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Dr Aditi Kumar
Professor Matthew Brookes
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract.1 Diarrhoea is the presenting complaint in the majority of patients, with 85% reporting it as their initial symptom.2 It can become confusing whether persistent diarrhoea is due to active IBD or other co-existing diseases, often leading physicians to believe that a patient has refractory IBD when they do not respond to standard IBD treatment.3 In this instance, measuring faecal calprotectin levels and comparing them with previous measurements during active disease can be useful to confirm active inflammation.4,5 A full list of potential causes of diarrhoea is given in Table 1. This article focuses on three common causes seen with stable IBD: bile acid malabsorption (BAM), small intestinal bacterial overgrowth (SIBO) and irritable bowel syndrome (IBS).
Table 1: Differential Diagnosis of Diarrhoea3
Enterohaemorrhagic Escherichia coli
Enterohaemorrhagic E coli
Small intestinal bacterial overgrowth
Bile acid malabsorption
Irritable bowel syndrome
(NSAIDs: non-steroidal anti-inflammatory drugs)
Bile acid malabsorption
There is a well-known association between BAM and diarrhoea accompanying other intestinal diseases. However, while BAM is a frequent condition, with an estimated prevalence of 4–5%,6 it is often neglected.2
Bile acids are produced from cholesterol in the liver and excreted into the small intestine to aid with fat digestion, after which 95% are absorbed in the terminal ileum.7 Thus, patients with a history of ileal disease or resection are at particular risk of developing diarrhoea.8 One study found that the incidence of BAM in patients with Crohn’s disease (CD) who had had an ileal resection was 97%, compared with and 54% those with CD and no resection.9 Another study estimated the prevalence of BAM in patients with resected CD to be >90% versus 11–52% in patients without ileal resection.6 Resection of <100 cm of the terminal ileum leads to mild BAM and can present with secretory diarrhoea. Severe BAM occurs when >100 cm of the terminal ileum is resected and can lead to fat maldigestion and steatorrhoea.3
SeHCAT testing is the gold standard diagnostic test for BAM, having high sensitivity of 80–90% and specificity of 70–100%.8 However, it is not widely available; it used in only 12 European countries and Canada, but is not used in the USA. This test is expensive test and is mostly available in tertiary centers.10 Consequently, many clinicians opt for an empirical trial of bile acid sequestrants, which is less time consuming and cheaper, although compliance can be variable.11 The full list of bile acid sequestrant treatment options is provided in Table 2. Smith et al.9 found that the response to bile acid sequestrants in patients with CD who had undergone ileal resection was 60% and in those without ileal resection was 40%. There was an estimated 70% response rate in people with a diagnosis of IBS with diarrhoea and a 64% response rate if patients had had previous gastric surgery (i.e. gallbladder removal).9
Table 2: Bile acid sequestrant prescribing options and appropriate dosing12
|Bile acid sequestrant||Dose||Availability||Side-effects|
|Colestyramine||4 g once daily, increased by 4 g weekly to a maximum dose of 36 g per day (1–4 divided doses)||Sachets||Unpleasant taste, constipation, nausea, borborygmus, flatulence, bloating, abdominal pain|
|Colestipol||5 g 1–2 times per day, increased by 5 g monthly to a maximum dose of 30 g per day||Sachets or tablets|
|Colesevelam*||625 mg 1–2 times per day, increased to three times per day maximum||Tablets||Constipation, gastrointestinal discomfort, headache, nausea, vomiting|
*Not currently licensed for use in BAM.12
Small Intestinal Bacterial Overgrowth
SIBO is characterised by excessive and/or abnormal microbiota in the small bowel.13 The most common symptom associated with SIBO is diarrhoea, followed by abdominal pain and then bloating.14 There is an increased prevalence of SIBO in patients with IBD, and it is commonly seen in patients with CD (18–30%).15 Risk factors include previous small bowel resection (especially involving resection of the ileocaecal valve), ileal involvement and the presence of fistulising or fibrostenosing disease.16 Risk does not appear to increase with disease activity or duration or with the use of immunotherapy.15,16
