07. In-depth review 4 (김현진).hwp

Size: px

Start display at page:

Download "07. In-depth review 4 (김현진).hwp"

소희 자
5 years ago
Views:

1 대한내과학회지 : 제 92 권제 4 호 In-depth review 로마기준 IV 이해하기 : 과민성장증후군과기능성설사 경상대학교의과대학내과학교실 김현정 차라리 김현진 Understanding the Rome IV: Irritable Bowel Syndrome and Functional Diarrhea Hyun Jung Kim, Ra Ri Cha, and Hyun Jin Kim Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Korea Irritable bowel syndrome (IBS) is a common, chronic functional gastrointestinal disorder affecting the large intestine, and presents as abdominal pain and/or discomfort, bloating, gas retention, diarrhea, and constipation. IBS impairs quality-of-life and requires long-term management. In 2016, the Rome Foundation introduced new IBS diagnostic criteria (the Rome IV criteria), and also revised the diagnostic algorithms for, and the multidimensional clinical profile (MDCP) of, functional gastrointestinal disorders. The IBS MDCP includes clinical data, the extent to which normal daily activities are affected, and psychosocial and physiological measures. The criteria seek to aid physicians in choosing appropriate treatment for IBS patients. Herein, we seek to provide evidence-based practical information on IBS and functional diarrhea. We review the new Rome diagnostic IV criteria, the MDCP, and the various IBS treatment options. We suggest that, in clinical practice, combination therapies may be useful to treat patients with IBS of various grades. (Korean J Med 2017;92: ) Keywords: Irritable bowel syndrome; Functional diarrhea; Rome IV; Multidimensional clinical profile 서론과민성장증후군 (irritable bowel syndrome, IBS) 은기질적이상없이복통과배변형태의변화를동반한기능성장질환으로정의하는것이전통적이지만 [1], 최근에는구조적이상, 생화학적이상, 과도한염증이없으며, 반복적인복통, 복부팽창, 무른변이나설사혹은변비를특징으로하는만성소화기기능성질환으로정의하고있다 [2]. 과거에장내염증이있는경우는기질적이상으로판단하여배제하였다면, 현재는심한염증이아니면포함한다는것이다. 이러한변화는 지난 20년간의연구로다양한병태생리에서저도염증이중요한역할을한다는것이알려지면서나타났고, IBS의생체표지자 (biomarker) 를찾는연구까지이어지고있다 [3]. 서구에서는매우흔하여전체인구의 7-10% 에서증상을가지고있으며 [4], 한국에서도지역사회주민을대상으로한연구들에서 8-9.6% 로외국과유사한유병률을보인다 [5,6]. IBS의진단기준은로마기준 (Rome criteria) 이가장흔하게사용되며 [1], 로마기준 III이발표된이후에도 [7] 기질적인질환은가능한배제하고기능성질환이누락되지않는정확한진단을위하여전세계적인증상조사를비롯한효과적인 Correspondence to Hyun Jin Kim, M.D., Ph.D. Department of Internal Medicine, Gyeongsang National University College of Medicine, 15 Jinju-daero 816beon-gil, Jinju 52727, Korea Tel: , Fax: , imdrkim@naver.com Copyright c 2017 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 - Hyun Jung Kim, et al. Irritable bowel syndrome and functional diarrhea - 치료방침을결정하기위해필요한명확한진단기준을제정하기위해노력해왔다 [8]. 본고에서는 2016년개정된로마기준 IV의범주 C에해당하는장질환 (bowel disorders) 중에서 IBS를중심으로진단기준의변경의배경과의미를알리고자한다 [9]. 본론개정의배경 IBS는임상증상의원인을찾기위한다양한임상검사에서이상소견이보이지않는경우로, 종양질환, 염증성장질환, 셀리악병, 유당불내성, 미세장염과같은다양한기질적질환을배제하는것이중요하다 [1]. 그러므로 IBS를뇌-장축의이상질환으로보는개념이다른질환과의감별에중요하다 [10]. 로마기준 IV의개정과함께 Rome 재단의홈페이지에개재되어있는 Frequently Asked Questions 페이지의일부에 로마기준 IV로개정이되면서기능성질환의몇몇증거를가지고기능적- 기질적으로양분화하여낙인을찍는것에대한종지부를내리기를기대한다 라는문장이있다 [11]. 이는질 환에대한개념이 단순히기질적이상이없다 가아닌, 점막면역이상반응과장내미생물균총의이상에대한이해에서오는것으로 IBS에대해서는지속적으로이러한변화된관점에서연구와교육그리고진단과치료가이루어지게될것이다. 로마기준 IV에서는이전기준에서기능성장질환에서 기능성 단어를삭제하였고이는 개정의배경 에서설명한내용에의한것이다. 장질환은범주 C에해당하며, 표 1과같이 6가지로구성되어있다. C1. 과민성장증후군은이전과같지만 4가지아형을명기한것이다른점으로점차로각각의아형에대한치료방법이달라지고있는것을반영한것이다. C2. 기능성변비, C3. 기능성설사, C5. 비특이적기능성장이상은이전과같다. C4. 기능성복부팽만감 / 팽창은이전에복부팽만감에서용어를바꾸었다. C6. 오피오이드유발변비는신설되었다 [9]. IBS 진단을위한로마기준은복통과함께기능성질환을시사하는소견을동반한경우로, 이러한기준은여러차례의개정을통하여변경되어왔다. 로마기준 IV에서가장두드러진변화는, 첫째, 복통 이진단의가장중요한증상이다 (Table 2). 이전의 복통또는복 Table 1. The category C classifications of bowel gastrointestinal disorders Rome III (2006) Rome IV (2016) C1. Irritable bowel syndrome C1. Irritable bowel syndrome (IBS) C2. Functional bloating IBS with predominant constipation (IBS-C) C3. Functional constipation IBS with predominant diarrhea (IBS-D) C4. Functional diarrhea IBS with mixed bowel habits (IBS-M) C5. Unspecified functional bowel disorder IBS unclassified (IBS-U) C2. Functional constipation C3. Functional diarrhea C4. Functional abdominal bloating/distension C5. Unspecified functional bowel disorder C6. Opioid-induced constipation Table 2. The criteria used for diagnosis of irritable bowel syndrome Rome III (2006) Rome IV (2016) At least 2 days per month in past 12 weeks of continuous or Recurrent abdominal pain, on average, at least 1 day a week in the recurrent abdominal pain or discomfort. last 3 months, associated with two or more of the following criteria: With at least 2 of the following Relief with defecation Related to defecation Altered stool frequency Associated with a change in a frequency of stool Altered stool form Associated with a change in form (appearance) of stool Onset of symptoms more than 6 months before diagnosis Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis

