Advances in the Etiology of Chronic Diarrhea in Adults

doi:10.12114/j.issn.1007-9572.2019.00.378

Abstract

Abstract: Chronic diarrhea is a group of clinical syndromes with multiple and numerous causes and the complex pathogenesis.According to the lesions，chronic diarrhea can be divided into gastric-derived type，intestinal-derived type，hepatobiliary and pancreatic-derived type，endocrine disease，neuroendocrine tumor and types with other causes of diarrhea in this article.The causes of chronic diarrhea which can be triggered by multiple organ system diseases are complex.To improve the clinical diagnosis and treatment of chronic diarrhea，the etiology of this disease is now reviewed in this article in order to effectively guide the clinical practice.

Key words: Diarrhea, Pathologic processes, Adult, Review

摘要： 慢性腹泻是一组多病因导致的临床综合征，病因繁多，发病机制复杂。本文依据病变部位，将慢性腹泻分为胃源性、肠源性、肝胆胰源性、内分泌疾病、神经内分泌肿瘤及其他病因所致的腹泻。慢性腹泻病因复杂，多器官系统疾病均可引发，本文对其病因进行综述，旨在提高临床医生对慢性腹泻的认识、有效地指导临床实践、提高临床诊治水平。

关键词: 腹泻, 病理过程, 成年人, 综述

ZHANG Lijuan,JIANG Yong,LIU Binghua, et al. Advances in the Etiology of Chronic Diarrhea in Adults　[J]. Chinese General Practice, 2019, 22(22): 2760-2765. DOI: 10.12114/j.issn.1007-9572.2019.00.378.
张莉娟,江勇,刘炳华等. 成年人慢性腹泻病因的研究进展[J]. 中国全科医学, 2019, 22(22): 2760-2765. DOI: 10.12114/j.issn.1007-9572.2019.00.378.

