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Chronic Diarrhea: Diagnosis and Management

2016; Elsevier BV; Volume: 15; Issue: 2 Linguagem: Inglês

10.1016/j.cgh.2016.07.028

1542-7714

Lawrence R. Schiller, Darrell S. Pardi, Joseph H. Sellin,

Gastrointestinal motility and disorders

Chronic diarrhea is a common problem affecting up to 5% of the population at a given time. Patients vary in their definition of diarrhea, citing loose stool consistency, increased frequency, urgency of bowel movements, or incontinence as key symptoms. Physicians have used increased frequency of defecation or increased stool weight as major criteria and distinguish acute diarrhea, often due to self-limited, acute infections, from chronic diarrhea, which has a broader differential diagnosis, by duration of symptoms; 4 weeks is a frequently used cutoff.Symptom clusters and settings can be used to assess the likelihood of particular causes of diarrhea. Irritable bowel syndrome can be distinguished from some other causes of chronic diarrhea by the presence of pain that peaks before defecation, is relieved by defecation, and is associated with changes in stool form or frequency (Rome criteria).Patients with chronic diarrhea usually need some evaluation, but history and physical examination may be sufficient to direct therapy in some. For example, diet, medications, and surgery or radiation therapy can be important causes of chronic diarrhea that can be suspected on the basis of history alone. Testing is indicated when alarm features are present, when there is no obvious cause evident, or the differential diagnosis needs further delineation. Testing of blood and stool, endoscopy, imaging studies, histology, and physiological testing all have roles to play but are not all needed in every patient. Categorizing patients after limited testing may allow more directed testing and more rapid diagnosis.Empiric antidiarrheal therapy can be used to mitigate symptoms in most patients for whom a specific treatment is not available. Chronic diarrhea is a common problem affecting up to 5% of the population at a given time. Patients vary in their definition of diarrhea, citing loose stool consistency, increased frequency, urgency of bowel movements, or incontinence as key symptoms. Physicians have used increased frequency of defecation or increased stool weight as major criteria and distinguish acute diarrhea, often due to self-limited, acute infections, from chronic diarrhea, which has a broader differential diagnosis, by duration of symptoms; 4 weeks is a frequently used cutoff. Symptom clusters and settings can be used to assess the likelihood of particular causes of diarrhea. Irritable bowel syndrome can be distinguished from some other causes of chronic diarrhea by the presence of pain that peaks before defecation, is relieved by defecation, and is associated with changes in stool form or frequency (Rome criteria). Patients with chronic diarrhea usually need some evaluation, but history and physical examination may be sufficient to direct therapy in some. For example, diet, medications, and surgery or radiation therapy can be important causes of chronic diarrhea that can be suspected on the basis of history alone. Testing is indicated when alarm features are present, when there is no obvious cause evident, or the differential diagnosis needs further delineation. Testing of blood and stool, endoscopy, imaging studies, histology, and physiological testing all have roles to play but are not all needed in every patient. Categorizing patients after limited testing may allow more directed testing and more rapid diagnosis. Empiric antidiarrheal therapy can be used to mitigate symptoms in most patients for whom a specific treatment is not available. This clinical perspective addresses the definition, pathogenesis, diagnosis, and treatment of chronic diarrhea, which is based on a systematic review produced for the World Congress of Gastroenterology in 20131Schiller L.R. Pardi D.S. Spiller R. et al.Gastro 2013 APDW/WCOG Shanghai working party report: chronic diarrhea—definition, classification, diagnosis.J Gastroenterol Hepatol. 