1. IRRITABLE BOWEL SYNDROME
Irritable Bowel Syndrome Slide Cover

2. Earliest descriptions of symptoms defining IBS
IBS – History
Earliest descriptions of symptoms defining IBS
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
Physicians have been aware of the symptoms of irritable bowel syndrome (IBS) for well over a century. The first reports in medical journals of patients with functional abdominal symptoms appeared in the early 19th century. In 1849, Cumming aptly described IBS when he stated: “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 ”1 Throughout the 19th and into the 20th century, some of the other terms used to describe IBS were neurogenic mucous colitis,2 spastic colon,3 and irritable colon syndrome.4
However, it wasn’t until just over 30 years ago that the term irritable bowel syndrome was coined. In 1966, DeLor referred to the irritable bowel syndrome, defining it as a functional enteropathy, characterized by one or a combination of symptoms, including abdominal pain, diarrhea, constipation, dyschezia, and passage of mucus in the stool.5
References: 1. Cumming W. Electro-galvanism in a peculiar affection of the mucous membrane of the bowels. Lond Med Gazette. 1849;NS9:
2. Bockus HL, Bank J, Wilkinson SA. Neurogenic mucous colitis. Am J Med Sci ;176:
3. Ryle JA. Chronic spasmodic affections of the colon and the diseases which they simulate. Lancet. December 1928;215:
4. Chaudhary NA, Truelove SC. The irritable colon syndrome. Q J Med. July ;31:
5. DeLor CJ. The irritable bowel syndrome. Am J Gastroenterol. May 1967;47:

3. Historical perspective
IBS – History
Historical perspective
Long dismissed as a psychosomatic condition1
– no clear etiology – affects predominantly women (~70% of sufferers are women) – condition not fatal
Attitudes now changing
Incidence and prevalence not extensively monitored in past
IBS was long dismissed as a psychosomatic condition.1 It has no clear etiology or pathophysiology, affects mainly women, and is not fatal.2
However, attitudes are changing as physicians learn more about the pathophysiology of IBS.
The incidence and prevalence of IBS have not been extensively monitored, so it is difficult to discern historical trends. Also, only a small proportion of IBS sufferers seek treatment,3 and diagnosis of the condition is difficult.4
References:
1. Maxwell PR, Mendall MA, Kumar D. Irritable bowel syndrome. Lancet. December ;350:
2. Sandler RS. Epidemiology of irritable bowel syndrome in the United States. Gastroenterology. August 1990;99:
3. Drossman DA, Thompson WG. The irritable bowel syndrome: review and a graduated multicomponent treatment approach. Ann Intern Med. June 1992;116(pt 1):
4. Paterson WG, Thompson WG, Vanner SJ, et al. Recommendations for the management of irritable bowel syndrome in family practice. Can Med Assoc J. July 1999;161:

4. Hallmark symptoms of IBS
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
IBS is one of over 20 functional gastrointestinal (GI) disorders.1 The functional GI disorders vary clinically and are characterized by chronic or recurrent symptoms not explained by structural or biochemical abnormalities. It appears that these disorders relate to abnormalities in motility and/or afferent sensitivity as modulated by the central nervous system.2
IBS is defined as a functional bowel disorder in which abdominal pain is associated with a change in bowel habit with features of disordered defecation.3
Features of disordered defecation include3
 Urgency
 Altered stool consistency
 Altered stool frequency
 Incomplete evacuation
References:
1. Drossman DA, Thompson WG, Talley NJ, Funch-Jensen P, Janssens J, Whitehead WE. Identification of sub-groups of functional gastrointestinal disorders. Gastroenterol Int. December 1990;3:
2. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
3. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(suppl 2):

5. IBS – Overview
Key facts about IBS
Up to 20% of the US population report symptoms consistent with IBS
The most common GI diagnosis among gastroenterology practices in the US
One of the top 10 reasons for family physician visits
The most common functional bowel disorder
Prevalence estimates from surveys among American adults suggest that up to 20% of the population report symptoms consistent with IBS.1 These surveys have shown that, in general, female patients outnumber male patients 3:1.2
Irritable bowel syndrome is the most common functional bowel disorder,3 the most common GI diagnosis among US gastroenterology practices,4 and is one of the top 10 reasons for primary care physician visits.5
Estimates of prevalence of IBS are, however, diverse. This is likely to be a consequence of the differences between epidemiological studies (e.g., the use of different diagnostic criteria, selected populations, and the source of the data).2,6
References:
1. Camilleri M, Choi M-G. Review article: irritable bowel syndrome. Aliment Pharmacol Ther. 1997;11:3-15.
2. Sandler RS. Epidemiology of irritable bowel syndrome in the United States. Gastroenterology. August 1990;99:
3. Thompson WG, Creed F, Drossman DA, Heaton KW, Mazzacca G. Functional bowel disease and functional abdominal pain. Gastroenterol Int. 1992;5:75-91.
4. Everhart JE, Renault PF. Irritable bowel syndrome in office-based practice in the United States. Gastroenterology. April 1991;100:
5. Physician Drug & Diagnosis Audit (PDDA), April 1999, Scott-Levin.
6. Drossman DA, Li Z, Andruzzi E, et al. US householder survey of functional gastrointestinal disorders—prevalence, sociodemography, and health impact. Dig Dis Sci. September 1993;38:

6. Key facts about IBS (cont.)
IBS – Overview
Key facts about IBS (cont.)
Can cause great discomfort, sometimes intermittent or continuous, for many decades in a patient’s life
Can significantly disrupt daily life
Can have negative impact on quality of life2
Current treatment options
– dietary modification
– fiber supplements
– pharmacologic agents
– psychotherapy
Success of current treatment options in addressing multiple symptoms of IBS has been limited
IBS can cause great discomfort and can affect an individual for many years. The symptoms can be either persistent or recurrent and may vary over time.1
Patients suffer from altered bowel habits accompanied by pain or discomfort, which can significantly disrupt their daily lives.2
Current treatment options include
 Dietary restrictions—avoiding fatty foods or lactose3
 Supplementing diet with fiber3,4
 Pharmacologic agents—antidiarrheals,3 laxatives,3 antispasmodics,3 tricyclic antidepressants, and SSRIs4
 Psychotherapy—hypnotherapy, relaxation exercises, psychological treatment3,4
Success of current treatment options in addressing multiple symptoms of IBS has been limited.5
References:
1. Hahn B, Watson M, Yan S, Gunput D, Heuijerjans J. Irritable bowel syndrome symptom patterns: frequency, duration, and severity. Dig Dis Sci. December 1998;43:
2. Hahn BA, Yan S, Strassels S. Impact of irritable bowel syndrome on quality of life and resource use in the United States and United Kingdom. Digestion. 1999;60:77-81.
3. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
4. American Gastroenterological Association. Medical position statement: irritable bowel syndrome. Gastroenterology. June 1997;112:
5. Klein KB. Controlled treatment trials in the irritable bowel syndrome: a critique. Gastroenterology. July 1988;95:

7. IBS consultation pattern
IBS – Epidemiology
IBS consultation pattern
Specialists
Primary care
~25%
Consulters
~75%
Non-consulters
~70%
Female
~30%
Male
Although IBS affects up to one fifth of the population, only 25% seek medical advice. It is unclear as to why the other 75% do not consult their physicians.1 Some patients may have received unsatisfactory treatment in the past1 or simply may have learned to live with their condition and to accept their current quality of life.2,3
References:
1. Drossman DA, Thompson WG. The irritable bowel syndrome: review and a graduated multicomponent treatment approach. Ann Intern Med. June 1992;116(pt 1):
2. Wells NEJ, Hahn BA, Whorwell PJ. Clinical economics review: irritable bowel syndrome. Aliment Pharamacol Ther. 1997;11:
3. Data on file (Irritable bowel syndrome in American women, a landmark survey, July 1999), Glaxo Wellcome Inc.

8. IBS vs other important disease states
IBS – Epidemiology
IBS vs other important disease states
US prevalence up to 20%
US prevalence rates for other common diseases:
– diabetes 3%
– asthma 4%
– heart disease 8%
– hypertension 11%
When compared with prevalence rates of other common diseases, IBS ranks the highest and has nearly twice the rate of hypertension, the next most prevalent disease state.1 Although it is not a life-threatening disease, it is important to note the dramatic impact that IBS can have on the quality of life of those who are affected.
Reference:
1. Adams PF, Benson V. Current estimates from the National Health Interview Survey, Vital Health Stat 10. Hyattsville, Md: US Dept of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Health Statistics; December 1991:83. DHHS Publication no (PHS)

