Transcript An evidence based approach to IBS

Irritable Bowel
Syndrome
Dr. A. Azad
Gastroentrologist
Internal ward in YUMS
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
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?
Abdominal Pain
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prerequisite clinical feature of IBS.
highly variable in intensity and location.
frequently episodic and crampy, but it may be superimposed on a background
of constant ache.
Pain may be mild enough to be ignored may interfere with daily activities.
malnutrition due is exceedingly rare.
Sleep deprivation is also unusual because abdominal pain is almost uniformly
present only during waking hours. However, patients with severe IBS
frequently wake repeatedly during the night; thus, nocturnal pain is a poor
discriminating factor between organic and functional bowel disease.
Pain is often exacerbated by eating or emotional stress
improved by passage of flatus or stools.
In addition, female patients with IBS commonly report worsening symptoms
during the premenstrual and menstrual phases.
Altered Bowel Habits
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The most consistent clinical feature in IBS.
The most common pattern is constipation
alternating with diarrhea, usually with one of these symptoms predominating. At first,
constipation may be episodic, but eventually it becomes continuous and increasingly
intractable to treatment with laxatives.
Stools are usually hard with narrowed caliber, possibly reflecting excessive dehydration
caused by prolonged colonic retention and spasm.
Incomplete evacuation, thus leading to repeated attempts at defecation in a short time
span.
If predominant symptom is constipation ,it may have weeks or months of
constipation interrupted with brief periods of diarrhea.
Diarrhea resulting from IBS usually consists of small volumes of loose stools. Most
patients have stool volumes of <200 mL. Nocturnal diarrhea does not occur in IBS.
Diarrhea may be aggravated by emotional stress or eating. Stool may be accompanied
by passage of large amounts of mucus.
Gas and Flatulence
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Patients with IBS frequently complain of abdominal distention and increased
belching or flatulence, all of which they attribute to increased gas.
Although some patients with these symptoms actually may have a larger
amount of gas, quantitative measurements
reveal that most patients who complain of increased gas generate no more
than a normal amount of intestinal gas.
Most IBS patients have impaired transit and tolerance of intestinal gas loads.
In addition, patients with IBS tend to reflux gas from the distal to the more
proximal
intestine, which may explain the belching.
Upper Gastrointestinal Symptoms
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Between 25 and 50% of patients with IBS complain of dyspepsia, heartburn, nausea,
and vomiting. This
suggests that other areas of the gut apart from the colon may be involved. Prolonged
ambulant recordings of small-bowel motility in patients with IBS show a high
incidence of abnormalities in the small bowel during the diurnal (waking) period;
nocturnal motor patterns are not different from those of healthy controls. The overlap
between dyspepsia and IBS is great. The prevalence of IBS is higher among patients
with dyspepsia (31.7%) than among those who reported no symptoms of dyspepsia
(7.9%). Conversely, among patients with IBS, 55.6% reported symptoms of dyspepsia.
Those with predominant dyspepsia or IBS can flux between the two
Thus it is conceivable that functional dyspepsia and IBS are two manifestations of a
single, more extensive digestive system disorder. Furthermore, IBS symptoms are
prevalent in non cardiac chest pain
patients, suggesting overlap with other functional gut disorders.
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Bleeding is not a feature of IBS unless
hemorrhoids are present, and malabsorption or
weight loss does not occur.
Pathophysiology
Gastrointestinal Motor
Abnormalities
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Studies of colonic myoelectrical and motor activity under unstimulated
conditions have not shown consistent abnormalities in IBS. In contrast,
colonic motor abnormalities are more prominent under stimulated conditions
in IBS.
IBS patients may exhibit increased rectosigmoid motor activity for up to 3 h
after eating.
Similarly, inflation of rectal balloons both in IBS-D and IBS-C patients leads
to marked and prolonged distention-evoked contractile activity. Recordings
from the transverse, descending, and sigmoid colon showed that the motility
index and peak amplitude of high-amplitude propagating contractions
(HAPCs) in diarrhea-prone IBS patients were greatly increased compared to
those in healthy subjects and were associated with rapid colonic transit and
accompanied by abdominal pain.