2014; 29: 6-25Crossref PubMed Scopus (43) Google Scholar and updated by the authors in 2016. Fifteen clinical questions are posed, followed by 24 recommendations pertinent to those questions with supporting evidence. In many instances there is not high-quality evidence to support the recommendations, and that is noted. A search of PubMed for the years from 1975 to 2015 was conducted by using the following major search terms and subheadings including “diarrhea,” “stool analysis,” “irritable bowel syndrome,” “chronic diarrhea AND diagnosis,” “chronic diarrhea AND therapy,” and “breath tests.” Systematic reviews and meta-analyses were given priority for each topic when available, followed by clinical trial evidence. The GRADE system was used to evaluate the strength of the recommendations and the overall quality of evidence.2Atkins D. Best D. Briss P.A. et al.Grading quality of evidence and strength of recommendations.BMJ. 2004; 328: 1490Crossref PubMed Google Scholar A recommendation was graded as “strong” when the desirable effects of an intervention clearly outweigh the undesirable effects and as “conditional” when there is uncertainty about the tradeoffs. The quality of evidence ranged from “high” (implying that further research is unlikely to change the authors’ confidence in the conclusion or in the estimate of the effect) to “moderate” (further research is unlikely to have an effect on the conclusion but might have an impact on the estimate of effect) or “low” (further research would be expected to have an important impact on the estimate of the effect or might change the conclusion altogether). For each recommendation, strength is abbreviated as “1” (strong) or “2” (conditional) and quality of evidence as “a” (high), “b” (moderate), or “c” (low). 1.Patients define diarrhea as loose stools, increased stool frequency, or urgency; physicians should note precisely what the patient means. (1b)2.Chronic diarrhea is defined by a duration of >4 weeks. (2b) Diarrhea can refer to urgency or high stool frequency, although most patients use the term to describe changes in consistency (loose or watery stools).3Lacy B.E. Mearin F. Chang L. et al.Bowel disorders.Gastroenterology. 2016; 150: 1393-1407Abstract Full Text Full Text PDF Scopus (1535) Google Scholar In fact, frequent defecation with normal consistency is termed pseudodiarrhea; therefore, abnormal stool form and not frequency should be used to define diarrhea. Most diarrheal episodes in developed countries are acute and self-limited and are usually due to infections. In immunocompetent patients, acute infectious diarrhea typically resolves within 4 weeks (most commonly within 1 week). Therefore, chronic diarrhea is defined as that lasting longer than 4 weeks. It is estimated that 1%–5% of adults suffer from chronic diarrhea.4Schiller L.R. Chronic diarrhea.Gastroenterology. 2004; 127: 287-293Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar In immunocompetent patients in developed countries, chronic diarrhea is generally not infectious. The challenge in managing these patients is the fact that the differential diagnosis is vast. However, a careful history and thorough physical examination with judicious use of selected tests often lead to a specific diagnosis and an appropriate treatment plan. 3.Consider comorbid symptoms and epidemiologic clues when constructing a differential diagnosis. (2c) The main distinction in patients with chronic diarrhea is between functional and organic etiologies. The functional category includes irritable bowel syndrome (IBS), when abdominal pain accompanies the diarrhea, and functional diarrhea, when abdominal pain is absent.3Lacy B.E. Mearin F. Chang L. et al.Bowel disorders.Gastroenterology. 2016; 150: 1393-1407Abstract Full Text Full Text PDF Scopus (1535) Google Scholar IBS can be prospectively characterized by symptoms such as those defined by the Rome IV criteria (recurrent abdominal pain at least 3 days per month in the last 3 months, associated with a change in stool frequency or form, and improvement with defecation).3Lacy B.E. Mearin F. Chang L. et al.Bowel disorders.Gastroenterology. 2016; 150: 1393-1407Abstract Full Text Full Text PDF Scopus (1535) Google Scholar Functional diarrhea is defined as similar stool changes without prominent pain.3Lacy B.E. Mearin F. Chang L. et al.Bowel disorders.Gastroenterology. 