1. Chronic Diarrhoea Dr Tien Huey Lim Gastroenterologist Middlemore Hospital & MacMurray Gastroenterology

2. Chronic Diarrhoea- Definition O Symptoms >4 weeks O Passage of 3 or more loose or liquid stools per day (or more frequent passage than is normal for the individual) or daily stool weight >200g/day O Prevalance: 7-14% in western population (Talley NJ, et al. Am J Epidemiol1992;136:165–77)

3. Common causes O Irritable bowel syndrome (IBS) O Inflammatory bowel disease (IBD) O Malabsorption O Lactose intolerance O Chronic pancreatitis O Celiac disease O Bacterial overgrowth of small intestine O Bile salt diarrhoea O Medication side effects

4. Chronic infections O Clostridium difficile O Aeromonas O Giardia O Cryptosporidium O Consider in patients with specific risk factors eg travel, HIV, antibiotic use, consumption of potentially contaminated drinking water

6. Guidelines for investigation O Aim: to maximise positive diagnoses whilst minimising number and invasiveness of investigations O Low threshold for use of colonoscopy in older subjects O Less need for extensive investigations where probability of benign disease is high eg young patients with functional symptoms

7. O Good history is vital O Symptoms that suggest organic bowel disease: O Diarrhoea within the last 3 months O Nocturnal diarrhoea O Continuous rather than intermittent diarrhoea, O Weight loss

8. Initial investigations O Screening blood tests should include FBC, CRP, U+E, LFTs, calcium, B12, folate, iron studies and thyroid function. These have high specificity but low sensitivity for presence of organic disease (B). O Although infectious diarrhoea is uncommon in immunocompetent patients from the developed world with chronic symptoms, stool for M+C+S should be performed (C).

9. O Coeliac disease is the most common small bowel enteropathy in Western populations. Patients with diarrhoea should be screened using serological tests (A). O Factitious diarrhoea is common, and screening for laxative abuse should be performed early in the course of investigation (B).

10. Guidelines (cont’d)… O In patients <45 years with typical symptoms of functional bowel disease, normal examination and screening blood tests, a positive diagnosis can be made with no further investigations required (C). O Patients <45 years with chronic diarrhoea and/or atypical symptoms should undergo flexible sigmoidoscopy in the first instance as diagnostic yield differs little from colonoscopy in this age group (B).

11. Guidelines (cont’d) O In patients >45 years, colonoscopy is preferred (B).

12. Pancreatic dysfunction O Quantification of 3 day fecal fat is poorly reproducible, unpleasant and non diagnostic, and its use should be discouraged (C). O Newer specific tests of pancreatic dysfunction, such as stool elastase, are preferred (B) (sensitivity 63%, 100% and 100% for mild, moderate and severe pancreatic insufficiency) O Treatment = Creon tds with meals

13. Lactose intolerance O Tests available in adults O Hydrogen breath test O Brush border enzyme levels (duodenal biopsy) O Practical test: glass of milk challenge + lactase capsules

14. Bile acid malabsorption O Occurs in 5-12% of patients post cholecystectomy O Also occurs post ileal resection O 2* to excessive bile acids O Treatment = cholestyramine

15. Tolerability of cholestyramine

17. Coeliac disease O Coeliac serology should be done in all cases O Anti-gliadin antibody test: O Sensitivity: 75-95% O Specificity: 80-95% O Anti-endomysial antibody: O Sensitivity: >90% O Specificity >97% O Transglutaminase antibody: O Sensitivity: >90% O Specificity >97% Beware IgA deficiency (1:200 prevalence)

18. Small bowel bacterial overgrowth O Bacterial concentrations in proximal jejunum in normal healthy state <10 4 cfu/mL (colon 10 9 to 10 12 cfu/mL) O Risk factors: intestinal dysmotility 2* to systemic disease eg diabetes, scleroderma, intestinal pseudoobstruction; previous surgery or strictures of small bowel, gastric surgery, jejunal diverticulosis

19. Small bowel bacterial overgrowth O Gold standard = small bowel aspirate and culture O Positive culture = >10 6 cfu/mL O Limited by lack of standardisation, sampling errors, need for intubation O Breath tests available but poor sensitivity (60%) and acceptable specificity (75%) (useful when positive) O Empiric trial of antibiotics is an option (ciprofloxacin/norfloxacin/cotrimoxazole)

20. Medications O Responsible for up to 4% chronic diarrhoea O Magnesium containing products O NSAIDs O Theophyllines O Antibiotics O Antineoplastic agents O Metformin O Antidepressants

21. Case 1 O 50 yr old man O Approximately 7 year history loose bowels 5x/day O Occasional nocturnal symptoms O Mild discomfort before motions O Systemically well O No family history O Managed with diastop prn at work

22. O Diarrhoea predominant IBS? …possibly O 80-90% will have a treatable underlying cause

23. Diarrhoea predominant IBS O Trial of low fibre diet O No more than 3 pieces fruit/day O No excess caffeine/ETOH O No excess sorbital/fizzy drinks O If fails, then consider other investigations depending on age O Trials of cholestyramine/antibiotics/creon

