GHNHSFT/CCG Collaboration: Ibs clinical pathway and Direct Access service Dr Alex di Mambro – Consultant Gastroenterologist Claire Oldale – Specialist Dietitian 2015/16

Objectives Recognize the symptoms of IBS and how to differentiate from IBD Optimize non invasive investigations To identify the role of new referral pathways and diagnostics in Primary Care in patients with GI symptoms Discuss treatments and dietary manipulation in the management of IBS

IBS IBS affects 5-10 % of adults aged 25 to 55, resulting in approximately 1 to 3 million patients being affected in the UK. Each year there are approximately 78,000 new patients diagnosed with IBS Each GP will have approximately 30-100 patients on their register IBS most commonly affects people between the ages of 20 and 30 years and is twice as common in women as in men. Recent evidence shows that there is also a significant prevalence of IBS in older people. (NICE 2013)

IBS Rome III Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months. Associated with two or more of the following: Pain is relieved by a bowel movement Onset of pain is related to a change in frequency of stool Onset of pain is related to a change in the appearance of stool.

IBS – the costs £45.6 million per year spent by NHS on IBS Cost per patient per year Up to £5341 direct costs Up to £2041 indirect costs (e.g. absenteeism) Up to 15 visits to physician 8-21 days off work (Maxion-Bergemann et al. 2006) 35% of disorders seen by Gastroenterologists (Russo et al., 1999)

Subtypes of IBS IBS-D, where diarrhoea is the predominant bowel habit, IBS-C, where constipation predominates; hard or lumpy stools (scored as 1 or 2 on the Bristol Stool Form Scale) ≥25% of defecations and, in conjunction, loose or watery stools (scored as 6 or 7 on the Bristol Stool Form Scale <25% of defaecations IBS-M (mixed), where both diarrhoea and constipation occur, and, IBS-U (unclassified), does not fit into one of the above categories (!)

Drug Treatments Diarrhoea Predominant: Mebeverine, Buscopan, Peppermint, Amitriptylline (10-20mg on increasing as tolerated) Constipation predominant: Linaclotide (guanylate cyclase-C agonist) 290mcg od (NICE guidance) Lubiprostone (chloride channel activator) 8mcg bd for 2/52 Prucalopride 1-2mg od ( a highly selective serotonin 5-HT4 receptor agonist which has been shown to stimulate gut motility in vitro and in vivo [Sanger and Quigley, 2010])

Faecal Calprotectin A biomarker of bowel inflammation Calprotectin is a 36kDa calcium and zinc binding protein expressed by the gene S100 calcium-binding protein. It accounts for 30 to 40% of neutrophils' cytosol. In vitro studies show it has bacteriostatic and fungistatic properties. Resistant to enzymatic degradation, and can be easily measured in faeces FC levels above 150 mg/g will point towards the existence of active IBD rather than IBS, with a sensitivity of 100% and a specificity of 97%

Dietary Management of IBS 9

Current dietary advice – BDA 2011/NICE 2015 1st line : 2nd line: Short term single exclusion Lactose Wheat 3rd LINE: Complex exclusion low FODMAP NICE recommend exclusion diets are undertaken with appropriate dietetic support

What are FODMAPs and how do they trigger symptoms?

FODMAP Fermentable Oligosaccharides fructans / galactans Disaccharides lactose Monosaccharides fructose And Polyols sorbitol / mannitol

FODMAPs Group of short chain carbohydrates Poorly absorbed leading to fermentation and osmotic changes in the bowel Barrett JS et al (2010) Dietary poorly absorbed, short-chain carbohydrates increase delivery of water and fermentable substrates to the proximal colon. Aliment Pharmacol Ther 31, 874-882. Ong DK et al (2008) The intestinal fermentative response to dietary FODMAPs; failure to switch to methane production in patients with irritable bowel syndrome. J Gastroenterol Hepatol 23(s4), A219.

