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IBS Diagnosis by fdh56iuoui

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									 The Modern Approach to the
diagnosis and treatment of IBS

        Dr Martin Buckley
    Centre for Gastroenterology
     Mercy University Hospital
                Cork
             IBS - Definition


GI syndrome
  characterized by
  chronic abdominal
  pain and altered
  bowel habits in the
  absence of any
  structural abnormality
                 IBS Diagnosis

History

Investigations

Empirical Treatment


“Diagnosis of Exclusion”
 IBS – Diagnosis: Manning Criteria
Diagnose irritable bowel syndrome if 3 are present:

• Abdominal pain

• Relief of pain on defecation

• Increased stool frequency with pain

• Looser stools with pain

• Mucus in stools

• Feeling of incomplete evacuation
 Manning criteria and probability of
                IBS

Number of Criteria   Age 20   Age 40   Age 60

Any 2                64%      51%      38%

Any 4                82%      73%      61%

Any 6                92%      87%      80%
        I BS – Rome III Criteria
Recurrent abdominal pain or discomfort at least 3
 days per month in the last 3 months associated
 with 2 or more of the following;

• Improvement with defecation
• Onset associated with a change in frequency
• Onset associated with a change in shape
                    IBS
                 Watch out if:
•   Blood per rectum
•   Weight loss / progressive symptoms
•   Waking up with symptoms
•   Vomiting
•   Change in symptom pattern
•   Dehydration
•   Systemic symptoms
•   Late age of onset
•   Family history
                 IBS Diagnosis
                        History:
•   ? Family history of GI disease
•   ? History of gastroenteritis / travel
•   ? Medication change
•   ? Antibiotics
•   ? Dietary change
•   ? Lifestyle / stress
•   ? Abdo surgery
•   Systemic symptoms
               Family history
•   Colon cancer – ? Age
•   Coeliac disease
•   Crohn’s disease
•   Ulcerative colitis
•   Peptic ulcer disease
•   Pancreas disease
                Medications
•   ? New medications
•   ? Change in dose
•   ? Alternative medications
•   ? Antibiotics

• Bring medications
to doctor and dates
     IBS Diagnosis – Initial tests
•   Full blood count
•   Markers of Inflammation (ESR / CRP)
•   Coeliac blood test
•   Thyroid blood test




• Stools for Blood and Infections
             IBS - Types

• Constipation predominant

• Diarrhoea predominant

• Pain predominant

• Bloating predominant
    IBS – Constipation-type: Tests
• Thyroid function and blood calcium levels

•   Transit studies
•   Anorectal manometry
•   Defecating proctography
•   Dynamic MRI (rectoanal angle)
•   Rectal muscle Bx
     IBS Diarrhoea-type; Tests

• Small bowel aspirate and
  biopsy
• Colonic biopsies
• Exclude pancreas
  disease
• Exclude GI Hormone
  disease
• Exclude Sugar
  malabsorption
• Exclude bacterial
  overgrowth
  IBS Pain/Bloating-type; Tests
• Ultrasound of abdomen
  and Pelvis
• Plain x-ray during
  episode of pain
• Small bowel Barium meal
• CT abdomen/pancreas
• Capsule endoscopy
• ? Breath Tests
• ? Laparoscopy
Capsule Endoscopy
Endoscopic Ultrasound
                IBS Diagnosis
• History

• Investigations

• No diagnostic test for
  IBS
– avoid over investigation
             IBS Treatment
        Stress
• Cause of IBS
• Consequence of IBS

• Lifestyle
• Exercise
• Discuss with health
  care professional
                IBS Treatment

• Doctor / patient
  relationship

• Advertising / Alternative
  industry

• Reassurance

• ? Wait and see approach
• ? As required
 IBS Constipation type:Treatment
• Adequate fluids and exercise
• Adequate fibre
• Bulking Agents
  (Fybogel, Normacol, Regulan…)
• Osmotic Laxatives
  (Lactulose, Movicol, Tiolax…)
• Stool softeners/lubricants
  (Milpar, Microlax, Micolette)
  IBS Constipation - Treatment

