首都医科大学附属北京朝阳医院 呼吸与危重症医学科 肺血管炎 首都医科大学附属北京朝阳医院 呼吸与危重症医学科 北京呼吸疾病研究所 崔 瑷 2014-04-19 1

系统性血管炎（Systemic Vasculitides） CHCC II, 2012 Vasculitis is inflammation of blood vessel walls. Inflammation of blood vessel walls at least at some time during the course of the disease is a shared defining feature of all categories of vasculitis. Some categories of vasculitis also have characteristic tissue injury unrelated to the vasculitis. 2

系统性血管炎（Systemic Vasculitides） Inflammation Systemic Symptoms Local Symptoms fever fatigue malaise appetite and weight loss et al pain claudication bruits absent or diminished pulses loss of blood pressure haemorrhage et al 3

血管炎的命名和定义 （CHCC II, 2011） Large-vessel vasculitis (LVV) Takayasu arteritis (TAK) Giant cell arteritis (GCA) Medium-vessel vasculitis (MVV) Polyarteritis nodosa (PAN) Kawasaki disease (KD) 4

血管炎的命名和定义 （CHCC II, 2011） Small-vessel vasculitis (SVV) Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) Microscopic polyangiitis (MPA) Granulomatosis with polyangiitis (Wegener’s) (GPA) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Immune complex SVV Anti-glomerular basement membrane (anti-GBM) disease Cryoglobulinemic vasculitis (CV) IgA vasculitis (Henoch-SchÖnlein) (IgAV) Hypocomplementemic urticarial vasculitis (HUV) (anti-C1q vasculitis) 5

血管炎的命名和定义 （CHCC II, 2011） Variable vessel vasculitis (VVV) Behcet’s disease (BD) Cogan’s syndrome (CS) Single-organ vasculitis (SOV) Cutaneous leukocytoclastic angiitis Cutaneous arteritis Primary central nervous system vasculitis Isolated aortitis Others 6

血管炎的命名和定义 （CHCC II, 2011） Vasculitis associated with systemic disease Lupus vasculitis Rheumatoid vasculitis Sarcoid vasculitis Others Vasculitis associated with probable etiology Hepatitis C virus-associated cryoglobulinemic vasculitis Hepatitis B virus-associated vasculitis Syphilis-associated aortitis Drug-associated immune complex vasculitis Drug-associated ANCA-associated vasculitis Cancer-associated vasculitis 7

血管炎的命名和定义 （CHCC II, 2011） 8

大动脉炎 （Large-Vessel Vasculitis, LVV） CHCC II, 2011 LVV is defined as vasculitis affecting the aorta and its major branches more often than other vasculitides; however, any size artery may be affected. Takayasu Arteritis (TA) giant cell arteritis (GCA) Often granulomatous; predominantly affects the aorta and its major branches. Often granulomatous predominantly affects the aorta and its major branches ( carotid and vertebral arteries), often temporal artery. 50 9

大动脉炎 （Takayasu Arteritis, TA） Year Author Characters of patients 1830 Yamamoto fever, weight loss, dyspnoea, impalpable upper limb and carotid pulses (45y man) 1905 Takayasu dundal arteriovenous anastamoses (21y woman) Onishi absent radial pulses Kagosha 1920 Numano panarteritis, retinal ischaemia (25y woman) 1951 Shimizu Sano "pulseless disease" 10

大动脉炎 （Takayasu Arteritis, TA） 5000, Japan (1990) / incidence: 2.6/million/year, North American patients (1985) Sympotoms: pre-pulseless: non-specific inflammatory features (fever, night sweats, malaise, weight loss, arthralgia, myalgia, mild anaemia); chronic phase: vascular insufficiency. Pulmonary artery involvement in 14-100% of patients, Oligaemic lung fields on plain chest X ray correlate with pulmonary vasculopathy in approximately a third of cases. 11

大动脉炎 （Takayasu Arteritis, TA） Pathological feature: Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation. extensive destruction of the medial elastic fibers leads to aneurysm formation. 12

