I. Overview 1. Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that mainly involves small vessels and can invade small arteries, micro-arteries, capillaries and tiny veins in the kidneys, skin and lungs and other organs. It often presents as necrotizing glomerulonephritis and pulmonary capillaritis. Because it mainly involves small blood vessels including veins, it is mostly called MPA. 2. The 1990 American College of Rheumatology (ACR) classification criteria for vasculitis did not list MPA separately, so most previous MPAs were classified as polyarteritis nodosa, and very few were classified as Wegener’s granulomatosis (WG). MPA is currently considered to be a separate systemic necrotizing vasculitis with little or no immune complex deposition and is commonly seen in necrotizing glomerulonephritis and capillary vasculitis of the lung. 1993 ChapelHill Conference defined MPA as a necrotizing vasculitis involving mainly small vessels (such as capillaries, tiny veins or tiny arteries) without immune complex deposition. 4, The difference between polyarteritis nodosa (PAN) and MPA is that the former lacks vasculitis of small vessels, including tiny arteries, capillaries and tiny veins. 5. The disease is more common in men, with a male to female ratio of about 2:1. It mostly develops at the age of 50-60 years, with an incidence of (1-3)/100,000 people abroad, and the incidence in China is not yet known. The etiology and pathogenesis of MPA is unknown, and it is thought that ANCA may directly or indirectly cause vascular damage. Others believe that MPA is related to cytomegalovirus and bacterial infection. Pathology 1. Pulmonary: mainly capillaritis, diffuse alveolar hemorrhage, neutrophil infiltration in the alveolar septum and interstitium, nuclear dust can be seen, and erythrocytes in the interstitial lung. Small intravascular thrombosis and fibrinoid necrotizing capillaritis are rare. 2. Kidney: segmental, thrombotic, necrotizing glomerulonephritis with sparse or occult immune complexes in the glomerular and alveolar septa. 3. Vasculitis can also be seen in the skin and other organs. MPA can develop at any age, but is most common at the age of 40-50 years, with an incidence of (1-3)/100,000 people, with a slightly higher incidence in men than in women, with a male:female ratio of 1 to 1.8:1. The onset of MPA can be acute, showing rapidly progressive glomerulonephritis and pulmonary hemorrhage, and some can be very insidious for several years, with intermittent purpura, mild kidney damage, intermittent The presentation is characterized by intermittent purpura, mild renal damage, intermittent hemoptysis, etc. Typical cases have a skin-pulmonary-renal clinical manifestation. Systemic symptoms: fever, malaise, anorexia, arthralgia and loss of body mass may be present. 2. Skin manifestations: Various rashes may appear, with purpura and palpable congested maculopapular rash being the most common. There may also be reticular cyanosis, skin ulcers, skin necrosis, gangrene, and limb ischemia, necrotic nodules, urticaria, and vasculitis-related urticaria often lasting more than 24h. (30% of patients may develop renal-skin vasculitis syndrome: typical skin manifestations are erythema, maculopapular rash, red painful nodules, eczema and urticaria, etc.) Renal damage: The most common clinical manifestation of the disease, most patients develop proteinuria, hematuria, various tubular patterns, edema and renal hypertension, etc. Some patients develop renal insufficiency, which can progressively deteriorate to renal failure. However, very few patients may have no renal lesions. Lung damage: (1) The most susceptible organ after the kidney, half of the patients have pulmonary damage and alveolar capillaritis, 12%-29% have diffuse alveolar hemorrhage. (2) Clinical manifestations are asthma, cough, hemoptysis or coughing up bloody sputum, respiratory distress can be seen on examination, and woven S-pigment can be smelled in the lungs. l/3 of patients have cough, hemoptysis, anemia, and massive pulmonary hemorrhage leading to respiratory distress and even death. Some patients may develop interstitial pulmonary fibrosis on the basis of diffuse alveolar hemorrhage. 5, neurological system: Some patients have symptoms of neurological damage, multiple mononeuritis or polyneuropathy, and may also have central nervous system involvement, often manifested as seizures. 6, digestive system: The digestive tract can also be involved, manifested as gastrointestinal bleeding, pancreatitis and abdominal pain caused by intestinal ischemia, and in severe cases, perforation, etc., which is caused by small vasculitis and thrombosis of the gastrointestinal tract resulting in ischemia. 7, cardiovascular system: Some patients also have chest pain and heart failure symptoms, which can be seen clinically as hypertension, myocardial infarction and pericarditis. 