대한소화기학회지 2009;53:187-193 REVIEW 베체트장염진단가이드라인 연세대학교의과대학내과학교실 *, 아주대학교의과대학내과학교실, 가톨릭대학교의과대학내과학교실, 서울대학교의과대학내과학교실 천재희 * ㆍ신성재 ㆍ김상우 ㆍ이강문 ㆍ김주성 ㆍ김원호 * ㆍ대한장연구학회 IBD 연구회 Diagnosis of Intestinal Behçet s Disease Jae Hee Cheon, M.D.*, Sung Jae Shin, M.D., Sang Woo Kim, M.D., Kang Moon Lee, M.D., Joo Sung Kim, M.D., Won Ho Kim, M.D.*, and IBD Study Group of the Korean Association of the Study of Intestinal Diseases Department of Internal Medicine, Yonsei University College of Medicine*, Seoul, Ajou University College of Medicine, Suwon, The Catholic University of Korea College of Medicine, Seoul National University College of Medicine, Seoul, Korea Due to similar manifestations of intestinal Behçet s disease (BD) to those of other colitis such as Crohn s disease or intestinal tuberculosis, it is still challenging for gastroenterologist to accurately diagnose intestinal BD in patients with ileo-colonic ulcers. Moreover, no reliable diagnostic criteria for intestinal BD have been developed yet. Therefore, IBD Study Group of KASID was formulated to establish the guideline for the diagnosis of intestinal BD using a modified Delphi process. The novel diagnostic criteria for intestinal BD were developed based on two aspects; colonoscopic findings and extra-intestinal systemic manifestations, in which patients were categorized into 4 groups including definite, probable, suspected, and non-diagnostic for intestinal BD. Furthermore, Disease Activity Index for intestinal BD was developed through a Korean multicenter study. These diagnostic and disease activity guidelines will contribute to understand intestinal BD. (Korean J Gastroenterol 2009;53:187-193) Key Words: Intestinal Behçet s disease; Diagnostic criteria 서론베체트병은 1937년터키피부과의사인 Behçet가재발구강궤양, 외음부궤양및안구염증의 3대증상을특징으로하는만성재발질환으로처음기술한전신질환으로그밖에도피부, 관절, 혈관계, 신경계및위장관등을침범할수있다. 1 그러나베체트병은아직정확한질병원인이나병태생리가밝혀져있지않고특이치료가없으며기존의류마티스질환이나염증성장질환에사용되고있는약제를경험적으로사 용하고있는실정이다. 베체트병이장관을침범할경우치료에대한반응이나쁘며천공등의합병증이흔하므로베체트장염은베체트병의중요한유병및사망원인이된다. 2 하지만지금까지제안된베체트병진단기준에서예후에중요한영향을주는베체트장염은포함되어있지않고있는것은이에대한관심과연구가부족하다는것을반영한다. 베체트장염을정확하게진단하기위해서는진단가이드라인이필요하나, 아직까지체계화된미국및유럽의진단가이드라인이확립되어있지않다. 이는베체트장염의진단기준이명확하지 연락처 : 김원호, 120-752, 서울시서대문구신촌동 134 연세대학교의과대학내과학교실 Tel: (02) 2228-1950, Fax: (02) 393-6884 E-mail: kimwonho@yuhs.ac * 본연구는보건복지부보건의료기술진흥사업의지원에의하여이루어진것임 ( 과제고유번호 : A080588). Correspondence to: Won Ho Kim, M.D. Department of Internal Medicine, Yonsei University College of Medicine, 134, Sinchon-dong, Seodaemun-gu, Seoul 120-752, Korea Tel: +82-2-2228-1950, Fax: +82-2-393-6884 E-mail: kimwonho@yuhs.ac
