1. BSG Guidelines (2003) for the Investigation of Chronic Diarrhoea

2. Definition Chronic diarrhoea may be defined as the abnormal passage of three or more loose or liquid stools per day for more than four weeks and/or a daily stool weight greater than 200 g/day.

3. Prevalence Talley et al reported a prevalence of chronic diarrhoea of between 7% and 14% in an elderly population estimates of the prevalence of chronic diarrhoea in a Western population are of the order of 4–5%

4. Algorithm for investigation of chronic diarrhoea

5. Causes of chronic diarrhoea Colonic Colonic neoplasia Ulcerative and Crohns colitis Microscopic colitis Small bowel Coeliac disease Crohns disease Other small bowel enteropathies (for example, Whipples disease, tropical sprue, amyloid, intestinal lymphangiectasia) Bile acid malabsorption Disaccharidase deficiency Small bowel bacterial overgrowth Mesenteric ischaemia Radiation enteritis Lymphoma Giardiasis (and other chronic infection)

6. Causes of Chronic Diarhoea Pancreatic Chronic pancreatitis Pancreatic carcinoma Cystic fibrosis Endocrine Hyperthyroidism Diabetes Hypoparathyroidism Addisons disease Hormone secreting tumours (VIPoma, gastrinoma, carcinoid) Other Factitious diarrhoea Surgical causes (e.g. small bowel resections, internal fistulae) Drugs Alcohol Autonomic neuropathy

7. Initial investigations History and Examination Aim to establish: (a) organic vs functional, (b) malabsorptive vs colonic/inflammatory forms of diarrhoea (c) to assess for specific causes of diarrhoea.

8. Symptoms of Organic Disease less than three months duration, Predominantly nocturnal or continuous (as opposed to intermittent) diarrhoea, significant weight loss.

9. Functional Disease The absence of symptoms of organic disease, in conjunction with positive symptoms such as those defined in the Manning or Rome criteria and a normal physical examination, are suggestive of a functional bowel disturbance, but only with a specificity of approximately 52–74%. Unfortunately, these criteria do not reliably exclude inflammatory bowel disease.

10. MalabsorptionColonic/Inflam mtory steatorrhoealiquid loose stools with blood bulky malodorous pale stools mucous discharge Inspection of the stool may be helpful in distinguishing these two

11. Risk Factors for Organic Disease Family history. Particularly of neoplastic, inflammatory bowel, or coeliac disease. Previous surgery. Previous Pancreatic disease Systemic disease i.e. Thyrotoxicosis/parathyroid disease Alcohol Drugs Recent overseas travel or other potential sources of infectious gastrointestinal pathogens Recent antibiotic therapy and Clostridium difficile infection Lactase deficiency

12. Basic Investigations FBC U and Es liver function tests, including albumin vitamin B12 and folate, calcium, ferritin, ESR and CRP TFTs Coeliac screen- EMA (anti endomysial antibodies), Anti TTG (anti tissue tranglutaminase )

13. Stool Tests Inspection of stool Stool collection - 24-48hrs If less than 200g/day, no further investigations may be warranted Stool cultures Protozoan, giardasis and amoebiasis ELISA for giardiasis Stool osmolality – limited use may help in differentiating secretory and osmotic diarrhoea

14. Functional Disease Symptoms suggestive of Functional disease < 45 years Normal basic investigations Diagnosis = Irritable bowel syndrome

15. Factitious Diarrhoea a common cause of reported chronic diarrhoeal symptoms in Western populations. Due to laxative abuse adding of water or urine to stool specimens Up to 20% of patients that are seen in tertiary centres. Often underlying psychiatric hx such as eating disorders High index of suspicion

16. Colonic/Terminal Ileal Disease Flexible Sigmoidoscopy Recommended in patients under 45 because covers most pathology in this age group Allows assessment and sampling of sigmoid and descending colon In a study (n=809) of non HIV Non bloody chronic diarrhoea it was demonstrated that 15% of patients had colonic pathology 99.7% of these diagnoses could have been made from biopsies of the distal colon using a flexible sigmoidoscope, primary diagnoses being microscopic colitis, Crohns disease, melanosis coli, and ulcerative colitis.