8, other: some patients also have the performance of the ear, nose and throat, such as sinusitis, which is more easily confused with WG. A few patients may also have arthritis, arthralgia and testicular pain due to orchitis. Ocular symptoms include eye redness, pain and vision loss, and ophthalmic examination shows retinal hemorrhage, sclerositis and uveitis. Laboratory tests 1. Routine tests: Indicators reflecting acute inflammation such as elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), some patients have anemia, leukocytosis and thrombocytosis. Proteinuria, microscopic hematuria and erythrocyte tubular pattern are seen when the kidneys are involved, and serum creatinine and urea nitrogen levels are elevated. 2. Anti-neutrophil cytoplasmic antibody (ANCA): (1) About 80% of MPA patients are positive for ANCA, which is an important diagnostic basis for MPA and an important serological indicator for monitoring disease activity and predicting recurrence, and its titer is usually related to the activity of vasculitis. About 60% of these antigens are positive for myeloperoxidase (MPO)-ANCA (perinuclear-ANCA), which is often present in those with lung involvement, and about 40% of patients are positive for anti-proteinase-3 (PR3)-ANCA (cytoplasmic-ANCA). (2) Anti-cardiolipin antibodies (ACI) can be detected in about 40% of patients, and a small number of patients are positive for antinuclear antibodies and rheumatoid factor (RF). 3, imaging changes: chest X-ray examination in the early stage can be found without characteristic pulmonary infiltrative shadow or small vesicular infiltrative shadow, bilateral irregular nodular lamellar shadow, lung cavity is rare, can be seen secondary to alveolar capillaritis and pulmonary hemorrhage diffuse parenchymal infiltrative shadow. Interstitial fibrosis of the lung may appear in the middle and late stages. 4, biopsy pathology: lesions involving the kidney, skin, lung and gastrointestinal tract, (1) pathological features: segmental fibrinoid necrosis of small vessels without necrotizing granulomatous inflammation, infiltration of multinucleated leukocytes and mononuclear cells in the walls of small arteries, microarteries, capillaries and veins, and thrombosis may be present. Leukocytoclastic vasculitis is seen in the post-capillary microvenules. (2) Renal pathology is characterized by segmental fibrinoid necrosis of the glomerular capillary plexus, thrombosis and crescent formation, with occasional massive neutrophil infiltration within and around the necrotic segments. Immunological examination showed no or only sparse immunoglobulin deposition, and rarely immune complex deposition, which is of diagnostic importance. (3) Lung tissue biopsy shows pulmonary capillaritis and fibrosis with no or minimal immune complex deposition. (4) Muscle and peroneal nerve biopsies show necrotizing vasculitis of small to medium-sized arteries. The diagnosis of MPA should be considered if there is systemic damage with pulmonary involvement, renal involvement and palpable purpura, especially if there is also MPO-ANCA positivity. Renal biopsy and skin or other visceral biopsies are useful for the diagnosis of MPA. Infective endocarditis needs to be excluded in some patients. Before determining the diagnosis, it needs to be differentiated from PAN and WC. (2) The following conditions are helpful for the diagnosis of MPA: ① middle-aged and elderly, mostly males; ② with the above-mentioned prodromal symptoms; ③ manifestations of renal damage: proteinuria, hematuria or (and) acute renal insufficiency; ④ with clinical manifestations of pulmonary or pulmonary-renal syndrome (pulmonary-renal syndrome manifestations: proteinuria, hematuria, acute renal failure and pulmonary hemorrhage, etc.); ⑤ with manifestations of gastrointestinal, cardiac, ocular, ear, joint (6) Positive pANCA; (7) Kidney and lung biopsy can help the diagnosis. Differential diagnosis 1. Polyarteritis nodosa (PAN): The disease mainly involves medium-sized and/or small arteries, without capillaries, small veins and microarteries, and is a necrotizing vasculitis, rarely with granulomas. Peripheral nerve disorders are common (50%-80%). ANCA is rarely positive; 2. Allergic granulomatous vasculitis (CSS): This disease is a systemic vasculitis involving small and medium-sized vessels, with extravascular granuloma formation and hypereosinophilia, patients often present with allergic rhinitis, nasal polyps and asthma, which can invade the lungs and kidneys, with corresponding Patients often present with allergic rhinitis, nasal polyps and asthma. 3, WG: The disease is necrotizing granulomatous vasculitis, lesions involving small arteries, veins and capillaries, occasionally involving large arteries, clinical manifestations of necrotizing granulomas of the upper and lower respiratory tract, systemic necrotizing vasculitis and glomerulonephritis, severe cases of pulmonary hemorrhage-nephritis syndrome, cytoplasmic type-ANCA positive (88%-96% positive in the active phase). . 4. pulmonary hemorrhage and nephritis syndrome (Goodpasture’s syndrome): characterized by pulmonary hemorrhage and acute nephritis, positive anti-glomerular basement membrane antibodies, and significant immune complex deposits in the basement membrane seen on renal pathology. 