Chronic benign neutropenia in children
Introduction
Introduction to chronic benign neutropenia in children Chronic benign neutropenia (CBN) is a group of heterogeneous diseases of unknown etiology, also known as primary neutropenia, familial neutropenia, congenital neutrality Agranulocytopenia and chronic regenerative hyponeutropenia. It can be congenital or acquired, manifested as neutropenia that lasts for months to years without other primary disease. basic knowledge Sickness ratio: 0.05% Susceptible people: children Mode of infection: non-infectious Complications: meningitis sepsis pneumonia
Cause
Causes of chronic benign neutropenia in children
(1) Causes of the disease
The etiology is still unclear. Anti-neutrophil antibody positive and negative disease can be affected. Anti-neutrophil antibodies are mainly composed of IgG (80%-100%), and its clinical significance is still unknown.
(two) pathogenesis
In most cases, the number of clonal cells and the level of cloning stimulating factors in normal cells are normal or increased. The mechanism of formation is still unclear. It may be caused by different causes. Anti-neutrophil antibodies play an important role in the pathogenesis, but anti-neutrophils. There is no difference in the clinical manifestations of positive and negative cell-positive children. The antibody assay method has not been standardized, and its specificity and sensitivity are difficult to estimate. In 1975, the first anti-neutrophil-positive diseased child was found to be naturally relieved with the disease. The antibodies are also negative. These children have no risk of malignant tumors and other autoimmune diseases. Anti-neutrophil antibodies are mainly composed of IgG (80%-100%). The clinical significance is still unknown. Some believe that The clinical process is irrelevant, while others believe that antibodies directly affect early progenitor granulocytes and peripheral blood mature granulocytes, affecting the clinical process and the number of granulocytes, antibodies can also interfere with phagocytic sterilization, adhesion, conditioning and free radical production.
Prevention
Prevention of chronic benign neutropenia in children
1. Maternal health care: It is known that the occurrence of some immunodeficiency diseases is closely related to embryonic dysplasia. If pregnant women are exposed to radiation, receive certain chemical treatments or have viral infections (especially rubella virus infection), they may be damaged. The fetal immune system, especially in the first trimester, can involve multiple systems including the immune system. Therefore, it is important to strengthen maternal health care, especially in early pregnancy. Pregnant women should avoid radiation, use some chemical drugs with caution, and inject rubella vaccine. Wait, try to prevent viral infections, but also to strengthen the nutrition of pregnant women, and timely treatment of some chronic diseases.
2. Genetic counseling and family surveys: Although most diseases cannot determine the genetic pattern, it is valuable to conduct genetic counseling for diseases with defined genetic patterns. If adults have hereditary immunodeficiency diseases, they will provide the developmental risks of their children. If a child has an autosomal recessive or sexually linked immunodeficiency disease, tell the parents how likely they are to have the next child, and the immediate family members of the antibody or complement deficiency should check for antibodies and The level of complement determines the family's disease pattern. For some diseases that can be genetically located, such as chronic granulomatosis, the patient's parents, siblings and their children should be tested for localization. If a patient is found, the same should be given to him. The family members of (her) are examined and the child's children should be carefully observed at the beginning of the birth for any disease.
3. Prenatal diagnosis: Some immunodeficiency diseases can be used for prenatal diagnosis. For example, cultured amniotic fluid cell enzymology can diagnose adenosine deaminase deficiency, nucleoside phosphorylase deficiency and some combined immunodeficiency diseases; Fetal blood cell immunology test can diagnose CGD, X-linked no-gammaglobulinemia, severe combined immunodeficiency disease, thereby terminating pregnancy and preventing the birth of children. Chronic benign neutropenia is a relatively prognostic disease. Attention should also be paid to early and accurate diagnosis, early specific treatment and genetic counseling (prenatal diagnosis or even intrauterine treatment).
Complication
Complications of chronic benign neutropenia in children Complications meningitis sepsis pneumonia
A small number of meningitis and sepsis can occur, such as cellulitis, mastoiditis, otitis media, pharyngitis and pneumonia.
Symptom
Symptoms of chronic benign neutropenia in children Common symptoms Repeated infection of granulocytes reduces meningitis Mastoid septicemia Cellulitis
CBN is the most common type of neutropenia in infants and young children within 4 years of age. 90% of them occur within 14 months. The clinical manifestations can be severe infections in infants, and there are no symptoms. Infections such as cellulitis and mastoiditis , otitis media, pharyngitis and pneumonia, occasionally meningitis and sepsis can occur, the pathogen is mainly Gram-positive bacteria, the incidence of infection is not higher than the normal age when the neutrophil count >400/mm3; infection with age The incidence will also gradually decline.
Examine
Examination of chronic benign neutropenia in children
The total number of peripheral white blood cells is normal or slightly increased, and the absolute count of granulocytes is <0.5×10 9 /L. The variation is very large, and the non-periodic fluctuations are from zero to near normal. The granulocyte count can be increased in children with mild disease. To normal, almost daily changes, making diagnosis extremely difficult, peripheral blood mononuclear cells and eosinophils increased with the degree of neutropenia and infection, common mild anemia (caused by inflammation) and increased reactive platelets.
