Pulmonary hemorrhage-nephritic syndrome in children
Introduction
Brief introduction of pulmonary hemorrhage-nephritis syndrome in children Pulmonary hemorrhagic-nephritis syndrome, also known as Goodpasture syndrome, lung-renal syndrome, etc. This disease is characterized by rapid progressive nephritis and sudden pulmonary hemorrhage, and is characterized by a combination of uremia and respiratory failure. Group of symptoms. basic knowledge Sickness ratio: 0.5% Susceptible people: children Mode of infection: non-infectious Complications: anemia, nephrotic syndrome, hypertension, blood in the stool
Cause
Pediatric pulmonary hemorrhage - the cause of nephritis syndrome
Infection (30%):
Respiratory infections, especially with influenza virus infection, are the most common cause of this disease. Recent studies have found that patients with acquired immunodeficiency disease are infected with Pneumocystis Carinii Pneumonia, and the body is prone to produce anti-GBM antibodies. Calderon et al. Among the HIV-infected patients, 3 anti-type IV collagen 3 chain antibodies (anti-GBM antibodies) were positive, suggesting that alveolar damage can induce pulmonary hemorrhagic-nephritis syndrome in Pneumocystis carinii pneumonia.
Hydroxyl (20%):
Contact with gasoline vapors, hydroxylates, turpentine and inhalation of various hydrocarbons.
Inhaled cocaine (20%):
Patients with long-term smoking developed pulmonary hemorrhagic-nephritis syndrome after 3 weeks of cocaine use.
Pathogenesis
Because some causes cause the body to produce anti-alveolar, glomerular basement membrane antibodies, and thus attack the glomerulus and lung, type II allergic reaction, as well as the deposition of immune complexes to the alveoli and glomeruli There is no definitive explanation for the pathogenesis of activation of complement (type III allergy).
In 1962, Steblay et al. confirmed that glomerular basement membrane (GBM) damage in pulmonary hemorrhagic-nephritis syndrome was mediated by anti-GBM antibodies, and a large amount of research work focused on the isolation and study of GBM components in search of antibodies. The corresponding antigen and the molecular structure and characteristics of the antigen. In recent years, with the rapid development of molecular biology and biochemistry, the NC1 domain of the 3(IV) chain was confirmed in the newly discovered 3(IV) chain of collagen IV. It is Goodpasture's own antigen, also known as Goodpasture antigen, and then cloned the antigen gene Co14A3, which is located in the q35-37 region of the second chromosome.
Indirect immunofluorescence and immunoelectron microscopy confirmed that Goodpasture antigen is not only found in GBM, but also in renal tubular basement membrane (TBM), alveolar capillary basement membrane (ABM) and other tissue basement membranes (such as choroid, cornea, crystal, retinal blood vessels). The basement membrane and so on, but the pathogenic Goodpasture antigen is mainly distributed in GBM, TBM and ABM. The occultity of the antigen causes the reversibility of the exposure process. The 3NC1 structure can be exposed in vitro by 6 mol of guanidine hydrochloride or a strong acid condition of pH 3. Domain, but how the body antigen is exposed and produces an immune response damage GBM is not fully understood, it is speculated that under physiological conditions Goodpasture antigen is concealed in the collagen IV3NC1 domain, various predisposing factors (toxins, viral infections, bacterial infections, tumors, Immune genetic factors and endotoxin can activate epithelial, endothelial and mesangial cell proliferation, and release inflammatory mediators (IL-1, RDS, prostaglandins, neutral proteases, etc.), GBM, etc. under the action of cellular enzymes, collagen IV high-level structure dissociation, exposure of Goodpasture antigenic determinants, stimulation of the body to produce antibodies, resulting in immune damage, due to the whole body hair In the vascular endothelium, only the endothelial layer of the glomerular capillaries has a window, so that the antibody can be directly contacted with the GBM antigen and cause disease, while the ABM is only subject to certain external factors (such as infection, smoking, inhalation of gasoline or organic solvents). After the effect, the integrity of the basement membrane antigen is exposed to the lungs after exposure, which is why the kidney is most susceptible and the degree of involvement is consistent with the antibody titer, and the degree of involvement of the lung is inconsistent with the antibody titer.
