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1 대한소화기학회지 2009;53: REVIEW 크론병진단가이드라인 울산대학교의과대학내과학교실 *, 영남대학교의과대학내과학교실, 고려대학교의과대학내과학교실, 가톨릭대학교의과대학내과학교실, 서울대학교의과대학내과학교실 예병덕 * ㆍ장병익 ㆍ진윤태 ㆍ이강문 ㆍ김주성 ㆍ양석균 * ㆍ대한장연구학회 IBD 연구회 Diagnostic Guideline of Crohn s Disease Byong Duk Ye, M.D.*, Byung Ik Jang, M.D., Yoon Tae Jeen, M.D., Kang Moon Lee, M.D., Joo Sung Kim, M.D., Suk-Kyun Yang, M.D.*, and IBD Study Group of the Korean Association of the Study of Intestinal Diseases Department of Internal Medicine, University of Ulsan College of Medicine*, Seoul, Yeungnam University College of Medicine, Daegu, Korea University College of Medicine, The Catholic University of Korea College of Medicine, Seoul National University College of Medicine, Seoul, Korea Crohn s disease (CD) is a chronic inflammatory bowel disease (IBD) with uncertain etiopathogenesis. CD can involve any site of gastrointestinal tract from mouth to anus and is associated with serious complications such as bowel stricture, perforation, abscess, and fistula formation. The incidence and prevalence rates of CD in Korea are still low compared with those of Western countries, but are rapidly increasing during the past decades. The diagnosis of CD is a challenging issue in some clinical situations and it is often difficult to differentiate CD from intestinal tuberculosis or Behçet s enterocolitis which are more prevalent in Korea than in Western countries. Therefore, IBD Study Group of KASID has set out to establish the diagnostic guideline of CD in Korea. There is no single gold standard for the diagnosis of CD and diagnosis is made by clinical evaluation including detailed history, physical examination, and combination of endoscopic findings, histology, radiologic findings and laboratory investigations. The typical symptoms of CD are abdominal pain, diarrhea, and weight loss especially in late adolescence or early adulthood. Initial laboratory investigations include CBC, C-reactive protein, and serum chemistry. Ileocolonoscopy and biopsies are recommended as the first line procedures to establish the diagnosis. Typical endoscopic findings of CD are non-continuous distribution of longitudinal ulcers, cobblestone mucosal appearance, and aphthous ulcerations arranged in a longitudinal fashion. The evaluation of small bowel with small bowel follow-through is recommended for suspected CD to establish diagnosis and to determine the extent and location of disease. Focal and patchy chronic inflammation, focal crypt irregularity, and non-caseating granulomas are usual microscopic features of CD. This is the first Korean diagnostic guideline for CD and needs revision with further data on CD in Koreans. (Korean J Gastroenterol 2009;53: ) Key Words: Crohn s disease; Diagnosis; Guideline 연락처 : 양석균, , 서울시송파구풍납동 울산대학교의과대학내과학교실 Tel: (02) , Fax: (02) sky@amc.seoul.kr * 본연구는보건복지부보건의료기술진흥사업의지원에의하여이루어진것임 ( 과제고유번호 : A080588). Correspondence to: Suk-Kyun Yang, M.D. Department of Internal Medicine, University of Ulsan College of Medicine, 388-1, Pungnap-dong, Songpa-gu, Seoul , Korea Tel: , Fax: sky@amc.seoul.kr

2 162 대한소화기학회지 : 제 53 권제 3 호, 2009 서론크론병 (Crohn s disease) 은위장관전체를침범할수있는만성난치성염증장질환이다. 약 2세기이전부터크론병의소견에대한기술이있었으나, 년 Crohn 등에의해이들이 regional ileitis 로기술되었고, 2 이후크론병으로널리불리게되었다. 크론병의진단에대한표준진단방법 (gold standard criteria) 이없는관계로그유병률과발병률을정확히알수는없으나, 전세계적으로점차증가하는것으로보인다. 3 크론병은일반적으로임상소견, 내시경소견, 검사실소견, 영상의학소견, 조직검사소견, 수술소견등을종합하여진단을내리게된다. 그러나일부예는급성감염장염, 과민장증후군, 궤양성대장염, 장결핵, 베체트장염등기타장질환과의감별에어려움을겪는경우가많다. 특히우리나라는서양과비교하여장결핵과베체트장염의유병률이높으므로크론병과의감별진단이중요하다. 크론병의진단가이드라인, 합의안 (consensus) 이나진단기준 (diagnostic criteria) 이유럽, 일본에서는발표된바있고, 4-6 역학연구에서도진단기준이사용된바있으나, 7,8 우리나라에서는아직발표된바가없다. 이번크론병진단가이드라인은크론병의진단기준을제 시하는것이아니고, 일선에서진료를담당하는의사가크론병을진단하는데방향을제시하는것이다. 이를위하여현재까지국내외에서발표된다양한연구자료들을검토하였고, 국내에서크론병을진단하는데고려하여야할문제점들도반영하였다. 