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1 척추관절염 2013 년제 81 회추계전공의연수강좌 김성규 대구가톨릭대학교병원류마티스내과

2 Concept of spondyloarthritis (SpA) Characteristics of SpA Axial arthritis (sacroiliitis, spondylitis) HLA-B27 family history Rheumatoid factor (-) Asymmetric oligoarthritis Enthesitis (enthesopathy)

3 Concept of spondyloarthritis (SpA)

4 23 세남자 증례 1 ( 병력 ) C/C: 하부요추및둔부의통증 P/I: 2 년전부터허리와둔부의통증이있어왔고, 특히새벽과아침에통증으로깨어나거나조조강직이있어왔다고함. 통증은운동이나스트레칭에의해호전되는경향을보였다고함. Past Hx: HTN/DM/Tbc (-/-/-), 고등학교 3 학년때좌측무릎관절부종과통증으로 6 개월간치료받음.

5 증례 1 ( 검사소견 ) Physical examination Tenderness on both sacroiliac joints No active arthritis on hand, knee, ankle joints Laboratory findings WBC/Hb/Plt: 5,600/12.7/356,000 RUA: WBC(-), RBC (-), Albumin (-), Glucose (-) ESR 38 mm/hr, CRP 26 mg/l (N < 5) RF (-), anti-ccp (-), ANA (-) VDRL (-), HIV (-)

6 증례 1 ( 방사선검사 )

7 증례 1 ( 방사선검사 )

8 증례 1-1 ( 문제 ) 의심되는질환과관련된유전적병인은? 1) HLA-DQA1 2) HLA-B27 3) HLA-B51 4) HLA-DRB1 5) HLA-DR4

9 Definition of AS Prototype of spondyloarthritides Inflammatory disorder of unknown cause that primarily affects the axial skeleton Affect periarticular joint and extraarticular structures

10 Epidemiology of AS Prevalence of HLA-B27 in general population: 7% AS in HLA-B27 (+) subjects: 1-6% Country AS prevalence HLA-B27 prevalence US % 8% Netherlands 0.1% 8% Germany 0.55% 9% Norway % 14% Haida Indians 6.1% 50%

11 Epidemiology of AS Male to female prevalence: 2-3:1

12 AS in female Structural damage of spine: Male > female Female: more frequent involvement in C-spine and peripheral joints Higher burden of disease and less improvement in AS outcome, compared to men

13 증례 1-2 ( 문제 ) HLA-B27 검사에서양성소견을보였고, 피부병변이나최근감염의소견이없었다. 이환자의진단으로적합한것은? 1) 강직성척추염 2) 반응성관절염 3) 골관절염 4) 척추관협착증 5) 건선관절염

14 Historical look at classification criteria for SpA 1991, European Spondyloarthropathy Study group (ESSG) Criteria 1990, Amor Classification for SpA 2009, Assessment of Spondyloarthritis (ASAS) Criteria for Axial Spondyloarthritis 1984, Modified New York Criteria for AS

15 Diagnosis of AS Modified New York Criteria (1984) 1. Clinical criteria 1) low back pain and stiffness for more than 3 months which improves with exercise, but is not relieved by rest 2) Limitation of motion of the lumbar spine in both the sagittal and frontal planes 3) Limitation of chest expansion relative to normal values correlated for age and sex 2. Radiological criterion Sacroiliitis grade 2 bilaterally or grade 3-4 unilaterally Definite ankylosing spondylitis if the radiological criterion is associated with at least 1 clinical criterion.

16 Progression from non-radiographic to radiographic stage

17 ASAS Criteria for Classification of Axial Spondyloarthritis (2009)

18 27 세남자 증례 2 ( 병력 ) C/C: 전흉부동통과허리운동장애 P/I: 5 년전강직성척추염으로진단받았으나, 약물치료를불규칙적으로하던중, 전흉부통증과허리의운동장애가심해져서내원하였다. 전흉부통증은숨을쉴때나타나고, 촉지시압통이느껴진다고하였다. Past Hx: HTN/DM/Tbc (-/-/-), recent trauma history (-)

19 증례 2 ( 검사소견 ) Physical examination Tenderness on right costosternal junction No tenderness around both SI joints Laboratory findings WBC/Hb/Plt: 6,300/11.5/178,000 RUA: WBC(-), RBC (-), Albumin (-), Glucose (-) ESR 45 mm/hr, CRP 32 mg/l(n < 5)

20 증례 2-1 ( 문제 ) 이환자와같이강직성척추염에서척추관절의침범정도를측정할수있는이학적검사로적절하지않는것은? 1) Modified Schober test 2) Chest expansion test 3) Occiput to wall distance 4) Finger to ground distance 5) Patrick s test

21 Spinal mobility tests Lumbar spine Modified Schober test Normal 5cm Finger to ground distance Cervical spine Occiput to wall distance Thoracic spine Chest expansion test Normal 5cm

