microscopic polyangiitis
Introduction
Introduction to micro-polyangiitis Microscopic polyangitis (MPA) is a systemic vasculitis of small vessel involvement. The clinical manifestations are similar to those of PAN. The characteristics are characterized by rapid glomerulonephritis (RPGN) and pulmonary involvement, which is different from PAN. Classical PAN mainly invades the small and medium arteries. If the lesion involves smaller arteries, veins and capillaries, Then exclude the classic PAN and belong to MPA, its clinical features are lung-kidney vasculitis, serum anti-MPO positive. basic knowledge The proportion of illness: 0.003% Susceptible people: no specific population Mode of infection: non-infectious Complications: hypertension, hemoptysis, anemia
Cause
The cause of micro-polyangiitis
(1) Causes of the disease
The cause is unclear. There are reports of this disease and rapid nephritis in the homologous siblings of human leukocyte antigen (HLA) in the family. Therefore, it is believed that the gene sensitivity and the external environment jointly cause the disease, and the causative factors causing vasculitis may be complex rather than Single.
(two) pathogenesis
Since the 1980s, the anti-neutrophil cytoplasmic antibody (ANCA) has been highly valued for the pathogenesis of vascular disease. The positive rate of ANCA in MPA, which is mainly characterized by necrotizing glomerulonephritis, is significantly increased. The main component of the antigen is leukocyte myeloperoxidase (MPO) or protease 3 (PR3), which produces corresponding specific leukocyte cytoplasmic antibodies, causing damage to the blood vessel wall. The ANCA theory has attracted widespread international interest and is currently actively exploring research, causing The causative factors of vasculitis may be complex rather than singular.
Recently, ANCA is considered to be an important cause of vascular endothelial injury, especially in WG and MPA. In vitro experiments show that ANCA can stimulate neutrophil adhesion to endothelial cells and induce TNF- (tumor necrosis factor-) sensitization. Leukocyte-dissolved endothelial cells in culture, since the target antigens MPO and PR3 of ANCA are only present in the chlorophyll granules, the activation mechanism of ANCA-PMN (polymorphonuclear neutrophils) has not been elucidated, and has been sensitized from PMN cells. PR3 was measured on the plasma membrane, and then in vitro and in vitro studies showed that TNF- and IL-8 act synergistically on PR3, moving it from intragranular to neutrophil membrane.
Expression of cytokine-induced adhesion molecules (LFA-1, ICAM-1 and ELAM-1) causes close contact between PMN and endothelial cells, cytokine-sensitized neutrophils, coexistence of endothelial cells and ANCA in the blood circulation, causing subsequent ANCA initiation Vasculitis occurs in a cascade reaction, although both experimental and clinical findings, the specific role of PR3-ANCA and MPO-ANCA in the pathogenesis of vasculitis remains unknown.
Anti-endothelial cell autoantibodies (AECA) directly target endothelial cell surface antigens, which are considered to be the causative factors of vasculitis, but their target antigens in vasculitis and their significance in pathogenesis are still poorly understood. Primary vasculitis and secondary to systemic immune disease vasculitis can be detected, so it is a non-specific index, the study shows that 28% of patients with systemic vasculitis can be seen positive in serum AECA, some AECA positive serum can be Endothelial cells produce complement-dependent or antibody-dependent cellular cytotoxicity (ADCC), suggesting that AECA is involved in direct damage to endothelial cells, especially in primary vasculitis (WG, MPA and Kawasaki disease), which can pass through granules The binding of Fc-receptors of cells or monocytes enhances endothelial adhesion and causes endothelial damage. The adhesion itself or other toxic secretions can also activate cells, although there is a general increase in AECA in primary vasculitis. However, its specificity is poor, so the practical significance of such antibodies needs further evaluation. Cytokines may be associated with the pathogenesis of vasculitis. It has been reported that TNF- and IL-2 in PAN and CSS serum are significantly increased. TNF-, IL-1 is moderately elevated, and associated with this type of pathogenesis are IL-1 and TNF-, which activate endothelial cells and PMN to trigger or at least promote endothelial damage, Kelow et al reported TGF- ( Transforming growth factor ), IL-6, IL-8 is enhanced in vasculitis.
Immunohistochemical studies of peripheral nerve and muscle supply vessels in PAN patients showed that inflammatory infiltrates were mainly monocytes and T lymphocytes (especially CD4+), and infiltrating cells expressed immune activation antigens such as IL-2R, transferrin. The receptor and HLA-DR antigen suggest that the T cell-mediated immune mechanism participates in the development of PAN injury and prolongs the injury period.
Prevention
Miniature polyangiitis prevention
The cause of this disease is unknown. At present, there is no effective preventive measure. It is generally believed that people in good health should pay attention to self-protection in daily life, avoid unhealthy lifestyle, and make rational use of antibiotics to prevent allergic reactions, especially for people with high-sensitivity constitution. Avoid all kinds of sensitizing factors, and it is expected to prevent the disease.
Complication
Miniature polyangiitis complications Complications, hypertension, hemoptysis
19% to 33% of patients with hypertension, 12% to 29% of patients with this disease with pulmonary hemorrhage, and a large number of hemoptysis, such as long-term presence can be complicated with dyspnea and anemia.