• Misoprostol

• Mestinon,

• Tegaserod)

• Alternative Medicines
 IBS Diarrhoea-type: Treatment
• Reduced fibre
• Antidiarrhoeals as required
 (Immodium, Lomotil …)
• Antispasmodics
 (Colofac, Spasmonal, Buscopan..)
• Bile Absorbers
 (Questran, Colistipol))
• Amitriptyline **
       IBS Bloating;Treatment
• Fibre reduction
• Exclusion diets
• Peppermint / Aloe
  vera / Charcoal
• Probiotics

• ? Trial of Antibiotic
• ? Amitriptyline ……
        IBS – Antidepressants

                 Brain – Gut Axis
Peripheral Action

• Affect pain perception
• Affect motility

Central Action

• Reduced stress
• Increased coping
             IBS - Summary
• Adequate tools for
  diagnosis

• Expanding tools for
  treatment

• Research – Future of
  IBS

      Thank you!
Role of Nutrition in Irritable
     Bowel Syndrome
          Ellen O’Mahony
              Dietitian
      Cork University Hospital
          14th June, 2008
Contents
• What is IBS & why does it happen?
• Healthy eating
• Fibre and constipation
• Fibre and diarrhoea
• Resistant starch, fructose, sorbitol, caffeine
• Probiotics
• Food intolerance
What is Irritable Bowel Syndrome
(IBS)
•   A collection of symptoms rather than a disease in itself.
•   Affects 1 in 5 people (BDA, 2004).
•   More common in women than men.
•   Symptoms
       Constipation
       Diarrhoea
       Stomach pain
       Bloating and wind
       A feeling of urgency
       Loss of appetite
       Nausea
       Tiredness
Why does it happen?

• Possible causes:
  – Lifestyle, poor diet
  – Stressful life event, anxiety or depression
  – Stomach upset
  – Antibiotics
• Why is it a problem?
  – Harmless, but symptoms are uncomfortable
What can I do about it?

• Healthy well balanced diet
• Regular meals
• Avoid skipping meals / leaving long gaps
• Avoid over-indulging
• Eat slowly, avoid distractions
• The food pyramid
Focus on fibre
• Alternating the amount and type of fibre you eat
    may help with controlling your symptoms.
•   Two types of fibre:
      Soluble fibre – dissolves in water forming a gel
      (oats, beans, peas, lentils, fruit and vegetables).
      Insoluble fibre - course bulky fibre, ↑faecal bulk,
      shortening colonic transit (granary bread, wheat, bran
      breakfast cereals, brown rice and pastas, whole
      wheat crackers and skins of fruit and vegetables).
Focus on fibre
• An ↑ in fibre is often recommended as initial
    treatment.
•   Not always appropriate to recommend a high
    fibre diet to ALL people with IBS (NICE, 2008).
•   Each individual’s fibre intake should be assessed
    and adjusted depending on symptoms:
    –   Constipation dominant
    –   Diarrhoea dominant or alternating symptoms
    –   Abdominal bloating and flatus
Constipation

• Gradually ↑ fibre
  – Wholegrain bread and breakfast cereals,
    linseeds
  – 5 portions fruit and vegetables/day
• Pure bran is not recommended
  – Can irritate the bowel lining
  – Can affect the absorption of nutrients such as
    calcium and iron
Constipation
• Pulses
  – Peas, beans and lentils
  – Great source of fibre
  – Include them once or twice a week
• Fluid = 8-10 glasses/day
• Exercise
  – Important to stimulate and strengthen the bowel
    muscle
  – Maintain regular bowel habit
  – At least 30 minutes at least 5 days per week (DOH,
    2004)
Diarrhoea
Diarrhoea alternating with constipation
Just wind and bloating