188 대한소화기학회지 : 제 53 권제 3 호, 2009 않고, 치료제및치료반응과예후를파악할수있는객관적인지표등이없으며, 또한, 우리나라를포함한동아시아와는달리서구에서는베체트장염이드물기때문이다. 다만, 최근들어일본에서 2007년에전문가들에의해베체트장염의진단및치료에대한합의가처음으로제안되었으나, 이합의안역시아직검증되지않았고, 우리나라의의료환경및환자특성을고려할때그대로적용하기에는다소어려운실정이다. 따라서, 우리나라실정에맞는베체트장염진단가이드라인설정이필요하며, 이를통해치료의지연으로인한문제를예방하고질병에관한통일된용어를사용함으로써임상의사와연구자들서로간의사소통을원활하게하며, 특히일선에서진료를담당하는의사가베체트장염을진단하는데방향을제시할수있을것이다. 이를위하여본연구회는현재까지국내외에서발표된다양한연구자료들을검토하였고, 특히, 국내에서베체트장염을진단하는데고려하여야할문제점도반영하였다. 사안에따라근거자료가불충분할경우는대한장연구학회산하 IBD 연구회전문가들의토론을통해권고안을제시하였다. 다만, 궤양성대장염이나크론병과는달리아직까지베체트장염의경우질병에대한의학적인연구및자료가부족하고, 체계화된기존의가이드라인이없는관계로주로국내자료를이용하여가이드라인을제정하였다. 따라서, 가이드라인제정에의학근거등급 (evidence level) 및추천정도 (recommendation grade) 는제시하지못하였으며, 앞으로추가연구를통하여이를달성할수있으리라생각한다. 이번가이드라인은국내에서처음으로제정되는것이므로, 향후새로운진단방법이개발되거나, 새로운연구결과가발표되는경우그에따라수정및보완이필요하며, 특히전세계적으로볼때가장많은환자군을갖고있는우리나라의경우앞으로많은연구가이루어질것으로기대한다. 본론 1. 정의 (Definitions) 및분류 (Classification) 1) 전신베체트병의진단및분류현재널리쓰이는베체트병의임상진단기준은국제베체트병연구그룹 [International Study Group for Behçet s Disease (ISGBD), 1990] 과 1987년에일본베체트병연구회에서제안한진단기준이다. ISGBD 진단기준은간단하고명료하다는장점이있으나, 베체트장염이진단기준에는포함되어있지않다. 일본의진단기준은증상발현정도에따라여러단계의진단아형을두고있는복잡한구조를보이나다양한임상형태를반영할수있다는장점이있다. 베체트병은구강궤양, 외음부궤양, 포도막염, 피부병변을특징으로하며악화와호전을반복하는만성전신염증성질환이다. 3,4 현재널리사용되고있는임상진단기준은 1990년국제베체트병연구그룹 [International Study Group for Behçet s Disease (ISGBD), 1990] (Table 1) 과 1987년에일본베체트병연구회에서제안한진단기준이다 (Table 2). 5,6 ISGBD 진단기준은간단하고명료하다는장점이있으나, 베체트병증상이반드시동시에나타나는것이아니고시간차이를두며하나씩나타날수있으며구강궤양이반드시포함되어야하는불합리한점이있다. 또한, 베체트장염이진단기준에포함되어있지않으며, 우리나라의경우 pathergy test 의양성률이서구사회에비해 10-40% 이하로비교적낮은편으로진단기준만족률또한낮다. 7-10 반면, 일본의진단기준은증상발현정도에따라여러단계의진단아형을두고있는복잡한구조를보이나다양한임상형태를반영할수있다는장점이있다. Table 1. Diagnostic Criteria (International Study Group for Behçet s Disease, 1990) Recurrent oral ulceration Minor aphthous Major aphthous or herpetiform ulceration observed by a physician or reported reliably by patient Recurrent at least three times in one 12-month period Plus two of the following: Recurrent genital ulceration Recurrent genital aphthous ulceration or scarring, especially males, observed by physician or reliably reported by patient Eye lesions a. Anterior uveitis b. Posterior uveitis c. Cells in vitreous on slit lamp examination or d. Retinal vasculitis observed by qualified physician (ophthalmologist) Skin lesions a. Erythema-nodosum-like lesions observed by physician or reliably reported by patient b. Pseudofolliculitis c. Papulopustular lesions or d. Acneiform nodules consistent with Behçet s Disease observed by a physician and in post-adolescent patients not receiving corticosteroids Positive pathergy test An erythematous papule, >2 mm, at the prick site 48 h after the application of a sterile needle, 20-22 gauge, which obliquely penetrated avascular skin to a depth of 5 mm, read by physician at 48 h
