1. IRRITABLE BOWEL SYDNROME

2. IBS - Definition Altered bowel habit and/or Altered bowel habit and/or Abdominal discomfort or pain Abdominal discomfort or pain No demonstrable organic disease No demonstrable organic disease As no marker exists for IBS, As no marker exists for IBS, diagnosis is based on clinical features diagnosis is based on clinical features

3. Summary of Hypotheses on the Pathophysiology of IBS IBS is characterized by changes in motility in response to environmental or enteric stimuli 1 Visceral hypersensitivity is well documented in IBS patients 2 Serotonin, which has both motility and sensory modulating properties, could represent a common factor linking the symptoms of IBS 3

4. Epidemiology - 1 6-22% of the North America population have seen a physician for IBS symptoms 6-22% of the North America population have seen a physician for IBS symptoms Most cases diagnosed before age 45 but IBS is sometimes diagnosed in those above 65 years Most cases diagnosed before age 45 but IBS is sometimes diagnosed in those above 65 years Women are 3 times more frequently affected than men Women are 3 times more frequently affected than men Less common in Asians & Hispanic than Caucasians Less common in Asians & Hispanic than Caucasians

5. Epidemiology - 2 6-22% of population report symptoms but only about 1/5 to 1/3 of these seek medical care 6-22% of population report symptoms but only about 1/5 to 1/3 of these seek medical care Factors associated with physician consultations: Factors associated with physician consultations: –Personality disorders or depression –Long duration of symptoms

6. Impact on Society - 1 Visits to the doctor: Visits to the doctor: –12% primary care –28% gastroenterologist Health care costs: Health care costs: –Twice that of an asymptomatic person –More appendectomies, cholecystectomies and hysterectomies in those with IBS

7. Enteric nervous system Controls motility and secretory functions of the intestine Controls motility and secretory functions of the intestine Semiautonomous Semiautonomous –actions modified by parasympathetic and sympathetic nervous systems –may function independently Contains many neurotransmitters, including 5-HT, substance P, VIP (vasoactive intestinal peptide), and CGRP (calcitonin gene-related peptide) Contains many neurotransmitters, including 5-HT, substance P, VIP (vasoactive intestinal peptide), and CGRP (calcitonin gene-related peptide) IBS – Pathophysiology

8. IBS: Current thinking on pathophysiology Visceral hypersensitivity 1 Visceral hypersensitivity 1 – Increased visceral afferent response to normal as well as noxious stimuli – Mediators include 5-HT, bradykinin, tachykinins, CGRP, and neurotropins Primary motility disorder of GI tract 2 Primary motility disorder of GI tract 2 – Mediated by 5-HT, acetylcholine, ATP, motilin, nitric oxide, somatostatin, substance P, and VIP IBS – Pathophysiology Defects in the enteric nervous system may lead to the hallmark symptoms of IBS.

9. IBS – Pathophysiology 5-HT initiates peristaltic reflex mediated by the ENS Intraluminal Pressure Mucosa Mucosal Enterochromaffin Cell 5-HT 5-HT Receptor [Enteric Nervous System]

10. 5-HT receptor effects Mediate reflexes controlling gastrointestinal motility and secretion Mediate reflexes controlling gastrointestinal motility and secretion Mediate perception of visceral pain Mediate perception of visceral pain IBS – Pathophysiology

11. Impact on Society - 2 Impairment of QOL: worse than in patients with DM or CRF Impairment of QOL: worse than in patients with DM or CRF Time off work: 3 times more often than that for an asymptomatic person Time off work: 3 times more often than that for an asymptomatic person Restriction of activities: by 145 days per year Restriction of activities: by 145 days per year

12. Rome II Criteria for Diagnosis Symptoms for at least 12 weeks (which need not be consecutive), in the preceding 12 months: Symptoms for at least 12 weeks (which need not be consecutive), in the preceding 12 months: Abdominal pain or discomfort, which has 2 of the 3 following features: Abdominal pain or discomfort, which has 2 of the 3 following features:

13. Rome II Criteria - continued 1. Pain relieved with defecation; or 2. Altered bowel habit associated with a change in the frequency of stools; or 3. Altered bowel habit associated with a change in the form (appearance) of the stools

14. Rome II Criteria - continued Other symptoms that cumulatively support the diagnosis of IBS include the following: 1. Abnormal stool frequency (>3BMx/d or 3BMx/d or <3BMs/wk) 2. Abnormal stool form (lumpy and hard or loose and watery) 3. Abnormal stool passage (straining, urgency, feeling of incomplete evacuation) 4. Passage of mucus 5. Bloating or feeling of distention.