• Choose low fibre foods
• Too much fibre, especially the insoluble
  type, can make symptoms worse,
  particularly ‘wind’ or ‘bloating’
• If symptoms settle - gradually re-introduce
  fibre
• Find your tolerance level / identify
  particular foods which upset you
Diarrhoea
Diarrhoea alternating with constipation
Just wind and bloating

• Resistant starches are starches that resist
  digestion in the small intestine and
  therefore reach the colon intact.
• Limit foods which have been processed or
  re-cooked, e.g. biscuits, cakes and ready-
  made meals, soups and sauces.
• These foods contain ‘resistant starch’ -
  may make symptoms worse.
Diarrhoea with wind and bloating

• Limit fructose intake
  – 3 portions of fruit/day
  – 1 glass of fruit juice/day (SNDRI, 2004)
• Fructose is present as a free sugar in
  fruits, vegetables and honey
• Incomplete absorption in the small bowel
  can cause diarrhoea, wind and bloating.
Diarrhoea only
• Limit intake of sorbitol
• A natural component of fruits - dried apple,
    apricots, prunes, cherries, pears
•   Artificial, low calorie sweetener - sugar-free
    chewing gum, mints and cough syrups
•   A laxative effect - 30g/day (NICE, 2008)
Caffeine

• Coffee, tea, cocoa, chocolate and coke
• Excessive caffeine can have a laxative
  effect
• Some more sensitive than others
• A moderate intake of caffeine (up to
  300mg/day) is not harmful (NICE, 2008)
• Heartburn - most commonly symptom
Probiotics
• ‘Probiotics are beneficial microbes that are
    given to restore normal microflora’
    (Mcfarland, 2008)
•   Fermented milks and yogurts, cheese, frozen
    yogurt, ice cream and non-dairy foods
•   ? people with IBS may not have enough ‘good’
    bacteria, and that adding probiotics to the diet
    may help ease symptoms
•   ‘Bifidobacteria’ & ‘Lactobacilli’
Probiotics

• Effect is dose and strain dependent
• Duration - 4 weeks
• Take at the dose recommended by
  manufacturer
• Future studies are needed
• More data are needed regarding specific
  strains and doses
Food Intolerance
• ‘A non-immunologically mediated
    response to particular foods, which resolve
    following dietary elimination and re-occur
    with food challenge’ (NICE, 2008)
• Some people with IBS are unable to tolerate
    certain foods
•   Specific food intolerances have been reported in
    33-66% of IBS patients (BSG, 2007)
Food Intolerance
• Elimination or exclusion diet
    – A diet in which specific food products are
      totally excluded for a specified period of time’
      (NICE, 2008)
• The excluded food products are then gradually
    re-introduced one by one to confirm response
•   Intolerance = if symptoms resolved on
    elimination and reappeared on reintroduction
•   Under supervision of a dietitian
Summary

• Several causes of IBS
• Symptoms vary from person to person
• Variety of treatment options
• Changes to diet, depending on symptoms
  - one area to consider
• Eat a regular, healthy diet with adequate
  fibre, fluid and exercise
QUESTIONS
Introduction and Overview of
 Recent Progress in Irritable
      Bowel Syndrome.
      Eamonn M M Quigley
          CUH, APC
      UCC Medical School
The Angry Gut
          Irritable Bowel Syndrome
              Definition
• No pathology
• No blood test
• No diagnostic x-ray findings

      i.e. diagnosis is entirely clinical
                 Diagnosis
• By exclusion
  – IBS-type symptoms may occur with other
    conditions
    • There are many causes of diarrhoea
• Definitive; based on symptoms
                “Rome” Criteria
• IBS
  – Abdominal pain or discomfort present for at least
    12 weeks in the preceding 12 months and has 2 of
    the following 3 features:
     • Relieved by defecation
     • Onset associated with a change in stool frequency
     • Onset associated with a change in stool form
  – May be additional symptoms:
     •   bloating,
     •   distension,
     •   constipation,
     •   diarrhoea
Irritable Bowel Syndrome (IBS)
      a simpler definition


“IBS is defined by abdominal discomfort
 associated with altered bowel habits”

                ACG Position Statement 2002
Common
            How common?
• 10-15% of the population!
• Twice as common in females
• Equally common:
  – Diarrhoea-predominant
  – Constipation-predominant
  – Alternating
• A global problem
Causes Many and Potentially
    Severe Symptoms
       IBS in the Real World!

