대한소화관운동학회지 2008;14:39-44 원저 한국인의기능성위장장애의진단에있어서로마기준 Ⅲ 의유용성 연세대학교의과대학내과학교실 김익성 이병준 김영신 이상인 박효진 Validation of Rome III Criteria in the Diagnosis of Functional Gastrointestinal Disorders in Korean Patients Eak Seong Kim, M.D., Byung Jun Lee, M.D., Young Sin Kim, M.D., Sang In Lee, M.D. and Hyojin Park, M.D. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Background/Aims: We investigated the validation of Rome III criteria for diagnosis of functional gastrointestinal disorders in Koreans. Methods: Total of 157 patients who visited our hospital in the first time were enrolled. They filled out the Rome III diagnostic questionnaires of ROME Foundation. We evaluated the sensitivity and specificity of Rome III criteria in discriminating functional gastrointestinal disorders from organic diseases. Factor analysis was used to identify symptom clusters of the patients with functional gastrointestinal disorders. Results: The percentage of organic or functional disorders was 12% (19 patients) and 88% (138 patients) respectively. The sensitivity and specificity of Rome III criteria in discriminating functional gastrointestinal disorders from organic diseases for upper gastrointestinal tract was 60% and 53% each, and for lower gastrointestinal tract was 80% and 50% each. The percentage of overlap syndrome of functional gastrointestinal disorders was 49%. Twelve factors were detected except functional dysphagia, mixed-irritable bowel syndrome, proctalgia fugax in factor analysis. Conclusions: The Rome III criteria could be applied to Korean patients with functional gastrointestinal disorders. The Rome III criteria in the diagnosis of lower gastrointestinal tract in Korean was found to be relatively sensitive. (Kor J Neurogastroenterol Motil 2008;14:39-44) Key words: Functional gastrointestinal disorders, Rome III criteria, Validation 서 2006년발표된로마기준 Ⅲ 1-8 에서는기능성위장장애를해부학적인위치에따라식도, 위십이지장, 장, 기능성복통, 담도, 그리고직장항문으로범주를나누었으며, 각각의위치에따른기능성위장장애를특징적인임상증상에따라 28개의질환으로세분하였다. 로마기준 Ⅱ 9 에서로마기준 Ⅲ로바뀐내용은첫째기능성위장장애의시간기준의변화로 진단 6개월전에시작되었고지난 3개월동안진단기준에맞는증상이있어야한다 로바뀌었다. 이는 진단 12개월전에시작되어 12 주이상증상이있어야한다 는로마기준 Ⅱ보다는제한이 론 적고임상시험이나환자진료에도적용하기가수월해졌다. 둘째는질병군의분류의변화로성인되새김증후군은기능성식도장애에서기능성위십이지장장애으로옮겨갔다. 이러한변화는이질환이위와복부의장애로유래된다는증거를반영한것이다. 또한기능성복통증후군이기능성장질환에속해있다가새로운영역으로독립하였다. 1 Choung RS 등 10 은기질적질환을감별하는데있어서로마기준 Ⅲ의민감도는상부와하부위장관에서각각 53%, 67% 이고특이도는 49%, 59% 이라고보고를하였다. 2003년본교실 11 에서는한국인의기능성위장장애의진단에있어서로마기준 Ⅱ의유용성에대해서요인분석을통하여로마기준 Ⅱ는비교적유용하게사용될수있음을보고하였다. 또한요인분석을이용한기능성위장장애의진단에있어서아시아인에서로마기준 Ⅱ의타당성연구에서는로마기준 Ⅱ가비교적유용하게사용될수있음을보고하였다. 12