9. Absenteeism from work or school during the last 12 months
IBS – Burden of disease
Productivity burden
Absenteeism from work or school during the last 12 months 14 12 10 8
Days per year
P=0.0001 6
The impact of productivity is measured not only in terms of how businesses are affected by the high rate of absenteeism but also by the impact of consulters on the healthcare system.1
The purpose of the US Householder Survey reported by Drossman et al was to provide national data for the United States on the frequency and sociodemographic features of functional GI disorders and their relationship to absenteeism from work or school and healthcare use. A random sample of US householders was surveyed.1
The survey showed that in the previous year, patients with IBS had missed about 3 times as many days from work or school because of illness compared with those with no evidence of functional GI disorder (mean values: 13.4 days vs 4.9 days; P=0.0001). In addition, a higher proportion of those with IBS reported that they currently were too sick to work or to go to school compared with those without IBS (11.3% vs 4.2%).1
Drossman et al also found that persons with IBS were significantly more likely to see physicians for complaints unrelated to the GI tract (3.9/year vs 1.8/year; P=0.0001) as well as for GI complaints (1.6/year vs 0.1/year; P=0.0001) than were persons with no evidence of functional GI disorders.1
Reference:
1. Drossman DA, Li Z, Andruzzi E, et al. US householder survey of functional gastrointestinal disorders—prevalence, sociodemography, and health impact. Dig Dis Sci. September 1993;38: 4 2
IBS
Non-IBS

10. Evolution of mechanistic hypotheses in IBS
IBS – Physiology
Evolution of mechanistic hypotheses in IBS
5-HT mediated visceral
sensitivity and gut motility
Brain-gut interaction
Visceral hypersensitivity
The physiological understanding of IBS has evolved over the years. At one stage, IBS was described as a syndrome characterized by visceral hypersensitivity and abnormal gut motility.1 Studies using rectosigmoid balloon distension have shown that IBS patients have a significantly lower threshold for visceral pain than do healthy controls.2,3
The CNS regulates intestinal motor and sensory activity, and it was hypothesized that perhaps the interaction between the brain and gut altered the perception of pain in patients with IBS. A central concept to this theory is the development of hyperexcitability of neurons in the dorsal horn.4 This hyperexcitability can develop either in response to peripheral tissue irritation or to influences originating from the brain stem. It was then postulated that IBS may be a result of a disruption in the coordination of these centers.1
Knowing that 5-HT receptors may inhibit the activation of pain pathways in the peripheral nervous system led researchers to examine the role of 5-HT in IBS.5
References:
1. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
2. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut. 1973;14:
3. Whitehead WE, Engel BT, Schuster MM. Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients. Dig Dis Sci. June 1980;25:
4. Mayer EA, Gebhart GF. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology. July 1994;107:
5. Prior A, Read W. Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5-HT3-receptor antagonist, in patients with irritable bowel syndrome. Aliment Pharmacol Ther ;7:
Abnormal motility
1950
2000

11. Irritable Bowel Syndrome
Psychosocial
Factors
Altered
Motility
S2,3,4
Vagal nuclei
Sympathetic
Sensation
Biopsychosocial Disorder
Psychosocial
Motility
Sensory
? Infectious
Prevalence 10%, Incidence 1-2% per Year
Disturbs QOL, Social Function, Healthcare Utilization
Irritable Bowel Syndrome Slide 4
IBS as regarded as a biopsychosocial disorder in which 3 main etiopathogenetic factors are important: (1) psychosocial disturbance, (2) altered motility, (3) heightened sensation. There is some evidence that an infectious process may also be important in the development of IBS. Thus, about 1/3 of patients with IBS have a preceding episode of gastroenteritis which is presumed to be infectious. The overall prevalence in the U.S. is around 10%, and preliminary evidence suggests that the incidence (that is, the number of new cases per year) is 1-2%. IBS disturbs the quality of life and social function, and results in considerable healthcare utilization.
References
Camilleri M, Choi M-G: Irritable bowel syndrome. Aliment Pharmacol Ther 11:3-15, 1997
Drossman DA, Whitehead WE, Camilleri M: Irritable bowel syndrome: a technical review for practice guidelines. Gastroenterology 112: , 1997
Drossman DA, Corazziari E, Talley NJ, Thompson WG, Whitehead WE, et al. Rome II: A multinational consensus document on functional gastrointestinal disorders. Gut 45(Suppl. II):II1-II81, 1999
Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW: Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 355: , 2000
Prather CM, Camilleri M, Zinsmeister AR, McKinzie S, Thomforde GM: Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology 118: , 2000
Bouras EP, Camilleri M, Burton DD, Thomforde G, McKinzie S, Zinsmeister AR: Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology

12. Enteric nervous system
IBS – Pathophysiology
Enteric nervous system
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)

13. IBS: Current thinking on pathophysiology
IBS – Pathophysiology
IBS: Current thinking on pathophysiology
Defects in the enteric nervous system may lead to the hallmark symptoms of IBS.
Visceral hypersensitivity
– 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 tract
– Mediated by 5-HT, acetylcholine, ATP, motilin, nitric oxide, somatostatin, substance P, and VIP
Recent data suggest that there may be several mediators involved in visceral sensitivity and motility, one of which is 5-HT.1,2
References:
1. Bueno L, Fiormonti J, Delvaux M, Frexinos J. Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. Gastroenterology. May 1997;112:
2. Goyal RK, Hirano I. Review article: the enteric nervous sytem. N Engl J Med. April 1996;334:

14. Physiological distribution of 5-HT
IBS – Pathophysiology
Physiological distribution of 5-HT
CNS – 5%
GI tract – 95%
5-HT has been implicated both as a neurotransmitter and as a paracrine signaling molecule in the bowel.1 It serves as a neurotransmitter in bowel nociceptive afferent (sensory) fibers, and this has been a major focus of recent research.2
5-hydroxytryptamine is distributed throughout the gut, predominantly within enterochromaffin cells in the mucosal crypts and, to a lesser extent, within the nerve fibers of the myenteric and submucosal plexuses. The concentration of 5-HT in the bowel is substantially greater than that in the brain.1
Although there are many neurotransmitters in the CNS and the gut, 5-HT has received some considerable attention. It is well established that about 95% of the body’s 5-HT is synthesized and stored in the enterochromaffin cells of the gut.1
References:
1. Gershon MD. Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel. Aliment Pharmacol Ther. 1999;13(suppl 2):15-30.
2. Everhart JE, Renault PF. Irritable bowel syndrome in office-based practice in the United States. Gastroenterology. April 1991;100:
– enterochromaffin cells
– neuronal

15. 5-HT initiates peristaltic reflex mediated by the ENS
IBS – Pathophysiology
5-HT initiates peristaltic reflex mediated by the ENS
Intraluminal Pressure
Mucosa
Mucosal Enterochromaffin Cell
5-HT is secreted from enterochromaffin cells located in the mucosa of the gut. When secreted, 5-HT may act as a mediator by exciting afferent nerves of the mucosa, thus initiating the peristaltic reflex.1 The proposed role of 5-HT in the gut is associated with increased gastrointestinal motility.2
References:
1. Gershon MD. The enteric nervous system: a second brain. Hosp Pract. July :31-52.
2. Talley NJ. Review article: 5-hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical implications Aliment Pharmacol Ther. 1992;6:
5-HT
5-HT Receptor [Enteric Nervous System]

16. IBS – Pathophysiology
5-HT receptor effects
Mediate reflexes controlling gastrointestinal motility and secretion
Mediate perception of visceral pain

17. Comparison of pain thresholds of IBS patients and controls
IBS – Physiology
Comparison of pain thresholds of IBS patients and controls
Pain produced by rectosigmoid balloon distension 60
IBS 40
% Reporting Pain 20
Normal
Studies have demonstrated that patients with IBS have a heightened state of visceral sensitivity.1 In 1980, Whitehead et al evaluated pain thresholds of a total of 25 IBS patients and 20 healthy controls. By distending a rectosigmoid balloon in a stepwise fashion, the investigators found that pain thresholds in IBS patients were significantly lower than in controls (P<0.05).2 Studies evaluating the pain thresholds of other GI disorders involving the esophagus3 and stomach4 have shown similar findings.
References:
1. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut. 1973;14:
2. Whitehead WE, Engel BT, Schuster MM. Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients. Dig Dis Sci. 1980;25:6:
3. Richter JE, Barish CF, Castell DO. Abnormal sensory perception in patients with esophageal chest pain. Gastroenterology. October 1986;91:
4. Mearin F, Cucala M, Azpiroz F, Malagelada J-R. The origin of symptoms on the brain- gut axis in fuctional dyspepsia. Gastroenterology. October 1991;101: 20 60
100
140
180
Rectosigmoid balloon volume (mL)

18. Comparison of pain thresholds
IBS – Physiology
Comparison of pain thresholds
IBS
Normal
Studies have examined both visceral and somatic sensitivity among patients with IBS. Balloon distention studies as referred to in the previous slide have demonstrated that IBS patients may have visceral hypersensitivity. To determine whether IBS patients exhibit overall hypersensitivity, subjects were asked to immerse their right hands into a mixture of ice and water. The findings showed that there were no significant differences between patient groups and controls in terms of somatic pain tolerance.1
However, another study designed to evaluate somatic pain subjected patients and controls to electrical current with a frequency of 100 Hz. The results showed that IBS patients are less sensitive to low-intensity nonpainful stimuli and have a higher threshold for painful stimuli than controls.2
These findings suggest that IBS patients may experience hypersensitivity in the gut only, while they may have normal or supranormal tolerance thresholds to acute somatic pain.
References:
1. Whitehead WE, Holtkotter B, Enck P, et al. Tolerance for rectosigmoid distension in irritable bowel syndrome. Gastroenterology. May 1990;98:
2. Cook IJ, van Eeden A, Collins SM. Patients with irritable bowel syndrome have greater pain tolerance than normal subjects. Gastroenterology. October 1987;93:
Colonic Distension
Ice Water Immersion

