Irritable Bowel Syndrome

Current Concepts and Treatment

Johnny T. Go, M.D.

 What is IBS?
 A real and chronic gastrointestinal (GI) disorder of
function manifested by a group of symptoms
– abdominal pain/discomfort
– bloating/distention
– constipation and/or diarrhea

 No known structural or biochemical abnormalities

 Significantly affects quality of life

 Need to treat the multiple symptoms of IBS

Thompson et al. Gut 1999;45:43–7
 Worldwide prevalence of IBS

Sweden 13%
Canada Belgium 8%
Denmark 7%
12% UK 22%
Netherlands 9% China 23%
US France 20% Germany 12%
10–20% Spain 13% Japan 25%

Nigeria 30%

IBS data not included

Australia 12%

New Zealand 17%

Camilleri et al. Aliment Pharmacol Ther 1997;11:3–15 Müller-Lissner et al. Digestion 2001;64:200–4
Drossman. Dig Dis Sci 1993;38:1569–80 Talley. Balliêre’s Clin Gastroenterol 1999;13:371–84
Talley et al. Gastroenterology 1991;101:927–34 Thompson et al. Dig Dis Sci 2002;47:225–35
 IBS: alteration in bowel habit

 IBS is sub-classified into three types based

on the primary bowel symptom
– constipation: IBS-C
– diarrhea: IBS-D
– alternation between constipation
and diarrhea: IBS-A
 Patients may present with one or more
primary symptoms
 Sub-classification of IBS:
can vary with time
 156 IBS patients from a population survey

Time
0 months 6 months 12 months
(%) (%) (%)

IBS-C 12 10 7
IBS-D 34 32 34
IBS-A 54 58 59

BUT: 36% at 6 months and 37% at 12 months had changed sub-group

Koloski et al. Gastroenterology 2002;122(Suppl. 1):A507

A more clinician-friendly definition?

“IBS is defined by abdominal discomfort

associated with altered bowel habits”

ACG Position Statement 2002

GI disorders of function commonly co-
exist
Upper GI tract

Functional dysphagia

Non-cardiac chest pain

Heartburn

Gastroesophageal reflux
Lower GI tract disease (GERD)

Functional abdominal Functional

pain dyspepsia (FD)

Irritable bowel
syndrome (IBS)

Functional
constipation/diarrhea
IBS: overlap with GI and non-GI disorders
IBS (%) Controls (%)

GERD 21 7

Peptic ulcer 13 6

Dyspepsia 13 4

Depression 25 9

Asthma 13 7

Diabetes 6 5

Hungin et al. Aliment Pharmacol Ther 2003;17:643–50

 IBS pathophysiology
 Heredity; nature versus nurture

 Dysmotility, ‘spasm’

 Visceral hypersensitivity

 Altered CNS perception of visceral events

 Psychopathology

 Infection/inflammation
Drossman et al. Gastroenterology 1997;112:2120–37
Pathogenesis of IBS:
the brain–gut axis

Central nervous
system (CNS)

Autonomic nervous
system (ANS)
(brain–gut axis)

Enteric nervous
system (ENS)

Phillips, Wingate. Churchill Livingstone, 1998

 IBS pathophysiology: role of the ENS
 Dysfunction in the ENS may lead to the hallmark symptoms
of IBS
– visceral hypersensitivity1

• increased visceral afferent response to normal as well as noxious

stimuli
• mediators include 5-HT, bradykinin, tachykinins, calcitonin gene
related peptide (CGRP) and neurotrophins
– motor dysfunction 2

• mediated by 5-HT, acetylcholine, ATP, motilin, nitric oxide,

somatostatin, substance P and vasoactive intestinal peptide

1
Bueno et al. Gastroenterology 1997;112:1714–43
2
Goyal, Hirano. NEJM 1996;234:1106–15
 Pathogenesis of IBS:
intestinal inflammation

 Inflammation may lead to persistent gut motor

dysfunction via changes in enteric nerve and
muscle function 1

 Possible mechanisms
– changes in smooth muscle contractility
– changes in muscle morphology
– changes in neurotransmitter release

Collins et al. Gut 2001;49:743–

1

5
 Pathogenesis of IBS:
possible exacerbating factors
 Food and other dietary substances 1

 Drugs and medications 2

 Psychological problems/stress 3

 Hormones (menstrual cycle) 4

 Seasonal changes 5

1
Zar et al. Minerva Med 2002;93:403–12
Locke et al. Am J Gastroenterol 2000;95:157–65
2

3
Creed et al. Gut 1987;28:1307–18
4
Moore et al. Br J Obstet Gynaecol 1998;105:1322–5
5
Talley et al. Am J Gastroenterol 1995;90:2115–19
 Serotonin (5-HT): key mediator of
gut motility and visceral sensitivity

CNS – 5% Activation of 5-HT4

receptors regulates
GI function:
– increases motility
throughout the GI tract
(peristalsis)
GI tract – 95% – inhibits visceral sensitivity
(pain)
– enterochromaffin cells
– stimulates intestinal
– neuronal
secretion

Gershon. Aliment Pharmacol Ther 1999;13:15–30

Crowell. Am J Managed Care 2001;7(Suppl):S252–S260
Lacy, Yu. J Clin Gastroenterol 2002;34:27–33
 Sensory effects

5-HT in brainstem

Descending
5-HT3 (5-HT4) receptors
modulating
on primary sensory and 5-HT (gating)
vagal afferents
neurons

