IRRITABLE BOWEL SYNDROME Kimberly M. Persley, MD

IRRITABLE BOWEL IRRITABLE BOWEL SYNDROMESYNDROME

Kimberly M. Persley, MDKimberly M. Persley, MD

Earliest descriptions Earliest descriptions of symptoms defining IBSof symptoms defining IBS

1849 – W Cumming1849 – W Cumming11

““The bowels are at The bowels are at one time constipated, one time constipated, at another lax, in the at another lax, in the same person.same person.How the disease has How the disease has two such different two such different symptoms I do not symptoms I do not profess to explain. . . .”profess to explain. . . .”

IBS – HistoryIBS – History

Other historical termsOther historical terms–– mucous colitis mucous colitis –– colonic spasm colonic spasm –– neurogenic mucous colitis neurogenic mucous colitis –– irritable colon irritable colon –– unstable colon unstable colon–– nervous colon nervous colon–– spastic colon spastic colon–– nervous colitis nervous colitis–– spastic colitis spastic colitis

1962 – Chaudhary & Truelove1962 – Chaudhary & Truelove22

Irritable colon syndromeIrritable colon syndrome

1966 – CJ DeLor1966 – CJ DeLor33

Irritable bowel syndromeIrritable bowel syndrome

References: 1. Cumming. Lond Med Gazette. 1849;NS9;969-973. 2. Chaudhary and Truelove. Q J Med. July 1962;31:307-322. 3. DeLor. Am J Gastroenterol. May 1967;47:427-434.

Historical perspectiveHistorical perspective Long dismissed as a psychosomatic conditionLong dismissed as a psychosomatic condition11

–– no clear etiology no clear etiology – – affects predominantly women affects predominantly women

((~70%~70% of sufferers are women)of sufferers are women)22 –– condition not fatalcondition not fatal

Attitudes now changingAttitudes now changing

Incidence and prevalence not extensively Incidence and prevalence not extensively monitored in pastmonitored in past

IBS – HistoryIBS – History

References: 1. Maxwell et al. Lancet. December 1997;350:1691-1695. 2. Sandler. Gastroenterology. August 1990;99:409-415.

Hallmark symptoms of IBSHallmark symptoms of IBS

Chronic or recurrent GI symptomsChronic or recurrent GI symptoms

–– lower abdominal pain/discomfortlower abdominal pain/discomfort

–– altered bowel function (urgency, altered stool altered bowel function (urgency, altered stool consistency, altered stool frequency, incomplete consistency, altered stool frequency, incomplete evacuation)evacuation)

–– bloatingbloating

Not explained by identifiable structural or Not explained by identifiable structural or biochemical abnormalitiesbiochemical abnormalities

IBS IBS –– Signs and symptoms Signs and symptoms

Reference: Thompson et al. Gut. 1999;45(suppl 2):1143-1147.

Key facts about IBSKey facts about IBS

Up to 20% of the US population report symptoms Up to 20% of the US population report symptoms

consistent with IBSconsistent with IBS11

The most common GI diagnosis among The most common GI diagnosis among

gastroenterology practices in the US gastroenterology practices in the US22

One of the top 10 reasons for PCP visitsOne of the top 10 reasons for PCP visits33

Affects predominantly females (~70% of sufferers)Affects predominantly females (~70% of sufferers)44

The most common functional bowel disorderThe most common functional bowel disorder55

IBS IBS –– Overview Overview

References: 1. Camilleri and Choi. Aliment Pharmacol Ther. 1997;11:13-15. 2. Everhart and Renault. Gastroenterology. April 1991;100:998-1005. 3. Physician Drug & Diagnosis Audit (PDDA), April 1999, Scott-Levin. 4. Sandler. Gastroenterology. August 1990;99:409-415. 5. Thompson et al. Gastroenterol Int. 1992;5:75-91.

