Dr. Melvyn Letier Constantiaberg Mediclinic October 2016

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1 Dr. Melvyn Letier Constantiaberg Mediclinic October 2016

2 This presentation will enable you to: Understand the pathophysiology of IBS Recognize the clinical manifestations of IBS Make a confident diagnosis of IBS Be better able to treat your patients with IBS

3 IRRITABLE BOWEL SYNDROME The bowels are at one time constipated, at another lax, in the same person How the disease has two such different symptoms I do not profess to explain W Cumming, London Medical Gazette, 1849

Recurrent abdominal pain or discomfort for at least 3

following: Improved with defaecation Onset associated with

stool form Criteria fulfilled for at least 3 months, and

4 Recurrent abdominal pain or discomfort for at least 3 days/month in last 3 months, associated with 2 or more of the following: Improved with defaecation Onset associated with change in stool frequency Onset associated with change in stool form Criteria fulfilled for at least 3 months, and symptom onset at least 6 months prior to diagnosis Longstreth GF Gastroent 2006

loss Persistent Diarrhoea Severe Constipation Nocturnal symptoms Coeliac disease

6 The history and physical examination, and where appropriate selected laboratory tests, should exclude alarm symptoms and signs Anaemia Fever Unexplained weight loss Persistent Diarrhoea Severe Constipation Nocturnal symptoms Coeliac disease Rectal bleeding Family history of colorectal cancer or IBD New onset symptoms > 50

7 Not Routinely Recommended May be helpful Recommended FBC, ESR, CRP Coeliac serology in D- IBS, M-IBS s-ttg Colonoscopy in patients with family history of CRC; over 50 years Serum Chemistry Thyroid functions Stool MC+S* Abdominal imaging * H2 Breath testing for lactose intolerance H2 Breath test for small bowel bacterial overgrowth Am J Gastroenterol 2009; 104; S1

8 Enhanced Perception Vagal Nuclei 5-HT Sympathetic Altered Motility Visceral Hypersensitivity Adapted from Camilleri and Choi. Aliment Pharmacol Ther. 1997;11:3.

Have analgesic as well as mood improving effects Modes of action of TCAs and SSRIs are: endogenous endorphin release, blockade of noradrenalin reuptake, and blockade of serotonin A meta-analysis

10 Have analgesic as well as mood improving effects Modes of action of TCAs and SSRIs are: endogenous endorphin release, blockade of noradrenalin reuptake, and blockade of serotonin A meta-analysis showed antidepressants more effective than placebo for pain relief and global symptoms, in a 1-3 month period. (NNT=4) TCAs exert benefit at lower than antidepressant doses e.g mg nocte. Treat initially for 3-4 weeks

11 Post-infectious IBS (PI-IBS)-odds increased six fold after acute gastroenteritis Risk factors for PI-IBS include young age, prolonged fever, anxiety and depression, longer illness duration Causes of PI-IBS thought to include malabsorption, increased lymphocytes and entero-endocrine cells, and antibiotic use

12 Alteration in faecal microflora. Small intestinal bacterial overgrowth: positive H2- breath test, response to antibiotics Food sensitivity/food allergy; carbohydrate malabsorption, gluten sensitivity. FODMAPS (fermentable oligo-, di-, and monosaccharides and polyols) enter distal small bowel and colon and undergo fermentation

13 Abdominal Pain Chronic Variable sites and intensity Triggers include food and stress Nocturnal pain is unusual

14 HMO group (Kaiser Permanente) Surgical predisposition in IBS; misdiagnosis important underlying factor Women undergoing hysterectomy for pain more likely to have IBS Increased multidisciplinary collaboration may improve diagnosis and reduce surgery Longstreth, Yao. Gastroent 2004;126

15 Surgery IBS (%) N=4587 Non IBS(%) N=84421 Cholecyst Appendicec Hysterect Back surg CABG Peptic ulcer

16 Diarrhoea Small-moderate volume loose stools; more frequent Crampy pain, relieved after stool Constipation Hard, pellet-like stools; may have normal or loose stools; less frequent Crampy pain, relieved after stool Sense of incomplete evacuation Sense of incomplete evacuation Mucus in ± 50%