5-HT3
Gershon. Rev Gastroenterol Disord 2003;
3(Suppl. 2):S25–34
 Motor activity in IBS

Interneurons

Excitatory Inhibitory
motor neuron Sensory motor neuron (relaxation)
(concentration) neuron

5-HT4
receptors

5-HT
Enterochromaffin cells

Grider et al. Gastroenterology 1998;115:370–80

 Conclusions

 IBS is a chronic and real disorder, characterized by

abdominal pain and discomfort, bloating and altered
bowel function (constipation and/or diarrhea)

 A more clinician-friendly approach to the diagnosis

of IBS is needed

 IBS overlaps with other GI and non-GI conditions

 Serotonin has an important role in motor and sensory

events in the GI tract
 Relevant questions

 Can irritable bowel syndrome (IBS) be

recognized clinically?
Yes

 Do we use the correct diagnostic

approach?
Usually yes

 Is it as accurate as it is cheap?
Yes, if precautions are adopted
 The key steps

1. Identify: the characteristic ABC symptoms of IBS-C –

Abdominal pain/discomfort
Bloating
Constipation

2. Probe: if one symptom is present, inquire about the

others

3. Eliminate: ‘alarm’ and ‘atypical’ symptoms – focus on

age of patient at presentation and duration of illness
 Clinician’s variable concept of IBS
Somatized
‘Poor anxiety/
digestion’ Flatulence Proctalgia depression
Incomplete
defecation

Bloating
Abdominal pain/
Painless discomfort and bowel
diarrhea habit disturbance

Mucoid stools

Hepatic flexure
syndrome
 IBS: most bothersome symptoms
200

36%
160
Number of patients

28%
120
22%

80
12%
40
1%
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Northcutt et al. Gastroenterology 1999;116:A1036
Which IBS symptoms cause most worry
to patients and their physicians?

Worrying to physician Worrying to patient

Symptom (%) (%)
Bloating – 47

Changed bowel habit 86 –

Abdominal pain 7 53

Constipation 2 –

Diarrhea 5 –

Thompson. Can J Gastro 2001

 Who uses which diagnostic
criteria most?

Rome I and II Clinical investigators

Manning Gastroenterologists

ABC Primary care physicians

 IBS: Manning criteria
 Four symptoms are significantly more common among
patients with IBS than in patients with organic disease
– looser stools at onset of pain
– more frequent bowel movements at onset of pain
– pain eased after bowel movement
– visible abdominal distention

 Two further symptoms are more common among

patients with IBS
– passage of mucus
– feeling of incomplete evacuation
Manning et al. BMJ 1978;2:653–4
 IBS: Rome II criteria

 At least 12 weeks (which need not be consecutive)

in the previous 12 months of abdominal pain or
discomfort that has two of the three following
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):II43–7
 Restrictions of Manning
and Rome II criteria

Criteria exclude some clinical features that are

recognized by clinicians as part of IBS:

 Post-prandial urgency and abdominal pain/diarrhea

 Painless diarrhea with borborigmi and sense of

incomplete rectal evacuation
Watch for alarming or atypical symptoms!

Do not miss:
 Thyroid dysfunction

 Malabsorption (i.e. celiac disease)

 Food intolerance/allergy

 Infection

 Inflammatory bowel disease

 Colon cancer (family history)

 Psychological disorders
Adjustable diagnostic approach to patients
with suspected IBS (cont’d)
Patient profile Approach
Young, low risk, No test
no alarm features
Suspected IBS Basic testing

Diarrhea-predominant, constitutional Full investigation

signs, therapy failure (as above) plus:
 Stool microbiology/parasites
 Hormone panel
 Sugar intolerance tests
 UGI endoscopy
 Small bowel imaging
 Other
 IBS is a stable diagnosis

Evidence suggests that clinicians can be

confident once an IBS diagnosis is made

After an initial diagnosis of IBS,

there was no change over time in
the diagnosis of 97% of patients
(median follow up: 29 years) from
Olmsted County, Minnesota
No change in
IBS diagnosis: 97%

Owens et al. Ann Intern Med. 1995;122:107–22

Combining symptom-based diagnosis and
an absence of alarm symptoms is reliable

 In one study evaluating the specificity of Rome II

criteria, no diagnostic revision was necessary 2 years
later in 100% of patients
1

 Review of the literature shows that, in patients with no

alarm symptoms, the Rome II criteria have a positive
predictive value of approximately 98% 2

Vanner et al. Am J Gastroenterol 1999;94:2912–7

1

2
Olden. Gastroenterology 2002;122:1701–14
 Who should be treated?

Consider:

 Why did the patient consult?

 Any worrying or suffering?

 Social/cultural factors
 Treatment limitations facing physicians

May work Disadvantages

Interactive, positive physician- BUT Takes much time, empathy
patient and patience

Single-symptom treatment BUT No global relief – may

(fiber, antispasmodics, worsen other symptoms
laxatives, other)

Psychological approaches, BUT Few specialized centers,

(psychotherapy, time consuming, not
hypnotherapy, behavior appropriate for all patients –
modification, etc.) rejected
by some
 The future of IBS therapy

 Evidence-based

 Pathophysiology-oriented

 Multisymptom or global

 Satisfying to patients

 Maintenance versus on demand

 ARS LONGA, VITA BREVIS,
OCCASIO FUGIT,
EXPERIMENTUM PERICULOSUM,
JUDICIUM DIFFICILE.