Key facts about IBS Key facts about IBS (cont.)(cont.) Can cause great discomfort, sometimes intermittent Can cause great discomfort, sometimes intermittent

or continuous, for many decades in a patient’s lifeor continuous, for many decades in a patient’s life11

Can significantly disrupt daily lifeCan significantly disrupt daily life22

Can have negative impact on quality of lifeCan have negative impact on quality of life22 Current treatment optionsCurrent treatment options33

–– dietary modificationdietary modification–– fiber supplementsfiber supplements–– pharmacologic agentspharmacologic agents–– psychotherapypsychotherapy

Success of current treatment options in addressing Success of current treatment options in addressing multiple symptoms of IBS has been limitedmultiple symptoms of IBS has been limited44

IBS IBS –– Overview Overview

References: 1. Hahn et al. Dig Dis Sci. December 1998;43:2715-2718. 2. Hahn et al. Digestion. 1999;60:77-81. 3. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14. 4. Klein. Aliment Pharmacol Ther. 1999;13(suppl 2):15-30.

IBS consultation patternIBS consultation patternSpecialistsSpecialists11

Primary carePrimary care11

~25%~25%ConsultersConsulters11

~75%~75%NonconsultersNonconsulters11

~70% ~70% FemaleFemale22

~30%~30%MaleMale22

IBS IBS –– Epidemiology Epidemiology

References: 1. Drossman and Thompson. Ann Intern Med. June 1992;116(pt 1):1009-1016. 2. Sandler. Gastroenterology. August 1990;99:409-415.

IBS vs other IBS vs other important disease statesimportant disease states

US prevalence up to 20%US prevalence up to 20%11

US prevalence rates for other common US prevalence rates for other common diseasesdiseases22::

–– diabetesdiabetes 3% 3%

–– asthmaasthma 4%4%

–– heart diseaseheart disease 8% 8%

–– hypertensionhypertension 11%11%

IBS IBS –– Epidemiology Epidemiology

References: 1. Camilleri and Choi. Aliment Pharmacol Ther. 1997;11:3-15. 2. Adams and Benson. Vital Health Stat 10. December 1991:83. DHHS publication no (PHS)92-1509.

Productivity burdenProductivity burden

IBS IBS –– Burden of disease Burden of disease

00

22

44

66

88

1010

1212

1414

IBSIBS Non-IBSNon-IBS

Da

ys

pe

r y

ea

rD

ay

s p

er

ye

ar

PP=0.0001=0.0001

Absenteeism from work or school Absenteeism from work or school during the last 12 monthsduring the last 12 months

Reference: Drossman et al. Dig Dis Sci. September 1993;38:1569-1580.

Irritable Bowel SyndromeIrritable Bowel Syndrome

Biopsychosocial DisorderBiopsychosocial Disorder– PsychosocialPsychosocial– MotilityMotility– SensorySensory– ? Infectious? Infectious

Prevalence 10%, Incidence 1-2% per YearPrevalence 10%, Incidence 1-2% per Year Disturbs QOL, Social Function, Healthcare UtilizationDisturbs QOL, Social Function, Healthcare Utilization

PsychosocialFactors

AlteredMotility

S2,3,4

Vagal nuclei

Sympathetic

AlteredSensation

IBS: Current thinking on pathophysiologyIBS: Current thinking on pathophysiology

Visceral hypersensitivityVisceral hypersensitivity11

–– Increased visceral afferent response to normal as well as Increased visceral afferent response to normal as well as noxious stimulinoxious stimuli

–– Mediators include 5-HT, bradykinin, tachykinins, CGRP, and Mediators include 5-HT, bradykinin, tachykinins, CGRP, and neurotropinsneurotropins

Primary motility disorder of GI tractPrimary motility disorder of GI tract22

–– Mediated by 5-HT, acetylcholine, ATP, motilin, nitric oxide, Mediated by 5-HT, acetylcholine, ATP, motilin, nitric oxide, somatostatin, somatostatin, substance P, and VIP substance P, and VIP

IBS IBS –– Pathophysiology Pathophysiology

References: 1. Bueno et al. Gastroenterology. May 1997;112:1714-1743. 2. Goyal and Hirano. N Engl J Med. April 1996;334:1106-1115.

Defects in the enteric nervous system may lead Defects in the enteric nervous system may lead to the hallmark symptoms of IBS.to the hallmark symptoms of IBS.

Physiological Physiological distribution of 5-HTdistribution of 5-HT

CNS – 5%CNS – 5%

– enterochromaffin cellsenterochromaffin cells– neuronalneuronal


GI tract – 95% GI tract – 95%

Reference: Gershon. Aliment Pharmacol Ther. 1999;13(suppl 2):15-30.

