What Is Chronic Granulomatous Disease?

Patients often have a family history, children are more common, and parents are mostly married to close relatives. Onset is male and female is a carrier. A few are recessive for autosomal. Most cases occur within the age of 2 years, and a few can be as late as 10 years old.

Chronic granulomatosis

Chronic granulomatous disease (CGD) is a lethal hereditary defect of leukocyte function, mostly sexually recessive.

Epidemiology of chronic granulomatosis

Causes of chronic granulomatosis

All subtypes of sex-linked recessive chronic granulomatosis are caused by mutations in the qp91-phox subunit gene encoding cytochrome b. This gene is named CYBB (MIM306400) and contains 13 exons. It is located in X Chromosome xp21.1, occupying about 30kb. According to the analysis results of 261 children with sexually transmitted CGD in a multi-center international database, the mutations of this gene are obviously heterogeneous and mostly family-specific. Gene deletions, missense mutations, and nonsense mutations accounted for nearly 20% of all mutations, and splicing into point mutations (16%) and insertions (10%) accounted for most of the remaining mutations. At present, it is also found that there are two regulatory mutations CyBB gene mutation distribution without obvious mutation hot spots seems to have some randomness. In short, most sex-linked CGDs are caused by mutations in the CyBB coding and splicing regions, rather than deletions in the gene regulatory regions. Most mutations affect the stability of mRNA and / or the protein. The diversity of qp91-phox gene mutation parallels the clinical heterogeneity of sex-linked CGD. Analysis of O2 production by tetrozole nitrogen blue test (NBT) and flow cytometry revealed neutrophil respiratory burst activity in 5% of patients. Normal; 95% of granulocytes lack respiratory burst activity, and the total amount of cytochrome b is about 5% of normal. It is speculated that there may be only a few cell clones with normal cytochrome b levels and complete respiratory burst activity. Mutations in the regulatory region will be detrimental to cytochrome b expression.

Pathogenesis of chronic granulomatosis

Normal granulocytes produce hydrogen peroxide for phagocytosis of bacteria, and release new ecological oxygen after phagocytosis of bacteria, oxidizing iodine and chlorine compounds to free iodine and chlorine to form a complete hydrogen peroxide-peroxidase-iodide ion sterilization system. Due to the lack of glucose oxidase, the disease cannot produce hydrogen peroxide, so that it can kill bacteria that cannot produce hydrogen peroxide, such as Staphylococcus aureus Klebsiella albicans, group E coli, Serratia marcescens, etc. However, it still has a killing effect on streptococcus and pneumococcus that can produce hydrogen peroxide. In short, there is a disease caused by the lack of bactericidal power of peroxides in granulocytes.

Clinical manifestations of chronic granulomatosis

Recurrent purulent infections in various parts of the body, including Staphylococcus, Escherichia coli, Salmonella, Candida albicans, Actinomyces, etc., which cause purulent lymphadenitis, rhinitis, sinusitis, and pericardium, lung, and liver nervous system Such as purulent inflammation. May have skin granulomas, eczema dermatitis, liver and splenomegaly. Granuloma formed by histiocytic cells containing pigment lipids was seen in each affected organ.

complication:

The main complications are seen in various organ purulent infections. Such as abdominal abscess, liver abscess, meningitis, severe cases of sepsis and life-threatening.

Diagnosis of chronic granulomatosis

According to infants and young children with recurrent purulent skin and organ infections, with liver and splenomegaly. Increased granulocytes and reduced NBT function can confirm the diagnosis.

Molecular genetic analysis of myeloid cDNA or genomic DNA can assist diagnosis and typing, and identify mutation sites. DNA can be extracted from fetal chorion or amniotic fluid cells for prenatal diagnosis. If lack of the above means is available. Tetrazolium blue test and placental blood analysis.

Differential diagnosis:

It is mainly differentiated from those with recurrent infection and liver and splenomegaly. Tetrazolium blue test should be performed to screen leukocyte function. It should also be identified from the following diseases:

1. Patients with G-6-PD deficiency also have reduced G-6-PD activity in leukocytes, which is generally about 80% of normal. Such patients are prone to hemolytic anemia and repeated infections. Due to the lack of enzyme, no metabolic activity of hexose monophosphate bypass was detected in leukocytes. It cannot be corrected for methylene blue to distinguish this from CGD.

2. Leukocyte glutathione peroxidase deficiency is more severe than patients without heterozygosity in the CGD mild family.

3. Familial lipochrome histiocytosis has a late onset and only women have onset of granulocyte defects similar to CGD.

Examination of chronic granulomatosis

Laboratory inspection:

1. The total number of peripheral white blood cells and neutrophils, monocytes, plasma cells increased, red blood cells, hemoglobin and platelets were normal.

2. Incubation experiments of white blood cells and Staphylococcus aureus After normal white blood cells were cultured for 1 hour, only 10% of the bacteria remained in the cells, and 80% of the bacteria in the patients were not destroyed, indicating a bactericidal defect in neutrophils.

3. Tetrazolium blue test (NBT) reduced phagocytic function.

4. Neutrophil membrane and cytoplasmic granules Free cell oxidase activity experiments Using known p47-phox or p67-phox-deficient cytoplasmic granules to perform immunoblot analysis or compensation studies on free cell systems to determine which components have defect.

5. Immunoglobulin gamma globulin increased.

Other auxiliary inspections:

According to clinical manifestations, symptoms and signs, choose to do ECG, B-, X-ray, biochemical examination.

Treatment of chronic granulomatosis

The focus is on preventing and treating infections. Once infection occurs, broad-spectrum antibiotics should be used. Diclocillin (diclocillin), cephalosporins III, and rifampicin are more effective. Recently it was discovered that sulfisoxazole can promote the bactericidal ability of phagocytes in children Can enhance the bactericidal power of neutrophils. In addition, leukocyte infusion and bone marrow transplantation are beneficial for this disease. Granulocyte colony-stimulating factor (G-Csf) can reduce infection or shorten the course of disease. Adrenal corticosteroids should not be used to aggravate granulocyte function defects.