Transcript Document

Irritable Bowel Syndrome
John McLaughlin
Clinical Lecturer/Consultant
Gastroenterologist
Hope Hospital, Salford.
IBS
• What is (are?) IBS?
• Symptoms and
diagnosis
• Aetiology
• Therapy and
management
What is IBS?
• IBS is NOT a disease
• IBS is NOT a singular pathological entity
• IBS cannot have a single aetiology
– but
• IBS is a useful term, coined to group patients with
similar, medically unexplained symptoms
• IBS is difficult to manage, particularly
pharmacologically
IBS: features
• IBS patients have symptoms characterised by
– Unexplained abdominal pain
– Disturbed bowel habit
– Bloating
• No ‘red flags’: bleeding, weight loss, abdominal
masses, malnutrition etc
• Clinical diagnosis here VERY SAFE <40-50 yrs
• By definition, conventional investigations are
normal: colonoscopy, histology, blood tests,
radiology
Current Diagnostic Criteria:
Rome II 1999
• At least 12 weeks or more (in last year) of
abdominal pain or discomfort with 2 out of 3 of
the following:
– Relieved by defaecation
– Associated with change in stool frequency
• >3/day or <3/week
– Associated with change in stool form
• Also supported by passage of mucus, bloating,
straining, urgency, sense of incomplete evacuation
Problems with Rome II
• PATIENT A
• Abdominal pain
• Urgent loose stool 3-4
times each morning
• Sense of incomplete
evacuation
• PATIENT B
• Abdominal pain
• Strains to pass pellety
stool every 3-4 days
• Bloating++
Can these very different patients really have the
same disorder or common pathophysiology?
‘Diarrhoea-predominant’
IBS
– But when stools collected mean stool
weight= 150g/day in ‘severe diarrhoea’
group
– Diarrhoea is strictly >300g/day
– More accurate to define as increased
defaecatory frequency
Are symptoms confined to the
bowel in IBS patients?
• NO! Seek and you shall find:
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Functional Dyspepsia
Chronic Fatigue
Unexplained muscle pain (Fibromyalgia)
Temporomandibular dysfunction
Bladder symptoms
Gynaecological symptoms
Headaches
Backache
(All these body areas are normal too when investigated)
IBS symptoms are common
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3-30% prevalence in unselected subjects
5% of all visits to GPs
25% of all visits to gastroenterologists
Estimated 1% annual incidence
No mortality from the disorder itself
cf mortality from drugs, investigations,
surgical procedures
IBS symptoms are common
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3-30% prevalence in unselected subjects
5% of all visits to GPs
25% of all visits to gastroenterologists
Estimated 1% annual incidence
No mortality from the disorder itself
cf mortality from drugs, investigations,
procedures
Alosetron: 5-HT3 antagonist (GSK)
• Approved February 9, 2000, and voluntarily
withdrawn from the market November 28, 2000.
-Women with diarrhoea-predominant IBS.
• By November 10, 2000, FDA had reviewed 70
cases of serious post-marketing adverse events
– 49 cases of ischaemic colitis
– 21 cases of severe constipation.
– Of the 70 cases, 34 resulted in hospitalization without
surgery, 10 resulted in surgical procedures, and three
resulted in death.
• In some cases alosetron produced constipation
serious enough to require surgery.
• ?1:350-700 risk of ischaemic colitis.
• Put back on the market June 7, 2002 with stricter
criteria, patient-doctor agreement
Aetiology of FGID
FGD
? Hypervigilance
? Gut
Hypersensitivity
( ? Abnormal
processing )
Spinal Cord
?motility disorder
Central
Sensitisation
Altered Motility?- probably not
• Evidence is inconsistent: maybe just epiphenomena
of invasive study methods
• Stress induces colonic contractility in IBS and
control subjects
• ‘Diarrhoea’-predominant
– Prominent motility response to feeding
– Some reports of accelerated transit and fast propagation of
colonic contractions
• Constipation-predominant
– Some reports of reduced propagation of colonic
contractions
Where is the Problem ?
Hypersensitive
Gut ?
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Hypervigilant
CNS?
Functional gut disorders
• ‘VISCERAL HYPERSENSITIVITY’
– Low thresholds to gut pain (eg inflating
balloons in rectum, pain with lower volumes in
ballon)
– Perhaps reflects previous injury?
• Inflammation, infection, nerve fibre injury (TAH)
– akin to secondary hyperalgesia eg after burns
– However, problem may still lie in central
connections: why the associated disorders if
due to gut injury??
Post-infectious IBS
• Post Campylobacter best reported (Spiller)
• Persistent neuroimmune dysfunction
• Persistent subtle inflammation
– eg mast cell infiltration; increased permeability
• Enteroendocrine cell hyperplasia
– eg rectal 5-HT cells in rectum
– Increased circulating 5-HT reported in females
• ……‘IBS’ common in ‘IBD’
Where is the Problem ?
Hypersensitive
Gut ?
?
?
Hypervigilant
CNS?
Hypervigilance
• Can alter sensory thresholds by focussing
attention on any body area
• If in pain, convinced something’s wrong,
subject will focus attention there
• Vicious circle of increasing symptoms could
arise
• Anxiety/depression heightens this further
Prevalence of psychological
problems
• Community IBS: no excess
• GP
• Hospital
• Cause of symptoms or driver to seek medical
care?
• Psychological factors may worsen outcome
– eg physical or sexual abuse reportedly
Relative risk of postinfectious IBSboth biological and psychological!
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Adverse life events in the previous year: x 2
Female sex: x 3.4
Hypochondriasis: x 2
All 3 factors: x 7
Bacterial factors : 1 in 10 of Campylobacter
infected individuals developed post-infective
IBS compared with just 1 out of 100 with
Salmonella
‘Biopsychosocial model’
• Likely that components from each
of these dimensions contribute to
aetiology of IBS
• …. and other functional gut
disorders
Therapeutic approach to IBS
• Need a better understanding of precise
causes in mechanistically defined patient
subgroups, not just ROME compliant trials
– Peripheral/central origins
• Symptom-based approach: non-drug
– Behavioural, psychological, hypnotherapy
– Diet, exclusion
• Symptom-based approach: drugs
– NB 20-70% placebo responses
– Placebo benefits last 12 months or more
Therapeutic approach to IBS
• Positive diagnosis, rather than just failure to
find something else
• Reassurance, minimal investigation
• Explanation
• ‘problem with the wiring rather than the
plumbing’
Evidence for Therapy in IBS
• Fibre
– Relieves constipation but worsens bloating
• Loperamide: empirically helpful
• Antispasmodics/anticholinergics
– No good evidence
– But may safely provide the placebo
benefit
Evidence for Therapy in IBS
• Tricyclic antidepressants
– Superior to placebo in meta-analysis
• SSRIs
– No definite benefit from trials
• 5-HT3 antagonist (alosetron)
– 12-17% benefit in female D-IBS
• 5-HT4 agonist (tegasorod)
– 5-15% benefit in female C-IBS
• These need trials vs simple Rx not just placebo!
Evolving Therapy in IBS
• Novel agents in development
– Antihypersensitivity
• Peripheral opioid antagonists
• Substance P, NMDA
– Central pathways
• Corticotrophin releasing hormone antagonists
– Motility
• CCK antagonists
– Inflammation
• Steroids unhelpful in PI-IBS
– Probiotics….
Summary and prospects
• IBS will remain a major cause of morbidity
until its constituent causes are better
understood
• As it has a social and experiential
component, pharmacotherapy will largely
be adjunctive at best
• Naïve studies with agents affecting visceral
sensitivity are the best hope at present