姜林娣-類風(fēng)關(guān)

1、What is RA? RA is a chronic polyarticular inflammatory arthritis that involves not only small joints of the hands and feet but also systemic organs. Pathologic change: chronic synovitis with pannus (血管翳)formation. It will cause bony destruction, deformation, disability if joint inflammation repeated

2、ly occur. RF is present in the sera of more than 75%of patients. The prevalence rate of RA has been estimated to be 0.32%-0.36% in China, Women appear to be affected three times more commonly than men. ETIOLOGY1.Infectious agents: Epstein-Barr virus, mycoplasma, macobacteria, retrovirusesT lymphocyt

3、e and macrophage activationB lymphocyte activationChange of the gene expression Molecular mimicry2. Genetic factors A high incidence among monozygotic twins (30% 50%),first-degree relative Role of HLA-DR4 in the susceptibility to and severity of RA - 70% RA patients ，a relative risk of having RA wit

4、h HLA-DR4 of 4 to 5 - The susceptibility epitope (shared epitope 共同表位): QKRAA或QRRAA- It was considered to be related with the severity of established RA3. Gender: Predominance in women Improvement or remission of RA during pregnancy4.Induced factors: tiredness, humidity, cold, mulnutrition, psychica

5、l stimuli antigen :HLA-DR(QKRAA)、heat shock protein、IgG、type II collagen antigen processingmacrophages +MHCII-peptide complexes presentation T cell cytokine（IL-1、2、3、4、 6、TNF、r-INF） B cell activation immune damage RF and other antibody collagenase、stromolysin cartilage and bone destruction extra-art

6、icular symptomPATHOLOGYPATHOLOGIC FINDING1. chronic synovitis In acute phase: effusion and cell infiltration In chronic phase: the number of A type cell remarkably increases the pannus erodes cartilage, bone, ligaments and tendons. 2. extra-articular：vasculitis、rheumatoid noduleCLINICAL FAETURES The

7、 usually age at onset is 35-50 years The ratio of female to male is 3:1 The onset of RA is usually insidious Systemic symptom of fatigue, malaise, fever, weight loss may be seen 1. Joint manifestation（1）morning stiffness stiffness persisting for over 30 minutes is prominent in the morning or after d

8、aytime activity and subsides during the day The persisting length of morning stiffness is associated with the degree of joint inflammation. The duration of morning stiffness is used as the index of disease activity.（2）pain and tenderness： painful on rest location：small (PIP,MCP), symmetric joint cha

9、racteristic：persisting、dull or swollen pain（3）swelling：synovial proliferation, effusion, swelling of soft tissue（4）articular deformity：ulnar deviation of the fingers, “swan-neck” deformity, atrophy of skin and muscle (see figure1-5)（5）involvement of special joint: atlantoaxial subluxation，shoulders,

10、 temporomandibular joint, hips.Figure1-4: 尺側(cè)偏移 鈕扣花畸形 掌指關(guān)節(jié)腫脹 受累關(guān)節(jié)示意（6）Functional capacity 1991 ACR criteria for classification of functional status in RAClass I Completely able to perform usual activities of daily living (self-care, vocational, and avocational) Class II Able to perform usual self-car

11、e and vocational activities, but limited in avocational activitiesClass III Able to perform usual self-care activities, but limited in vocational and avocational activitiesClass IV Limited in ability to perform usual self-care vocational, and avocational activities 2. Extra-articular manifestations（

12、1）Rheumatoid nodules 20%-30% patients areas that are repeatedly subjected to friction, such as the extensor surface of the forearm The advent indicates the disease is in the active phase （2）rheumatoid vasculitis: episcleritis, scleritis（3）pulmonary manifestation diffuse interstitial fibrosis: abnorm

13、al on CT scan, restrictive diffuse pattern intrapulmonary nodules:：asymptomatic, infected, cavitate rheumatoid pleural disease：exudative, WBC5 000/mm3, lower level of glucose (4）pericarditis: 30% pericardial effusion, asymptomatic（5）gastrointestinal manifestation: nausea, loss of appetite（6）kidney：d

14、rug-induced，amyloid degeneration（7）Neurologic manifestations： A cervical myclopathy can result from atlantoaxial subluxation: sensory abnormity and loss of strength peripheral neuropathies can be produced by proliferating synovium causing compression of nerves and rheumatoid vasculitis: carpal tunne

