IBS(Irritable Bowel Syndrome) Management Update-2021

Some slides are taken from different textbooks of medicine like Davidson, Kumar and Clark and Oxford, and some from other presentations made by respected tutors. I'm barely responsible for compilation of various resources per my interest. These resources are free for use, and I do not claim any copyright. Hoping knowledge remains free for all, forever.

1. Updates in management of ibs Presenter: Dr. Pritom Das Registrar, Medicine, DAMCH Organized By: Society of Medicine, Faridpur Powered By: Renata Pharmaceuticals Ltd.

2. Updates in management of ibs Section 1 Definition Epidemiology Pathophysiology Diagnosis Investigations Section 2 Ways of intervention Lifestyle changes and Dietary approaches 1 st and 2 nd line drugs Approach to refractory case Section 3 Prognosis Follow-up Take-home messages Quiz

3. Guidelines reviewed World Gastroenterology Organisation Global Guidelines - Irritable Bowel Syndrome: a Global Perspective [WGO] American College of Gastroenterologists Clinical Guideline: Management of Irritable Bowel Syndrome [ACG] British Society of Gastroenterology guidelines on the management of irritable bowel syndrome [BSG] NICE Irritable bowel syndrome in adults: diagnosis and management Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome

4. definition World Gastroenterology Organization defines Irritable Bowel Syndrome as “a functional bowel disorder in which abdominal pain or discomfort is associated with defecation and/or a change in bowel habit .”

5. epidemiology Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. The prevalence of IBS in the global population is estimated at 11 % and in Asians ranges from 4% to 9% depending on the criteria used. The prevalence of IBS in women is about twice as high as in men and make up 80 % of the population with severe IBS. However, there is no sex predilection in South Asia , South America, and Africa. Half of patients report their first symptoms before the age of 35 .

6. Etiology - a disorder of gut-brain interaction In the multifactorial pathogenesis of IBS a key role is played by disorders of gut-brain interactions (DGBI) . The intestinal microbiota is an essential element of these interactions, and its dysregulation directly affects the other pathogenic mechanisms of IBS. Genetics, and epigenetic changes, infection and early adverse life events may predispose an individual to developing IBS, and chronic stress, psychological symptoms, negative beliefs about symptoms and illness and maladaptive coping mechanisms can increase the frequency and severity of symptoms.

7. Etiology - a disorder of gut-brain interaction IBS is a disorder of altered bidirectional communication between the gut and brain (via the gut-brain axis), and has a biopsychosocial aetiology . Major Components of this complex pathophysiology includes- Central nervous system and autonomic nervous system modulation Altered visceral perception Transit and motility Immune regulation, inflammation and epithelial permeability The microbiome Genetics and epigenetics

8. Etiology Activation of the immune system of the intestinal mucosa associated with dysbiosis, diet, stress and endogenous factors results in increased permeability of the intestinal barrier and the induction of motor-sensory functions of the gastrointestinal tract. In patients with IBS there are qualitative and quantitative changes in the composition of the gut microbiota , which has significant therapeutic implications. SIBO plays a special role in the pathogenesis of intestinal symptoms. Disturbed motor activity of the gastrointestinal tract and visceral hypersensitivity are typical but not completely specific features of IBS.

9. Etiology Central nervous system disorders occurring in patients with IBS may cause increased reactivity to stress stimuli and influence the severity of symptoms. Dietary factors, with particular emphasis on poorly absorbed, easily fermentable oligo-, di-, monosaccharides and polyols ( FODMAPs ), may influence the occurrence and severity of IBS symptoms. Psychosocial factors and coexisting psychiatric disorders have a significant impact on the course and results of IBS treatment.

10. The bio-psycho-social model of IBS

11. Following changes are notable in Rome IV as compared to ROME III „„ Term abdominal discomfort has been deleted considering the dubious nature of the term and also that it is not present in every language. „„ Abdominal pain to be present on at least 1 day/week based on scientific evidence „„ Bloating and distention are recognized as common symptoms „„ Improvement with defecation has been replaced with related to defecation as it has been found that many patients report increase in pain with defecation „„ Rome IV also mentions about the location of pain, which can be present anywhere in the abdomen in contrast to the older criteria which considered lower abdominal pain as consistent with IBS

12. Nice abc mnemonic for diagnosis The diagnosis of IBS should be considered if the patient has had the following for at least 6 months : A bdominal pain, and/or B loating, and/or C hange in bowel habit “Although the Rome IV criteria are the gold standard to define IBS for research purposes, they are probably overly restrictive for use, even in secondary care, and a pragmatic definition in line with that used in the NICE guideline, and outlined above, should be preferred.” [BSG]

