Microscopic polyangiitis (MPA), also known as microscopic polyarteritis, is a systemic, necrotizing vasculitis that is an autoimmune disease. The disease mainly affects small vessels, including capillaries, small veins or microarteries, but can also involve small and/or medium-sized arteries, so it needs to be differentiated from polyarteritis nodosa. Immunopathological examination is characterized by the absence or small amount of immune complex deposits in the vessel wall. It can invade several organs throughout the body, such as kidney, lung, eye, skin, joints, muscles, gastrointestinal tract and central nervous system, etc. Clinically, necrotizing glomerulonephritis is the prominent manifestation, but pulmonary capillaritis is also very common. The disease is more common in men, the ratio of men to women is about 2:1, mostly in the 50-60 years of age onset, the exact incidence of China is not clear. I. Clinical manifestations 1. Symptoms and signs: Prevalent in winter, most have upper respiratory tract infection or drug allergy-like prodromal symptoms. Non-specific symptoms include irregular fever, fatigue, skin rash, arthralgia, myalgia, abdominal pain, neuritis and weight loss, etc. (1) Kidney: About 70% to 80% of patients have renal involvement, almost all have hematuria, about 30% have carnal hematuria, accompanied by varying degrees of proteinuria, hypertension is uncommon or mild. About half of the patients present with an acute nephritis syndrome, manifesting as necrotizing crescentic nephritis, with early acute renal failure. (2) Lung: The most susceptible organ after the kidney (about 50%), clinically manifested as asthma, cough, hemoptysis and hemoptysis. In severe cases, it may manifest as pulmonary-renal syndrome with proteinuria, hematuria, acute renal failure, pulmonary hemorrhage, etc. It is very similar to pulmonary hemorrhage-nephritis syndrome (Goodpasture’s syndrome, also known as anti-basement glomerulonephritis), which is positive for anti-glomerular basement membrane antibodies for differentiation. (3) Gastrointestinal tract: manifestations of mesenteric vascular ischemia and gastrointestinal bleeding, such as abdominal pain, diarrhea, and black stools, may be present. (4) Heart: heart failure, pericarditis, arrhythmia, myocardial infarction, etc. may be present. (5) Ear: Ear involvement may include tinnitus, otitis media, neurological hearing loss, and eye involvement may include iridocyclitis, sclerositis, uveitis, etc. (6) Joints: often manifest as joint swelling and pain, of which only 10% of patients have joint oozing, synovial thickening and erythema. (7) Nerve: about 20%-25% of patients have neurological involvement, which may include polyneuritis, peripheral neuritis, central neurovascular inflammation, etc., manifesting as local peripheral sensory or motor disorders, ischemic encephalopathy, etc. (8) Skin: About 30% of patients have renal-skin vasculitis syndrome, with typical skin manifestations such as erythema, maculopapular rash, red painful nodules, eczema and urticaria. 2. Laboratory tests (1) General laboratory tests: leukocytosis, increased platelets, etc. and anemia disproportionate to bleeding, elevated sedimentation, increased C-reactive protein, positive rheumatoid factor, elevated gamma globulin, proteinuria, hematuria, blood urea nitrogen, elevated creatinine, etc. (2) Anti-neutrophil cytoplasmicantibody (ANCA): It is an important serologic indicator for the diagnosis of the disease, monitoring disease activity and predicting relapse. 50% to 80% of the titers are positive, and its titer is usually related to the activity of vasculitis. two major antigens targeted by ANCA are serine protease 3 ( MPO-ANCA is also known as pANCA (perinuclear type), 70% of MPA the antibody positive; PR3-ANCA is also known as cANCA (cytoplasmic type), mostly seen in Wegener’s granulomatosis, but no extra-renal manifestations of necrotizing crescentic glomerulonephritis patients in 20%-30% PR3-ANCA positive. (3) Renal biopsy: The pathology is characterized by segmental fibrinoid necrosis of the glomerular capillary plexus, thrombosis and crescent formation, with occasional massive neutrophil infiltration in and around the necrotic segments. Immunologic examination with no or only sparse immunoglobulin deposition and rarely immune complex deposition is diagnostically important. Lung tissue biopsy shows pulmonary capillaritis and fibrosis with no or minimal immune complex deposition. II. Diagnostic points There is no uniform diagnostic criteria for this disease, and the following conditions can help the diagnosis of MPA 1. middle-aged and elderly, mostly male; 2. with the above-mentioned prodromal symptoms; 3. renal damage: proteinuria, hematuria or (and) acute renal insufficiency; 4. with clinical manifestations of pulmonary or pulmonary-renal syndrome; 5. with manifestations of involvement of joints, eyes, ears, heart, gastrointestinal tract and other organs of the body; 6. p-ANCA positive; 7. kidney and lung biopsy can help the diagnosis. Differential diagnosis 1. polyarteritis nodosa (PAN): This disease mainly involves medium-sized and/or small arteries, without capillary, small vein and micro-artery involvement. It is a necrotizing vasculitis, rarely with granulomas. Renal damage is renal vasculitis, renal infarction and microaneurysm, without acute nephritis and without pulmonary hemorrhage. Peripheral nerve disorders are common (50%-80%), and about 20%-30% have skin damage, manifesting as painful erythematous subcutaneous nodules that appear in clusters along the arteries. anca is less positive (<20%), and angiography shows microangiomas, stenosis, and inflammatory cell infiltration on biopsy of small and medium-sized artery walls. 