15. Frequency of Symptoms In 154 consecutative patients diagnosed as IBS in a GI unit, there was Abdominal discomfort or pain 33% of days Abdominal discomfort or pain 33% of days Bloating 28% of days Bloating 28% of days Altered stool form 25% of days Altered stool form 25% of days Altered stool frequency 18% of days Altered stool frequency 18% of days Passage of mucus 7% of days Passage of mucus 7% of days

16. Abdominal Pain Intensity, location and characteristic of pain is highly variable – epigastric 10% – right side 20% – left sided 20% – hypogastric 25% – too variable 25% Cramping or an ache Cramping or an ache Post-prandial worsening of pain for 1-3 hours Post-prandial worsening of pain for 1-3 hours Stress or emotional turmoil worsens condition Stress or emotional turmoil worsens condition Worse before and/or during menstruation Worse before and/or during menstruation

17. Altered Bowel Habit Constipation-predominant Constipation-predominant ––hard pellet-like stools, infrequent (<1/day) Diarrhea-predominant Diarrhea-predominant – frequent loose stools – post prandial – urgency – straining – incomplete evacuation – mucoid discharge – 50%, no blood

18. Symptom Associations UGI – dyspepsia, heartburn, early satiety, nausea, all are more frequent in constipation- predominant IBS UGI – dyspepsia, heartburn, early satiety, nausea, all are more frequent in constipation- predominant IBS LGI – abdominal distention, bloating – more in women LGI – abdominal distention, bloating – more in women GUS – pelvic pain, dysmenorrhea, dyspareunia, urinary frequency, nocturia, incomplete bladder evacuation GUS – pelvic pain, dysmenorrhea, dyspareunia, urinary frequency, nocturia, incomplete bladder evacuation MSK – fibromyalgia, back pain, head & neck pain MSK – fibromyalgia, back pain, head & neck pain

19. Other Associations Increased risk of PUD, HBP, sicca syndrome & vague rashes Increased risk of PUD, HBP, sicca syndrome & vague rashes Triad of IBS, GERD & Asthma is 3-times more frequent than expected Triad of IBS, GERD & Asthma is 3-times more frequent than expected

20. ‘Red Flags’ - Alarm Symptoms/Signs Onset after 55 years Onset after 55 years Persistent anorexia & weight loss > 10 lbs Persistent anorexia & weight loss > 10 lbs Persistent “fever” in the evening Persistent “fever” in the evening Pain – changing pattern or increasing after food and persisting for a few hours Pain – changing pattern or increasing after food and persisting for a few hours Awakened by pain &/or diarrhea at night Awakened by pain &/or diarrhea at night Rectal bleeding, not just on wiping Rectal bleeding, not just on wiping Stools “like malabsorption syndrome” Stools “like malabsorption syndrome” P/E: palpable mass in the abdomen P/E: palpable mass in the abdomen

21. Differential Diagnosis 1. Dietary – e.g. lactose intolerance. 2. Infections – Giardia, Bacterial Overgrowth Syndrome 3. Inflammatory Bowel Disease – UC, CD 4. Malabsorption syndrome – Celiac Disease, Pancreatic Insufficiency 5. Psychological – Depression Anxiety 6. Other - Neuroses

22. Diagnosis - 1 Approach: before doing any tests: 1. Gain the confidence of the patient at the first consultation, let them talk and just listen 2. Remain aware that some IBS patients have a hidden agenda 3. Do not say to the patient what some FPs say, namely, “I don’t know what is wrong with you” 4. Do not say what some Specialists say, namely: “There is nothing wrong with you” or “it is in your head”

23. Diagnosis - 2 5. Get all the test reports from the other MDs files and 6. Show & discuss those test results with the patient 7. In those below 55 yrs and in the absence of “alarm symptoms”, if “routine” blood tests + ESR/CRP are normal, diagnosis of IBS has: 8. - 83% sensitivity - 97% specificity - 100% PPV Therefore, please do these tests Therefore, please do these tests

24. Diagnosis - 3 I ask the patient; “which single GI disease do you think you may have?” and I do one test first to exclude that and review the patient after the test: I ask the patient; “which single GI disease do you think you may have?” and I do one test first to exclude that and review the patient after the test: In my experience: In my experience: PainDiarrheaConstipation <50 yrsPUD, CDLI, MAS, “obstruction” >50 yrsGBD, CRCCRC are the commonest cause of anxiety for the patient

25. Diagnosis - 4 Two multicentre trials have found the following associations: Lactose Intolerance23% Lactose Intolerance23% “Structural abnormality”2% “Structural abnormality”2% Abnormal thyroid tests6% Abnormal thyroid tests6% Stools O&P 2% Stools O&P 2%

26. Diagnosis - Summary IBS remains a clinical diagnosis. IBS remains a clinical diagnosis. In those below 55 years and in the absence of alarm symptoms, Rome II Criteria (Clinical) has: In those below 55 years and in the absence of alarm symptoms, Rome II Criteria (Clinical) has: - Sensitivity 65% - Specificity 100% - PPV 100% - No diagnosis revision during 2 yr follow up Vanner etal (1999) Amer J Gast 94:2912

27. Traditional therapies focused on individual symptoms of IBS with constipation Bloating and distention  Dietary modifications  Antispasmodics  Antiflatulants  Digestive enzymes  Antibiotics Abdominal pain / discomfort  Antispasmodics  Tricyclics  Analgesics Irregular Bowel Habit  Fiber  Laxatives  Imodium Abdominal pain / discomfort Bloating / distention Constipation or Diarrhea  None of these medications effectively treat the multiple symptoms of IBS. May exacerbate individual symptoms e.g., fiber and bloating; antispasmodics and constipation