Pediatric secondary immunodeficiency disease
Introduction
Introduction to secondary immunodeficiency disease in children The immunodeficiency caused by acquired factors (physical factors, infection factors, nutritional factors, disease factors, physiological development, and degeneration of the elderly) is called secondary immunodeficiency (SID). SID manifests as a defect in mild immune function, and is often a reversible mutation. It is expected to restore normal immune function after timely removal of adverse factors. basic knowledge The proportion of sickness: 0.004% - 0.005% (rare for children) Susceptible people: young children Mode of infection: non-infectious Complications: meningitis osteomyelitis
Cause
The cause of secondary immunodeficiency in children
(1) Causes of the disease
In order to get early diagnosis and treatment, children with repeated infections should be immunologically examined, and infection is also the most common cause of SID; nutritional disorders are another important cause of SID, especially in developing countries. .
1. Causes and classification:
The causes of secondary immunodeficiency are many and complex. In addition to AIDS caused by human immunodeficiency virus (HIV), the more common secondary immunodeficiency can be classified into three categories from pathogenic analysis:
(1) Combined immunosuppression in other diseases: malnutrition, tumors and infections are the three major factors that cause secondary immunodeficiency.
1 Malnutrition: Insufficient intake of protein, fat, vitamins and minerals affects the maturation of immune cells and reduces the body's immune response to microorganisms.
2 Tumors: Tumor patients are susceptible to infection due to impaired cellular and humoral immunity. For example, patients with Hodgkin's disease often have no DTH response to intradermal injection of antigens such as tetanus toxoid, and other lymphocytes have no proliferative response to polyclonal stimulators in vitro. .
3 infection: various types of infection, especially viral infection, can lead to immunosuppression, measles virus and human T lymphotropic virus-1 (HTLV-1) infect CD4 T cells, HIV and HTLV-1 make Th cells Evil becomes mature T-cell leukemia/lymphoma, chronic infection of Mycobacterium tuberculosis and many fungi often leads to immunodeficiency, and parasitic infections such as chronic malaria-infected children in Africa have suppressed T cell function and may be related to the occurrence of malignant tumors caused by Epstein-Barr virus .
(2) Iatrogenic factors: immunodeficiency combined with the treatment of other diseases, or the use of immunosuppressive agents that kill or inactivate lymphocytes for the purpose of preventing transplant rejection, is the most common cause, such as drugs are more common in the clinic. Important reasons for low immunity, such as glucocorticoids, cytotoxic drugs and radioactive irradiation, can cause SID, which is called iatrogenic factors. These methods should be used to guard against SID in the treatment of various diseases such as autoimmune diseases and tumors. The occurrence of chemotherapy drugs is cytotoxic to mature and immature lymphocytes, granulocytes and monocyte precursors, so chemotherapy patients are often accompanied by immunosuppression, and radiation therapy has the same side effects. In addition, surgery, trauma, burns and splenectomy can cause secondary immunodeficiency.
(3) Physiological factors: Some physiological factors such as immature neonatal and degeneration of the elderly make them all have low physiological immune function, which is also a common cause of SID.
2. Common incidence factors:
(1) Protein-heat energy malnutrition, iron deficiency, zinc deficiency, vitamin A deficiency, obesity.
(2) Radiation, antibodies, glucocorticoids, cyclosporine, cytotoxic drugs, anticonvulsants.
(3) chromosomal abnormalities, chromosomal instability syndrome, enzyme deficiency, hemoglobinopathy, tonic muscular atrophy, congenital absence of spleen, skeletal dysplasia.
(4) Histiocytosis, sarcoma-like disease, lymphatic system tumor, leukemia, Hodgkin's disease, lymphoproliferative disease, aplastic anemia.
(5) The immune system is immature or inexperienced.
(6) bacterial infection, fungal infection, viral infection, parasitic infection.
(7) Diabetes, protein-losing enteropathy, nephrotic syndrome, uremia, surgery and trauma, organ degeneration.
