Goodpasture syndrome

　　Goodpasture syndrome, also known as pulmonary hemorrhage-nephritis syndrome, has an unclear etiology, and it is believed to be the result of the combined action of multiple causes. It is generally considered to be related to the following factors:

　　1. Infection

　　Respiratory tract infections, especially influenza virus infections, are the most common triggers for the disease. Recent research has found that patients with acquired immune deficiency syndrome (AIDS) are prone to produce anti-GBM antibodies after infection with Pneumocystis carinii pneumonia (Pneumocystis carinii pneumonia). Calderon et al. reported that in 4 HIV-positive cases, 3 were positive for anti-type IV collagen α3 chain antibody (anti-GBM antibody), indicating that alveolar damage during Pneumocystis carinii pneumonia can induce pulmonary hemorrhage-nephritis syndrome.

　　2. Inhaling hydrocarbons

　　Exposure to gasoline vapor, hydrocarbons, turpentine, and inhalation of various hydrocarbons. Inhaling these substances may trigger Goodpasture syndrome, and it is necessary to pay more attention and take preventive measures.

　　3. Cocaine inhalation

　　Perez et al. reported a case of a long-term smoker who developed pulmonary hemorrhage-nephritis syndrome 3 weeks after using cocaine.

　　The vast majority of patients with Goodpasture syndrome can experience massive or even life-threatening pulmonary hemorrhage, which can lead to respiratory failure. The main complications include pulmonary hemorrhage, clinical symptoms including dyspnea, tachypnea, cough, and hemorrhage. Severe cases may lead to life-threatening massive or continuous hemorrhage, which can cause iron deficiency anemia. Kidney damage can lead to oliguria or anuria, with a rapid increase in serum creatinine concentration. Renal damage progresses rapidly, leading to uremia within a few months. Some cases may develop into other types of kidney diseases.

　　Goodpasture syndrome can occur at any age, but it is most common in male youth aged 20 to 30. Patients generally have no fever except for common cold, and often have symptoms such as fatigue, weakness, and weight loss. The characteristic clinical triad is: pulmonary hemorrhage, rapidly progressive glomerulonephritis, and positive serum anti-GBM antibody.

　　1. Pulmonary hemorrhage

　　Typical patients, except for concurrent infection, generally do not have fever. The most important manifestation of the lungs is hemoptysis, with about 49% of patients presenting with hemoptysis as the first symptom, ranging from slight hemoptysis to massive hemoptysis. Severe cases (especially smokers) may experience continuous massive hemoptysis and even asphyxial death. Patients often have symptoms such as shortness of breath, cough, asthma, and difficulty breathing. Sometimes, there are symptoms of chest pain. The lung percussion sounds dull, and wet rales can be heard on auscultation. The pulmonary CO uptake rate (Kco) is an early and sensitive indicator of pulmonary function changes, and this value decreases in patients with renal failure and pulmonary edema, while it increases during pulmonary hemorrhage.

　　General pulmonary symptoms may appear several days, weeks, or even years before renal manifestations. Pulmonary hemorrhage can be mild or severe, and may be life-threatening. Large or persistent hemorrhage can lead to iron deficiency anemia. Once chest pain occurs, systemic lupus erythematosus, vasculitis, or pulmonary embolism should be ruled out. Pulmonary X-ray shows diffused punctate infiltration shadows scattered from the hilum to the periphery, with the lung apex often clear. Hemoptysis and pulmonary infiltration are characteristic of pulmonary lesions.

　　2. Renal lesions

　　Clinical manifestations of renal lesions are diverse. In patients with mild glomerular damage, urine analysis and renal function can be normal, with the main clinical manifestation being recurrent hemoptysis. Renal biopsy can still show the immunological characteristic of typical linear deposition of anti-basement membrane antibodies. In typical patients, renal function damage develops rapidly, with oliguria or anuria, and the serum creatinine concentration increases daily, reaching uremic levels within 3 to 4 days; in patients without oliguria, renal damage often develops rapidly, with the serum creatinine concentration increasing weekly, reaching uremia within a few months. The characteristic manifestation of most patients is progressive renal function damage. According to statistics, 81% of patients develop renal failure within one year, with normal or slightly elevated blood pressure, hematuria and proteinuria in urine analysis, often with red cell casts, and a few patients have large amounts of proteinuria and nephrotic syndrome.