- 대한내과학회지 : 제 92 권제 4 호통권제 677 호 2017 - 부불편감 에서명백한복통으로표기한것이다. 복부불편감은상당히모호한단어로전세계의다양한언어에의해이단어에대한의미가다르게사용될수있어 [4] 배제하게되었다. 둘째, 복통기간의변화이다.

이것은대규모환자를대상으로한연구에서배변후호전되는경우가아닌배변후에악화되는경우가많이보고되었기때문이다. 또한복통이시작되는 시점 (onset) 에서시점을생략하였는데이는복통이시작되는시점과동반증상이발생하는시점이반드시일치하지는않기때문이다.

3 - 대한내과학회지 : 제 92 권제 4 호통권제 677 호 부불편감 에서명백한복통으로표기한것이다. 복부불편감은상당히모호한단어로전세계의다양한언어에의해이단어에대한의미가다르게사용될수있어 [4] 배제하게되었다. 둘째, 복통기간의변화이다. 로마기준 III의 1달에 3일이상에서 1주일에하루이상으로기간을상승시킨것은 2014년에발표한 Rome Normative GI symptom survey의수치를참고로한것이다 [8]. 배변후증상호전 (improvement with defecation) 은 배변과연관되고 (related to defecation) 로변경되었다. 이것은대규모환자를대상으로한연구에서배변후호전되는경우가아닌배변후에악화되는경우가많이보고되었기때문이다. 또한복통이시작되는 시점 (onset) 에서시점을생략하였는데이는복통이시작되는시점과동반증상이발생하는시점이반드시일치하지는않기때문이다. 과민성장증후군의아형분류 IBS는증상에따라서변비형 (IBS with predominant constipation), 설사형 (IBS with predominant diarrhea), 혼합형 (IBS with mixed bowel habits) 의 3가지로분류하며, 분류가불가능한경우를비특이형 (IBS unclassified) 으로분류하였다. 아형의분류는주로대변의굳기정도에따라서평가하며 Bristol Stool Form Scale (BSFS) 을이용한다 (Fig. 1) [9,12]. IBS의아형분류는증상과연관된약제를사용하지않는경우의증상을평가한다. 임상실험을위해서는 2주간의배변일기를바탕으로평가한다. 대변의형태에따라서 BSFS type 1 또는 2의형태가전체배변의 25% 이상인경우를변비형, BSFS type 6 또는 7의형태가전체배변의 25% 이상인경우를설사형, BSFS type 1 또는 2의형태가전체배변의 25% 이상이면서 BSFS type 6 또는 7의형태가전체배변의 25% 이상이같이동반된경우를혼합형, IBS의진단기준에는합당하지 만아형분류가어려운경우를비특이형으로분류한다 (Fig. 2) [9]. 다차원임상프로파일 (multidimensional clinical profile, MDCP) Rome 재단에서는진단기준뿐만아니라다양한소화기기능성질환에대한진단알고리즘의개발과다양한증상을구분하여 [13], 근거중심의학을바탕으로치료방법의결정에도움을주기위한 MDCP 를제시하고있다 [14]. MDCP 는 5개의범주로분류된다 (Table 3). 카테고리 A는로마기준에따른진단명 (the categorical Rome diagnosis) 으로, 로마기준 IV에따라증상을분류하여기술하는것이다. 개정된로마기준 IV는장질환에대하여 6가지의진단명을제시하고있으며, C1. 과민성장증후군, C2. 기능성변비, C3. 기능성설사, C4. 기능성복부부글거림 / 팽만, C5. 명확하지않은기능성장이상, C6. 오피오이드유발변비가이에해당한다 (Table 1) [9]. 카테고리 B는좀더구체적인치료가필요한아형분류와증상에대한추가적인정보 (clinical modifiers) 로 IBS의경우는표 3과같은내용을표기하여환자의상태를파악하고치료약제의결정에도움을줄수있도록하였다 [14]. 카테고리 C는일상생활에미치는영향 (impact on daily activities) 을평가하는것으로없음 (none), 경도 (mild), 중등도 (moderate), 고도 (severe) 로분류한다. 환자의증상정도에따른일상생활의방해정도를나타내는것으로환자에게 장 Figure 1. The Bristol Stool Form Scale [12]. Figure 2. The subtypes of irritable bowel syndrome [12]. BM, bowel movement; IBS, irritable bowel syndrome; IBS-C, IBS with predominant constipation; IBS-D, IBS with predominant diarrhea; IBS-M, IBS with mixed bowel habits; IBS-U, IBS-unclassified