2016; 150: 1393-1407Abstract Full Text Full Text PDF Scopus (1535) Google Scholar However, many patients with organic causes of chronic diarrhea such as microscopic colitis often fulfill these criteria.5Limsui D. Pardi D.S. Camilleri M. et al.Symptomatic overlap between irritable bowel syndrome and microscopic colitis.Inflamm Bowel Dis. 2007; 13: 175-181Crossref PubMed Scopus (114) Google Scholar Therefore, these criteria are not sufficiently specific to rule out organic etiologies. However, for patients with relatively mild symptoms and no alarm features such as gastrointestinal (GI) bleeding, fevers, or significant weight loss, those meeting the Rome IV criteria for IBS or functional diarrhea can be managed with empiric therapy. If empiric therapy fails, then further diagnostic testing may be considered. Other symptom clusters can also be helpful in suggesting a specific diagnosis. Significant abdominal pain, fever, or GI bleeding suggests an inflammatory cause for diarrhea. Gas and bloating suggest carbohydrate malabsorption. Substantial weight loss suggests malabsorption, maldigestion, or a malignancy (particularly in an older person). Fatigue and night sweats suggest lymphoma, whereas anemia or change in stool caliber suggests colorectal malignancy. The positive predictive values of these symptoms for the underlying problems causing chronic diarrhea are unknown but likely are low. Physical findings can indicate the impact of diarrhea on nutrition and sometimes suggest a specific diagnosis (Supplementary Table 1). The characteristics of the stool also help. Small, frequent bowel movements with tenesmus and bleeding suggest proctitis, whereas larger volume, less frequent stools suggest a small bowel source of diarrhea. Steatorrhea indicates either fat maldigestion or malabsorption. Epidemiologic associations and patient characteristics also help limit the differential diagnosis6Schiller L.R. Sellin J.H. Diarrhea.in: Feldman M. Friedman L. Brandt L.J. Sleisenger and Fordtran's gastrointestinal and liver disease. 10th ed. Saunders Elsevier, Philadelphia2015: 211-232Google Scholar (Supplementary Table 2). Immunosuppressed patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome are at increased risk for common and uncommon, opportunistic infections. Recent travelers and migrants from endemic areas with chronic diarrhea should be tested for protozoa, atypical infections, Strongyloides, and tropical sprue. In patients with a history of constipation, the possibility of overflow diarrhea due to obstipation should be considered, especially if diarrhea worsens despite antidiarrheal therapy. Patients with diabetes or those attempting to lose weight should be questioned about consumption of diet foods containing poorly absorbed sugar alcohols. 4.The Rome criteria provide a framework for the diagnosis of IBS and emphasize pain. Other etiologies should be sought when these criteria are not met. (1a)5.Patients without alarm features who meet criteria for IBS should be treated without further testing. Those who do not respond should be evaluated further. (2b) Criteria have been proposed to distinguish IBS from organic diseases; however, the utility of these criteria is only partially understood at present.3Lacy B.E. Mearin F. Chang L. et al.Bowel disorders.Gastroenterology. 2016; 150: 1393-1407Abstract Full Text Full Text PDF Scopus (1535) Google Scholar The Rome criteria emphasize chronic abdominal pain that is relieved by defecation, associated with a change in stool frequency or consistency.3Lacy B.E. Mearin F. Chang L. et al.Bowel disorders.Gastroenterology. 2016; 150: 1393-1407Abstract Full Text Full Text PDF Scopus (1535) Google Scholar IBS with diarrhea is diagnosed in patients who meet these criteria and have loose stools more than 25% of the time and hard stools less than 25% of the time. The specificity of symptom-based criteria for the diagnosis of IBS versus other colonic pathology is only moderate (∼75%),7Mearin F. Lacy B.E. Diagnostic criteria in IBS: useful or not?.Neurogastroenterol Motil. 