IRRITABLE BOWEL SYNDROME

Kimberly M. Persley, MD

IBS History

Earliest descriptions of symptoms defining IBS

1849 W Cumming1

Other historical terms

mucous colitis colonic spasm neurogenic mucous colitis irritable colon unstable colon nervous colon spastic colon nervous colitis spastic colitis

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. . . .

1962 Chaudhary & Truelove2

Irritable colon syndrome

1966 CJ DeLor3
Irritable 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.

IBS History

Historical perspective

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 1997;350:1691-1695. 2. Sandler. Gastroenterology. August 1990;99:409-415.

IBS Signs and symptoms

Hallmark symptoms of IBS

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. 1999;45(suppl 2):1143-1147.

IBS Overview

Key facts about IBS

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. 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.

IBS Overview

Key facts about IBS (cont.)

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 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 Epidemiology

IBS consultation pattern

Specialists1 ~25% Consulters1 Primary care1

~75% Nonconsulters1

~70% Female2

~30% Male2

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

IBS Epidemiology

IBS vs other important disease states

US prevalence up to 20%1 US prevalence rates for other common diseases2:

diabetes asthma heart disease hypertension 3% 4% 8% 11%

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.

IBS Burden of disease

Productivity burden
Absenteeism from work or school during the last 12 months 14 12 Days per year 10 8 6 4 2 0 IBS Non-IBS P=0.0001

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

Irritable Bowel Syndrome

Psychosocial Factors
Vagal nuclei

Biopsychosocial Disorder

Psychosocial Motility Sensory ? Infectious

Sympathetic S2,3,4

Altered Motility

Altered Sensation

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

IBS Pathophysiology

IBS: Current thinking on 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 1997;112:1714-1743. 2. Goyal and Hirano. N Engl J Med. April 1996;334:1106-1115.

IBS Pathophysiology

Physiological distribution of 5-HT

CNS 5%

enterochromaffin cells neuronal

GI tract 95%

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

IBS Pathophysiology

5-HT receptor effects

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

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

IBS Physiology

Comparison of pain thresholds of IBS patients and controls

60

Pain produced by rectosigmoid balloon distension

IBS
% Reporting Pain

40

20

Normal
0 20 60 100 140 180
Rectosigmoid balloon volume (mL)

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

IBS Physiology

Comparison of pain thresholds

IBS Normal

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

Ice Water Immersion

IBS Diagnosis

Make a positive diagnosis1,2

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 1999;161:154-160. 2. American Gastroenterological Association. Gastroenterology. June 1997;112:2120-2137.

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

IBS Diagnosis

Red flags may suggest an alternative or coexisting 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 1999;161:154-160.

IBS Diagnosis

Diagnostic testsWhat? When? Who?

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 1997;112:2120-2137. 2. Paterson et al. Can Med Assoc J. July 1999;161:154-160.

IBS Diagnosis

Differential diagnosis

Malabsorption1 Dietary factors1

Infection1
Inflammatory bowel disease1 Psychological disorders1

Gynecological disorders2
Miscellaneous1

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.

IBS Diagnosis

Current management of IBS

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. 1999;13(suppl 2):3-14. 2. Klein. Gastroenterology. July 1988;95:232-241.

IBS Management

Current management components of IBS

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

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

IBS Management

Currently available Rx treatments for IBS

Dicyclomine HCl1 Hyoscyamine sulfate

( other anticholinergics/sedatives)2

Belladonna and phenobarbital1

Clidinium bromide with chlordiazepoxide1 Tegaserod Alosetron

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

IBS Management

Antispasmodics/anticholinergics
Symptomatic treatmentpain1

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

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

IBS Management

Antidiarrheals
Symptomatic treatmentdiarrhea

Increase stool firmness Decrease stool frequency

Examples: loperamide, diphenxylate-atropine

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

IBS Management

Laxatives and bulking agents

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 1997;112:2120-2132. 2. Camilleri and Choi. Aliment Pharmacol Ther. 1997;11:3-15. 3. Drug Facts and Comparisons. 1999:316-317a.

IBS Management

Tricyclic antidepressants and SSRIs

Symptomatic treatmentpain

Reserved for patients with severe or refractory pain

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

IBS Management

Multiple medications needed to treat multiple symptoms

Lower abdominal pain Anticholinergics1 Tricyclic antidepressants and SSRIs2 Antidiarrheals1 Bulking agents1 Laxatives3 X X X X X X X X X X Bloating X Altered stool form Altered stool passage Urgency

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 IBS

Symptom Features

Constipation Review Diet History Re: Fiber Intake Additional Tests Therapeutic Trial

Diarrhea
Yes

Pain/Gas/Bloat
Yes

Yes

No Increase Fiber (20g), Osmotic Laxative

H2 Breath Test Celiac panel Antidiarrheal

Abdominal X-ray (KUB During Pain) Antispasmodic + Antidepressant

Camilleri & Prather. 1992

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

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

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

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

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