Jtg Slides-edited

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

Canada 12% US 10–20%

Sweden 13% Belgium 8% Denmark 7% UK 22% Netherlands 9% France 20% Germany 12% Spain 13%

China 23% Japan 25%

Nigeria 30% IBS data not included

Australia 12% New Zealand 17% Camilleri et al. Aliment Pharmacol Ther 1997;11:3–15 Drossman. Dig Dis Sci 1993;38:1569–80 Talley et al. Gastroenterology 1991;101:927–34

Müller-Lissner et al. Digestion 2001;64:200–4 Talley. Balliêre’s Clin Gastroenterol 1999;13:371–84 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 coexist Upper GI tract Functional dysphagia Non-cardiac chest pain Heartburn

Lower GI tract Functional abdominal pain Irritable bowel syndrome (IBS) Functional constipation/diarrhea

Gastroesophageal reflux disease (GERD) Functional dyspepsia (FD)

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

6

5

Diabetes

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 hypersensitivity

1

• 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– 5

1

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

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

2

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% – enterochromaffin cells – neuronal

– inhibits visceral sensitivity (pain) – stimulates intestinal 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

5-HT3 (5-HT4) receptors on primary sensory and vagal afferents

5-HT

5-HT3

Descending modulating (gating) neurons

Gershon. Rev Gastroenterol Disord 2003; 3(Suppl. 2):S25–34

Motor activity in IBS

Interneurons Excitatory motor neuron (concentration)

Inhibitory Sensory motor neuron (relaxation) 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 ‘Poor digestion’

Flatulence

Proctalgia Incomplete defecation

Bloating Painless diarrhea

Abdominal pain/ discomfort and bowel habit disturbance

Mucoid stools Hepatic flexure syndrome

Somatized anxiety/ depression

IBS: most bothersome symptoms 160

36% 28%

120

22%

80

12%

40 1% uc st us oo in l

N um m bo be ov w r em el of en ts

Parameters

M

B lo at in g

U rg en cy

0 Ab d di om sc in om al fo pai rt n/

Number of patients

200

Northcutt et al. Gastroenterology 1999;116:A1036

Which IBS symptoms cause most worry to patients and their physicians? Worrying to physician (%)

Worrying to patient (%)

Bloating

–

47

Changed bowel habit

86

–

Abdominal pain

7

53

Constipation

2

–

Diarrhea

5

–

Symptom

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 alarm features

No test

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 2 Olden. Gastroenterology 2002;122:1701–14

1

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 physicianpatient

BUT

Takes much time, empathy and patience

Single-symptom treatment (fiber, antispasmodics, laxatives, other)

BUT

No global relief – may worsen other symptoms

Psychological approaches, (psychotherapy, hypnotherapy, behavior modification, etc.)

BUT

Few specialized centers, time consuming, not appropriate for all patients – 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.