2012; 24: 791-801Crossref PubMed Scopus (34) Google Scholar, 8Jellema P. van der Windt D.A. Schellevis F.G. et al.Systematic review: accuracy of symptom-based criteria for diagnosis of irritable bowel syndrome in primary care.Aliment Pharmacol Ther. 2009; 30: 695-706Crossref PubMed Scopus (76) Google Scholar, 9Whitehead W.E. Drossman D.A. Validation of symptom-based diagnostic criteria for irritable bowel syndrome: a critical review.Am J Gastroenterol. 2010; 105: 814-820Crossref PubMed Scopus (86) Google Scholar but the incorporation of alarm features can improve specificity to ∼90%.9Whitehead W.E. Drossman D.A. Validation of symptom-based diagnostic criteria for irritable bowel syndrome: a critical review.Am J Gastroenterol. 2010; 105: 814-820Crossref PubMed Scopus (86) Google Scholar However, the predictive value of symptoms in identifying organic disease is less than 10%.10Whitehead W.E. Palsson O.S. Feld A.D. et al.Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome.Aliment Pharmacol Ther. 2006; 24: 137-146Crossref PubMed Scopus (88) Google Scholar The performance of symptom-based criteria was highly variable and might not be able to reliably distinguish IBS from other diseases.8Jellema P. van der Windt D.A. Schellevis F.G. et al.Systematic review: accuracy of symptom-based criteria for diagnosis of irritable bowel syndrome in primary care.Aliment Pharmacol Ther. 2009; 30: 695-706Crossref PubMed Scopus (76) Google Scholar Thus, symptoms may be more useful in identifying patients requiring additional evaluation than in identifying patients with organic illnesses.11Cash B.D. Chey W.D. Diagnosis of irritable bowel syndrome.Gastroenterol Clin North Am. 2005; 34: 205-220Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Because functional diarrheal problems are so common, the pretest probability of organic disease is low, suggesting that an extensive diagnostic evaluation is not needed in most patients.8Jellema P. van der Windt D.A. Schellevis F.G. et al.Systematic review: accuracy of symptom-based criteria for diagnosis of irritable bowel syndrome in primary care.Aliment Pharmacol Ther. 2009; 30: 695-706Crossref PubMed Scopus (76) Google Scholar, 12Spiegel B.M. Farid M. Esrailian E. et al.Is irritable bowel syndrome a diagnosis of exclusion? a survey of primary care providers, gastroenterologists, and IBS experts.Am J Gastroenterol. 2010; 105: 848-858Crossref PubMed Scopus (139) Google Scholar Diagnostic tests such as radiography, serology, and biochemistries are generally not helpful in patients who meet criteria for IBS.13O'Connor O.J. McSweeney S.E. McWilliams S. et al.Role of radiologic imaging in irritable bowel syndrome: evidence-based review.Radiology. 2012; 262: 485-494Crossref PubMed Scopus (24) Google Scholar, 14Lembo A.J. Neri B. Tolley J. et al.Use of serum biomarkers in a diagnostic test for irritable bowel syndrome.Aliment Pharmacol Ther. 2009; 29: 834-842Crossref PubMed Scopus (77) Google Scholar One area of uncertainty is testing for celiac disease (CD). One meta-analysis suggested that the prevalence of CD in patients meeting criteria for IBS was more than 4-fold that of controls without IBS,15Ford A.C. Chey W.D. Talley N.J. et al.Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis.Arch Intern Med. 2009; 169: 651-658Crossref PubMed Scopus (204) Google Scholar whereas a more recent study showed no increased prevalence of CD in patients presenting with IBS.16Cash B.D. Rubenstein J.H. Young P.E. et al.The prevalence of celiac disease among patients with nonconstipated irritable bowel syndrome is similar to controls.Gastroenterology. 2011; 141: 1187-1193Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar Likewise, microscopic colitis may be present in 1.5%–10% of patients meeting criteria for IBS17Guagnozzi D. Lucendo A.J. Angueira-Lapena T. et al.Prevalence and incidence of microscopic colitis in patients with diarrhoea of unknown aetiology in a region in central Spain.Dig Liver Dis. 2012; 44: 384-388Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 18Chey W.D. Nojkov B. Rubenstein J.H. et al.The yield of colonoscopy in patients with non-constipated irritable bowel syndrome: results from a prospective, controlled US trial.Am J Gastroenterol. 