13. Alarm Features for Organic Disorders

14. classification IBS is categorized into four main subtypes based on the predominant bowel habit: IBS with constipation ( IBC-C ); IBS with diarrhea ( IBS-D ); IBS with mixed symptomology ( IBSM ); Unclassified IBS

15. Severity assessment of IBS patients on the MDCP model

16. Non-gastrointestinal features of ibs IBS patients suffer from a number of non-intestinal symptoms, which may be more intrusive than the classical features. IBS coexists with chronic fatigue syndrome, fibromyalgia and temporomandibular joint dysfunction. Gynaecological symptoms • Painful periods ( dysmenorrhoea ) • Pain following sexual intercourse (dyspareunia) Urinary symptoms • Frequency • Urgency • Passing urine at night (nocturia) • Incomplete emptying of bladder Other symptoms • Joint hypermobility • Back pain • Headaches • Bad breath, unpleasant taste in the mouth • Poor sleeping • Fatigue

17. investigations Clinicians should make a positive diagnosis of IBS based on symptoms , in the absence of alarm symptoms or signs , and abnormalities on simple blood and stool tests In people who meet the IBS diagnostic criteria, the following tests should be undertaken to exclude other diagnoses: FBC ESR or CRP patients <45 years of age with diarrhoea, a faecal calprotectin to exclude IBD antibody testing for coeliac disease

18. investigations All guidelines suggest serologic testing be performed to rule out celiac disease (CD) in patients with IBS and diarrhea symptoms . There is no role for colonoscopy in IBS , other than in those with alarm symptoms or signs, or those with symptoms suggestive of IBS with diarrhoea who have atypical features and/or relevant risk factors that increase the likelihood of them having microscopic colitis.

19. Summary of section 1

20. Types of interventions 1 st line 2 nd & 3 rd line 1 . Exercise, diet, and dietary manipulation 2 . Fiber 3 . Interventions that modify the microbiota: prebiotics, synbiotics , probiotics, and antibiotics 4 . Antispasmodics and peppermint oil 5 . Antidepressants 6 . Pro-secretory agents: linaclotide, plecanatide , and lubiprostone 7 . Eluxadoline 8 . Loperamide 9 . Serotonergic agents 10 . Psychological interventions

21. Reassurance is key

22. Exercise, diet and dietary manipulation All guidelines suggest Exercise helps overall symptom improvement in IBS patients, particularly for constipation, with beneficial effects still apparent at 5 years in one trial. A low FODMAP diet helps with overall symptom improvement in IBS patients. Guidelines suggest against a gluten-free or exclusion diet . Poorly fermentable, soluble fiber such as psyllium (ispaghula) remains an evidence- based treatment for IBS. Insoluble fiber may exacerbate in and bloating in IBS , and has no evidence for efficacy. Osmotic laxatives shouldn’t be used. Soluble fiber should be commenced at a low dose (3–4 g/day) and built up gradually to avoid bloating

23. diet and dietary manipulation First-line dietary advice should be offered to all patients with IBS. Which includes - adopting healthy eating patterns, such as regular meals, maintaining adequate nutrition, limiting alcohol and caffeine intake, adjusting fiber intake, and reducing consumption of fatty and spicy foods.

24. What steps can I take if I have IBS? eat three regular meals a day try not to skip any meals or eat late at night (smaller meal sizes may ease symptoms)  reduce intake of caffeine-containing drinks e.g. no more than two mugs (three cups) a day reduce intake of soft drinks drink at least eight cups of fluid per day , especially water or other non-caffeinated drinks, for example herbal teas cut down on rich or fatty foods reduce your intake of manufactured foods and cook from fresh ingredients where possible limit fresh fruit to three portions per day. 

25. Helpful tips If symptoms include bloating and wind If symptoms include constipation If symptoms include diarrhoea Limit intake of gas producing foods e.g. beans pulses, cauliflower, and also sugar-free mints/chewing gum. You may find it helpful to eat oats. Try to gradually increase your fibre intake – any sudden increase may make symptoms worse. Rich sources include wholegrains, oats, vegetables, fruit and linseeds. They help to soften stools and make it easier to pass. Replace lost fluids by drinking plenty . Limit caffeine intake from tea, coffee and soft drinks to three drinks per day. Try reducing intake of high- fibre food Avoid sugar-free sweets, mints, gum and drinks containing sorbitol, mannitol and xylitol. Take time to relax – relaxation tapes, yoga, aromatherapy or massage may help Take regular exercise such as walking, cycling, swimming Take time to eat meals – chew your food well Keep a food and symptom diary whilst you are making changes so you can see what has helped

26. What is a low FODMAP diet? The catchy acronym stands for fermentable oligosaccharides, disaccharides, monosaccharides and polyols , which are more commonly known as carbohydrates. These can be further divided into five groups called fructans , galacto -oligosaccharides, lactose, excess fructose and polyols. These sugars are poorly absorbed and pass through the small intestine and enter the colon, where they are fermented by bacteria. Gas is then produced , which stretches the sensitive bowel causing bloating, wind and pain .  This can also cause water to move into and out of the colon, causing diarrhoea, constipation or a combination of both .

