Understanding IBS

7/31/2019 Understanding IBS

1/66


2/66

IBS Background


3/66

Functional Gastrointestinal(GI) Disorders

Lower GI tract Upper GI tract

Functionalconstipation/diarrhea

Irritable bowelsyndrome (IBS)

Functional abdominal

pain/bloating

Dysphagia

Noncardiac chest pain

Heartburn

Functionaldyspepsia (FD)

Functionalbiliary disorders

Gastroesophageal refluxdisease (GERD)


4/66

Overlap in the Symptomatologyof Functional GI Disorders

Functionalabdominalbloating

Functionalabdominal

pain

Functionalconstipation

Functionaldiarrhea

IBS


5/66

What is IBS?

A common functional GI disorder manifestedby a group of symptoms

Abdominal pain/discomfort

Bloating/distention

Constipation and/or diarrhea

No known structural or biochemical abnormalities

Symptoms may be exacerbated by eating, stressand some pharmacologic agents

Significantly affects quality of life

Thompson WG et al. Gut 1999;45(Suppl. 2):437


6/66

IBS History

. . . occasional pain in the intestines and derangement

of their powers of digestion, with flatulence . . .Powell, 1818

. . . spasmodic stricture of the colon an occasionalcause for confinement of the bowels . . .

Howship, 1830

. . . the bowels are at one time constipated, at anothertime lax, in the same person . . . how the disease hastwo such different symptoms I do not profess toexplain . . .

Cumming, 1849


7/66

Historical Perspective

Long dismissed as a psychosomatic condition1

No clear etiology

Predominantly affects women

(~70% of sufferers are women)2

Condition not fatal

Attitudes now changing

Incidence and prevalence not extensivelymonitored in past

1Maxwell R et al. Lancet 1997;350:16915

2Sandler S. Gastroenterology 1990;99:40915


8/66

Epidemiology and Impact of IBS


9/66

Worldwide Prevalence of IBS

0

10

20

30

40

50

60

70

Prevalence

(%)

1Heaton K et al. 1992;2Longstreth G, Wolde-Tsadnik P 19933Welch G, Pomare W 1990; 4Bommalaer G et al. 1986

5Bi-zhen W, Qi-Ying P 1988;6Olubuyide O et al. 1995; 7Kay L et al. 1994

UK1 USA2 New France4 China5 Nigeria6 Denmark7Zealand3


10/66

Rates of Self-reported IBSin the USA by Sex and Age

Sandler RS. Gastroenterology 1990;99:40915

20

15

10

5

0

Male

Female

65

Age (years)

Averagerateper1,00

0subjects


11/66

IBS versus OtherImportant Disease States

US prevalence of IBS up to 20%1

US prevalence rates for other common

diseases2

Diabetes 3%

Asthma 4%

Heart disease 8%

Hypertension 11%

1Camilleri M, Choi M. Aliment Pharmacol Ther 1997;11:315

2Adams P, Benson V. Vital Health Stat 10 1991;181:1212


12/66

IBS in General Practice

Approached (3,157)

Screened (3,111)

Gut problem (300)

Reclassified,refused, died (21)

Interviewed(279)

Gut problem (255)Not GI (22) Moved, died (2)

Otherfunctional (36)

IBS(76)

Organic(100)

Unknown(43)

Screen

Patient interview

Doctorinterview

6-monthfollow-up

Thompson WG et al. Gut 2000;46:7882


13/66

IBS Consultation Pattern

Specialists1

Primary care1~25%Consulters1

~75%Nonconsulters1

~70%Female2

~30%Male2

1Drossman D, Thompson WG. Ann Intern Med 1992;116(Pt 1):100916

2Sandler S. Gastroenterology 1990;99:40915


14/66

Key Facts About IBS

Up to 20% of the US population report symptomsconsistent with IBS1

The most common GI diagnosis among

gastroenterology practices in the US2

One of the top 10 reasons for PCP visits3

Predominantly affects females (~70% of sufferers)4

The most common functional bowel disorder5

1Camilleri M, Choi M. Aliment Pharmacol Ther 1997;11:1352Everhart J, Renault P. Gastroenterology 1991;100:9981005