2010; 105: 859-865Crossref PubMed Scopus (130) Google Scholar and even higher in older patients. The yield of tests for small intestinal bacterial overgrowth (SIBO) is quite variable.19Bratten J.R. Spanier J. Jones M.P. Lactulose breath testing does not discriminate patients with irritable bowel syndrome from healthy controls.Am J Gastroenterol. 2008; 103: 958-963Crossref PubMed Scopus (135) Google Scholar 6.Specific dietary components may cause or aggravate chronic diarrhea. A careful dietary history is essential. (1a)7.True food allergies are rare causes of chronic diarrhea in adults. (2b) Specific foods and diets are often incriminated as causes of diarrhea, some with good evidence and others less so.20Schiller L.R. Nutrition management of chronic diarrhea and malabsorption.Nutrition in Clinical Practice. 2006; 21: 34-39Crossref PubMed Scopus (7) Google Scholar In considering associations with foods, one must consider (1) substances that in sufficient quantities cause diarrhea in a normal gut (eg, fructose), (2) foods that cause diarrhea because of an underlying condition (eg, dairy products in lactase deficiency), (3) gut alterations that limit digestion or absorption (eg, short bowel, pancreatic insufficiency), and (4) idiosyncratic food intolerances. The identification of a dietary cause of diarrhea may be facilitated by a food diary. Poorly absorbed carbohydrates are commonly linked to diarrhea.20Schiller L.R. Nutrition management of chronic diarrhea and malabsorption.Nutrition in Clinical Practice. 2006; 21: 34-39Crossref PubMed Scopus (7) Google Scholar For example, fructose is absorbed by facilitated diffusion with limited capacity; when the amount ingested exceeds that capacity, malabsorption and diarrhea may occur. Disaccharides must be split by disaccharidases such as sucrase or lactase, which may be insufficient because of mucosal disease or genetic downregulation. Unabsorbed carbohydrates lead to osmotic retention of fluid in the intestine and bacteria fermentation to gases. Therefore, flatus and bloating are important clues suggesting carbohydrate malabsorption. For many clinicians, concurrent diarrhea and bloating are taken as evidence of IBS, missing the opportunity to diagnose diet-induced diarrhea. Lactose is a common cause of diet-induced diarrhea.21Mattar R. de Campos Mazo D.F. Carrilho F.J. Lactose intolerance: diagnosis, genetic, and clinical factors.Clin Exp Gastroenterol. 2012; 5: 113-121Crossref PubMed Scopus (140) Google Scholar Worldwide, most adults are lactose-intolerant and learn to avoid dairy products. Inadvertent lactose ingestion can occur from commercial foods fortified with milk. Lactose intolerance also can develop if the mucosa is diseased or bypassed. Fructose is found in certain fruits, and it is difficult to exceed absorptive capacity with natural foods. However, high fructose corn syrup is widely used as a sweetener in processed foods and soft drinks, leading to a striking increase in fructose intake,22Vos M.B. Kimmons J.E. Gillespie C. et al.Dietary fructose consumption among US children and adults: the Third National Health and Nutrition Examination Survey.Medscape J Med. 2008; 10: 160PubMed Google Scholar which makes it easier to exceed the absorptive capacity of the gut. Sugar alcohol malabsorption also is increasingly recognized as a cause of diarrhea. Sorbitol, mannitol, and xylitol are poorly absorbed non-nutritive sweeteners in items such as “sugar-free” chewing gum and candy; excessive intake may cause diarrhea.23Fernandez-Banares F. Esteve M. Viver J.M. Fructose-sorbitol malabsorption.Curr Gastroenterol Rep. 2009; 11: 368-374Crossref PubMed Scopus (33) Google Scholar The recognition that these carbohydrates can cause diarrhea and other symptoms led to development of the Fermentable Oligosaccharides, Disaccharides Monosaccharides and Polyols (FODMAP) diet.24Shepherd S.J. Lomer M.C. Gibson P.R. Short-chain carbohydrates and functional gastrointestinal disorders.Am J Gastroenterol. 2013; 108: 707-717Crossref PubMed Scopus (206) Google Scholar In a randomized trial, a FODMAP diet alleviated intestinal symptoms in 75% of IBS patients.25Shepherd S.J. Parker F.C. Muir J.G. et al.Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence.Clin Gastroenterol Hepatol. 