천재희외 5 인. 베체트장염진단기준 189 Table 2. Diagnostic Criteria (Behçet s Disease Research Committee of Japan, 1987) 1. Major (1) Recurrent aphthous ulceration of the oral mucous membrane (2) Skin lesions: Erythema nodosum Subcutaneous thrombophlebitis Folliculitis, acne-like lesions Cutaneous hyperirritability (3) Eye lesions: Iridocyclitis Chorioretinitis, retinouveitis Definite history of chorioretinitis or retinouveitis (4) Genital ulcers 2. Minor (1) Arthritis without deformity and ankylosis (2) Gastrointestinal lesions characterized by ileocecal ulcers (3) Epididymitis (4) Vascular lesions (5) Central nervous system symptoms Diagnosis (1) Complete type: 4 major features (2) Incomplete type: a. 3 major features b. 2 major+2 minor c. Typical ocular symptom+1 major or 2 minor features (3) Suspected type: a. 2 major features b. 1 major+2 minor 2) 베체트장염진단및분류 (1) 진단기준 일반적으로베체트장염은전신베체트병이있으며전형적인장궤양이증명되면진단이가능하다. 하지만전신베체트병의진단기준을만족시키지못하나, 베체트장염이의심되는환자에서시간경과에따라전신증상의발현이뒤늦게나타날수있음을고려할때, 베체트병진단기준에합당하고전형적인장궤양소견을가진경우베체트장염확정형 (definite type), 전신베체트병진단기준에합당하나비전형적인장궤양이있을경우혹은전신베체트병증상이있으나진단기준에합당하지않으면서전형적인장궤양이있을때는유력형 (probable type), 전형적인장궤양이있으나전신증상이전혀없는경우는의심형 (suspected type) 으로분류하기로한다. 일반적으로베체트장염이라고진단을내리기위해서는상기 ISGBD 혹은일본진단기준을만족하는환자에서실 Table 3. Guideline Statements for Diagnosis of Intestinal Behçet s Disease (Japan) 11 Diagnosis of intestinal Behçet s disease can be made if A. There is a typical oval-shaped large ulcer in the terminal ileum, OR B. There are ulcerations or inflammation in the small or large intestine, AND clinical findings meet the diagnostic criteria of Behçet s disease 제적인장관의병변이있어야하며이러한병변은다른원인에의한것이아니어야하고일시적인급성병변이아니어야한다. 최근일본에서도베체트장염진단기준을제안하였는데그기준에서는반드시전신베체트병이있어야베체트장염으로진단하도록하였다 (Table 3). 11 반면, 실제임상에서는소화기내과의사의판단에따라전신베체트병기준을만족하지못하더라도베체트장염으로진단하고경과관찰하는경우가더욱흔하며이에대해명확하고일관된진단기준이필요하다. 이에대한근거로상기진단기준을만족시키지못하면서전형적인베체트장염을보이는경우를단순궤양 (simple ulcer) 이라고부르기도하며, 12 이러한환자의경우시간이경과함에따라진단기준을만족시키는경우가많으므로주의깊은추적관찰이필요하다. 12-14 또한전신증상의동반여부가전형적인베체트장염에일치하는궤양을갖고있는환자의임상경과에영향을미치지못하며두군의임상양상이다르지않다는연구결과가있다. 15 따라서베체트장염의진단은일반적인임상양상, 내시경소견, 조직검사소견등을종합적으로고려하여판단하여야한다. 장연구학회 IBD 연구회에서베체트장염전문가들이문헌고찰과임상경험, 변형된 Delphi 합의과정을거쳐제안하는가이드라인은다음과같다. 즉전신증상이베체트병에합당하고전형적인내시경소견을보이는말단회장또는대장궤양이있으면베체트장염으로확정진단한다 ( 확정형, definite type). 전신베체트병이있으면서전형적이지않은궤양이있을때, 구강궤양이나전신베체트병증상이있으나진단기준에합당하지않는경우전형적인장궤양이있을때는유력형 (probable type) 으로진단한후베체트장염에준하여치료하면서추적관찰한다. 전형적인장궤양이있으나전신증상이없는경우에는의심형 (suspected type) 으로하여역시경과관찰한다. 전신베체트병의진단기준은시간변화에따른단계별분류가가능한일본베체트병연구회진단기준을사용한다.