3Physician Drug and Diagnosis Audit (PDDA), April 1999, ScottLevin4Sandler S. Gastroenterology 1990;99:40915

5Thompson W et al. Gastroenterol Int 1992;5:7591


15/66

Productivity Burden

IBS Non-IBS

Daysperyear

p=0.0001

Absenteeism from work or schoolduring the last 12 months

Drossman D et al. Dig Dis Sci 1993;38:156980

14

12

10

8

6

4

2

0


16/66

Impact on Work Due to IBS

*Over the previous 4 weeks

Adapted from Hahn B et al. Digestion 1999;60:7781

Patients with some missed workdays 30%

Average number missed workdays* 1.7

Patients who cut back some days 46%

Average number days cut back*

3


17/66

Physician Visits Per Year

Drossman DA et al. Dig Dis Sci 1993;38:156980

AGA Teaching Unit in IBS, 1997

0

1

2

3

4

5

6

IBS Non-IBS

Numberofvisit

speryear

GI

Non-GI


18/66

Direct Medical CostsAssociated with IBS

IBS results in an estimated $8 billion in directmedical costs annually

IBS sufferers incur 74% more direct healthcarecosts than non-IBS sufferers

IBS patients have more physician visits forboth GI and non-GI complaints


19/66

All can contribute to a significant negative quality-of-life impact3

Lower abdominalpain/discomfort1

Sense of bowel urgency1,2

Diarrhea1,2

Constipation1,2

Alternating diarrhea andconstipation1,2

Reduced sense of well-being1

Alteredbowelhabits

Abdominalpain

Psychologic factors

1Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):3142Thompson WG et al. Gut 1999;45(Suppl. 2):9437

3Hahn B et al. Digestion 1999;60:7781

IBS Symptoms ReduceQuality of Life


20/66

Impact of IBS on Quality of LifeCompared with Other Medical Conditions

Adapted from Wells N et al. Aliment Pharmacol Ther 1997;11:101930

MeanSF-36score

National norm

Diabetes type II

IBS

Clinical depression

90

80

70

60

50

40

30


21/66

The Landmark Survey

IBS in American Women

The 1999 IBS in American women survey, conducted by a national publicopinion research organization, is the largest, most comprehensive nationalsurvey ever conducted on IBS

More than 1,000 women with IBS, >1,000 women in the general public,

>700 healthcare providers were surveyed in July and August 1999

Of >1,000 women diagnosed with IBS

Nearly 40% experience abdominal pain and discomfort, which they describe asintolerable without relief

Regardless of severity of abdominal pain, women with IBS reported their symptomsforced them to miss days from work, limit travel, or avoid social outings

Of women in the general public 8% reported having a diagnosis of IBS

12% reported experiencing repeated pain or discomfort in the lower abdomen that ischaracteristic of IBS


22/66

IBS in American Women (Contd)

Women with active IBS, compared with women in thegeneral public, reported

Taking three times as many sick days

Being twice as likely to limit the kind or amount of work theycan do

Nearly one in 20 reported being hospitalized in theprevious year

25% reported being hospitalized for IBS in the past

71% reported more abdominal or intestinal surgeries thanwomen without IBS (58% versus 34%)

Rates of reported gallbladder operations, hysterectomiesand appendectomies were higher

The Landmark Survey


23/66

IBS in American Women (Contd)

Women with IBS reported seeing an averageof three physicians over a 3-year period beforethey were given a definitive diagnosis of IBS

Most women reported seeing physicians asa primary source of health information

Almost all doctors (87%) admitted thatphysicians need better education about IBS

The Landmark Survey


24/66

Drossman DA et al. Gastroenterology 1997;112:212037

Epidemiology of IBS: Summary

Affects up to 20% of the population

More common in women

Prevalence decreases with age

Most with IBS do not seek a physicians help

IBS accounts for a large percentage of primarycare and gastroenterologists practices

Can be a considerable health burden


25/66

Pathophysiology of IBS


26/66

1

Almy TP 1951;2

Rogers J et al. 1989;3

Sullivan MA et al. 1978

Pathophysiology Findings:Motility in IBS

Over 50 years ago

Stress found to affect colonic function in normalsubjects1

Beginning in the 1950s

Motor reactivity of the sigmoid colon shown to bemuch greater in IBS patients than in control subjects2

