Recent Developments in the Diagnosis and Treatment of Refractory Irritable Bowel Syndrome

doi:10.12114/j.issn.1007-9572.2021.00.546

Abstract

Abstract: Irritable bowel syndrome （IBS） is a functional gastrointestinal disorder that often seen in clinical practice.Monotherapy may not be effective for IBS due to its complex pathogenesis，as a result，some patients' condition is prolonged to become refractory.So far，there are no uniform definition，diagnostic criteria and treatments for refractory IBS.This article summarizes the diagnostic criteria and treatments for refractory IBS worldwide，which will contribute to its clinical diagnosis and treatment，benefiting more patients.

Key words: Irritable bowel syndrome, Diagnosis, Therapy, Research progress

摘要： 肠易激综合征是临床常见的功能性胃肠病之一，病理机制复杂，临床采用单一治疗模式多难以奏效，部分患者病情迁延成为难治性肠易激综合征。目前国内外对难治性肠易激综合征并无准确定义和诊断标准，亦无统一的治疗方法。本文就目前国内外难治性肠易激综合征的诊断标准及治疗进展做一概述，以期为难治性肠易激综合征的临床诊治提供指导，使更多患者获益。

关键词: 肠易激综合征, 诊断, 治疗, 研究进展

XIE Xin,CHEN Min,YE Kun, et al. Recent Developments in the Diagnosis and Treatment of Refractory Irritable Bowel Syndrome　[J]. Chinese General Practice, 2021, 24(21): 2640-2645. DOI: 10.12114/j.issn.1007-9572.2021.00.546.
谢欣,陈敏,叶坤等. 难治性肠易激综合征诊治的研究进展[J]. 中国全科医学, 2021, 24(21): 2640-2645. DOI: 10.12114/j.issn.1007-9572.2021.00.546.