사안에따라근거자료가불충분한경우는대한장연구학회산하 IBD 연구회전문가들의토론을통해권고안을제시하였다. 이번진단가이드라인은국내에서처음으로제정되는것이므로, 향후새로운진단방법이개발되거나, 새로운연구결과가발표되는경우그에따라수정, 보완되어야할것이다. 이번가이드라인의증거수준 (levels of evidence) 및권고등급 (grades of recommendation) 은 Centre for Evidence Based Medicine, Oxford (Table 1) 를근거로한 ECCO (European Crohn s and Colitis Organisation) 의합의안을인용하였다. 5,9 본론 1. 정의 (Definitions) 크론병은구강에서항문까지위장관전체를침범할수있는원인불명의만성염증성장질환이다. 크론병은복통, 설 Table 1. Levels of Evidence and Grades of Recommendation Based on the Oxford Center for Evidence Based Medicine Evidence levels (EL) Diagnostic study Therapeutic study 1a 1b 1c 2a 2b 2c 3a 3b 4 5 Systematic review (SR) with homogeneity of level 1 diagnostic studies Validating cohort study with good reference standards Specificity is so high that a positive result rules in the diagnosis or sensitivity is so high that a negative result rules out the diagnosis SR with homogeneity of level >2 diagnostic studies Exploratory cohort study with good reference standards SR with homogeneity of 3b and better studies Non-consecutive study; or without consistently applied reference standards Case-control study, poor or non-independent reference standard Expert opinion without explicit critical appraisal, or based on physiology, bench research or first principles Recommendation grades (RG) A B C D Consistent level 1 studies Consistent level 2 or 3 studies or extrapolations from level 1 studies Level 4 studies or extrapolations from level 2 or 3 studies Level 5 evidence or troublingly inconsistent or inconclusive studies of any level Systematic review (SR) with homogeneity of randomized controlled trials (RCTs) Individual RCT (with narrow confidence interval) All or none SR (with homogeneity) of cohort studies Individual cohort study (including low quality RCT; e.g., <80% follow up) Outcomes research; ecological studies SR with homogeneity of case-control studies Individual case-control study Case-series (and poor quality cohort and case-control studies) Expert opinion without explicit critical appraisal, or based on physiology, bench research or first principles

3 예병덕외 5 인. 크론병진단가이드라인 163 사, 체중감소를주증상으로하며, 호전과악화를반복하는만성경과를밟고협착, 천공, 농양, 누공등으로인해반복적인수술을필요로하는등난치경과를밟게된다. 1) 활동질환 (Active disease) 및관해 (Remission) 본정의를위해서는임상질병활동도 (disease activity) 에대한분류가필요하다. 크론병의질병활성도를평가하기위해사용되는지표로는 Crohn s disease activity index (CDAI) 및 Harvey-Bradshaw index (HBI) 가대표적이다 (Table 2, 3). 10,11 CDAI는여러임상연구들에서널리사용되고있고, HBI는 CDAI와비교적연관성이좋으며사용하기간편한장점이있다. 12 일반적으로임상진료및다수의임상연구에서 CDAI 150 미만은관해 (remission), 150 이상 220 미만은경증활동성 (mild activity), 220 이상 450 미만은중등도활동성 (moderate activity), 450 이상은중증활동성 (severe activity) 으로분류된다. 5 2) 국소질환 (Localized disease) 5 장침범길이가 30 cm 미만인경우를의미한다. 이는주로회맹부를침범한경우에해당되나, 대장에만국한된크론병또는근위소장을침범한크론병에도적용될수있다. 3) 광범위질환 (Extensive disease) 5 침범위치에관계없이침범길이가 100 cm 이상인경우이다. 이는비연속적인염증병변의총합으로계산된다. 2. 분류 (Classification) 1) 표현형 (phenotype) 에따른분류 1998년세가지분류기준 (parameter) 을사용한 Vienna classification이제안되었다 (Table 4). 13 이에의하면크론병환자를 24개의군으로분류할수있다. 2005년에는 Vienna classification을수정, 보완하여 Montreal classification이제안되었다 (Table 5). 14 이는진단시연령구 Table 2. Crohn s Disease Activity Index Items 1. Number of liquid or very soft stools* 2. Abdominal pain* (0=none, 1=mild, 2=moderate, 3=severe) 3. General well-being* (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible) 4. Number of 6 listed categories patient now has: 1) Arthritis/arthralgia 2) Iritis/uveitis 3) Erythema nodosum/pyoderma gangrenosum/aphthous stomatitis 4) Anal fissure, fistula, or abscess 5) Other fistula 6) Fever over 100 F (37.8 C) during past week 5. Taking lomotil/opiates for diarrhea (0=no, 1=yes) 6. Abdominal mass (0=none, 2=questionable, 5=definite) 7. Hematocrit [Males: (47-hematocrit), Females: (42-hematocrit)] 8. Percent below standard weight (normogram) * Sum