References

［1］FAGUNDES-NETO U.Persistent diarrhea：still a serious public health problem in developing countries［J］．Curr Gastroenterol Rep，2013，15（9）：345．DOI：10.1007/s11894-013-0345-1.
［2］曹艳菊，许连壮，张豫生.抗生素相关性腹泻死亡6例分析［J］．胃肠病学和肝病学杂志，2009，18（10）：965，967．DOI：10.3969/j.issn.1006-5709.2009.10.031.
CAO Y J，XU L Z，ZHANG Y S.The analysis of death cases from antibiotic-associated diarrhea［J］．Chinese Journal of Gastroenterology and Hepatology，2009，18（10）：965，967．DOI：10.3969/j.issn.1006-5709.2009.10.031.
［3］ABBAS Z，RAZA S，YAKOOB J，et al．Varied presentation of celiac disease in Pakistani adults［J］．J Coll Physicians Surg Pak，2013，23（7）：522-524．DOI：07.2013/JCPSP.522524.
［4］WANG X，LING L，LI S S，et al．The diagnostic value of gastrin-17 detection in atrophic gastritis：a meta-analysis［J］．Medicine（Baltimore），2016，95（18）：e3599．DOI：10.1097/MD.0000000000003599.
［5］CHEN W Q，ZHENG R S，BAADE P D，et al．Cancer statistics in China，2015［J］．Ca Cancer J Clin，2016，66（2）：115-132．DOI：10.3322/caac.21338.
［6］ZHAO R，WANG Y，HUANG Y Q，et al．Effects of fiber and probiotics on diarrhea associated with enteral nutrition in gastric cancer patients：a prospective randomized and controlled trial［J］．Medicine（Baltimore），2017，96（43）：e8418．DOI：10.1097/MD.0000000000008418.
［7］DOMíNGUEZ-LóPEZ M E，GONZáLEZ-MOLERO I，RAMíREZ-PLAZA C P，et al．Chonic diarrhea and malabsorption due to common variable immunodeficiency，gastrectomy and giardiasis infection：a difficult nutritional management［J］．Nutr Hosp，2011，26（4）：922-925．DOI：10.1590/S0212-16112011000400037.
［8］诸欣平，苏川.人体寄生虫学［M］．北京：人民卫生出版社，2013.
［9］ZHANG H，SI Y L，WANG X F，et al．Patterns of bacillary dysentery in China，2005—2010［J］．Int J Environ Res Public Health，2016，13（2）：164．DOI：10.3390/ijerph13020164.
［10］CHANG Z L，LU S T，CHEN L H，et al．Causative species and serotypes of shigellosis in mainland China：systematic review and meta-analysis［J］．PLoS One，2012，7（12）：e52515．DOI：10.1371/journal.pone.0052515.
［11］YANG G Y，ZHANG W Z，YU T Z，et al．The features of intestinal tuberculosis by contrast-enhanced ultrasound［J］．Jpn J Radiol，2015，33（9）：577-584．DOI：10.1007/s11604-015-0459-5.
［12］李兰娟，任红.传染病学［M］．北京：人民卫生出版社，2013.
［13］周晓农，汪天平，王立英，等．中国血吸虫病流行现状分析［J］．中华流行病学杂志，2004，25（7）：555-558.
ZHOU X N，WANG T P，WANG L Y，et al．The current status of schistosomiasis epidemics in China［J］．Chinese Journal of Epidemiology，2004，25（7）：555-558.
［14］杨宝峰.药理学［M］．8版.北京：人民卫生出版社，2015.
［15］TAKAISHI H，MATSUKI T，NAKAZAWA A，et al．Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease［J］．Int J Med Microbiol，2008，298（5/6）：463-472．DOI：10.1016/j.ijmm.2007.07.016.
［16］CHEY W D，KURLANDER J，ESWARAN S.Irritable bowel syndrome［J］．JAMA，2015，313（9）：949．DOI：10.1001/jama.2015.0954.
［17］SAHA L.Irritable bowel syndrome：pathogenesis，diagnosis，treatment，and evidence-based medicine［J］．World J Gastroenterol，2014，20（22）：6759-6773．DOI：10.3748/wjg.v20.i22.6759.
［18］PIMENTEL M，MORALES W，REZAIE A，et al．Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects［J］．PLoS One，2015，10（5）：e0126438．DOI：10.1371/journal.pone.0126438.
［19］秦湘红，胡海棠，刘思德，等．口服双歧杆菌活菌散剂治疗急慢性腹泻的随机对照双盲双模拟多中心临床研究［J］．中国微生态学杂志，2009，21（9）：844-847．DOI：10.13381/j.cnki.cjm.2009.09.028.