References

［1］GWEE K A，GONLACHANVIT S，GHOSHAL U C，et al．Second Asian consensus on irritable bowel syndrome［J］．J Neurogastroenterol Motil，2019，25（3）：343-362．DOI：10.5056/jnm19041.
［2］CHEY W D，KURLANDER J，ESWARAN S.Irritable bowel syndrome：a clinical review［J］．JAMA，2015，313（9）：949-958．DOI：10.1001/jama.2015.0954.
［3］SPERBER A D，DUMITRASCU D，FUKUDO S，et al．The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies：a Rome Foundation working team literature review［J］．Gut，2017，66（6）：1075-1082．DOI：10.1136/gutjnl-2015-311240.
［4］吴寒，张振玉.肠易激综合征东西方指南对比解读［J］．胃肠病学和肝病学杂志，2019，28（9）：961-967.
WU H，ZHANG Z Y.An interpretation of the eastern and western guidelines for irritable bowel syndrome［J］．Chinese Journal of Gastroenterology and Hepatology，2019，28（9）：961-967.
［5］H?USER W，MARSCHALL U，LAYER P，et al．The prevalence，comorbidity，management and costs of irritable bowel syndrome［J］．Dtsch Arztebl Int，2019，116（27/28）：463-470．DOI：10.3238/arztebl.2019.0463.
［6］VU J，KUSHNIR V，CASSELL B，et al．The impact of psychiatric and extraintestinal comorbidity on quality of life and bowel symptom burden in functional GI disorders ［J］．Neurogastroenterol Motil，2014，26（9）：1323-1332．DOI：10.1111/nmo.12396.
［7］徐心田，徐丹华，陆为民.神经-内分泌-免疫系统调控异常与肠易激综合征相关性的研究进展［J］．中国全科医学，2020，23（26）：3369-3374．DOI：10.12114/j.issn.1007-9572.2019.00.727.
XU X T，XU D H，LU W M.Relationship between irritable bowel syndrome and regulatory abnormalities of neuroendocrine-immune network ［J］．Chinese General Practice，2020，23（26）：3369-3374．DOI：10.12114/j.issn.1007-9572.2019.00.727.
［8］SIMRéN M，T?RNBLOM H，PALSSON O S，et al．Management of the multiple symptoms of irritable bowel syndrome［J］．Lancet Gastroenterol Hepatol，2017，2（2）：112-122．DOI：10.1016/s2468-1253（16）30116-9.
［9］何力，杨力，凌志维，等．基于脑肠交互机制探讨肠道微生物调节IBS-D内脏高敏的研究进展［J］．中国实验方剂学杂志，2019，25（11）：224-229.
HE L，YANG L，LING Z W，et al．Effect of intestinal microbiota in regulating visceral hypersensitivity of IBS-D based on brain-gut interacting mechanism ［J］．Chinese Journal of Experimental Traditional Medical Formulae，2019，25（11）：224-229.
［10］刘涛，刘霞，张驰，等．基于脑-肠-菌轴阐述针刺与肠易激综合征的关系［J］．中国中医药现代远程教育，2018，16（8）：152-155.
LIU T，LIU X，ZHANG C，et al．Discussion on the relationship between acupuncture and irritable bowel syndrome based on the brain-gut-microbiota axis ［J］．Chinese Medicine Modern Distance Education of China，2018，16（8）：152-155.
［11］NG Q X，SOH A Y S，LOKE W，et al．The role of inflammation in irritable bowel syndrome （IBS）［J］．J Inflamm Res，2018，11：345-349．DOI：10.2147/JIR.S174982.
［12］朱诗玮，王志仁，段丽萍.中国肠易激综合征和抑郁症患者具有相同的遗传易感性位点［J］．中华内科杂志，2020，59（5）：391.
ZHU S W，WANG Z R，DUAN L P.Shared genetic susceptibilities for irritable bowel syndrome and depressive disorder in Chinese patients ［J］．Chinese Journal of Internal Medicine，2020，59（5）：391.
［13］SIBELLI A，MOSS-MORRIS R，CHALDER T，et al．Patients' perspectives on GP interactions after cognitive behavioural therapy for refractory IBS：a qualitative study in UK primary and secondary care［J］．Br J Gen Pract，2018，68（674）：e654-662．DOI：10.3399/bjgp18x698321.
［14］DUAN T Y，CIL O，TSE C M，et al．Inhibition of CFTR-mediated intestinal chloride secretion as potential therapy for bile acid diarrhea［J］．Faseb J，2019，33（10）：10924-10934．DOI：10.1096/fj.201901166R.
［15］KUA C H，NG S T，LHODE R，et al．Irritable bowel syndrome and other gastrointestinal disorders：evaluating self-medication in an Asian community setting［J］．Int J Clin Pharm，2012，34（4）：561-568．DOI：10.1007/s11096-012-9644-0.
［16］CREED F.Review article：the incidence and risk factors for irritable bowel syndrome in population-based studies［J］．Aliment Pharmacol Ther，2019，50（5）：507-516．DOI：10.1111/apt.15396.
［17］KLEM F，WADHWA A，PROKOP L J，et al．Prevalence，risk factors，and outcomes of irritable bowel syndrome after infectious enteritis：a systematic review and meta-analysis［J］．Gastroenterology，2017，152（5）：1042-1054.e1．DOI：10.1053/j.gastro.2016.12.039.