The gold standard for diagnosis is jejunal aspirate and culture, but there are several limitations to this investigation.17 It is time-consuming and expensive and has a high false-negative rate.17 Hydrogen breath testing is now more commonly used, as it is simple, cheap and non-invasive.14 However, it has a low sensitivity rate of 62.5% and specificity of 81.7%.15 Prior to the test, patients are required to go on a low-fibre diet for 24 hours and asked to avoid smoking, antibiotics, laxatives and exercise, as these can affect test accuracy.17 Most physicians opt for a therapeutic trial, taking clinical response to antibiotics as an affirmation of SIBO, although there is currently no consensus on the choice of antibiotic, dose or duration of treatment.18 As a result, clinical response rates range from 35% to 100%.13 Treatment with ciprofloxacin or rifaximin have both shown a 70% response rate, and a regimen with amoxicillin-clavulanic acid and cefoxitin has eradicated more than 90% of strains isolated from SIBO patients.15,16 Rifaximin is a popular choice as it is not absorbed, has few side-effects and shows little evidence of resistance. Regardless of the antibiotic choice, most patients will need to be re-treated, leading to long-term antibiotic use.19 Other management approaches to consider include treating the underlying disease or structural defect and correction of any nutritional deficiencies.19
Further information on SIBO is available in a British Society of Gastroenterology web education article.20
Irritable Bowel Syndrome
As per the Rome IV Diagnostic Criteria for IBS, patients must have had recurrent abdominal pain on average at least 1 day per week in the past 3 months, associated with two or more of the following:
- Defecation either increasing or improving pain
- Change in stool frequency
- Change in stool form (appearance).21
The global prevalence of IBS is 11.2%, with higher rates seen in females and individuals younger than 50 year.22 Patients with IBD can also develop IBS in the absence of any objective evidence of inflammation.23 In fact, 40% of IBD patients in remission may suffer from IBS-like symptoms. Prevalence of these is 33% in patients with ulcerative colitis and 42–57% in those with CD.24 The crucial difference between IBD and IBS is the lack of alarm symptoms, such as weight loss or rectal bleeding.3 Both conditions are associated with an equal magnitude of impairing psychological effects and reduced quality of life.25
Treatment options are varied and include antibiotics (rifaximin), antidiarrhoeals, antidepressants, antispasmodics and laxatives.3 Studies have shown that antidepressants have a greater efficacy than placebo in the improvement of somatic bowel symptoms.26 Dietary changes, such as maintaining a low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) diet, may also help with symptoms, and have been shown to have most benefit in patients with CD, in particular those who have a history of bowel surgery.27
Although IBS-like symptoms are common among IBD patients in remission, they may still reflect ongoing (albeit subclinical) activity of IBD, and their presence should always be initially interpreted as such.24 Until an IBD flare is excluded through laboratory tests and/or endoscopic evaluation with tissue diagnosis, the diagnosis should not simply be considered to be IBS.24
Diarrhoea is a common presenting feature in many different conditions and its presence can significantly reduce a patient’s quality of life.28 Clinicians are often challenged to interpret this symptom in patients with IBD who appear to be in remission.29 Although it is important to understand and consider other potential causes of diarrhoea in stable IBD, the first priority should always be to exclude the possibility of an acute IBD flare.24
- Loddo I, Romano C. Inflammatory bowel disease: genetics, epigenetics, and pathogenesis. Inflamm Bowel Dis 2015;6:1–6.
- Vitek, L. Bile acid malabsorption in inflammatory bowel disease. Inflamm Bowel Dis 2015;21:476–83.
- Chachu KA, Osterman MT. How to diagnose and treat IBD mimics in the refractory patient who does not have IBD. Inflamm Bowel Dis 2016;22:1262–74.
- Brookes MJ, Whitehead S, Gaya DR, et al. Practical guidance on the use of faecal calprotectin. Frontline Gastroenterol 2018;9:87–91.
