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1 대한내과학회지 : 제 76 권제 6 호 2009 특집 (Special Review) - 궤양성대장염 (Ulcerative colitis) 궤양성대장염의진단 1 중앙대학교의과대학내과학교실, 2 성균관대학교의과대학내과학교실 최창환 1 김영호 2 Diagnosis of ulcerative colitis Chang Hwan Choi, M.D. 1 and Young-Ho Kim, M.D. 2 1 Department of Internal Medicine, College of Medicine Chung-Ang University, Seoul, Korea; 2 Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that is confined to the mucosa and submucosa. The diagnosis is based on a combination of clinical, endoscopic, and histological characteristics, as no single finding is diagnostic for UC. The most important symptoms of UC are rectal bleeding, urgency, and diarrhea. The typical endoscopic feature of UC is continuous, circumferential, and symmetric colonic involvement. The inflammation involves the rectum and may extend proximally. The mucosal biopsy shows crypt architecture distortion, mixed inflammatory cell infiltration in the lamina propria, increased plasma cells near the crypt bases, and basal lymphoid aggregates. In addition, many diseases, such as infectious causes, should be excluded from the differential diagnosis. Finally, an evaluation of the extent and severity of UC is important in determining how to treat patients. (Korean J Med 76: , 2009) Key Words: Ulcerative colitis; Diagnosis; Colonoscopy 서론염증성장질환이란원인불명으로장에염증이발생하는질환으로궤양성대장염과크론병이대표적인질환이다. 궤양성대장염은크론병과달리점막과점막하층만을침범하며직장에서부터연속적으로대장을침범하고대장전절제술로완치할수있는질환이다. 궤양성대장염은최근국내에서도발생률이급격히증가하고있는질환으로정확한진단에대한중요성이강조되고있다. 그러나한가지소견으로정확히진단할수없고임상적, 내시경적, 조직학적, 영상의학적소견등을종합하여진단하여야한다. 또한여러가지다양한질환들이궤양성대장염과유사하게나타날수있어궤양성대장염을진단하고치료하는데있어감별이필요한질환에대한정확한이해가필요하다. 최근대한장연구학회 에서는한국에서의궤양성대장염진단가이드라인을발표한바있어 1) 이를중심으로궤양성대장염의진단에필요한핵심소견을살펴보고다른질환과의감별진단에대해서간략하게살펴보고자한다. 본론궤양성대장염진단은합당한증상이있으면서이에부합하는내시경소견과조직검사소견이있고궤양성대장염과유사한질환들을배제하는것이다 2-5). 1. 궤양성대장염의증상궤양성대장염의가장중요한증상은혈변이며, 설사, 점액변, 복통, 변못참음, 뒤무직등의증상이발생할수있다

2 - The Korean Journal of Medicine: Vol. 76, No. 6, 이외에도전신증상으로체중감소, 발열, 식욕부진, 전신쇠약감, 구역, 구토등을호소하기도한다. 국내의연구결과에따르면증상의빈도는혈변 90.8%, 변못참음 70.7%, 뒤무직 70.7%, 설사 64.1%, 점액변 55.3%, 복통 53.9%, 직장통 21.4%, 체중감소 14.5% 였다 6). 이러한증상이급성으로발생하는경우도있으나대개는수주일에서수개월에거쳐발생한다. 간헐적으로누공을포함하는항문주위병변이동반할수있으나, 반복혹은복합적항문주위누공이발생한다면크론병과의감별이필요하다. 궤양성대장염은장에의한증상뿐아니라다양한장외증상이나타날수있기때문에장외증상이동반된경우진단에도움이될수있다. 동반될수있는장외증상으로는결절홍반, 괴저농피증, 구강궤양과같은피부질환과말초관절염, 천장골염, 강직성척추염과같은관절질환에의한증상이나타날수있다. 이외에도포도막염, 홍채염, 공막염, 상공막염, 홍채모양체염, 지방간, 담석증, 원발경화성담관염, 요로결석, 혈관색전증등이동반될수있다. 특히원발경화성담관염이동반된경우담관암과대장암의발생률이높아주의를요한다. 2. 궤양성대장염의내시경소견및기타검사소견궤양성대장염이의심되는경우에는구불결장경검사또는대장내시경검사를시행하여야한다. 