22 Clinical characteristics of AS Articular and periarticular involvement Spinal and sacroiliac involvement: LBP (75%), buttock pain, limited spinal mobility Hip and shoulder ( root joint) involvement: hip arthritis (25-35%) Costovertebral, manubriosternal, sternoclavicular, costochondral involvement: chest wall pain Inflammation of extraspinal entheses Peripheral arthritis, dactylitis

23 Peripheral articular involvement

24 증례 2-2 ( 문제 ) 이환자와같은강직성척추염에서나타날수있는관절외증상으로보기어려운것은? 1) Anterior uveitis 2) Sicca syndrome 3) Aortic insufficiency 4) Ileum or colon inflammation 5) Psoriasis

25 Extra-articular manifestation

26 Clinical characteristics of AS Extra-articular involvement Acute anterior uveitis Cataract, glaucoma Colon or ileum inflammation Psoriasis Aortic insufficiency 3 rd degree heart block Cauda equina syndrome Upper pulmonary lobe fibrosis Prostatitis

27 32 세여자 C/C: 좌측무릎부종 증례 3 ( 병력 ) P/I: 1 년전강직성척추염으로진단받고개인의원에서간헐적으로소염제만투여하고지내다가최근에좌측무릎관절의통증과부종이심해져서다시내원하였다. Past Hx: HTN/DM/Tbc (-/-/-), trauma Hx (-)

28 증례 3 ( 검사소견 ) Physical examination Tenderness on lower lumbar spine Active arthritis on left knee, but not hand, foot, ankle joints Laboratory findings WBC/Hb/Plt: 12,700/11.0/478,000 RUA: WBC(-), RBC (-), Albumin (-), Glucose (-) ESR 56 mm/hr, CRP 32.5 (N < 5)

29 증례 3 ( 검사소견 )

30 증례 2-1 ( 문제 ) 이환자에게가장적당한조치는? 1) Intraarticular steroid injection 2) TNF blocker 3) Leflunomide 4) Arthroscopic irrigation 5) Antibiotics

31 ASAS/EULAR Recommendations for the management of AS

32 Efficacy of NSAIDs for treatment of AS

33 Conventional DMARDs are largely not effective for treatment of AS

34 증례 2-2 ( 문제 ) 이환자는 sulfasalazine 2000mg, prednisolone 5mg, aceclofenac 200mg 에도 2 개월투여하였으나무릎관절증상은호전되지않았고, 이후 methotrexate 12.5mg 추가와다른소염제로교체해도치료반응을보이지않았다. 다음으로선택할수있는조치는? 1) TNF blocker 2) Thalidomide 3) Arthroscopic synovectomy 4) Bisphosphonate 5) Leflunomide

35 ASAS Recommendations for use of TNF blocker in SpA

36 TNF blocker TNF blockers Infliximab (chimeric human/mouse anti-tnf-a monoclonal antibody) Etanercept (soluble p75 TNF-a receptor IgG fusion protein) Adalimumab or golimumab (human anti-tnf-a monoclonal antibodies) Usages of TNF blockers Infliximab: IV, 3 5 mg/kg BW, and then repeated 2 weeks later, again 6 weeks later, and then at 8-week intervals Etanercept: SC, 50 mg once weekly Adalimumab: SC, 40 mg biweekly Golimumab: SC, 50 or 100 mg every 4 weeks

37 Radiographic response to TNF blockers

38 AS treated with TNF blockers: 24 weeks ASAS 40 response

39 Long term (2 years) efficacy of TNF blockers in AS patients

40 Anti-TNF blocker over 2 years does not inhibit radiographic progression

41 Predictive factors for response to TNF blockers Young age Short disease duration High BASDAI Elevated acute phase reactant (CRP) Low BASFI (functional disability) Widespread inflammation as the spine as demonstrated by MRI

42 증례 2-3 ( 문제 ) 이환자는 adalimumab 을투여후증상이호전되었고, 현 재임신을계획하고있다. 적당한약제는? 1) Adalimumab 2) Bisphosphonate 3) Methotrexate 4) Oral prednisolone 5) Leflunomide

43 TNF blockers Side effects (1) Serious infections, including disseminated tuberculosis (2) Hematologic disorders, such as pancytopenia (3) Demyelinating disorders (4) Exacerbation of congestive heart failure (5) SLE related autoantibodies and clinical features (6) Hypersensitivity for infusion or injection site reactions (7) Severe liver disease

44 TNF blockers TNF blocker 와결핵 치료전에 tuberculin 검사를시행하고 5mm 이상인경우항결핵제로치료를해야한다. Absolute contraindication Active infection or high risk of infection Malignancy or premalignancy History of SLE, multiple sclerosis, or related autoimmunity Relative contraindication Pregnancy and lactation

45 Take home messages Ankylosing spondylits is common inflammatory rheumatic disease that affects the axial skeleton and peripheral articular and extra-articular structures. HLA-27 has a crucial role in the pathogenesis of AS. ASAS classification criteria for axial SpA is newly introduced, which useful for patients early in the detection of SpA. The standard treatment of AS includes physical therapy, NSAIDs, DMARDs, and TNF-a blockers.

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