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1 대한내과학회지 : 제 85 권제 3 호 특집 (Special Review) - 척추관절병증 강직성척추염의임상상과진단 서울대학교의과대학내과학교실류마티스내과 신기철 Clinical Manifestation and Diagnosis of Ankylosing Spondylitis Kichul Shin Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea Ankylosing spondylitis (AS) is the main disease entity within spondyloarthritides. AS patients can present with both articular and extra-articular manifestations. Especially, inflammatory back pain has been recognized as the main symptom of AS, however it should be noted that mechanical back pain could also ensue in advanced cases. Peripheral arthritis mostly involves in lower extremities in the form of asymmetric oligoarthritis. Enthesitis could develop in the heel, iliac crest, anterior tibial tuberosity, or anterior chest wall. As for imaging, plain radiographs are used to assess the presence or degree of sacroiliac joint and spinal involvement. Magnetic resonance imaging (MRI) is useful in detecting non-radiographic sacroiliitis, for its ability to delineate bone marrow edema. In this regard, MRI has recently been incorporated as a modality to help diagnose axial spondyloarthritis (2010 ASAS classification). Early diagnosis of AS should be based on the combination of clinical, laboratory, and imaging findings, not on solely structural changes. (Korean J Med 2013;85: ) Keywords: Ankylosing spondylitis; Spondyloarthritis; Magnetic resonance imaging; Inflammatory back pain; HLA-B27 서론강직성척추염 (ankylosing spondylitis) 은척추관절염 (spondyloarthritis) 질환군중에서가장주된질환으로축성 (axial) 관절의운동장애및경직을특징으로한다 [1]. 최근관절염질환의조기진단및치료에대한관심이높아짐에따라경추- 요추관절이융합되어목을제대로가누지못하는심한상태로병원을처음방문하는사례는적어졌다. 하지만조조경 직이동반된강직성척추염을추간판탈출증, 요추부위의염좌등기계적요통 (mechanical pain) 으로먼저오인하는경우가적지않다. 또한강직성척추염에의해발생한말초관절염이나다양한관절외임상상이간혹타질환으로간주되고있다. 이기회를통하여강직성척추염때보이는염증성요통 (inflammatory back pain) 의주요특성을살펴보고이질환의진단에자기공명영상이어떤도움을줄수있는지살펴보고자한다. Correspondence to Kichul Shin, M.D. Division of Rheumatology, SMG-SNU Boramae Medical Center, 20 Boramae-ro-5-gil, Dongjak-gu, Seoul , Korea Tel: , Fax: , kideb1@snu.ac.kr Copyright c 2013 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 - Kichul Shin. Clinical manifestation and diagnosis of ankylosing spondylitis - 본론강직성척추염의임상상강직성척추염의임상상은크게관절및관절외임상상으로구분된다. 관절은축성관절외에도말초관절이침범될수있으며축성관절침범때나타나는주요증상중하나는염증성요통이다 [2] (Table 1). 