disease Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1116022-workup

  Periodic acid-Schiff (PAS) staining demonstrates the presence of carbohydrates, particularly polysaccharides such as mucoproteins. These substances stain reddish purple with the PAS reaction. […] Electron microscopic findings suggest that the pigment represents lipofuscin bodies and appears to be derived from lysosomes. Granulomas consist of neutrophils and macrophages that contain yellow inclusions with areas of necrosis.

• #30 Chronic granulomatous disease – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/703

  Risk factors include family history of CGD, age 5 years, male sex, abnormally skewed X chromosome inactivation in X-linked carriers, and myeloperoxidase and FCgammaRIIIb polymorphisms. […] 1st investigations to order include FBC, ESR, CRP, faecal calprotectin, CT chest, CT or ultrasound for active infection, whole body PET scan with F-18 fluorodeoxyglucose (FDG), MRI scan, colonoscopy, pulmonary function tests, nitroblue tetrazolium test (NBT), and dihydrorhodamine (DHR) 123 test. […] Investigations to consider include genetic sequencing for genes encoding NADPH oxidase components, Western blotting, and flow cytometric analysis of individual NADPH oxidase components.

• #31 Chronic granulomatous disease (CGD) and other phagocytic cell disorders | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/chronic-granulomatous-disease-cgd-and-other

  If you suspect CGD, it is important that you talk to your doctor. […] Your doctor should consult or refer you to a specialist if they are unfamiliar with primary immunodeficiencies such as CGD. […] The most accurate test for chronic granulomatous disease (CGD) measures hydrogen peroxide in phagocytes using a chemical called dihydrorhodamine. The test is called dihydrorhodamine reduction or DHR. […] There are other types of tests still used to diagnose CGD, such as the Nitroblue Tetrazolium (NBT) slide test. […] Once the diagnosis of CGD is made, it is useful to confirm the genetic sub-type of CGD for genetic counseling because some types of CGD need bone marrow.

• #32 Chronic Granulomatous Disease (CGD) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/chronic-granulomatous-disease-cgd

  Most children with CGD are diagnosed by age 5. […] Chronic granulomatous disease (CGD) is diagnosed through: […] Neutrophil function tests to determine how well these white blood cells are functioning. […] Dihydrorhodamine reduction test. […] Genetic testing to confirm the presence of a specific gene mutation that results in CGD. […] After all tests are completed, doctors will be able to outline the best treatment options.

• #33 Chronic granulomatous disease – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/703

  Other diagnostic factors include fatigue, diarrhea, abdominal pain, cough, anorexia, arthralgias, nausea and vomiting, bloody urine, abnormal urinary flow, hepatosplenomegaly, family history of discoid lupus, oral ulcer, and skin rash. […] 1st tests to order include CBC, ESR, CRP, fecal calprotectin, CT chest, CT or ultrasound for active infection, whole body PET scan with F-18 fluorodeoxyglucose (FDG), MRI scan, colonoscopy, pulmonary function tests, nitroblue tetrazolium test (NBT), and dihydrorhodamine (DHR) 123 test. […] Tests to consider include genetic sequencing for genes encoding NADPH oxidase components, Western blotting, and flow cytometric analysis of individual NADPH oxidase components.

• #34 Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

  https://www.mdpi.com/2077-0383/13/15/4435

  CGD testing is indicated where there is history of repeated invasive bacterial or fungal infections typical for this disorder, tissue granulomas, inflammatory manifestations or complications, especially in the context of a suggestive family history or characteristic histologic or radiologic findings. […] The main differential diagnoses for CGD are disorders of recurrent severe or atypical infection, granulomas and hyperinflammation, including cystic fibrosis, severe G6PD deficiency, glutathione synthetase deficiency, protein kinase C delta deficiency, leukocyte adhesion deficiency, combined or common variable immunodeficiency, MyD88/IRAK4 deficiency, hyper-IgE syndrome, allergic bronchopulmonary aspergillosis, sarcoidosis, IBD, MPO deficiency and SAPHO syndrome. […] Defective ROS production mediates the effect of genotype on phenotype in CGD, and diagnosis requires demonstration of a significantly impaired respiratory burst.

• #35 Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/chronic-granulomatous-disease-pathogenesis-clinical-manifestations-and-diagnosis

  Chronic granulomatous disease (CGD) is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. […] The diagnosis is made by neutrophil function testing for superoxide production (nitroblue tetrazolium reduction or dihydrorhodamine [DHR] 123 flow cytometry assay). […] The exact molecular defect is determined by genotyping. […] Diagnosis may also be delayed because of newer, potent antimicrobials that inadvertently treat many CGD-associated infections, postponing diagnosis until more severe infections indicate CGD as the underlying cause.