- Brookes M, Gaya D, Hawthorne B. Updated guidance document on use of faecal calprotectin- both in assessment of GI symptoms, and also in patients with known IBD. 2016. Available at https://www.bsg.org.uk/resource/bsg-guidance-on-the-use-of-faecal-calprotectin-testing-in-ibd.html
- Barkun A, Love J, Gould M, et al. Bile acid malabsorption in chronic diarrhea: pathophysiology and treatment. Can J Gastroenterol 2013;11:653–59.
- Arasaradnam RA, Brown S, Forbes A, et al. Guidelines for the investigation of chronic diarrhoea in adults: British society of Gastroenterology, 3rd Edition. Gut 2018;67:1380–99.
- Pattni S, Walters JRF. Recent advances in the understanding of bile acid malabsorption. Br Med Bull 2009;92:79–93.
- Smith MJ, Cherian O, Raju GS, et al. Bile acid malabsorption in persistent diarrhoea. J R Coll Phys Lond 2000;34:448–51.
- Fani B, Bertani L, Paglianiti I, et al. Pros and cons of the SeHCAT test in bile acid diarrhoea: a more appropriate use of an old nuclear medicine technique. Gastroenterol Res Pract 2018;2018:2097359.
- Walters JRF. Pattni S. Managing bile acid diarrhoea. Ther Adv Gastroenterol 2010;3:349–57.
- NICE. SeHCAT (Tauroselcholic[75Selenium] acid) for the investigation of diarrhoea due to bile acid malabsorption in people with diarrhoea-predominant irritable bowel syndrome (IBS-D) or Crohns disease without ileal resection. 2012. Available at www.nice.org.uk/guidance/dg7
- Bures J, Cyrany J, Kohoutova D et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol 2010;16:2978–90.
- Grace E, Shaw C, Whelan K, et al. Review article: small intestinal bacterial overgrowth- prevalence, clinical features, current and developing diagnostic tests, and treatment. Aliment Pharmacol Ther 2013;38:674–88.
- Sachez-Montes C, Ortiz V, Bastida G, et al. Small intestinal bacterial overgrowth in inactive Crohns disease: influence of thiopurine and biological treatment. World J Gastroenterol 2014;20:13999–4003.
- Shah A, Morrison M, Burger D, et al. Systematic review with meta-analysis: the prevalence of small intestinal bacterial overgrowth in inflammatory bowel disease. Aliment Pharmacol Ther 2019;49:624–35.
- Simren M, Stotzer PO. Use and abuse of hydrogen breath tests. Gut 2006;55:297–303.
- Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth A comprehensive review. Gastroenterol Hepatol 2007;3:112–22.
- Sachdev AH, Pimentel M. Gastrointestinal bacterial overgrowth: pathogenesis and clinical significance. Ther Adv Chronic Des 2013;4:223–31.
- Andreyev J, Poon D. Management of difficult-to-treat small-intestinal bacterial overgrowth. Available at https://www.bsg.org.uk/education/web-education/difficult-clinical-scenarios/management-of-difficult-sibo.html
- Schmulson MJ, Drossman DA. What is new in Rome IV. J Neurogastroenterol Motil 2017;23:151–63.
- Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol 2012;10:712–21.
- Ishihara S, Kawashima K, Fukuba N, et al. Irritable bowel syndrome-like symptoms in ulcerative colitis patients in clinical remission: association with residual colonic inflammation. Digestion 2019;99:46–51.
- Keohane J, O’Mahoney C, O’Mahoney L, et al. Irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease: a real association or reflection of occult inflammation? Am J Gastroenterol 2010;105:1788.
- Gracie DJ, Williams CJ, Sood R, et al. Negative effects on psychological health and quality of life of genuine irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2017;15:376–84.
- Macer BJD, Prady SL, Mikocka-Walus A. Antidepressants in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis 2017;23:534–50.
- Pedersen N, Ankersen DV, Felding M, et al. Low-FODMAP diet reduces irritable bowel symptoms in patients with inflammatory bowel disease. World J Gastroenterol 2017;23:3356–66.
- Buono JL, Carson RT, Flores NM. Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea. Health Qual Life Outcomes 2017;15:35.
- Ryu KH, Huh KC. Irritable bowel syndrome in inflammatory bowel disease. Intest Res 2010;8:95–105.