척추관절염환자의 75% 에서첫증상이염증성요통으로나타나며대개요추나요천추부위에서부터시작된다 [1]. 스트레칭이나비스테로이드성항염제를복용한후증상이나아지며휴식후에는오히려악화되는경향이있다. 보통조조경직이 30분이상동반되며통증때문에새벽에잠을설칠수있다. 염증성요통은때로는경미하게나타나기때문에모르고지나갈수있으며대개반복되는증상호전및악화의경과를보인다. 척추관절간융합으로강직이발생되면염증성요통은감소하면서관절운동제한에서오는기능장애가발생한다. 즉운동후증상이나빠지는특징을가지는기계적요통이염증성요통과동반될수있다. 나아가척추간인대와늑골척추 (costovertebral) 관절, 흉늑 (sternocostal) 관절의골화로요추전만증, 흉추후만증이발생하고목이구부정해진다. 강직이심하지않더라도관절운동장애가심할수있는데, 이는이차적인근육연축 (spasm) 때문이다. 강직성척추염환자의 1/3에서고관절, 어깨관절을침범하는바, 고관절의경우양측으로올수있고관절파괴및심한관절변형을야기할수있다 [3]. 말초관절침범은류마티스관절염과는달리주로하지관절에발생하는비대칭성소수성관절염 (oligoarthritis) 으로나타난다. 때로는손가락이나발가락의관절과주위연부조직까지종창되는지염 (dactylitis) 이발생하기도한다. 건, 인대, 근막, 관절피막이뼈와부착되는부위에염증이발생하는부착부염 (enthesitis) 은강직성척추염을비롯한척추관절염에서보이는주요임상상이다. 부착부염은아킬레스건이나족저근막이부착하는발뒤꿈치에잘발생하는데 Table 1. Expert criteria for inflammatory back pain Improvement with exercise Pain at night Insidious onset Age at onset 40 years No improvement with rest The criteria area fulfilled if at least 4 out of 5 parameters are present. 아침에일어나서발뒤꿈치가땅에닿을때심하게아프고걸으면서호전된다. 부착부염은장골능선이나경골조면 (tibial tuberosity), 가슴전면에도발생할수있다. 부착부염외에도흉쇄골 (sternoclavicular) 관절, 흉골병연골 (manubriosternal) 관절, 흉늑관절의관절염으로가슴전면이아플수있으며, 심해지면흉곽의팽창을저해하기도한다. 강직성척추염에서동반되는관절외임상상으로포도막염 (uveitis), 건선 (psoriasis), 염증성장질환 (inflammatory bowel disease) 등이있다. 이중포도막염이가장흔하며 ( 환자의 20-30%) 대개전방에발생한다 [4]. HLA-B27 유전자양성인환자에서더잘생기고한쪽눈의통증, 발적, 눈부심과눈물증가가나타난다. 포도막염이의심될경우바로안과검진이필요하며치료가늦어지면유착이나시력감소등합병증이발생한다. 강직성척추염환자에서건선이동반될경우, 축성관절을침범한건선관절염의가능성이있는지도살펴보는것이필요하다. 염증성장질환과강직성척추염이함께발견하는경우가있는데 [5], 한보고에서는장증상이없는강직성척추염환자의 20-70% 에서대장점막에염증이존재하였다. 반대로염증성장질환환자의 28-35% 에서천장관절염 (sacroiliitis) 을비롯한축성척추관절염이있는것으로발표되었다 [6]. 이외도드물지만심장차단, 대동막판막부전, 간질성폐렴, IgA 신장병증이강직성척추염과동반될수있다. 강직성척추염의진단을위한검사혈액검사아직까지강직성척추염을확진할수있는혈액검사는없다. 적혈구침강지수 (erythrocyte sedimentation rate) 와 C-반응단백 (C-reactive protein, CRP) 상승은약 40% 의환자에서발견된다. CRP가진단을위한필수검사는아니지만 CRP가높은환자군에서 TNF-α 길항제에반응이더좋으나신생골형성 (new bone formation) 이더잘일어날수있는것으로알려져있다 [7,8]. 강직성척추염환자의약 90% 에서 HLA-B27 유전자검사가양성이나 [9] 이검사단독으로강직성척추염을진단내릴수는없다. 국내연구에서도보였듯이 1,700명의건강대조군중 100명 (5.9%) 에서 HLA-B27유전자가양성이기때문이다 [10]. HLA-B27유전자검사는척추관절염이의심되지만영상소견이이에합당하지않은경우에만도움이될수있다

- 대한내과학회지 : 제 85 권제 3 호통권제 637 호 2013 - 척추관절의영상검사 강직성척추염의진단을위한필수적인검사로천장관절이포함된골반의단순 X-선검사가근간이되는영상이다. 근래에는척추관절염의조기진단이나정밀한척추관절평가를위하여자기공명영상이부각되고있다. 단순 X-선검사강직성척추염환자의척추관절침범은대개천장관절부터시작된다.

척추체변화가있을때감별해야할질환으로미만성원발성뼈대과골증 (diffuse idiopathic skeletal hyperostosis, DISH) 을들수있다. 두질환모두척추의운동제한, 척추의뼈돌기과형성이동반될수있지만 DISH에서 Table 2.