17 Reproduced by kind permission of Dr K W Heaton, Reader in Medicine at the University of Bristol Norgine Ltd.

18 Often worse postprandial Worse as day goes on Increased abdominal girth, without increase in total gas content Mechanism: gas trapping in small intestine

20 Family Practice Gastroenterology IBS OTHER IBS OTHER 12% of GP Visits 28% of Gastro Visits

Prevalence 4 to 30% (average + 20%) Up to 75% of persons with IBS do not seek medical attention 8 15% of primary care and 20 40% of referrals to gastroenterologists

21 Prevalence 4 to 30% (average + 20%) Up to 75% of persons with IBS do not seek medical attention 8 15% of primary care and 20 40% of referrals to gastroenterologists Remains common in the elderly (Often misdiagnosed as symptomatic diverticulosis) Increased health care burden and more days off work Medical costs - + $8 billion in USA annually

22 The North-West University (Potchefstroom) study. The purpose of the study: To investigate the relationship of job burnout and work engagement with self-reported received treatment for health conditions (Cardiovascular condition, High cholesterol, Depression, Diabetes, Hypertension and Irritable bowel syndrome), while controlling for age, gender, smoking and alcohol use. Results: The results showed that job burnout had a positive relationship with self-reported received treatment for Depression, Diabetes, Hypertension and Irritable bowel syndrome. Reference : Leon T. de Beer1*, Jaco Pienaar1 & Sebastiaan Rothmann Jr.2 Published online 10 April 2014 in Wiley Online Library (wileyonlinelibrary.com) DOI: /smi.2576

23 Reference : Leon T. de Beer1*, Jaco Pienaar1 & Sebastiaan Rothmann Jr.2 Published online 10 April 2014 in Wiley Online Library (wileyonlinelibrary.com) DOI: /smi.2576

24 1. Why present now? 2. Establish therapeutic relationship 3. Patient education 4. Dietary modification 5. Physical activity 6. Psychosocial therapy 7. Medication 8. Alternative therapies

25 Change in symptoms e.g. medication, diet Concern about serious illness Stressors Hidden agenda e.g. disability, request for opiates or tranquillizers Psychological co-morbidity

26 Non-judgmental Establish realistic expectations Involve patient in treatment decisions Patients with established, positive physician interactions have fewer IBS related follow-up visits

27 Education helps validate patients illness experience Sets the basis for therapeutic intervention Stress the chronic, benign nature of IBS The diagnosis of IBS (well validated) is robust and unlikely to change over time IBS has no effect on lifespan

28 Take a careful dietary history Consider Lactose intolerance, trial of Lactose-free diet, FODMAP diet Reduced intake of gas forming foods in patients with increased gas Food allergy testing not recommended Gluten restriction in non- Coeliac patients may be of benefit

29 Fermentable oligo-di-monosaccharide and polyols (FODMAPs) enter distal small bowel and colon, fermented, and cause symptoms FODMAPs include Fructans, Galactans, Lactose, Fructose, Sorbitol, Xylitol and Mannitol Several studies on low FODMAPs diet have been shown to be of benefit in patients with IBS A trial of low FODMAPs diet is reasonable, provided nutritional status is monitored Gibson PR APT 2005

30 30

31 Modes of action: increased water holding in stool; gel formation to lubricate stool; bulking of stool; bile salt binding Bulking agents showed no benefit over placebo for reducing IBS global symptoms Hi-fiber foods e.g. All Bran may aggravate bloating Because of safety and placebo effect a trial of therapy is reasonable, especially in C-IBS (<30g/d)

32 Increased physical activity may help with symptoms of IBS In a Scandinavian study of 102 IBS patients, moderate to vigorous exercise 3-5 times per week showed significant benefit over non-exercising. Active Exercise Group Non-active Group Decrease in symptom score Worsening Symptoms % 23% Am J Gastroent 2011

