1、.,1,(General Introduction),2004 Spring Teacher：畢黎琦,Rheumatic Diseases,Rheumatology,.,2,Section 1 General Introduction(總論) of Rheumatic Diseases Requirements(要求)：1. To know (了解)the definition of rheumatic diseases and its common pathology. 2. To be familiar with (熟悉)the classification of rheumatic di

2、seases and the common characteristics of connective tissue diseases. 3. To grasp(掌握) the features of joint manifestation of rheumatic diseases and clinical importance (意 義)of auto-antibodies detection.4. To be familiar with(熟悉) the classification and mechanism of 3 kinds of anti-rheumatic drugs.,.,3

3、,Definition: 1、Rheumatism (風濕)：Its defined as the chronic pain of joint, peri-articular tissues,muscle and bone. （風濕：是指關(guān)節(jié)、關(guān)節(jié)周圍軟組織、肌肉、 骨出現(xiàn)的慢性疼痛。）,.,4,2、Rheumatic diseases(風濕性疾病)： Its a disease entity involving joints and peri-articular tissues with different causes.(風濕性疾?。菏侵敢淮箢惒∫蚋鞑幌嗤奂?關(guān)節(jié)及其周圍組織的疾病

4、。) It encompasses diffuse connective tissue diseases, and other disorders involving joints and peri-articular tissues (including muscle,tendon, ligament, etc).(它包括：彌漫性結(jié) 締組織病及各種病因引起的關(guān)節(jié)和關(guān)節(jié)周圍軟組織，包括肌、 肌腱、韌帶等的疾病。,.,5,概念： 3、 diffuse connective tissue disease(彌漫性結(jié)締組織病)， 簡稱結(jié)締組織病(CTD). Its the main kind of r

5、heumatic diseases. It belongs to organ nonspecific autoimmune diseases(器官非特異性自身免疫病). Its also called collagenic disease(膠原病).,.,6,Common characters of diffuse CTD: （1）pathogenesis :autoimmunity; （2）pathologic change :chronic inflammation of vessels and connective tissue; （3）multisystem involvement.

6、Heterogeneous (4) course:onsetremissionrecurrence remission. Lifelong diseases. （5）gluco-corticosteroid hormone and immuno- suppressants; （6）Improved prognosis.,.,7,The nomenclature and classification of arthritis and rheumatic diseases from American society of Rheumatology in 1993 美國風濕病學學會對關(guān)節(jié)炎和 風濕性

7、疾病的命名和分類 （Arth Rheum 26:10291032,1993） 一、 Diffuse connective tissue diseases (彌漫性結(jié)締組織病) 1、Rheumatoid arthritis，RA (類風濕關(guān)節(jié)炎) 2、Juvenile rheumatoid arthritis，JRA (幼年類風濕關(guān)節(jié)炎) 3、 Systemic lupus erythematosus，SLE (系統(tǒng)性紅斑狼瘡) 4、 Systemic sclerosis，SSc (系統(tǒng)性硬化病) 5、 Diffuse fasciitis，EF (彌漫性筋膜炎),.,8,6、 Polymyosi

8、tis/Dermatomyositis，PM/DM (多肌炎/皮肌炎) 7、 Vasculitis (血管炎) 8、 Sjogren syndrome，SS (干燥綜合征) 9、 Overlapping syndrome，OS (重疊綜合征) 10、 others :Polymyalgia rheumatica ( 風濕性多肌痛) 二、Arthritis associated with spodylitis (并發(fā)脊柱炎的關(guān)節(jié)炎) Seronegative spondyloarthropathies (血清陰性脊柱關(guān)節(jié)病) 1、Ankylosing spondylitis，AS (強直性脊柱炎