5-HT5-HT receptor effectsreceptor effects

Mediate reflexes controlling gastrointestinal Mediate reflexes controlling gastrointestinal

motility and secretionmotility and secretion

Mediate perception of visceral painMediate perception of visceral pain


Reference: Gershon. Aliment Pharmacol Ther. 1999;13(suppl 2):15-30.

20 60 100 140 180

Comparison of pain thresholds Comparison of pain thresholds of IBS patients and controlsof IBS patients and controls

IBS IBS –– Physiology Physiology

% R

epo

rtin

g P

ain

% R

epo

rtin

g P

ain

Rectosigmoid balloon volume (mL)Rectosigmoid balloon volume (mL)

Reference: From Whitehead et al. Dig Dis Sci. June 1980;25:404-413. With permission.

0

20

40

60

IBSIBS

NormalNormal

Pain produced by rectosigmoid balloon distensionPain produced by rectosigmoid balloon distension

Comparison of pain thresholdsComparison of pain thresholds

IBS IBS –– Physiology Physiology

Colonic DistensionColonic Distension Ice Water ImmersionIce Water Immersion

IBSIBS

NormalNormal

Reference: Whitehead et al. Gastroenterology. May 1990;98:1187-1192.

Make a positive diagnosisMake a positive diagnosis1,21,2

IBS – IBS – DiagnosisDiagnosis

Identify abdominal pain as dominant Identify abdominal pain as dominant symptom with altered bowel functionsymptom with altered bowel function

Perform diagnostic tests/physical exam Perform diagnostic tests/physical exam to rule out organic diseaseto rule out organic disease

Initiate treatment program as part Initiate treatment program as part of diagnostic approachof diagnostic approach

Follow up in 3 to 6 weeksFollow up in 3 to 6 weeks

Look for “red flags”Look for “red flags”

References: 1. Paterson et al. Can Med Assoc J. July 1999;161:154-160. 2. American Gastroenterological Association. Gastroenterology. June 1997;112:2120-2137.

Make/confirm diagnosisMake/confirm diagnosis

IBS ROME II CRITERIAIBS ROME II CRITERIA

At Least 12 Weeks, Which Need Not Be At Least 12 Weeks, Which Need Not Be Consecutive, in the Preceding 12 Consecutive, in the Preceding 12 Months, of Abdominal Discomfort or Months, of Abdominal Discomfort or Pain That Has Two of Three Features:Pain That Has Two of Three Features:

1. Relieved with Defecation; and/or1. Relieved with Defecation; and/or2. Onset Associated with a Change 2. Onset Associated with a Change

in Frequency of Stool; and/orin Frequency of Stool; and/or3. Onset Associated with a Change 3. Onset Associated with a Change

in Form (Appearance) of Stoolin Form (Appearance) of Stool

ConstipationConstipation DiarrheaDiarrhea

““Red flags” may suggest an Red flags” may suggest an alternative or coexisting diagnosisalternative or coexisting diagnosis

AnemiaAnemia

FeverFever

Persistent diarrheaPersistent diarrhea

Rectal bleedingRectal bleeding

Severe constipationSevere constipation

Weight lossWeight loss


Reference: Paterson et al. Can Med Assoc J. July 1999;161:154-160.

Additional diagnostic screening needed for atypical Additional diagnostic screening needed for atypical presentations such aspresentations such as

Nocturnal symptoms of pain Nocturnal symptoms of pain and abnormal bowel functionand abnormal bowel function

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

New onset of symptoms in New onset of symptoms in patients 50+ years of agepatients 50+ years of age

Diagnostic tests—What? When? Who?Diagnostic tests—What? When? Who?

If patient has typical features of IBS:If patient has typical features of IBS:

If If 50 years of age, order CBC, electrolytes, LFTs, 50 years of age, order CBC, electrolytes, LFTs, screen stool for occult blood, and consider screen stool for occult blood, and consider sigmoidoscopy.sigmoidoscopy.11

If If 50 years of age, order CBC, electrolytes, LFTs, 50 years of age, order CBC, electrolytes, LFTs, and perform a colonoscopy or air-contrast barium and perform a colonoscopy or air-contrast barium enema with sigmoidoscopy.enema with sigmoidoscopy.1,21,2


References: 1. American Gastroenterological Association. Gastroenterology. June 1997;112:2120-2137. 2. Paterson et al. Can Med Assoc J. July 1999;161:154-160.

