Irritable Bowel Syndrome

Irritable Bowel Syndrome Dr John Hamlin PhD MRCP Consultant Gastroenterologist Leeds General Infirmary

Areas to cover: • What is IBS? • What are the typical symptoms? • Taking a good history • What examination should the GP do? • What investigations should the GP do? • Can it be diagnosed by the GP without a Ba enema or without referral ie. On clinical history? • Treatments – what are they / the evidence / what about probiotics and yoghurt type drinks?

Epidemiology • Diagnosis of exclusion vs. disease entity • Affects 10-25% of the population. • 75% don’t seek medical care • 50% of GI consults • 1/3 diarrhoea 1/3 constipation 1/3 pain predominant symptom • 2:1 F:M (4:1 in secondary care) • Oscillating course

Great effect on QOL • Large drain on healthcare and economy • Accounts for 20% self certification • Av 14.8 sick days vs. 8.7 average • Illness seeking behaviour: 3-4 times chance of abdominal surgery

Aetiology?? • Visceral hypersensitivity. Decrease balloon distension thresholds on the colon (Ritchie GUT 1973) Normal somatic pain thresholds Not seen in non medical seeking IBS • Altered motility (inconsistent results) • Psychological factors/central processing • Post infectious (30% cases) • Food intolerances

Visceral hyperalgesia • Evidence of visceral hyperalgesia (increased sensitivity to noxious stimuli in the gut) includes perception of pain from distention of a rectal balloon at smaller volumes than in normal patients • Post-infectious or post-antibiotic • Onset of IBS after an episodes of enteritis or antibiotics have been described. A meta-analysis found the prevalence of IBS to 9.8% after enteritis as compared to 1.2% in controls. • Food allergies and sensitivities

Bacterial overgrowth • Stress • Hormones • The role of hormones in IBS is not yet fully understood. Menstruation frequently triggers or exacerbates IBS symptoms, while pregnancy and menopause can either worsen or improve symptoms.

Defining the disease • No biological markers • Reliant on grouping of symptom patterns • Manning Criteria 1978 • Rome Criteria 1988 • Rome II 2000 • Study by Vanner et al. showed 100% PPV in a retrospective study and 98% in a prospective study (Am J Gastro 1999)

Rome Criteria (1) • 3 months of continuous or recurring symptoms of abdo pain or irritation that: May be relieved with a bowel movement May be coupled with changed frequency May be coupled with changed consistency • (2 out of 3 features) and……………

Rome criteria (2) • Two or more of the following are present at least 25% of the time: • A change in stool frequency (>3 day <3 week • Noticeable difference in stool form • Passage of mucous in stools • Bloating or feeling of abdo distension • Altered stool passage (tenesmus, straining)

Supportive symptoms of IBS: • A) Fewer than three bowel movements a week • B) More than three bowel movements a day • C) Hard or lumpy stools • D) Loose (mushy) or watery stools • E) Straining during a bowel movement • F) Urgency (having to rush to have a bowel movement) • G) Feeling of incomplete bowel movement • H) Passing mucus (white material) during a bowel movement • I) Abdominal fullness, bloating, or swelling Diarrhoea-predominant: At least 1 of B, D, F and none of A, C, E; or at least 2 of B, D, F and one of A or E. Constipation-predominant: At least 1 of A, C, E and none of B, D, F; or at least 2 of A, C, E and one of B, D, F

Red flag symptoms which are not typical of IBS: • Pain that awakens/interferes with sleep • Diarrhoea that awakens/interferes with sleep • Blood in the stool (visible or occult) • Weight loss • Fever • Abnormal physical examination

Examination findings • Nil

Investigation • Do we over investigate and over ‘medicalise’ the patient • Systematic review: ‘the utility of diagnostic tests in IBS’ Cash et al. Am J Gastro 2002 • Chances of organic disease in patients meeting the symptom based criteria in IBS as normal population

Pretest probability of organic GI disease in patients meeting symptom based criteria for IBS

Investigation cont. • <1% pickup of IBD/CCA • 10 times incidence of coeliac • Colonic imaging <1% chance of picking up significant pathology overall • Routine biochem/coeliac serology probably useful • BSG Blood screen and flexi in secondary care • Value of reassurance not assessed

BSG Guidelines 2000

Diagnostic accuracy for IBS is over 95% when Rome II criteria are met, history and physical exam do not suggest any other cause, and initial laboratory testing is negative.

Treatment • Reassurance • Lifestyle changes • Dietary intervention • Psychological intervention • Drug intervention

Dietary intervention • No conclusive/consistent evidence • Food intolerances: ‘challenge studies’ in IBS pts suggest intolerance in 6-50% • Exclusion diets or elimination diets used • 6/8 trials showed no improvement with fibre increase • High sorbitol/fructose rich diets eg. slimming • Caffeine although little evidence in literature

Diet • Dietary changes may prevent the overreaction of the gastrocolic reflex and lessen pain, discomfort, and bowel dysfunction. • Having soluble fibre foods and supplements, substituting soy or rice products for milk products, being careful with fresh fruits and vegetables that are high in insoluble fibre, and eating frequent meals of small amounts of food, can all help to lessen the symptoms of IBS. • Foods and beverages to be avoided or minimized include red meat, oily or fatty and fried products, milk products (even when there is no lactose intolerance), solid chocolate, coffee (regular and decaffeinated), alcohol, carbonated beverages (especially those also containing sorbitol), and artificial sweeteners.

Definitive determination of dietary issues can be accomplished by testing for the physiological effects of specific foods. • The ELISA food allergy panel can identify specific foods to which a patient has a reaction. Other testing can determine if there are nutritional deficiencies secondary to diet that may also play a role. • Removal of foods causing IgG immune response as measured using the ELISA food panel has been shown to substantially decrease symptoms of IBS in several studies.