17. Colonic/Terminal Ileal Disease Colonoscopy Recommended in patients over 45 years old Diarrhoea may be caused by colorectal neoplasia One study showed prevalence of colonic neoplasms of 27% in those patients undergoing colonoscopy for a change in bowel habit 50% of neoplasms are proximal to splenic flexture Higher diagnostic yield with ileoscopy particularly in IBD preferred modality to exclude or confirm microscopic colitis Barium Enemas useful in complementing colonoscopy but has lower sensitivity in detecting neoplasms

18. Colonic/Terminal Ileal Disease If colonoscopy and barium enema negative: Barium follow through – further imaging of terminal ileum and proximal colon in patients with negative findings on colonoscopy and biopsy Enteroclysis/Technetium scan ?Superseded by CT with contrast and video endoscopy

19. Malabsorption- Small Bowel Upper GI endoscopy with duodenal biopsies even in absence of EMA/TTG antibodies Small bowel imaging (barium follow through or enteroclysis) should be reserved for cases where small bowel malabsorption is suspected and distal duodenal histology is normal (C).

20. Malabsorption- Small Bowel If enteropathy (e.g. Whipples, tropical sprue amyloid)- Fat malabsorption – faecal elastase and EMA is superior to 3 day stool samples for fat measurement. Breath tests 14C-triolein absorption to measure fat absorption in high faecal fat content

21. Malabsorption- Pancreatic Severe pancreatic insufficiency with malabsorption is normally associated with pancreatic duct abnormalities. ERCP offers the greatest sensitivity for the diagnosis of ductal changes- (however since the publication of this guideline in 2003 practice has changed as mentioned below MRCP has replaced ERCP as diagnostic option) MRCP has the potential to replace ERCP as the imaging modality of choice and has the advantage of avoiding the risks associated with ERCP

22. Malabsorption- Pancreatic Urine tests such as the Pancreolauryl test and stool tests such as faecal elastase or chymotrypsin –poor sensitivity in mild/moderate pancreatic dysfunction Serum levels of pancreatic dysfunction are only affected in severe pancreatic dysfunction

23. Small bowel bacterial overgrowth Culture of small bowel aspirates is the most sensitive test for SBBO but methods are poorly standardised and positive results may not reflect clinically significant SBBO (B). Hydrogen breath tests have poor sensitivity but acceptable specificity, and are of value when a positive result is obtained. The glucose hydrogen breath test is recommended

24. Bile Acid Malabsorption Bile acid malabsorption (BAM) may occur when there isterminal ileal disease or resection. Measurement of serum 7 α hydroxy-4-cholesten-3-one is an effective test for this but is seldom performed. 75Se homotaurocholate (75Se-HCAT) testing is more widely available and is a sensitive measure In the absence of these tests a therapeutic trial of cholestyramine is sometimes employed as a test for the presence of BAM, but the validity of this approach has not been subject to study

25. Hormone Secreting Tumours Diarrhoea due to hormone secreting tumours is extremely rare and testing for the presence of excess vasoactive intestinal peptide, gastrin, or glucagon in plasma is recommended only in the presence of high volume watery diarrhoea when other causes of diarrhoea have been excluded

26. Summary History and examination extremely important Important to exclude functional diarrhoea with basic investigations and thorough history Coeliac serology tests should be done early in investigation In patients under the age of 45, flexible sigmoidoscopy is recommended In patients with one first degree relative with bowel neoplasm and above age of 45 warrant a colonoscopy

27. Summary Obvious deficiencies in the investigation of SBBO, pancreatic insufficiency, BAM Empirical therapy is often employed

28. Gut. 2003 July; 52(Suppl 5): v1–v15.Guidelines for the investigation of chronic diarrhoea, 2nd edition P Thomas, A Forbes, J Green, P Howdle, R Long, R Playford, M Sheridan, R Stevens, R Valori, J Walters, G Addison, P Hill, and G Brydon