The frequency of HLA-DR2 and other antigens in patients with this disease was significantly increased (up to 89%, normal control was only 32%), and the use of gene DNA restriction fragment length polymorphism analysis also showed that the disease and HLA-DR4, HLA-DQ chain gene DQWLb and DQW3 related, indicating that HLA class II antigen-associated lymphocytes play a role in this disease. Some experiments have found that if only anti-GBM antibodies are given to the test animals, GBM can form a line-like deposition, but it does not occur, only the diseased animals are simultaneously input. After T cells, the test animals only developed disease, which confirmed that T cells play an important role in the pathogenesis of this disease. Recent studies have also found that certain cytokines such as tumor necrosis factor and IL-1 can aggravate the development of this disease.
Pulmonary lesions showed pulmonary fullness and swelling, and there were many bleeding spots on the surface. Under the light microscope, there were a lot of red blood cells in the alveolar cavity and many macrophages containing hemosiderin. The alveolar wall was focally thickened and fibrosis. The alveolar cells are hypertrophied. Under the electron microscope, the alveolar basement membrane is thickened and broken. The electron dense substance under the endothelium is spotted, while the endothelial cells are normal. Immunofluorescence shows that there are IgG in the capillary wall, and C3 is continuous or discontinuous. Deposition.
Renal lesions can be seen in soft kidneys with grayish white color, with many small bleeding spots on the surface. Most of the light microscopic lesions are characterized by crescentic nephritis, but the proliferation of endothelial and mesangial cells is generally not heavy, and capillary fibrinoid necrosis is seen. Late glomerular fibrosis, renal interstitial inflammatory cell infiltration and interstitial arteritis, tubular degeneration, atrophy and necrosis, electron microscopically visible balloon epithelial cell hyperplasia, formation of crescentic, mesangial matrix hyperplasia, basal Membrane rupture, glomerular capillary wall is generally no dense deposit, occasionally there is a dense deposit of electron dense substance under the endothelium, immunofluorescence examination shows IgG (100%), C3 (60% ~ 70%) along the glomerulus The capillary wall is linearly deposited, and some patients are positive for antibody IgG on the basement membrane of the distal convoluted tubule.
Previously, this symptom was mainly caused by the desorption of the basement membrane (GBM) antibody. Immunofluorescence showed that IgG was deposited along the glomerular basement membrane. Only a part of this disease can be diagnosed as pulmonary hemorrhagic-nephritis syndrome, and another part of the patient. The clinical resembles pulmonary hemorrhagic-nephritis syndrome, but its immunofluorescence shows that IgG is deposited along the GMB in granular form, and the anti-GBM antibody is negative in the blood. Actually, this part of the case is immune complex nephritis (ICGN), and the autoimmune mechanism starts from this disease. The important role, manifested as ICGN, is caused by the deposition of immune complexes in the corresponding parts of the glomerulus and alveoli. Clinically, the lung lesions appear before the renal lesions, and the renal function is rapidly deteriorated, which can be several weeks to several months. death.
Prevention
Pediatric pulmonary hemorrhage - prevention of nephritis syndrome
The etiology of this disease is still unclear, and various predisposing factors (such as respiratory infections, exposure to gasoline vapor, hydroxyls, turpentine and inhaled various hydrocarbons, and inhalation of cocaine Perez) and endotoxin (toxins, viral infections) should be actively prevented. , bacterial infection, tumor, immune genetic factors, etc., to avoid stimulating the body to produce antibodies, leading to immune damage to the occurrence of pulmonary hemorrhagic nephritis syndrome.
Complication
Pediatric pulmonary hemorrhage - nephritic syndrome complications Complications anemia nephrotic syndrome hypertension blood in the stool
The vast majority of patients have anemia, a large number of or even fatal pulmonary hemorrhage can occur, respiratory failure can occur; in the presence of nephrotic syndrome, renal dysfunction develops rapidly, about 81% of cases develop renal failure; hypertension can occur Liver splenomegaly, enlarged heart, abnormal fundus changes, purpura, blood in the stool, etc.
Symptom
Pediatric pulmonary hemorrhagic-nephritis syndrome symptoms common symptoms weakness leukocytosis edema nephrotic syndrome hypertension vocal hemoptysis fatigue pale pale chest pain
For hemoptysis, anemia, interstitial inflammation of the lungs and progressive renal failure.
1. Age: Children can develop from the elderly, more common in 16 to 30 years old (75% to 95.4%) without ethnic differences, pediatric cases are more common, males are significantly more than females, from 3:1 to 10:1.