통상적으로는말단회장부까지관찰이가능한대장내시경검사를시행하여침범된범위를파악하는것이치료에도움이되나중증의궤양성대장염에서는대장내시경에의한합병증과질병의악화를고려하여구불결장경검사를시행할수있다 7,8). 특징적인내시경소견은직장을침범하고근위부결장으로연속적으로진행하는대칭적염증소견이다. 전체대장을침범하는환자에서말단회장에서도육안적, 조직학적염증소견이관찰될수있는데이를역류성회장염이라고한다. 경도의궤양성대장염에서는홍반, 울혈, 혈관투시상의소실등이관찰되며, 중등도의경우에는점막의거친과립상, 점막미란, 가벼운접촉에도출혈이생기는점막의유약성등이관찰된다. 중증의경우에는자연출혈과궤양이관찰된다 4). 궤양은다양한모양으로얕은궤양에서깊은궤양까지나타날수있는데궤양사이의주위점막에서도염증소견이관찰된다. 깊은궤양은나쁜예후를시사하는소견이다 9). 질병이오래되면점막위축, 협착, 결장주름의소실및가성용종이관찰될수있다. 궤양성대장염의전형적인조직검사소견은만성염증에의한광범위한움구조변형, 기저부의형질세포증가증및림프구응집그리고점막고유판내다량의미만성세포증가이다. 궤양성대장염을진단할수있는특징적인혈액검사법은없다. 가장많이연구가되어온것은주로궤양성대장염에서양성으로나타나는 panca와크론병에서양성으로나타나는 anti-saccharomyces cerevisiae antibodies (ASCA) 이다. 지금까지연구결과에의하면 panca는궤양성대장염환자의 40~60% 에서양성으로나타나며, 크론병환자에서는 10% 미만으로나타난다. 하지만낮은민감도로인해임상에서궤양성대장염의진단과치료방법선택을위한 panca 검사는일반적으로권장되지않는다 1,10). 대변을이용하여염증성장질환을선별하려는연구들도진행되고있는데대변내 calprotectin, elastase, lysozyme, lactoferin 등과같은중성구유도단백 (neutrophil-derived protein) 을측정하는방법이다 11-14). 그러나이러한방법들도민감도와특이도의문제로실제로임상에서이용하기에는제한점이많다. 궤양성대장염에서관찰되는혈액검사의이상소견으로는빈혈, 백혈구증가증, 혈소판증가증, 저알부민혈증, ESR 상승, CRP 상승등이있는데궤양성대장염의진단에직접적인도움을주지는않으나질병의중증도를간접적으로평가할수있으며환자의진료에도움을줄수있기에시행하는것이좋다. 3. 궤양성대장염의감별진단 1) 치질궤양성대장염은항문출혈을주증상으로하는질환이기때문에하부위장관출혈의가장흔한원인중의하나인치질과의감별이필요하다. 치질에의한출혈은대개선홍색의출혈이변과섞이지않고나오는것이특징으로휴지에묻거나대변의가장자리에묻거나변을보기위해힘을줄때, 또는배변후에떨어지는양상을보인다. 그렇지만궤양성대장염에서와같이설사나점액변, 변못참음, 뒤무직등과동반되는경우는드물다. 2) 비특이대장염특별한증상이없는사람에서도대장내시경검사에서직장점막에비특이적인발적소견이관찰될수있는데간혹이를궤양성직장염으로오인하는경우가있다. 그러나조직검사를하여보면특별한소견을관찰할수없다

3 - Chang Hwan Choi, et al. Diagnosis of ulcerative colitis - 3) 전처치에의한장점막변화전처치로인한점막변화도염증성장질환으로오인될수있으므로주의를요한다. Sodium phosphate는아프타궤양을일으키며조직학적으로도국소적움염을일으키지만, 움구조에는변화를주지않고고유판에도단핵구의침윤이저명하지않다는점이다르다 15). Bisacodyl 좌약을사용한경우에도점막발적이나혈관상소실등의소견을관찰할수있다 16). 4) 감염성장염감염성장염환자들은설사를주소로병원을방문하며때로는혈변이동반되기때문에궤양성대장염과감별을요한다. 실제로혈성설사로염증성장질환이의심된환자의약 1/3은감염성장염이다 17). 궤양성대장염과감염성장염을감별하기위해서는내시경시술자의경험, 병리학의사와의토의, 그리고질병의경과관찰이중요하다. 감염성대장염은갑자기발병하는경우가흔하고발열, 복통, 구토를동반하는경우가많다. 내시경소견으로는두질환을감별하는것이매우어려우므로조직검사소견과임상경과를같이고려하여야정확한진단을할수있다. 궤양성대장염과유사한양상을보일수있는원인균으로는 E. histolytica, Campylobacter, Chlamydia trachomatis, Clostridium difficile, Cytomegalovirus, E. coli, Herpes simpex virus, Neisseria gonorrheae, Schistosoma, Shigella, Treponema pallidum, Yersinia 등이있다. 직장이침범되어있지않고그근위부에병변이균일하지않게분포하면감염성질환을시사하는소견이며전반적으로노란색의삼출물이덮여있고발적이심한소견도감염성장염에서더흔히보이는소견이다 18). 궤양성대장염에서조직학적으로가장중요한것은앞에서기술된바와같이만성염증에의한광범위한움구조변형, 기저부의형질세포증가증및림프구응집, 그리고점막고유판내다량의미만성세포증가등으로이러한소견들은궤양성대장염을시사하는소견이다 19). Campylobacter나결핵균, 아메바등에의한감염은만성경과를취할수있기때문에혈성설사가지속되는경우에도감염성장염을감별하여야한다. 5) 허혈성대장염허혈성대장염도궤양성대장염으로오인되는경우가있으나주의깊게관찰하면감별이가능하다. 임상적으로허혈성대장염은노인연령에서주로발생하며심장질환과같은위험인자를가지고있는경우도있다. 