　　3. Special manifestations

　　(1)Goodpasture syndrome transforms into other pathological types of glomerular diseases: Elder et al. reported a patient with typical pulmonary-kidney pathological and clinical manifestations, with good renal function, positive serum and tissue anti-GBM antibodies, significant iron deficiency anemia. Improvement in anemia after immunosuppressive therapy, disappearance of serum anti-GBM antibodies, and 9 months later, nephrotic syndrome occurred. Renal biopsy review showed membranous nephropathy without intrarenal deposition of anti-GBM antibodies.

　　(2)Other pathological types of glomerular diseases transform into Goodpasture syndrome: Thitiarchakul reported a case of a patient with idiopathic membranous nephropathy, in whom renal function deteriorated acutely during the course, accompanied by hemoptysis, severe hypertension, and positive serum anti-GBM antibodies. Renal tissue examination showed typical anti-GBM immunopathological manifestations, and treatment with high-dose corticosteroids, CTX, and plasma exchange was ineffective.

　　(3)Goodpasture syndrome is limited to only one organ, either the lung or the kidney: Patron et al. reported a case of simple pulmonary hemorrhage-nephritis syndrome, Perez et al. reported a case of Goodpasture syndrome induced by cocaine, which only had typical renal changes, without IgG and C3 linear deposition on the alveolar basement membrane. Other conditions such as anti-basement membrane antibody binding to the choroid, eyes, ears, and occasionally causing corresponding manifestations, such as fundus hemorrhage and exudation, may occur, with an incidence as high as 11%, possibly due to acute hypertension.

　　Patients with Goodpasture syndrome may experience symptoms of pulmonary hemorrhage and nephritis, and in severe cases, it can be life-threatening, so it is essential to do a good job of prevention work.

　　1. Personal hygiene

　　Kindergarten teachers actively cultivate good personal hygiene habits in children, wash their hands thoroughly before and after meals, frequently trim their nails, and correct the bad habit of finger-sucking in time to prevent the entry of worm eggs.

　　2. Diet hygiene

　　All staff of kindergartens wash their hands with soap and running water before work and disinfect their hands with a 1:1000 disinfectant solution; ensure that children do not drink unboiled water and wash and peel fruits and vegetables before eating.

　　3. Environmental hygiene

　　Cultivate good habits of defecation and urination in children, use children's toilets exclusively, flush immediately after defecation to keep it clean and odorless, and disinfect at least once a day.

　　Some Goodpasture syndrome patients have mild lung and/or renal manifestations, or the two organs may not occur simultaneously. Sometimes, the anti-GBM autoimmune process occurs only in one organ, the lung or kidney. Therefore, auxiliary examinations are needed to diagnose the disease.

　　1. Urine examination

　　Under the microscope, hematuria, red blood cell casts, granular casts, leukocytosis, and most of the moderate amount of urinary protein can be seen. A few cases show a large amount of proteinuria.

　　2. Sputum examination

　　Microscopic examination of sputum shows macrophages containing hemosiderin and bloody sputum.

　　3. Blood examination

　　If pulmonary hemorrhage is severe or prolonged, there may be severe anemia with small cells and hypochromia, negative Coomb's test, and half of the patients have white blood cell counts exceeding 10×10^9/L.

　　4. Blood biochemistry

　　Early BUN, Scr, and Ccr are normal, but as the condition progresses, BUN and Scr progressively increase, and Ccr progressively decreases. In patients with severe renal function impairment, GFR

　　5. Specific examination

　　In the early stage of the disease, indirect immunofluorescence and radioimmunoassay methods are used to measure circulating anti-GBM antibodies in the blood. The serum anti-GBM antibodies are mostly positive, with a sensitivity of 80% for indirect immunofluorescence and a sensitivity greater than 95% for radioimmunoassay. Both have a specificity of up to 99%. Under certain conditions, anti-NC1 antibodies can be measured by immunoblotting and ELISA methods to specifically diagnose Goodpasture syndrome.

　　6. Imaging examination

　　Lung X-rays show diffuse punctate infiltrative shadows scattered from the hilum to the periphery. The lung apex is usually clear. Lung infiltration is a feature of lung lesions, and the early changes in lung X-rays are similar to pulmonary edema. They can be absorbed in the short term after hemoptysis stops.

　　7. Electron microscopy examination

　　(1) The typical lung lesions are alveolar hemorrhage, hemosiderin deposition, and fibrosis. Electron microscopy shows变性, rupture, and focal proliferation of the alveolar wall capillary basement membrane, with electron-dense deposits visible. Immunofluorescence examination reveals linear deposition of IgG and C.

