Irritable Bowel Syndrome John McLaughlin Clinical Lecturer/Consultant Gastroenterologist Hope...
-
Upload
juliet-evans -
Category
Documents
-
view
217 -
download
2
Transcript of Irritable Bowel Syndrome John McLaughlin Clinical Lecturer/Consultant Gastroenterologist Hope...
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
• NO! Seek and you shall find:– 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)
Are symptoms confined to the bowel in IBS patients?
IBS symptoms are common
• 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
• 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 FGDAetiology of FGID
? Gut
Hypersensitivity
? Gut
Hypersensitivity
? Abnormal
processing
? Abnormal
processing
Spinal CordSpinal Cord
? Hypervigilance? Hypervigilance
((
))
Central
Sensitisation?motility disorder
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 ?
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 IBS- both biological and psychological!
• 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