of 7 days. Factor X 2 X 5 X 7 X 20 X 30 X 10 X 6 X 1 Table 3. Harvey-Bradshaw Index Items 1. General well-being* (0=very well, 1=slightly below par, 2=poor, 3=very poor, 4=terrible) 2. Abdominal pain* (0=none, 1=mild, 2=moderate, 3=severe) 3. Number of liquid stools per day* 4. Abdominal mass (0=none, 1=dubious, 2=definite, 3=definite and tender) 5. Complications: arthralgia, uveitis, erythema nodosum, aphthous ulcers, pyoderma gangrenosum, anal fissure, new fistula, abscess (score 1 per item). * Scored for the previous day. Factor X 1 X 1 X 1 X 1 X 1

4 164 The Korean Journal of Gastroenterology: Vol. 53, No. 3, 2009 Table 4. Vienna Classification of Crohn s Disease Age at diagnosis: A1 <40 years A2 40 years Location: L1 Terminal ileum (the lower third of the small bowel with or without spill over into cecum) L2 Colon L3 Ileocolon (terminal ileum+any location between ascending colon and rectum) L4 Upper GI [any disease location proximal to the terminal ileum (excluding the mouth) regardless of additional involvement of the terminal ileum or colon] Behavior: B1 Nonstricturing nonpenetrating B2 Stricturing B3 Penetrating Table 5. Montreal Classification of Crohn s Disease Age at diagnosis: A1 16 years A years A2 >40 years Location: L1 Terminal ileum (the lower third of the small bowel with or without spill over into cecum) L2 Colon L3 Ileocolon (terminal ileum+any location between ascending colon and rectum) L4 Isolated upper disease (a modifier that can be added to L1-L3 when concomitant upper gastrointestinal disease is present) Behavior: B1 Nonstricturing nonpenetrating B2 Stricturing B3 Penetrating p Perianal disease modifier (added to B1-B3 when concomitant perianal disease is present) 분을더세분화하였고, L4를 L1-L3에추가할수있게하였으며, behavior에 p (perianal disease modifier) 를추가할수있게한것이특징이다. 3. 역학 (Epidemiology) 1) 발병률및유병률서양에서크론병의연간발병률은인구 10만명당 3-7명, 유병률은인구 10만명당 명으로보고되고있다. 15 우리나라에서전국규모로시행된크론병역학연구는아직없는상태이나, 송파구-강동구를대상으로한약 20년의인구기반역학연구를살펴봄으로써그역학양상을추정할수있다. 그연구에따르면 년에는연간인구 10만명당 0.05명의발병률을보였으나, 년에는 1.34명의발병률을보였고, 또한 20년에걸쳐발병률이지속적으로증가하는추세였다. 3 또한 2005년 12월 31일을기준으로할때송파구-강동구지역의성별, 연령보정유병률은인구 10 만명당 11.24명이었다. 3 이러한연구결과는우리나라의크론병발병률및유병률이아직은서양보다낮으나지속적으로증가하는추세임을보여준다. 2) 우리나라크론병의역학특성구미의보고들을살펴보면크론병이가장호발하는연령은 10대중반에서 20대후반이었고, 8,16-19 이러한역학특성은국내연구에서도동일하였다. 3,20,21 또한송파구-강동구를대상으로한인구기반연구에서 60-69세에작은이차적인발병률증가가있었는데, 3 이는서양의연구들에서도유사한경향을보였다. 16,18,19 이러한이차적인발병률증가는일본및중국의연구에서는관찰되지않았다. 6,22 국내연구를살펴보면서양과는다른몇가지특성이관찰된다. 첫번째는남녀성비의차이이다. 송파구-강동구역학연구에서 년연령보정연간발병률은남자에서인구 10만명당 0.79명, 여자에서 0.27명으로남자에서의미있게더높았다. 이결과는여성발병률이약간더높은경향을보였던서양연구들과차이를보인다 남자에서의높은크론병발병률은일본및홍콩에서도역시관찰되어이러한경향이서구와다른아시아인의고유한특성일가능성이있겠다. 6,27 또한국내연구에서대장에만국한된크론병의비율은약 10% 로낮으나, 3 서양연구에서는대장국한크론병의비율이가장높다고보고되었다. 15,16,28,29 국내연구결과는대장크론병의비율을약 16% 로보고한일본의보고와유사하다. 30 한편크론병에흔히동반되는치루의발생빈도는단일

5 Ye BD, et al. Diagnostic Guideline of Crohn s Disease 165 의뢰센터의환자들을대상으로한연구에서 48.5% 를보여, 31 서양인구기반연구에서의 20-23% 및서양의뢰센터연구의 13-38% 보다더높은경향을보였다 이러한높은치루발생률은향후인구기반연구를통해확인되어야할것이다. 4. 진단 (Diagnosis) 크론병으로진단할수있는 gold standard는없다. 크론병의진단은병력, 신체검진소견등임상평가와내시경검사, 조직검사, 영상의학검사, 혈액검사등을종합하여내리게된다 [EL5, RG D]. 크론병의진단을위해각단계에서필수적으로시행해야할기본항목및진단절차는다음과같다. <크론병의진단을위한기본항목> 1. 병력청취 2. 신체검진 3. 혈액검사 : 일반혈액검사, CRP, 혈청생화학검사 4. 대장내시경 5. 영상의학검사 : 소장조영술 6. 조직검사 1) 임상양상병력청취는다음을반드시포함하여야한다 : 증상시작시점, 야간증상의여부, 최근여행력, 음식불내성 (intolerance), 장염환자접촉력, 항균제및비스테로이드성소염제를포함한약물사용력, 흡연, 가족력, 장관외증상 ( 구강, 피부, 안구, 관절 ), 항문주위병변 ( 치열, 치루, 항문주위농양 )[EL5, RG D]. (1) 연령우리나라에서크론병이가장호발하는연령은 10대중반-20대후반이다. 우리나라크론병의역학특성에서언급하였듯이국내연구에서크론병이가장호발하는연령은 10대중반에서 20대후반으로이연령대에서복통, 설사, 체중감소등을호소하는환자의경우크론병을꼭의심하여야한다. (2) 주증상크론병의증상은다양하나, 체중감소를동반하거나하지않는 6주이상의설사및복통이흔하다. 이러한증상이있을때크론병을고려해야하고특히젊은연령층에서는더욱그러하다 [EL5, RG D]. 전신증상으로는전신쇠약감, 식욕부진, 발열이흔하다 [EL5, RG D]. 우리나라크론병환자가가장흔히호소하는증상은복통, 체중감소및설사이다. 일반적으로크론병환자가가장흔히호소하는증상은복통, 설사및체중감소로, 우리나라에서도크게다르지않아국내연구에서는 % 의환자가복통, % 의환자가설사, % 의환자가체중감소를호소하였다. 