　　(2) Typical renal lesions include diffuse glomerular injury, enlargement of the kidneys with the formation of a large number of crescents, which are of the peripheric type (capillary proliferative glomerulonephritis), and may be accompanied by capillary necrosis. The GBM shows linear deposition of IgG. Second, severe glomerular atrophy results in diffuse glomerular fibrosis and interstitial fibrosis. Electron microscopy reveals变性断裂, wrinkling, or diffuse thickening of the glomerular basement membrane.

　　8. Light microscopy examination

　　Focal or diffuse necrosis can be seen, with anti-glomerular basement membrane antibodies deposited in the glomeruli, and epithelial cell proliferation forming crescents accounting for more than 50%.

　　After the treatment of the acute phase of Goodpasture syndrome, attention should also be paid to dietary adjustment.

　　1. Selection of staple foods and beans: millet, sorghum, broad beans, adzuki bean, corn flour, rice, wheat starch, etc.

　　2. Meat, egg, and milk selection: crucian carp, crucian carp, yellowfish, silver carp, black carp, silver fish, pork, pork kidney, mackerel, chicken, duck, etc.; individuals with high cholesterol should mainly supplement high-quality protein from fish.

　　3. Vegetable selection: winter melon, cucumber, carrot, shepherd's purse, lettuce, green pepper, zucchini, eggplant, cabbage, chrysanthemum, cauliflower, lettuce, tomato, luffa, Japanese pumpkin, eggplant, amaranth, bamboo shoots, malan head, yam, lotus root, straw mushroom, seaweed, water chestnut, etc.

　　4. Fruit selection: watermelon, melon, grape, orange, tangerine, kiwi, strawberry, pineapple, olive, plum, apple, etc.

　　5. Avoid spicy and刺激性 food such as chili, pepper, mustard, and curry. Excessive use of monosodium glutamate can cause thirst and a desire to drink water, so monosodium glutamate should also be used sparingly.

　　6. Avoid nitrogenous extracts. Due to poor kidney function, kidney disease patients cannot excrete nitrogen elements in a timely manner. Nitrogen is one of the metabolic waste products of the body. Under the condition of weakened kidney function, the intake of nitrogen-containing substances should be reduced. These substances include simple chicken soup, fish soup, meat soup, and duck soup without medicinal food coordination.

　　7. Limit salt intake and avoid pickled vegetables, soy sauce, pickled bean curd, and preserved products.

　　8. Avoid plant proteins, as they contain a large amount of purine bases, which can increase the burden on the middle metabolism of the kidneys. Therefore, they are not suitable for consumption, such as soybeans, mung beans, broad beans, soy milk, tofu, and sprouts.

　　9. Avoid foods high in purines, such as pork head meat, sardines, chicken soup, beef soup, celery, spinach, lamb, dog meat, sparrow meat, rabbit meat, and oily products like peanuts.

　　10. Avoid vegetables high in calcium oxalate, such as bamboo shoots, chive, and lotus root.

　　The key to treating Goodpasture syndrome lies in early diagnosis, timely removal of triggers, and effective treatment.

　　1. General treatment

　　Strengthen nursing care, pay attention to keeping warm, prevent and treat colds, quit smoking, and reduce and avoid various possible pathogenic causes. If combined with infection, it often causes repeated and severe lung lesions, and it is necessary to use antibacterial drugs early, actively, and effectively to prevent and treat secondary infections and exacerbate the condition. Clinical studies have shown that the third-generation cephalosporin cefotaxime (cefotaxime carboxylate), known as Fortum, is effective and can be administered intravenously in doses of 2-6g/d, divided into 2-3 doses.

　　Severe and persistent hemoptysis in this disease can lead to severe iron deficiency anemia, which should be corrected. Iron supplements can be supplemented once a day, commonly using ferrous sulfate (Ferrosii Sulfate) 0.3g, folic acid (Acid Folic) 20mg three times a day, vitamin B12 (Vitamin B12) 500μg intramuscular injection, once a day; fresh blood transfusion is necessary if required.