(two) pathogenesis
1. Infection: infection can go to immunodeficiency disease, a common cause of SID, aquired immunodeficiency syndrome (AIDS) is a typical example of SID caused by infection, in fact any An infection can cause temporary immune damage to varying degrees.
2. Nutritional disorders: Nutritional disorders are often an important cause of SID. Since 1980, China has conducted extensive research on the mechanism and treatment of immune damage caused by magnesium deficiency. In 1990, it reported the lack of immunodeficiency caused by nutrient deficiency such as subclinical vitamin A. And found that vitamin A deficiency, often natural killer cell activity decreased, lymphoid tissue atrophy, CD4 T cells decreased, B cell antibody production decreased, mucosal local immune response decreased, total IgA and secretory IgA antibody decreased; zinc deficiency Decreased cytotoxic T cell activity, impaired bactericidal ability of macrophages, lack of T cell help, decreased ability of B cells to produce antibodies, impaired skin mucosal barrier function; iron deficiency can reduce lymphocyte proliferation response, IL-6, IL -4 decreased activity, neutrophil bactericidal ability decreased, B cell antibody synthesis was not converted to T cell help, and the ability to secrete antibodies decreased, IgG subclass defects, etc., confirmed the various problems related to SID caused by nutritional disorders, Degree or severe protein-thermal malnutrition is often accompanied by a variety of trace elements and vitamin deficiency, which further affects immune function.
3. Clinical disease: In addition to its own pathological changes, some clinical diseases are often accompanied by some low immune function, such as low IgGemia of nephrotic syndrome, and low cellular immune function of tumor patients.
4. Physiological factors: The immature immune function of infants and young children and the degeneration of immune function in the elderly make them all have low physiological immune function, which is also a common cause of SID.
5. Iatrogenic factors: drugs such as glucocorticoids, cytotoxic drugs and radioactive irradiation can cause SID. In the treatment of autoimmune diseases, tumors and other diseases, these treatments are often used, and all should be alert to SID. happened.
Prevention
Prevention of secondary immunodeficiency in children
The relationship between immunity and infection is complex. Although immunodeficiency can cause infection or become the basis of tumor and autoimmune diseases, infection or tumor and malnutrition can also cause secondary immunodeficiency disease, malignant tumor, malnutrition, Cytotoxic drugs, as well as therapeutic immunosuppressive agents and metabolic diseases, have been shown to cause different types of secondary immunodeficiency, so the clinical should be vigilant.
AIDS is still incurable, but it can be prevented. The most powerful preventive weapon is publicity and education. The vaccine that can prevent HIV infection is called preventive vaccine. The vaccine that can prevent the progression to AIDS after infection is called therapeutic vaccine. So far, there is no clear The prospective HIV vaccine can be widely used. The main difficulty in the development of vaccines is that the HIV pathogenesis and host immune response to HIV are still insufficient. Another important obstacle is the emergence of HIV variants in HIV-infected individuals. The mutation rate of HIV-1 is 0.1% to 1% per year, which means that there is not only one virus in each HIV (+) person, but a group of HIV variants, the pathogenicity of each variant, Growth rates and transmission characteristics vary, and genetic variation in HIV affects its pathogenesis.
A good prophylactic vaccine should be able to induce long-term, stable, systemic and mucosal protective immunity at small doses, and protect the world's most popular antigenic HIV strains. It must be effective and safe. Stable, easy to store, easy to use and inexpensive.
Complication
Secondary complications of secondary immunodeficiency in children Complications meningitis osteomyelitis
Repeated occurrence of various infections or opportunistic infections, delayed growth and development, common septicemia, meningitis, osteomyelitis and other deep serious infections, repeated respiratory infections and pneumonia, aplastic anemia and thrombocytopenia may occur, gangrene pus can occur Skin disease, bronchiectasis, and severe post-inoculation reactions, and can be complicated by tumors and autoimmune diseases.