QIN X H，HU H T，LIU S D，et al．Live bifidobacterium oral powder in treatment of acute and chronic diarrhea：a randomized，controlled，double-blind double-dummy，multicenter clinical study［J］．Chinese Journal of Microecology，2009，21（9）：844-847．DOI：10.13381/j.cnki.cjm.2009.09.028.
［20］INGLE S B，PATLE Y G，MURDESHWAR H G，et al．A case of early eosinophilic gastroenteritis with dramatic response to steroids［J］．J Crohns Colitis，2011，5（1）：71-72．DOI：10.1016/j.crohns.2010.10.002.
［21］PINETON DE CHAMBRUN G，DESREUMAUX P，CORTOT A.Eosinophilic enteritis［J］．Dig Dis，2015，33（2）：183-189．DOI：10.1159/000369540.
［22］DOULBERIS M，PANAGOPOULOS P，SCHERZ S，et al．Update on ischemic colitis：from etiopathology to treatment including patients of intensive care unit［J］．Scand J Gastroenterol，2016，51（8）：893-902．DOI：10.3109/00365521.2016.1162325.
［23］SHERID M，SIFUENTES H，SAMO S，et al．Ischemic colitis：a forgotten entity.Results of a retrospective study in 118 patients［J］．J Dig Dis，2014，15（11）：606-613．DOI：10.1111/1751-2980.12182.
［24］KALAISELVAN R，THEIS V S，DIBB M，et al．Radiation enteritis leading to intestinal failure：1994 patient-years of experience in a national referral centre［J］．Eur J Clin Nutr，2014，68（2）：166-170．DOI：10.1038/ejcn.2013.251.
［25］STACEY R，GREEN J T.Radiation-induced small bowel disease：latest developments and clinical guidance［J］．Ther Adv Chronic Dis，2014，5（1）：15-29．DOI：10.1177/2040622313510730.
［26］JEPPESEN P B.Spectrum of short bowel syndrome in adults：intestinal insufficiency to intestinal failure［J］．JPEN J Parenter Enteral Nutr，2014，38（suppl 1）：s8-13．DOI：10.1177/0148607114520994.
［27］薛聪龙.短肠综合征［C］//《医学参考报一营养学频道》编辑部，广州抗癌协会肿瘤营养与支持治疗专业委员会，《中华普通外科学文献：电子版》编辑部．2011广州国际肿瘤营养与支持治疗研讨会论文集，2011.
［28］PARDI D S，SMYRK T C，TREMAINE W J，et al．Microscopic colitis：a review［J］．Am J Gastroenterol，2002，97（4）：794-802．DOI：10.1111/j.1572-0241.2002.05595.x.
［29］TINA P，DAVID C，CHRISTOPHER M.Microscopic colitis：a review of etiology，treatment and refractory disease［J］．World Journal of Gastroenterology，2015，21（29）：8804-8810.
［30］GUAGNOZZI D，LUCENDO A J，ANGUEIRA T，et al．Drug consumption and additional risk factors associated with microscopic colitis：case-control study［J］．Rev Esp Enferm Dig，2015，107（6）：347-353.
［31］BRODY H.Colorectal cancer［J］．Nature，2015，521（s1）：7551．DOI：10.1038/521S1a.
［32］NAKAMURA S，MATSUMOTO T，IIDA M，et al．Primary gastrointestinal lymphoma in Japan：a clinicopathologic analysis of 455 patients with special reference to its time trends［J］．Cancer，2003，97（10）：2462-2473．DOI：10.1002/cncr.11415.
［33］张汝钢，刘迎娣，聂燕，等．以反复腹泻为主要临床表现的肠病相关T细胞淋巴瘤1例［J］．胃肠病学和肝病学杂志，2016，25（7）：837-838．DOI：10.3969/j.issn.1006-5709.2016.07.030.
ZHANG R G，LIU Y D，NIE Y，et al．Enteropathy-associated T-cell lymphoma with recurrent diarrhea as the main clinical manifestations：one case report［J］．Chinese Journal of Gastroenterology and Hepatology，2016，25（7）：837-838．DOI：10.3969/j.issn.1006-5709.2016.07.030.
［34］鲍德明，胡乃中.原发性肠道淋巴瘤临床特点分析［J］．中华消化杂志，2007，27（3）：193-195．DOI：10.3760/j.issn：0254-1432.2007.03.017.
BAO D M，HU N Z.Analysis of clinical features of primary intestinal lymphoma［J］．Chinese Journal of Digestion，2007，27（3）：193-195．DOI：10.3760/j.issn：0254-1432.2007.03.017.