190 The Korean Journal of Gastroenterology: Vol. 53, No. 3, 2009 (2) 질병활성도아직까지정립된베체트장염고유의질병활성도측정기준은없다. 대한장연구학회에서는 Disease Activity Index for Intestinal Behçet s Disease를다기관연구를통해제시하고자하며임상에서의적용가능성과이에대한검증이필요한상태이다. 현재까지베체트장염에서확립된질병의활성도측정기준은없었으며그동안임상의사의주관적인경험으로판단하거나크론병질병활성도지수등이사용되어왔다. 따라서대한장연구학회에서 Disease Activity Index for Intestinal Behçet s Disease를만들기위한다기관연구가진행되었다. 그결과고유의질병활성도측정기준을만들었으며이에대한임상적용가능성에대한검증이필요한상태이다. 16 상기항목에대한점수를더하여관해기 (<20), 경도 (20-44), 중등도 (45-74), 중증 (75 이상 ) 으로분류한다. 2. 역학 (Epidemiology) 베체트장염은서양이나지중해연안국가에비하여우리나라와일본에흔하다. 베체트병이진단되고나서평균적으로 4-6년경과한 30대중반에많이진단되며, 남자에서다소많다. 베체트병은주로지중해및중동으로부터우리나라를비롯한동아시아에이르는지역에서호발되고있으며 20-30대의젊은환자들이많다. 17 소화기내과의사가관심을갖는베체트병의위장관침범빈도는연구자마다결과가다른데, 이는베체트병의어떤진단기준을채택하였는지에따라모집단의범위가달라질수있고, 장관에병변이확인된경우에한해진단을내려야하나일부연구는위장관증상만으로진단하는오류를범하고있고, 위장관증상이있는경우에한해장검사를시행할경우무증상베체트장염환자를발견하지못해유병률이낮게평가될수있기때문이다. 따라서, 정확한유병률을구하기위해서는정확한진단기준에의해확진된모든베체트병환자들을대상으로장검사를시행하여야할것이다. 2 베체트장염은지역에따라큰편차를보이는데, 터키를포함한지중해연안국가들은유병률이가장높은지역이지만중동이나서양환자들에서는 0-5% 로드물며, 주로우리나라를비롯한동아시아에서는 10-30% 정도로비교적흔하게발생하는것으로알려져있다. 18-20 베체트장염은베체트병진단후평균 4-6년내외에많이진단되며, 진단당시의평균연령은 36-38세로알려져있고, 남녀비는전신베체트병과는달리 1.1-2.0:1 로남자에서다소높다. 2,10,15,21,22 3. 진단 베체트장염의진단은일반적인임상양상, 내시경소견, 조직검사소견등을종합적으로고려하여판단하여야한다. 가장중요한소견은내시경을통한전형적인베체트궤양을육안으로확인하는것이다. 대장내시경소견및조직검사에서베체트장염이진단되거나의심되면 Table 4와같은검사를진행한다. 식도, 위침범유무를파악하기위해상부위장관내시경을시행할수있으며, 소장침범유무를알기위해소장조영술이나 CT 소장조영술을시행한다. 대변검사는세균및기생충에의한감염성장염과감별진단을위해시행한다. 전신베체트병침범정도를파악하기위해피부과, 안과, 신경과, 류마티스내과의협의진료가필요하다. 1) 임상양상 베체트장염의증상으로서가장흔히나타나는것은복통이며약 90% 에서발생한다고알려져있다. 23,24 특히, 우하복부의통증및반발통이나타날수있으며심할경우종괴가만져지기도한다. 그이외에흔히보이는증상으로혈변및흑색변, 설사, 누공, 그리고전신증상으로발열등이있다. 그이외에베체트병의전신증상이동반되었는지확인하면진단에도움이된다. 2) 검사실소견 일반혈액검사에서는백혈구증가, ESR 또는 CRP의상승, 철분결핍빈혈, 혈소판증가, 그리고저알부민혈증이동반될수있으며, 궤양성대장염이나크론병에서발견되는질병특이적인혈청표지자는알려져있지않다. 일반혈액검사에서는백혈구증가, ESR 또는 CRP의상승, 철분결핍빈혈, 혈소판증가, 그리고저알부민혈증이 Table 4. Tests for the Diagnosis of Intestinal Behçet s Disease Colonoscopy Esophagogastroduodenoscopy Small bowel follow-through or CT enterography Blood tests (CBC, chemistry, ESR, CRP) Stool examinations (stool parasites, stool WBC, bacteria) Dermatology, ophthalmologic, neurologic, and rheumatologic evaluations Pathergy test CT, computed tomography; CBC, complete blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; WBC, white blood cell.
