Irritable Bowel Syndrome
Dr Junaid Saleem
Conflict of Interest Statement
• Sponsored by Abbott for this lecture
• No other conflicts of interest
2
Short Version
• Irritable Bowel Syndrome– Definition?– Aetiology?– Pathology?– Clinical Features– Diagnosis?– Treatment?– Prognosis +/-
3
Introduction
• First described in 1771.• 50% of patients present <35 years old.• 70% of sufferers are symptom free after 5 years.• GPs will diagnose one new case per week.• GPs will see 4-5 patients a week with IBS.• Point prevalence of 40-50 patients per 2000
patients.
4
What Is IBS?• A syndrome.• One man’s
constipation is another man’s normality.
• Cause unknown.• 20% seem to start
after an episode of gastroenteritis.
5
Psychosocial factors •IBS aetiology is multi-factorial•Emotions significantly affect colonic response in IBS
– Stressful stimuli disrupt upper GI motility in several ways, including mean
• oesophageal peristaltic amplitude, • rate of gastric emptying, • small bowel transit, and • increased upper oesophageal sphincter pressure
Aetiology
Psychosocial factors •The response to stress is mediated by corticotrophin releasing factor (CRF) secreted by the enteric neurons, enteroendocrine cells and immune cells
– CRF binds to CRF receptors present on smooth muscle cells and increase the number of discrete cluster contractions
– Psychosocial factors exacerbate the symptoms of IBS but a definite link has not been established
Aetiology
Pathophysiology
• Exact pathophysiology remains uncertain
• Dysregulation within the brain gut axis, • interactions between genetics, • psychosocial factors, • post-inflammatory changes and • motor and sensory dysfunction
are all likely to influence the development of IBS
Pathophysiology
Spiller R, Aziz Q, Creed F, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007;56:1770-1798.Mawe GM, Coates MD, Moses PL. Intestinal serotonin signalling in irritable bowel syndrome. Aliment Pharmacol Ther 2006;23:1067-1076.
• Exact pathophysiology remains uncertain
• Visceral hypersensitivity – enhanced pain sensitivity of the gut – may play an important role in the development of chronic pain and discomfort in IBS1
• Heightened sensitivity of the peripheral nervous system is caused by immune and inflammatory mediators acting at the site of tissue injury and inflammation
Pathophysiology
Spiller R, Aziz Q, Creed F, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007;56:1770-1798.Mawe GM, Coates MD, Moses PL. Intestinal serotonin signalling in irritable bowel syndrome. Aliment Pharmacol Ther 2006;23:1067-1076.
• Exact pathophysiology remains uncertain
• Serotonin (5-HT) – present extensively in the GI tract – is the most important neurotransmitter in the pathogenesis of IBS,
• peripheral sensitisation causes an area of hypersensitivity to develop in the surrounding uninjured tissue – this phenomenon is called central sensitisation
Pathophysiology
Spiller R, Aziz Q, Creed F, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007;56:1770-1798.Mawe GM, Coates MD, Moses PL. Intestinal serotonin signalling in irritable bowel syndrome. Aliment Pharmacol Ther 2006;23:1067-1076.
Disturbances in GI motility•A proportion of IBS patients, specifically those reporting constipation or dyspeptic symptoms, exhibit delayed gastric emptying, especially of solids, this correlates with absence of post-prandial increase in electrogastrography (EGG) amplitude
Pathophysiology
Hammerle CW, Surawicz CM. Updates on treatment of irritable bowel syndrome. World J Gastroenterol 2008;14(17):2639-2649.
Disturbances in GI motility•Disturbances in small bowel motor activity occur, including
• frequency and duration of discrete cluster contractions, • increased frequency of migrating motor complex (MMC), • more retrograde duodenal and jejunal contractions• exaggerated motor response to meal ingestion
Pathophysiology
Hammerle CW, Surawicz CM. Updates on treatment of irritable bowel syndrome. World J Gastroenterol 2008;14(17):2639-2649.
Disturbances in GI motility•Corticotrophin releasing hormone, e.g. secreted in response to stress, increases the number of discrete cluster contractions. •More commonly observed in IBS patients with diarrhoea than in those with constipation
Pathophysiology
Hammerle CW, Surawicz CM. Updates on treatment of irritable bowel syndrome. World J Gastroenterol 2008;14(17):2639-2649.