Symptom
Symptoms of secondary immunodeficiency in children Common symptoms Repeated infection Immunodeficiency diarrhea Hepatosplenomegaly Lymph node swelling Septicemia
The clinical manifestations of immunodeficiency diseases are extremely complicated due to different causes, but their common performance is concentrated, especially repeated infections. If the survival period is long, tumors and autoimmune diseases are also prone to occur, and most primary immunodeficiency diseases (PID) There is a clear genetic tendency to ask family history in detail when screening suspicious cases and looking for patients with the disease. Unfavorable environmental factors and other underlying diseases may be important clues to secondary immunodeficiency disease (SID), SID The clinical manifestations are similar to those of PID, but the degree is often lighter than the latter, and the treatment effect is also good. Repeated infection is prominent, and there are relatively few opportunities for tumors and autoimmune diseases. SID can often find the primary disease and Initiating factors, clinical manifestations of primary disease.
Examine
Examination of secondary immunodeficiency disease in children
The etiology of immunodeficiency disease is complicated, and its laboratory examination methods are more diverse. It should be combined with family history, medical history, physical examination, and related items. In short, the possibility of immunodeficiency should be considered when repeatedly unexplained infections occur. To the clear cause, and a positive family history, the possibility of PID should be considered, but whether the diagnosis of PID or SID should have the corresponding laboratory test basis, in order to clarify the nature of immunodeficiency, the immune network is extremely complicated, and all immune cells and Immune molecules are almost impossible, and some experimental techniques can not be carried out in general medical institutions. They need to be carried out in research centers. In order to avoid unnecessary testing, in the selection of laboratory items for immunodeficiency diseases, they can be divided into three levels: Screen tests, further tests, special or research experiments are summarized below:
Primary screening test
B cell defects, IgG, A, M levels, homologous lectins, phagocytosis, anti-streptolysin "O" antibodies, secretory IgA levels, T cell defects, peripheral blood lymphocyte counts and morphology, chest X-ray Thymus, delayed skin allergy test (mumps, candida, tetanus toxoid, mucorin, tuberculosis or derivatized organisms), phagocytic defects, white blood cell count and morphology, NBT test, IgE level determination, complement deficiency , CH50 activity, C3 level, C4 level.
2. Further inspection
B cell count (CDL9 or CD20), IgG subclass, IgD and IgE levels, antibody response (tetanus, diphtheria, rubella, influenza bacillus vaccine), antibody response (typhoid, pneumococcal vaccine), lateral X-ray thyroid gland Body image, T cell subset count CD3/CD4/CD8, mitogen proliferative response or mixed lymphocyte culture, HLA matching chromosome analysis, chemiluminescence assay, white blood cell dynamic observation (white blood cell special, morphology, movement and chemotaxis ), phagocytic function measurement, bactericidal function measurement, opsonization measurement, determination of each complement component, and determination of each complement component (C3a, C4a, C4d, C5a).
3. Special / research experiments
Further B cell phenotyping, lymph node biopsy, antibody response [phage (X) 174, keyhole hemocyanin (KLH)], in vitro Ig synthesis, B cell activation and proliferation, gene mutation analysis, in vivo Ig Half-life, further T cell phenotype analysis, cytokine and its receptor assay (eg IL-2, IFN-, TNF-), cytotoxic cell function [natural killer cells (NK), cytotoxic T cells (CTL) , antibody-dependent killer cells (ADCC), adenosine deaminase (ADA), purine nucleoside phosphatase (PNP), skin, thymus biopsy, thymosin assay, cell activation/proliferation function, adhesion molecule assay (CDL1b/ CDL8, selectin ligand), deformability adhesion and agglutination function determination, oxidative metabolism function determination, enzyme assay [myeloperoxidase (MPO), glucose-6-phosphate dehydrogenase (G-6-PD), NAD, Oxidase], gene mutation analysis, complement bypass assay, complement function assay, chemokine, immunoadhesion, allogeneic analysis.
4. Regular X-ray, chest X-ray, B-ultrasound, electrocardiogram, etc.
X-ray examination: combined with positive lateral chest fluoroscopy or plain film, pay attention to the existence and size of thymus shadow, lack of thymus shadow in infants within 6 months, suggesting thymic dysplasia, small or no shadow of nasopharyngeal adenoid tissue Direct clues for the diagnosis of cellular immunodeficiency should be combined with clinical lymph node palpation and cellular immunoassay to confirm the diagnosis and help differential diagnosis.