4 - 김현정외 2 인. 과민성장증후군과기능성설사 - Table 3. The general, multidimensional, clinical profile categories Category A. Categorical diagnosis Category B. Clinical modifiers - Stool pattern: IBS-D, -C, -M or U - FODMAP sensitivity - IBD-IBS, ulcerative colitis in remission - Lactose or other disaccharide intolerance - Post-infection - Frequent vs. sporadic - With bloating - With fecal incontinence - With pain predominance - With postprandial symptoms - With urgency Category C. Impact on daily activities None/mild/moderate/severe Category D. Psychosocial modifiers Psychological/psychiatric symptoms/syndrome - Axis I or Axis II diagnosis from DSM-5 diagnoses - Current symptoms of depression, anxiety, anticipatory anxiety, post traumatic stress disorder (PTSD), excessive worry about symptoms, obsessive-compulsive behaviors, psychosocial flags Major stressors - Traumatic life events: Emotional, sexual or physical abuse history, war trauma, major work disruption, major loss that is either recent or longstanding but unresolved Rome IV psychosocial flags (9 items) - Anxiety - Depression - Suicidal ideation - Abuse and trauma history - Partner abuse - Pain severity - Somatic symptoms associated with distress and health concerns - Impairment/disability - Drug/alcohol use Category E. Physiological modifiers of function and biomarkers Wall structure and activity: manometry, MRI Movement of contents: radio-opaque markers, scintigraphy, smart pill, MRI Sensitivity: barostat Evidence of inflammation: biochemistry, histology, calprotectin, perfusion/diffusion, Cytokines, mrna, serology (celiac disease) Other analytical technique (disease specific): permeability, fecal tryptase, microbiota (HITChip) IBS, irritable bowel syndrome; IBD, inflammatory bowel disease; FODMAP, fermentable oligosaccharides, disaccharides and polyols; DSM, the diagnostic and statistical manual of mental disorders; MRI, magnetic resonance imaging 관증상이나장외증상으로인하여전반적인직장, 학교, 사회생활, 개인생활등에어느정도불편한지를, 없음, 저도, 증등도, 고도중에서선택해주세요 로질문하여작성한다. 입원이필요할정도의증상은고도로, 결석이나결근이잦은경우나외식이힘든경우가증등도에해당한다 [14]. 카테고리 D는정신사회적정보를평가하는것으로, 현재 까지진단된정신과적질환이나동반된증상, 스트레스요인이모두포함된다. 정신과적질환은 the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 에근거한진단명이포함되고, 현재뿐만아니라과거에진단받은경우도표시하여야한다. 해당하는내용은표 3과같다 [14]

