Korean J Gastroenterol Vol. 72 No. 5, 252-257 https://doi.org/10.4166/kjg.2018.72.5.252 pissn 1598-9992 eissn 2233-6869 BRIEF SUMMARY OF PRACTICE GUIDELINE 2017 과민성장증후군의임상진료지침개정안소개 정혜경 이화여자대학교의과대학내과학교실 Review of the Clinical Practice Guidelines for Irritable Bowel Syndrome in Korea, 2017 Revised Edition Hye-Kyung Jung Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea This guidance is an updated version of the irritable bowel syndrome (IBS) guidelines based on evidence-based medicine. IBS is a common chronic gastrointestinal syndrome that occurs in approximately 10% of the population and causes chronic abdominal pain as well as bowel habit changes, such as stool frequency or consistency. The final diagnosis of IBS is based on the exclusion of organic diseases that would explain the symptoms and the absence of endoscopic abnormalities. IBS can reduce the quality of life and cause a major disease burden, such as repeated examinations and continuous drug use, by mistaking organic diseases including malignancy. The major changes are as follows: 1) when to perform a colonoscopy under the impression of IBS; 2) effect of a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet; 3) impact of probiotics in IBS; and 4) role of antibiotics in IBS. The Korean Society of Neurogastroenterology and Motility recently updated these guidelines to support physicians for qualified medical services and reduce the socioeconomic burden of IBS. (Korean J Gastroenterol 2018;72:252-257) Key Words: Evidence-based practice; Irritable bowel syndrome; Practice guideline 서론 과민성장증후군이란반복적으로복통과함께복부불편감, 배변습관의변화, 복부팽만감등다양한하부위장관증상이나타나는증후군으로만성적으로호전과악화를반복한다. 1,2 과민성장증후군의최종진단은증상을설명할만한다른기질적인질환이없다는것을검사를통하여확인한다음에내린다. Rome IV 기준에의하면과민성장증후군은평균주 1일이상의복통이 6개월전에시작되고지난 3개월동안반복되면서두가지이상의동반증상 ( 배변과연관된복통, 배변횟수의증가혹은감소, 대변이물러지거나단단해지는배변굳기의변화 ) 이함께있을때로정의한다. 3 로마기준은적용기 준이엄격하여주로임상연구등을목적으로할때많이사용되며, 실제임상에서는그빈도나강도보다더융통성이있는진단기준으로진단한다. 과민성장증후군은지역사회인구기반연구에서 10% 가량으로흔한기능성위장관질환이고, 아시아국가에서증가추세에있으며, 4-7 이로인한사회경제적비용은상당할것으로추정된다. 8 과민성장증후군은로마기준에합당한증상이있으면서이와유사한증상을유발하는기질질환을제외하여진단하기때문에진단을위한비용이많이들뿐아니라, 질환자체가만성적으로호전과악화를반복하여치료를위한의료이용비용도높다. 대한소화기기능성질환 운동학회는 2005년에 과민성장증 Received October 1, 2018. Revised October 23, 2018. Accepted November 3, 2018. CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2018. Korean Society of Gastroenterology. 교신저자 : 정혜경, 07985, 서울시양천구안양천로 1071, 이화여자대학교의과대학내과학교실 Correspondence to: Hye-Kyung Jung, Department of Internal Medicine, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea. Tel: +82-2-2650-2874, Fax: +82-2-2655-2874, E-mail: junghk@ewha.ac.kr, ORCID: https://orcid.org/0000-0002-6653-5214 Financial support: None. Conflict of Interest: None. Korean J Gastroenterol, Vol. 72 No. 5, November 2018 www.kjg.or.kr