20,21 1 복통부위, 양상, 시기및호전 / 악화인자를파악한다. 크론병에동반되는복통의발생기전은잘알려져있지않으나, 장막 (serosa) 으로의염증파급, 소장의물리적인협착, 염증의벽측복막 (parietal peritoneum) 으로의파급등이원인이될수있다. 일반적으로크론병환자는배꼽주위및하복부, 특히우하복부의쥐어짜는듯하고간헐적인양상의통증을흔히호소한다. 또감별진단에중요한점은복통의시기인데, 과민장증후군과달리크론병에서의복통은수면중에도발생하여수면방해를유발할수있다. 소장의물리적인협착이나염증에의한기능적인협착이동반된경우음식섭취에의해악화, 금식에의해완화되는경향을보인다. 그러나복강내농양등이벽측복막을침범한경우, 복막자극에의한지속적인통증이발생할수있다. 2 설사하루중배변횟수, 성상, 혈변또는점액변여부및최근의양상변화를파악한다. 크론병환자가호소하는가장흔한증상중하나가만성설사이다. 설사발생에는점막의염증에의한수분및전해질흡수장애, 점막투과성증가로인한단백및수분소실, 장관운동이상 (dysmotility), 담즙산 (bile salt), 장-장누공 (enteroenteric fistula) 등이관여하는것으로생각된다. 혈변, 점액변, 뒤무직 (tenesmus) 은원위부대장을침범한경우발생할수있고, 이들은크론병보다궤양성대장염환자가더흔히호소하는증상이다. 설사의지속여부도중요한데갑자기발생하여서서히호전되는설사는급성감염장염등을시사하나, 크론병에동반된설사는점진적호전없이수개월이상지속된다. 젊은연령에서크론병과감별하여야할과민장증후군에서는크론병과달리야간설사는드물고, 44 설사와변비가반복되는양상을보이는경우가많다. 3 체중감소인위적인체중감량시도나다른특별한원인없는단기간의급격한체중감소가복통과설사에동반된경우, 과민장증후군등기능장질환보다는크론병등기질적인질환을의심하여야한다. (3) 동반증상 : 발열, 전신쇠약감, 식욕부진, 구역, 구토여부를문진한다. 이동반증상들만으로장결핵이나다른염증성장질환과의감별에결정적인증거는얻을수는없으나, 과민성장증후군과의감별에는도움이된다. 크론병에서는흔히미열 (low-grade fever) 이동반되나, 오한을동반한

6 166 대한소화기학회지 : 제 53 권제 3 호, 2009 지속적인고열은중대한감염증이합병되지않은크론병자체에서는흔하지않다. 장결핵에서도발열이동반될수있으나 38.5 C 이상의고열은감염증이없는크론병보다장결핵에서더흔하다. 45 기타장결핵에서동반될수있는기침, 객담, 객혈등의호흡기증상도확인해야한다. (4) 장관외증상 : 관절, 피부, 외음부, 구강, 안구증상등을확인한다. 우리나라에서 113명의크론병환자를대상으로한연구에서장관외증상이 23%, 그중구강궤양이 13.3%, 관절통이 9.7% 에서발생한것으로보고되었다. 21 외국의연구를살펴보면, 크론병에서장관외침범은약 33% 에서발생하는것으로보고된바있다. 46 염증성장질환의가장흔한장관외이상은근골격계이상이다. 36 관절침범으로질병활동도와관련이있는말초관절염 (peripheral arthritis) 이동반될수있고, 5개미만의관절을침범하는경우는크론병환자중 6%, 5개이상의관절을침범하는경우는 4% 에서동반된다고보고되었다. 47 관절통은관절염보다더흔하고, 대개비대칭적으로큰관절을침범한다. 천장골염 (sacroilitis) 은방사선검사및핵의학검사를시행하는경우염증성장질환환자의약 10% 에서관찰되나, 48 영상검사에서이상이있는환자의대부분은증상이없다. 천장골염은장질환의활동도와도무관하다. 크론병에잘동반되는대표적인피부병변은, 결절홍반 (erythema nodosum) 과괴저농피증 (pyoderma gangrenosum) 이다. 결절홍반과괴저농피증은하지에호발하나, 일반적으로장질환의활동도와비례하지는않는다. 47 베체트병과의감별을위하여외음부궤양이있는지도문진한다. 크론병에서외음부궤양은매우드문것으로알려져있다. 46 구강병변은크론병환자의약 6-30% 에서동반되며, 47 입술, 잇몸, 구강점막의궤양등이있다. 안구병변은홍채염 (iritis) 과포도막염 (uveitis) 이대표적으로, 10% 미만의환자에서동반된다. 49 기타공막염 (scleritis), 상공막염 (episcleritis), 홍채모양체염 (iridocyclitis) 이발생할수있다. 이와같은안구병변이동반된경우, 시야혼탁, 눈물, 작열감, 소양감, 통증, 광선공포 (photophobia), 결막이나공막의충혈, 시력저하등을호소하게된다. 원발경화담관염 (primary sclerosing cholangitis) 에의한담즙정체가있는경우소양감, 황달을호소할수있다. 원발경화담관염은염증성장질환환자의 2-8% 에서발생하는것으로보고되었다. 50,51 임상상은다양하여, 검사실소견의이상과내시경적역행담췌관조영술 (endoscopic retrograde cholangiopancreatography, ERCP) 에서경미한이상소견을보이며수년간무증상상태로있는환자도있으며, 일부는급속하게간경변증으로진행되는경과를밟기도한다. 염증성장질환에동반된원발경화담관염은간세포암종 (hepatocellular carcinoma) 의발생위험이높고, 또한원발경화담 관염과대장염이동반된경우대장암의위험이증가되는것으로알려져있다. 47 (5) 과거병력결핵병력및항문주위병변에대한병력청취가중요하다 [EL5, RG D]. 1 폐혹은기타부위결핵병력크론병과장결핵의감별점은여러가지가있지만, 과거폐혹은기타부위결핵병력은임상의에게장결핵의가능성을생각하게하는실마리가될수있다. 2 치열, 치루, 항문주위농양수술및치료력, 기타부위누공크론병에서치열, 치루, 항문주위농양등난치항문병변이흔히동반된다. 국내단일기관의보고에따르면크론병환자의 48.5% 가치루를호소하였고, 15.0% 의환자가크론병의다른증상이없이, 첫증상으로치루를호소하였다. 31 또한크론병진단때 29.2% 의환자가치루를호소하였다는연구도있다. 21 따라서복통, 설사, 체중감소등을호소하는환자에서치열, 치루, 항문주위농양수술및치료력, 재발여부는크론병의중요한단서가될수있다. 궤양성대장염, 베체트장염에서항문주위병변은흔하지않고, 장결핵에서항문주위병변역시크론병보다는드물게동반된다. 그러나, 남아프리카에서는수술을시행한치루의 17% 가결핵치루였다는보고가있고, 52 대만에서도 8% 의장결핵환자가직장항문병변으로발현하였다는보고가있어, 53 항문주위병변만으로장결핵을배제할수는없다. (6) 기타 : 여행력, 증상발생전음식섭취력, 접촉자및가족내유사증상자여부는설사의양상및지속기간과더불어기본적으로파악할내용들로급성감염설사와의감별을위하여중요하다. 특정음식물에대한불내성 (intolerance) 으로인한만성설사의가능성을배제하기위해이에대한병력도청취한다. 또한항균제, 비스테로이드소염제등다양한약물들이설사를유발할수있으므로최근복용한약물뿐아니라, 타의료기관에서크론병으로진단받은후복용한약물도파악한다. 흡연은크론병의위험인자및악화요인으로잘알려져있다. 54 흡연시작시기, 흡연량, 금연시기등환자의흡연력을가능한정확히파악한다. 흡연력으로기타장질환과의감별에도움을얻을수는없다. (7) 염증성장질환의가족력 : 이는크론병의위험인자로알려져있어 54 진단에참고가될수있다. (8) 신체검진신체검진은아래항목을포함한다 : 전신상태, 혈압, 맥박, 체온, 체중및체질량지수, 복부팽만, 복부압통, 복부종괴, 직장손가락검사 [EL5, RG D]. 일반적으로크론병으로확