대개갑작스러운 복통과혈변을호소하며대장내시경을해보면점막부종과발적소견이관찰되지만직장을침범하지않는것이특징이다. 6) 방사선대장염여성의자궁경부암이나남성의전립선암으로인해서방사선치료를받은경우방사선대장염이발생할수있다. 구불결장원위부와직장근위부가가장흔하게침범되는부위이다. 가장중요한소견은방사선치료를받은과거력이며내시경소견은점막취약성, 점막과립상, 다발성모세혈관확장증이며이중가장특징적인소견은모세혈관확장증이다. 7) 고립성직장궤양증후군고립성직장궤양증후군은직장점막에발적과궤양소견이보이는질환으로혈변과점액성변을호소하며배변장애와관련되어있다. 내시경적으로딱지로덮인편평하고불규칙한궤양이관찰되며가장자리는발적된점막에둘러싸여있다. 궤양성대장염과감별이어려운경우도있으나병변이주로항문연에서 4~15 cm 위치의전벽에국한되어발생한다는점이다르고조직학적소견이비교적특징적이다. 8) 크론병궤양성대장염과크론병은임상적, 내시경적, 방사선학적소견으로대부분감별진단이가능하지만경우에따라서는매우어려운경우도있다. 궤양성대장염의경우거의대부분직장을침범하지만 5% 에서는내시경적으로정상소견이다. 이들환자들은육안적으로는정상이어도현미경적으로염증소견을관찰할수있는경우도많아반드시조직검사를시행하여야한다 20). 한편궤양성대장염환자의 15~75% 는충수개구부에염증소견이관찰되어마치건너뛰기병변이있는것처럼보이는경우도있다 21). 따라서크론병을시사하는소견이없이단지염증소견이균일하게분포하지않고비연속적이라는이유만으로크론병으로진단해서는안된다. 궤양성대장염의염증소견은미만성이고대칭적이며대개원위부에서근위부로갈수록염증소견이약해지는경향을보인다는점을고려하여야한다. 4. 궤양성대장염의침범범위및중증도평가 1) 병변의범위평가궤양성대장염병변의범위는치료의방침을정하는데매

4 - 대한내과학회지 : 제 76 권제 6 호통권제 586 호 우중요한소견이다. 대장내시경검사소견에서육안적으로염증이있는대장의구역에따라궤양성직장염 ( 염증이항문연에서 15 cm까지만침범 ), 좌측대장염 ( 직장에서비장만곡부위까지침범 ) 그리고광범위대장염 ( 비장만곡이상의부위까지침범 ) 으로분류하는데 22,23) 예를들어궤양성직장염의경우좌약제제를좌측대장염의경우관장제제를사용해볼수있다. 국내의연구들에의하면직장염 24.1~44.1%, 좌측대장염 22.7~48.1% 그리고광범위대장염 27.8~33.2% 였다 6,24). 2) 중증도평가궤양성대장염의중증도에는임상적중증도와내시경적중증도가있다. 임상적중증도로가장많이이용되는것은 Truelove and Witts 25) 에의해 1955년에제안된궤양성대장염분류기준이다 ( 표 1). 궤양성대장염에서임상적중증도는내시경적중증도와비교적잘일치하기때문에치료방침의결정에주로이용된다 26). 또한임상적중증도에내시경적중증도를결합시킨 Mayo Score도널리이용된다 ( 표 2). Mayo Score 에따라분류한국내연구에의하면경도, 중등도, 중증의비율은각각 49.0%, 41.0%, 10.0% 였다 6). Table 1. Truelove and Witts score for the clinical severity of ulcerative colitis 25 Mild Diarrhea <4 times/day, non-bloody No fever Pulse <90 beats/min Erythrocyte sedimentation rate (ESR) <30 mm/h Moderate Intermediate between mild and severe Severe Diarrhea 6 times/day, bloody Hemoglobin 75% or below Evening temperature >37.5 Pulse >90 beats/min ESR >30 mm/h 결론반복적인혈변을주증상으로하는궤양성대장염은증가추세에있어이제는드물지않게접하는질환으로다른질환을궤양성대장염으로오인하여과잉치료하거나궤양성대장염을다른질환으로오인하여치료가늦어지는경우가종종있다. 궤양성대장염은진단을위한특이검사가없기때문에정확한진단을위해서는임상소견과내시경검사및조직검사소견을기반으로가능성이있는다른질환들을배제하는것이중요하다. 경우에따라서한번에진단이 Table 2. Mayo Score; Ulcerative Colitis Disease Activity Index (UCDAI; range 0~12) 27 Variables/Score Criteria Stool Frequency 0 Normal number of stools stools more than normal stools more than normal 3 5 stools more than normal Rectal Bleeding 0 No blood seen 1 Streaks of blood with stool less than half the time 2 Obvious blood with stool most of the time 3 Blood alone passed Findings at proctosigmoidoscopy 0 Normal or inactive disease 1 Mild disease (erythema, decreased vascular pattern, mild friability) 2 Moderate disease (marked erythema, absent vascular pattern, friability, erosions) 3 Severe disease (spontaneous bleeding, ulceration) Physician s global assessment 0 Normal 1 Mild 2 Moderate 3 Severe Mild UC, UCDAI 3~5; Moderate UC, UCDAI 6~10; Severe UC, UCDAI 11~