General performance: There are often symptoms of general exhaustion such as fatigue, weakness, weight loss, and most patients have anemia, showing pale, dizziness, and shortness of breath.
2. Onset may be related to infection, especially viral infection. Wilson reported 32 cases, 44% had pioneer upper respiratory tract infection, 17% had flu-like symptoms, viral infection or other factors, how to make the body produce lung and glomal basement membrane The common antibodies are not known.
3. Pulmonary: Pulmonary manifestations: About 2/3 of patients with pulmonary hemorrhage before nephritis, the length of time from hemoptysis to renal lesions varies from several days to several years, with an average of about 3 months, clinically hemoptysis For the earliest symptoms, blood stasis accounts for 82% to 86%, usually a small amount of hemoptysis, bright red, a small number of cases may have a large number of fatal pulmonary hemorrhage, patients with gas and cough symptoms, sometimes chest pain and fever, 10 %30% of patients with respiratory symptoms are the initial symptoms, lung percussion is voiced, auscultation can smell wet voice, acute onset, fever, cough, cough, hemoptysis, difficulty breathing, even respiratory failure, hemoptysis The degree can range from blood stasis to a larger amount of hemoptysis.
4. Kidney: Proteinuria is not obvious in the early stage of onset, but it always exists in the course of the disease, or even the appearance of nephrotic syndrome. The main manifestation of hematuria is 80%-90%. The hematuria and cast type are visible under the microscope. At the time of appearance, gross hematuria and renal dysfunction develop rapidly. About 81% of cases develop renal failure within 1 year. On average, about 3 and a half months, dialysis is required to maintain renal function, blood urea nitrogen is elevated, and serum complement is more common. In addition, there are still less urine, headache, high blood pressure, edema and so on.
5. Others: Anti-basement membrane antibody binds to choroid, eye, ear, and even can appear correspondingly. According to statistics, about 10% of patients may have abnormal changes in fundus, pale, hepatosplenomegaly, enlarged heart, purpura, blood in the stool, white blood cells The increase in neutral multinucleated leukocytes is most pronounced, and the anemia and lung manifestations of this disease are very similar to pulmonary hemosiderosis.
Examine
Examination of pulmonary hemorrhage-nephritis syndrome in children
1. Urine examination: Hematuria can be seen under the microscope, red blood cell cast, granular cast, leukocytosis, most of which are moderate urine protein, and a small amount of proteinuria can be seen.
2. Sputum examination: sputum microscopic examination showed macrophage with hemosiderin and bloody sputum.
3. Blood test: If the intrapulmonary hemorrhage is severe or lasts for a long time, there may be more serious small cells, hypochromic anemia, and the Coomb test is negative. Half of the patients have leukocytes exceeding 10×109/L.
4. Blood biochemistry: early BUN, Scr, Ccr normal, but BUN and Scr progressively increased with the progress of the disease, Ccr progressive reduction, severe renal function loss GFR <5ml / min.
5. Specificity examination: In the early stage of the disease, indirect immunofluorescence and radioimmunoassay were used to measure circulating anti-basement membrane antibodies in the blood. The serum anti-GBM antibody was mostly positive, and the sensitivity of indirect immunofluorescence was 80%. Radioimmunoassay The sensitivity of the assay is greater than 95%, and the specificity of both is up to 99%. It is possible to measure anti-NC1 antibody by immunoblotting and ELISA, and specifically diagnose pulmonary hemorrhagic-nephritis syndrome.
Auxiliary inspection
1. Imaging examination X-ray of the lung showed diffuse point-like infiltration shadow, scattered from the hilum to the periphery, the tip of the lung was often clear, and the lung infiltration was characteristic of lung lesions. The early X-ray changes of the lung were similar to pulmonary edema. The hemoptysis can be absorbed in the short term after stopping.
2. Electron microscopy
(1) typical lung lesions are alveolar hemorrhage, hemosiderin deposition and fibrosis, electron microscopy showed alveolar wall capillary basement membrane degeneration, fracture and focal hyperplasia, visible electron dense deposits, immunofluorescence showed IgG and C showed Linear deposition.