Diagnosis
Diagnosis and differential diagnosis of secondary immunodeficiency in children
diagnosis
The onset of SID depends entirely on the condition of the primary disease or adverse environmental factors. Therefore, repeated or chronic infection can occur at any age, and the performance of immunodeficiency disease is ever-changing. Clinicians should conduct targeted screening according to some general rules. Common performance is an important clue to screening:
1. General clinical manifestations of immunodeficiency diseases
Briefly summarized as follows:
(1) The most common clinical manifestations: repeated respiratory infections, serious bacterial infections, persistent infections, and anti-infective treatments are not effective.
(2) Common clinical manifestations: slow growth and development, multiple chances of infection, skin lesions (rash, seborrheic dermatitis, pyoderma, abscess, alopecia, eczema, telangiectasia, viral sputum), intractable goose Mouth sores, diarrhea and malabsorption, chronic sinusitis and mastoiditis, recurrent bronchitis and pneumonia, evidence of autoimmune response, lack of lymph nodes and tonsils, hematologic abnormalities (aplastic anemia, hemolytic anemia, thrombocytopenia) Purpura, neutropenia).
(3) Less common clinical manifestations: weight loss, fever, chronic conjunctivitis, periodontitis, swollen lymph nodes, hepatosplenomegaly, severe viral infection, chronic liver disease, joint pain or arthritis, chronic encephalitis, Recurrent meningitis, skin purulent gangrene, biliary tract inflammation or hepatitis, vaccination spread, bronchiectasis, urinary tract infection, delayed umbilical cord loss, chronic stomatitis.
2. Repeated or chronic infection
Repeated and chronic infections are the most common manifestations of immunodeficiency diseases. Children often need long-lasting antibiotics. The most common infections are respiratory diseases such as recurrent or chronic otitis media, sinusitis, bronchitis or pneumonia; followed by gastrointestinal infections; skin infections. Can be purulent, abscess or granuloma, also visible systemic infections, such as sepsis, sepsis, meningitis and bone, arthritis.
The general rule is that antibody defects are prone to purulent infections, T cells are prone to virus, fungal or protozoal infections, complement component defects are good for neisseria infection, and neutrophil defects are often Staphylococcus aureus. Infected pathogens in immunodeficiency patients are often not strong, often for opportunistic infections. Most patients have poor therapeutic effects after infection, and the effect of using bacteriostatic agents is worse. It is necessary to use fungicides, and the dosage is large and the course of treatment is long.
3. Tumors and autoimmune diseases
Patients with immunodeficiency disease are prone to autoimmune diseases and tumors, and SID has fewer chances of developing autoimmune diseases and tumors than PID patients.
If a patient has certain diseases and factors that can cause SID, especially when there are certain clinical features that increase the susceptibility to infection, the presence of SID should be suspected. The increased susceptibility to infection is not necessarily an immunodeficiency. Further immunological tests are performed to determine the presence or absence of immunodeficiency and defects in the immune system.
Differential diagnosis
Attention should be paid to the identification of primary immunodeficiency diseases. The important differences between SID and primary immunodeficiency disease (PID) are:
1. SID is often damaged by multiple links in the immune system
PIDs are almost all specific single gene deletions, resulting in damage to the corresponding immunocompetent cells or immune molecules, showing complete loss of this function, and irreversible changes; and SID is often damaged by multiple links of the immune system, but The degree of damage is lighter than that of PID, and only part of the function is impaired, which is manifested as immunocompromise.
2. SID is triggered by acquired environmental factors
PID system key gene mutation, unless immune reconstruction, otherwise its immune function defects will be lifelong, SID is the immune function defect caused by acquired environmental factors, although it can also affect gene expression, but only the gene incomplete expression disorder, removal is unfavorable After the factor, the immune function will probably return to normal.