27. Avoid these High fodmap foods foods containing fructans foods containing galacto -oligosaccharides foods containing lactose foods containing  excess fructose foods containing polyols Wheat Rye Barley Garlic Onion Lentils Chickpeas Legumes Cashews Baked beans Lentils Chickpeas Soybeans Animal milks Custard Ice cream Condensed milk Yogurt Dairy desserts Apples Pears Mangoes Watermelon Honey Peaches Plums Cauliflower Mushrooms Chewing gum Confectioney with polyols

28. Interventions that modify the microbiota: prebiotics, synbiotics , probiotics and antibiotics Prebiotics are food or dietary supplements that result in specific changes in the composition and/or activity of the GI microbiota. Probiotics have been defined as “ live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. Synbiotics , which are also food or dietary supplements, are a mixture of probiotics and prebiotics that act synergistically to promote the growth and survival of beneficial organisms.

29. Interventions that modify the microbiota: prebiotics, synbiotics , probiotics and antibiotics Guidelines suggest against the use of prebiotics and synbiotics for overall symptom improvement in IBS patients. All Guidelines suggest probiotics , taken as a group, to improve global symptoms, as well as bloating and flatulence in IBS patients. It is reasonable to advise patients wishing to try probiotics to take them for up to 12 weeks , and to discontinue them if there is no improvement in symptoms. [BSG] ACG suggest the non-absorbable antibiotic rifaximin for reduction in global IBS symptoms, as well as bloating in non-constipated IBS patients.

30. Drugs used first line for IBS - Antispasmodics and peppermint oil All guidelines suggest Certain antispasmodics [ antimuscarinics and smooth muscle relaxants- (trimebutine- TRITIN , otilonium , hyoscine, cimetropium , pinaverium, dicyclomine and mebeverine , alverine citrate- ALRIN ] as an effective treatment for global symptoms and abdominal pain in IBS. Dry mouth, visual disturbance and dizziness are common side effects. All guidelines suggest Peppermint oil as an effective treatment for global symptoms and abdominal pain in IBS. Gastro- oesophageal reflux is a common side effect. The risk of adverse events is no greater with peppermint oil than with a placebo.

31. Drugs used first line for IBS – recommendation against continuous loperamide use All guidelines recommend against continuous Loperamide ( s ynthetic μ- opioid agonist) except for diarrhea in IBS. It is no more effective than a placebo in reducing pain, bloating, and global symptoms of IBS, but it is an effective agent for the treatment of diarrhea. A bdominal pain, bloating, nausea and constipation are common, and may limit tolerability. Titrating the dose carefully may avoid this.

32. Drugs used first line for IBS Gut-brain neuromodulators Dysfunction within the bidirectional gut-brain axis is considered to play an important role in the genesis and maintenance of symptoms in IBS. Although IBS is often considered a functional gastrointestinal disorder, it has been re-termed as disorders of gut-brain interaction . Patients with IBS often have comorbid anxiety and depression , and these are also risk factors for the subsequent development of IBS in healthy people. This, together with their peripheral effects on gastrointestinal function, is part of the rationale for the use of gut-brain neuromodulators, such as TCAs and SSRIs .

33. Gut brain modulators TCA and ssri TCAs and SSRIs impact on bowel function, with TCAs improving diarrhea by slowing GI transit, and SSRIs ameliorating constipation by accelerating GI transit. Tricyclic antidepressants used as gut-brain neuromodulators are an effective second-line drug for global symptoms and abdominal pain in IBS. [BSG] They should be commenced at a low dose ( eg , 10 mg amitriptyline once a day) and titrated slowly to a maximum of 30–50 mg once a day. [BSG] TCAs are associated with significant adverse effects in treating IBS-D and should be avoided in IBS-C ; clinicians should expect one adverse effect for every three patients who benefit from therapy [WGO]

34. Gut brain modulators TCA and ssri SSRIs may be considered in resistant IBS-C , although it is not currently recommended that SSRIs should be routinely prescribed for IBS in patients without comorbid psychiatric conditions. [WGO] Selective serotonin reuptake inhibitors used as gut-brain neuromodulators may be an effective second-line drug for global symptoms in IBS. [BSG/ ACG] Whether all IBS sufferers, or only certain sub-populations, respond to anti-depressants is also unclear, and therapy with these agents may be limited by patient acceptance and adverse events.