33 Behavioral treatment e.g. Hypnotherapy, Biofeedback, Psychotherapy may be useful They reduce anxiety levels, encourage health promoting behavior, involve patients in treatment and improve pain tolerance A 2009 meta-analysis of 20 studies (n=1278) showed Psychological therapy including Antidepressants to be significantly more effective vs. control or standard of care Ford AC GUT 2009

34 Medication must be considered an ADJUNCT to IBS treatment Drug selection will vary with dominant symptoms Chronic drug use should be minimized: IBS is a lifelong condition; lack of convincing evidence of efficacy High placebo response rate in IBS

35 1. Antispasmodics 2. Antidepressants 3. Anti-diarrhoeal agents 4. Anti-constipation agents 5. Probiotics 6. Alternative therapies

36 IBS Drug Treatment Pain and Bloating IBS Anti-spasmodics Tricyclics SSRIs Constipation Laxatives Prucalopride* Lubiprostone* Linaclotide* Diarrhoea Loperamide 5HT3 Antagonists e.g. Alosetron*

37 Most widely used drugs in IBS Should be used on demand rather than on a regular basis May be useful in patients with post-prandial pain, gas, bloating and faecal urgency Agents available in SA include Mebeverine, Hyoscine, Peppermint oil, Librax Poynard T et al APT 2001

38 More effective than placebo for pain relief and global symptom improvement; NNT=4 Tricyclics effective at lower than antidepressant doses e.g. amitriptyline mg daily. Use with caution in constipated patients. Aim at 3-4 week trial of therapy given delayed onset of action SSRI treatment data less consistent than TCAs Reupert L Cochrane Database 2011

39 Use step-up approach Others Irritant Laxatives Irritant laxatives + Bulking agent Osmotic laxatives; Bulking agents

40 Administration of Bifidobacterium Infantis alleviated IBS symptoms including abdominal pain, bloating and normalized bowel movement. An abnormal IL10/IL12 ratio at baseline was normalized by feeding B. Infantis. B. Infantis changed a pro-inflammatory ratio to an antiinflammatory state i.e. Immune modulating effect A prospective placebo-controlled study found patients with diarrhoea predominant IBS taking Saccharomyces Boulardii, a probiotic yeast, had a significant reduction on the number and improvement in consistency of bowel movements. O Mahoney et al Clin Gastroenterol Hepatol 2005

41 Meta-analysis of 14 probiotic trials: Small improvement in overall IBS symptoms Effects on individual symptoms i.e. bloating, pain, flatulence conflicting evidence No adverse effects Systematic review of 18 trials: Most used combination or Lactobacilli/ Bifidobacteria Statistically significant effect over placebo wrt Global IBS symptoms, pain & flatulence but not bloating ACG guidelines give probiotics a weak recommendation due to lack of long term data Hoveyda et al Gastroenterology 2009; Moayyedi et al Gut 2010

42 Iberogast (German Herbal medication) Rifaximin (Antibiotic not available in S.A) Tranquilizers e.g. Librax Hypnotherapy Acupuncture

43 Recent studies have suggested that Rifaximin, a non-absorbable antibiotic, can be used as an effective treatment for abdominal bloating and flatulence, giving more credibility to the potential role of bacterial overgrowth in some patients with IBS. A double-blind, randomized, placebo-controlled trial compared the multi-herbal extract Iberogast versus placebo in the treatment of all three forms of irritable bowel syndrome. This multi-target phytopharmaceutical was found to be significantly superior to placebo via both an abdominal pain scale (p value = ) and an IBS symptom score (p value = 0.001) after four weeks of treatment. Enteric coated Peppermint oil capsules has been advocated for IBS symptoms in adults and children; however, results from trials have been inconsistent. Peppermint may exacerbate GORD.