Jung HK. Guidelines for Irritable Bowel Syndrome 253 후군의진단및치료가이드라인 을발표하였고 2010년과 2011년에걸쳐그개정안을발표하였다. 9-12 이번에개정된진료지침은 2011년진료지침에서근거가강화되거나새로운근거가창출된주제에관하여체계적문헌고찰을통하여그근거와권고등급을결정하였다 (Table 1). 본고에서는새로이개정되거나변화된네개의주제, 즉과민성장증후군이의심되는환자에서언제대장내시경을시행할것인지, 저포드맵식이의유용성, 과민성장증후군치료에서생균제와항생제의역할을중심으로고찰하여보고자한다. 이이외의내용은영문으로출간된 Clinical Practice Guidelines for Irritable Bowel Syndrome in Korea, 2017 Revised Edition 에자세히소개되어있으니참고하기바란다. 13 본론 1. 대장내시경 1) 과민성장증후군이의심되는환자에서경고증상, 측항문출혈, 원인불명의체중감소, 50세이상에서의배변습관변화가있거나소화기암의가족력이있을때대장내시경을고려할수있다. 전문가의견 : 전적으로동의함 (37.5%), 대체로동의함 (47.5%), 일부동의함 (10.0%), 대체로동의하지않음 (2.5%), 전적으로동의하지않음 (2.5%), 모르겠음 (0%) 과민성장증후군은로마기준에따라특징적인증상이있을 경우에진단할수있다. 3 증상만으로과민성장증후군과유사한증상을유발하는기질적질환을감별하기어렵다. 대장내시경은과민성장증후군환자를진단하는효용은낮으나경고징후가있는경우대장내시경을시행하면염증성장질환, 대장암, 현미경적장염등을감별하는데도움을줄수있다. 따라서혈변, 빈혈, 원인불명의체중감소, 최근배변습관의변화등경고증상이있으면과민성장증후군을생각하기에앞서다른진단을고려해야한다. 2,14-16 로마기준과같은엄격한과민성장증후군의증상진단기준은경고징후가없는경우에과민성장증후군을진단하는데높은예측도를지닌다. 14 2. 식이 1) fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) 제한식이는과민성장증후군증상조절에효과적이다. 전문가의견 : 전적으로동의함 (5.0%), 대체로동의함 (67.5%), 일부동의함 (25.0%), 대체로동의하지않음 (2.5%), 전적으로동의하지않음 (0%), 모르겠음 (0%) FODMAP은장내세균에의하여발효될수있는저분자탄수화물등을통칭하며, 장관내의삼투압을증가시켜배변의양상을변화시키거나가스를생성하여과민성장증후군환자의증상의악화를초래할수있다. 17 최근연구에서 FODMAP 이많이함유된음식을제한하는식이가증상을완화시키는데도움이되었다. 흔하게접하는고농도의 FODMAP 식이를 Table 1. Level of Evidence and Grade of Recommendation Item Definition Level of evidence A. High quality Further research is unlikely to change our confidence in the estimate of effect. Consistent evidence from the RCTs without important limitations or exceptionally strong evidence from observational studies. B. Moderate quality Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Evidence from RCTs with important limitations (inconsistent results, methodologic flaws, indirect or imprecise), or very strong evidence from observational studies. C. Low quality Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Evidence for at least one critical outcome from observational studies, case series, or from RCTs with serious flaws, or indirect evidence, or expert s consensus. Strength of recommendation 1. Strong Recommendation can apply to most patients in most circumstances. The desired effect is certainly greater than the harmful effect. 2. Weak The best action may differ depending on circumstances or patient or society values. Other alternatives may be equally reasonable. The desired effect may be slightly larger than the harmful effect. RCT, randomized controlled trial. Vol. 72 No. 5, November 2018
254 정혜경. 2017 과민성장증후군의임상진료지침개정안소개 Table 2에정리하였다. 17,18 세개의전향적연구의결과 FODMAP 제한식이는복통및복부팽만감 (bloating) 을호전시켰다. 19-21 FODMAP 제한식이의부작용은보고되지않았으나, 이연구들의시행기간이 4주이하로상대적으로짧아, 장기간의 FODMAP 제한식이가어떠한영향을끼칠지에대한후속연구가필요하다. 5. 삼투성완하제 1) 삼투성완하제는변비우세형과민성장증후군에서배변빈도를증가시켜증상을완화시킬수있다. 3. 신체활동 1) 신체활동은과민성장증후군환자의증상호전에도움을줄수있다. 6. 진경제 (Table 3) 1) 진경제는과민성장증후군의복부불편감을완화시키는데효과적이다. 권고수준 : 강함 4. 부피형성완하제 1) 부피형성완하제는과민성장증후군환자의전반적인증상을호전시킬수있다. 7. 지사제 1) 로페라마이드는설사우세형과민성장증후군에서대변성상을정상화시키고배변빈도를감소시킨다. 권고수준 : 강함 Table 2. Common Food Sources of High FODMAPs Food Oligosaccharides Disaccharides Monosaccharides Polyols Sauce Chicory drinks, ketchup, cream pasta source, tomato-based pasta sauce, energy bar, strawberry jam, kimchi, doenjang, gochujang, ssamjang, dumpling, dim- sum, tom-yum soup, thai curry paste Honey, high-fructose corn syrup Food additives Inulin, wasabi powder, FOS Sorbitol, mannitol, maltitiol, xylitol, isomalt Fruits Peach, persimmon, watermelon