• Community survey of over 40,000 adults in 8
  European countries:
   – Overall prevalence 11.5% (6.2-12%)
      • 9.6% current symptoms
          – Only 2.8% formally diagnosed as IBS
      • Symptoms:
          –   Abdominal Pain : 88%
          –   Bloating        : 80%
          –   Trapped wind : 66%
          –   Tiredness       : 60%
          –   Constipation    : 53%
          –   Diarrhoea       : 59%
          –   Heartburn        : 47%

                                                  Hungin et al, APT 2003
        Symptom Frequency
No. of Days    Frequency (%)
Affected per
Month
1-3            40

4-9            29              Average:
                                7 days
10-20          17               per
                                month
> 21           8
                               Hungin et al, APT 2003
 Extra-intestinal Associations
Fibromyalgia               49% have IBS

Chronic Fatigue Syndrome   51%

Temporo-Mandibular Joint   64%
Syndrome

Chronic Pelvic Pain        50%


                                 Whitehead et al, 2002
Impairs Quality of Life
             Quality of Life
• Significant impact on quality of life
  (QOL):
  – School
  – Work
  – Family
• Costly
  – Doctor visits
  – Health care costs
Impact of IBS on QOL




  Community sample of 25,986 in US
   Overall prevalence of IBS 6.6%
                                     Andrews et al, APT 2005
Socio-Economic Impact
    Economic Impact of IBS
• US vs UK
• Total Direct Costs:
  – $US 348-8750
• Total Indirect Costs:
  – $US 355-3344
• Days lost from work per year due to
  IBS:
  – 8.5-21.6
                          Maxon-Bergemann et al, Pharmacoeconomics 2006
   What is the Cause of IBS
• Probably no single cause
• Different causes in different patients
  – Infection
    • Post-infectious IBS
  – Inflammation
  – Brain-Gut Axis problems
  – Etc.
                   Stress
                   Anxiety/Depression
                   Abnormal Gut Perception
                   Abnormal Hormonal Responses



                    THE GUT-BRAIN AXIS



Spasm
Sensitivity
Food Intolerance
Infection/SIBO
Inflammation
             IBS Susceptibility
• Demographics similar:
   – Female
   – Pre-morbid psychopathology
• Genetics:
   – Twin studies:
        • Mother or father with IBS stronger predictor of IBS
          than a twin with IBS

                                          Levy et al, 2001
   –   G-protein polymorphisms
   –   IL-10 polymorphisms
   –   SERT polymorphisms
   –   CTLA-4 haplotypes
             Post-Infectious IBS
• 10-14% incidence
  following confirmed
  bacterial
  gastroenteritis
              Dunlop et al, 2003
              Mearin et al, 2005



• Risk factors
   – Female
   – Severe illness
   – Pre-morbid psyche
      • depression
   – Persistent inflammation
      • EC cells
      • T lymphocytes
                                   Dunlop et al, 2003
       The Catalan Experience!

