IRRITABLE BOWEL SYDNROME

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IRRITABLE BOWEL SYDNROME

• Provash C. Ganguli MBBS, FRCPE, FRCPC
• Clinical Professor of Medicine
• University of Saskatchewan
• Saskatoon, SK

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IBS - Plan of Presentation

• Today I will talk about the
• Definition, epidemiology, pathophysiology,
  clinical features, differential diagnosis,
  investigations and
• clinical trial data on various treatments and
  end with a practical approach to management for
  IBS

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IBS - Definition

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

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Summary of Hypotheses on the Pathophysiology of
IBS

• IBS is characterized by changes in motility in
  response to environmental or enteric stimuli1
• Visceral hypersensitivity is well documented in
  IBS patients2
• Serotonin, which has both motility and sensory
  modulating properties, could represent a common
  factor linking the symptoms of IBS3

1AGA Patient Care Committee Gastroenterology
19971122120-2137 2 Adapted from Camilleri and
Choi et al., Aliment Pharmacol Ther 1997 11 3
3Kim and Camilleri et al., Am J Gastroenterol
2000 95(10) 2698
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Epidemiology - 1

• FRAP in childhood may herald IBS in adulthood
• 6-22 of the NA population have seen a
  physician for IBS symptoms
• 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
• Less common in Asians Hispanic than
  Caucasians

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Epidemiology - 2

• 6-22 of population report symptoms but only
  about 1/5 to 1/3 of these seek medical care
• Factors associated with physician
  consultations
• Personality disorders or depression
• Long duration of symptoms
• Patients opinion re cause of symptoms
• Drossman etal (1992)Dig Dis Sci 381569
• Taltey etal (1997) Gut 41394

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Impact on Society - 1

• Visits to the doctor
• 12 primary care
• 28 gastroenterologist
• Mitchell Drossman (1987) Gastroent.921282
• Health care costs
• Twice that of an asymptomatic person
• More appendectomies, cholecystectomies and
  hysterectomies in those with IBS

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Impact on Society - 2

• Impairment of QOL worse than in patients
  with DM or CRF
• Gralneck etal (2000) Gastroent 119654
• Time off work 3 times more often than that
  for an asymptomatic person
• Restriction of activities by 145 days per year
• Creed etal (2001) Ann Int Med 134860

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Rome II Criteria for Diagnosis

• 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

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Rome II Criteria - continued

• Pain relieved with defecation or
• Altered bowel habit associated with a change in
  the frequency of stools or
• Altered bowel habit associated with a change in
  the form (appearance) of the stools

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Rome II Criteria - continued

• Other symptoms that cumulatively support the
  diagnosis of IBS include the following
• Abnormal stool frequency (gt3BMx/d or lt3BMs/wk)
• Abnormal stool form (lumpy and hard or loose and
  watery)
• Abnormal stool passage (straining, urgency,
  feeling of incomplete evacuation)
• Passage of mucus
• Bloating or feeling of distention.

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Frequency of Symptoms

• In 154 consecutative patients diagnosed as IBS
  in a GI unit, there was
• Abdominal discomfort or pain 33 of days
• Bloating 28 of days
• Altered stool form 25 of days
• Altered stool frequency 18 of days
• Passage of mucus 7 of days
• Hahn etal (1978) Dig Dis Sci 432715

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• 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
• Post-prandial worsening of pain for 1-3 hours
• Stress or emotional turmoil worsens condition
• Worse before and/or during menstruation

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• Altered Bowel Habit
• Constipation-predominant
• hard pellet-like stools, infrequent (lt1/day)
• Diarrhea-predominant
• frequent loose stools
• post prandial
• urgency
• straining
• incomplete evacuation
• mucoid discharge 50, no blood

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Symptom Associations

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

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Other Associations

• Increased risk of PUD, HBP, sicca syndrome
  vague rashes
• Triad of IBS, GERD Asthma is 3-times more
  frequent than expected
• Kennedy etal (1998) Gut 43770
• Fass etal (1998) Digestion 5979
• Sperker etal (1999) Amer J Gast 943541

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Red Flags - Alarm Symptoms/Signs

• Onset after 55 years
• Persistent anorexia weight loss gt 10 lbs
• Persistent fever in the evening
• Pain changing pattern or increasing after
  food and persisting for a few hours
• Awakened by pain /or diarrhea at night
• Rectal bleeding, not just on wiping
• Stools like malabsorption syndrome
• P/E palpable mass in the abdomen