Cheon JH, et al. Diagnosis of Intestinal Behçet s Disease 191 동반될수있다. 그러나, 다른염증성장질환인궤양성대장염이나크론병에서관찰되는 panca (perinuclear antineutrophilic cytoplasmic antibody) 혹은 ASCA (anti-saccharomyces cerevisiae antibody) 와같은혈청지표의의의는베체트장염의경우알려져있지않다. 25-28 최근베체트장염환자중약 44% 정도에서 ASCA 양성이었으며이들에서음성인환자들보다누적수술률이높았고, 29 항alpha-enolase 항체는베체트병환자중베체트장염이동반되어있을경우약 65% 에서양성을보여이런혈청검사의베체트장염진단유용성에대해추후귀추가주목된다. 30 3) 내시경검사소견전형적인베체트장염의대장내시경소견은주로회맹부에국한된소수의큰둥근혹은난원형의깊은궤양으로궤양의가장자리는융기되어있고주변정상점막과의경계는명확하며궤양의바닥은두터운백태로덮혀있는경우가많다. 비전형적인경우로아프타궤양, 지도상궤양, 다발분절형및미만궤양등으로나타날수있다. 전형적인베체트장염의대장내시경소견은주로회맹부에존재하는소수의큰둥근혹은난원형의깊은궤양으로궤양의가장자리는융기되어있고주변정상점막과의경계는명확하며궤양의바닥은두터운백태로덮혀있는경우가많다 (Table 5). 그외에도비전형적인경우로아프타궤양, 지도상궤양, 다발분절형및미만궤양등으로나타날수있다. 13,31,32 한연구결과전형적인내시경소견, 즉궤양의모양과분포, 개수를종합할때크론병과의감별이대부분에서가능하였다. 32 전형적인베체트장염소견이있을때전신베체트병진단기준의만족여부에따른임상양상이나내시경소견의차이가없으며, 13 궤양의모양이예후에관련되어있다는연구결과가있다. 31 이는베체트장염진단에전신증상유무가처음부터필수조건이아닐가능성을제시한다. 또한처음베체트장염에전형적인궤양이있을때전신증상이없어도추적관찰중상당수의환자들에서전신증상이장침범이후에나타나므로처음부터전신증상을만족시켜야베체트장염을진단하게되면많은수의환자들에서진단이늦어지게된다. 11,15 4) 영상의학검사소견베체트장염의소장조영술소견은주로회장말단부위에단독혹은다발성의뚜렷한궤양이관찰되며점막주름비대, 형태의변형 (contour deformity), 장관의협착소견이관찰된다. 대장조영술에서는심부관통궤양이나다발궤양, 염증종괴, 누공및가성용종등이관찰될수있다. 33-35 Table 5. Endoscpic Findings of Intestinal Behçet s Disease Typical findings 1. Single or a few large ulcer in ileo-cecal area 2. Round or oval shape deep ulceration 3. Discrete and elevated margin 4. Ulcer base covered with exudates Atypical findings 1. Aphthoid or geographic ulcers 2. Multi-segmental or diffuse distribution 5) 조직검사소견 전형적인베체트장염의조직학적인특징은혈관염과그주변으로의림프구침윤이나, 많은경우에서이러한소견을보이지않으므로임상특성과내시경소견을고려하여진단을내려야한다. 조직학적으로작은혹은중간크기혈관의염증 (vasculitis involving small and medium sized vessels) 이관찰되며혈관주변으로림프구의침윤 (lymphocyte infiltration in the perivascular space) 소견을보인다. 또한육아종 (granuloma) 형성은드문것으로알려져있다. 그러나, 이런전형적인소견을보이는경우는 50% 이하이며생검조직에서비특이적인염증소견만을보이는경우가많기때문에전형적인조직검사소견을보이지않더라도임상특성을고려하여판단하여야한다. 36-38 6) 감별진단 베체트장염과감별을요하는질환으로아래와같은장질환이있다. (1) 크론병 (2) 대장결핵 (3) 약인대장염 (4) CMV 대장염 (5) 아메바장염및살모넬라장염 (6) 대장암 이중특히크론병과의감별이중요한데크론병이분절혹은미만성의분포를보이는경우가많으나베체트장염은대부분회맹부위에국소분포하며, 궤양의모양이베체트장염의경우둥근난원형이많으나크론병의경우는부정형및종주형이많다. 또한, 궤양의깊이에있어서도베체트장염에서크론병에비하여깊고경계부위가뚜렷하다. 32,39 결 베체트장염진단에서가장중요한것은전신베체트병증 론
192 대한소화기학회지 : 제 53 권제 3 호, 2009 상과전형적인내시경소견이다. 이를토대로대한장연구학회에서는베체트장염을진단하는가이드라인을제시하였다. 앞으로이가이드라인에대한검증작업뿐만아니라베체트장염에대한병태생리, 진단방법, 질병특이혈청지표, 질병활성도측정, 특이치료제및치료반응률, 예후등에관한추가연구가필요하리라생각한다. 참고문헌 1. O'Duffy JD. Behçet's disease. Curr Opin Rheumatol 1994; 6:39-43. 2. Yang SK. Intestinal Behçet s disease. Intest Res 2005;3:1-10. 3. Behçet H. Uber rezidivierende apthuse durch ein virus verusachte Geswure am Mund, am Auge und an den Genitalien. Dermatol Wochenschr 1937;105:1152-1157. 4. Sakane T, Takeno M, Suzuki N, Inaba G. Behçet's disease. N Engl J Med 1999;341:1284-1291. 