                   1878




         677               1201


At 12Prior RR
           to    C.I.
                Exposed     Non-
months
     Exposure              Exposed
FD        5.2
         FD     2.7-9.8
                  2.5%       3.8%

IBS      7.8
       IBS      3.1-19.7
                  2.9%       2.5%
                                     Mearin et al, 2005
Walkerton, Ontario




         Marshall et al, 2006
          CSGNA Outbreak
            - norovirus
Time   Exposed          Un-exposed      OR
(mo)
  3     23.6                  3.4       6.9


 6      12.5                 10.3       NS


 12     15.1                  7.8       NS


24      19.5                  8.3       NS


                 Marshall et al, 2007
                  Lessons from
                     PI-IBS
                                     Inflammatory Response
Disturbed Flora




                  Susceptible Host

                        Myo-Neural
    SYMPTOMS            Dysfunction
What is going on the in the rest
            of IBS?
 I. Evidence of Inflammation
              Mucosal Compartment
• Increased mast cells
• More degranulating
  mast cells
             Barbara et el, 2004
• Frank inflammation
• Immune Activation
   – ↑ IEL’s
   – ↑ CD3+, CD25+
       Chadwick et al, 2002
• Close relationship
  between mast cells &
  sensory afferents
  predicts symptom
  severity in IBS
         Barbara et el, 2004
               Protease Activity
• Colonic biopsy              Biopsies


  samples release
  increased levels of
  proteolytic activity
  (NF-κB dependent)
• Increased
  proteolytic activity        Supernatants

  from colonic washes
• Trypsin and tryptase
  expression increased
  in colonic biopsies
                         Cenac et al 2007
Mucosal Immunology
Quantitative RT-PCR
                              Systemic Compartment
                                     PBMC’s
                        300
                                                                                  Pre-treatment
                        250                                                       Post-treatment
    IL-10:IL-12 ratio




                        200

                        150
                                  *
                        100

                         50

                          0
                              B. infantis 35624 L. salivarius 4331   Placebo         Healthy
                                                                                    volunteers

                                                                               O’Mahony et al,
                                                                               Gastroenterology, 2005
*   p =.001
                         Systemic Compartment
                                Serum
                   *    IL-6                                *     sIL-6r
              6                                    150000
              5
IL-6(pg/ml)




              4                                    100000




                                          sIL-6r
              3

              2                                    50000

              1

              0                                        0
                  IBS          Controls                     IBS            Controls




                        Dinan et al, Gastroenterology 2006
                           IL-10                                                          TNFα
                40                                                             60

                                                                               50
                30
IL-10 (pg/ml)




                                                                  TNF(pg/ml)
                                                                               40

                20                                                             30

                                                                               20
                10
                                                                               10

                0                                                              0
                     IBS                      Controls                              IBS          Controls

                                                         * IL-8
                                             10.0


                                              7.5
                              IL-8 (pg/ml)




                                              5.0


                                              2.5


                                              0.0
                                                         IBS      Controls
              Serum Cytokines influence Gut-Brain
                            Axis
                                    ACTH Response to CRH
         30
                        **                                 Healthy subjects
                              **                           IBS
         20
ACTH
(ng/l)




         10



         0
              -15   0   15    30   45     60   90   120
                             Time (min)

          Significant correlation between the ACTH
                      response (δACTH)
           and IL-6 levels (r= 0.61, df=40, p<0.05).
        Other “Inflammatory”
               Factors
• IBS and IBD
  – IBS symptoms in IBD “in remission”
    represent sub-clinical inflammation
          Keohane et al, DDW 2007

• IBS and “food allergy”
• IBS and “food intolerance”
• D-IBS and gluten
What is going on the in the rest
            of IBS?
         II. Gut Flora
               Gut flora in IBS
• Altered gut flora
  – SIBO
  – Altered Colonic Flora
     • Qualitative
     • Quantitative
• Changes in flora
  – Affect stool
     • Reduce bile salt deconjugation
  – Affect gas
     • Decrease fermentation
           Small Intestinal Bacterial
          Overgrowth (SIBO) in IBS
• SIBO at baseline
  –   20% controls
  –   84% IBS
  –   100% Fibromylagia
  –   Associated with lower MMC frequency
           » Pimentel et al, 2002, 2004
  – Pattern of gas excretion predicts symptom
Response to eradication
    10 days rifaximin; follow-up for 10 weeks