1970s An anticholinergic drug shown to reduce meal-

stimulated sigmoid motility in IBS patients3


27/66

1Kumar D, Wingate DL 1985; 2Camilleri M, Phillips SF 1989;3

Kellow JE, Phillips SF 1987;4

Quigley EM et al. 1984

Pathophysiology Findings:Motility in IBS

Findings in the 1980s

IBS involves the small as well as the large intestine, anddysmotility does not always cause symptoms1

The migrating motor complex (MMC), the 3-phase cyclethat sweeps intestinal contents from duodenum to colon,may be disrupted in IBS2

Discrete clustered contractions (DCCs) and prolonged

propagated contractions (PPCs), are more common andmore often cause pain in IBS patients than controls3,4


28/66

Evolution of MechanisticHypotheses in IBS

Abnormal motility2

Visceral hypersensitivity2

Brain-gut interaction2

5-HT mediated visceralsensitivity and gut motility1

1950 2000

1Prior A, Read N. Aliment Pharmacol Ther 1993;7:175802

Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):314


29/66

Altered Intestinal Motility in IBS

Hypomotility

Bowelmovements

Hypermotility

IBS with symptoms ofconstipation

IBS with symptoms ofdiarrhea

Constipation Diarrhea


30/66

Pathogenesis of IBS:Visceral Hypersensitivity

Altered sensation

AbnormalCNS motorcontrol

Abnormal GIsmooth muscle

activity

AbnormalCNS sensoryprocessing

Abnormal GImechanoreceptor

sensitivity


31/66

1Ness TJ et al. Pain 1990;43:377862

Munakata J et al. Gastroenterology 1997;122:5563

Visceral Sensitivity

Visceral hypersensitivity

Can be induced in normal subjects

Is more prevalent in IBS patients1,2


32/66

Whitehead WE et al. Dig Dis Sci 1980;25:40413.

Comparison of Pain Thresholdsin IBS Patients and Controls

Reportingpain(%)

Rectosigmoid balloon volume (mL)

IBS

Normal

60

40

20

0

20 60 100 140 180


33/66

Comparison of Pain Thresholds

Whitehead W et al. Gastroenterology 1990;98:118792

Colonic distention Ice water immersion

IBS

Normal


34/66

Pathogenesis of IBS:The Brain-gut Axis

Central nervoussystem (CNS)

Autonomic nervoussystem (ANS)(brain-gut axis)

Enteric nervoussystem (ENS)

Phillips S, Wingate DL. Churchill Livingstone, 1998


35/66

Enteric Nervous System

Controls motility and secretory functionsof the intestine

Semiautonomous Actions modified by parasympathetic and

sympathetic nervous systems

May function independently

Contains many neurotransmitters, including5-HT, substance P, VIP (vasoactive intestinalpeptide), and CGRP (calcitonin gene-related

peptide)


36/66

IBS: Current Thinking onPathophysiology

Defects in the ENS may lead to the hallmarksymptoms of

IBS

Visceral hypersensitivity1 Increased visceral afferent response to normal as well as noxious

stimuli

Mediators include 5-HT, bradykinin, tachykinins, CGRP andneurotropins

Primary motility disorder of GI tract2 Mediated by 5-HT, acetylcholine, ATP, motilin, nitric oxide,

somatostatin, substance P and VIP

1Bueno L et al. Gastroenterology 1997;112:1714432

Goyal R, Hirano I. N Engl J Med 1996;334:110615


37/66

Physiologic Distribution of 5-HT

CNS 5%

Enterochromaffin cells Neuronal

GI tract 95%

Gershon MD. Aliment Pharmacol Ther1999;13(Suppl. 2):1530


38/66

Grider JR et al. Gastroenterology 1998;115:37080

5-HT

Excitatorymotor neuron(concentration)

5-HTreceptors

Inhibitorymotor neuron (relaxation)