5. International Study Group for Behçet's disease. Criteria for diagnosis of Behçet's disease. Lancet 1990;335:1078-1080. 6. Mizushima Y, Inaba G, Mimura Y, Ono S. Diagnostic criteria for Behçet's disease in 1987, and guidelines for treating Behçet's disease. Saishin-Igaku 1988;43:382-391. 7. Friedman-Birnbaum R, Bergman R, Aizen E. Sensitivity and specificity of pathergy test results in Israeli patients with Behçet's disease. Cutis 1990;45:261-264. 8. Yoon MS, Lee SH, Bang D, Lee S. Cutaneous manifestations of Behçet's syndrome. Yonsei Med 1987;28:291-296. 9. Chang HK, Cheon KS. The clinical significance of a pathergy reaction in patients with Behçet's disease. J Korean Med Sci 2002;17:371-374. 10. Bang D, Lee JH, Lee ES, et al. Epidemiologic and clinical survey of Behçet's disease in Korea: the first multicenter study. J Korean Med Sci 2001;16:615-618. 11. Kobayashi K, Ueno F, Bito S, et al. Development of consensus statements for the diagnosis and management of intestinal Behçet's disease using a modified Delphi approach. J Gastroenterol 2007;42:737-745. 12. Muto T. Historical review of so called simple ulcer of the intestine. Stomach Intestine 1979;14:739-748. 13. Jung HC, Rhee PL, Song IS, et al. Temporal changes in the clinical type or diagnosis of Behçet's colitis in patients with aphthoid or punched-out colonic ulcerations. J Korean Med Sci 1991;6:313-318. 14. Kim JE, Han DS, Cho HS, et al. Clinical features of intestinal Behçet's disease according to disease subtypes. Intest Res 2007;5:26-32. 15. Lee CR, Kim WH, Cho YS, et al. Colonoscopic findings in intestinal Behçet's disease. Inflamm Bowel Dis 2001;7:243-249. 16. Cheon JH. Development of a novel disease activity index for intestinal Behçet s disease. The 2nd Korea-Japan IBD Symposium. 17. Suzuki Kurokawa M, Suzuki N. Behçet's disease. Clin Exp Med 2004;4:10-20. 18. Bayraktar Y, Ozaslan E, Van Thiel DH. Gastrointestinal manifestations of Behçet's disease. J Clin Gastroenterol 2000;30: 144-154. 19. Lakhanpal S, Tani K, Lie JT, Katoh K, Ishigatsubo Y, Ohokubo T. Pathologic features of Behçet's syndrome: a review of Japanese autopsy registry data. Hum Pathol 1985;16: 790-795. 20. Kim HJ, Bang D, Lee SH, et al. Behçet's syndrome in Korea: a look at the clinical picture. Yonsei Med J 1988;29:72-78. 21. Bang DS, Oh SH, Lee KH, Lee ES, Lee SN. Influence of sex on patients with Behçet's disease in Korea. J Korean Med Sci 2003;18:231-235. 22. Kim DK, Yang SK, Byeon JS, et al. Clinical manifestations and course of intestinal Behçet s disease: an analysis in relation to disease subtype. Intes Res 2005;3:48-54. 23. Shin SJ, Kim BC, Park SY, Kim TI, Kim WH. Systemic manifestations of Behçet's disease in diagnosis of intestinal Behçet's disease. Gut 2006;55(suppl):A120. 