40 대한소화관운동학회지 : 제 14 권 1 호, 2008 Table 1. Investigations to Rule Out Organic Gastrointestinal Disorders Functional gastrointestinal disorders A Functional esophageal disorders Functional heartburn Functional chest pain of presumed esophageal origin Functional dysphagia Globus B Gastroduodenal disorders C Functional bowel disorders D Functional abdominal pain syndrome E Functional anoretal disorders Investigations Upper endoscopy, 24 hour ph study, PPI test Upper endoscopy, Manometry, PPI test, ECG, treadmill Upper endoscopy, Manometry Upper endoscopy Upper endoscopy Colonoscopy, blood calcium, thyroid hormone Abdomen US/CT Sigmoidoscopy/Colonoscopy 이에본연구에는로마기준 Ⅲ에의해기능성위장장애를가지고있는환자를대상으로서로독립적인증상군을가려내어로마기준 Ⅲ에서정의한질환의증상군과일치하는지알아봄으로써한국인에서로마기준 Ⅲ를적용하여기능성위장장애를진단하는것이타당한지알아보고자하였다. 또한기질적위장장애를감별하는데있어서로마기준 Ⅲ의민감도와특이도를조사하여로마기준 Ⅲ가한국인에서적용이가능한지알아보고자하였다. 대상및방법 1. 대상 2007년 9월부터 2008년 2월까지다른병, 의원에서소화기암등의기질적인질환으로진단을받고의뢰된환자를제외한, 소화기증상으로 3차의료기관 ( 영동세스란스병원 ) 을내원한초진환자를대상으로하였다. 전체 166명의환자중에서 9명 (5.4%) 은기질적질환의평가를위한검사를거부하여연구대상에서제외하였다. 2. 방법 1) 질문지대상환자는 72개의소화기증상에관한질문을포함하는질문지를작성하였다. 소화기증상에관한문항은 Rome Ⅲ 진단용질문지 (ROME Foundation) 를대한소화관운동학회에서한글로번역한것을사용하였다. 세부문항은 1 기능성식도질환이 12항목, 2 기능성소화불량증이 18항목, 3 구역, 구토, 트림장애 13항목, 4 과민성장증후군 10 항목, 5 기능성복통증후군이 19항목, 6 기능성변비 17 항목, 7 기능성장장애 26항목이었다 ( 중복질문문항이있어서총 72문항임 ). 2) 기질적질환에대한평가기질적질환에대한평가는문진, 전신신체검사와함께말초혈액검사, 혈액화학검사를실시하여이루어졌다. 말초혈액검사에서설명되지않는이상소견이있거나크레아티닌과 AST/ALT가정상상한치의 2배이상인경우에는기질적질환이있는것으로평가하였다. 또한환자가호소하는소화기증상에합당한각각의개별질환에대해정해진검사방법을통해기질적질환의유무를평가하였다 (Table 1). 상기검사방법으로기질적질환이없는경우는기능성질환으로분류를하였다. 3) 예민도및특이도기질적질환에대한검사를시행후에상부위장관및하부위장관의기질적장애또는기능성장애등 4가지로최종진단을시행하였고, 이최종진단을로마기준 Ⅲ 설문지에의한진단과비교하여로마기준 Ⅲ의기질적장애를감별하는데있어서상부위장관및하부위장관의예민도및특이도를구하였다. 4) 통계처리임상적최종진단및로마기준 Ⅲ에의해기능성위장장애를동시에가지고있는환자 97명을대상으로서로독립적인증상군을가려내기위해위장증상에대해서요인분석을실시하였다. 요인분석방법중에서주성분분석을시행하였고, 요인회전방법으로는배리맥스회전을사용하였다. 아이겐값 (Eigen value) 이 1.0이상, 요인적재량 (factor loading) 은 0.4 이상일경우를하나의요인으로간주하였다. 결과 1. 연구집단의특성
김익성외 4 인. 한국인의기능성위장장애의진단에있어서로마기준 Ⅲ 의유용성 41 157명의전체연구대상중 19명 (12.1%) 이기질적질환을가지고있었으며, 138명 (87.9%) 에서는기질적질환의증거가없어기능성위장장애를가지고있는것으로판단되었다. 기능성위장장애를가지고있는 138명중에서 41 명 (29.7%) 은증상의기간을만족하지않아로마기준 Ⅲ를만족시키지못하였고 97명 (70.3%) 이로마기준 Ⅲ를만족하였다. 로마기준 Ⅲ에의해기능성위장장애를가지고있는 97명의평균나이는 47.3±13.3세였고남녀비는 1:1.4로여자가많았다. 4. 기능성위장장애의해부학적분포기능성위장장애의해부학적분포는식도 24명 (24.7%), 위십이지장 45명 (46.4%), 기능성복통 1명 (1.0%), 장 70명 (72.2%), 그리고직장항문 20명 (20.6%) 이었다 (Table 4). 해부학적분포가두군데이상의기능성위장장애를동시에가지고있는환자는 48명 (49.4%) 이었다 (Table 5). 과민성장증후군과기능성소화불량증은 15명 (15.5%) 에서동반되었다. 2. 로마기준 Ⅲ 의예민도및특이도 기질적질환은 19명에서있었고상부위장관은역류성식도염 11명, 위궤양 4명, 식도이완불능증 1명, 조기위암 1명있었다. 하부위장관은직장탈출증 1명, 갑상선기능항진증 1명있었다. 기능성질환은 138명에서있었고상부위장관및하부위장관기능성질환이각각 67명과 71명이었다. 기질적질환을감별하는데있어서로마기준 Ⅲ의상부위장관에서예민도및특이도는각각 59.7% 와 52.9% 였다. 하부위장관에서예민도및특이도는각각 80.3% 와 50.0% 였다 (Table 2). 3. 요인분석결과 로마기준 Ⅲ 에의해기능성위장장애를가지고있는 97 명을대상으로요인분석을실시한결과 12개의요인이검출되었다. 12개의요인중에서 7개의요인은로마기준 Ⅲ 에의하면인두구, 공기삼킴증, 기능성변비, 과민성장증후군-변비형, 만성직장통, 기능성배변장애, 기능성대변실금에해당되었다. 그리고기능성가슴쓰림과기능성흉통이하나의요인으로, 식후불편증후군과상복부통증증후군이하나의요인으로, 만성특발성구역과성인되새김증후군이하나의요인으로, 과민성장증후군- 설사형과기능성복통증후군이하나의요인으로, 그리고기능성팽만과기능성설사가하나의요인으로통합되었다. 검출된요인들과각각의요인을구성하는소화기증상들은 Table 3에표시하였다. Table 2. The Sensitivity and Specificity of Rome Ⅲ Criteria Compared to Clinical Diagnosis Upper Functional vs Orgainc Lower Functional vs Orgainc Sensitivity (%) 59.7 80.3 Sensitivity (%) 52.9 50.0 고찰현재까지국내외에서보고되고있는기능성위장장애에관한연구는대부분기질적질환의배제를위한검사를시행하지않고연구대상의위장관증상만을조사하여이루어지고있는실정이다. 