5 - 최창환외 1 인. 궤양성대장염의진단 - 내려지지않는경우간격을두고내시경검사및조직검사를다시시행하여확인하는것이필요하며진단이내려진후에도주의깊은경과관찰로환자의변화를파악하여야한다. 중심단어 : 궤양성대장염 ; 진단 ; 대장내시경 REFERENCES 1) Choi CH, Jung SA, Lee BI, Lee KM, Kim JS, Han DS. Diagnostic guideline of ulcerative colitis. Korean J Gastroenterol 53: , ) Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 99: , ) Nikolaus S, Schreiber S. Diagnostics of inflammatory bowel disease. Gastroenterology 133: , ) Stange EF, Travis SP, Gebes K. European Consensus on the diagnosis and management of ulcerative colitis: definitions and diagnosis. J Crohn s & Colitis 2:1-23, ) Su C, Lichtenstein GR. Ulcerative colitis. In: Feldman MF, Brandt LJ, eds. Sleisenger and Fordtran s gastrointestinal and liver disease: pathophysiology, diagnosis, management. Volume 2. 8th ed. p , Philadelphia, Saunders, ) Kim YM, Park SH, Yang SK, Choi JW, Kim SH, Byeon JS, Myung SJ, Cho YK, Yu CS, Choi JW, Kim B, Choi KD, Kim JH. Clinical characteristics and long-term course of ulcerative colitis in Korea. Intest Res 4:12-21, ) Deutsch DE, Olson AD. Colonoscopy or sigmoidoscopy as the initial evaluation of pediatric patients with colitis: a survey of physician behavior and a cost analysis. J Pediatr Gastroenterol Nutr 25:26-31, ) Fefferman DS, Farrell RJ. Endoscopy in inflammatory bowel disease: indications, surveillance, and use in clinical practice. Clin Gastroenterol Hepatol 3:11-24, ) Pera A, Bellando P, Caldera D, Ponti V, Astegiano M, Barletti C, David E, Arrigoni A, Rocca G, Verme G. Colonoscopy in inflammatory bowel disease: diagnostic accuracy and proposal of an endoscopic score. Gastroenterology 92: , ) Plevy S. Do serological markers and cytokines determine the indeterminate? J Clin Gastroenterol 38(5 Suppl):S51-S56, ) Konikoff MR, Denson LA. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. Inflamm Bowel Dis 12: , ) Langhorst J, Elsenbruch S, Mueller T, Rueffer A, Spahn G, Michalsen A, Dobos GJ. Comparison of 4 neutrophil-derived proteins in feces as indicators of disease activity in ulcerative colitis. Inflamm Bowel Dis 11: , ) Poullis A, Foster R, Northfield TC, Mendall MA. Review article: faecal markers in the assessment of activity in inflammatory bowel disease. Aliment Pharmacol Ther 16: , ) Vermeire S, van Assche G, Rutgeerts