9、) 2、 Reiter syndrome，RS (賴特綜合征) 3、 Psoriatic arthritis，PA (銀屑病關(guān)節(jié)炎) 4、 Enteropathic arthritis，EA (炎性腸病關(guān)節(jié)炎),.,9,三、 Osteoarthritis，OA (骨性關(guān)節(jié)炎) 四、Infection (感染所致風濕性綜合征) 1、 Reactive arthritis (反應性關(guān)節(jié)炎) Rheumatic fever (Rheumatic aithritis)，RF (風濕熱) 2、 Direct infection (直接) 五、Metabolic and endocrinologic di

10、seases (伴有風濕性疾病的 代謝或內(nèi)分泌疾病) 1、 Gout (痛風) 2、 Pseudogout (假性痛風) 六、Others (其他) 1、Osteoporosis (骨質(zhì)疏松) 2、Fibromyalgia syndrome，F(xiàn)S (纖維肌痛綜合征) 3、Palindromic rheumatism，PR (復發(fā)性風濕病),.,10,Epidemiology of rheumatic diseases in China The incidence some rheumatic diseases: SLE：0.07% RA:0.320.36% AS：0.25% pSS：0.3%

11、OA：50%（50 years old） Gout：increased day by day Rheumatic arthritis：decreased markedly,.,11,History taking and physical examination (病史采集和體格檢查),History taking： 1.Articular and peri-articular tissue involvement (關(guān)節(jié)及其周圍組織受累情況) involved joint(site); disease course; swelling; pain; morning stiffness; rel

12、ieving and aggravation factors; reaction to therapy; and so on. 2.Organ system involvement (各器官系統(tǒng)受累情況) Kidney, heart, brain, liver, gastro-intesting, respiratory and hematologic system, skin, muscle. (Tab 8-1-1, P1029),.,12,History taking and physical examination (病史采集和體格檢查),Physical examination： th

13、e general physical examination 一般內(nèi)科體格檢查 Muscle examination:（myagia, myasthenia, myotrophy, myodynamia -6 grades:0-5） 2. Skin-mucosa examination:(rashes, mucous membrane lesions) 3. Joints:(site, symmetric, effusion, redness, swelling, heat, tenderness, active and passive motion of the joints and spi

14、ne).,.,13,.,14,.,15,.,16,.,17,.,18,.,19,Differentiating features of common arthritides RA AS OA Gout SLE peripheral arthritis Onset slow,insidious slow,insidious slow,insidious abrupt uncertain First metacarpophalangeal knee knee,lumber, 1st metatarso- hand Involved joint,proximal inter- hip distal

15、inter- phalangeal joint or Joint phalangeal joint,wrist ankle phalangeal joint joint others Pain persistent pain pain at severe pain uncertain Feature pain at rest at rest activity night pain Swelling soft tissue soft tissue bony redness,heat less Feature hypertrophy swelling common Deformity common

16、 and obvious most in less rare rare joint function is limited hip joint common Changes symmetric asymmetric weight-bearing recurrent multiarthritis lower limbs joint Axial skeleton occationaly must present lumber hyperplasia no no And/or sacro- joint function condensing osteitis iliac joints is limi

17、ted lip-like change,.,20,常見關(guān)節(jié)炎的關(guān)節(jié)特點 關(guān)節(jié) RA AS OA 痛風 SLE 周圍關(guān)節(jié)炎 起病 緩 緩 緩 急驟 不定 首發(fā) MCP 膝、髖、 膝、腰、 大拇趾 手關(guān)節(jié)或 PIP、腕 踝 DIP 其他部位 痛性質(zhì) 持續(xù)性 休息后 活動后 痛劇烈 不定 休息后加重 加重 加重 夜間重 腫性質(zhì) 軟組織為主 軟組織為主 骨性肥大 紅、腫、熱 少數(shù) 畸形 常見，明顯 多見于髖 小部分 少見 偶見 影響功能 演變 對稱性 不對稱 負重關(guān)節(jié) 反復發(fā)作 多關(guān)節(jié)炎 下肢大關(guān)節(jié) 癥狀明顯 脊柱炎和（或） 偶有 必有 腰椎增生 無 無 骶髂關(guān)節(jié)病變 功能受限 唇樣變,.,21,La