Pimentel, M. et. al. Ann Intern Med 2006;145:557-563
                      SIBO in IBS
Other studies:
   – Walters and Vanner, Am J Gastro 2005
       • Abnormal lactulose breath test in 10%
       • Abnormal d-xylose breath test in 13%
             – No difference from controls
   – Parisi et al, Am J Gastro 2003
       • 85 IBS subjects
       • No positive glucose breath hydrogen test
   – Ruff et al, ACG 2006
       • Jejunal culture results from 690 patients
       • IBS + 6%; Bloating + 11%
   – Posserud et al, Gut 2007
       •   162 IBS subjects
       •   All had jejunal cultures
       •   SIBO (> 105) in 4% of IBS and controls
       •   Mild increase in bacterial counts 43% IBS, 12% controls
       •   Enteric dysmotility more common in IBS with SIBO
               GI Flora in IBS
• ↓ Bifidobacteria, ↑ Enterobacteriaceae
  in stool samples of 25 Rome II IBS
          » Si et al, 2004.

• Other studies provide conflicting
  results, a “deficiency” in bifidobacteria
  being the most consistent finding
• ? Relevance of faecal flora and culture
  methods
                Biopsy                                     Feces

1   2   3   4   5    6   7   8       9   10 11   12   13   14   15   16   17   18   19 20




                                                  2
                                 6
                         8
                 5
                                                  3


                         9                                            1


                             7                    4




    Considerable variability in fecal flora
          IBS and Controls differ
      Minimal variability in Biopsy flora
                       Variability in Flora

                                           IB S
               1 0 0
                          H e a lth y
                9 0

                8 0

                7 0

                6 0
% similarity




                5 0

                4 0

                3 0

                2 0

                1 0

                  0




                         Control          IBS


                                        Marchesi et al, 2008
         The Fecal                                      7
                                                             C-IBS


        Flora in IBS                      C and M-IBS        D-IBS



        10

                                                        10




             13                                                M-IBS
   7



                                                        13




    G+C Content
         of
Genomic Bacterial DNA                    Cloning and
                  Kassinen et al, 2007   Sequencing
           Can we begin to put
             this together?
                             Mucosa
   Flora
                            (Immune
(Dysbiosis)
                           Dysfunction)
           Immune Activation


               Dysmotility
              Dysmotility
        Visceral Hypersensitivity
        Visceral Hypersensitivity
       Gut-Brain Axis Dysfunction
       Gut-Brain Axis Dysfunction
           Is this of any Clinical
                Relevance?
• Diagnosis:
  • Biomarker
• Prognosis
• Therapy:
  • Anti-inflammatories
    • Steroids
    • Mesalamine
  • Antibiotics
  • Probiotics
                    300
                                                                           Pre-treatment
                    250                                                    Post-treatment
IL-10:IL-12 ratio




                    200

                    150

                    100
                               *
                     50

                      0
                          B. infantis 35624 L. salivarius 4331   Placebo     Healthy
                                                                            volunteers



                                                             O’Mahony et al,
                          *   p =.001                        Gastroenterology 2005
                                           Global Assessment of Symptom
                              80
                                                       Relief
                                                                             P=0.0118


                              70
% answering “yes” at Week 4




                              60


                              50



                              40



                              30


                                   B. infantis 1X1010 B. infantis 1X108   B. infantis 1x106   placebo
                  Summary
• A real, global disorder of significant impact
  – Significant and diverse symptoms
  – Impacts QOL
  – Socio-economic implications
• Unmet therapeutic need
  – Lack of efficacy of “old” therapies
  – Adverse event issues with some “new” therapies
  – Many unproven approaches
            The Good News
• IRRITABLE BOWEL SYNDROME IS
  BEING TAKEN SERIOUSLY:
 –   By clinicians
 –   By researchers
 –   By those who fund research
 –   By pharmaceutical companies
 –   By society!

								
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