Visceral hypersensitivity •Visceral pain and discomfort cause considerable morbidity in IBS1
•Visceral hypersensitivity seen in two-thirds of patients with IBS and plays an important role in abdominal pain and discomfort1
•Animal and human studies suggest that visceral hypersensitivity is caused by a combination of factors involving heightened sensitivity of peripheral and central nervous system1
Pathophysiology
Spiller R, Aziz Q, Creed F, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007;56:1770-1798
Subj
ects
repo
rting
pai
n (%
)
Whitehead et al. Dig Dis Sci 1980
Distending volume (mL)
Healthy controls
20 60 100 140 180
IBS
RECTAL HYPERSENSITIVITY IN IBS
0
10
20
30
40
50
IBS(n=86)
Healthy volunteers
(n=25)
Pres
sure
(mm
Hg)
Barostat rectal distensionDiscomfort/Pain
Bouin et al. Gastroenterology 2002
Rectal barostat at 40 mmHg, to identify IBS patients from HV and non-IBS pts sensitivity = 96%, specificity = 72%; PPV = 85% , NPV = 90%.
RECTAL HYPERSENSITIVITY IN IBS
0
20
40
60
80
100
IBS(n=126)
Healthy volunteers
(n=30)
Subj
ects
with
hyp
erse
nsiti
vity
Barostat rectal distensionDiscomfort/Pain
Ludidi et al. Neurogastro Motil 2012
Optimal cutoff for visceral hypersensitivity at pressure 26
mmHg with a VAS ≥20 mm
RECTAL HYPERSENSITIVITY IN IBS
64%
7%
Diagnostic Criteria• Manning’s Criteria.• Rome II Diagnostic criteria.
19
Manning Kruis Rome
Rome I Rome II Rome III
1978 1984 1989 1990 1999 2006
IBS diagnostic criteria
Manning’s Criteria.
• Three or more features should have been present for at least 6 months:– Pain relieved by defecation.– Pain onset associated with more frequent stools.– Looser stools with pain onset.– Abdominal distension.– Mucus in the stool.– A feeling of incomplete evacuation after defecation.
21
Rome Publications
Gastroenterology
International Journal
1989 1990 19941999 2000
20061st IBS criteria
1992-19955 Rome I
publications
2003Rome
Foundation
Gastroenterology Supplement
+Rome III BookDegnon Assoc.
1683
1st FGID classificatio
n
Rome I BookLittle Brown
Rome IIGut
Supplement
Rome II BookDegnon Assoc.
Rome II Diagnostic criteria for IBS
At least 12 weeks, which need not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has two of three features:
Relieved with defecation; and/or Onset associated with a change in frequency of stool;
and/or Onset associated with a change in form (appearance)
of stool.
Thompson et al Gut 1999;45 Suppl 2:II43-II47
Rome II Diagnostic Criteria.• Supportive symptoms.
– Constipation predominant: one or more of:• Bowel movement less than 3 times a week.• Hard or lumpy stools.• Straining during a bowel movement.
– Diarrhoea predominant: one or more of:• More than 3 bowel movements per day.• Loose [mushy] or watery stools.• Urgency.
24
Rome II Diagnostic Criteria.
– General:• Feeling of incomplete evacuation.• Passing mucus per rectum.• Abdominal fullness, bloating or swelling.
25
Rome III Committees – Issues and Limitations
Criteria Not Fully Evidence BasedLimited data for most functional GI disorders Original criteria by consensusChanges based on new evidenceNew changes need validation
The Field is Expanding and GrowingInformation not “set in stone”Knowledge can quickly become outdated Classifications will change – e.g., “Organification”
Need for Quality ControlDisclosure of relationships with PharmaceuticalsConfidentiality statementsInternational Resource CommitteeEmbargo on information until final editing stages
1778
Rome III Diagnostic Criteria for IBS*
Recurrent abdominal pain or discomfort 3 days per month in the last three monthsassociated with two or more of the following Improvement with defecation; and/or Onset associated with a change in frequency of stool; and/or
Onset associated with a change in form (appearance) of stool
* Criteria fulfilled for the last 3 months with symptom onset 6 months prior to diagnosis
Rome III Criteria* – Irritable Bowel Syndrome
Improvement with
defecation
Recurrent abdominal pain or discomfort at least 3 days/month
In the last 3 months associated with 2 or more :
Onset associated
with a change in frequency
of stool
Onset associated
with a change in form
(appearance) of stool
and and
Longstreth GF, Gastroenterology 2006 1782
• Introduction of a frequency threshold of 3 days/ month over 3 months for symptoms
• Reduction of the duration of symptoms before one can make firm diagnosis from 12 to 6 months
• Refining of subtypes
Main Changes in IBS Criteria
Subclassifying IBS Why bother?