5 - The Korean Journal of Medicine: Vol. 92, No. 4, 카테고리 E는생체표지자와기능성질환의생리학적이상 (physiologic modifier) 을기술하는것이다. 즉내압검사, 표지자검사등의검사에서이상소견이있는경우기술하는것이다. 과민성장증후군과연관된검사는표 3과같고, 모두표기대상이된다 [14]. 증례시나리오 IBS에서 MDCP 를이용하여증례를분석하고치료약제를선택하는것은훈련이필요하며, 시간이요구되는일이다. 이러한시간을줄이는데에는정리된증례를경험하는것이도움이될것으로판단되어다수의전문가에의해분석된증례를제시하고자한다 [14,15]. 증례 : 45세여자가심한복통과설사로내원하였다. 증상은 20대중반부터시작되었고, 반복적인복통과무른변, 급변감이동반되었다. 지난 2년전부터는증상이심해져서평균적으로주당 1-2일로증상이나타났으나, 최근에복통이더심해져서주당 4-5일정도로심한복통이자주생기고하루에 6-8번정도화장실에가야하는데, 가는도중변실금을경험하기도하였다. 얼마전 섬유근육통 (fibromyalgia) 으로진단받았으며, 가정과직장에서심한스트레스를겪고있었다. 체중감소, 혈변, 발열의소견은없었다. 증상이심해져서결근의횟수가잦아지고있어실직을걱정하고있다. 5년전대장내시경과조직검사에서는특이소견은없었고, 다양한혈액검사와대변검사에서도별다른이상소견은보이지않았다. 이전부터수차례저FODMAP (fermentable oligosaccharides, disaccharides and polyols) 식이를시도하였으나증상의일부만좋아져서현재는시도하지않고있었다. Loperamide 복용후설사는좋아졌으나, 복통은좋아지지않았고, 지속적으로복용하면변비가생겨불편감이더심해졌다. Rifaximin 치료를두차례시도하였으나호전의정도는미미하였다. 다양한종류의진경제치료를시도하였지만효과가없어현재 Table 4. The Rome Foundation multidimensional clinical profiles Category A. Categorical diagnosis: irritable bowel syndrome Category B. Clinical modifiers: IBS-D, with urgency, with fecal incontinence Category C. Impact on daily activities: severe Category D. Psychosocial modifiers: fibromyalgia, anxiety, severe stress Category E. Physiological modifiers of function and biomarkers: none known IBD, inflammatory bowel disease. 는복용하고있지않다. 저용량삼환계항우울제는효과가있는데, 입마름이심해서복용하지못하고있었다. 증례요약과분석 : 중년의여성으로오랫동안소화관증상이있다가최근에증상의정도가악화된경우로, IBS 진단기준을만족하고있으며, 경고증상은없지만이전에비하여증상이심해져서기질적질환의가능성을배제해서는안된다. 다양한검사소견이음성이지만대장내시경검사가 5년전이므로다시검사를시행할필요가있으며미세장염을감별하기위하여조직검사가필요하다. 다양한스트레스로인한불안감이있으며, 섬유근육통도동반되었다. 증상의정도는복통의정도도심하고결근과실직문제가동반된중증에해당한다. 이미다양한약제를사용하였으나증상호전에도움이되지않는상태이다. 표 4에 MDCP 를이용하여증례를정리하였다. 치료의선택 : 심한증상을동반한 IBS에서는약물요법과비약물요법을모두시도해야한다. 대부분의약제에크고작은부작용이동반되었고비약물요법으로는저FODMAP 식이에반응을보였으므로, 환자의식이에대한재교육을시행하고저FODMAP 식이를다시시도해볼수있으며, 완전하지않지만증상호전을기대할수있을것이다. 불안감과스트레스조절을위하여다양한정신과적치료 ( 인지치료, 최면요법, 자아강화요법, 이완요법등 ) 가도움이될수있다. 약제는세로토닌 3형수용체길항제인 ramosetron 2.5 μg 하루 1회요법을시도할수있으며, 복통과설사, 변실금의감소를기대할수있다. 섬유근육통의적절한치료로갑작스러운통증에서시작되는불안감을감소시켜주어야한다. 삼환계항우울제를대신하여세로토닌재흡수차단제또는세로토닌- 노르에피네프린재흡수억제제를선택해볼수있다. 새로운지사제인 exuladolin 100 mg 하루 2회요법또한치료선택의한가지가될수있으나우리나라에서는아직처방이어려운상태이다. 결론 IBS의진단은증상을중심으로이루어지며, 기질적인이상을배제하고기능성질환을충분히포함할수있는진단기준을마련하기위하여여러차례개정하였다. 로마기준 IV 는이전에비하여좀더근거중심의학을기반으로하고있으며, 전세계인의증상평가를바탕으로하고있어실제진료에적용하는경우기질적인질환을배제하고증상을기반