　　2. Adrenal cortical hormones and immunosuppressants

　　The combined use of adrenal cortical hormones and immunosuppressants can effectively inhibit the formation of anti-GBM antibodies and can quickly alleviate the severity of pulmonary hemorrhage and control life-threatening massive hemoptysis. Generally, methylprednisolone (Methylprednisolone) pulse therapy can be selected, intravenous infusion of 1.0-1.5g/d, finished within a few hours (not less than 15 minutes), 3 times as one course, which can be repeated 2-3 times. After 2 months of intensive treatment, the dose is gradually reduced, and the treatment is maintained for at least 3-6 months. This therapy can also prevent the feedback hyperproduction of anti-GBM antibodies after plasma exchange. If immunosuppressants such as cyclophosphamide (Cytoxan, CTX) 2-3mg/(kg/d) or azathioprine (Imuran) 1mg/(kg/d) are used simultaneously, the efficacy is better. It is also possible to start with prednisone (Prednisone) (prednison) orally, 1-1.5mg/(kg/d), and then add immunosuppressants. After the condition is controlled, immunosuppressants are discontinued, and prednisone (Prednisone) is slowly reduced to a maintenance dose of 5-15mg/d for continued oral treatment, with the full course lasting 0.5-1 year.

　　3. Plasma exchange and immunoadsorption therapy

　　Plasma exchange or immunoadsorption can remove anti-GBM antibodies. Active plasma exchange therapy, combined with the use of immunosuppressants and moderate doses of corticosteroid therapy, can effectively stop pulmonary hemorrhage and improve renal function. The replacement plasma is 2-4L/d, and the duration and frequency of plasma exchange can be determined according to the level of circulating anti-GBM antibodies. Generally, it is once a day or every other day, and can be extended to twice or thrice a week when the condition is stable. It is combined with the use of prednisone (Prednisone) 60mg/d orally and high-dose cytotoxic drugs (mainly cyclophosphamide). Under normal circumstances, plasma exchange combined with immunosuppressive therapy must be continued until the level of circulating antibodies significantly decreases or becomes negative (usually about 7-14 days), and immunosuppressive therapy is gradually withdrawn over the next few weeks to several months. After the above treatment, 80% of patients have improved renal function.

　　This therapy is only of value in the early stage of the disease, when the crescent is in the cellular or cellular-fibrous type, and the patient has not entered the irreversible terminal renal failure. For patients with rapidly progressive onset who have not yet developed oliguria, Scr 530μmol/L, or those who require dialysis treatment to maintain life, the efficacy is poor.

　　4. Anticoagulation and Fibrinolysis Therapy

　　Because fibrinogen-related antigen appears at the damaged site, theoretically, anticoagulants combined with corticosteroids and cytotoxic drugs are beneficial for the treatment of this disease. However, studies have not proven that heparin at conventional doses improves renal function or the pathological changes of rabbit anti-GBM nephritis renal tissue. High-dose warfarin is only effective in experimental studies when used in high doses that can cause frequent gastrointestinal bleeding. Coagulation function disorder in uremic stage is very dangerous, and the risk is even higher for anti-GBM antibody disease. The risk of severe hemorrhage caused by renal biopsy is also high.

　　5. Renal Replacement Therapy

　　For patients with end-stage renal disease who have entered due to ineffective conventional treatment or late treatment, and maintain life through hemodialysis or peritoneal dialysis, renal transplantation can be considered if the condition is stable and the level of circulating anti-base membrane antibodies in the blood is reduced to undetectable levels.

　　The recurrence rate of this disease after renal transplantation is 10% to 30%. Renal transplantation between monozygotic twins without immunosuppressive treatment has a higher risk of recurrence if renal transplantation is performed soon after onset or if renal transplantation is accepted with a high titer of serum anti-GBM antibody. The clinical recurrence rate can drop to below 10% after renal transplantation is delayed for several months and the titer of serum anti-GBM antibody decreases or becomes negative, or after immunotherapy. Recurrence can occur several months or even years after the onset, and recurrence can also occur even if the anti-GBM antibody level does not rise. Conversely, recurrence of serological changes does not necessarily accompany the recurrence of clinical symptoms. Daly et al. reported that 10 patients underwent cadaveric renal transplantation, and 7 patients maintained functional kidneys for 8.2 years.

　　6. Other

　　For patients diagnosed with this disease, if renal biopsy proves irreversible damage, it is difficult to control pulmonary hemorrhage with high-dose hormone shock therapy and plasma exchange. Bilateral nephrectomy can be considered to replace renal function with dialysis treatment. Anticoagulation and anti-aggregation therapy should not be used in patients with a risk of aggravating pulmonary hemorrhage during the treatment process. In addition, supportive therapy and prevention of secondary infection should be strengthened.