2. Allergic granulomatous vasculitis (Churg-Strass Syndrome): 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 may invade the lungs and kidneys, with corresponding symptoms, and may be positive for ANCA, but more often positive for pANCA. 3. Wegener's granulomatosis (Wegener'sgranulomatosis): this 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 renal syndrome. Positive cANCA (88%-96% positive in active phase). 4. pulmonary hemorrhage - nephritis syndrome (Goodpasture's syndrome): characterized by pulmonary hemorrhage and acute nephritis, positive anti-glomerular basement membrane antibodies, renal pathology can be seen in the basement membrane with significant immune complex deposits. 5. Lupus nephritis: with typical SLE manifestations, plus proteinuria can be diagnosed, and a large number of various immune complexes are seen on renal biopsy, which can be differentiated from MPA. Treatment plan and principles Treatment can be divided into three phases: induction period, maintenance of remission period and treatment of relapse. (1) Glucocorticoid: Prednisone (Long) 1mg/(kg.d), morning dose or divided dose, generally reduce the dose after 4~8 weeks, and then treat with maintenance amount after remission, the maintenance amount has individual differences. A small amount of prednisone (Long) (10~20mg/d) is recommended to maintain for 2 years, or longer. For patients with severe disease and progressive deterioration of renal function, methylprednisone(Long) shock therapy can be used, 0.5~1.0g intravenously each time, once daily or every other day, three times as a course of treatment, which can be repeated after one week as needed. Pay attention to the prevention and control of adverse reactions during hormone therapy. Treatment with prednisone alone is not advisable, as the remission rate decreases and the recurrence rate increases. (2) Cyclophosphamide (CYC): can be given orally at a dose of generally 2-3 mg/(kg.d) for 12 weeks. CYC can be used intravenous shock therapy, the dose of 0.5 ~ 1g / O body surface area, once a month for 6 months, severe cases can be shortened to 2 to 3 weeks between doses, and every 3 months thereafter, until the disease is stable 1 ~ 2 years (or longer) can be discontinued for observation. Oral side effects are higher than those of shock therapy. Blood tests and liver and kidney functions need to be monitored during drug administration. (3) Azathioprine: Due to the many side effects of long-term CYC use, induction therapy can also be switched to azathioprine once remission is achieved (usually after 4~6 months), 1~2mg/(kg.d) orally, maintained for at least 1 year. Adverse effects should be noted. (4) Mycophenolate: Mycophenolate 1.0~1.5g/d for maintenance remission and treatment of relapsing MPA has some efficacy, but information is scarce and discontinuation of the drug may cause relapse. (5) Methotrexate (MTX): MTX 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 (IVIG 0.4g/(kg.d)), 3~5d as a course of treatment) is used, which is effective in some patients, but expensive. 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) Specific immunosorbent: specific antigen binding resin is applied to adsorb the corresponding ANCA in the patient's serum, and a few reports have confirmed its effectiveness, but this treatment method is still being explored. 2, treatment of fulminant MPA: at this time, pulmonary - renal failure can occur, often with massive alveolar bleeding and rapid deterioration of renal function, can be prednisone (dragon) and CYC combined shock therapy, as well as supporting symptomatic treatment while using plasma replacement therapy. Each plasma exchange is 2-4 liters of plasma once a day for several days and then every other day or several days as appropriate. This therapy is effective for some patients, but it is expensive and has side effects such as bleeding and infection. Plasma exchange has poor effect on the removal of small molecule toxins such as creatinine and urea nitrogen, and it is advisable to combine with hemodialysis treatment if the patient's blood creatinine is significantly elevated. However, it is controversial whether to continue to use immunosuppressive and cytotoxic drugs in patients who have entered the uremic phase, because these patients respond poorly to drugs and have significantly more side effects. Treatment of relapse: Most patients may relapse after discontinuation of immunosuppressive drugs. CYC does not prevent relapse. If the patient also has a milder relapse during the initial treatment, the dose of prednisone may be temporarily increased to control the disease, and if treatment is ineffective, plasma exchange may be performed. 4.Dialysis and kidney transplantation: A small number of patients who enter end-stage renal failure need to rely on maintenance dialysis or kidney transplantation, and a very small number of patients will still relapse after kidney transplantation, and glucocorticoids and immunosuppressive therapy are still available after relapse. 5. Others: 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. V. Prognosis The one-year survival rate after treatment with glucocorticoids combined with immunosuppressants is 80%~100%, and the five-year survival rate has increased from 10% to about 70%~80% in untreated patients. The prognosis is closely related to the patient's age, creatinine level at the time of presentation, and the presence of pulmonary hemorrhage. Due to the rapid progression of nephritis, early and aggressive treatment is of utmost importance.