2012 개원의와함께하는임상강좌 경희대학교의학전문대학원류마티스내과학교실 홍승재 진단의중요성 치료의첫단계 : 정확한진단은아무리강조해도지나치지않음 감별진단의중요성 : 진단이달라짐에따라치료시기와약제의선택, 진행경과, 합병증여부, 예후및삶의질에차이가있다. 류마티스관절염 (Rheumatoid arthritis) : 비교적젊은나이에발병하며, 진단초기부터관절염증에의한골파괴소견이가능함. 진행될경우관절의심한변형과기능상실이유발 골관절염 (Osteoarthritis) : 나이가들어감에따라발생이증가하며, 염증보다연골감소로인한변화가서서히생김. 류마티스관절염진단기준의변천 1956/8 1961 1966 1987 2010 American Rheumatism association Rome criteria Now York criteria ACR* criteria 2010 ACR/EULAR** classification criteria * : ACR(American College Of Rheumatollogy) ** : EULAR(The European League Against Rheumatism)
홍승재 : 류마티스관절염의새로운진단기준 1987 년 ACR 류마티스관절염진단기준 1. 조조강직 : 1시간이상 2. 관절염 : 3관절이상적어도 6주이상지속 3. 수부관절염 4. 대칭성관절염 5. 류마티스결절 6. 류마티스인자 : 양성 7. 방사선학적변화 : 골미란또는탈칼슘화 7 개중 4 개이상이면진단됨 류마티스관절염과골관절염의관절침범분포 Ulnar deviation swan neck deformity boutonniere deformity DIP: Heberden s node PIP: Bouchard s node 류마티스관절염의주요공격타겟 관절을싸고있는활막조직 2012 개원의와함께하는임상강좌
길라잡이 : 개정된가이드라인을중심으로 류마티스관절염의진행 Inflammation Disability Joint damage (X-rays) Severity (arbitrary units) 0 5 10 15 20 25 30 Duration of Disease (years) DMARDs 치료시점에따른류마티스관절염진행 류마티스관절염에서 Anti-CCP antibody 의의미 Citrulline containing peptide (CCP) Highly specific for RA (specificity 90-96%) Sensitivity low (47-76%) Anti-CCP positive with early RA : increased risk of progressive joint damage test sensitivity specificity Anti-CCP 56% 90% IgM RF 73% 82% IgM RF+anti-CCP 48% 96%
홍승재 : 류마티스관절염의새로운진단기준 Anti-CCP antibody 와 IgM RF 의진단적가치 Anti-cyclic citrullinated peptide (anti-ccp) Sensitivity, % (95% CI) 67 (62 72) Specificity, % (95% CI) 95 (94 97) Positive likelihood ratio (range) 12.46 (9.72 15.98) Negative likelihood ratio (range) 0.36 (0.31 0.42) Immunoglobulin M rheumatoid factor (IgM-RF) 69 (65 73) 85 (82 88) 4.86 (3.95 5.97) 0.38 (0.33 0.44) Meta-analysis of 37 studies of anti-ccp antibody and 50 studies of RF; data generated using the DerSimonian-Laird random-effects method Ann Intern Med 2007;146:797-808 Anti-CCP and/or RF can be detected in RA - up to 14 years before disease onset - Arthritis Rheum 2004;50:380-386 RF and anti-ccp are key predictive factors for rapid radiographic progression (RRP) in RA Risk of RRP by predictive factor, showing that RF, anti-ccp status, baseline CRP and erosion score were significant independent predictors of RRP CRP (mg/l) RF and anti-ccp status -/- +/- or -/+ +/+ Baseline erosion score 47 69 78 4 35 24 44 56 1 4 19 37 49 0 22 42 54 4 10 35 9 20 29 1 4 7 16 23 0 16 32 43 4 <10 6 14 21 1 4 6 11 17 0 Risk of RRP (%) 50 20 50 10 20 <10 Adapted from Visser et al. EULAR 2009 2012 개원의와함께하는임상강좌