Apple, cherry, mango, pear, watermelon Vegetables Garlic, leek, onion, peas, beetroot, brussels sprout, chicory, fennel, artichokes Asparagus, artichokes, sugar snap peas, pickled onion Milk and milk products Milk, yogurt, ice cream, custard, soft cheeses Grains and cereals Wheat, rye, barley Nuts and seeds Almond, pistachios Legumes Legumes, chickpeas, lentils FODMAP, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols; FOS, fructooligosaccharides. Apple, pear, prune, cherry, blackberries, apricot, avocado, nectarine, plum Mushroom, white cabbage, cauliflower, snow peas The Korean Journal of Gastroenterology
Jung HK. Guidelines for Irritable Bowel Syndrome 255 8. 세로토닌 3 형수용체길항제 (5-HT 3 receptor antagonist) 10. 항생제 1) 세로토닌 3형수용체길항제인 ramosetron은설사우세형과민성장증후군환자들의대변의굳기, 복통, 복부팽만감및건강과관련된삶의질을향상시킨다. 증거수준 : 높음 9. 세로토닌 4형수용체작용제 (5-HT 4 receptor agonist) 1) 리팍시민은설사우세형과민성장증후군의전신증상을완화시키는데효과적일수있다. 전문가의견 : 전적으로동의함 (7.5%), 대체로동의함 (42.5%), 일부동의함 (45.0%), 대체로동의하지않음 (2.5%), 전적으로동의하지않음 (0%), 모르겠음 (2.5%). 1) 다른하제에반응이없는변비우세형과민성장증후군환자에게 prucalopride는관련증상개선과삶의질향상에도움이될수있다. 리팍시민 (rifaximin) 은과민성장증후군에서동반할수있는소장세균과증식에항생제를투여하면그증상이호전된다는보고가있다. 22 최근에발표된몇몇의무작위대조시험에서리팍시민은설사우세형과민성장증후군에서복통, 복부팽만감, 대변성상의정상화에효과가있으며증상이재발하는경우에도반복적인치료가효과적이다. 23-27 소화관에서흡수가잘되지않아부작용이거의없다. 그러나항생제내성위험성을고려하여, 다른약제로도호전되지않은일부환자들에한하여제한적으로투약하는것을권장한다. Table 3. Summary of Antispasmodics for the Treatment of Irritable Bowel Syndrome Drugs Starting dosages Maximal dosages Adverse effects Comments Alverine citrate 60-180 mg/day 360 mg/day Abdominal pain, diarrhea, vomiting, nausea, allergic reactions Mebeverine 300 mg/day 405 mg/day Urticaria, angioedema, anaphylaxis Otilonium bromide 60 mg/day 120 mg/day Increased intraocular pressure Pinaverium bromide 150 mg/day 300 mg/day Abdominal distension, abdominal pain, allergic skin reaction, diarrhea Phloroglucinol 160 mg/day - Dry mouth, dizziness, and blurred vision IBS, irritable bowel syndrome. Only combination with simethicone reduced abdominal pain and discomfort compared to placebo Superior in controlling IBS symptoms compared to placebo Reduced abdominal pain frequency and bloating and improved stool frequency and patient global assessment compared to placebo; lower symptom recurrence after treatment Superior in improving global symptoms compared to placebo Significantly improved subjects' global assessment and decreased stool frequency Table 4. Summary of Antidepressants for the Treatment of Irritable Bowel Syndrome Psycho-trophics Drugs Starting dosages Maximal dosages Adverse effects TCAs Amitriptyline 10-25 mg/day 30 mg/day Dry mouth, constipation, difficulty Imipramine 25 mg/day 50 mg/day sleeping, difficulty urinating, sexual difficulties, headache, nausea, Desipramine 50 mg/day 150 mg/day dizziness and/or drowsiness Trimipramine 50 mg/day - SSRIs Paroxetine 10-20 mg/day 50 mg/day Agitation, dizziness, nausea, Citalopram Fluoxetine 20 mg/day 20 mg/day 40 mg/day - headache, vivid dreams, sleep disturbances, sexual difficulties, and/or diarrhea TCA, tricyclic antidepressant; SSRI, selective serotonin reuptake inhibitor. Comments Begin with low dose (at bedtime) and titrate by response Begin with low dose and titrate by response Vol. 72 No. 5, November 2018