(2) typical renal lesions, first, diffuse glomerular damage, kidney often increased and a large number of crescent formation, crescentic body is a peripheral type (extravascular proliferative nephritis), may be associated with capillary necrosis, GBM has IgG deposition, and the second is severe glomerular atrophy with diffuse glomerular fibrosis and interstitial fibrosis. Electron microscopy shows glomerular basement membrane degeneration, shrinkage or diffuse thickening.
3. Light microscopy showed focal or diffuse necrosis, glomerular anti-glomerular basement membrane antibody deposition, epithelial cell proliferation formed crescent moon accounted for more than 50%.
4. Immunofluorescence can be seen along the glomerular basement membrane endothelial deposits (mainly IgG, IgA, IgM, C3 and fibrinogen), if the sediment is high and low particles, it is the lung caused by other diseases, Renal syndrome.
Diagnosis
Diagnosis and diagnosis of pulmonary hemorrhage-nephritis syndrome in children
diagnosis
The diagnostic conditions proposed by Teichman in 1976 were: 1 repeated hemoptysis; 2 hematuria, tubular urinary glomerulonephritis-like changes; 3 small cells, hypochromic anemia, effective with iron; 4 rapid absorption in the lungs Walking spotted infiltrates; macrophages containing hemosiderin can be found in 5, which can be diagnosed; 6 by direct immunofluorescence or radioimmunoassay, repeated examination of blood can prove anti-glomerular basement membrane antibody; 7 kidney or lung biopsy, immunoglobulin deposition in the glomerular or alveolar basal membrane, and arranged in a line.
Diagnose based on
1. Clinical features: acute onset, most of the signs of respiratory infection appear first, and there is a trend of progressive aggravation, first hemoptysis, rapid onset of nephritis, and renal failure, can also be different glomerular glomeruli Nephritis is onset, and abnormal lung symptoms can be revealed later in the course of the disease.
2. Laboratory examination: leukocytosis, proteinuria, urinary sediment, red blood cell tube type, in addition to red blood cells in the sputum, epithelial cells containing "hemosiderin" can be seen.
3. Auxiliary examination: X-ray examination, pathological examination of tissues such as kidneys, help to confirm the diagnosis.
Differential diagnosis
The disease must be associated with idiopathic hemosiderosis, nodular arteritis, vasculitis, systemic lupus erythematosus, diffuse intravascular coagulation, rheumatic pneumonia, pulmonary hemorrhage and nephritis associated with immune complexes Identification of diseases and the like.
1. Idiopathic pulmonary hemosiderosis: the hemoptysis of the disease, the hemosiderin cell test in the sputum and the X-ray findings of the lung are very similar to the pulmonary hemorrhagic-nephritis syndrome, when the lungs of Goodpasture are affected first. When the nephritis is not obvious, the two should be identified. The disease is more common in adolescents under the age of 16 years. The disease progresses slowly, there is no symptoms of nephritis, and the prognosis is good. The lung and kidney biopsy can help identify the serum anti-basement membrane antibody test.
2. Primary or secondary systemic vasculitis, lung and kidney are involved in three types of acute glomerulonephritis, in addition to anti-GBM antibody-positive type, immune complex-mediated (more common in SLE) and small vasculitis nephritis (Wegener granulomatosis and micro-polyarteritis) can be associated with hemoptysis. Lupus nephritis is more common in older children and young adults. It is more common in women. It usually has skin, joint damage and systemic multi-system damage. Serum immunology And renal biopsy can help identify, systemic symptoms (weakness, hypothermia, anorexia, weight loss, etc.) in patients with small vasculitis nephritis, blood neutrophil cytoplasmic antibody positive, Wegener granulomatosis patients may have infiltration The micro-polyarteritis showed interstitial inflammation in the lungs.
3. Nephritis with hemoptysis: all kinds of acute, chronic glomerulonephritis due to severe circulatory congestion, cardiac insufficiency or with pneumonia, pulmonary embolism, can occur hemoptysis, should be identified with the disease, clinical manifestations, lung X-ray features, Renal biopsy has a radionuclide lung scan to help identify.
4. Others: There is also a report of pulmonary hemorrhagic nephritis syndrome in diffuse intravascular coagulation. Combined with the clinical laboratory examination of the primary disease, the identification is generally not difficult. The respiratory symptoms may precede the nodular arteritis. Other system signs, can also be accompanied by nephritis; allergic purpura occasionally see symptoms of pulmonary hemorrhage, which should be noted for identification.
