IRRITABLE BOWEL SYNDROME

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IRRITABLE BOWEL SYNDROME

• Kimberly M. Persley, MD

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Earliest descriptions of symptoms defining IBS
IBS History

• 1849 W Cumming1
• The bowels are at one time constipated, at
  another lax, in the same person.How the disease
  has two such different symptoms I do not profess
  to explain. . . .

• Other historical terms
• mucous colitis colonic spasm
  neurogenic mucous colitis irritable colon
  unstable colon nervous colon spastic
  colon nervous colitis spastic colitis
• 1962 Chaudhary Truelove2
• Irritable colon syndrome
• 1966 CJ DeLor3
• Irritable bowel syndrome

References 1. Cumming. Lond Med Gazette.
1849NS9969-973. 2. Chaudhary and Truelove. Q J
Med. July 196231307-322. 3. DeLor. Am J
Gastroenterol. May 196747427-434.
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Historical perspective
IBS History

• Long dismissed as a psychosomatic condition1
• no clear etiology affects predominantly
  women (70 of sufferers are women)2
  condition not fatal
• Attitudes now changing
• Incidence and prevalence not extensively
  monitored in past

References 1. Maxwell et al. Lancet. December
19973501691-1695. 2. Sandler. Gastroenterology.
August 199099409-415.
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Hallmark symptoms of IBS
IBS Signs and symptoms

• Chronic or recurrent GI symptoms
• lower abdominal pain/discomfort
• altered bowel function (urgency, altered stool
  consistency, altered stool frequency, incomplete
  evacuation)
• bloating
• Not explained by identifiable structural or
  biochemical abnormalities

Reference Thompson et al. Gut. 199945(suppl
2)1143-1147.
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Key facts about IBS
IBS Overview

• Up to 20 of the US population report symptoms
  consistent with IBS1
• The most common GI diagnosis among
  gastroenterology practices in the US2
• One of the top 10 reasons for PCP visits3
• Affects predominantly females (70 of
  sufferers)4
• The most common functional bowel disorder5

References 1. Camilleri and Choi. Aliment
Pharmacol Ther. 19971113-15. 2. Everhart and
Renault. Gastroenterology. April
1991100998-1005. 3. Physician Drug Diagnosis
Audit (PDDA), April 1999, Scott-Levin. 4.
Sandler. Gastroenterology. August
199099409-415. 5. Thompson et al. Gastroenterol
Int. 1992575-91.
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Key facts about IBS (cont.)
IBS Overview

• Can cause great discomfort, sometimes
  intermittent or continuous, for many decades in
  a patients life1
• Can significantly disrupt daily life2
• Can have negative impact on quality of life2
• Current treatment options3
• dietary modification
• fiber supplements
• pharmacologic agents
• psychotherapy
• Success of current treatment options in
  addressing multiple symptoms of IBS has been
  limited4

References 1. Hahn et al. Dig Dis Sci. December
1998432715-2718. 2. Hahn et al. Digestion.
19996077-81. 3. Drossman. Aliment Pharmacol
Ther. 199913(suppl 2)3-14. 4. Klein. Aliment
Pharmacol Ther. 199913(suppl 2)15-30.
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IBS Epidemiology
IBS consultation pattern
References 1. Drossman and Thompson. Ann Intern
Med. June 1992116(pt 1)1009-1016. 2. Sandler.
Gastroenterology. August 199099409-415.
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IBS vs other important disease states
IBS Epidemiology

• US prevalence up to 201
• US prevalence rates for other common diseases2
• diabetes 3
• asthma 4
• heart disease 8
• hypertension 11

References 1. Camilleri and Choi. Aliment
Pharmacol Ther. 1997113-15. 2. Adams and
Benson. Vital Health Stat 10. December 199183.
DHHS publication no (PHS)92-1509.
9
Direct medical costs associated with IBS
IBS Burden of disease

• IBS results in an estimated 8 billion in direct
  medical costs annually1
• IBS sufferers incur 74 more direct healthcare
  costs than non-IBS sufferers1
• IBS patients have more physician visits for both
  GI and non-GI complaints2

References 1. Talley et al. Gastroenterology.
December 19951091736-1741. 2. Drossman et al.
Dig Dis Sci. September 1993381569-1580.
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Productivity burden
IBS Burden of disease
Absenteeism from work or school during the last
12 months
14
12
10
8
P0.0001
Days per year
6
4
2
0
IBS
Non-IBS
Reference Drossman et al. Dig Dis Sci. September
1993381569-1580.
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IBS Burden of disease
Impact on work due to IBS
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
Over the previous 4 weeks.
Adapted from Hahn et al. Digestion. 19996077-81.
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Evolution of mechanistic hypotheses in IBS
IBS Physiology
5-HT mediated visceral sensitivity and gut
motility2
Brain-gut interaction1
Visceral hypersensitivity1
Abnormal motility1
1950
2000
References 1. Drossman. Aliment Pharmacol Ther.
199913(suppl 2)3-14. 2. Prior and Read. Aliment
Pharmacol Ther. 19937175-180.
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Irritable Bowel Syndrome