7 예병덕외 5 인. 크론병진단가이드라인 167 진할수있는특이적인신체검진소견은없다 [EL5, RG D]. 1 신장, 체중, 체질량지수전형적인크론병환자의경우, 일반적인궤양성대장염환자와달리저체중이다. 47 소아및청소년의경우성장저하여부를판단하기위해표준곡선과비교, 신장과체중의 z-score 를구해야하고, 이전의신장및체중의변화속도, 목표성장치를구하기위해부모의신장, 체중도조사한다. 55 소아및청소년은 Tanner stage를이용한성조숙도도측정한다 피부및구강크론병에동반될수있는피부및구강병변여부를확인해야한다. 3 복부검진 i) 시진 : 기계적인장폐쇄 (mechanical intestinal obstruction) 가있는경우, 폐쇄근위부장관의확장에의한복부팽만및연동운동이관찰될수있다. ii) 장음 : 장음은다양하게청진될수있다. 기계적인장폐쇄의경우장음이항진되고, 장마비 (paralytic ileus) 의경우장음은감소된다. iii) 공명음 : 장폐쇄혹은마비로인해장내가스가증가된경우, 타진때공명음이증가된다. iv) 촉진 : 장침범부위에따라압통이있을수있다. 우하복부의압통은원위및말단회장부의침범을시사하고, 반발통은벽측복막까지염증이파급되었음을나타낸다. v) 복부종괴 : 복부종괴가촉진되는경우일반적으로종양을의심하게된다. 그러나크론병이의심되는환자에서는염증종괴 (inflammatory mass) 의가능성을고려해야한다. 궤양성대장염은대장만을침범하므로염증종괴가촉진되는경우는드물다 항문및회음부치열, 치루, 항문주위농양등을육안으로관찰하고, 국소발열, 발적, 압통, 분비물여부도촉진으로확인한다. 또한직장손가락검사로항문협착여부도확인한다. 궤양성대장염에서항문주위병변이동반되는경우는드물고 57 베체트장염에서도항문침범이흔하지않다 관절통증을호소하는부위의관절부종, 압통등을확인한다. 2) 검사실소견기본적으로시행해야할검사는일반혈액검사 [EL5, RG D], CRP [EL2, RG B]( 불가능한경우 ESR [EL5, RG D]), 혈청생화학검사이고, 기타검사는임상상황에따라선택적으로시행할수있다 [EL5, RG D]. 크론병으로진단할수있는특이적혈액검사등검사실 검사는없다. 아래와같은검사들로진단에보조적인도움을얻는다. (1) 일반혈액검사 : 크론병에서가장흔히관찰되는빈혈은철결핍빈혈이고그다음은만성질환에동반된빈혈 (anemia of chronic disorders) 이나, 59,60 광범위한소장절제술을받은경우, 광범위한회장침범이있는경우는비타민 B 12 또는엽산흡수부전으로인한거대적아구빈혈도관찰될수있다. 60 빈혈여부를확인하고빈혈이있는경우평균적혈구용적 (mean corpuscular volume, MCV), 평균적혈구혈색소 (mean corpuscular hemoglobin, MCH), 평균적혈구혈색소농도 (mean corpuscular hemoglobin concentration, MCHC) 소견에따라빈혈의유형을확인하기위한망상적혈구 (reticulocyte), 말초혈액도말검사, 철 (iron), 저장철 (ferritin), 총철결합능 (total iron binding capacity, TIBC), 비타민 B 12, 엽산 (folate) 검사등을추가로시행한다. 일반혈액검사에서백혈구와혈소판상승은급성염증반응을시사한다. (2) CRP: CRP는비특이적인급성기반응물질이만, 크론병의질병활동도를비교적잘반영하는지표이다 ESR은 CRP보다크론병질병활동도와의관련성이낮지만, CRP 측정이곤란한경우 ESR을측정한다. ESR은소장병변보다는대장병변과더관련성이높은것으로알려져있다. 64 과민장증후군환자에서는혈색소감소, 백혈구증가, 혈소판증가, CRP 증가, ESR 증가등이상소견을보일확률이매우낮으므로, 이러한검사실항목들은소장및대장검사가필요한환자들을선별해내는데매우유용하게활용될수있다. (3) 혈청생화학검사 : 약 40% 의크론병환자는혈청 transaminase, bilirubin, alkaline phosphatase가증가되어있다는보고가있다. 47 그러나우리나라에서이러한이상소견을보이는환자의비율은밝혀져있지않다. 혈청 transaminase, bilirubin, alkaline phosphatase, gamma-glutamyl transferase의상승은원발경화담관염에서의담즙정체혹은 overlap syndrome에서자가면역간염이동반되어있을때관찰될수있다. 그러나검사수치의이상을흔히유발할수있는약제, 간염바이러스감염등을배제해야한다. 총단백과알부민의저하는장기간의단백소실혹은흡수부전으로인한영양결핍상태를반영한다. (4) 대변검사 : 병력및신체검진에서급성감염장염이의심되는경우감별을위하여대변기생충검사, 일반세균도말및배양을시행한다. 그러나, 급성감염장염에서대변배양검사의양성률은 40-80% 로, 진단에도움을얻지못하는경우가많다. 65 (5) Clostridium difficile 배양및독소검사 : 항균제복용력등위막성대장염이의심되는경우에는시행한다. (6) ASCA와 panca: ASCA (anti-saccharomyces cere-

8 168 The Korean Journal of Gastroenterology: Vol. 53, No. 3, 2009 visiae antibody) 는크론병환자의 35-50% 에서양성이나, 궤양성대장염환자의 1% 미만에서양성이다. 20,47 반면, panca (perinuclear anti-neutrophil cytoplasmic antibody) 는궤양성대장염에서흔히양성이다. 4,019명의크론병환자와 3,841명의궤양성대장염환자를대상으로한메타분석에서는 ASCA 양성, panca 음성인경우크론병진단에대한민감도가 55%, 특이도가 93% 였고 panca의궤양성대장염진단에대한민감도는 55%, 특이도는 89% 였다. 66 그러나한국내연구에서는 panca가음성이고 ASCA가양성일경우크론병진단에대한민감도는 48%, 특이도는 87% 라고보고하였다. 67 따라서 ASCA와 panca는크론병과궤양성대장염의감별이어려울때보조적으로도움이될수있다. 3) 내시경검사내시경은크론병을진단하는데가장중요하고기본적인검사이다. (1) 대장내시경대장내시경은크론병진단에일차적으로추천되는검사로, 말단회장부를포함한전체대장을관찰하고, 이상병변에대한생검을시행한다. 크론병에특징적인대장내시경소견은종주궤양 (longitudinal ulcer), 조약돌점막모양 (cobblestone mucosal appearance) 또는종주로배열된아프타궤양 (aphthous ulcer) 이비연속적으로나타나는것이다 [EL5, RG D]. 대장내시경및생검이크론병의진단에일차적으로추천되는검사이다 적절한장정결후대장전체를관찰하고, 말단회장부로내시경을삽입하여말단회장부병변을반드시확인한다. 크론병을시사하는내시경소견은다음과같다. 1 종주궤양 (longitudinal ulcer) 일본에서종주궤양은 4-5 cm 혹은그이상길이의궤양이장의주행과평행한방향으로관찰되는것으로정의하고있다. 71,72 우리나라크론병환자에서종주궤양의길이에대한연구는없으나, 이러한정의는우리나라진단가이드라인에도그대로적용될수있을것으로생각된다. 크론병궤양의경계는뚜렷하여주변점막과잘구별되고, 깊이는깊다. 궤양의주변점막은비교적정상소견을보이고, 이는궤양주변의점막도염증변화를보이는궤양성대장염과의감별점이다. 2 조약돌점막모양 (cobblestone mucosal appearance) 크론병의궤양들이사방으로연결되면, 심한궤양들사이사이에남은점막들이과형성및부종변화로인해돌출되어보임으로써마치조약돌을깔아놓은듯한양상으로관찰된다. 73 이러한조약돌점막모양은크론병에매우특징적인 소견이므로진단가치가높은것으로생각된다 종주로배열된아프타궤양아프타궤양혹은미란은크론병의초기에나타나는특징적병변으로알려져있으나, 베체트장염, 장결핵, 아메바장염, Yersinia 장염, 장티푸스, 위막대장염등다른질환이나정상인에서도드물게나타날수있다 아프타궤양은크기가 5 mm 이하의편평하거나약간함몰된표재궤양으로궤양의바닥은회백색또는황색삼출물로덮여있고궤양의경계는융기되어있지않으며발적을보이는테두리로둘러싸여있다. 73 종주로배열된아프타궤양의경우크론병의가능성이더높다고알려져있으나, 6,73 위에서언급한질환들을배제하고, 임상상및기타소견을고려해야할것이다. 크론병에서는위와같은병변들이비연속적으로나타나는것이특징적이다. 국내단일기관에서크론병으로처음진단받은환자들에서는아프타궤양이 59.3%, 종주궤양이 37.2%, 조약돌점막모양이 23.9% 에서관찰되었다 내시경감별진단장결핵에서는장관을둘러싸는방향의횡행궤양 (transverse ulcer) 이특징적으로관찰되고, 크론병에서는종주궤양이특징적이나, 두질환에서횡행궤양과종주궤양이함께나타나는경우도많다. 