24. Choi IJ, Kim JS, Cha SD, et al. Long-term clinical course and prognostic factors in intestinal Behçet's disease. Dis Colon Rectum 2000;43:692-700. 25. Cambridge G, Rampton DS, Stevens TR, McCarthy DA, Kamm M, Leaker B. Anti-neutrophil antibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 1992;33:668-674. 26. Quinton JF, Sendid B, Reumaux D, et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 1998;42:788-791. 27. Duerr RH, Targan SR, Landers CJ, et al. Anti-neutrophil cytoplasmic antibodies in ulcerative colitis: comparison with other colitides/diarrhoeal illnesses. Gastroenterology 1992;100: 1590-1596. 28. Peeters M, Joossens S, Vermeire S, Vlietinck R, Bossuyt X, Rutgeerts P. Diagnostic value of anti-saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. Am J Gastroenterol 2001;96:730-734. 29. Choi CH, Kim TI, Kim BC, et al. Anti-Saccharomyces cer-
천재희외 5 인. 베체트장염진단기준 193 evisiae antibody in intestinal Behçet s disease patients: relation to clinical course. Dis Colon Rectum 2006;49:1849-1859. 30. Shin SJ, Kim BC, Park S, et al. Anti α-enolase antibody in intestinal Behçet s disease patients: useful serologic marker and relation to clinical course. J Gastroenterol Hepatol 2005; 20(S):143A. 31. Kim JS, Lim SH, Choi IJ, et al. Prediction of the clinical course of Behçet's colitis according to macroscopic classification by colonoscopy. Endoscopy 2000;32:635-640. 32. Kim TI, Kim WH, Lee JH, et al. Differential diagnosis of intestinal Behçet s disease and Crohn s disease by colonoscopic findings. J Gastroenterol Hepatol 2002;16(S):144A. 33. Chung SY, Ha HK, Kim JH, et al. Radiologic findings of Behçet's syndrome involving the gastrointestinal tract. Radiographics 2001;21:911-926. 34. Kim JH, Choi BI, Han JK, Choo SW, Han MC. Colitis in Behçet s disease: characteristics on double-contrast barium enema examination in 20 patients. Abdom Imaging 1994;19: 132-136. 35. You JK, Kim MJ, Park S, Chung JJ, Kim WH. Intestinal Behçet's disease: breath-hold MR imaging. Abdom Imaging 2001;26:309-314. 36. Lee RG. The colitis of Behçet's syndrome. Am J Surg Pathol 1986;10:888-893. 37. Bradbury AW, Milne AA, Murie JA. Surgical aspects of Behçet's disease. Br J Surg 1994;81:1712-1721. 38. Kasahara Y, Tanaka S, Nihino M, Umemura H, Shiraha S, Kuyama T. Intestinal involvement in Behçet s disease: review of 136 surgical cases in the Japanese literature. Dis Colon Rectum 1981;24:103-106. 39. Kim KJ, Yang SK, Myung SJ, et al. Diagnostic value of colonoscopic findings in the differential diagnosis between Crohn's disease and intestinal Behçet's disease. Gastrointest Endosc 2002;55:AB263.