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Differential Diagnosis

• Dietary e.g. lactose intolerance, Xs caffeine
  etc
• Infections Giardia, Bacterial Overgrowth
  Syndrome
• Inflammatory Bowel Disease UC, CD, Microscopic
  Colitis
• Malabsorption syndrome Celiac Disease,
  Pancreatic Insufficiency
• Psychological Depression Anxiety, Somatization
• Other - Neuroses

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Diagnosis - 1

• Approach before doing any tests
• Gain the confidence of the patient at the first
  consultation, let them talk and just listen
• Remain aware that some IBS patients have a
• hidden agenda
• 3. Do not say to the patient what some FPs say,
  namely, I dont 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

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Diagnosis - 2

• Get all the test reports from the other MDs files
  and
• Show discuss those test results with the
  patient
• In those below 55 yrs and in the absence of
  alarm symptoms, if routine blood tests
  ESR/CRP are normal, diagnosis of IBS has
• - 83 sensitivity
• - 97 specificity
• - 100 PPV
• Therefore, please do these tests
• Tolliver etal (1994) Amer J Gast 89176

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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
• In my experience
• Pain Diarrhea Constipation
• lt50 yrs PUD, CD LI, MAS, obstruction
• gt50 yrs GBD, CRC CRC
• are the commonest cause of anxiety for the
  patient

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Diagnosis - 4

• Two multicentre trials have found the following
  associations
• Lactose Intolerance 23
• Structural abnormality 2
• Abnormal thyroid tests 6
• Stools OP 2
• Hamm etal (1999) Amer J Gast 941279

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Diagnosis - Summary

• IBS remains a clinical diagnosis.
• 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 942912

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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

Abdominal pain /discomfort
Bloating /distention
Constipation or Diarrhea

• Irregular Bowel Habit
• Fiber
• Laxatives
• Imodium

• None of these medications effectively treat the
  multiple symptoms of IBS. May exacerbate
  individual symptoms e.g., fiber and bloating
  antispasmodics and constipation

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Placebo-Response Rate in GI Clinical Trials

• Placebo Author Drug Response ()
• Piai Prifinium 50
• Milo Domperidone 34
• Page Dicyclomine 54
• Heefner Desipramine 60
• Myren Trimipramine 67
• Longstreth Psyllium 40
• Fielding Timolol 59
• Fielding Trimebutine 58

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Meta-Analysis of Antidepressants in IBS
Ganguli 2003
JL Jackson Am J Med 200010865-72
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Dicetel and Colonic Transit in IBS-D
Ganguli 2003
Colonic Transit time (Hrs)

• RCT of 91 pts with IBS-D randomized to a) Dicetel
  50 mg TID \ x 2 wks
• b) Mebeverine 100 mg TID /
• Improvement in global well being in both groups
  of patients (73 and 72 respectively)
• Meta-analyses has shown Dicetel OR of global
  improvement of 2.15 with NNT 6, Plt0.05

Plt0.01
J Gast and Hepatol 200015925-30 J Jailwala An
Int Med 2000133136-147
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Treatment of IBS-Diarrhea
Ganguli 2003

• A recent systematic review found that 4 of 4
  studies of loperamide (Imodium) showed an
  improvement in diarrhea, and 2 of 2 showed global
  improvement.
• One trail had enough data to calculate ARR of
  0.28 for global improvement yielding a NNT of 3.6

J Jailwala An Int Med 2000133136-147
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IBS Symptomatic Therapy
Smooth muscle relaxants 5-HT agonists/antagonists
Antiflatulents
Smooth muscle relaxants 5-HT agonists/antagonists
TCAs, SSRIs
Abdominal pain/discomfort
Bloating
Altered bowel function
DIARRHEA Loperamide Cholestyramine 5-HT3
antagonists
CONSTIPATION Fibres Osmotic agents 5-HT4 agonists
Prokinetics
Dr. Marc Bradette
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Evidence-Based Position Statement on Management
of IBS
Ganguli 2003

• Summary (Grades of Evidence)
• 1) IBS defined by abdominal discomfort plus
  altered bowel habits (C)
• 2) IBS significantly decrease quality of life
  (QOL) of most patients seeking care (C).
• 3) Treatment indicated when patient physician
  believe QOL is diminished (C)
• 4) IBS therapies should improve global symptoms
  including discomfort, bloating, and altered bowel
  habits (C).

Am J Gastro 200297S1-S5
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Management - Summary

1. Lifestyle (no data)
2. Diet (poor data)
3. Pain management (meta-analysis)
4. Antidiarrheals (db, pc trials)
5. Osmotic laxatives (no data)
6. Psychotherapy (no good data)
7. Antidepressants (meta-analysis)
8. Probiotics (no data)
9. Others - Alternative Medical Therapies (no data)