또한장결핵에서는크론병보다반흔변화및가성용종이더흔하고, 회맹판이열려있는경우가더많으며아프타궤양은더드물게나타난다. 76 한편 4개이상의분절에병변이관찰되는경우는장결핵보다는크론병에서더흔히나타난다. 76 궤양성대장염은역류회장염이동반되지않는한말단회장부는특이소견이없고, 대장병변은직장에서부터연속적으로근위부로분포한다. 궤양성대장염에서는미소궤양, 얕은궤양, 점막의취약성 (friability), 가성용종이크론병보다더흔히관찰되고, 종주궤양, 아프타궤양, 조약돌점막모양은흔하지않다. 57 궤양성대장염에동반된역류회장염은회맹판이열려있고, 염증의범위가더넓은반면, 크론병의회장염은회맹판이수축 (constriction) 및협착을보이는경우가많다. 77 우리나라베체트장염환자에서는회맹부에대개 1개내지수개의궤양이나타나는경우가많다. 베체트장염의궤양은주로원형또는타원형으로바닥은깨끗하고두꺼운백태로덮여있고, 경계는분명하며궤양주변점막은발적, 부종을보일수있으나, 취약성이없다. 베체트병에서얕고불규칙한궤양은비교적드물다. 73 (2) 에스자결장경 : 크론병진단에일차적으로추천되지않는다. 중증의증상으로대장내시경시천공의위험이있는경우또는적절한장정결이불가능한경우우선시행하고이후에대장내시경을시행할수있다. 4

9 Ye BD, et al. Diagnostic Guideline of Crohn s Disease 169 (3) 상부위장관내시경상부위장관내시경은상부위장관증상이있는경우에만추천된다 [EL5, RG D]. 상부위장관을침범하는크론병은거의모든경우소장혹은대장침범을보이는것으로보고되었다 식도, 위를침범하는크론병은발적, 미란, 궤양등비특이병변으로나타날수있다. 81 또한위에서 bamboo joint-like (BJL) appearance 를보일수도있는데, 이는상부위체부의소만부와분문부를따라미란이나고랑 (furrow) 이횡축방향으로가로지르는두꺼운점막주름의형태로나타나는것이다. 81,82 이러한특징적인점막변화는크론병의환자의 % 에서발견되나, 크론병이아닌환자에서는 % 에서만발견되어, 크론병에특이한소견으로보고되고있다 국내한연구에서도크론병환자에서 BJL appearance 가 47.6% 에서관찰되어, 궤양성대장염환자의 3.6%, 비염증성장질환환자의 0.1% 보다의미있게더높은비율을보인바있다. 81 (4) 캡슐내시경크론병에서캡슐내시경의진단가치에대해서는대규모의전향연구가필요하다. 캡슐내시경은소장크론병이의심되는유증상환자에서 1) 협착이배제되고, 2) 말단회장부에대한내시경검사가정상이거나불가능하며, 3) 투시혹은단층검사등영상의학검사에서특이소견이없는경우고려될수있다 [EL2, RG B]. 캡슐내시경은방사선노출없이소장전역을관찰할수있는비침습검사로각광받고있다. 캡슐내시경에서크론병을시사하는소견은종주궤양, 조약돌점막모양, 아프타궤양, 협착등이다. 최근한메타분석에서는협착이없는크론병의진단에캡슐내시경이소장조영술 (small bowel follow-through), 대장내시경, 전산화단층촬영 (computed tomography, CT), 소장자기공명영상 (magnetic resonance imaging, MRI) 등기타검사보다더우수하다고보고하였다. 85 그러나캡슐내시경은생검이불가능하다는단점이있고, 관찰되는영상의해석에대해서도향후좀더명확한합의가필요하다. 일반적으로는병력, 신체검진, 혈액검사등에서크론병이의심되나대장내시경 ( 말단회장부관찰포함 ) 및생검에서크론병을의심할만한소견이없고, 영상의학검사에서소장크론병의증거가뚜렷하지않은경우소장병변의확인을위해시행할수있다. 캡슐내시경시행전에는영상의학검사에서소장의협착을배제해야하고, 영상의학검사에서협착의증거가없는경우도캡슐저류의위험이있음을주지해야한다. (5) 소장내시경 : 과거밀기방식의소장내시경 (push enteroscopy) 이소장관찰을위해사용되었으나, 내시경을삽입할수있는깊이는제한적이었다. 그러나, 최근이중풍선내시경 (double balloon endoscopy) 이개발되어소장전역의관찰이가능해졌다. 소장내시경의적응증은캡슐내시경과유사하고, 크론병의진단소견역시캡슐내시경과유사하다. 소장내시경은캡슐내시경과비교시침습적이고, 고가이며검사에장시간이소요되나, 시술자에의하여내시경의조정, 흡기와송기, 세척이가능하고, 생검이가능한장점이있다. 일반적으로는비침습적인캡슐내시경을우선시행하는것이추세이나캡슐내시경또는소장내시경의선택에대해아직합의안은없고, 임상소견에따라판단해야할것으로생각된다. 4) 영상의학검사대장내시경에서크론병의증거가있는경우, 말단회장부의내시경, 조직소견에관계없이소장침범의위치및범위를알기위해소장검사가추천된다 [EL1b, RG A]. 소장조영술 (small bowel follow-through) 이소장크론병진단에일차적인방법이다. 전산화단층촬영이나자기공명영상을이용한소장촬영법도기존의소장조영술에필적하거나더우수한성적을보이고있어향후그활용이기대된다 [EL5, RG D]. 누공, 농양등장관외합병증이의심될때에는초음파, 전산화단층촬영또는자기공명영상이적절한검사방법이다 [EL1c, RG A]. 다음과같은다양한영상의학검사들이크론병의진단을위해사용된다. 크론병진단의첫단계에서는흉부 X-선과소장조영술을기본적으로시행하고, 기타검사들은임상상황에맞게적절히시행하는것이좋다. (1) 흉부 X-선 : 장의병변으로크론병과장결핵의감별이어렵고흉부촬영에서활동폐결핵이동반된경우, 크론병보다장결핵을의심할수있는중요한단서가된다. 그러나, 장결핵에서폐결핵이동반되는것은 50% 미만으로알려져있어많은경우에도움을얻을수없다 (2) 단순복부촬영 (plain abdominal radiography): 단순복부촬영으로크론병을진단할수는없고, 급성장폐쇄, 장천공등이의심되는경우등에서우선적으로신속히시행하여진단에도움을얻을수있다. 그러나장폐쇄의원인을진단할수는없다. (3) 소장조영술 (small bowel follow-through)/ 소장고위관장법 (small bowel enteroclysis): 이중조영 (doublecontrast) 소장조영술혹은고위관장법이소장의영상의학평가에일차적으로추천되는검사이다. 소장조영술은삽관이필요없으므로환자가더용이하게검사를받을수있어우선적으로추천할수있겠다. 점막병변, 누공, 위, 십이지

10 170 대한소화기학회지 : 제 53 권제 3 호, 2009 장병변의진단에소장조영술이고위관장법보다더우수하다고보고된바있으나, 91,92 소장협착이의심되는경우소장을확장시킬수있는고위관장법이더우수하며, 비가역적인협착과기능적인경련 (functional spasm) 을감별할수있다. 소장영상에서장간막면 (mesenteric border) 을따라주행하는종주궤양, 조약돌점막모양, 협착, 누공등이크론병의진단소견이다. 47 국내연구에서는 107명의크론병환자에서종주궤양이 45.8%, 협착이 27.1%, 누공이 4.7% 에서관찰되었다. 21 고위관장법의소장크론병진단에대한민감도와특이도는각각 93% 및 92% 로보고된바있다 두검사모두투시하에진행되는동적인 (dynamic) 검사로, 주된이상소견은검사진행중에관찰가능하므로, 경험이풍부한의사가시행해야한다. 또하나의문제점은고용량의방사선조사이다. (4) 대장조영술 : 대장내시경이널리시행되면서대장조영술은최근드물게사용되고있다. 그러나, 이중조영바륨관장법 (double-contrast barium enema) 은대장협착으로인해내시경의진입이불가능한경우점막병변의양상및병변범위를확인하기위하여시행할수있는첫번째검사법이다. 96 크론병에서관찰되는초기소견은아프타궤양, 종주궤양, 조약돌점막모양등이비연속적으로관찰되는것이며, 진행된크론병의소견으로는주름의소실, 누공, 소낭변화 (sacculation), 협착, 가성용종등이다. 97 (5) 복부전산화단층촬영 : 크론병진단에일차적으로추천되지는않는다. 단, 급성복증, 장천공이나복강내농양이의심되는경우일차적으로시행한다. 또한급성장폐쇄의원인을찾는데도유용하다. 