• Biopsychosocial Disorder
• Psychosocial
• Motility
• Sensory
• ? Infectious
• Prevalence 10, Incidence 1-2 per Year
• Disturbs QOL, Social Function, Healthcare
  Utilization

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Enteric nervous system
IBS Pathophysiology

• Controls motility and secretory functions of the
  intestine
• Semiautonomous
• actions modified by parasympathetic and
  sympathetic nervous systems
• may function independently
• Contains many neurotransmitters, including 5-HT,
  substance P, VIP (vasoactive intestinal
  peptide), and CGRP (calcitonin gene-related
  peptide)

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IBS Current thinking on pathophysiology
IBS Pathophysiology
Defects in the enteric nervous system 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, CGRP, and neurotropins
• Primary motility disorder of GI tract2
• Mediated by 5-HT, acetylcholine, ATP,
  motilin, nitric oxide, somatostatin,
  substance P, and VIP

References 1. Bueno et al. Gastroenterology. May
19971121714-1743. 2. Goyal and Hirano. N Engl J
Med. April 19963341106-1115.
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Physiological distribution of 5-HT
IBS Pathophysiology
CNS 5
GI tract 95
enterochromaffin cells neuronal
Reference Gershon. Aliment Pharmacol Ther.
199913(suppl 2)15-30.
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5-HT initiates peristaltic reflex mediated by
the ENS
IBS Pathophysiology
Intraluminal Pressure
Mucosa
Mucosal Enterochromaffin Cell
5-HT
5-HT Receptor Enteric Nervous System
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5-HT receptor effects
IBS Pathophysiology

• Mediate reflexes controlling gastrointestinal
  motility and secretion
• Mediate perception of visceral pain

Reference Gershon. Aliment Pharmacol Ther.
199913(suppl 2)15-30.
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Comparison of pain thresholds of IBS patients
and controls
IBS Physiology
Pain produced by rectosigmoid balloon distension
60
IBS
40
Reporting Pain
20
Normal
0
20
60
100
140
180
Rectosigmoid balloon volume (mL)
Reference From Whitehead et al. Dig Dis Sci.
June 198025404-413. With permission.
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Comparison of pain thresholds
IBS Physiology
IBS
Normal
Colonic Distension
Ice Water Immersion
Reference Whitehead et al. Gastroenterology. May
1990981187-1192.
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Make a positive diagnosis1,2
IBS Diagnosis
Identify abdominal pain as dominant symptom with
altered bowel function
Look for red flags
Perform diagnostic tests/physical exam to rule
out organic disease
Make/confirm diagnosis
Initiate treatment program as part of diagnostic
approach
Follow up in 3 to 6 weeks
References 1. Paterson et al. Can Med Assoc J.
July 1999161154-160. 2. American
Gastroenterological Association.
Gastroenterology. June 19971122120-2137.
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History of diagnostic approaches
IBS Diagnosis

• 1950s Increased gut motility1
• 1970s Specific motility markers1
• 1980 to 1999 Symptom-based criteria1
• Manning criteria
• Rome criteria
• 1999 Rome II criteria2

References 1. Drossman. Aliment Pharmacol Ther.
199913(suppl 2)3-14. 2. Thompson et al. Gut.
199945(suppl 2)1143-1147.
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IBS ROME II CRITERIA

• At Least 12 Weeks, Which Need Not Be Consecutive,
  in the Preceding 12 Months, of Abdominal
  Discomfort or Pain That Has Two of Three
  Features
• 1. Relieved with Defecation and/or
• 2. Onset Associated with a Change in Frequency
  of Stool and/or
• 3. Onset Associated with a Change in Form
  (Appearance) of Stool

Constipation
Diarrhea
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Red flags may suggest an alternative or
coexisting diagnosis
IBS Diagnosis
Additional diagnostic screening needed for
atypical presentations such as

• Anemia
• Fever
• Persistent diarrhea
• Rectal bleeding
• Severe constipation
• Weight loss

• Nocturnal symptoms of pain and abnormal bowel
  function
• Family history of GI cancer, inflammatory bowel
  disease, or celiac disease
• New onset of symptoms in patients 50 years of age

Reference Paterson et al. Can Med Assoc J. July
1999161154-160.
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Diagnostic testsWhat? When? Who?
IBS Diagnosis

• If patient has typical features of IBS
• If ?50 years of age, order CBC, electrolytes,
  LFTs, screen stool for occult blood, and consider
  sigmoidoscopy.1
• If ?50 years of age, order CBC, electrolytes,
  LFTs, and perform a colonoscopy or air-contrast
  barium enema with sigmoidoscopy.1,2

References 1. American Gastroenterological
Association. Gastroenterology. June
19971122120-2137. 2. Paterson et al. Can Med
Assoc J. July 1999161154-160.
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Differential diagnosis
IBS Diagnosis

• Malabsorption1
• Dietary factors1
• Infection1
• Inflammatory bowel disease1
• Psychological disorders1
• Gynecological disorders2
• Miscellaneous1

References 1. Drossman. Aliment Pharmacol Ther.
199913(suppl 2)3-14. 2. Moore et al. Br J
Obstet Gynaecol. December 19981051322-1325.
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Current management of IBS
IBS Diagnosis

