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irritable bowel syndrome

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irritable bowel syndrome Powered By Docstoc
					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)
                 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?
            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:
1.   A change in stool frequency (>3 day
     <3 week
2.   Noticeable difference in stool form
3.   Passage of mucous in stools
4.   Bloating or feeling of abdo distension
5.   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
                 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?
          Examination findings
   Nil
                 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?
                   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
Organic GI       IBS patients %     Prevelance in
disease          (pre test prob.)   General pop. %
Colitis/IBD      0.51-0.98          0.3-1.2
Colorectal Ca    0-0.51             4-6
Coeliac          4.67               0.25-0.5
GI infection     0-1.7              NA
Thyroid abn.     6                  5-9
Lactose malabs   22-26              25
              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
                 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?
   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.
                 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?
                   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 inhibitor anti-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                                Beware alarm symptoms:
             diagnosis with Rome criteria                        Wt loss, PR bleeding, recent change
                 history, examination                                     in bowel habit etc


           Basic Ix: stool culture, FBC, U&E, LFT,                   Refer for further investigation
           CRP, TFT, anti TTG Ab, glucose, Ca

   Explanation, reassurance, dietary and lifestyle advice

   IBS-C                               IBS-D                                 Pain/bloating

Increase dietary fibre / fluid    Dietary modification           Reduced fibre intake
Bulk forming laxative(s)          Anti-diarrhoeal agents         Increased fluids
Consider citalopram               Consider amitriptyline         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

				
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