98 전산화단층촬영소장조영술 (CT enterography) 및전산화단층촬영고위관장법 (CT enteroclysis) 에서는장벽비후, 장벽조영증강, 누공, 협착등의소견으로크론병을진단할수있다. 99 전산화단층촬영소장조영술및고위관장법은그영상의질이점차향상되어, 기존의소장조영술을대치할수있거나더우수하다고보고된바있으나, 100,101 그진단가치에대해아직더많은연구가필요하다. 전산화단층촬영대장조영술 (CT colonography) 은최근대장내시경과의비교연구에서염증성장질환진단에유사한성적을보였다고보고된바있다. 102 그러나이는점막양상을간접적으로관찰하는방법이고, 생검을할수없다는단점이있어, 아직대장내시경을대치할수는없을것으로생각된다. (6) 복부자기공명영상 : 자기공명영상은수분함유도의차이를이용하여, 활동성염증과섬유화에의한협착을감별할수있는장점이있다. 103 자기공명영상고위관장법 (MR enteroclysis) 은크론병에서의소장협착진단에기존의소장조영술과유사한성적을보인다고보고되었다. 104 또한크론병의일차진단에대한민감도와특이도가각각 95%, 93% 로소장고위관장법의 85%, 77% 보다더우수한성적을보고한연구도있다. 105 더불어치루나항문주위농양등직장항문병변의경우자기공명영상으로 3차원적인정보를얻을수있다. (7) 내시경초음파 (endoscopic ultrasound): 치루, 항문주위농양등직장항문병변을진단하는데자기공명영상대신이용할수있다. 내시경초음파로단순치루 (simple fistula) 및복잡치루 (complex fistula) 를감별할수있고, 또한치루와괄약근의해부학적인관계에대한정보도얻을수있다. 47 내시경초음파는안전하고간편하며, 치루및항문주위농양의진단에자기공명영상및마취하검사 (examination under anesthesia) 와유사한민감도와특이도를보인다고보고되었으나, 106 숙련된시술자가필요하다. (8) 복부초음파 : 복부초음파는염증성장질환진단을위한비침습검사로, 소, 대장의염증부위를장벽의직경, 혈류상태를통해진단할수있다. 47 또한림프절비대, 농양, 장협착, 누공등도초음파로진단할수있다. 초음파는시술자의숙련도에크게좌우되나, 전문가에의해시행되는경우크론병진단에대한민감도는 87-95% 로알려져있다 우리나라크론병환자에서복부초음파의진단적인역할에대한연구는아직부족하다. 5) 조직검사 (1) 검체의채취및처리생검검체는임상정보 ( 환자의연령, 이환기간, 치료종류및기간 ) 와함께병리의사에게제공되어야한다 [EL5, RG D]. 생검검체는포르말린용액또는동등용액에즉시고정하여이송해야한다 [EL1b, RG A]. 병변이경미하거나국소적일수있으므로각검체에대해여러개의조직절편 (section) 을얻을것이추천된다 [EL2, RG B]. 병리조직소견만으로크론병을진단할수없는경우가대부분이다. 임상의사는임상적정보를병리의사에게충분히제공해야하고, 내시경시행시병변부위뿐아니라정상부위도생검하여제공할것이추천된다. 112 장결핵의경우궤양부위생검시진단율이높다고알려져있으므로크론병과장결핵의감별진단을위해궤양변연 (margin) 뿐아니라궤양저부 (base) 도함께여러부위를생검하는것이좋다. 86,113 생검개수는표준이없으나, 생검부위당최소 2개이상의생검이추천된다. 5,114,115 병변이경미하거나국소적일수있으므로내시경생검검체는여러개의조직절편이필요하고, 많은절편을만들수록진단율은증가된다. 이상적인조직절편의수는확립되지않았으나연구에따라 2-6개로보고되었다. 116,117 염색법으로는 hematoxylin과 eosin을이용한염색이추천되고기타특수염색, 면역화학염색은일반

11 예병덕외 5 인. 크론병진단가이드라인 171 적으로필요하지않다. 5 (2) 크론병의조직소견국소 (focal) 및반점상 (patchy) 만성염증 ( 림프구및형질세포침윤 ) 과국소음와구조변형, 음와손상과인접하지않은육아종이일반적으로크론병에서관찰될수있는조직소견이다 [EL2, RG B]. 내시경점막생검에서관찰할수있는크론병에특징적인소견은비건락육아종 (noncaseating granuloma) 이나질병특유적 (pathognomonic) 이지않고, 또한민감한소견은아니다 [EL5, RG D]. 1 비건락육아종 (noncaseating granuloma) 크론병에특징적인비건락육아종 (collection of epithelioid histiocytes) 은수술검체의 40-60%, 118 내시경생검검체의 15-36% 에서만관찰되어민감한진단소견은아니다. 119 국내보고에서는내시경생검및수술절제조직을통틀어 50% 에서비건락육아종양성인것으로보고되었고, 20 다른보고에서는진단시점에서 70.9% 에서육아종이관찰되었다. 21 육아종은각종감염장염 (Mycobacterium species, Chlamydia species, Yersinia paratuberculosis, Yersinia enterocolitica, Treponema species, Salmonella species, Campylobacter species 감염등 ) 및위장관을침범하는유육종증 (sarcoidosis) 에서도발견될수있다. 5 고유층에서관찰되며음와손상에인접하지않은육아종이크론병에진단적이고, 5 음와손상과관련되어형성된것으로추정되는육아종은진단가치가낮다 염증소견육아종이외에도크론병에서는음와염 (cryptitis), 음와농양 (crypt abscess), 만성염증을시사하는음와구조의변형 [crypt distortion (non-parallel crypts, variable diameter, cystically dilated crypts), crypt branching, crypt shortening], 121 고유층 (lamina propria) 에 T 세포와단핵구 (monocyte), 형질세포 (plasma cell) 침윤등이관찰될수있다. 수술검체에서크론병을시사하는현미경소견은전층염증 (transmural inflammation), 전층림프증식 (lymphoid hyperplasia), 점막하층의비후, 점막하신경섬유의비후 (nerve fiber hyperplasia) 및신경절염 (ganglionitis) 등이다. 5 그러나, 하나의조직검사소견만으로크론병으로진단하기는충분하지못하다. 따라서수술검체에서는육아종이없는경우 3가지이상, 육아종이있는경우는다른한가지병변이동반된경우 ( 단, 감염성장염이배제된경우 ), 크론병으로진단가능하다고제안된바있다. 122 내시경점막생검검체에서는위와같은기준이제안된바없으나, 같은기준이적용될수있을것으로생각된다. 5 3 다른염증성장질환과의감별점크론병에서는궤양성대장염보다는덜심하고비연속적인음와구조의파괴, 비연속적인염증 (focal or patchy inflammation), 음와숫자의보존, 비교적정상적인술잔세포가관찰되고, 궤양성대장염과달리전층염증을특징으로하나, 이는내시경생검검체로는확인할수없고수술검체가필요하다. 장결핵은건락육아종및항산균양성으로진단할수있으나이는 30% 미만에서나타난다. 112, 크론병에서는장결핵보다서로융합하는육아종 (confluent granuloma) 및점막하의육아종이드물고, 육아종의크기가더작으며, 하나의생검검체에하나의육아종이있는경우가많다고보고된바있다. 112,125,126 급성감염설사의조직검사소견은만성장염과는달리, 음와구조의파괴및변형이거의없고, 고유층염증세포의침윤도더적다 그러나염증성장질환도그질병경과가길지않을때는만성적인변화가잘관찰되지않을수도있어주의를요한다. 4 국소활동위염 (focal active gastritis) 소장및대장생검만으로크론병의진단이확실하지않은경우위생검에서육아종이관찰되거나 Helicobacter pylori 감염이없는국소활동위염소견을보이는경우크론병을의심할수있으나, 민감도와특이도가높지는않다. 130,131 6) 복강경 / 수술소견수술시절제한소장혹은대장검체는상세히육안관찰하고, 가능한절제한시점에사진촬영을해야한다 [EL5, RG D]. 검체를육안관찰후장축방향을따라 (antimesenteric 또는 antimesocolic border를따라서 ) 연후, 슬라이드제작을위한부분 ( 림프절, 말단회장부, 충수포함 ) 을채취한다 [EL2, RG B]. 수술검체에서채취해야하는최적의검체수는확립되지않았으나, 많은검체를채취할수록높은진단율을기대할수있다. 또한육안이상부위만을채취하지않도록한다 [EL5, RG D]. 크론병에서흔히관찰되는육안소견은다발장협착, 장을둘러싸는장간막지방 (mesenteric fat wrapping, creeping fat), 장간막림프절비대등이다. 일차진료에서보다는이전에크론병으로진단받지않은환자가장천공등에의한급성복증으로수술을받는경우, 그육안소견으로크론병을의심할수있다. 복강경또는수술에서관찰할수있는크론병의육안소견은다발장협착, 장을둘러싸는장간막지방 (mesenteric fat wrapping, creeping fat), 장간막림프절비대등이다. 크론병에서전층염증이지속되면인접한장간막의부종과섬유화도동반되고, 장간막지방이장막 (serosa) 표면을따라서장을손가락모양으로둘러싸는특징적모양을나타내게된다. 이는크론병진단에높은양성예측도를가진소견으로보고되었다. 5,132,133 한편 225예의소장절제수술검체분석에서이러한소견은크론병환자에서만관찰되었다고기술되었으나, 134 인도에서