19. Make a positive diagnosis1,2
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
Precision in diagnosing IBS has been enhanced and simplified through the use of symptom-based criteria.
If a patient presents with chronic (12 weeks) bowel function disorders including abdominal pain as the dominant symptom with altered bowel function, a diagnosis of IBS is quite likely. To rule out an alternative or coexisting diagnosis, look for red flags such as weight loss, rectal bleeding, or anemia. Next, order laboratory studies and perform a physical exam to confirm the absence of organic disease.1
Once the diagnosis has been confirmed, initiate a treatment program and follow up in 3 to 6 weeks.2
References:
1. Paterson WG, Thompson WG, Vanner SJ, et al. Recommendations for the management of irritable bowel syndrome in family practice. Can Med Assoc J. July 1999;161:
2. American Gastroenterological Association. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology. June 1997;112:
Initiate treatment program as part of diagnostic approach
Follow up in 3 to 6 weeks

20. History of diagnostic approaches
IBS – Diagnosis
History of diagnostic approaches
1950s – Increased gut motility
1970s – Specific motility markers
1980 to 1999 – Symptom-based criteria
Manning criteria
Rome criteria
1999 – Rome II criteria
Diagnostic approaches continue to change. In the 1950s, physicians believed increased gut motility was the underlying cause of IBS. In the 1970s, specific motility markers were used to define IBS, and in the 1980s, diagnostic criteria were developed to help doctors make more positive diagnoses. The Manning criteria, introduced in 1988, identified a number of key features that were predictive of IBS. These criteria were further refined by the Rome Committee for use in clinical research and are referred to as the Rome criteria.1 The Rome II criteria are a simplification of the original criteria for application to clinical practice.2
References:
1. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
2. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(suppl 2):

21. 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
Irritable Bowel Syndrome Slide 2
IBS is a common clinical syndrome which is characterized by abdominal pain and altered bowel habit. The Rome II criteria defined IBS as a syndrome occurring for at least 12 weeks, which need not be consecutive, in the previous 12 months in which the patient experiences abdominal discomfort or pain that has two of the three features: (1) relief with defecation, and/or (2) onset associated with a change in frequency, and/or (3) onset associated with a change in the form or appearance of stool. The change in bowel function may be characterized by either diarrhea, constipation, or alternating bowel habit.
References
Camilleri M, Choi M-G: Irritable bowel syndrome. Aliment Pharmacol Ther 11:3-15, 1997
Drossman DA, Whitehead WE, Camilleri M: Irritable bowel syndrome: a technical review for practice guidelines. Gastroenterology 112: , 1997
Drossman DA, Corazziari E, Talley NJ, Thompson WG, Whitehead WE, et al. Rome II: A multinational consensus document on functional gastrointestinal disorders. Gut 45(Suppl. II):II1-II81, 1999
Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW: Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 355: , 2000
Prather CM, Camilleri M, Zinsmeister AR, McKinzie S, Thomforde GM: Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology 118: , 2000
Bouras EP, Camilleri M, Burton DD, Thomforde G, McKinzie S, Zinsmeister AR: Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology

22. The Rome III Diagnostic Criteria*
A SYSTEM FOR DIAGNOSING FUNCTIONAL GASTROINTESTINAL DISORDERS BASED ON SYMPTOMS FOR IBS:
Recurrent abdominal pain or discomfort** at least 3 days per month over the last 3 months associated with 2 or more of the following:
Improvement with defecation
Onset associated with a change in frequency of stool
Onset associated with a change in form (appearance) of stool
* Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. ** "Discomfort" means an uncomfortable sensation not described as pain.
IBS guidelines (NICE, American Gastrenterology Society, ECPCG), Rome III diagnostic criteria, Bristol Stool Chart

23. IBS EXAMINATIONS (Roma III criteria)
RECOMMENDED
NOT RECOMMENDED
1. Full blood count (FBC)
1. Ultrasound
2. Erythrocyte sedimentation rate
(ESR) or plasma viscosity
2. Rigid/flexible sigmoidoscopy
3. C-reactive protein (CRP)
3. Colonoscopy; Barium enema
4. Antibody testing for coeliac disease
(endomysial antibodies [EMA]
or tissue transglutaminase [TTG])
4. Hydrogen breath test (for lactose
intolerance and bacterial
overgrowth)
5. Thyroid function test (TSH)
6. Faecal ova and parasite test
7. Faecal occult blood test