그러나, 본연구에서는로마기준 Ⅲ에의해서기능성질환으로분류되는환자중에서기질적질환에대한평가를하여 8.5% (9/106명) 에서기질적질환으로확진하였다. 로마기준 Ⅲ에의해서기질적질환을감별하는데하부위장관은민감도가 80.3% 로상부위장관의 59.7% 보다높았다. 특이도는상부위장관및하부위장관이각각 52.9%, 50.0% 로이전의미국의보고와유사하였다. 10 하부위장관에서는로마기준 III의민감도가 80.3% 로높으나과민성장증후군환자에서기질적질환의증거가 18% 에서나타난보고 11 가있어서기능성위장장애를진단하는데있어서기질적질환에대한평가후에로마기준 III를적용하는것이도움이될것이다. 국내에서 3차의료기관을내원한환자들의기능성위장장애의양상을보고한문헌에서는기능성소화불량증이 37%, 과민성장증후군이 18% 였다. 13 본연구에서는기능성소화불량증이 35%, 과민성장증후군이 43% 로과민성장증후군의양성률이높았는데이는병원혹은전문의료진에대한환자의인지도에의한선택오차로추정된다. 국내연구에서는대개기능성소화불량증이가장높은빈도를보였다. 14,15 과민성장증후군의우리나라에서유병률은로마기준 Ⅱ에의해서아산시지역에서 2.2% 였고, 건강검진자를대상으로 8.3% 였으며, 전화설문방법에의해서는 6.6% 였다. 13,16-18 기능성위장장애로진단된환자들중 49% 가로마기준 Ⅲ에서제시한각질환의진단기준을 2가지이상만족하는경우가관찰되었는데, 로마기준 Ⅱ의경우 20% 에서중복
42 Kor J Neurogastroenterol Motil: Vol. 14, No. 1, 2008 Table 3. Results of Factor Analysis of Gastrointestinal Symptoms A Esophageal disorders 1. F. heartburn and F. chest pain 2. Globus Factor Item Loading Variance (%) B. Gastroduodenal disorders 1. Postprandial distress Sx and Epigastric pain Sx 2. Chronic idiopathic nausea And Ruminaion Sx 3. Belching disorders C. F. bowel disorders D. F. abdominal pain Sx 1. IBS-diarrhea and F. abdominal pain 2. F. bloating and F. diarrhea 3. F. constipation 4. IBS-constipation E. F. Anorectal disorder 1. Chronic proctalgia 2. F. defecation disorder 3. F. fecal incontinence F. functional Sx syndrome Burning discomfort or pain in your chest Pain or discomfort in the middle of chest Absenece of dysphagia or odynophagia Absenece of heartburn Sensation of foreign body in the throat Pain in the middle of abdomen Not relieved by defecation or passage of flatus Early satiation Bring up food Hold food in mouth before splitting Not usually associated with vomiting Troublesome repetitive belching Pain or discomfort associated with looser stools No relation of pain with change of stool form Loose or watery stools Onset of pain with more stools Continuous abdominal pain Some loss of daily functioning Watery stools at least 3/4 of time Feeling of bloating or visible distension Fewer than three defecations per week Straining during defecation Sensation of incomplete evacuation Lumpy or hard stools Sensation of anorectal abstrution at defecation Manual Maneuvers to facilitate defecation Recurrent abdominal pain or discomfort Pain relieved with defecation Pain or discomfort associated with harder stools Pain or discomfort associated with fewer stools Chronic or recurrent rectal pain or aching Difficulty relaxing to allow defecation Manual Maneuvers to facilitate defecation Straining during bowel movements Sensation of blocked stools Accidental passing of stool 1.00 0.97 0.97 0.68 0.93 0.97 0.85 0.78 0.76 0.93 0.93 0.90 0.76 0.70 0.99 0.89 0.94 0.91 0.90 0.85 0.78 0.57 0.95 0.92 1.00 0.95 34.2% 26.4% 25.8% 23.3% 20.9% 16.2% 15.5% 14.7% 13.7% 27.3% 25.9% 25.3% 질환이관찰되었다. 본연구에서기능성위장장애의중복질환의빈도가높은이유는기능성담낭및오디조임근장애를제외한모든기능성위장장애에대한설문지를작성했기때문이다. 참고로김등 13 은기능성위장장애에서기 능성항문직장장애에관한조사를하지않았고, 지등 11 은기능성항문직장통증, 구역및구토장애및성인되새김증후군에대한조사가부족하였다. 그래서중복질환은 3 차병원을내원한환자중에는 20% 이상으로보는것이