Enterochromaffin cells

Interneurons

Sensoryneuron

Motor Activity in IBS


39/66

5-HTReceptor Effects

Mediate reflexes controlling GI motility andsecretion

Mediate perception of visceral pain

Gershon M. Aliment Pharmacol Ther 1999;13(Suppl. 2):1530


40/66

Pathogenesis of IBS:Intestinal Inflammation

IBS-type symptoms reported in one-thirdof patients after salmonella gastroenteritis

Inflammation may lead to persistentdysfunction of GI motility via changesin enteric nerve and muscle function

Possible mechanisms

Changes in smooth muscle contraction

Changes in muscle growth

Changes in neurotransmitter release


41/66

Psychologic Factors in IBS

Motility

Sensitivity PsychologyLife stress

Psychologic state

Coping

Social support


42/66

Psychologic Factors thatAffect GI Function

Anxiety, panic, depression

Somatoform disorders

(unexplained bodily symptoms)Physical, sexual or emotional abuse

Alcohol or substance abuse

Eating disorders


43/66

IBS or Functional GI Disorder (FGID) and OrganicGI Disease Patients with Psychiatric Illnesses

100

80

60

40

20

0McDonald Colgan Craig Ford Blanchard

and Bouchier et al. and Brown et al. et al.1980 1998 1984 1987 1990

IBS/FGID

Organic GI

Patients(

%)

Camilleri M, Choi C. Aliment Pharmacol Ther 1997;11:315


44/66

Conceptual Model of IBS

Psychosocial factors Life stress Psychologic state Coping Social support

Early life Genetics Environment

Physiology Motility Sensation

Outcome Medications MD visits Daily function Quality of life

IBS Symptom

experience Behavior

CNS ENS

P h i f IBS


45/66

Pathogenesis of IBS:Contributory Factors/Triggers

Food and other dietary substances

Drugs and medications

Psychologic problems/stress

Hormones (menstrual cycle)

Seasonal changes


46/66

Diagnosis of IBS


47/66

History of Diagnostic Approaches

1950s Increased gut motility1

1970s Specific motility markers1

1980 to 1999 Symptom-based criteria1

Manning criteria

Rome criteria

1999 Rome II criteria2

1Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):3142



48/66

Altered Bowel Function in IBS

Change infrequency of

bowel movement

Urgency Change in stoolconsistency

Straining

Bloating(fullness/swelling)

Feeling ofincomplete bowel

movement

Passage of mucus

Altered bowel function


49/66

The Manning Criteria (1978)

Four symptoms significantly more common in IBSthan in organic disease

Pain relieved by defecation

More frequent stools at the onset of painLooser stools at the onset of pain

Visible abdominal distention

A strong trend for the followingPassage of mucus

Sensation of incomplete bowel emptying

Manning AP et al. Br Med J 1978;2:6534


50/66

The Rome Criteria (1992)

3 months continuous/recurrent symptoms of the following

Abdominal pain or discomfort that is

Relieved with defecation

Associated with a change in frequency of stool and/or

Associated with a change in consistency of stool; and

Two or more of the following at least on one quarter of the time

Altered stool frequency (>3/day or


51/66

At least 3 months of continuous orrecurrent symptoms of abdominalpain or discomfort that is

Relieved by defecation and/or

Associated with a change infrequency of stool; and/or

Associated with a change inconsistency of stool

Two or more of the following atleast 25% of the time

Altered stool frequency

Altered stool formAltered stool passage (straining,urgency, feeling of incompleteevacuation)

Passage of mucus; and/or

Bloating or feeling of abdominaldistention

1Thompson WG et al. Gastroenterol Int 1992;5:75912


Rome I Criteria1 Rome II Criteria2

At least 12 weeks, which need not beconsecutive, in the last 12 months ofabdominal discomfort or pain that hastwo of three features

Relieved by defecation; and/or

Onset associated with a change infrequency of stool; and/or

Onset associated with a change in form(appearance) of stool


52/66

The Rome II Criteria12 weeks or more in the last 12 months of abdominal discomfortor pain that has two out 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 consistency of stoolThe following symptoms are not essential, but the more of themthat are present, the more confident is the diagnosis