大动脉炎 （Takayasu Arteritis, TA） 13

大动脉炎 （Takayasu Arteritis, TA） 14

大动脉炎 （Takayasu Arteritis, TA） Treatment CORTICOSTEROIDS (CS) standard initial dose: 1mg/kg/day prednisolone or its equivalents two-thirds of the total daily dose is given early in the morning the rest of the total daily dose is given in the evening after meals. 15

大动脉炎 （Takayasu Arteritis, TA） Treatment IMMUNOSUPPRESSIVE (IS) MTX AZA CYP (2mg/kg/day): retinal vasculitis; pulmonary artery involvement; severe aortic regurgitation; myocarditis. MMF CSA、FK-506、LEF 16

大动脉炎 （Takayasu Arteritis, TA） Treatment Biologic agents anti-TNF agents: infliximab (IFX) CD20 monoclonal antibody: RTX IL-6 monaclonal antibody: Tocilizumab 17

大动脉炎 （Takayasu Arteritis, TA） Treatment Surgical treatment and invasive interventions surgical treatment: hypertension with critical renal artery stenosis, et al. balloon angioplasty stent percutaneous transluminal angioplasty (PTA) 18

大动脉炎 （Takayasu Arteritis, TA） Treatment Supportive measures Diet Low salt intake Calcium and vitamin D supplementation Regular exercise Antiplatelet agents: 80 mg/day aspirin 19

大动脉炎 （Takayasu Arteritis, TA） Turkish TA Study Group: refractory disease in TA angiographic or clinical progression despite treatment or the presence of any of the following characteristics prednidolone dose>7.5mg/day after 6 months of treatment, despite administration of conventional IS agents; new surgery due to persistent disease activity; frequent attacks (more than three per year); death associated with disease activity. 20

大动脉炎 （Takayasu Arteritis, TA） Kerr criteria two of the following four criteria shows active disease: systemic features like fever and arthralgia that cannot be explained by other reasons; elevated ESR; findings of vascular ischaemia and inflammation; typical angiographic findings. 21

大动脉炎 （Takayasu Arteritis, TA） 56y, female, “Exertional dyspnea for 10 years, Lower extremity edema for 9 years” 22

大动脉炎 （Takayasu Arteritis, TA） 23

大动脉炎 （Takayasu Arteritis, TA） 24

ANCA相关血管炎 （ANCA-associated vasculitis） Antineutrophil cytoplasmic autoantibody (ANCA) (1988, International Workshop on ANCA, Copenhagen) 25

ANCA相关血管炎 （ANCA-associated vasculitis） Antineutrophil cytoplasmic autoantibody (ANCA) 26

ANCA相关血管炎 （ANCA-associated vasculitis） Antineutrophil cytoplasmic autoantibody (ANCA) 27

ANCA相关血管炎 （ANCA-associated vasculitis） Antineutrophil cytoplasmic autoantibody (ANCA) Radiopraphic abnormalities: nodules, bilateral fluffy opacities; lobar consolidation, honeycomb lung. 28

ANCA相关血管炎 （ANCA-associated vasculitis） ANCA-associated vasculitis vs NSIP 29

ANCA相关血管炎 （ANCA-associated vasculitis） ANCA-associated vasculitis vs NSIP 30

ANCA相关血管炎 （ANCA-associated vasculitis） ANCA-associated vasculitis vs NSIP 31

ANCA相关血管炎 （ANCA-associated vasculitis） ANCA-associated vasculitis vs NSIP 32

ANCA相关血管炎 （ANCA-associated vasculitis） Antineutrophil cytoplasmic autoantibody (ANCA) Csernok E, et al. Blood. 2006;107(11):4440-4448. Voswinkel J, et al. Ann Rheum Dis. 2006;65(7):859-864. 33

ANCA相关血管炎 （ANCA-associated vasculitis） Antineutrophil cytoplasmic autoantibody (ANCA) Csernok E, et al. Blood. 2006;107(11):4440-4448. Voswinkel J, et al. Ann Rheum Dis. 2006;65(7):859-864. 34