P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut 55: , ) Wong NA, Penman ID, Campbell S, Lessells AM. Microscopic focal cryptitis associated with sodium phosphate bowel preparation. Histopathology 36: , ) Meisel JL, Bergman D, Graney D, Saunders DR, Rubin CE. Human rectal mucosa: proctoscopic and morphological changes caused by laxatives. Gastroenterology 72: , ) Tedesco FJ, Hardin RD, Harper RN, Edwards BH. Infectious colitis endoscopically simulating inflammatory bowel disease: a prospective evaluation. Gastrointest Endosc 29: , ) Chutkan RK, Scherl E, Waye JD. Colonoscopy in inflammatory bowel disease. Gastrointest Endosc Clin N Am 12: , viii, ) Surawicz CM, Belic L. Rectal biopsy helps to distinguish acute self-limited colitis from idiopathic inflammatory bowel disease. Gastroenterology 86: , ) Spiliadis CA, Spiliadis CA, Lennard-Jones JE. Ulcerative colitis with relative sparing of the rectum: clinical features, histology, and prognosis. Dis Colon Rectum 30: , ) D'Haens G, Geboes K, Peeters M, Baert F, Ectors N, Rutgeerts P. Patchy cecal inflammation associated with distal ulcerative colitis: a prospective endoscopic study. Am J Gastroenterol 92: , ) Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, Caprilli R, Colombel JF, Gasche C, Geboes K, Jewell DP, Karban A, Loftus EV Jr, Pena AS, Riddell RH, Sachar DB, Schreiber S, Steinhart AH, Targan SR, Vermeire S, Warren BF. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 19(Suppl A):5-36, ) Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus and implications. Gut 55: , ) Choi CH, Chung HW, Lee JH, Park JY, Lee HW, Park YS, Kim TI, Kim WH. Clinical course in ulcerative colitis: analysis of the factors affecting the clinical courses during the first year, and the changes of the clinical courses during 5 years. Korean J Gastroenterol 38: , ) Truelove SC, Witts LJ. Cortisone in ulcerative colitis: final report on a therapeutic trial. Br Med J 2: , ) Higgins PD, Schwartz M, Mapili J, Krokos I, Leung J, Zimmermann EM. Patient-defined dichotomous end points for remission and clinical improvement in ulcerative colitis. Gut 54: , ) Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: a randomized study. N Engl J Med 317: ,

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<C3CAB7CFC1FD322DBABBB9AE2E687770> Essentials of Primary Care: 소화기 염증성장질환종류에따른치료전략 가톨릭대학교의과대학내과학교실 이강문 서론염증성장질환은장관에원인미상의만성염증을일으키는질환으로악화와호전을반복하면서진행하는임상경과를보이며궤양성대장염과크론병이대표적인질환이다. 두질환은복통, 설사등유사한위장관증상을나타내고스테로이드나면역억제제같은치료에반응한다는공통점이있으나, 유전적배경및병태생리에차이가있고침범부위,