18、boratory test 實驗室檢查 1. Special examination Autoantibody examination： (1) ANA and ANA spectrum（抗核抗體譜） Anti ds-DNA SLE(50%) high specificity Anti-histone drug-induced lupus(95-100%),SLE(70%),RA(30%) Anti-Sm SLE(20-30%), marker antibody Anti-U1RNP MCTD(100%), SLE,SSc,etc Anti-SSA(Ro) SS(60-76%), SLE(30

19、-40%) Anti-SSB(La) SS(50-60%), SLE(30-40%) Anti-Scl-70 SSc(15-20%) marker antibody Anti-Centromere SSc(CREST)(80%) marker antibody Anti-Ku SLE(10%), PM+SS overlap(55%) Anti Jo-1 PM(31%), marker antibody ,.,22,Laboratory test 實驗室檢查 （2） ANCA(antineutrophil cytoplasmic antibody,抗中性粒細胞胞漿抗體) 。 c-ANCA (cy

20、toplasmic, 胞漿染色) proteinase 3(PR3) p-ANCA (perinuclear, 核周邊染色) MPO diagnosis of vasculitis c-ANCA for Wegener granulomatosis (30-90% sensitivity, 98% specificity) （3）Antiphospholipid antibodies (抗磷脂抗體): include: Anticardiolipin antibody (抗心磷脂抗體) Lupus anticoagulant (狼瘡抗凝物) False-positive serologic t

21、est for syphilis (假陽性梅毒血清試驗) 1.multiple thromboses positive Antiphospholipid 2.thrombocytopenia + anti- phospholipid antibody syndrome 3.recurrent spontaneous antibody (抗磷脂綜合征) abortion,.,23,Laboratory test 實驗室檢查 （4）RF (Rheumatoid factor, 類風濕因子 ) 80-90% RA. HLA-B27: 90% AS. Complement: CH50(serum to

22、tal complement) ,C3, C4 for SLE and vasculitis. Analysis of synovial fluid: Common items: routine test(WBC count and differential count) biochemistry test(glucose, chloride) smear and culture for bacteria test RF Crystal test under micropolariscope(偏振光顯微鏡),.,24,Classification and differentiation of

23、synovial effusions Diseases WBC differentiation neutrophil micro- count of WBC (%) polariscope 1. Normal 0-200 10 2. Non- OA 1000-2000 monocyte/ inflammation lymphocyte 20 3. Mild SLE 2000-5000 neutrophil 30 inflammation 4. Severe RA 5000-50000 neutrophil -70 inflammation Gout 5000-75000 neutrophil

24、-70 crystal of urate (noninfectious) Pseudogout 5000-75000 neutrophil -70 crystal of CPPD* *CPPD:calcium pyrophosphate dihydrate 5. Severe inflammation Bacterial (infectious) infections 5000-250000 neutrophil -90,.,25,2. General examination Blood routine for WBC,RBC, pletlet count Urine routine to t

25、est WBC, RBC, casts in urine, also glucose, protein, crystal, pH, gravity, bacteria, bilirubin, urobilinogen,etc. Hepatic function test(AST, ALT) Renal function test (BUN-blood uric nitrogen, creatinine),.,26,2. Radiographic studies 1. Plain film： convenient,economic; but samll erosion of joint may

26、be missed. 2. CT： for sacro-iliac joint (sacroiliitis in AS) for brain (SLE) for lung(interstitial fibrosis) 3. MRI (magnetic resonance imaging) : expensive,for brain,spinal cord,muscle,bone,small erosion. 4. Angiography (血管造影) expensive and traumatic; for vasculitis (polyarteritis nodosa, Takayasus

27、 arteritis大動脈炎）,.,27,Pathology (病理) Biopsy : renal biopsy-lupus nephritis(SLE) muscle biopsy-myositis(PM/DM) labial mucosa,parotid gland-cheilitis lupus band test-SLE 1. Inflammatory reaction： Its manifested by infiltration gathering of lymphocytes, macrophages and plasma cells due to immunologic reaction