5.5 lupus nephritis: with typical systemic lupus erythematosus manifestations, plus proteinuria can be diagnosed, and a large number of various immune complex deposits seen on renal biopsy, which can be differentiated from MPA can be differentiated. Treatment plan and principles Treatment can be divided into 3 stages: induction period, maintenance remission period and treatment relapse. (1) Glucocorticoid: Prednisone (Long) 1mg kg-1 d-1, morning dose or divided dose, generally reduce the dose after 4-8 weeks, and wait for the remission of the disease to maintain the amount of treatment, the maintenance amount of individual differences. Small doses of prednisone (Long) (10-20 mg/d) are recommended to maintain for 2 years or longer. For patients with severe disease and progressive deterioration of renal function, methylprednisolone shock therapy can be used, 0.5-1.0g intravenously each time, once daily or every other day, 3 times as a course of treatment, which can be repeated after 1 week as needed. Pay attention to the prevention and control of adverse reactions during hormone therapy. Treatment with prednisone alone is not advisable because the remission rate decreases and the recurrence rate increases. (2) Cyclophosphamide: can be used orally, the dose is generally 2-3mg?kg-1?d-1 for l2 weeks. Can also use cyclophosphamide intravenous shock therapy, the dose of 0.5-1g/m2 body surface area, once a month for 6 months, severe cases can be shortened to 2-3 weeks between doses, and then once every 3 months, until the disease is stable 1-2 years (or longer) can be discontinued for observation. Oral adverse reactions are higher than shock therapy. Blood tests and liver and kidney functions should be monitored during the drug administration period. (3) Azathioprine: Because of the high number of adverse reactions to long-term use of cyclophosphamide, induction therapy can also be switched to azathioprine once remission is achieved (usually after 4-6 months), 1-2 mg?kg-1?d-1 orally, maintained for at least 1 year. Adverse effects should be noted. (4) Mycophenolate: 1.0-1.5g/d for maintenance remission and treatment of relapsing MPA, with some efficacy, but less information and discontinuation of the drug may cause relapse. (5) Methotrexate: Methotrexate 5-25mg once a week has been reported to be effective in oral or intravenous treatment, and adverse effects should be noted. (6) Gammaglobulin: High-dose intravenous gammaglobulin (IVIC) 0.4g?kg-1d-1, 3-5d as a course of treatment, some patients are effective. It can be used alone or in combination when glucocorticoids and cytotoxic drugs cannot be used due to co-infection, frailty, or serious illness. (7) Plasma exchange: It may be beneficial for patients who are already on dialysis at the time of consultation. Because of the lack of data, the use of plasma exchange is based on clinical experience and requires careful weighing of the risks associated with plasma exchange (e.g., complications related to deep venous line placement, infection, etc.) against the potential benefits. Plasma exchange may be considered when there are also anti-glomerular basement membrane antibodies, severe alveolar hemorrhage, or severe renal pathology in the acute phase of the disease. (8) Biological agents: monoclonal antibodies against tumor necrosis factor (TNF)-α, CD20, etc. are mainly used in refractory patients or patients with multiple relapses after conventional treatment, and some patients have achieved better efficacy, but more clinical data are needed to confirm the final efficacy. 2, fulminant MPA treatment At this time, pulmonary and renal failure can occur, often with massive alveolar bleeding and rapid deterioration of renal function, can be combined with methylprednisolone and cyclophosphamide shock therapy, as well as supporting symptomatic treatment at the same time using plasma exchange therapy. Each plasma exchange is 2-4L, once a day for several days, and then every other day or several days as appropriate. This therapy is effective in some patients, with adverse effects such as bleeding and infection. Plasma exchange has poor effect on the removal of small molecule toxins such as creatinine and urea nitrogen, so if the patient’s blood creatinine is significantly elevated, it should be combined with hemodialysis treatment. 3.Dialysis and kidney transplantation A small number of patients with end-stage renal failure need to rely on maintenance dialysis or kidney transplantation, and a very small number of patients will relapse after kidney transplantation. 4. Other Patients with renal impairment should have their blood pressure strictly controlled within the normal range, and the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists is recommended. IX. Prognosis After treatment 90% of MPA patients can be improved, 75% of patients can be in complete remission, and about 30% of patients relapse after 1-2 years. The 2- and 5-year survival rates after treatment of this disease are about 75% and 74%. Similar to PAN, the major causes of death in this disease are uncontrolled disease activity, renal failure and secondary infections, and pulmonary involvement. The titer of ANCA in MPA should be closely monitored for ESR levels during the course of the disease and correlates poorly with disease activity.