Dr Melanie Lockett. BSc MBBS MD FRCP Consultant Physician and Gastroenterologist

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1 Dr Melanie Lockett BSc MBBS MD FRCP Consultant Physician and Gastroenterologist

2 Background & definitions Differential diagnoses NICE guidance 2008 Newer drugs FODMAPs Faecal calprotectin Common IBS mimics you might not know Bile acid malabsorption SIBO

3 Very common Community prevalence 10-20% Annual incidence in primary care 0.8% Prevalence in primary care 3-4% Young women (20-30yrs; 2F: 1M) Also in older people Chronic, relapsing and often lifelong Symptoms often overlap with other disorders Difficult to treat

4 Majority do not seek medical help 12% Primary Care Consultations (Drossman Gastroenterology, 1997) 30-50% GI consultations (Gunn et al Postgrad Med J, 2003) Economic burden Impaired QOL

5 7-10 min consultations long enough? It is not easy More complex cases Atypical symptoms Making a positive diagnosis without invasive Ix IBS patients develop other pathology Continuity of care is challenging More awareness of bowel cancer & symptoms

6 Recurrent abdominal pain, on average, at least 1 day/week in the last 3 months, associated with two or more of the following criteria: Related to defaecation Associated with a change in frequency of stool Associated with a change in form (appearance) of stool. Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis. Lacy BE, et al. Bowel Disorders. Gastroenterology 2016;150:

7 Updated Feb 2015

8 Establishing a positive diagnosis Identifying symptoms that require prompt referral Long term partnership working with person with IBS Patient-centred care

9 Abdo pain/discomfort Relieved by defaecation Associated with altered bowel frequency or stool form Varying sites And at least 2 of: Altered stool passage (straining, urgency, incomplete evacuation) Abdo bloating, distension, tension or hardness Symptoms worse after eating Mucus PR Lethargy, nausea, backache & bladder symptoms support the diagnosis

10 Symptoms for at least 6 months: A bdominal pain/discomfort B loating C hange in bowel habit

12 1. Unintentional and unexplained weight loss 2. Rectal bleeding (>minimal) 3. FHx of bowel or ovarian cancer, IBD, coeliac 4. Looser and/or more frequent stools > 6 weeks in a person aged over 40yr 5. Anaemia 6. Abdominal / rectal masses 7. Raised inflammatory markers 8. Nocturnal symptoms 9. Elevated faecal calprotectin (>200)

13 Coeliac disease (anti-ttg Ab) Food intolerance (food challenge) Disaccharide intolerance (breath test/challenge) IBD (faecal calprotectin) Infection or bacterial overgrowth (stool culture, breath test) Colonic diverticulosis (colonic imaging) Colorectal cancer (colonic imaging) Bile acid diarrhoea (Hx, SeHCAT)

14 Bile acid malabsorption (32%) Small bowel bacterial overgrowth (10-65%) Pancreatic insufficiency (6%) Coeliac disease (4%) Inflammatory bowel disease (0-1%) Cancer (<0.5%) Wedlake Alimentary Pharmacology & Therapeutics 2009

15 FBC ESR or plasma viscosity CRP Coeliac antibodies Ca 125 (females with symptoms suggestive of ovarian cancer (NICE CG 122)

16 US Rigid/flexible Sigmoidoscopy Colonoscopy / barium enema TSH Faecal ova & parasite test Faecal occult blood Hydrogen breath test

17 Information on self-help in IBS General lifestyle (leisure & relaxation) Physical activity (GPPAQ) - increase Diet (66% symptoms food related) Symptom-targeted medication

18 Regular meals, take time to eat Do not skip meals At least 8 cups of fluid per day Restrict tea and coffee (3 cups per day) Reduce intake of alcohol and fizzy drinks

19 Reduce insoluble fibre Reduce resistant starch (processed or re-cooked food) Limit fruit to 3 portions per day Diarrhoea: avoid sorbitol (artificial sweetener) Wind & bloating Oats Linseeds

20 Insoluble Fibre Bran, whole grains, corn, wheat, fruit and vegetables Soluble Fibre Pectins, fruit and vegetables Oats, barley, seeds Psyllium, ispaghula

21 Primary Care n=100 Secondary Care n=82 Bran Soluble Fibre Improved 27% 10% Worse 22% 55% Improved 25% 38% Worse 19% 24% Miller et al Digest Liver Dis 2006