15、l syndrome.（8）Hematologic manifestations ：anemia, Feltys syndrome LABORATORY FINDING1. Anemia: a hypochromic normocytic anemia 2. Elevated ESR and CRP are demonstrated an active condition of the disease3. Joint fluid examination: WBC in the range 5000 to 20 000/mm3，with 5070% as polymorphonuclear le

16、ukocytes , a poor mucin clot, normal level of glucose 6. RF RF is an IgG,IgA, IgM antibody directed against the Fc fragment RF is Present in the sera of more than 60%-70% patients Despite the extremely strong association of RFs with RA, they clearly do not cause the disease. RF production occurs com

17、monly in other disorders: syphilis, sarcoidosis, infective endocarditis, tuberculosis, leprosy ,viral infection and parasitic infections, other autoimmune disease (SLE, PSS, DM), healthy people(10%).7.X- ray changes Class I swollen of soft tissue, juxta-articular osteoporosis Class II joint space na

18、rrowing Class III bony cysts and bony erosions Class IV subluxation, fibrous and bony ankylosis8. Pathologic findingRheumatoid nodule and synovial biopsy 1988 Revised ARA Criteria for Classification of RA Criterion definition1.Morning stiffness lasting at least 1hr 2.Arthritis of three at least thre

19、e joint areas simultaneously or more joint areas having soft tissue swelling or fluid 3.Arthritis of hand joints at least one joint area swollen or above in wrist, MCP,PIP joint 4.Symmetric arthritis simultaneous involvement of the same areas on both sides of the body 5.Rheumatoid nodules6.Serum rhe

20、umatoid factor7.Radiographic changes including erosions or unequivocal bony decalcificationDifferential DiagnosisOsteoarthritis: occurs in 40 or more pain increase through day or with use involve DIP, weight-bearing joints radiologic findings: subchondral sclerosis, osteophytes lab findings: normal

21、RA AS HLA-DR4 HLA-B27 women,30-50 years young maleSmall joint,symmetric lower extremity,asymmetric polyarticular oligoarthropathy wrist, finger sacroilitis,lumbar spine synovitis periarticular soft tissue inflammation ulnar deviation marginal bridging sundesmophytes, swan-neck deformity bamboo spine

22、 RF(+) RF(-) TREATMENT The primary objective:Reduction of inflammation and painPrevention of joint deformity Preservation of muscle strength and joint functionMinimizing undesirable drug side effects and improvement of quality of life1. General approach： Acute phase: rest and restriction of motion I

23、nactive phase: exercise therapyDrug therapyNSAIDs (nonsteroidal anti-inflammatory drugs)GlucocorticoidsDMARDs (disease modifying anti-inflammatory drugs)NSAIDs NSAIDs is used as the first drug of treating RA NSAIDs have analgesic and anti-inflamatory effects but are believed not to be capable of pre

24、venting erosions or altering progression of the disease. NSAIDs: ibuprofen,naproxen,sulindac, diclofenac NSAIDs share a common spectrum of clinical toxicities: gastrointestinal tract , kidney, hematopoietic system, central nervous system and liver. Cell membrane phospholipidsInhibited by glucocortic

25、oidsphospholipase Arachidonic acidInhibited by NSAIDsO2+CyclooxygenaseCyclic endoperoxides(PGG2, PGH2)Thromboxane B2PGE2PGF2ThromboxaneA26-Keto-PGE1Toxic oxygen radicalsPGI2Advance Two isoforms of COX have been discovered: COX-1 and COX-2 COX-1 is expressed constitutively in gastric mucosa, Kidney,

26、platelets. COX-2 expression is inducible by cytokines and growth factors in macrophages, monocytes, synoviocytes. COX-2 played a key role in inflammatory conditions Selective COX-2 inhibitors have been developedDMARDs(disease-modifying antirheumatic drugs)DMARDs have the potential to inhibit the abn

27、ormal immune response and delay the progression of the disease. DMARDs should be suggested within 3 to 6 months.The time of action will be retarded 3-6 month after taking DMARDs.Careful monitoring for toxicity is required.DMARDsMTX: gastrointestinal and oral ulceration, liver failure,7.5-15mg/qwDP: hematocytopenia, proteinuria, myasthenia gravis, Good-pastures syndromeSASP: head ache, gastrointestinal upset ,2- 3g/dAntimalarials: retinal lesion,loss of vision hydroxychloroquine200mg/qdGlucocorticoid GC is the most powerful anti-inflammtory and immuno