［18］LACKNER J M，QUIGLEY B M，RADZIWON C D，et al．IBS patients' treatment expectancy and motivation impacts quality of the therapeutic alliance with provider：results of the IBS outcome study［J］．J Clin Gastroenterol，2021，55（5）：411-421．DOI：10.1097/mcg.0000000000001343.
［19］EVERITT H A，LANDAU S，O'REILLY G，et al．Assessing telephone-delivered cognitive-behavioural therapy （CBT） and web-delivered CBT versus treatment as usual in irritable bowel syndrome （ACTIB）：a multicentre randomised trial［J］．Gut，2019，68（9）：1613-1623．DOI：10.1136/gutjnl-2018-317805.
［20］HOLVOET T，JOOSSENS M，VáZQUEZ-CASTELLANOS J F，et al．Fecal microbiota transplantation reduces symptoms in some patients with irritable bowel syndrome with predominant abdominal bloating：short-and long-term results from a placebo-controlled randomized trial［J］．Gastroenterology，2021，160（1）：145-157.e8．DOI：10.1053/j.gastro.2020.07.013.
［21］WINDGASSEN S，MOSS-MORRIS R，EVERITT H，et al．Cognitive and behavioral differences between subtypes in refractory irritable bowel syndrome［J］．Behav Ther，2019，50（3）：594-607．DOI：10.1016/j.beth.2018.09.006.
［22］LACKNER J M，JACCARD J，KEEFER L，et al．Improvement in gastrointestinal symptoms after cognitive behavior therapy for refractory irritable bowel syndrome［J］．Gastroenterology，2018，155（1）：47-57．DOI：10.1053/j.gastro.2018.03.063.
［23］LACKNER J M，JACCARD J，RADZIWON C D，et al．Durability and decay of treatment benefit of cognitive behavioral therapy for irritable bowel syndrome：12-month follow-up［J］．Am J Gastroenterol，2019，114（2）：330-338．DOI：10.1038/s41395-018-0396-x.
［24］KAWANISHI H，SEKIGUCHI A，FUNABA M，et al．Cognitive behavioral therapy with interoceptive exposure and complementary video materials for irritable bowel syndrome （IBS）：protocol for a multicenter randomized controlled trial in Japan［J］．Biopsychosoc Med，2019，13：14．DOI：10.1186/s13030-019-0155-2.
［25］HUANG H L，CHEN H T，LUO Q L，et al．Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota［J］．J Dig Dis，2019，20（8）：401-408．DOI：10.1111/1751-2980.12756.
［26］CRUZ-AGULIAR R M，WANTIA N，CLAVEL T，et al．An open-labeled study on fecal microbiota transfer in irritable bowel syndrome patients reveals improvement in abdominal pain associated with the relative abundance of Akkermansia muciniphila［J］．Digestion，2019，100（2）：127-138．DOI：10.1159/000494252.
［27］KROUWEL M，JOLLY K，GREENFIELD S.How do people with refractory irritable bowel syndrome perceive hypnotherapy?：Qualitative study［J］．Complement Ther Med，2019，45：65-70．DOI：10.1016/j.ctim.2019.05.020.
［28］FORD A C，LACY B E，TALLEY N J.Irritable bowel syndrome ［J］．N Engl J Med，2017，376（26）：2566-2578.
［29］BLACK C J，THAKUR E R，HOUGHTON L A，et al．Efficacy of psychological therapies for irritable bowel syndrome：systematic review and network meta-analysis［J］．Gut，2020，69（8）：1441-1451．DOI：10.1136/gutjnl-2020-321191.
［30］HARVEY R F，HINTON R A，GUNARY R M，et al．Individual and group hypnotherapy in treatment of refractory irritable bowel syndrome［J］．Lancet，1989，1（8635）：424-425．DOI：10.1016/s0140-6736（89）90013-5.
［31］FORD A C，LACY B E，HARRIS L A，et al．Effect of antidepressants and psychological therapies in irritable bowel syndrome：an updated systematic review and meta-analysis［J］．Am J Gastroenterol，2019，114（1）：21-39．DOI：10.1038/s41395-018-0222-5.
［32］QUIGLEY E M，FRIED M，GWEE K A，et al．World gastroenterology organisation global guidelines irritable bowel syndrome：a global perspective update September 2015［J］．J Clin Gastroenterol，2016，50（9）：704-713．DOI：10.1097/mcg.0000000000000653.
［33］HOOKWAY C，BUCKNER S，CROSLAND P，et al．Irritable bowel syndrome in adults in primary care：summary of updated NICE guidance［J］．BMJ，2015，350：h701．DOI：10.1136/bmj.h701.
［34］BECK A T.Thinking and depression：Ⅱ.theory and therapy［J］．Arch Gen Psychiatry，1964，10（6）：561-571.
［35］LACKNER J M.Skills over pills? A clinical gastroenterologist's primer in cognitive behavioral therapy for irritable bowel syndrome［J］．Expert Rev Gastroenterol Hepatol，2020，14（7）：601-618．DOI：10.1080/17474124.2020.1780118.
［36］EVERITT H A，LANDAU S，O'REILLY G，et al．Cognitive behavioural therapy for irritable bowel syndrome：24-month follow-up of participants in the ACTIB randomised trial［J］．Lancet Gastroenterol Hepatol，2019，4（11）：863-872．DOI：10.1016/s2468-1253（19）30243-2.