Differential diagnosisDifferential diagnosis

MalabsorptionMalabsorption11

Dietary factorsDietary factors11

InfectionInfection11

Inflammatory bowel diseaseInflammatory bowel disease11

Psychological disordersPsychological disorders11

Gynecological disordersGynecological disorders22

MiscellaneousMiscellaneous11


References: 1. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14. 2. Moore et al. Br J Obstet Gynaecol. December 1998;105:1322-1325.

CurreCurrentnt management of IBS management of IBS

Establish a Establish a positivepositive diagnosis diagnosis11

Reassure patient that there is no serious Reassure patient that there is no serious organic disease or alarming symptomsorganic disease or alarming symptoms11

Success of current treatment options in Success of current treatment options in addressing multiple symptoms of IBS has addressing multiple symptoms of IBS has been limitedbeen limited22


References: 1. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14. 2. Klein. Gastroenterology. July 1988;95:232-241.

Current management Current management components of IBScomponents of IBS

EducationEducation ReassuranceReassurance Dietary modificationDietary modification FiberFiber Symptomatic treatmentSymptomatic treatment Psychological/behavioral optionsPsychological/behavioral options Realistic goalsRealistic goals

IBS – IBS – ManagementManagement

Reference: Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.

Currently available Currently available Rx treatments for IBSRx treatments for IBS

Dicyclomine HClDicyclomine HCl11

Hyoscyamine sulfate Hyoscyamine sulfate (± other anticholinergics/sedatives)(± other anticholinergics/sedatives)22

Belladonna and phenobarbitalBelladonna and phenobarbital11

Clidinium bromide with chlordiazepoxideClidinium bromide with chlordiazepoxide11

TegaserodTegaserod

AlosetronAlosetron


References: 1. PDR® Generics™. 1998:314, 559-561, 873-875. 2. Physicians’ Desk Reference®. 1999:2910-2911.

Antispasmodics/anticholinergicsAntispasmodics/anticholinergics

Symptomatic treatment—painSymptomatic treatment—pain11

Smooth muscle relaxants via Smooth muscle relaxants via anticholinergic effects and/or direct anticholinergic effects and/or direct action on smooth muscleaction on smooth muscle22


References: 1. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14. 2. Drug Facts and Comparisons®. 1999:298-298c.

AntidiarrhealsAntidiarrheals

Symptomatic treatment—dSymptomatic treatment—diarrheaiarrhea

Increase stool firmnessIncrease stool firmness

Decrease stool frequencyDecrease stool frequency

– Examples: loperamide, diphenxylate-atropineExamples: loperamide, diphenxylate-atropine


Reference: Drug Facts and Comparisons®. 1999:324b.

Laxatives and bulking agentsLaxatives and bulking agents

Symptomatic treatment—constipationSymptomatic treatment—constipation


References: 1. American Gastroenterological Association. Gastroenterology. June 1997;112:2120-2132. 2. Camilleri and Choi. Aliment Pharmacol Ther. 1997;11:3-15. 3. Drug Facts and Comparisons®. 1999:316-317a.

Increased dietary fiber or psylliumIncreased dietary fiber or psyllium11

Osmotic laxatives (MgSOOsmotic laxatives (MgSO44, lactulose), lactulose)22

Stimulant laxativesStimulant laxatives33

Some laxatives and bulking agents can Some laxatives and bulking agents can exacerbate abdominal pain and bloatingexacerbate abdominal pain and bloating33

Tricyclic antidepressants Tricyclic antidepressants and SSRIsand SSRIs

Symptomatic treatment—painSymptomatic treatment—pain

Reserved for patients with severe Reserved for patients with severe or refractory painor refractory pain


Reference: Drossman and Thompson. Ann Intern Med. 1992;116(pt 1):1009-1016.