Abnormal stool frequency (>3/day or


53/66

Differential Diagnosis of IBS

Malabsorption1

Dietary factors1

Infection1

Inflammatory bowel disease1

Psychologic disorders1

Gynecologic disorders2

Miscellaneous1

1Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):3142

Moore J et al. Br J Obstet Gynaecol 1998;105:1322

5


54/66

Red Flags May Suggest an

Alternative or Coexisting Diagnosis

Anemia

Fever

Persistent diarrhea

Rectal bleeding

Severe constipationWeight loss

Paterson WG et al. CMAJ 1999;161:15460

Additional diagnostic screening needed for atypicalpresentations such as

Nocturnal symptoms of

pain and abnormal bowelfunction

Family history of GI cancer,inflammatory bowel disease,or celiac disease

New onset of symptoms inpatients 50+ years of age


55/66

Symptom assessment1Abdominal pain/discomfort and disturbed defecationChange in stool frequency or consistencyBloating and visible distention

Limited screen for organic disease2Blood workThyroid function testsStools (e.g. occult blood)Fiberoptic sigmoidoscopy

1Hammer J, Talley NJ. Am J Med 1999;107(5A):5S11S2

Schmulson MW, Chang L. Am J Med 1999;107(5A):20S

6S

Check for red flags

Basic Diagnosis of IBS


56/66

Make a Positive Diagnosis1,2

Identify abdominal pain as dominantsymptom with altered bowel function

Perform diagnostic tests/physical examto rule out organic disease

Initiate treatment program as partof diagnostic approach

Follow up in 3 to 6 weeks

Look for red flags

1Paterson WG et al. CMAJ 1999;161:154602

American Gastroenterological Association. Gastroenterology 1997;112:212037

Make/confirm diagnosis

Persistence of Diagnosis and


57/66

Persistence of Diagnosis andSymptoms of IBS

No change indiagnosis, 97%

Symptomsretained at

5 years, 75%

Most have no change indiagnosis after adequate

initial evaluation

Majority retain symptoms at5 years after initial diagnosis

AGA Teaching Unit on IBS, 1997


58/66

Management of IBS


59/66


60/66

Patient Education in IBS

Education and reassurance are essentialelements of clinical management

Patients need information about the nature oftheir condition, such as its high prevalence,the causes and symptoms

Patients should be made aware of the available

treatment options e.g. pharmacologic and non-pharmacologic therapies


61/66

Dietary and Lifestyle Modification

Stress management/reduction techniqueshave been shown to improve patientwell-being

Diet diaries may be used to identify dietaryfactors that tend to trigger IBS symptoms.Elimination or reduction in intake of these

foods may reduce the frequency and severityof symptoms

D f D i t


62/66

Drugs for DominantSymptoms in IBS

AntispasmodicsAntiflatulents

Anticholinergic/AntispasmodicsTCAs

SSRIs

LoperamideCholestyraminePsylliumMethylcellulose

TegaserodCalcium polycarbophilLactulose70% sorbitolPEG solution

Abdominalpain

Bloating

Alteredbowel

motility

New Therapeutic Approaches to


63/66

New Therapeutic Approaches tothe Treatment of IBS

Psychosocialfactors

Alteredsensation

Alteredmotility

Sympathetic

S2, 3, 4

Vagal nuclei

Camilleri M, Choi M-G. Aliment Pharmacol Ther 1997;11:315

5-HT


64/66

Psychologic Treatments for IBS

Some patients with IBS may also benefit from

Referral to a psychologist or psychiatrist

Hypnotherapy

Biofeedback

Psychodynamic therapy

Stress management/relaxation

Cognitive behavioral programs

Drossman DA et al. The Functional GI Disorders, 2000

A Comprehensive


65/66

A ComprehensiveMulticomponent Approach

Treatment program is based on dominantsymptoms and their severity, and onpsychosocial factors

Medical management

Diet

Psychologic or behavioral options Psychotherapy

Stress management

Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):314


66/66

Conclusion

Current treatment of symptoms of IBS oftenrequires use of more than one medication tocontrol the multiple symptoms

Current medical therapies for symptoms of IBShave been insufficiently effective and thereis a need for novel approaches to treatment

Documents

Understanding IBS