Visceral Hypersensitivity
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As with studies of motor activity, IBS patients frequently exhibit
exaggerated sensory responses to visceral stimulation. The
frequency of perceptions of food intolerance is at least twofold
more common than in the general population. Postprandial pain
has been temporally related to entry of the food bolus into the
cecum in 74% of patients. On the other hand, prolonged fasting
in IBS patients is often associated with significant improvement
in symptoms. Rectal balloon inflation produces nonpainful and
painful sensations at lower volumes in IBS patients than in
healthy controls without altering rectal tension, suggestive of
visceral afferent dysfunction in IBS. Similar studies show gastric
and esophageal hypersensitivity in patients with
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Non ulcer dyspepsia and non cardiac chest pain, raising the
possibility that these conditions have a similar pathophysiologic
basis. Lipids lower the thresholds for the first sensation of gas,
discomfort, and pain in IBS patients. Hence, postprandial
symptoms in IBS patients may be explained in part by a nutrientdependent exaggerated sensory component of the gastrocolonic
response.
The afferent pathway disturbances in IBS appear to be selective
for visceral innervation with sparing of somatic pathways. The
mechanisms responsible for visceral hypersensitivity are still
under investigation.
Central Neural Dysregulation
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The role of central nervous system (CNS) factors in the pathogenesis of IBS
is strongly suggested by the clinical association of emotional disorders and
stress with symptom exacerbation and the therapeutic response to therapies
that act on cerebral cortical sites. Functional brain imaging studies such
as magnetic resonance imaging (MRI) have shown that in response to
distal colonic stimulation, the mid-cingulate cortex—a brain region
concerned with attention processes and response selection—shows greater
activation in IBS patients. Modulation of this region is associated with
changes in the subjective unpleasantness of pain. In addition, IBS patients
also show preferential activation of the prefrontal lobe, which contains
a vigilance network within the brain that increases alertness. These may
represent a form of cerebral dysfunction leading to the increased perception
of visceral pain.
Abnormal Psychological Features
Abnormal psychiatric features are recorded in up to 80% of IBS patients, especially in
referral centers;
however, no single psychiatric diagnosis predominates. Most of these patients
demonstrated exaggerated symptoms in response to visceral
distention, and this abnormality persists even after exclusion of psychological
factors. Psychological factors influence pain thresholds in IBS patients, as stress alters
sensory thresholds.
An association between prior sexual or physical abuse and development of IBS has
been reported. Abuse is associated with greater pain reporting, psychological distress, and
poor health outcome. Brain functional MRI studies show greater activation of the
posterior and middle dorsal cingulate cortex, which is implicated in affect
processing in IBS patients with a past history of sexual abuse. Thus, patients with
IBS frequently demonstrate increased motor reactivity of the colon and small bowel to a
variety of stimuli and altered visceral sensation associated with lowered sensation
thresholds. These may result from CNS–enteric nervous system dysregulation
Post infectious IBS
IBS may be induced by GI infection. In an investigation of 544 patients with confirmed
bacterial gastroenteritis, one quarte developed IBS subsequently. Conversely, about a third
of IBS patients experienced an acute “gastroenteritis-like” illness at the onset of their
chronic IBS symptomatology. This group of “post infective” IBS occurs more commonly
in females and affects younger rather than older patients. Risk factors for
developing postinfectious IBS include, in order of importance, prolonged duration
of initial illness, toxicity of infecting bacterial strain, smoking, mucosal markers
of inflammation, female gender, depression, hypochondriasis, and adverse life
events in the preceding 3 months. Age older than 60 years might protect against
postinfectious IBS, whereas treatment with antibiotics has been associated with
increased risk. The microbes involved in the initial infection are Campylobacter, Salmonella,
and Shigella. Those patients with Campylobacter infection who are toxin-positive are more
likely to develop postinfective IBS. Increased rectal mucosal entero endocrine cells, T
lymphocytes, and increased gut permeability are acute changes following Campylobacter
enteritis that could persist for more than a year and may contribute to postinfective IBS.