How do they trigger symptoms? Fructose Fructans Lactose Galactans Polyols DIETARY COMPONENT Osmotically active Rapidly fermented  water delivery PHYSIOLOGICAL EFFECTS  gas production Motility changes Bloating Pain/discomfort Wind SYMPTOM INDUCTION Luminal distension

Does it work in clinical practice? Shephard and Gibson 2006: Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management .J Am Diet Assoc 106:1631-1639. Shephard et al 2008: Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol and Hepatol 6: 765-771. Staudacher et al 2011: Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet.;24(5):487-95 Halmos et al (2014)A diet low in FODMAPs reduces symptoms of irritable bowel syndrome Gastroenterology 2014;146:67–75

Halmos et al (2014) A Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome Gastroenterology 2014;146:67–75 Randomised crossover trial - 21 days low FODMAP diet or typical Australian diet with washout period of at least 21 days <0.5 g intake of FODMAPs per meal for the low-FODMAP diet. Equivalent nutritional quality in both diets. Subjects had lower overall gastrointestinal symptom scores (100mm VAS) low FODMAP diet 22.8mm; 95% CI 16.7–28.8 mm Typical Australian diet 44.9mm; 95% CI 36.6–53.1 mm; P < .001 Bloating, pain, and wind reduced. Patients of all IBS subtypes had greater satisfaction with stool consistency Objective effect of low FODMAP diet on stool modest – improvement in frequency / consistency in IBS-D sub-group only.

IBS Care Pathway Collaboration between GCCG and GHNHSFT G-Care: Comprehensive NICE based guidance including: Diagnosis, differential diagnosis and red flags Medications First line dietary advice with patient information available to download. Signposting to other sources of support 2gether Trust ‘Lets Talk’ IBS course IBS Network Criteria for referral to Complex IBS Service

DIAGNOSIS OF IRRITABLE BOWEL SYNDROME ROME CRITERIA 1. >3 months continuous or recurrent symptoms of abdominal pain. Relieved by defaecation and/or associated with change in stool frequency +/- change in stool consistency 2. >/=2 of the following for at least ¼ occasions or days: Altered stool consistency >3/day or <3/week Altered stool form Altered stool passage (strain/urgency/incomplete evacuation) Passage of mucus Bloating or abdominal distension Patient aged 16-45 presenting with symptoms Consistent with IBS (Rome Criteria) Alarm Symptoms/Signs? Blood in stool Unintentional/unexplained weight loss Nocturnal symptoms Anaemia OR significant FHx of bowel or ovarian cancer YES NO Refer to gastroenterology CRP, LFT, U&E, FBC, TTG, TSH Haematinics and stool culture NAD Measure Faecal Calprotectin No response to treatment algorithm Manage in Primary Care as per Gloucestershire IBS Care Pathway including diet, physical activity, medication (eg. Mebeverine, colpermin, Amitriptylline, linaclotide) FC >150 FC <149 Refer to gastroenterology Refer to Direct Access Dietetic IBS Service

Complex IBS Service E-referral service (link to referral form) Information on Trust website e-mail and phone queries accepted. Referrals triaged and allocated to dietetic led clinic if accepted. Regualar liaison with Cons. Gastroenterolgist.

Dietetic led clinics 2-3 face to face appointments. 1st appt – 1 hour - nutritional and symptom assessment and dietary exclusion as appropriate. Review appt – 30minutes – symptom review and food re-challenge /further advice 2nd review (if needed) – 30 minutes. Comprehensive accredited supporting literature provided. Patient access to email and telephone support between appointments.

Faecal Calprotectin – the rules Age 18-45 No red flags No nocturnal symptoms No NSAIDs for 6 weeks prior to test (false positive) Rome III criteria Referral via ICE (prospectively monitored)

In summary Aim for non invasive diagnosis of IBS where possible Sub-classification of IBS will help tailor treatments The use of faecal calprotectin will help to differentiate difficult to manage IBS from inflammatory disease The direct access IBS service will help stream line referral process and give patients quicker access to treatments that work Dietary manipulation is an effective approach to the treatment of IBS

Thank you for listening….. Any questions?