3 - 대한내과학회지 : 제 85 권제 3 호통권제 637 호 척추관절의영상검사 강직성척추염의진단을위한필수적인검사로천장관절이포함된골반의단순 X-선검사가근간이되는영상이다. 근래에는척추관절염의조기진단이나정밀한척추관절평가를위하여자기공명영상이부각되고있다. 단순 X-선검사강직성척추염환자의척추관절침범은대개천장관절부터시작된다. 골반전후의단순 X-선검사에서서천장관절염의단계를평가할수있다 [11] (Table 2, Fig. 1). 단순 X-선검사는강직성척추염환자의척추체 (vertebral body) 변화-인대결합 (syndesmophyte), 척추체의사각화 (squaring), 융합 (fusion)- 를보는데도사용된다. 척추체변화가있을때감별해야할질환으로미만성원발성뼈대과골증 (diffuse idiopathic skeletal hyperostosis, DISH) 을들수있다. 두질환모두척추의운동제한, 척추의뼈돌기과형성이동반될수있지만 DISH에서 Table 2. Grading of radiographic sacroiliitis Grade 0: Normal Grade 1: Suspicious changes Grade 2: Minimal abnormality; small localized areas with erosion or sclerosis, without alteration of joint width Grade 3: Unequivocal abnormality; moderated or advanced sacroiliitis with one or more of: erosions, evidence of sclerosis, widening, narrowing, or partial ankylosis Grade 4: Severe abnormality; total ankylosis 는척추의퇴행성변화가관찰되고천장관절의침범이드물다는차이점이있다. 이외에도천장관절의골관절염, 출산과연관된천장관절변화 (osteitis condensans ilii) 등이감별진단에포함된다. 단순 X-선검사는검사비용이저렴하고판독이용이하나골변화가발생하기전에는진단을내릴수없다는단점이있다. 자기공명영상 (magnetic resonance imaging, MRI) 천장관절 MRI가제공해줄수있는주요정보는관절혹은관절주위의 염증 소견이다 [12]. MRI 의 T2 fat suppression 영상을통하여관절주위의골수부종 (bone marrow edema) 을보여줌으로써단순 X-선검사보다조기에천장관절염을진단할수있다 (Fig. 2). 조영제를사용한 T1 강조영상도천장관절주위의골염 (osteitis) 을진단하는데도움을줄수있다. 이로써 MRI로단순 X-선검사소견만으로는불분명한 비방사선천장관절염 (non-radiographic sacroiliitis) 을진단할수있게되었다 [12]. 하지만 MRI는고가의검사이고강직성척추염환자이거나그진단이의심되는경우 1회에한하여보험급여가인정되고있다. 때로는 MRI에서염증이라고생각되는소견이지방변성 (fat degeneration) 과감별이어려울수있다 [13]. 척추 MRI에서척추체의모서리에보이는염증병변이신생골의전구병변이라는가설이대두되었지만이러한병변중일부에서만인대결합, 신생골형성으로진행하는것으로밝혀졌다 [14]. 최근연구에서는염증성병변과지방변성이동시에존재하는척추체모서리에서신생골이많이 A B Figure 1. Sacroiliitis shown in plain film radiography of pelvis (A) both grade 3 (B) both grade 4 with syndesmophyte (arrow)

4 - 신기철. 강직성척추염의임상상과진단 - Figure 2. Active inflammatory lesion around left sacroiliac joint (arrow) in T2 fat suppression image. 형성된다는주장이제기되었다 [15]. 컴퓨터단층촬영천장관절의컴퓨터단층촬영은골미란 (bone erosion), 골경화 (bone sclerosis) 등을관찰하는데유용하나초기염증변화를관찰하는데는적합하지않다. 골스캔 (bone scan, bone scintigraphy) 골스캔은강직성척추염환자의천장관절, 척추관절, 그리고말초관절침범을평가하는검사로사용되어왔다. 골반후면상의 SI/S (sacroiliac joint/sacrum) 비율이상승되어있으면천장관절염을시사하는소견이다. 하지만이검사의제한점은해상도나검사특이도는낮다는것이며최근보고에의하면골스캔이조기강직성척추염의진단에도움이되지않는다고하였다 [16]. 하지만강직성척추염환자에서말초관절침범이나흉쇄골관절, 늑연골염 (costochondritis) 을평가하는데는도움을줄수있다. 강직성척추염의진단 강직성척추염의분류기준은 1984년도에제안된 modified New York criteria 가널리사용되고있다 [11] (Table 3). 이기준에의하면강직성척추염으로분류하기위해서는단순 X-선검사에서천장관절염이양측으로 grade 2 이상이거나일측으로 grade 3 이상이어야한다 (Table 2, Fig. 1). 이는진행된질환의진단에는유용하나단순 X-선검사에서관절변화가미미하면강직성척추염진단을내릴수없으며천장관절 Table 3. Modified New York criteria for ankylosing spondylitis (AS) Diagnosis Clinical criteria Low back pain and stiffness for more than 3months which improves with exercise but is not relieved by rest Limitation of motion of the lumbar spine in both the sagittal and the frontal planes Limitation of chest expansion relative to normal value, corrected for age and sex Radiological criterion Sacroiliitis grade > 2 bilaterally or sacroiliitis grade 3-4 unilaterally Definite AS if the radiological criterion is present with at least one clinical criterion. Table 4. ASAS classification criteria for axial spondyloarthritis (SpA) In patients with 3 months back pain and age at onset < 45 years Sacroiliitis on imaging plus 1 SpA feature * OR HLA B27 plus 2 other SpA features * * SpA features Inflammatory back pain Arthritis Enthesitis (heel) Uveitis Dactylitis Psoriasis Crohn s disease/colitis Good response to NSAIDs Family history of SpA HLA-B27 Elevated CRP NSAIDs, non-steroidal anti-inflammatory drugs; CRP, C-reactive protein. 및척추변화에만집중할뿐관절외임상상을포함하지않는다는제한점이있다. 이같이축성관절을침범하는척추관절염질환군을더조기에진단하기위해 MRI 소견을포함하는한편관절외임상상, 가족력문진을더하는새로운분류기준이제안되었다 [17] (Table 4). 임상이나임상시험에서활용되는강직성척추염분류기준은현재 modified New York criteria이지만향후는강직성척추염을포함한축성척추관절염을대상으로하여임상연구및치료지침제정이