길라잡이 : 개정된가이드라인을중심으로 Patients meeting ACR criteria: 1 st visit 40 RA Non-RA 30 % 20 10 0 0 1 2 3 4 5 6 Number of ACR criteria Arthritis Rheum 2001;44:2485-91 1987 ACR 진단기준의한계점 초기 2~3 년대부분의관절손상이일어나게되지만, 1987 진단기준은 Early RA 진단 sensitivity 가낮다. 관절손상은환자의예후와직결되지만, 1987 진단기준은골미란이생긴후진단하게된다. Anti-CCP antibody 와같은새로운진단혈청검사들이개발되었으며이를진단에포함시켜야한다. Early RA 진단이어려워 DMARDs 의조기적용이안된다. DMARDs 보다강력한 TNF-a blocker 등이개발되었으며, 조기사용시관절파괴를막을수있다. 2010 ACR/EULAR 진단기준개발의목적 만성또는골미란의 risk 가있는 early inflammatory arthritis 를조기에진단하기위해. Early RA 환자에서 DMARDs 사용의근거를제공하기위해. New serologic test 를진단에적용하기위해. Scoring system 의도입으로진단의객관성을얻기위해. Later course of RA 환자의진단을배제하지않는다.
홍승재 : 류마티스관절염의새로운진단기준 2010 ACR/EULAR criteria 의개발 (Phase I) 3115 patients from 9 cohorts Enrolled in or after 2000 Duration of arthritis < 3 years Purpose : to identify the contributions of clinical and laboratory variables : predictive to initiate DMARDs in patients with early arthritis Summary of Phase I results Acute-phase response, ESR or CRP; RF, rheumatoid factor; ACPA, anti-citrullinated protein antibody Arthritis Rheum 2010;62:2569-81 Conclusion of Phase I Swelling of small joint regions has independent effects Tenderness also considered as a sign of joint involvement Symmetrical involvement not have a incremental effect over unilateral involvement Abnormal APR (acute phase response) has a effect, especially CRP 2012 개원의와함께하는임상강좌
길라잡이 : 개정된가이드라인을중심으로 2010 ACR/EULAR criteria 의개발 (Phase II) 12 rheumatologists from Europe & 12 from North America 2009 ACR RA classification preliminary criteria 1 swollen joint Not currently classified as RA NO YES NO Better explained by another disease? YES Typical RA erosion on conventional radiograph? NO YE S APPLY Classification Classified as Criteria for RA RA Not currently classified as RA Summary of Phase II results Arthritis Rheum 2010;62:2569-81
홍승재 : 류마티스관절염의새로운진단기준 The 2010 ACR/EULAR classification criteria for Rheumatoid Arthritis Arthritis Rheum 2010;62:2569-81 Small joints MCP, PIP 2~5 th MTP 1 st IP wrists Large joint Shoulder Elbow Hip Knee ankle JOINT INVOLVEMENT (0-5) 1 Large joint 0 2-10 Large joints 1 1-3 small joints 2 4-10 small joints 3 10> joints (at last 1 small joint) 5 SEROLOGY (0-3) Neither RF or ACPA positive 0 At least one test low positive titer 2 At least one test high positive titer 3 DURATION of SYNOVITIS (0-1) Score 6 Indicates definite RA <6 weeks 0 6 weeks 1 ACUTE PHASE REACTANTS (0-1) Neither CRP or ESR abnormal 0 Abnormal CRP or abnormal ESR 1 2012 개원의와함께하는임상강좌
길라잡이 : 개정된가이드라인을중심으로 Tree algorithm for classifying definite RA Arthritis Rheum 2010;62:2569-81 SUMMARY Eligibility for use of the new criteria : evidence of active clinical synovitis in at least 1 joint : synovitis is not explained by expert assessor Algorithm incorporates 4 weighted domains : through joint evaluation : at least 1 serologic test (RF or ACPA) : history of symptom duration : 1 acute-phase response measure (ESR or CRP) Cut-off point 6