A closer look at the LOW FODMAP diet

FODMAP Fermentable Oligo- Di- Monosaccharides A P nd olyols Fructans, GOS Di- Lactose Monosaccharides Fructose A P nd olyols Sorbitol, Mannitol

Fructose Fermentable O D M onosaccharides A P

Fructose Monosaccharide Often absorbed well 30% of population malabsorb it when: in excess of glucose or if taken in large loads Found in honey, corn syrups, apples, sugar snaps.

Lactose F O D isaccharides M A P

Lactose Lactose Galactose Glucose

Lactose Lactase enzyme Lactose Galactose Glucose

…. Lactose is malabsorbed Lactase deficiency …. Lactose is malabsorbed and becomes a FODMAP Wide prevalence from 2%-90% in some asian countries

Oligosaccharides F O ligosaccharides D M A P

Fructans Naturally in foods – wheat, onions, garlic, leek, rye Chains of fructose units with a glucose terminal end Lack of enzyme to break bonds <5% absorption Naturally in foods – wheat, onions, garlic, leek, rye Added to food in form of inulin, oligofructose, fructo-oligosaccharides F G Most dietary sources of fructans are FOS -are being added for its putative health benefits

Galacto-oligosaccharides Various types e.g. Raffinose (1 F + 1G + 1 Gal) Stachyose (1R + 1 Gal) Humans lack α-galactosidase enzyme Found in wheat, pulses, beans and some nuts F G Ga F G Ga These are oligo-saccharides with a beta-fructosidic linkage and an alpha-galactosidic linkage. Rapidly fermented and induce gas formation

Polyols F O D M And Polyols

Polyols Sugar alcohols sorbitol, xylitol, mannitol, maltitol isomalt, erythritol Poorly absorbed in the small intestine (<20%) passive absorption only Naturally occurring in fruits and vegetables Mushrooms, cauliflower, stone fruits, pears Also added as a sweetener Chewing gum, sugar-free mints, diabetic foods. Used as a non stimulant laxative

The low FODMAP diet Regular balanced diets are moderate to high FODMAP Healthy individuals don’t feel the effects IBS patients suffer the effects of poor absorption due to gut hypersensitivity

The low FODMAP diet Restriction of all FODMAPs for up to 8 weeks Comprehensive resources and advice about suitable alternative products is imperative to prevent nutritional / calorie deficits Structured reintroduction of FODMAPs to tolerance increases dietary variety while maintaining symptom improvement enables long-term symptom management on a modified FODMAP diet

Conclusion The low FODMAP diet offers an exciting future for the management of IBS patients Implementation by a specialist trained dietitian is required for clinical effectiveness

FODMAP Research – further details

Shepherd and Gibson (2006) Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management .J Am Diet Assoc 106:1631-1639. Retrospective study of 64 IBS patients on the low FODMAP diet 77% adhered 3/4 had marked improvement of all IBS abdominal symptoms

Staudacher et al (2010) UK service evaluation assessed response to the low FODMAP diet compared to those given NICE guideline advice Dietitians completed questionnaires for each IBS review patient seen Symptom and satisfaction questions Total n=82 (n=39 standard; low FODMAP n=43)

n/N (%) of patients reporting symptom improvement Standard advice Low FODMAP advice P Bloating 17/35 (49) 32/39 (82) 0.002 Abdominal pain 20/33 (61) 29/34 (85) 0.02 Diarrhoea 18/29 (62) 30/36 (83) 0.052 Flatulence 14/28 (50) 33/38 (87) 0.001 Constipation 10/22 (45) 14/21 (67) 0.2 Global satisfaction 20/37 (54) 32/42 (76) 0.04

Shepherd et al (2008) 25 IBS patients Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol and Hepatol 6: 765-771. 25 IBS patients Already had symptomatic improvement on low FODMAP diet Blind challenges with fructose and fructans: induced symptoms Improvement not a placebo effect or due to change in other dietary components e.g. gluten