2008; 6: 765-771Abstract Full Text Full Text PDF PubMed Scopus (430) Google Scholar It is important to carefully quantify the amount of caffeine consumed in coffee and energy drinks.26Wagner S.M. Mekhjian H.S. Caldwell J.H. et al.Effects of caffeine and coffee on fluid transport in the small intestine.Gastroenterology. 1978; 75: 379-381Abstract Full Text PDF PubMed Scopus (26) Google Scholar The diagnosis of CD is based on symptoms, serology, and intestinal histology.27Rubio-Tapia A. Hill I.D. Kelly C.P. et al.ACG clinical guidelines: diagnosis and management of celiac disease.Am J Gastroenterol. 2013; 108: 656-676Crossref PubMed Scopus (1164) Google Scholar It has become clear that CD can present with a wider range of symptoms than previously appreciated. Recently, it has been recognized that “gluten responsive symptoms” can be present in the absence of positive serologies or with less severe pathologic criteria (Marsh 1/2).28Biesiekierski J.R. Newnham E.D. Irving P.M. et al.Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.Am J Gastroenterol. 2011; 106: 508-514Crossref PubMed Scopus (600) Google Scholar Non-celiac gluten sensitivity requires additional research, but it seems likely that gluten-free diets may benefit a broader segment of the population than previously thought. Most patients with chronic diarrhea should be screened for CD. It is less clear when a gluten-free diet should be tried in patients with diarrhea who do not have CD.29Verdu E.F. Armstrong D. Murray J.A. Between celiac disease and irritable bowel syndrome: the “no man's land” of gluten sensitivity.Am J Gastroenterol. 2009; 104: 1587-1594Crossref PubMed Scopus (248) Google Scholar Fatty and fried foods frequently are implicated in the pathogenesis of diarrhea and other symptoms.30Bohn L. Storsrud S. Tornblom H. et al.Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life.Am J Gastroenterol. 2013; 108: 634-641Crossref PubMed Scopus (394) Google Scholar Although fat malabsorption stimulates colonic secretion to cause diarrhea,31Ramakrishna B.S. Mathan M. Mathan V.I. Alteration of colonic absorption by long-chain unsaturated fatty acids: influence of hydroxylation and degree of unsaturation.Scand J Gastroenterol. 1994; 29: 54-58Crossref PubMed Scopus (31) Google Scholar it seems that fat may precipitate symptoms without demonstrable steatorrhea. Food allergies are immune reactions that may cause diarrhea and other symptoms. Food intolerances are not immune-based and are more common.32Boyce J.A. Assa'ad A. Burks A.W. et al.Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.J Allergy Clin Immunol. 2010; 126: S1-S58PubMed Google Scholar Epidemiologic studies suggest that 1%–2% of adults have bona fide food allergy.33Bischoff S. Crowe S.E. Gastrointestinal food allergy: new insights into pathophysiology and clinical perspectives.Gastroenterology. 2005; 128: 1089-1113Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar The frequency in children is higher.34Nowak-Wegrzyn A. Conover-Walker M.K. Wood R.A. Food-allergic reactions in schools and preschools.Arch Pediatr Adolesc Med. 2001; 155: 790-795Crossref PubMed Scopus (162) Google Scholar Certain foods more frequently trigger allergic reactions. Recent studies have linked banana, avocado, walnut, and kiwi to a latex–food allergy syndrome.35Yagami T. Allergies to cross-reactive plant proteins: latex-fruit syndrome is comparable with pollen-food allergy syndrome.Int Arch Allergy Immunol. 2002; 128: 271-279Crossref PubMed Scopus (73) Google Scholar Although true food allergy is uncommon in adults, it should be considered when other allergic features are present such as hives. Some food-allergic patients have elevated tryptase and eosinophilic cationic protein; however, fecal calprotectin is not elevated.33Bischoff S. Crowe S.E. Gastrointestinal food allergy: new insights into pathophysiology and clinical perspectives.Gastroenterology. 2005; 128: 1089-1113Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar, 36Simren M. Mansson A. Langkilde A.M. et al.Food-related gastrointestinal symptoms in the irritable bowel syndrome.Digestion. 