Goodpasture syndrome
Introduction
Introduction to Goodpasture Syndrome Goodpasture syndrome, also known as anti-base glomerulonephritis, pulmonary hemorrhagic-nephritis syndrome or Goodpasture disease, may be caused by viral infection and/or inhalation of certain chemical substances. It is a serious damage of the glomerular and alveolar wall basement membrane caused by anti-base membrane antibody, clinical manifestations of pulmonary hemorrhage, rapid glomerulonephritis and serum anti-glomerular basement membrane (GBM) antibody-positive triad. Most patients progress rapidly and the prognosis is dangerous. basic knowledge The proportion of illness: the incidence rate is about 0.004% - 0.007% Susceptible people: no special people Mode of infection: non-infectious Complications: anemia, nephrotic syndrome, hypertension, blood in the stool
Cause
The cause of Goodpasture syndrome
The exact cause is unclear and may be the result of a combination of multiple causes. It is generally considered to be related to the following factors:
Infection (40%):
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.
Inhalation of hydrocarbons (20%):
Contact with gasoline vapors, hydroxylates, turpentine and inhalation of various hydrocarbons. Inhalation of these substances may cause Goodpasture syndrome, and more attention needs to be paid to preventive measures.
Inhaled cocaine (10%):
Perez et al reported that a patient 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%, only 32% in normal controls). 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.
Prevention
Goodpasture Syndrome Prevention
1. Personal hygiene: Kindergarten teachers actively cultivate children's good personal hygiene habits, wash hands carefully before and after eating, cut nails frequently, and correct bad habits of sucking fingers in time to eliminate the chance of egg entry.
2. Dietary Hygiene: All faculty and staff in kindergartens wash their hands with soap and running water before work, and disinfect them with 1:1000 disinfectant; ensure that children do not drink raw water, and wash and peel when eating raw fruits.
3. Environmental Hygiene: Cultivate good urination habits for young children. Toilets should be used exclusively for young children. Afterwards, they should be washed and kept clean and odorless at least once a day.
Complication
Goodpasture 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
Goodpasture syndrome symptoms Common symptoms Hematuria dyspnea lung hemoptysis oliguria fever with cough, slightly... proteinuria short kidney failure without urine
Goodpasture syndrome can occur at any age, but most of the young men between the ages of 20 and 30 years old. Patients usually show signs of triad unless they have a cold, no fever, often fatigue, weakness, weight loss, etc. Pulmonary hemorrhage, rapid glomerulonephritis and serum anti-GBM antibody positive.
1. Pulmonary hemorrhage: typical patients have no fever unless they are infected. The most important manifestation of lung is hemoptysis. About 49% of patients have hemoptysis as the first symptom, ranging from hemoptysis to large hemoptysis, and severe (especially smokers). Hemoptysis does not stop or even suffocate death, patients with shortness of breath, cough and asthma, difficulty breathing, sometimes chest pain symptoms, lung percussion is voiced, auscultation can smell wet voice, lung CO uptake rate (Kco) for early and sensitive lung function The indication was changed, and this value decreased in patients with renal failure and pulmonary edema, and this value increased during pulmonary hemorrhage.
General lung symptoms can occur several days, weeks, or years before the kidneys. Pulmonary hemorrhage can be light or severe, or severely life-threatening. Iron deficiency anemia can occur in large or persistent bleeding. Once chest pain occurs, Should pay attention to the exclusion of systemic lupus erythematosus, vasculitis or pulmonary embolism and other lesions, lung X-ray shows diffuse point-like infiltration shadow, scattering from the hilar to the periphery, the lung tip is often clear, hemoptysis and lung infiltration is a lung lesion feature.
2. Renal lesions: The clinical manifestations of renal lesions are diverse. Patients with mild glomerular damage, urine analysis and renal function can be normal. The main clinical manifestations are repeated hemoptysis. Renal biopsy can still show typical anti-basement membrane linear deposition. The immunological characteristics, typical patients with renal dysfunction develop faster, with oliguria or no urine, serum creatinine concentration increased day by day, reaching uremia level within 3 to 4 days; no oliguria, kidney damage is often rapid Development, serum creatinine concentration increased weekly, to uremia within a few months, the majority of patients characterized by progressive renal impairment, according to statistics, 81% of patients developed renal failure within 1 year, normal blood pressure or Mild elevation, urine analysis showed hematuria and proteinuria, often red blood cell cast, a small number of patients with a large number of proteinuria and nephrotic syndrome.