Important for choosing therapies which alter bowel habit
Subtypes likely to have different pathophysiology Transit Stool consistency Rectal sensitivity?
Previous Features Used to subclassify IBS Patients
Diarrhea-predominant 1 or more of 2, 4, or 6 and none of 1, 3, or 5 (or 2 of 2, 4 or 6 and 1 of 1 or 5 but not 3)
Constipation-predominant 1 or more of 1, 3, or 5 and none of 2, 4, or 6 (or 2 of 1, 3 or 5 and 1 of 2, 4 or 6)
1. Fewer than three bowel movements a week 2. More than three bowel movements a day 3. Hard or lumpy stools4. Loose (mushy) or watery stools 5. Straining during a bowel movement 6. Urgency (having to rush to have a bowel movement)
Problems With Old System
Complex to apply and caused confusion in both patients and clinicians!
Multidimensional but different dimensions don’t correlate well
Failed to deal adequately with patients with both hard and loose stools
IBS Patients with Features of Both Constipation and Diarrhea are Common
Reference N IBS-D IBS-C IBS-M
Mearin 2003 209 10 24 37
Tillisch 2005
1102 32 17 32
Drossman 2005
317 36 34 31
Rome III subtyping is based on Stool Consistency alone
• Assessed from stool form
Defining Stool ConsistencyBristol Stool Form Scale
Hard
Normal
Loose
Why Stool Consistency as Main Determinant of Subtype?
Correlates best with colonic transit
Why Stool Consistency as Main Determinant of Subtype?
Correlates best with colonic transit
Correlates best with what patients and community samples think of as “diarrhoea”
Principle determinant of incontinence
Other features occur in IBS with both loose & hard stools Stool frequency <3/weeks or >3/day
Urgency, Sense of incomplete evacuation
Association of bowel symptoms with stool consistency
Tillisch et al Am J Gastroenterol. 2005; 100:896-904
Proposed New Subtyping Based on Stool Consistency Alone
IBS with constipation - IBS-C IBS with diarrhoea - IBS-D IBS mixed type - IBS-M IBS unsubtyped - IBS-U
IBS-mixed : patients with both hard & loose stools over periods of hours or days
0
25
50
75
100
%Hard or
lumpy stools
0 25 50 75 100% Loose or watery stools
IBS-U
IBS-C IBS-M
IBS-D
Rome III – Subtypes of IBS
1709
Alternating IBS Patients who change subtype over
periods of weeks and months
Quantifying Stool FormDate Pain Pain
SeverityUrgencyY/N
BloatingY/N
1 2 3 4 5 6 7 8
Pain: grade 0-10 0= absent 5=moderate 10 very severeStool form1= separate hard lumps, like nuts 6 = fluffy pieces with ragged edges2= sausage shaped but lumpy 7 = watery, no solid pieces 3= like a sausage or snake, but with cracks
on its surface4= like a sausage or snake, smooth and soft5= soft blobs with clear cut edges
Changes to IBS classificationRome III Summary
No change to basic criteria Length of time needed to define chronicity reduced
to 6 months Threshold 3 days / month introduced for
frequency of pain / discomfort Subtyping simplified (stool consistency) Stability of subtypes and link to other features like
visceral sensitivity and response to treatment remain to be determined
Manning Kruis Rome
Rome I Rome II Rome III
1978 1984 1989 1990 1999 2006
IBS diagnostic criteria
Rome IV
2016
INTERNAL USE ONLY. DO NOT COPY. DO NOT DISTRIBUTE EXTERNALLY.
Associated Symptoms
• In people with IBS in hospital OPD.– 25% have depression.– 25% have anxiety.
• Patients with IBS symptoms who do not consult doctors [population surveys] have identical psychological health to general population.
• In one study 70% of women IBS sufferers have dyspareunia.
45
Associated Symptoms
• Stressful life events are associated.• Compared with controls people with IBS are
less well educated and have poorer general health.