44 There is a strong brain-gut component to IBS, and Cognitive therapy may improve symptoms in a proportion of patients in conjunction with Antidepressants. In a randomized controlled trial of referred patients, Cognitive behavioural therapy helped even though patients in this study did not have any psychiatric diagnoses. Gut-directed or gut-specific Hypnotherapy or self-hypnosis is one of the most promising areas of IBS treatment. Current research shows that symptom reduction/elimination from IBS hypnotherapy can last at least five years.

61 Pharmaceutical companies Financial potential (High prevalence, Affliction of affluence, Lack of effective therapy) Will these patients ever uniformly benefit from drug treatment? Animal models for functional disorders do not accurately reflect the human condition Recent phase 3 trials fundamentally flawed

Only 6/93 trials of IBS intervention found to be scientifically adequate in recent review Great difficulty in defining end-points in clinical trials to

62 Only 6/93 trials of IBS intervention found to be scientifically adequate in recent review Great difficulty in defining end-points in clinical trials to reflect beneficial effect on global well-being & IBS symptoms Pressure groups may have +ve or ve impact on decisions by licensing authorities and politicians

It s not life-threatening, after all, it s not cancer. You need to learn to live with it. Come back and see me if you get a new symptom, but otherwise it s just IBS.

64 It s not life-threatening, after all, it s not cancer. You need to learn to live with it. Come back and see me if you get a new symptom, but otherwise it s just IBS. Heck I can't even find a doctor to actually diagnose me for IBS. A virus that needs to work its way out? Has this doctor never heard of the Rome 3 criteria? Don t they teach this stuff in Medical school?

65 Aim to make a positive diagnosis with Rome criteria history, examination Beware alarm symptoms: Wt loss, PR bleeding, recent change in bowel habit, etc Basic Ix: stool culture, FBC, U&E, LFT, CRP, TFT, anti ttg Ab, glucose, Ca Refer for further investigation Explanation, reassurance, dietary and lifestyle advice IBS-C IBS-D Pain/Bloating Increase dietary fibre / fluid Bulk forming laxative(s) Consider Citalopram Dietary modification Anti-diarrhoeal agents Consider Amitriptyline Reduced fibre intake Increased fluids Antispasmodics Consider TCA s/citalopram In refractory cases consider Counselling, Hypnotherapy, Biofeedback, role of Probiotics

IBS is a chronic medical condition characterized by abdominal pain, diarrhoea or constipation, bloating, passage of mucus and feelings of incomplete evacuation Precise etiology of IBS is unknown and

66 IBS is a chronic medical condition characterized by abdominal pain, diarrhoea or constipation, bloating, passage of mucus and feelings of incomplete evacuation Precise etiology of IBS is unknown and therefore treatment is focused on relieving symptoms rather that curing disease A complex multifactorial disease Huge resource usage Probably grossly over investigated in many cases Targeted drug therapy difficult New therapies but modest results

67 Although many IBS patients complain of symptoms after eating, true food allergies are uncommon Specific therapies are determined by individual patient symptoms Life-style modifications and possible alternative therapies may relieve symptoms

68 Current drug therapy often provides inadequate relief of IBS symptoms, leading many patients to consider CAM therapies (Complementary and Alternative Medicine). Aloe barbadensis Miller Extract (AVH200 ) is a CAM therapy that is well tolerated, safe and has been shown to be a promising treatment option for patients with IBS.

The results from the study showed that symptoms in adults with diagnosed IBS improved significantly when the diet was

69 PROIBS which contains AVH200 has successfully completed a randomized placebo study at the Sahlgrenska University Hospital in Sweden. The results from the study showed that symptoms in adults with diagnosed IBS improved significantly when the diet was supplemented with AVH200 compared to the placebo. AVH200 was seen to reduce problems of discomfort and perceived feeling of bloating. Thus, PROIBS containing this unique extract is seen as a promising treatment adjunct for the dietary management of IBS.

Diagnosis and Management of Irritable Bowel Syndrome (IBS) For the Primary Care Provider

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