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