12 172 The Korean Journal of Gastroenterology: Vol. 53, No. 3, 2009 는장결핵으로개복수술을받은환자에서도유사한소견이관찰되었다고보고된바있다 한편활동크론병에서는장간막림프절의비대및집적화 (conglomeration) 가관찰될수있으나특이적소견은아니다. 5. 감별진단아래의질환들은크론병과반드시감별해야할질환이다. 개개의감별점은각진단과정에서기술하였다. 1) 과민장증후군 2) 급성감염장염 3) 궤양성대장염 4) 장결핵 5) 베체트장염결론크론병은국내에서점차발병률과유병률이증가하고있고, 따라서일선의의사도점차적으로많이접하고있다. 한국인의크론병은역학및임상양상등이구미와는차이가있는것으로생각되며, 이를반영한한국진단가이드라인이필요하다. 이에대한장연구학회 IBD 연구회는국내에서처음으로크론병의진단가이드라인을제정하게되었다. 이번가이드라인은일선의사들의비판적인임상적용및최신지견의반영등으로향후지속적으로수정, 보완되어야할것이다. 참고문헌 1. Kirsner JG. Historical aspects of inflammatory bowel disease. J Clin Gastroenterol 1988;10: Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis: a pathologic and clinical entity. JAMA 1932;9: Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, : a KASID study. Inflamm Bowel Dis 2008;14: Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004; 3:S1-S Stange EF, Travis SP, Vermeire S, et al. European evidence based consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis. Gut 2006;55: Yao T, Matsui T, Hiwatashi N. Crohn's disease in Japan: diagnostic criteria and epidemiology. Dis Colon Rectum 2000;43:S85-S Gollop JH, Phillips SF, Melton LJ 3rd, et al. Epidemiologic aspects of Crohn's disease: a population based study in Olmsted County, Minnesota, Gut 1988;29: Loftus EV Jr, Silverstein MD, Sandborn WJ, et al. Crohn's disease in Olmsted County, Minnesota, : incidence, prevalence, and survival. Gastroenterology 1998;14: Centre for Evidence Based Medicine, Oxford. Levels of evidence and grades of redommendation. evles_of_evidence.asp. 10. Best WR, Becktel JM, Singleton JW, et al. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology 1976;70: Harvey RF, Bradshaw JM. A simple index of Crohn s disease activity. Lancet 1980;1: Best WR. Predicting the Crohn s disease activity index from the Harvey-Bradshaw index. Inflamm Bowel Dis 2006;12: Gasche C, Scholmerich J, Brynskov J, et al. A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna Inflamm Bowel Dis 2000;6: Satsangi J, Silverberg MS, Vermeire S, et al. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006;55: Yang SK. Current status and clinical characteristics of inflammatory bowel disease in Korea. Korean J Gastroenterol 2002;40: Lapidus A. Crohn's disease in Stockholm County during : an epidemiological update. World J Gastroenterol 2006;12: Moum B, Vatn MH, Ekbom A, et al. Incidence of Crohn's disease in four counties in southeastern Norway, A prospective population-based study. The Inflammatory Bowel South-Eastern Norway (IBSEN) Study Group of Gastroenterologists. Scand J Gastroenterol 1996;31: Tragnone A, Corrao G, Miglio F, et al. Incidence of inflammatory bowel disease in Italy: a nationwide populationased study. Gruppo Italiano per lo Studio del Colon e del Retto (GISC). Int J Epidemiol 1996;25: Loftus CG, Loftus EV Jr, Harmsen WS, et al. Update on the incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota, Inflamm Bowel Dis 2007;13: Kim CG, Kim JW, Kim HD, et al. Clinical features of Crohn's disease in Korea. Korean J Gastroenterol 2002;40: Park JB, Yang SK, Myung SJ, et al. Clinical characteristics at diagnosis and course of Korean patients with Crohn's

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