24. Case 2 O 40 year old female O Gastroenteritis during overseas trip to Thailand 4 months ago O Ongoing loose motions and bloating, no weight loss, no bleeding O Bloods and stool NAD

25. Post infectious IBS O Does it exist??

26. Post infectious IBS- The Walkerton Experience O Walkerton, Ontario, Canada O May 2000: Heavy rains washed livestock fecal residue from nearby farms into inadequately chlorinated drinking water supplied from shallow well O 2300 cases gastroenteritis O E coli 0157, Campylobacter O 27 cases of hemolytic uremic syndrome O 8 deaths O After 2 years follow up, prevalence of IBS 36% vs 10% in non infected controls (OR 4.8, p<0.001)

27. Post-infectious IBS O Occurs 3-36% of patients after acute gastroenteritis O More likely with O Increasing severity, duration>7 days, bacterial etiology, female sex, pre-existing depression/anxiety Thought 2* to low grade ongoing inflammation, increased intestinal permeability, altered gut flora, altered gut motility

28. Post infectious IBS O Treatment O Reassurance (may need a normal test) O Treat as per IBS subtype- often diarrhoea predominant O Hopefully will resolve with time

29. Other variations O Post infectious visceral hypersensitivity O Often requires pain team involvement O Post infectious hyperemesis O Young patients, ongoing vomitting post GI infection O Treat with long term PPI + Anti-emetics, reassurance O Very slow to resolve

30. Case 3 O 30 year old male O 2 months diarrhoea 9-10x/day O 7kg unintentional weight loss O No family history of IBD O Bloods normal apart from CRP of 9

31. Case 3 O Colonoscopy:

32. Case 3 O Started on pentasa, prednisone and enemas

33. 5-ASA in IBD O Variety of formulations: Pentasa, Asacol, Dipentum O Meta-analysis of oral 5ASA for active UC O 19 trials with 2032 patients, half placebo controlled O Mesalazine more than twice as effective as placebo (OR 0.39: CI 0.29-0.52)

34. 5-ASA in active Crohns ileocolitis O Meta-analysis of 3 placebo-controlled trials O Pentasa 4g daily for 16 weeks x 615 patients O Mean reduction of CDAI from baseline of -63 points, compared with 45 points for placebo (p=0.04)

35. Maintaining remission O All 5-ASA derivatives are effective for maintaining remission in UC O Less effective in maintaining remission in Crohns O Reduces relapse after surgery (NNT=8) O Reduces the risk of colorectal cancer by up to 75% (OR 0.25, CI 0.13 to 0.48)

36. Case 4 O 28 year old female O Recent delivery of healthy baby girl 6 months ago O 6 month history of outlet sounding PR bleeding and variable bowel motions 1- 5x/day O Initial weight loss but now regained O Family history of Crohns disease (mother)

37. Case 4 O Bloods: normal Hb but microcytosis O Ferritin 16 O B12, folate, coeliac serology normal O CRP 8 O Stool NAD

38. Case 4 O Fecal calprotectin 328 (<50) O Colonoscopy:

39. Case 4 O Started on pentasa + azathioprine O Now pregnant again with 2 nd baby

40. Fecal calprotectin O Protein released by WBC O Found in inflamed areas of bowel O Meta-analysis of 28 studies O For distinguishing IBD and IBS in adults, pooled sensitivity 93%, specificity 94% at cut-off level 50ug/g O Gray area = 50-150ug/g O Used mostly for its negative predictive value Waugh N, Health Technol Assess 2013; 17(55), 1-211.

41. Microscopic colitis O Lymphocytic colitis and collagenous colitis O Uncommon 5:100,000, increase with age O No increased risk of colon cancer O High false negative yield from rectosigmoid histology (34-43%)(Offner 1999) O Can co-exist with coeliac disease

42. Microscopic colitis

43. Microscopic colitis- treatment O Avoid caffeine, lactose, NSAIDs O 1 st line: loperamide O 2 nd line: mesalamine (pentasa/asacol) 3g/day O 3 rd line: budesonide 9mg/day for 6 weeks O >80% remission rate by 6 weeks but relapse rate 40% O Can retreat if symptoms recur

44. Case 5 O 30 year old female O Diarrhoea up to 48 times per day (!) O Nocturnal diarrhoea 8x overnight O Loose, watery, no blood or mucus O No weight loss O Trialled FODMAP, gluten free, vegetarian diet

45. Case 5 O Previous history of functional dyspepsia 2003- gastroscopy and barium swallow normal O Colonoscopy 2011 normal including biopsies O Taking 10 loperamide per day O Codeine + colofac O Denies family history or stressors

46. Case 5 O Blood tests: normal apart from CRP 5 O Stool tests: no WCC/RCC/growth on culture O Fecal calprotectin and elastase normal O Where to from here?

47. Case 5 O Admitted for inpatient investigations O 24 hour watch with bowel monitoring and fecal weighing O  x6 small amounts of formed brown motion over 24 hours in hospital O Each motion ~50mL at most O Discharged with diagnosis of irritable bowel syndrome and referred to health psychologist

48. Difficult diarrhoea O Persistent diarrhoea despite multiple negative investigations O Consider factitious diarrhoea (prevalence may be as high as 4%) O May need inpatient tests O 48 hour stool collection O Trial of fasting