22 Genus Linum Rich source of Omega-3 Source of insoluble and soluble fibre Less bloating c.f psyllium (Tarpilla2004)

23 Delayed physiological reaction to food 20% population Up to 65% IBS patients Non-immunological Food related factors Pharmacological agents (caffeine, tyramine) Enzyme deficiency (lactase) Idiosyncratic Exclusion and challenge Tolerance

24 Fermentable Oligo- Di- Monosaccharides And Polyols Fructans, GOS Lactose Fructose E.g. Sorbitol

25 Diet Fructose Fructans Lactose GOS Polyols Osmotically active Rapidly fermented Physiological effects water delivery gas production Luminal distension Symptom induction Motility changes Bloating Pain/discomfort Wind

26 Symptom Standard low FODMAP P Bloating 17/35 (49) Abdominal pain 20/33 (61) Diarrhoea 18/29 (62) Flatulence 14/28 (50) Constipation 10/22 (45) Nausea 4/14 (29) Poor energy 11/30 (37) Composite score 19/39 (49) Global satisfaction 20/37 (54) 32/39 (82) /34 (85) /36 (83) /38 (87) /21 (67) /15 (67) /32 (63) /43 (86) < /42 (76) 0.04 Staudacher et al, 2010

29 General dietary advice Advice about fibre Exclusion diets FODMAPs

30 Try for at least 4 weeks Dose recommended by manufacturer Monitor effect Evidence of effect for some people Try different brands

31 Single/combination Rx based on predominant symptom(s) Pain: Antispasmodics (hyoscine) Constipation: Laxatives (ispaghula, not lactulose) Diarrhoea: Loperamide (syrup) Peppermint oil Adjust dose according to stool consistency

32 NNT Fibre 11.5 Ispaghula 6 Bran (NS) - Antispasmodics 5 Hyoscine 3.5 Peppermint oil 2.5

33 If no improvement: 1. Increase dose 1 2. Rational combination e.g. stool softener & stimulant laxative 1, 3, 4 or bulking agent 1

34 Tricyclic antidepressants (TCA) for their analgesic effect 5-10mg ON initially Increase to max 30mg ON SSRIs only if TCAs ineffective Counsel on side effects Follow up after 4 wks then every 6-12 months

35 Alosetron (Lotronex) 5HT 3 inhibitor N. America only, named patient basis Rifaximin (Xifaxan) (SIBO) Minimally absorbed antibiotic Unlicensed indication Eluxadoline (Truberzi) Prucalopride (Resolor) Linaclotide (Constella) Lubiprostone (Amitiza) IBS-D IBS-C

Prucalopride (Resolor) Jan 2010 5-HT 4 agonist, no effect on QT interval Accelerates colonic transit (& SB transit, improves GE) NICE TA211 Women

36 Prucalopride (Resolor) Jan HT 4 agonist, no effect on QT interval Accelerates colonic transit (& SB transit, improves GE) NICE TA211 Women and now men Failed 2 classes of laxatives at max dose for 6 months Invasive treatment being considered Response assessed after 4 weeks Dose: 1-2mg OD

37 Linaclotide (Constella) Apr 2013 Binds to guanylate cyclase-c receptor Decreased pain fibre activity, increased intestinal fluid and accelerated transit Significant benefit in 2 RCTs Dose: 290 mcg OD

38 Lubiprostone (Amitiza) Nov 2013 Locally acting type 2 chloride channel activator Promotes fluid secretion into gut lumen NICE TA318 IBS-C, idiopathic constipation & opioid induced constipation Dose: 8-24mcg BD

39 Eluxadoline (Truberzi) Aug 2017 Opioid receptor agonist and delta-opioid receptor antagonist Slows down the movement of food through the gut NICE TA471 Pharmacological treatments are contraindicated, not tolerated or no response It is started in secondary care Dose: 100mg BD

40 No response to medication after 12 months, consider: Cognitive behavioural therapy (CBT) Hypnotherapy Psychological therapy Relaxation therapy

43 Most patients (especially those <40 years with typical symptoms) can be safely managed in primary care Have a plan Expect to see the patient for a few consultations Make those follow up appointments with you If symptoms not improving check faecal calprotectin then refer

44 First isolated in 1980 Neutrophil derived Ca and Zn binding protein Potent chemotactic factor for neutrophils Level directly proportional to neutrophil migration into the GI tract CRP of the gut Non-specific & is not diagnostic of IBD

45 Raised in IBD Neoplasia Infection Polyps NSAIDS, omeprazole Increasing age

46 Faecal calprotectin <50ug/g: IBD is unlikely In patients with symptoms suggestive of IBD a faecal calprotectin level <50ug/g has a negative predictive value of 98% >200ug/g: Faecal calprotectin suggests organic pathology Refer urgently to gastroenterology