24. “Red flags” may suggest an alternative or coexisting diagnosis
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
To rule out alternative or coexisting disease, there are some red flags that may appear either during the intake or physical exam that would suggest a condition other than IBS.
Reference:
Paterson WG, Thompson WG, Vanner SJ, et al. Recommendations for the management of irritable bowel syndrome in family practice. Can Med Assoc J. July 1999;161:

25. Diagnostic tests—What? When? Who?
IBS – Diagnosis
Diagnostic tests—What? 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.
If 50 years of age, order CBC, electrolytes, LFTs, and perform a colonoscopy or air-contrast barium enema with sigmoidoscopy.
Precision in the diagnosis of IBS has been enhanced and simplified through the use of symptom-based criteria. If a patient has typical features of IBS and is less than 50 years of age, order a CBC, electrolytes, LFTs, screen stool for occult blood, and consider sigmoidoscopy.1 If the patient is 50 years of age or older, order CBC, electrolytes, LFTs, and perform a colonoscopy or air-contrast barium enema with sigmoidoscopy.1,2
References:
1. Paterson WG, Thompson WG, Vanner SJ, et al. Recommendations for the management of irritable bowel syndrome in family practice. Can Med Assoc J. July 1999;161:
2. American Gastroenterological Association. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology. June 1997;112:

26. Differential diagnosis
IBS – Diagnosis
Differential diagnosis
Malabsorption
Dietary factors
Infection
Inflammatory bowel disease
Psychological disorders
Gynecological disorders
Miscellaneous
The following categories should be considered in the differential diagnosis of recurrent abdominal discomfort and bowel dysfunction.
Malabsorptive conditions, such as postgastrectomy, intestinal diseases (e.g., sprue), or pancreatic insufficiency. These conditions may cause cramps and/or diarrhea.1
Dietary factors, such as lactose (in lactose-intolerant patients), caffeine, alcohol, and fat-containing or gas-producing (e.g., cruciferous vegetables) foods. Some foods may act as triggers and may therefore cause and/or intensify symptoms.2
Infections due to bacteria (e.g., Campylobacter jejuni, Salmonella spp) or common parasites like Giardia lamblia.1
Inflammatory bowel disease, like Crohn’s disease or ulcerative colitis. Symptoms of these diseases can often mimic those of IBS. Other less common microscopic colitides such as collagenous colitis or mast-cell disease can be diagnosed by colonic biopsy.1
Psychological disorders, including panic disorder, depression, and somatization. These disorders may be associated with an increase in symptom reporting.1
Miscellaneous conditions, including gynecological conditions such as endometriosis or dysmenorrhea,3 as well as endocrine tumors (e.g., carcinoid, Zollinger-Ellison syndrome, VIPoma) and HIV disease and other associated infections.1
References:
1. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
2. American Gastroenterological Association: Irritable bowel syndrome; a technical review for practice guideline development. Gastroenterology. June 1997;112:
3. Moore J, Barlow D, Jewell D, Kennedy S. Do gastrointestinal symptoms vary with the menstrual cycle? Br J Obstet Gynaecol. December 1998;105:

27. Current management of IBS
IBS – Diagnosis
Current management of IBS
Establish a positive diagnosis
Reassure patient that there is no serious organic disease or alarming symptoms
Success of current treatment options in addressing multiple symptoms of IBS has been limited
Patients need to be told that their symptoms of IBS are in fact real and that they are not suffering from a serious organic disease. The best time to reassure patients that they are not seriously ill and that their disorder is manageable is after the evaluation. Listening to the patient’s concerns and establishing a supportive relationship is critical to establishing a successful treatment plan.1
Currently, many of the pharmacological agents that are available for the treatment of IBS generally target only one symptom. Therefore, patients may need to take more than one medication in order to get their symptoms under control. The use of medications directed at the gut should be targeted for the predominant symptom (e.g., pain, diarrhea, or constipation).2,3 Tricyclic antidepressants and SSRIs are often prescribed for patients with severe or refractory pain.3
References:
1. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
2. Maxwell PR, Mendall MA, Kumar D. Irritable bowel syndrome. Lancet. December 1997;350:
3. Drossman DA, Thompson WG. The irritable bowel syndrome: review and a graduated multicomponent treatment approach. Ann Intern Med. June 1992;116(pt 1):