Symptom
Minimal polyangiitis symptoms common symptoms nephrotic syndrome oliguria protein urinary edema no urinary muscle pain abdominal pain sputum with bloodshot oral ulcer weight loss
The disease may have a long period of asymptomatic period before diagnosis. It may also have systemic symptoms such as joint pain or hemoptysis within a few days or years before the outbreak, and the course spans from 4 weeks to 2 years. Most patients are diagnosed before diagnosis. There are systemic symptoms, such as systemic discomfort without cause, fever, weight loss, etc., often diagnosed, 56% to 70% of patients with significant changes in the body, and some patients from the initial onset of symptoms to the diagnosis for more than 1 year, most patients The interval from the onset of kidney symptoms to renal biopsy is shorter than one month.
Kidney change
The main feature of MPA is 100% kidney involvement. Most patients show RPGN, oliguria or no urine, hematuria, and 1/3 of gross hematuria, proteinuria, severe cases of nephrotic syndrome proteinuria, severe hypertension is not much See, renal function can be progressively reduced.
2. Lung involvement
12% to 29% of patients with this disease are associated with pulmonary hemorrhage, which is also one of the important factors of morbidity and mortality. The hemoptysis is a common pulmonary involvement, but the blood in the sputum is bloody, and the hemoptysis is heavy. Most cases are within 1 month of admission. Appear, but also long-term, with breathing difficulties and anemia, pulmonary hemorrhage can lead to severe hypoxemia, common imaging features of alveolar shadow without pulmonary edema or infection, increased carbon monoxide conversion coefficient ( 30%) also prompted Pulmonary hemorrhage can be diagnosed by bronchoalveolar lavage. The clinical imaging function of some patients with small vascular pulmonary vasculitis is consistent with the interstitial lesion process, similar to idiopathic pulmonary fibrosis.
3. Other clinical manifestations
Similar to PAN, 65% to 72% of patients have skeletal muscle involvement (myalgia, joint pain, arthritis); 44% to 58% have skin changes (purpura, flaky hemorrhage); gastrointestinal symptoms have abdominal pain (32 %58%) and gastrointestinal bleeding (29%); only 14%36% of patients have peripheral neuropathy, which is less common than PAN; lesions in eyes, ears, nose, and throat are more common than PAN, and some patients have oral ulcers. .
Examine
Examination of micro-polyangiitis
There is no specific examination for this disease.
Blood test
Mainly for the increase of erythrocyte sedimentation rate, platelet and white blood cell count increased, a small number of patients with eosinophilia, hemoglobin decreased positive cell anemia; plasma albumin levels decreased, almost all patients were negative for hepatitis B surface antigen, C-reactive protein increased The level of 2-globulin increased, total complement, C3, C4 levels were normal or partially elevated, and 39% to 50% of patients were RF positive, more common than antinuclear antibodies (21% to 33%).
2. Renal function test
All patients had renal involvement, serum creatinine >120mol/L, 15% serum creatinine level was normal in Jerra group, and mean creatinine was 574mol/L in Hammersmith group (fluctuated from 1471405mol/L), often accompanied by microscopy Hematuria, more than 90% of patients have proteinuria, more than 3g / 24h.
3.ANCA testing
Indirect immunofluorescence (IFT), enzyme-linked immunosorbent assay (ELISA) and other methods, IFT often has false positives due to anti-nuclear antibodies, so IFT results must be combined with ELISA to detect target antigen antibodies, IFT combined with ElLSA method The diagnosis of small vasculitis is as high as 90%. There are two kinds of patterns in IFT examination: cytoplasmic C-ANCA, uniform granulocyte staining, perinuclear P-ANCA, coloration concentrated around the nucleus of the nucleus, IWT Mainly manifested as perinuclear P-ANCA, ELISA target antigen is myeloperoxidase (MPO), active rate positive rate of 50% to 75% or more, domestic Zhang Shaoling measured 19 cases of MPA, anti-MPO positive 6 cases, all and Renal damage, 5 cases with lung damage, suggesting that anti-MPO antibodies are more common in the lungs and kidney lesions, which can be increased in the first month before the active period and decreased in the remission period.
Auxiliary inspection
Tissue biopsy
Small arteriovenous lesions are the same as classic PAN. The differential diagnosis is in renal pathological examination. The renal biopsy shows focal segmental necrotic glomerulonephritis (FSNG) and crescent formation, most immunofluorescence is negative, 80% rapid progressive nephritis type III ( No immune complexes have no fluorescence response) caused by microangiitis.
Angiography
No microaneurysms and stenosis.
Diagnosis
Diagnosis and identification of micro-polyangiitis
diagnosis
There are many system damages, especially lung and kidney damage, histopathology is small blood vessel inflammation without granuloma formation, renal pathology is segmental necrotic glomerulonephritis, with crescent formation, immunofluorescence negative, serum P-ANCA positive, Anti-MPO antibody positive, can diagnose the disease.
Differential diagnosis
Wegener granuloma
It is also a small vascular necrotic inflammation, mostly nasal, paranasal sinus, lung, kidney damage, the identification point is that Wegner's granulomatosis has granuloma formation, serum C-ANCA positive, anti-PR3 positive.
2. Goodpasture syndrome
Symptoms similar to MPA have pulmonary hemorrhage and rapid nephritis, but anti-basement membrane antibodies can be found in the blood. Renal pathological immunofluorescence has characteristic glomerular basement membrane linear IgG, C3 deposition.
3. Classical nodular polyarteritis
Classical multi-invasion of the medium artery and its branches, while the latter involves small arteries and venules, characterized by small and medium arterial necrosis, non-granulomatous vasculitis, glomerulonephritis is a classic nodular polyarteritis and micro-multiple The main distinguishing points of arteritis, such as moderate arteries and small arteries, are called nodular arteritis overlap syndrome, and the clinical manifestations and prognosis of the two diseases are different.