47 First faecal calprotectin ug/g: Borderline faecal calprotectin. In patients without alarm symptoms or a pre-existing diagnosis of IBD repeat sample. Ensure NSAID s and PPI s have been withheld for 4-6 weeks. Exclude alternative causes of mildly elevated calprotectin such as coeliac disease, diverticulitis and gut infections. If repeat calprotectin is persistently raised a gastroenterology referral will be indicated Second calprotectin ug/g: Persistently raised calprotectin. Please refer routinely to gastroenterology

48 Meta-analysis of 30 prospective studies of faecal calprotectin (5983 patients) Sensitivity Specificity IBD vs no IBD 95% 91% Von Roon et al. Inflammatory bowel disease (6);

49 Substantial cost savings in secondary care Not evaluated in primary care

50 Recommendations: Adults or children Recent onset LGI symptoms Differentiate IBD from IBS Specialist assessment is being considered, if: Cancer is not suspected, having considered the risk factors (for example, age) and Appropriate quality assurance processes and locally agreed care pathways are in place for the testing.

51 1. Anxiety disorders Generalised anxiety Panic 2. Mood disorder Depression Dysthymia 3. Somatoform disorders Somatisation disorder Hypochondriasis 4. Eating disorders (anorexia/bulimia) 5. Hypochondriacal or somatic delusional disorder 6. Anal erotism 7. Deliberate self harm & factitious disorders 8. Opiate addiction 9. Masked depression 10. Frank psychosis Schizophrenia Manic depressive psychosis

52 581 non-pregnant women, years in primary care with chronic functional abdominal pain 26% childhood sexual abuse 28% adult sexual abuse Abused patients were more likely to have dysmenorrhoea, dyspareunia, pelvic pain and other chronic pain such as headaches or low back pain Jamieson & Steege 1997

A good psychosocial history Enquire about possible sexual or physical abuse Psychological distress Look for features of psychiatric illness such as

53 A good psychosocial history Enquire about possible sexual or physical abuse Psychological distress Look for features of psychiatric illness such as panic & depression You need time (45 mins to 1 hour) Avoid unrelenting medical Ixs and Rxs Incorporate psychopharmacologic & behavioural strategies

54 Bile acid malabsorption (32%) Small bowel bacterial overgrowth (10-65%) Pancreatic insufficiency (6%) Coeliac disease (4%) Inflammatory bowel disease (0-1%) Cancer (<0.5%) Wedlake Alimentary Pharmacology & Therapeutics 2009

55 Islam RS & DiBaise JK. Bile Acids: An under-recognized and underappreciated cause of chronic diarrhoea. Practical Gastroenterology October 2012: 32-41

56 Diarrhoea (watery) Faecal hurry, urgency, incontinence Bloating Sound like anything you know? Does not feature in IBS guidelines!

57 100cm from IC valve

58 Difficult to know: poorly recognised Limited testing worldwide Data from IBS-D population and extrapolated: 1/3 of all IBS-D have evidence of BAM Estimated UK prevalence of >1%

59 Primary/idiopathic 30 40% Association with microscopic colitis Terminal ileal Disease e.g. Crohn s Resection (distal 100cm) Bypass Other conditions interfering with bile acid cycling, small intestine motility or composition of ileal contents: Small intestinal bacterial overgrowth (deconjugation) Post-cholecystectomy Post-vagotomy Coeliac disease Radiation enteropathy Exocrine pancreatic insufficiency (reduced bicarbonate secretion)

60 SeHCAT (selenium homocholic acid taurine retention test) Retention value <15% Sensitivity 80 90% Specificity % (14C-glycocholate breath test)? Future role for serum 7-a-hydroxy-4-cholesten-3-one (C4) blood test not available for routine testing yet Therapeutic trial of bile acid sequestrants

61 Address any underlying cause

63 Large number of colonic-type bacteria in SI Predispositions: diabetes, scleroderma, Crohns, radiation enteropathy, SB diverticulae, surgical blind loops Symptoms: bloating, flatulence, abdominal discomfort, or watery diarrhoea Diagnosis: H2 breath test Treatment: Rifaximin 550mg TDS 7-10 days

64 IBS NICE guidance - ABC Newer drugs IBS-C & IBS-D FODMAPs diet Faecal calprotectin Common IBS mimics Bile acid malabsorption SIBO

Irritable bowel syndrome in adults

Irritable bowel syndrome in adults NICE provided the content for this booklet which is independent of any company or product advertised Welcome In February 2008, NICE published a clinical guideline on