• Women:Men = 3:1.
46
Reasons to Refer• Age > 45 years at
onset.• Family history of
bowel cancer.• Failure of primary care
management.• Uncertainty of
diagnosis.• Abnormality on
examination or investigation.
47
Urgent Referral
• Constant abdominal pain.
• Constant diarrhoea.• Constant distension.• Rectal bleeding.• Weight loss or
malaise.
48
Differential Diagnosis
• Inflammatory bowel disease.• Cancer.• Diverticulosis.• Endometriosis.
• A positive diagnosis, based on Manning’s criteria may provoke less anxiety than extensive tests.
49
Examination
• Results should be normal or non-specific.
• Abdomen and rectal examination.
• FBC, CRP.• No consensus as to
whether FOBs or sigmoidoscopy is needed.
50
Treatment
• Patients’ concerns.• Explanation.• Treatment approaches.
51
Patients’ Concerns.• Usually very concerned about a serious cause
for their symptoms– Cancer phobias
• Take time to explore the patients agenda.• Remember that investigations may heighten
anxiety.
52
Explanation.
53
• Must offer a plausible reason for symptoms.
• Even if cause is unknown, patients require some explanation.
• Drawing a parallel with baby colic may help.
• Stress is currently a socially acceptable explanation for many symptoms in life.
Treatment Approaches.
54
• Placebo effect of up to 70% in all IBS treatments.
• Treatment should depend on symptom sub-type.
• Often considerable overlap between sub-groups.
Psychotherapy
• Antidepressants– Poor evidence for efficacy– Better evidence for tricyclics
• May have some effect other than antidepressant effect
– Very little evidence for SSRIs• Relaxation therapies may be useful adjunct.• CBT (Cognitive Behavioral Therapy)
55
5HT related drugs
• 5HT Receptor Antagonists– Allosetron
• 5HT Rerceptor Agonists– Tegarasod
56
Constipation Predominant.• Increased fibre.• Osmotic laxatives helpful, Ispaghula
husk is one.• Stimulant laxatives make symptoms
worse.• Lactulose may aggravate distension
and flatulence.
57
Pain Predominant.
• Antispasmodics will help 66%.• Mebeverine is probably first choice.• Hyoscine 10mg qid can be added.• Bloating may be helped by peppermint
oil.• Nausea may require metoclopramide.
58
IRRITABLE BOWEL SYNDROMESpasmolytic agents
AlverineCimetropiumDicyclomineHyoscineMebeverineOtiloniumPinaveriumPirenzipinePrifiniumPropinoxRociverineTrimebutine
others
• Antibiotics– Rifaximin
• Pre-biotics• Pro-biotics
Sept 2001 Bruce Davies 60
Diet• Dietary manipulation may help.• Food intolerance is common • Food allergy is rare.
61
Spiller and Thompson 2010World Gastroenterology Organisation Global Guideline 2009
IBS-C, irritable bowel syndrome with constipation; IBS-D, irritable bowel syndrome with diarrhoea;SSRI, selective serotonin reuptake inhibitor
IRRITABLE BOWEL SYNDROMERome/WGO management cascade
Patient with chronic or recurrentabdominal
pain/discomfort associated with
disordered bowel habit
no
History and clinical examination
Alarm features?
yes
Investigations as indicated
Consider limited screening tests
Any abnormality identified?
yes
IRRITABLE BOWEL
SYNDROME (IBS)
Initial therapy: treat primary symptom:
spasmolytic
yesSymptom relief?
no
Assess symptom pattern
Long-term management
IRRITABLE BOWEL
SYNDROME WITH DIARRHOEA (IBS-
D)
IRRITABLE BOWEL
SYNDROME WITH CONSTIPATION
(IBS-C)
IRRITABLE BOWEL
SYNDROME WITH PAIN
Alosetron, rifaximin, ….?
Lubiprostone, linaclottide, ….. Tricytlic, SSRI, …..
Referral• About 15% of patients seen by GPs with IBS
are referred.• Gastroenterology – Mainly upper GI
symptoms.• General Surgical – Lower GI symptoms.•
63
Psychological Thoughts
• Should a mental health assessment always be done?
• Should all therapy be directed at psychological causes?
• Is IBS a physical or a somatisation disorder?
64
Thank you
• Questions?
Sept 2001 Bruce Davies 65
Top Related