256 정혜경. 2017 과민성장증후군의임상진료지침개정안소개 11. 생균제 결 론 1) 생균제는과민성장증후군환자의전반적인증세및가스관련증상등의호전을위하여보조적으로투약해볼수있다. 전문가의견 : 전적으로동의함 (7.5%), 대체로동의함 (55.0%), 일부동의함 (27.5%), 대체로동의하지않음 (7.5%), 전적으로동의하지않음 (0%), 모르겠음 (2.5%) 과민성장증후군환자에게생균제를투약하여장내미생물무리의조성을바꾸어줌으로써증상을호전시켰다는임상연구가보고되어왔다. 2014년메타분석에의하면위약대비생균제의투약은증상을비교위험도 0.79 (95% CI 0.70-0.89) 로유의하게증상을개선시킬수있었고, 7명의투약으로한명의호전을기대할수있는수준이었다. 28 과민성장증후군의전반적증상의개선, 복통의호전, 가스관련증상의호전등모든영역에서위약대비효과가있었다. 국내에서도각종 Lactobacillus 및 Bifidobacterium의혼합제제, Bacillus subtillis, Streptococcus faecium, Saccharomyces boulardii 등을사용한임상연구들이있었다. 29-32 하지만이제까지의연구결과로는과민성장증후군환자에게특정균주나용량을추천할수는없고, 다만그효과를판정하기위해서는 4주이상지속적으로투약하여볼것을권고하고있다. 12. 항우울제 (Table 4) 1) 삼환계항우울제 (tricyclic antidepressants) 는과민성장증후군환자의복통과전반적인증상개선을위하여사용해볼수있다. 증거수준 : 높음 13. 기타치료들 : chloride channel activators 및정신건강의학과적치료 1) 선택적세로토닌재흡수억제제는과민성장증후군환자의안녕감을향상시키기위하여사용해볼수있다. 2017년개발된과민성장증후군영문임상진료지침은 2011 년에발표된진료지침을근간으로근거중심의학에기반하여개정하였다. 과민성장증후군에서대장내시경의역할과최근활발히연구가진행된 FODMAP 식이, 항생제및생균제에대하여체계적문헌고찰을실시하였고, 델파이방법을통하여전문가합의를도출하여새로운권고문을개발하였다. 과민성장증후군의임상접근을쉽게하기위하여과민성장증후군진료알고리즘및치료약제의구체적인방법을표로요약하였다. 본진료지침은진료를담당하는의사와환자가일선에서사용하여최선의치료를제공하고만족할만한치유경험을통하여궁극적으로삶의질을향상시키고의료비용을줄이는것을목표로한다. 뿐만아니라내과및가정의학과를비롯한다양한임상과의수련의및의과대학학생, 간호대학생등의교육을위하여적용될수있다. REFERENCES 1. Spiller R, Aziz Q, Creed F, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007; 56:1770-1798. 2. Hookway C, Buckner S, Crosland P, Longson D. Irritable bowel syndrome in adults in primary care: summary of updated NICE guidance. BMJ 2015;350:h701. 3. Mearin F, Lacy BE. Diagnostic criteria in IBS: useful or not? Neurogastroenterol Motil 2012;24:791-801. 4. Lee SY, Lee KJ, Kim SJ, Cho SW. Prevalence and risk factors for overlaps between gastroesophageal reflux disease, dyspepsia, and irritable bowel syndrome: a population-based study. Digestion 2009;79:196-201. 5. Lee YY, Waid A, Tan HJ, Chua AS, Whitehead WE. Rome III survey of irritable bowel syndrome among ethnic Malays. World J Gastroenterol 2012;18:6475-6480. 6. Siah KT, Wong RK, Chan YH, Ho KY, Gwee KA. Prevalence of irritable bowel syndrome in Singapore and its association with dietary, lifestyle, and environmental factors. J Neurogastroenterol Motil 2016;22:670-676. 7. Miwa H. Prevalence of irritable bowel syndrome in Japan: internet survey using Rome III criteria. Patient Prefer Adherence 2008;2:143-147. 8. Buono JL, Mathur K, Averitt AJ, Andrae DA. Economic burden of inadequate symptom control among US commercially insured patients with irritable bowel syndrome with diarrhea. J Med Econ 2017;20:353-362. 9. Lee OY, Yoon CO. Review : evidence based guideline for diagnosis and treatment : diagnostic guideline for irritable bowel syndrome. Kor J Neurogastroenterol Motil 2005;11:30-35. 10. Park HJ. Review : evidence based guideline for diagnosis and treatment : therapeutic guideline for irritable bowel syndrome. Kor J Neurogastroenterol Motil 2005;11:36-43. The Korean Journal of Gastroenterology
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