35. Drugs used second line for the treatment of IBS-D Who do not experience symptom improvement with antidiarrhoeals 5-Hydroxytryptamine 3 receptor antagonists are efficacious second-line drugs for IBS with diarrhoea in secondary care. [ Ondansetron titrated from a dose of 4 mg once a day to a maximum of 8 mg tds ] Constipation is the most common side effect. (EMEREN/EMESET) The non-absorbable antibiotic rifaximin is an efficacious second-line drug for IBS with diarrhoea in secondary care. Other options- Eluxadoline , a mixed opioid receptor drug; contraindicated in patients with cholecystectomy, pancreatitis or severe liver impairment

36. Drugs used second line for the treatment of IBS-C Who do not experience symptom improvement with laxatives Lubiprostone , a chloride channel activator, is an efficacious second-line drug for IBS with constipation in secondary care. (LAXANA) This secretagogue is less likely to cause diarrhoea than others. However, patients should be warned that nausea is a frequent side effect Other options: Linaclotide and Plecanatide (guanylate cyclase-C agonist), Tenapanor (sodium-hydrogen exchange inhibitor), Tegaserod ( 5-Hydroxytryptamine 4 receptor agonist ) – not available in the market yet

37. Psychological therapies All guidelines suggest IBS-specific cognitive behavioural therapy as an efficacious treatment for global symptoms in IBS. Psychological therapies should be considered when symptoms have not improved after 12 months of drug treatment . [BSG] General nonpharmacological recommendations • Discuss the patient’s anxieties. This reduces complaints; aim to eliminate unnecessary worries. • Aim to reduce avoidance behavior. Patients may avoid activities that they fear are causing the symptoms, but avoidance behavior has a negative influence on the prognosis. • Discuss and aim to resolve stressful factors.

38. Novel approaches for the future Fecal Microbiota Transplant (FMT) Mast Cell Stabilizer and Other Anti-inflammatory Drugs Ghrelin Receptor Agonists: Relamorelin 5-HT3 Antagonists : Ramosteron Drugs Acting on Bile Acids Modulating the Central Pain Mechanism - IBStim Device: The Cranial Nerve Stimulator IBStim device

39. BSG Treatment algorithm for IBS *Review efficacy after 3 months of treatment and discontinue if no response TCAs should be first choice, starting at a dose of 10 mg at night, and titrating slowly ( eg , by 10 mg/week ) according to response and tolerability. Continue for at least 6 months if the patient reports symptomatic response. recommended strongly when symptoms are refractory to drug treatment for 12 months Summary of section 2

40. if bloating/pain main feature if pain main feature CAG Consensus guided algorithm for the management of IBS

41. prognosis For most patients with IBS, symptoms are likely to persist, but not worsen. Symptoms will deteriorate in a smaller proportion, and some patients will recover completely. Factors that may negatively affect the prognosis include: • Avoidance behavior related to IBS symptoms • Anxiety about certain medical conditions • Impaired function as a result of symptoms • A long history of IBS symptoms • Chronic ongoing life stress • Psychiatric comorbidity

42. Follow-up In mild cases, there is generally no medical need for follow-up consultations in the long term, unless: • Symptoms persist , with considerable inconvenience or dysfunction. • The patient is seriously worried about the condition . • Persistent diarrhea > 2 weeks . • Constipation persists and does not respond to therapy . • Warning signs for possibly serious gastrointestinal disease developing • One should beware of eating disorders developing: — The tendency for eating disorders to develop is more common in female IBS patients.

43. Take home messages IBS is a very common illness that can hamper productivity and reduce the quality of life . Previously thought to be a functional disorder, now it’s more commonly recognized as complex result of intestinal dysbiosis causing altered gut-brain interaction . Usually a clinical diagnosis and intervention needs to be managed with empathy and sharing as much information as possible with the patient. Dietary and lifestyle modifications, soluble fibers, antispasmodics and probiotics are universally proven to improve global symptoms. Antidepressant and anti-diarrheal drugs need to be used judiciously keeping respective side effects in mind. Any refractory case should be managed with psychotherapy and needs long-term follow up.

44. quiz Suspected IBS patients will need colonoscopy to confirm the diagnosis. (T/F) Previous gastroenteritis can be a risk factor for IBS. (T/F) Probiotics have no role managing IBS. (T/F) Psychotherapy is usually offered as a first-line treatment. (T/F) TCAs should be offered in IBS patients with Diarrhea as predominant symptom. (T/F)

45. Thanks to Renata pharmaceuticals for making this program possible