5 - The Korean Journal of Medicine: Vol. 85, No. 3, 진행될것으로전망된다. 요 강직성척추염은척추관절염질환군중가장근간이되는질환으로, 주된관절증상은염증성요통이지만기계적요통과때로는구분이어렵거나같이동반될수있다. 염증성요통은조조경직이있고운동을하면증상이호전되며새벽에악화되는경향이있다. 척추외에도어깨, 고관절침범이가능하며말초관절염은주로하지관절에발생한다. 부착부염은건, 인대, 근막등이뼈에붙는부위에생기는염증으로발뒤꿈치, 발바닥, 무릎, 가슴등통증을호소할때의심해보아야한다. 강직성척추염을진단하고추적관찰하는데쓰이는기본적인영상검사는단순 X-선검사이다. 조기에천장관절염을진단하는데 MRI 가도움이될수있으며골스캔은검사해석에주의를요한다. 그동안강직성척추염의분류기준으로염증성요통과관절운동장애, 단순 X-선검사소견으로이루어진 modified New York criteria 를주로사용해왔지만이제는조기진단및치료의필요성이대두되면서축성 척추관절염 질환명을중심으로한진단툴이정립될것으로보인다. 중심단어 : 강직성척추염 ; 척추관절염 ; 자기공명영상 ; 염증성요통 ; HLA-B27 약 REFERENCES 1. Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007;369: Sieper J, van der Heijde D, Landewé R, et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis 2009;68: Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing spondylitis: an overview. Ann Rheum Dis 2002;61 (Suppl 3):iii Edmunds L, Elswood J, Calin A. New light on uveitis in ankylosing spondylitis. J Rheumatol 1991;18: Meuwissen SG, Dekker-Saeys BJ, Agenant D, Tytgat GN. Ankylosing spondylitis and inflammatory bowel disease: I. prevalence of inflammatory bowel disease in patients suffering from ankylosing spondylitis. Ann Rheum Dis 1978;37: Rudwaleit M, Baeten D. Ankylosing spondylitis and bowel disease. Best Pract Res Clin Rheumatol 2006;20: Arends S, Brouwer E, van der Veer E, et al. Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study. Arthritis Res Ther 2011;13:R Poddubnyy D, Conrad K, Ruiz-Heiland G, et al. Predictive and protective value of biomarkers in patients with ankylosing spondylitis who are at high risk of radiographic spinal progression [Abstract]. Arthritis Rheum 2011;63(Suppl 10): Reveille JD. The genetic basis of ankylosing spondylitis. Curr Opin Rheumatol 2006;18: Oh WI. HLA-B27 Subtypes in Korean Patients with Spondyloarthropathies and Healthy Controls. Seoul: Seoul National University, Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 1984;27: Rudwaleit M, Jurik AG, Hermann KG, et al. Defining active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI group. Ann Rheum Dis 2009; 68: Braun J, Baraliakos X. Imaging of axial spondyloarthritis including ankylosing spondylitis. Ann Rheum Dis 2011;70 (Suppl 1):i Chiowchanwisawakit P, Lambert RG, Conner-Spady B, Maksymowych WP. Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis. Arthritis Rheum 2011;63: Maksymowych WP, Morency N, Conner-Spady B, Lambert RG. Suppression of inflammation and effects on new bone formation in ankylosing spondylitis: evidence for a window of opportunity in disease modification. Ann Rheum Dis 2013;72: Song IH, Carrasco-Fernández J, Rudwaleit M, Sieper J. The diagnostic value of scintigraphy in assessing sacroiliitis in ankylosing spondylitis: a systematic literature research. Ann Rheum Dis 2008;67: Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:

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ÀÇ»çÈ¸º¸-1202-443È£-14, page 1-12 @ Normalize ( 1202-443È£-14 ) THE DAEGU MEDICAL ASSOCIATION NEWS THE DAEGU MEDICAL ASSOCIATION NEWS THE DAEGU MEDICAL ASSOCIATION NEWS (월간) (제443호 / 광역시 제33호) 0년 월 8일 3 인도 캘커타 외각 오지서 의료봉사 ➊ ➏ ➋ ➌ ➍ ➎ ➐ ➊ 캘커타 라자핫 지역 고등학교 앞 ➋ ➌ 진료를 하는