3. Special performance:
(1) Goodpasture syndrome is transformed into glomerular diseases of other pathological types: Elder et al reported that one patient had typical lung-kidney pathological manifestations and clinical manifestations, renal function remained good, and serum and tissue anti-GBM antibodies were positive, significant Iron deficiency anemia, anemia after immunosuppressive treatment improved, serum anti-GBM antibody disappeared, nephrotic syndrome occurred 9 months later, renal biopsy showed that membranous nephropathy was not associated with anti-GBM antibody intrarenal deposition.
(2) Other pathological types of glomerular disease were converted to Goodpasture syndrome: Thitiarchakul reported a case of idiopathic membranous nephropathy, acute deterioration of renal function during the course of the disease, accompanied by hemoptysis, severe hypertension and serum anti-GBM antibody positive, Renal tissue examination showed typical anti-GBM immunopathological manifestations, using high doses of hormones, CTX and plasma exchange were ineffective.
(3) Goodpasture syndrome is limited to one lung or kidney: Patron et al reported a case of simple pulmonary hemorrhagic-nephritis syndrome. Perez et al reported a case of cocaine-induced Goodpasture syndrome with only typical renal changes and no alveolar basement membrane. IgG and C3 are linearly deposited. Others such as anti-basement membrane antibody binding to choroid, eye, ear, and even can cause corresponding performance, such as fundus hemorrhage and exudation, the incidence can be as high as 11%, may be a sharp development The blood pressure is up.
Examine
Examination of Goodpasture syndrome
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.
6. Imaging examination: X-ray of the lung shows diffuse point-like infiltrating shadow, scattering from the hilum to the periphery, the tip of the lung is often clear, and the lung infiltration is a feature of lung lesions. The lung X-ray changes are similar to pulmonary edema in the early stage. The hemoptysis can be absorbed in the short term after stopping.
7. 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.
8. Light microscopy: visible focal or diffuse necrosis, glomerular anti-glomerular basement membrane antibody deposition, epithelial cell proliferation formed crescent moon accounted for more than 50%.
Diagnosis
Diagnosis of Goodpasture Syndrome
1. The key to the diagnosis of Goodpasture syndrome is to determine whether the body has anti-GBM-alveolar basement membrane humoral immunity process, and the characteristic performance of this process:
(1) Serum anti-GBM antibody is positive.
(2) IgG was deposited in the alveolar and renal basement membranes.
2. The diagnosis of a typical patient is in full compliance with the following triads:
(1) Pulmonary hemorrhage, alveolar basement membrane IgG is linearly deposited.
(2) Rapid progressive nephritic syndrome, a large number of crescentic formation of the kidney (extravascular proliferative nephritis), may be associated with capillary necrosis, and GBM has IgG deposition.
(3) Serum anti-GBM antibody is positive.
3. Note on the diagnosis of Goodpasture syndrome:
(1) Some patients have mild manifestations of lungs and/or kidneys, or two organs are not synchronized, and sometimes the anti-basement autoimmune process occurs only in any organ in the lungs or kidneys.
(2) Anti-GBM nephritis sometimes changes with other types of glomerular diseases (mainly membranous nephropathy) (see clinical manifestations).
(3) Occasionally, autoimmune dysfunction produces non-specific basement membrane antibodies and can cause organ damage other than lung and kidney.
(4) In some cases, if autoimmune is highly active, a large amount of anti-GBM antibody deposition may occur, and transient serum anti-GBM antibody may be negative. One patient with typical Goodpasture syndrome renal clinical and pathological findings has been reported. There is lung damage and serum anti-GBM antibodies are negative, which he believes may be due to the massive deposition of antibodies in the target organs during periods of high activity.
