Transcript An evidence based approach to IBS

Irritable Bowel
Syndrome
Dr John Hamlin PhD MRCP
Consultant Gastroenterologist
Leeds General Infirmary
Areas to cover:
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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
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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
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Great effect on QOL
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Large drain on healthcare and economy
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Accounts for 20% self certification
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Av 14.8 sick days vs. 8.7 average
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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
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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
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Bacterial overgrowth
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Stress
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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.
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Defining the disease
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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:
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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……………
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Rome criteria (2)
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1.
2.
3.
4.
5.
Two or more of the following are present at least
25% of the time:
A change in stool frequency (>3 day
<3 week
Noticeable difference in stool form
Passage of mucous in stools
Bloating or feeling of abdo distension
Altered stool passage (tenesmus, straining)
Supportive symptoms of IBS:
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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:
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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:
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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
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Nil
Areas to cover:
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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
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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
disease
Colitis/IBD
IBS patients %
(pre test prob.)
0.51-0.98
Prevelance in
General pop. %
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.
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<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:
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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?
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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:
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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
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Reassurance
Lifestyle changes
Dietary intervention
Psychological intervention
Drug intervention
Dietary intervention
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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
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Diet
Dietary changes may prevent the overreaction of the gastrocolic
reflex and lessen pain, discomfort, and bowel dysfunction.
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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.
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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.
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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.
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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.
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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
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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
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Drug intervention cont.
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Antispasmodics: 3 RCTs. Questionable benefit. Only
short term trials. A meta-analysis by the Cochrane
Collaboration suggest NNT = 6.
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Antidepressants: TCADs: Meta analysis in 2000 Am J
Gastro showed significant effect over placebo NNT 3
(best for D-IBS).
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SSRIs: Citalopram (Tack et al., Gut 2006) improved
pain, bloaring and QOL. Better for C-IBS?
Drugs affecting serotonin (5-HT)
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Serotonin stimulates the gut motility and so agonists can help constipation
predominate irritable bowel while antagonists can help diarrhea predominant irritable
bowel:
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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.
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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 sideeffects 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
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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
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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
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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
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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
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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
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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.
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A double-blind, randomized, placebo-controlled trial compared the multiherbal 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.
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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
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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.
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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.
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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
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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
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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
diagnosis with Rome criteria
history, examination
Basic Ix: stool culture, FBC, U&E, LFT,
CRP, TFT, anti TTG Ab, glucose, Ca
Beware alarm symptoms:
Wt loss, PR bleeding, recent change
in bowel habit etc
Refer for further investigation
Explanation, reassurance, dietary and lifestyle advice
IBS-C
Increase dietary fibre / fluid
Bulk forming laxative(s)
Consider citalopram
IBS-D
Dietary modification
Anti-diarrhoeal agents
Consider amitriptyline
Pain/bloating
Reduced fibre intake
Increased fluids
Antispasmodics
Consider TCADs/citalopram
In refractory cases consider counselling, hypnotherapy, biofeedback, role of probiotics
Conclusions
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A complex multifactorial ‘disease’
Huge resource useage
Targeted drug therapy difficult
New therapies but modest results
Probably grossly over investigated in many cases