Multiple medications needed Multiple medications needed to treat multiple symptomsto treat multiple symptoms


AnticholinergicsAnticholinergics11 XX XX

TricyclicTricyclicantidepressantsantidepressants XX and SSRIsand SSRIs22

AntidiarrhealsAntidiarrheals11 XX XX XX

Bulking agentsBulking agents11 X X XX XX

LaxativesLaxatives33 XX XX

Lower Lower abdominal painabdominal pain BloatingBloating

Altered Altered stool formstool form

Altered Altered stool passagestool passage UrgencyUrgency

References: 1. American Gastroenterological Association. Gastroenterology. June 1997;112:2120-2137. 2. Drossman and Thompson. Ann Intern Med. 1992;116(pt 1):1009-1016. 3. Drug Facts and Comparisons®. 1999:316.

INITIAL MANAGEMENT OF IBSINITIAL MANAGEMENT OF IBS

Review Diet History Review Diet History Re: Fiber IntakeRe: Fiber Intake

YesYes

Increase Fiber (20g),Increase Fiber (20g),Osmotic LaxativeOsmotic Laxative

YesYes

H2 Breath TestH2 Breath TestCeliac panelCeliac panel

AntidiarrhealAntidiarrheal

YesYes

Abdominal X-ray Abdominal X-ray (KUB During Pain)(KUB During Pain)

AntispasmodicAntispasmodic++ Antidepressant Antidepressant

NoNo

Camilleri & Prather. 1992Camilleri & Prather. 1992

Additional TestsAdditional Tests

Therapeutic TrialTherapeutic Trial

Constipation Diarrhea Pain/Gas/Bloat

Symptom Features

Tegaserod (Zelnorm)Tegaserod (Zelnorm)(serotinin 4 receptor agonist)(serotinin 4 receptor agonist)

Approved for constipation predominant Approved for constipation predominant IBSIBS

1 pill given twice daily1 pill given twice daily Improvement of symptoms in women Improvement of symptoms in women

but not menbut not men Use up to 12 weeksUse up to 12 weeks Mild side effects: diarrhea the most Mild side effects: diarrhea the most

prominent side effectprominent side effect

Non-Traditional RemediesNon-Traditional Remedies

Chinese Herbal MedicineChinese Herbal Medicine– 116 pts randomized to CHM did better than pts 116 pts randomized to CHM did better than pts

receiving placeboreceiving placebo Peppermint OilPeppermint Oil

– Relaxation of GI smooth muscleRelaxation of GI smooth muscle– Meta-analysis showed significant improvement Meta-analysis showed significant improvement

of IBS symptomsof IBS symptoms AcupuntureAcupunture ProbioticsProbiotics AntibioticsAntibiotics Benoussan A. JAMA 1998Benoussan A. JAMA 1998

Pittler M. AJG 1998Pittler M. AJG 1998

Surgical Therapy for IBSSurgical Therapy for IBS

IBS symptoms may be attributed to:IBS symptoms may be attributed to:– Non-functioning gallbladder disease, Non-functioning gallbladder disease,

chronic appendicitis, uterine fibroids, chronic appendicitis, uterine fibroids, tortuous colontortuous colon

IBS symptoms rarely improve after IBS symptoms rarely improve after surgerysurgery

IBS patients 2 to 3 times more likely to IBS patients 2 to 3 times more likely to undergo unnecessary surgeryundergo unnecessary surgery

Take Home PointsTake Home Points

IBS is a chronic medical condition IBS is a chronic medical condition characterized by abdominal pain, characterized by abdominal pain, diarrhea or constipation, bloating, diarrhea or constipation, bloating, passage of mucus and feelings of passage of mucus and feelings of incomplete evacuationincomplete evacuation

Precise etiology of IBS is unknown and Precise etiology of IBS is unknown and therefore treatment is focused on therefore treatment is focused on relieving symptoms rather that “curing relieving symptoms rather that “curing disease”disease”

Take Home PointsTake Home Points

Although many IBS patients complain Although many IBS patients complain of symptoms after eating, true food of symptoms after eating, true food allergies are uncommonallergies are uncommon

Specific therapies are determined by Specific therapies are determined by individual patient symptomsindividual patient symptoms

Life-style modifications and possible Life-style modifications and possible alternative therapies may relieve alternative therapies may relieve symptomssymptoms

Surgery has NO Role in treatment of IBSSurgery has NO Role in treatment of IBS

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IRRITABLE BOWEL SYNDROME Kimberly M. Persley, MD