Immune Activation and Mucosal
Inflammation
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Some patients with IBS display persistent signs of low-grade
mucosal inflammation with activated lymphocytes, mast cells,
and enhanced expression of pro inflammatory cytokines. These
abnormalities may contribute to abnormal epithelial secretion
and visceral hypersensitivity. There is increasing evidence that
some members of the superfamily of transient receptor
potential (TRP) cation channels such as TRPV1 (vanilloid)
channels are central to the initiation and persistence of visceral
hypersensitivity.
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Mucosal inflammation can lead to increased expression of
TRPV1 in the enteric nervous system. Enhanced expression of
TRPV1 channels in the sensory neurons of the gut has been
observed in IBS, and such expression appears to correlate with
visceral hypersensitivity and abdominal pain. Interestingly,
clinical studies have also shown increased intestinal permeability
in patients with IBS-D. Psychological stress and anxiety can
increase the release of pro inflammatory cytokine, and this in
turn may alter intestinal permeability. This provides a functional
link between psychological stress, immune activation, and
symptom generation in patients with IBS.
Altered Gut Flora
A high prevalence of small intestinal bacterial overgrowth in IBS patients has
been noted based on positive lactulose hydrogen breath test. This finding,
however, has been challenged by a number of other studies that found no
increased incidence of bacterial overgrowth based on jejunal aspirate culture.
Abnormal H2 breath test can occur because of small-bowel rapid transit
and may lead to erroneous interpretation.
Studies using culture-independent approaches such as 16S Rrna gene-based
analysis found significant differences between the molecular profile of the fecal
microbiota of IBS patients and that of healthy subjects. IBS patients had
decreased proportions of the genera Bifidobacterium and Lactobacillus and increased
ratios of Firmicutes:Bacteroidetes. It has been speculated that these changes may
be related to stress and diet.
A temporary reduction in lactobacilli has been reported in animal models of
early-life stress. On the other hand, Firmicutes is the dominant phylum in adults
consuming a diet high in animal fat and protein. However, it is still unclear
whether such changes in fecal microbiota are causal, consequential, or merely the
result of constipation and diarrhea. In addition, the stability of the change in the
microbiota needs to be determined.
Abnormal Serotonin Pathways
The serotonin (5-HT)-containing enterochromaffin cells in the
colon are increased in a subset of IBS-D patients compared to
healthy individuals or patients with ulcerative colitis. Furthermore,
postprandial plasma 5-HT levels were significantly higher in this
group of patients compared to healthy controls.
Because serotonin plays an important role in the regulation of GI
motility and visceral perception, the increased release of serotonin
may contribute to the postprandial symptoms of these patients and
provides a rationale for the use of serotonin antagonists in the
treatment of this disorder.
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Bowel pattern subtypes are highly unstable.
~33% prevalence rates of IBS-diarrhea
predominant (IBSD),
~33% IBS-constipation predominant (IBS-C),
~33% IBS-mixed (IBS-M)
75% of patients change subtypes and 29%
switch between IBS-C and IBS-D over 1 year.
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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
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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
Complete physical examination, especially
abdomen, should be done, but pure IBS has
no significant findings in physical
examination
Because IBS is a disorder for which no
pathognomonic abnormalities have been
identified, its diagnosis relies on recognition of
positive clinical features and elimination of other
organic diseases.
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?
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
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?
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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Exclusion of gas producing foods
Lactose avoidance
Low fermentable oligo-di and monosaccharides
and polyols (FODMAPS)
Gluten avoidance
Fiber
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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.
Constipation
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Psyllium
Lactulous, PEG
LUBIPROSTONE
Linactolide
Tegaserod (5HT4 agonist)
Diarrhea
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Loperamide
Cholestyramine
Alestron( antagonist serotonin)
Abdominal pain
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At first constipation should be treatment
Dicyclomin
hyoscine
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
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