［35］LI L J，WU Z W，XIAO D S，et al．Changes of gut flora and endotoxin in rats with D-galactosamine-induced acute liver failure［J］．World J Gastroenterol，2004，10（14）：2087-2090．DOI：10.3748/wjg.v10.i14.2087.
［36］KIYICI M，NAK S G，BUDAK F，et al．Lymphocyte subsets and cytokines in ascitic fluid of decompensated cirrhotic patients with and without spontaneous ascites infection［J］．J Gastroenterol Hepatol，2006，21（6）：963-969．DOI：10.1111/j.1440-1746.2006.04229.x.
［37］吴仲文，李兰娟.肝硬化并发症与肠道菌群［J］．国际流行病学传染病学杂志，2006，33（1）：34-37，44．DOI：10.3760/cma.j.issn.1673-4149.2006.01.010.
WU Z W，LI L J.Cirrhotic complications and intestinal microflora［J］．International Journal of Epidemiology and Infectious Disease，2006，33（1）：34-37，44．DOI：10.3760/cma.j.issn.1673-4149.2006.01.010.
［38］ROBLES-MEDRANDA C，LUKASHOK H P，NOVAIS P，et al．Chronic diarrhea as first manifestation of liver cirrhosis and hepatocarcinoma in a teenager：a case report and review of the literature［J］．J Pediatr Gastroenterol Nutr，2006，42（4）：434-436．DOI：10.1097/01.mpg.0000189342.38634.ac.
［39］ZHOU D，GUAN W B，WANG J D，et al．A comparative study of clinicopathological features between chronic cholecystitis patients with and without helicobacter pylori infection in gallbladder mucosa［J］．PLoS One，2013，8（7）：e70265．DOI：10.1371/journal.pone.0070265.
［40］FISHER M，SPILIAS D C，TONG L K.Diarrhoea after laparoscopic cholecystectomy：incidence and main determinants［J］．ANZ J Surg，2008，78（6）：482-486．DOI：10.1111/j.1445-2197.2008.04539.x.
［41］YUEH T P，CHEN F Y，LIN T E，et al．Diarrhea after laparoscopic cholecystectomy：associated factors and predictors［J］．Asian J Surg，2014，37（4）：171-177．DOI：10.1016/j.asjsur.2014.01.008.
［42］JASIM H.Postcholecystectomy bowel motion changes and diarrhea a prospective study［J］．Iraqi Medical Journal，2018，64（1）：1500.
［43］BARKUN A N，LOVE J，GOULD M，et al．Bile acid malabsorption in chronic diarrhea：pathophysiology and treatment［J］．Can J Gastroenterol，2013，27（11）：653-659.
［44］PATTNI S，WALTERS J R.Recent advances in the understanding of bile acid malabsorption［J］．Br Med Bull，2009，92：79-93．DOI：10.1093/bmb/ldp032.
［45］LUACES-REGUEIRA M，IGLESIAS-GARCíA J，LINDKVIST B，et al．Smoking as a risk factor for complications in chronic pancreatitis［J］．Pancreas，2014，43（2）：275-280．DOI：10.1097/01.mpa.0000437324.52598.ee.
［46］SZüCS á，MARJAI T，SZENTESI A，et al．Chronic pancreatitis：multicentre prospective data collection and analysis by the Hungarian Pancreatic Study Group［J］．PLoS One，2017，12（2）：e0171420．DOI：10.1371/journal.pone.0171420.
［47］BUSTILLO I，LARSON H，SAIF M W.Small intestine bacterial overgrowth：an underdiagnosed cause of diarrhea in patients with pancreatic cancer［J］．JOP，2009，10（5）：576-578.
［48］FABIAN E，KUMP P，KREJS G J.Diarrhea caused by circulating agents［J］．Gastroenterol Clin North Am，2012，41（3）：603-610．DOI：10.1016/j.gtc.2012.06.008.
［49］RAFF H，SHARMA S T，NIEMAN L K.Physiological basis for the etiology，diagnosis，and treatment of adrenal disorders：Cushing's syndrome，adrenal insufficiency，and congenital adrenal hyperplasia［J］．Compr Physiol，2014，4（2）：739-769．DOI：10.1002/cphy.c130035.
［50］BERNA M J，HOFFMANN K M，SERRANO J，et al．Serum gastrin in Zollinger-Ellison syndrome：I.Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2 229 cases from the literature［J］．Medicine（Baltimore），2006，85（6）：295-330．DOI：10.1097/01.md.0000236956.74128.76.