28. Current management components of IBS
IBS – Management
Current management components of IBS
Education
Reassurance
Dietary modification
Fiber
Symptomatic treatment
Psychological/behavioral options
Realistic goals
The key to helping patients better manage their IBS is education. By explaining that the intestines overreact to a variety of stimuli such as food, hormonal changes, medication, and stress, patients can be made more aware of what may trigger an episode or intensify existing symptoms. Make it clear that stimuli can produce spasm or stretching of the gut, enhance sensitivity of nerves, or both. When this happens, the patient experiences pain, diarrhea, constipation, bloating, or a combination of any of these symptoms.1
Patients need to be reassured that their symptoms are real and not life threatening. By understanding how to modify their diet in order to minimize their symptoms (e.g., reduction in alcohol, fat, caffeine, and sorbitol), coupled with medical treatment, patients should be better equipped to manage their disease.1
The current treatment of IBS includes antispasmodics, anticholinergics, tricyclic antidepressants, SSRIs, antidiarrheals, laxatives, bulking agents, and opioids.1 Some patients may seek alternative therapies.2
It is also important to set realistic goals. IBS is a condition that can be managed, not cured. Patients need to know what they can expect and to what degree their quality of life can be improved.1
References:
1. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
2. Smart HL, Mayberry JF, Atkinson M. Alternative medicine consultations and remedies in patients with the irritable bowel syndrome. Gut. 1986;27:

29. Currently available Rx treatments for IBS
IBS – Management
Currently available Rx treatments for IBS
Dicyclomine HCl
Hyoscyamine sulfate (± other anticholinergics/sedatives)
Belladonna and phenobarbital
Clidinium bromide with chlordiazepoxide
Tegaserod
Alosetron

30. Antispasmodics/anticholinergics
IBS – Management
Antispasmodics/anticholinergics
Symptomatic treatment—pain
Smooth muscle relaxants via anticholinergic effects and/or direct action on smooth muscle
IBS is a complex of symptoms, and each individual symptom typically is treated with a specific agent. For abdominal pain, the most frequently used medications are antispasmodics. Antispasmodics are relaxants that affect and/or have direct action on smooth muscle by blocking the passage of impulses through the parasympathetic nerves.1 In the United States, anticholinergics are widely used, especially when the pain is postprandial.2
Possible class side effects may involve many systems, including GI, genitourinary, ocular, cardiovascular, CNS, or dermatologic.1
References:
1. Drug Facts and Comparisons®. St Louis, Mo: Facts and Comparisons; 1999: c.
2. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.

31. Antidiarrheals Symptomatic treatment—diarrhea Increase stool firmness
IBS – Management
Antidiarrheals
Symptomatic treatment—diarrhea
Increase stool firmness
Decrease stool frequency
Examples: loperamide, diphenxylate-atropine
Antidiarrheals slow intestinal transit and enhance intestinal water and ion absorption, resulting in decreased stool frequency and increased stool consistency.1,2 For diarrhea due to idiopathic bile salt malabsorption, cholestyramine may be helpful.1
References:
1. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
2. Drug Facts and Comparisons®. St Louis, Mo: Facts and Comparisons; 1999:324b.

32. Laxatives and bulking agents
IBS – Management
Laxatives and bulking agents
Symptomatic treatment—constipation
Increased dietary fiber or psyllium
Osmotic laxatives (MgSO4, lactulose)
Stimulant laxatives
Some laxatives and bulking agents can exacerbate abdominal pain and bloating
For many patients who experience constipation, fiber is often tried.1 Increased dietary fiber or psyllium decreases whole gut transit time and intracolonic pressure but does not reduce colonic contractile activity.2 If this is not helpful, osmotic laxatives may be prescribed.3
Stimulant laxatives (e.g., bisacodyl, phenolphthalein) enhance intestinal motility and stimulate accumulation of water and electrolytes in the colonic lumen. These agents are effective in relieving constipation associated with IBS. In some patients, laxatives can exacerbate abdominal pain and bloating.4
References:
1. Camilleri M, Choi M-G. Review article: irritable bowel syndrome. Aliment Pharmacol Ther ;11:3-15.
2. American Gastroenterological Association. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology. June 1997;112:
3. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
4. Drug Facts and Comparisons®. St. Louis, Mo: Facts and Comparisons; 1999: a.

33. Tricyclic antidepressants and SSRIs
IBS – Management
Tricyclic antidepressants and SSRIs
Symptomatic treatment—pain
Reserved for patients with severe or refractory pain
For patients with severe or refractory pain, impaired daily function, or associated depressive or panic-like symptoms, tricyclic antidepressants and SSRIs can be helpful.1,2
References:
1. Drossman DA, Thompson WG. The irritable bowel syndrome: review and a graduated multicomponent treatment approach. Ann Intern Med. 1992;116(pt 1):
2. Drug Facts and Comparisons®. St. Louis, Mo: Facts and Comparisons; :262I-262M.