Bone marrow examination revealed active myeloid hyperplasia and early developmental maturation of the granulocyte system, occasionally the same as Kostmann syndrome, a late maturation disorder (late myeloid/stranded granulocytes).
Choose chest X-ray, B-ultrasound, CT, etc. according to clinical needs.
Diagnosis
Diagnosis and diagnosis of chronic benign neutropenia in children
Repeated measurements of peripheral blood granulocyte counts have been found to be persistently low (temporarily low and then normal, but non-periodic) to make a diagnosis.
Differential diagnosis
1. Periodic neutropenia Cyclic neutropenia is characterized by repeated infections with periodic circulating neutrophil counts, approximately 21 days per cycle, first reported in 1910, 1930 In the year, the disease has been further recognized, both men and women can be sick, and about 25% of cases have a genetic background.
(1) Pathogenesis: Cyclic neutropenia is caused by endogenous regulatory disorders of early hematopoietic progenitor cells. This hypothesis is supported by a microenvironmental change after bone marrow transplantation to improve the clinical process.
(2) Clinical manifestations: The severity of infection depends on the degree of neutropenia in peripheral blood, regardless of the number of monocytes. During the interval between two neutropenia, the sick child often has no symptoms of infection; Unexplained fever, gingivitis, stomatitis, cellulitis and rectal abscess can occur during the reduction period. Although most of the disease has a good prognosis, 10% die from serious infection, some sick children grow with age, and granulocyte periodicity The reduction is gradually less obvious, the symptoms of infection are also reduced, and the periodic neutropenia lasts for a lifetime, but it does not develop into aplastic anemia and leukemia.
(3) Laboratory examination: Severe neutropenia with a period of 21 days occurred in 70% of the sick children, and the period of granulocytopenia in the remaining sick children was between 14 and 36 days, and the neutropenia continued for 3 times. ~10 days, the number of other blood cells is normal, bone marrow examination found that the neutropenia is dysplasia and maturity disorder, while the granulocyte hyperplasia is active in the interstitial phase.
(4) Diagnosis and differential diagnosis: neutropenia and repeated infection with a period of 21 days are the basis for the diagnosis of this disease. For this reason, the granulocyte count should be measured repeatedly within 2 months, 2 to 3 times per week (observed two Week), the possibility of other chronic neutropenia should be ruled out.
(5) splenectomy, androgen, lithium and glucocorticoids have a certain effect on blocking periodic neutropenia. Recently, rhG-CSF was used 3 times a week to achieve better results, but there was recurrence after stopping the drug. Report.
2. Severe congenital neutropenia (Kostmann syndrome) This disease was first reported by Kostmann in 1956, also known as infant congenital neutropenia, manifested as severe suppurative infection in early infants, severely neutral Granulocyte reduction and dysplasia of granulocyte/myeloblasts.
(1) Pathogenesis: Most of the disease is considered to be an endogenous defect of stem cells. The detailed mechanism is still unknown. G-CSF, GM-CSF and its receptors are normal, and no granulocyte production inhibitory factor is found. Related to intracellular information transmission disorders.
(2) Clinical manifestations: life-threatening infections occur repeatedly within 1 year, including cellulitis, stomatitis, sepsis, meningitis and peritonitis, pathogens are Staphylococcus aureus, Escherichia coli and patina Monocytogenes, more than 2 years of age without effective treatment, the best midline survival age is 13 years; very few cases develop leukemia, since the widespread use of rhG-CSF, with the prolongation of survival, malignant tumors The rate has also increased, the disease is autosomal recessive, and there are reports of autosomal dominant inheritance and dissemination.
(3) Laboratory examination: neutropenia can be found at birth, the absolute count is less than 0.1×109/L, and occasionally within 1 year of age or life-threatening infection, the granulocyte count can be higher than 1×109/ L, there may be mild anemia, normal or increased platelet count.
(4) The previous treatment was supportive therapy and anti-infective treatment. Before using rhG-CSF, bone marrow transplantation was the only treatment. The effects of glucocorticoid, lithium and splenectomy were not satisfactory. In 1988, rhG- was used. CSF, clinical observations show that not only can increase granulocytes, but also promote its bactericidal ability, the dose of rhG-CSF is larger than that of CBU, and the effect of recombinant human granule-mononuclear-CSF (rhGM-CSF) is not as good as that of rhG-CSF. Interleukin-3 (IL-3) may be synergistic with rhG-CSF, and bone marrow transplantation is still effective in cases of ineffective rhG-CSF.
3. Intramedullary destruction of granulocytes increases the intramedullary destruction of granulocytes (myelokathexis) is characterized by moderate anemia, abnormal granulocyte nucleus with nucleus is connected by filaments, vacuoles in the cytoplasm, and bone marrow shows proliferative activity. Leaf nucleated cell degeneration, leukocyte dynamics and morphological studies suggest that the increase of neutrophil intramedullary destruction is the basis of the disease, one case with hypogammaglobulinemia, and the other with G-CSF can be successful Control severe gingivitis and periodontitis.