［37］EVERITT H，LANDAU S，LITTLE P，et al．Therapist telephone-delivered CBT and web-based CBT compared with treatment as usual in refractory irritable bowel syndrome：the ACTIB three-arm RCT［J］．Health Technol Assess，2019，23（17）：1-154．DOI：10.3310/hta23170.
［38］UDO I，GASH A.Management of refractory irritable bowel syndrome and comorbid mental ill-health：challenges，reflections and patient's perspective of life on the body-mind divide ［J］．BMJ Case Rep，2013：bcr2013009545．DOI：10.1136/bcr-2013-009545.
［39］游乐卿，贾林，刘静，等．小剂量阿米替林治疗84例难治性腹泻型肠易激综合征的时-效关系及长期疗效的资料分析［J］．中华行为医学与脑科学杂志，2014（12）：1105-1107.
［40］SONG K H，JUNG H K，KIM H J，et al．Clinical Practice Guidelines for Irritable Bowel Syndrome in Korea，2017 Revised Edition ［J］．J Neurogastroenterol Motil，2018，24（2）：197-215．DOI：10.5056/jnm17145.
［41］WANG Y T，KWOK K F，TAN S M，et al．Comprehensive psychological intervention to improve outcome in functional gastrointestinal disorder：a cohort study［J］．Singapore Med J，2015，56（7）：385-392．DOI：10.11622/smedj.2015109.
［42］MOSER G，TR?GNER S，GAJOWNICZEK E E，et al．Long-term success of GUT-directed group hypnosis for patients with refractory irritable bowel syndrome：a randomized controlled trial ［J］．Am J Gastroenterol，2013，108（4）：602-609．DOI：10.1038/ajg.2013.19.
［43］FLIK C E，LAAN W，ZUITHOFF N P A，et al．Efficacy of individual and group hypnotherapy in irritable bowel syndrome （IMAGINE）：a multicentre randomised controlled trial［J］．Lancet Gastroenterol Hepatol，2019，4（1）：20-31．DOI：10.1016/s2468-1253（18）30310-8.
［44］SPILLER R，AZIZ Q，CREED F，et al．Guidelines on the irritable bowel syndrome：mechanisms and practical management［J］．Gut，2007，56（12）：1770-1798．DOI：10.1136/gut.2007.119446.
［45］李宁，田宏亮，陈启仪，等．菌群移植治疗肠道疾病2010例疗效分析［J］．中华胃肠外科杂志，2019，22（9）：861-868.
LI N，TIAN H L，CHEN Q Y，et al．Efficacy analysis of fecal microbiota transplantation in the treatment of 2010 patients with intestinal disorders ［J］．Chinese Journal of Gastrointestinal Surgery，2019，22（9）：861-868.
［46］DOBBIN A，DOBBIN J，ROSS S C，et al．Randomised controlled trial of brief intervention with biofeedback and hypnotherapy in patients with refractory irritable bowel syndrome［J］．J R Coll Physicians Edinb，2013，43（1）：15-23．DOI：10.4997/jrcpe.2013.104.
［47］LAM J Y，KIDANE B，MANJI F，et al．Improved health-related quality of life after surgical management of severe refractory constipation-dominant irritable bowel syndrome［J］．Int Surg，2015，100（1）：63-69．DOI：10.9738/intsurg-d-13-00212.1.
［48］ATTALI T V，BOUCHOUCHA M，BENAMOUZIG R.Treatment of refractory irritable bowel syndrome with visceral osteopathy：short-term and long-term results of a randomized trial［J］．J Dig Dis，2013，14（12）：654-661．DOI：10.1111/1751-2980.12098.
［49］ZOMORODI S，ABDI S，TABATABAEE S K.Comparison of long-term effects of cognitive-behavioral therapy versus mindfulness-based therapy on reduction of symptoms among patients suffering from irritable bowel syndrome［J］．Gastroenterol Hepatol Bed Bench，2014，7（2）：118-124.
［50］MEARIN F，CIRIZA C，MíNGUEZ M，et al．Clinical Practice Guideline：irritable bowel syndrome with constipation and functional constipation in the adult［J］．Rev Esp Enferm Dig，2016，108（6）：332-363．DOI：10.17235/reed.2016.4389/2016.
［51］BERENS S，STROE-KUNOLD E，KRAUS F，et al．Pilot-RCT of an integrative group therapy for patients with refractory irritable bowel syndrome （ISRCTN02977330）［J］．J Psychosom Res，2018，105：72-79．DOI：10.1016/j.jpsychores.2017.12.002.
［52］CHEN M，TANG T C，WANG Y，et al．Randomised clinical trial：Tong-Xie-Yao-Fang granules versus placebo for patients with diarrhoea-predominant irritable bowel syndrome［J］．Aliment Pharmacol Ther，2018，48（2）：160-168．DOI：10.1111/apt.14817.
［53］MANHEIMER E，WIELAND L S，CHENG K，et al．Acupuncture for irritable bowel syndrome：systematic review and meta-analysis［J］．Am J Gastroenterol，2012，107（6）：835-848．DOI：10.1038/ajg.2012.66.

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