2001; 63: 108-115Crossref PubMed Scopus (410) Google Scholar 8.Many drugs cause diarrhea. Careful review of current medications is essential. (1a) More than 700 drugs have been implicated as causing diarrhea, accounting for approximately 7% of drug adverse effects.37Chassany O. Michaux A. Bergmann J.F. Drug-induced diarrhoea.Drug Safety. 2000; 22: 53-72Crossref PubMed Scopus (146) Google Scholar The mechanism by which some drugs cause diarrhea is unknown.38Abraham B.P. Sellin J.H. Drug-induced, factitious, and idiopathic diarrhoea.Best Pract Res Clin Gastroenterol. 2012; 26: 633-648Crossref PubMed Scopus (28) Google Scholar Some patients produce factitious diarrhea by taking laxatives. Osmotic agents usually produce typical changes on fecal electrolyte analysis. Laxatives producing secretory diarrhea may be detected in stool water by toxicologic tests. The key to diagnosis is keeping the possibility of factitious diarrhea in mind when the diagnosis is not forthcoming by routine testing, especially when the patient experiences a secondary gain from the illness.38Abraham B.P. Sellin J.H. Drug-induced, factitious, and idiopathic diarrhoea.Best Pract Res Clin Gastroenterol. 2012; 26: 633-648Crossref PubMed Scopus (28) Google Scholar 9.Radiation can cause chronic diarrhea, sometimes starting years after exposure. Clinicians should ask about a history of radiation therapy. (1a)10.Patients with chronic diarrhea who have had abdominal surgery may require empiric therapy or diagnostic evaluation. (1a) Radiation enteritis occurs in up to 20% of patients treated with pelvic irradiation, typically 1.5–6 years after irradiation, although later presentations are possible.39Theis V.S. Sripadam R. Ramani V. et al.Chronic radiation enteritis.Clin Oncol (R Coll Radiol). 2010; 22: 70-83Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar Risk factors include low body mass index, prior abdominal surgery, certain comorbidities, radiation dose, fractionation, and technique, as well as the concomitant chemotherapy.39Theis V.S. Sripadam R. Ramani V. et al.Chronic radiation enteritis.Clin Oncol (R Coll Radiol). 2010; 22: 70-83Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar Radiation enteritis is caused by direct damage to enterocytes and ischemia that is due to blood vessel damage. Submucosal fibrosis and lymphatic damage are commonly seen. The damaged bowel loses absorptive capacity and is predisposed to SIBO, particularly if strictures develop. If the distal ileum is involved, bile acid malabsorption (BAM) can be present. SIBO and BAM are discussed in more detail below. GI surgeries can lead to diarrhea that is due to intentional or inadvertent vagotomy, SIBO, BAM, and short bowel syndrome (SBS). Truncal vagotomy results in rapid gastric emptying of liquids and diarrhea.40Mahvi K.S. Stomach.in: Townsend C.M. Evers B.M. Mattox K.L. Sabiston textbook of surgery. 19th ed. Elsevier, Philadelphia2012Crossref Google Scholar The incidence of diarrhea is increased if vagotomy is accompanied by antrectomy and decreased after highly selective vagotomy without antrectomy.40Mahvi K.S. Stomach.in: Townsend C.M. Evers B.M. Mattox K.L. Sabiston textbook of surgery. 19th ed. Elsevier, Philadelphia2012Crossref Google Scholar In health, the bacterial count in the proximal jejunum is 105/mL.41Bures J. Cyrany J. Kohoutova D. et al.Small intestinal bacterial overgrowth syndrome.World J Gastroenterol. 2010; 16: 2978-2990Crossref PubMed Scopus (399) Google Scholar Abdominal surgery predisposes to SIBO through disruption of the protective effect of stomach acid (eg, after vagotomy), stasis (eg, with an anastomotic stricture or partial bowel obstruction from adhesions), a blind limb (such as with an end-to-side anastomosis), or removal of the ileocecal valve. Bacterial overgrowth causes diarrhea by bile acid deconjugation, interfering with enzymatic action, and damage to the mucosa.41Bures J. Cyrany J. Kohoutova D. et al.Small intestinal bacterial overgrowth syndrome.World J Gastroenterol. 2010; 16: 2978-2990Crossref PubMed Scopus (399) Google Scholar Bacterial overgrowth can be difficult to diagnose, because available tests are invasive and expensive (aspiration and culture of jejunal fluid) or have inadequate sensitivity and specificity (various breath tests).42Quigley E.M. Abu-Shanab A. Small intestinal bacterial overg