• #36 Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

  https://www.mdpi.com/2077-0383/13/15/4435

  Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. […] Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. […] We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. […] Like many inborn errors of immunity (IEI), early diagnosis of CGD is important for several reasons, which together support optimal clinical outcomes: (1) early instigation of effective preventative care, (2) appropriate and tailored management of acute infections and complications, (3) early definitive treatment, and (4) early identification of affected family members.

• #37 Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

  https://www.mdpi.com/2077-0383/13/15/4435

  Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. […] Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. […] We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. […] Like many inborn errors of immunity (IEI), early diagnosis of CGD is important for several reasons, which together support optimal clinical outcomes: (1) early instigation of effective preventative care, (2) appropriate and tailored management of acute infections and complications, (3) early definitive treatment, and (4) early identification of affected family members.

• #38 Chronic granulomatous disease: Treatment and prognosis – UpToDate

  https://www.uptodate.com/contents/chronic-granulomatous-disease-treatment-and-prognosis

  Chronic granulomatous disease (CGD) is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. CGD is caused by defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (phox). The treatment and prognosis of CGD are reviewed here. […] The management of CGD focuses on aggressive diagnosis and treatment of infections. The reduction in mortality and morbidity seen over the past few decades is largely attributable to antimicrobial prophylaxis and rapid recognition and treatment of infections in these patients.

• #39 Diagnosing Chronic Granulomatous Disease: Advances and Challenges in the Genomic Era

  https://www.hilarispublisher.com/open-access/diagnosing-chronic-granulomatous-disease-advances-and-challenges-in-the-genomic-era-109463.html

  NGS has transformed the genetic diagnosis of CGD by enabling comprehensive screening of multiple genes simultaneously. This approach reduces diagnostic time and improves accuracy. WES focuses on coding regions of the genome, providing detailed information on mutations affecting protein function. WGS offers a broader view of the genome, including non-coding regions and structural variants, potentially revealing novel mutations. Advanced bioinformatics tools and databases facilitate the interpretation of genetic variants, helping to distinguish pathogenic mutations from benign polymorphisms. Custom gene panels specific to CGD can streamline the diagnostic process by targeting known disease-associated genes. […] Combining genetic testing with functional assays can confirm the clinical significance of identified mutations and improve diagnostic certainty. Efforts to reduce the cost of genomic testing and improve accessibility will facilitate broader use and earlier diagnosis. Building and maintaining comprehensive databases of genetic variants and their associated phenotypes will support better interpretation of genomic data. Understanding the specific genetic mutations in CGD patients can lead to more personalized treatment strategies and improved management of the disease.

• #40 Diagnosing Chronic Granulomatous Disease: Advances and Challenges in the Genomic Era

  https://www.hilarispublisher.com/open-access/diagnosing-chronic-granulomatous-disease-advances-and-challenges-in-the-genomic-era-109463.html

  The genomic era has brought significant advancements in the diagnosis of Chronic Granulomatous Disease, offering more precise and comprehensive methods for identifying pathogenic mutations. While these advancements present exciting opportunities, challenges related to genetic heterogeneity, technical limitations, and accessibility remain. Continued progress in genomic technologies, coupled with efforts to address these challenges, will enhance diagnostic accuracy and patient care for individuals with CGD.

• #41 Chronic granulomatous disease: a review of the infectious and inflammatory complications | Clinical and Molecular Allergy | Full Text

  https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/1476-7961-9-10

  Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. […] Major advances have occurred in the diagnosis and treatment of this disease, with the potential for gene therapy or stem cell transplantation looming on the horizon. […] The approach to the diagnosis of CGD is shown in Table 9. Many of the clinical and laboratory abnormalities suggest the diagnosis. The confirmatory test is measurement of the oxidative burst (superoxide production) of the neutrophil in response to stimulation. […] The DHR test has the ability to distinguish X-linked from the AR forms of the disease as well as pick up the carrier state.

• #42 Chronic granulomatous disease: a review of the infectious and inflammatory complications | Clinical and Molecular Allergy | Full Text

  https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/1476-7961-9-10

  Molecular mutational analysis can help confirm the diagnosis, define the defect, and classify the patient into specific subtypes. […] Treatment of CGD includes prophylaxis of infections using interferon gamma and appropriate antimicrobials (such as trimethoprim sulfamethoxazole/TMP-SMX and itraconazole), and management of infections using appropriate antimicrobials based on pathogen likelihood or identification. […] In select situations, granulocyte transfusions may be required. […] The roles for stem cell transplant (HLA identical sibling umbilical cord stem cell transplantation (UCSCT) after myeloablative conditioning) and gene therapy need to be defined. […] Allogeneic hematopoietic stem cell transplantation from a HLA-identical donor may, at present, be the only proven curative treatment for CGD.

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