6 - Hyun Jung Kim, et al. Irritable bowel syndrome and functional diarrhea - 으로하는치료에도움이될것으로기대된다. 또한 IBS의치료에환자의증상정도, 동반증상, 정신사회적문제, 이전치료의경험, 약제에대한부작용병력등을모두고려하여 MDCP 를작성하는것이근거중심의학적치료에도움을줄것이다. 중심단어 : 과민성장증후군 ; 기능성설사 ; 로마기준 IV; 다차원임상프로파일 REFERENCES 1. Kasper D, Fauci A, Hauser S et al. Harrison's principles of internal medicine. 19th ed. New York: McGraw-Hill, Medical Pub. Division, 2016; Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA 2015;313: Kim JH, Lin E, Pimentel M. Biomarkers of irritable bowel syndrome. J Neurogastroenterol Motil 2017;23: American College of Gastroenterology Task Force on Irritable Bowel Syndrome, Brandt LJ, Chey WD, et al. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol 2009;104 Suppl 1:S1-S 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: Park DW, Lee OY, Shim SG, et al. The differences in prevalence and sociodemographic characteristics of irritable bowel syndrome according to Rome II and Rome III. J Neurogastroenterol Motil 2010;16: Rome Foundation. Guidelines--Rome III diagnostic criteria for functional gastrointestinal disorders. J Gastrointestin Liver Dis 2006;15: Palsson OS, Whitehead WE, van Tilburg MA, et al. Development and validation of the Rome IV diagnostic questionnaire for adults. Gastroenterology 2016;150: Drossman DA, Hasler WA. Rome IV-functional GI disorders: disorders of gut-brain interaction. Gastroenterology 2016;150: Begtrup LM, Engsbro AL, Kjeldsen J, et al. A positive diagnostic strategy is noninferior to a strategy of exclusion for patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 2013;11: e Rome Foundation. Rome IV FAQs [Internet]. Raleigh (US): Rome Foundation, c2017 [cited 2017 July 1]. Available from: Patel P, Bercik P, Morgan DG, et al. Prevalence of organic disease at colonoscopy in patients with symptoms compatible with irritable bowel syndrome: cross-sectional survey. Scand J Gastroenterol 2015;50: Kellow J, Drossman DA, Chang Lin, et al. Diagnostic algorithms for common GI symptoms. 2nd ed. Raleigh: Rome foundation, Drossman DA, Chang L, Chey WD, et al. Multidimensional Clinical Profile for Functional Gastrointestinal Disorders. 2nd ed. Raleigh; Rome foundation, Lucak S, Chang L, Halpert A, Harris LA. Current and emergent pharmacologic treatments for irritable bowel syndrome with diarrhea: evidence-based treatment in practice. Therap Adv Gastroenterol 2017;10:

<B0E6C8F1B4EBB3BBB0FAC0D3BBF3B0ADC1C E687770>

<B0E6C8F1B4EBB3BBB0FAC0D3BBF3B0ADC1C E687770> 개원의와함께하는임상강좌 2011 역류성식도질환제대로이해하기 Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea Jae-Young Jang, M.D., PhD. 개원의와함께하는임상강좌 2011 109 최신치료