Lee BJ. et al. Validation of Rome III Criteria in the Diagnosis of Functional Gastrointestinal Disorders in Korean Patients 43 Table 4. Summary of 97 Patients that Meet the Rome Ⅲ Location Functional GI disorders No (%) Esophagus Gastroduodenum Bowel Abdominal pain Anorectum Functional heartburn Functional chest pain Functional dysphagia Globus Functional dyspepsia Postprandial distress Syndrome Epigastric pain Syndrome Unspecified Belching disorders Nausea and vomiting disorders Chronic idiopathic nausea Functional vomiting Cyclic vomiting syndrome Rumination syndrome Irritable bowel syndrome constipation diarrhea mixed unsubtyped Functional bloating Functional constipation Functional diarrhea Functional Fecal incontinence Functional anorectal pain Chronic proctalgia Proctalgia fugax Functional defecation disorders 10 (10%) 34 (35%) 23 (24%) 2 (2%) 9 (9%) 3 (3%) 0 (0%) 0 (0%) 2 (2%) 42 (43%) 13 (13%) 21 (22%) 2 (2%) 9 (9%) 13 (13%) 1 (1%) 1 (1%) 14 (14%) 10 (10%) 5 (5%) Table 5. Overlap Features of Functional GI Disorders in 97 Patients Type of functional GI disorders No (%) Isolated functional esophageal disorders Isolated functional gastroduodenal disorders Isolated functional bowel disorders Isolated functional abdominal pain Isolated functional anorectal disorders Combinations Only one group Any 2 of the above groups Any 3 of the above groups 8 (8%) 32 (33%) 1 (1%) 34 (35%) 14 (14%) 타당하리라생각된다. 이렇듯기능성위장장애가있는환자는다른해부학적위치에도기능성위장장애가동반될수있음을고려해야한다. 과민성장증후군과다른질환의동반질환은기능성흉통 (functional chest pain) 의 27% 에서과민성장증후군이동반되었다. 19 본연구에서는 2명 (2%) 이식도기원으로추정되는기능성흉통이동반되었다. 기능성소화불량증과과민성장증후군은 15% 에서동반되었는데로마기준 Ⅱ에의한기능성위장장애에서는 11% 에서두질환이동반되었다. 13 과민성장증후군이동반된기능성소화불량증의
44 Kor J Neurogastroenterol Motil: Vol. 14, No. 1, 2008 특징은증상의정도가심하고, 위의팽창에대한과민성을갖는경우가유의하게많았다. 17 요인분석의결과기능성삼킴곤란, 과민성장증후군- 미분류형, 일과성직장통을제외하고는모두요인으로검출되었고, 7개의요인 ( 인두구, 공기삼킴증, 기능성변비, 과민성장증후군- 변비형, 만성직장통, 기능성배변장애, 기능성대변실금 ) 이로마기준 Ⅲ이정의한질환에해당함으로써로마기준 Ⅲ은한국인에서비교적유용하게사용되리라생각한다. 본연구의제한은첫째, 연구대상이일반인구가아닌 3차의료기관을내원한환자들이었기때문에본연구결과의설득력이다소떨어질수있다는것이다. 하지만일반인구를대상으로할경우기질적질환의평가를위한검사는사실상불가능하여기질적질환을가진환자가연구대상에포함되어연구의정확도를떨어뜨릴가능성이있다. 둘째, 기능성담도장애에대한설문조사가빠져있었다. 그러나국내의경우기능성담도장애에관한유병률조사는찾아보기힘들며, 1149명의캐나다거주민을대상으로기능성위장장애를조사한연구 20 에서기능성담도장애가한명도없었다는사실을감안하면기능성담도장애에대한조사가누락되었다는사실이연구결과에는크게영향을미치지못했을것으로생각된다. 마지막으로, 대상환자수가적어서요인분석을식도, 위십이지장, 장, 기능성복통, 그리고직장항문의각각범주안에서만시행하였고 28개의세부질환모두에대한요인분석을시행하지못하였다. 결론적으로로마기준 Ⅲ는한국인의기능성위장장애의진단에비교적유용하게사용될수있음을알수있고, 기능성하부위장관의진단에있어서민감도가높음을알수있었다. 참고문헌 1. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006;130:1377-1390. 2. Drossman DA, Dumitrascu DL. Rome III: New standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis 2006;15:237-241. 3. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006;130: 1480-1491. 4. Clouse RE, Mayer EA, Aziz Q, et al. Functional abdominal pain syndrome. Gastroenterology 2006;130:1492-1497. 5. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology 2006;130:1466-1479. 6. Galmiche JP, Clouse RE, Balint A, et al. Functional esophageal disorders. Gastroenterology 2006;130:1459-1465. 7. Behar J, Corazziari E, Guelrud M, Hogan W, Sherman S, Toouli J. Functional gallbladder and sphincter of oddi disorders. Gastroenterology 2006;130:1498-1509. 8. Bharucha AE, Wald A, Enck P, Rao S. Functional anorectal disorders. Gastroenterology 2006;130:1510-1518. 9. Drossman DA. The functional gastrointestinal disorders and the Rome II process. Gut 1999;45 Suppl 2:II1-5. 10. Choung RS, Talley NJ, Crowell MD, et al. Validation of Rome III criteria for functional GI disorders. Gastroenterology 2007;132(abstr): 676A. 11. Ji SW, Park H, Choi JP, Lee TH, Lee DY, Lee SI. Validation of Rome II criteria for functional gastrointestinal disorders in Korean patients. Korean J Gastroenterol 2003;41:183-189. 12. Kwan AC, Bao TN, Chakkaphak S, et al. Validation of Rome II criteria for functional gastrointestinal disorders by factor analysis of symptoms in Asian patient sample. J Gastroenterol Hepatol 2003;18:796-802. 13. Kim JS, Lee KJ, Kim JH, Hahm KB, Cho SW. Functional gastrointestinal disorders in patients referred to specialist gastroenterologists in a tertiary hospital. Korean J Gastrointest Motil 2004;10:111-117. 14. Choi H, Choi MG, Kim SW, et al. Functional gastrointestinal disorders in patients with gastrointestinal symptoms. Korean J Gastroenterol 1999;33:741-748. 15. Rhie SY, Choi CH, Lee HW, et al. The frequency of functional dyspepsia subtypes and its related factors for health check up subjects. Korean J Gastrointest Motil 2007;13:31-37. 16. Cho YS, Choi MG, Shin SJ, et al. The prevalence of irritable bowel syndrome in Asan city: Questionnaire survey in random Korean population. Korean J Gastrointest Motil 2004;10:49-56. 17. Hwang SY, Choi CH, Rhie SY, et al. The frequency and related factors of irritable bowel syndrome in health check up subjects. Korean J Gastrointest Motil 2006;12:136-143. 18. Han SH, Lee OY, Bae SC, et al. Prevalence of irritable bowel syndrome in Korea: population-based survey using the Rome II criteria. J Gastroenterol Hepatol 2006;21:1687-1692. 19. Mudipalli RS, Remes-Troche JM, Andersen L, Rao SS. Functional chest pain: esophageal or overlapping functional disorder. J Clin Gastroenterol 2007;41:264-269. 20. Thompson WG, Irvine EJ, Pare P, Ferrazzi S, Rance L. Functional gastrointestinal disorders in Canada: first population-based survey using Rome II criteria with suggestions for improving the questionnaire. Dig Dis Sci 2002;47:225-235.