There is no evidence that digestion of food or absorption of nutrients is problematic for those with IBS at rates different from those without IBS. • However, the very act of eating or drinking can provoke an overreaction of the gastrocolic response in some patients with IBS due to their heightened visceral sensitivity, and this can lead to abdominal pain, diarrhoea, and/or constipation.

Diet -Fibre • In patients who do not have diarrhoea predominant irritable bowel, soluble fibre at doses of 20 grams per day can reduce overall symptoms but will not reduce pain. • The research supporting dietary fibre contains conflicting, small studies that are complicated by the heterogeneity of types of fibre and doses used . • The one meta-analysis that controlled for solubility found that only soluble fibre improved global symptoms of irritable bowel and neither type of fibre reduced pain. • Positive studies have used 20-30 grams per day of psyllium seed (also called ispaghula husk).

Drug intervention • High placebo response 30-70%. Difficult to assess. • Laxatives: No RCTs, Limited benefit • Antidiarrhoeals: eg loperamide. 4 RCTs show some effect on decreasing abdo pain but no effect on global symptoms or bloating

Drug intervention cont. • Antispasmodics: 3 RCTs. Questionable benefit. Only short term trials. A meta-analysis by the Cochrane Collaboration suggest NNT = 6. • Antidepressants: TCADs: Meta analysis in 2000 Am J Gastro showed significant effect over placebo NNT 3 (best for D-IBS). • SSRIs: Citalopram (Tack et al., Gut 2006) improved pain, bloaring and QOL. Better for C-IBS?

Drugs affecting serotonin (5-HT) • Serotonin stimulates the gut motility and so agonists can help constipation predominate irritable bowel while antagonists can help diarrhea predominant irritable bowel: • Agonists • Tegaserod, a selective 5-HT4 agonist for IBS-C, is available for relieving IBS constipation in women and chronic idiopathic constipation in men and women. A meta-analysis by the Cochrane Collaboration (NNT = 17) • Selective serotonin reuptake inhibitoranti-depressants (SSRIs), because of their serotonergic effect, would seem to help IBS, especially patients who are constipation predominant. Initial crossover studies and randomized controlled trials support this role. • Antagonists • Alosetron, a selective 5-HT3 antagonist for IBS-D, which is only available for women in the United States under a restricted access program, due to severe risks of side-effects if taken mistakenly by IBS-A or IBS-C sufferers. • Cilansetron, also a selective 5-HT3 antagonist, is undergoing further clinical studies in Europe for IBS-D sufferers. In 2005, Solvay Pharmaceuticals withdrew Cilansetron from the United States regulatory approval process after receiving a "not approvable" action letter from the FDA requesting additional clinical trials.

New drugs • Aloesetron (GSK) 5HT3 antagonist • FDA approved 2000 • Withdrawn 2000 Ischaemic colitis (1:1000) • A few deaths attributed to it • Reintroduced 2002 • Reduced dose • Severe restrictions (counselling, consent)

Aloesetron • Slows colonic transit times • 5 RCTs • Significant benefit over mebeverine • Consistent modest improvement in global symptoms in diarrhoea predom. females • No application for license in the UK or Europe

Tegaserod • 5HT4 agonist • Increase GI motility in healthy subjects and IBS patients. • Possible visceral analgesic property: Reduced sensitivity to rectal stimuli in healthy volunteers (Coffin et al. Aliment Pharmacol Ther 2003) • Applying for European license (exp 2005)

Tegaserod • 6 RCTs show modest but statistically significant improvement in global symptoms in constipation predominant IBS • 3 month trial of 1519 pts with constipation predom. IBS showed therapeutic gain of 15% at 1/12 but only 5% at 3/12 in global symptoms. • Side effects Diarrhoea, headache

Future therapies • Abdo pain: Muscarinic antagonists, Beta 3 agonists vs spasm. Kappa opioid agonists for analgesia eg. Fedozotine • Constipation: Other 5HT4 agonists, 5HT3 agonists, CCK antagonists, opioid antagonists • Diarrhoea: Other 5HT3 agonists, 5HT4 agonists, alpha 2 agonists

Alternative treatments • 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 = 0.0009) 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 gastroesophageal reflux disease.

Psychotherapy and hypnotherapy • 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 behavioral 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.

Acupuncture • The meta-analysis by the Cochrane Collaboration concluded 'Most of the trials included in this review were of poor quality and were heterogeneous in terms of interventions, controls, and outcomes measured. With the exception of one outcome in common between two trials, data were not combined. Therefore, it is still inconclusive whether acupuncture is more effective than sham acupuncture or other interventions for treating IBS

Alternative treatments • Probiotics are generally accepted to be potentially beneficial strains of bacteria and yeast, often found in the human gut. • One research study has shown a clear link between the ingestion of Lactobacillus plantarum LP299V and sufferers of IBS who reported resolution of their abdominal pain. • B. infantis 35625, a strain of Bifidobacteria in normalizing bowel movement frequency in sufferers of IBS. • VSL #3? • 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.

Psychological intervention • Hypnotherapy: good results for refractory cases with limited psychopathology • Significant improvement vs. counselling (Whorwell et al Lancet 1984) • Reduced motor and sensory gastrocolonic response post hypnotherapy (Simren et al Psychosomatic Medicine 2004) • CBT shown significant results in trials • Expensive and time consuming

BSG Guidelines 2000

Summary 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 TCADs/citalopram In refractory cases consider counselling, hypnotherapy, biofeedback, role of probiotics

Conclusions • A complex multifactorial ‘disease’ • Huge resource useage • Targeted drug therapy difficult • New therapies but modest results • Probably grossly over investigated in many cases

Irritable Bowel Syndrome