• Establish a positive diagnosis1
• Reassure patient that there is no serious
  organic disease or alarming symptoms1
• Success of current treatment options in
  addressing multiple symptoms of IBS has been
  limited2

References 1. Drossman. Aliment Pharmacol Ther.
199913(suppl 2)3-14. 2. Klein.
Gastroenterology. July 198895232-241.
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Current management components of IBS
IBS Management

• Education
• Reassurance
• Dietary modification
• Fiber
• Symptomatic treatment
• Psychological/behavioral options
• Realistic goals

Reference Drossman. Aliment Pharmacol Ther.
199913(suppl 2)3-14.
29
Currently available Rx treatments for IBS
IBS Management

• Dicyclomine HCl1
• Hyoscyamine sulfate ( other anticholinergics/sed
  atives)2
• Belladonna and phenobarbital1
• Clidinium bromide with chlordiazepoxide1
• Tegaserod
• Alosetron

References 1. PDR Generics. 1998314, 559-561,
873-875. 2. Physicians Desk Reference.
19992910-2911.
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Antispasmodics/anticholinergics
IBS Management

• Symptomatic treatmentpain1
• Smooth muscle relaxants via anticholinergic
  effects and/or direct action on smooth muscle2

References 1. Drossman. Aliment Pharmacol Ther.
199913(suppl 2)3-14. 2. Drug Facts and
Comparisons. 1999298-298c.
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Antidiarrheals
IBS Management

• Symptomatic treatmentdiarrhea
• Increase stool firmness
• Decrease stool frequency
• Examples loperamide, diphenxylate-atropine

Reference Drug Facts and Comparisons. 1999324b.
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Laxatives and bulking agents
IBS Management

• Symptomatic treatmentconstipation

• Increased dietary fiber or psyllium1
• Osmotic laxatives (MgSO4, lactulose)2
• Stimulant laxatives3
• Some laxatives and bulking agents can exacerbate
  abdominal pain and bloating3

References 1. American Gastroenterological
Association. Gastroenterology. June
19971122120-2132. 2. Camilleri and Choi.
Aliment Pharmacol Ther. 1997113-15. 3. Drug
Facts and Comparisons. 1999316-317a.
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Tricyclic antidepressants and SSRIs
IBS Management

• Symptomatic treatmentpain
• Reserved for patients with severe or refractory
  pain

Reference Drossman and Thompson. Ann Intern Med.
1992116(pt 1)1009-1016.
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Multiple medications needed to treat multiple
symptoms
IBS Management
References 1. American Gastroenterological
Association. Gastroenterology. June
19971122120-2137. 2. Drossman and Thompson. Ann
Intern Med. 1992116(pt 1)1009-1016. 3. Drug
Facts and Comparisons. 1999316.
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A comprehensive multicomponent approach
IBS Management

• Treatment program is based on dominant symptoms
  and their severity and on psychosocial factors
• Medical management
• Diet
• Psychological or behavioral options
• psychotherapy stress management

Reference Drossman. Aliment Pharmacol Ther.
199913(suppl 2)3-14.
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INITIAL MANAGEMENT OF IBS
Symptom Features
Constipation
Diarrhea
Pain/Gas/Bloat
Review Diet History Re Fiber Intake
Yes
Yes
Yes
Additional Tests
H2 Breath Test Celiac panel
Abdominal X-ray (KUB During Pain)
No
Increase Fiber (20g), Osmotic Laxative
Antidiarrheal
Antispasmodic Antidepressant
Therapeutic Trial
Camilleri Prather. 1992
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Tegaserod (Zelnorm)(serotinin 4 receptor agonist)

• Approved for constipation predominant IBS
• 1 pill given twice daily
• Improvement of symptoms in women but not men
• Use up to 12 weeks
• Mild side effects diarrhea the most prominent
  side effect

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Non-Traditional Remedies

• Chinese Herbal Medicine
• 116 pts randomized to CHM did better than pts
  receiving placebo
• Peppermint Oil
• Relaxation of GI smooth muscle
• Meta-analysis showed significant improvement of
  IBS symptoms
• Acupunture
• Probiotics
• Antibiotics

Benoussan A. JAMA 1998 Pittler M. AJG 1998
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Surgical Therapy for IBS

• IBS symptoms may be attributed to
• Non-functioning gallbladder disease, chronic
  appendicitis, uterine fibroids, tortuous colon
• IBS symptoms rarely improve after surgery
• IBS patients 2 to 3 times more likely to undergo
  unnecessary surgery

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Take Home Points

• IBS is a chronic medical condition characterized
  by abdominal pain, diarrhea or constipation,
  bloating, passage of mucus and feelings of
  incomplete evacuation
• Precise etiology of IBS is unknown and therefore
  treatment is focused on relieving symptoms rather
  that curing disease

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Take Home Points

• Although many IBS patients complain of symptoms
  after eating, true food allergies are uncommon
• Specific therapies are determined by individual
  patient symptoms
• Life-style modifications and possible alternative
  therapies may relieve symptoms
• Surgery has NO Role in treatment of IBS