Upload
fitri-dwiyani
View
230
Download
0
Embed Size (px)
Citation preview
7/31/2019 Understanding IBS
1/66
7/31/2019 Understanding IBS
2/66
IBS Background
7/31/2019 Understanding IBS
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)
7/31/2019 Understanding IBS
4/66
Overlap in the Symptomatologyof Functional GI Disorders
Functionalabdominalbloating
Functionalabdominal
pain
Functionalconstipation
Functionaldiarrhea
IBS
7/31/2019 Understanding 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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
8/66
Epidemiology and Impact of IBS
7/31/2019 Understanding 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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding 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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
25/66
Pathophysiology of IBS
7/31/2019 Understanding 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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
29/66
Altered Intestinal Motility in IBS
Hypomotility
Bowelmovements
Hypermotility
IBS with symptoms ofconstipation
IBS with symptoms ofdiarrhea
Constipation Diarrhea
7/31/2019 Understanding IBS
30/66
Pathogenesis of IBS:Visceral Hypersensitivity
Altered sensation
AbnormalCNS motorcontrol
Abnormal GIsmooth muscle
activity
AbnormalCNS sensoryprocessing
Abnormal GImechanoreceptor
sensitivity
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
33/66
Comparison of Pain Thresholds
Whitehead W et al. Gastroenterology 1990;98:118792
Colonic distention Ice water immersion
IBS
Normal
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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)
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
37/66
Physiologic Distribution of 5-HT
CNS 5%
Enterochromaffin cells Neuronal
GI tract 95%
Gershon MD. Aliment Pharmacol Ther1999;13(Suppl. 2):1530
7/31/2019 Understanding IBS
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
7/31/2019 Understanding 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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
41/66
Psychologic Factors in IBS
Motility
Sensitivity PsychologyLife stress
Psychologic state
Coping
Social support
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding 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
7/31/2019 Understanding IBS
46/66
Diagnosis of IBS
7/31/2019 Understanding 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
Thompson WG et al. Gut 1999;45(Suppl. 2):437
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
Thompson WG et al. Gut 1999;45(Suppl. 2):437
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding 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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
58/66
Management of IBS
7/31/2019 Understanding IBS
59/66
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
62/66
Drugs for DominantSymptoms in IBS
AntispasmodicsAntiflatulents
Anticholinergic/AntispasmodicsTCAs
SSRIs
LoperamideCholestyraminePsylliumMethylcellulose
TegaserodCalcium polycarbophilLactulose70% sorbitolPEG solution
Abdominalpain
Bloating
Alteredbowel
motility
New Therapeutic Approaches to
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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
7/31/2019 Understanding IBS
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