［51］TRUMP D L，LIVINGSTON J N，BAYLIN S B.Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma：identification of vasoactive intestinal peptide，calcitonin，and catecholamines and assessment of their biologic activity［J］．Cancer，1977，40（4）：1526-1532.
［52］NOTT J，KHAN A，MADHOTRA R，et al．An unusual diagnosis for persistent diarrhoea and vomiting［J］．Gastroenterol Hepatol Bed Bench，2017，10（1）：73-74.
［53］TANG B，YONG X，XIE R，et al．Vasoactive intestinal peptide receptor-based imaging and treatment of tumors（review）［J］．Int J Oncol，2014，44（4）：1023-1031．DOI：10.3892/ijo.2014.2276.
［54］PATEL T S，CRUTCHLEY R D，TUCKER A M，et al．Crofelemer for the treatment of chronic diarrhea in patients living with HIV/AIDS［J］．HIV AIDS（Auckl），2013，5：153-162．DOI：10.2147/HIV.S30948.
［55］KHALIL S，MIRDHA B R，SINHA S，et al．Intestinal parasitosis in relation to anti-retroviral therapy，CD4（+）T-cell count and diarrhea in HIV patients［J］．Korean J Parasitol，2015，53（6）：705-712．DOI：10.3347/kjp.2015.53.6.705.
［56］STEIN A，VOIGT W，JORDAN K.Review：chemotherapy-induced diarrhea：pathophysiology，frequency and guideline-based management［J］．Ther Adv Med Oncol，2010，2（1）：51-63．DOI：10.1177/1758834009355164.
［57］REDMAN M G，WARD E J，PHILLIPS R S.The efficacy and safety of probiotics in people with cancer：a systematic review［J］．Ann Oncol，2014，25（10）：1919-1929．DOI：10.1093/annonc/mdu106.
［58］LIAPIS G，BOLETIS J，SKALIOTI C，et al．Histological spectrum of mycophenolate mofetil-related colitis：association with apoptosis［J］．Histopathology，2013，63（5）：649-658．DOI：10.1111/his.12222.
［59］ROBAK K，ZAMBONELLI J，BILINSKI J，et al．Diarrhea after allogeneic stem cell transplantation：beyond graft-versus-host disease［J］．Eur J Gastroenterol Hepatol，2017，29（5）：495-502．DOI：10.1097/MEG.0000000000000833.
［60］MURALI A R，CHANDRA S，STEWART Z，et al．Graft versus host disease after liver transplantation in adults：a case series，review of literature，and an approach to management［J］．Transplantation，2016，100（12）：2661-2670．DOI：10.1097/TP.0000000000001406.
［61］KAISER L，SURAWICZ C M.Infectious causes of chronic diarrhoea［J］．Best Pract Res Clin Gastroenterol，2012，26（5）：563-571．DOI：10.1016/j.bpg.2012.11.001.
［62］SCHWILLE-KIUNTKE J，MAZURAK N，ENCK P.Systematic review with meta-analysis：post-infectious irritable bowel syndrome after travellers' diarrhoea［J］．Aliment Pharmacol Ther，2015，41（11）：1029-1037．DOI：10.1111/apt.13199.
［63］CHENG H C.Hookworm infestation diagnosed by capsule endoscopy［J］．J Gastrointest Dig Syst，2011（s1）：s3．DOI：10.4172/2161-069x.s1-003.
［64］DEESOMSAK M，SAWANYAWISUTH K，PRACHAYAKUL V.An unusual cause of chronic diarrhoea［J］．Tropical Biomedicine，2014，31（1）：187-189.
［65］XIE C，LI J，WANG K，et al．Probiotics for the prevention of antibiotic-associated diarrhoea in older patients：a systematic review［J］．Travel Medicine & Infectious Disease，2015，13（2）：128-134．DOI：10.1016/j.tmaid.2015.03.001.
［66］VIDELOCK E J，CREMONINI F.Meta-analysis：probiotics in antibiotic-associated diarrhoea［J］．Alimentary Pharmacology & Therapeutics，2012，35（12）：1355-1369．DOI：10.1111/j.1365-2036.2012.05104.x.

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