(5) Goodpasture syndrome coexists with vasculitis. Rydel et al reported a case of 18-year-old male pulmonary hemorrhagic-nephritis syndrome with refractory epilepsy during plasma exchange and cytotoxic drugs. MRI showed multiple lumens. Multiple Lacunar Infarcts, cerebrospinal biopsy showed vasculitis, but serum ANCA continued to be negative, after administration of high-dose corticosteroids and cytotoxic drugs, anti-epileptic drugs can be used for symptom control, Kalluri et al reported 1 case In patients with pulmonary infiltration and acute renal failure, c-ANCA was positive, renal tissue examination showed crescentic and necrotizing nephritis, IgG and C3 were deposited in the glomerulus, and serum had high titer against GBM-IgG.
Differential diagnosis
1. Pulmonary and renal syndrome: diseases that can cause pulmonary and renal syndrome besides pulmonary hemorrhagic-nephritis syndrome, such as ANCA-related systemic vasculitis, SLE and infection-induced nephritis, in addition, renal vein thrombosis Caused by pulmonary embolism, congestive heart failure caused by end-stage renal failure can also occur hemoptysis, Ent et al reported 2 cases of children, immune complex deposition also caused pulmonary hemorrhage and glomerulonephritis, Hernandez reported a case of special hair Acute glomerulonephritis occurs in patients with Idiopathic Bronchiolitis Obliterans, and histological examination of large amounts of IgA deposits occurs in both the lung and kidney.
In immune complex nephritis, glomerular capillaries have granular deposits. Electron microscopy shows electron dense substances, serum anti-GBM antibodies are negative, and circulating immune complexes can be positive, which is not difficult to distinguish from pulmonary hemorrhagic-nephritis syndrome.
2. Lupus nephritis: patients with acute leukemia in this disease may have symptoms of acute renal failure with pulmonary hemorrhage, which is easily confused with pulmonary hemorrhagic-nephritis syndrome, but the disease is more common in young women, usually with skin, joints, etc. Systemic multi-system damage, serum immunological examination can help diagnose.
3. small vasculitis nephritis: such diseases may have pulmonary hemorrhage performance and approximate Goodpasture syndrome, but the disease is more common in middle-aged and elderly people aged 50 to 70 years old, with weak, low fever, weight loss and other systemic symptoms, blood resistance to neutral The granulocyte cytoplasmic antibodies (antibodies to neutrophil eytoplasmic antigens, ANCA) are positive. Among them, Wegener's granulomatosis may be interstitial inflammation, and both may exist at the same time.
In many vasculitis, there are two types of small vasculitis, Wegener granulomatosis and microscopic vasculitis. The target antigens of these two small vasculitis are Proteinase 3 and Myeloperoxidase, respectively. Antibodies (c-ANCA and p-ANCA) are the original sin antigens that cause small vessel damage and have important diagnostic value for small vasculitis. In Wegener granulomatosis and microscopic vasculitis, the upper and lower respiratory tract and kidney are most often affected, Wegener granulation. The morphological changes of the swelling are various, and the ulceration changes mainly in the oropharynx, paranasal sinus, trachea, etc., and the granulomatous changes are optional, so histological examination, especially small biopsy When we can not easily rule out the diagnosis of Wegener granulomatosis, Wegener granulomatosis and microscopic vasculitis can be characterized as focal segmental necrotic glomerulonephritis in the kidney, often accompanied by crescent formation, glomerular Immunoprecipitation is rare.
4. Acute nephritis with left heart failure: This disease may have blood stasis and dyspnea, similar to pulmonary hemorrhagic-nephritis syndrome, but the disease is more common in adolescent patients, with a history of streptococcal infection, often due to severe hypertension, water Sodium edema and edema, congestive heart failure, renal biopsy can be identified.
5. Rapid progressive nephritis: the immune pathogenesis of rapid progressive nephritis (crescent nephritis) In addition to anti-GBM nephritis, immune complex nephritis and cellular immune vasculitis can also cause typical crescentic nephritis and progressive renal failure .
6. Idiopathic pulmonary hemosiderosis: the hemoptysis of this disease, the hemosiderin cells in the sputum and the X-ray findings of the lungs are very similar to Goodpasture syndrome, but the disease mostly occurs in adolescents under the age of 16. The disease progresses slowly, the prognosis is good, and lung and kidney biopsy can help identify.