34. Multiple medications needed to treat multiple symptoms
IBS – Management
Multiple medications needed to treat multiple symptoms
Anticholinergics1 X X
Tricyclic antidepressants X and SSRIs2
Antidiarrheals1 X X X
Bulking agents1 X X X
Laxatives3 X X
Lower abdominal pain
Bloating
Altered stool form
Altered stool passage
Urgency
Since IBS generally presents as a complex of symptoms, management options traditionally have included specific agents for specific symptoms. For example, anticholinergics have been useful in cases of severe pain. When constipation is the predominant symptom, fiber or psyllium products can be beneficial. When diarrhea is the predominant symptom, antidiarrheals are used to decrease intestinal transit, enhance water and ion absorption, and strengthen rectal sphincter tone.
Reference:
Drossman, DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999:13(suppl 2):3-14.

35. A comprehensive multicomponent approach
IBS – Management
A comprehensive multicomponent approach
Treatment program is based on dominant symptoms and their severity and on psychosocial factors
Medical management
Diet
Psychological or behavioral options
– psychotherapy – stress management
IBS is a complex disease and needs to be managed on several levels. Medical management may include treatments that help keep symptoms under control even though this may mean prescribing lifestyle changes and a regimen of products.
Diet plays a key role in IBS, and patients need to learn what their triggers are and which foods provide relief (e.g., high fiber foods for constipation).
Patients with chronic diseases may become discouraged or have a preexisting psychological condition. Psychotherapy and/or stress management may be helpful for some patients.
Reference:
Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.

36. INITIAL MANAGEMENT OF IBS
Symptom Features
Constipation
Diarrhea
Pain/Gas/Bloat
Review Diet History Re: Fiber Intake
Yes
Yes
Yes
Additional Tests No
H2 Breath Test
Celiac panel
Abdominal X-ray (KUB During Pain)
Irritable Bowel Syndrome Slide 6
This slide shows the initial management of IBS which is based on the predominant symptom of the patient. In patients who have predominant constipation, it is important to review the dietary history for fiber intake since most people do not have an adequate amount of fiber in their diet. Thus, the U.S. population average is 12 grams per day, and it has been demonstrated in different studies that 20 or more grams per day of fiber are required. In these patients, no additional tests are usually applied, and a therapeutic trial with 20 grams of fiber supplementation with or without an osmotic laxative such as Milk of Magnesia is the first line of therapy. In patients with predominant diarrhea, the dietary history is reviewed in order to screen for possible carbohydrate malabsorption, and additional tests may be a therapeutic trial excluding such carbohydrate malabsorption or a sugar substrate hydrogen breath test, most commonly, the lactose hydrogen breath test. In the absence of lactose maldigestion, a therapeutic trial with an antidiarrheal such as loperamide, 2 mg up to 4 times per day, is prescribed. In patients with predominant syndrome of pain, gas, and bloating, it is useful to review the dietary history to determine whether the patient might be taking too much dietary fiber. Thus, it is known that sensitivity to dietary fiber varies, necessitating the usual practice of starting with a relatively low dose and increasing gradually. In patients with predominant gas and bloating, it is not uncommon to find excessive intake of fiber and symptoms can be relieved by reducing the fiber intake. Additional tests are indicated including an abdominal x-ray or KUB during an episode of pain to exclude the possibility of mechanical obstruction of the intestine. Finally, a therapeutic trial is embarked upon including an antispasmodic on a p.r.n. basis such as levsin, mg, and, in many patients, a low dose of an antidepressant such as elavil, mg, or prozac, 20 mg q.h.s., is prescribed.
References
Camilleri M, Choi M-G: Irritable bowel syndrome. Aliment Pharmacol Ther 11:3-15, 1997
Drossman DA, Whitehead WE, Camilleri M: Irritable bowel syndrome: a technical review for practice guidelines. Gastroenterology 112: , 1997
Drossman DA, Corazziari E, Talley NJ, Thompson WG, Whitehead WE, et al. Rome II: A multinational consensus document on functional gastrointestinal disorders. Gut 45(Suppl. II):II1-II81, 1999
Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW: Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 355: , 2000
Prather CM, Camilleri M, Zinsmeister AR, McKinzie S, Thomforde GM: Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology 118: , 2000
Bouras EP, Camilleri M, Burton DD, Thomforde G, McKinzie S, Zinsmeister AR: Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology
Therapeutic Trial
Increase Fiber (20g),
Osmotic Laxative
Antidiarrheal
Antispasmodic
+ Antidepressant

37. Tegaserod (Zelnorm) STOPPED BY FDA (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
new safety analysis has found a higher chance of heart attack, stroke, and worsening heart chest pain that can become a heart attack in patients treated with Zelnorm compared to those treated with a sugar pill they thought was Zelnorm

38. 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

39. 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

40. 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”

41. 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