ANCA相关血管炎 （ANCA-associated vasculitis） Antineutrophil cytoplasmic autoantibody (ANCA) mm Drug-induced systemic vasculitis Inflammatory bowel disease and autoimmune liver disease Arthritis Lung diseases: cystic fibrosis Infections 35

ANCA相关血管炎 （ANCA-associated vasculitis） Antineutrophil cytoplasmic autoantibody (ANCA) 36

ANCA相关血管炎 （ANCA-associated vasculitis） Pulminary affectation of ANCA-associated vasculitis 37

ANCA相关血管炎 （ANCA-associated vasculitis） Granulomatosis with polyangiitis (GPA) A mean age of disgnosis: 65-70 years, without clear sex predominance. Rriggering factors: infectious agents, environmentaltriggers, drug. Clinical features: cutaneous signs, ear, nose, upper airway, lower airway manifestations,cardiovascular, gastrointestinal, renal, CNS presents M 38

ANCA相关血管炎 （ANCA-associated vasculitis） Granulomatosis with polyangiitis (GPA) 39

ANCA相关血管炎 （ANCA-associated vasculitis） Microscopic polyangiitis (MPA) A mean age of disgnosis: 60-65 years, men slightly predominance. 40

ANCA相关血管炎 （ANCA-associated vasculitis） Microscopic polyangiitis (MPA) 41

ANCA相关血管炎 （ANCA-associated vasculitis） Esinophilic granulomatosis with with polyangiitis (EGPA) A mean age of disgnosis: 48 years, without clear sex predominance. Rriggering factors: infectious agents, drugs, desensitization, vaccination. Clinical features: mononeuritis multiplex; necrotic vascular purpura, gut, kideney, heart Pathogenic features: eosinophil infiltration (52%), granuloma (18%), vasculitis (55%) Laboratory anomalies: blood hypereosinophilia, high IgE titers (75%), anti-MPO P-ANCA-positivity (30-40%); anemia (83%), rheumatoid factor-positivity (53.6%), Imagery: bilateral and migratory infiltrates or mixed interstitial patchy alveolar opacities; typical stenoses consistent with vasculitis 42

ANCA相关血管炎 （ANCA-associated vasculitis） Esinophilic granulomatosis with with polyangiitis (EGPA) 43

ANCA相关血管炎 （ANCA-associated vasculitis） 44

ANCA相关血管炎 （ANCA-associated vasculitis） 45

ANCA相关血管炎 （ANCA-associated vasculitis） 46

ANCA相关血管炎 （ANCA-associated vasculitis） 47

ANCA相关血管炎 （ANCA-associated vasculitis） Criteria for treatment response in ANCA-associated vasculitieds 48

ANCA相关血管炎 （ANCA-associated vasculitis） 49

ANCA相关血管炎 （ANCA-associated vasculitis） 50

血管炎 （vasculitis） Behcet’s disease 51

血管炎 （vasculitis） Behcet’s disease 52

血管炎 （vasculitis） Behcet’s disease 53

血管炎 （vasculitis） Behcet’s disease 54

血管炎的命名--2011 CHCC II Single organ associated with systemic disease associated with probable etiology variable vessel vasculitis (DB) 55

问题与展望 作为一种少见病，临床医生对其认识不足。有报道称血管炎的发病率 为20-100/106，累计发病率150-450/10； 缺乏特征性的症状和体征表现。一方面血管炎的临床表现与感染、胶原血管病、甚至恶性肿瘤相似；另一方面某种特定的血管炎其临床表现也各不相同，仅少数病人具有全部的典型表现； 缺乏高敏感性、高特异性的诊断标准； 对于血管炎的病因和发病机理尚缺乏充分的认识。 血管炎的准确诊断有赖于临床医生对这类疾病的临床表现、实验室检查、影像学特点和病理学特点的充分认识。 鉴于血管炎所具有的病理学改变特点，病理学检查对于明确血管炎的诊断、类型、受累范围，并除外其他疾病具有重要的意义。