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IRRITABLE BOWEL SYNDROME Kimberly M. Persley, MD
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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. . . .” IBS – History 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. 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.
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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 IBS – History References: 1. Maxwell et al. Lancet. December 1997;350:1691-1695. 2. Sandler. Gastroenterology. August 1990;99:409-415.
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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 – Signs and symptoms Reference: Thompson et al. Gut. 1999;45(suppl 2):1143-1147.
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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 IBS – 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.
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Key facts about IBS (cont.) Can cause great discomfort, sometimes intermittent or continuous, for many decades in a patient’s 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 IBS – 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.
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IBS consultation pattern IBS – Epidemiology References: 1. Drossman and Thompson. Ann Intern Med. June 1992;116(pt 1):1009-1016. 2. Sandler. Gastroenterology. August 1990;99:409-415.
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IBS vs other important disease states US prevalence up to 20%1 US prevalence rates for other common diseases2: – diabetes 3% – asthma 4% – heart disease 8% – hypertension 11% IBS – 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.
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Direct medical costs associated with IBS 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 IBS – Burden of disease References: 1. Talley et al. Gastroenterology. December 1995;109:1736-1741. 2. Drossman et al. Dig Dis Sci. September 1993;38:1569-1580.
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Productivity burden IBS – Burden of disease 0 2 4 6 8 10 12 14 IBS Non-IBS Days per year P=0.0001 Absenteeism from work or school during the last 12 months Reference: Drossman et al. Dig Dis Sci. September 1993;38:1569-1580.
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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. IBS – Burden of disease Adapted from Hahn et al. Digestion. 1999;60:77-81.
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Evolution of mechanistic hypotheses in IBS IBS – Physiology Abnormal motility1 Visceral hypersensitivity1 Brain-gut interaction1 5-HT mediated visceral sensitivity and gut motility2 1950 2000 References: 1. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14. 2. Prior and Read. Aliment Pharmacol Ther. 1993;7:175-180.
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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 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) IBS – Pathophysiology
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IBS: Current thinking on pathophysiology 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 IBS – 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 to the hallmark symptoms of IBS.
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Physiological distribution of 5-HT CNS – 5% – enterochromaffin cells – neuronal IBS – Pathophysiology GI tract – 95% Reference: Gershon. Aliment Pharmacol Ther. 1999;13(suppl 2):15-30.
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IBS – Pathophysiology 5-HT initiates peristaltic reflex mediated by the ENS Intraluminal Pressure Mucosa Mucosal Enterochromaffin Cell 5-HT 5-HT Receptor [Enteric Nervous System]
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5-HT receptor effects Mediate reflexes controlling gastrointestinal motility and secretion Mediate perception of visceral pain IBS – Pathophysiology Reference: Gershon. Aliment Pharmacol Ther. 1999;13(suppl 2):15-30.
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20 60 100 140 180 Comparison of pain thresholds of IBS patients and controls IBS – Physiology % Reporting Pain Rectosigmoid balloon volume (mL) Reference: From Whitehead et al. Dig Dis Sci. June 1980;25:404-413. With permission. 0 20 40 60 IBS Normal Pain produced by rectosigmoid balloon distension
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Comparison of pain thresholds IBS – Physiology Colonic Distension Ice Water Immersion IBS Normal Reference: Whitehead et al. Gastroenterology. May 1990;98:1187-1192.
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Make a positive diagnosis1,2 IBS – Diagnosis Identify abdominal pain as dominant symptom with altered bowel function Perform diagnostic tests/physical exam to rule out organic disease Initiate treatment program as part of diagnostic approach Follow up in 3 to 6 weeks 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 diagnosis
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History of diagnostic approaches 1950s – Increased gut motility1 1970s – Specific motility markers1 1980 to 1999 – Symptom-based criteria1 Manning criteria Rome criteria 1999 – Rome II criteria2 IBS – Diagnosis References: 1. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14. 2. Thompson et al. Gut. 1999;45(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 Anemia Fever Persistent diarrhea Rectal bleeding Severe constipation Weight loss IBS – Diagnosis Reference: Paterson et al. Can Med Assoc J. July 1999;161:154-160. Additional diagnostic screening needed for atypical presentations such as 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
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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.1 If 50 years of age, order CBC, electrolytes, LFTs, and perform a colonoscopy or air-contrast barium enema with sigmoidoscopy.1,2 IBS – Diagnosis References: 1. American Gastroenterological Association. Gastroenterology. June 1997;112:2120-2137. 2. Paterson et al. Can Med Assoc J. July 1999;161:154-160.
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Differential diagnosis Malabsorption1 Dietary factors1 Infection1 Inflammatory bowel disease1 Psychological disorders1 Gynecological disorders2 Miscellaneous1 IBS – Diagnosis 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.
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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 IBS – Diagnosis References: 1. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14. 2. Klein. Gastroenterology. July 1988;95:232-241.
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Current management components of IBS Education Reassurance Dietary modification Fiber Symptomatic treatment Psychological/behavioral options Realistic goals IBS – Management Reference: Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
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Currently available Rx treatments for IBS Dicyclomine HCl1 Hyoscyamine sulfate (± other anticholinergics/sedatives)2 Belladonna and phenobarbital1 Clidinium bromide with chlordiazepoxide1 Tegaserod Alosetron IBS – Management References: 1. PDR® Generics™. 1998:314, 559-561, 873-875. 2. Physicians’ Desk Reference®. 1999:2910-2911.
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Antispasmodics/anticholinergics Symptomatic treatment—pain1 Smooth muscle relaxants via anticholinergic effects and/or direct action on smooth muscle2 IBS – Management References: 1. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14. 2. Drug Facts and Comparisons®. 1999:298-298c.
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Antidiarrheals Symptomatic treatment—diarrhea Increase stool firmness Decrease stool frequency Examples: loperamide, diphenxylate-atropine IBS – Management Reference: Drug Facts and Comparisons®. 1999:324b.
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Laxatives and bulking agents Symptomatic treatment—constipation IBS – Management 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 psyllium1 Osmotic laxatives (MgSO4, lactulose)2 Stimulant laxatives3 Some laxatives and bulking agents can exacerbate abdominal pain and bloating3
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Tricyclic antidepressants and SSRIs Symptomatic treatment—pain Reserved for patients with severe or refractory pain IBS – Management Reference: Drossman and Thompson. Ann Intern Med. 1992;116(pt 1):1009-1016.
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Multiple medications needed to treat multiple symptoms IBS – Management 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.
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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 – Management Reference: Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
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INITIAL MANAGEMENT OF IBS Review Diet History Re: Fiber Intake Yes Increase Fiber (20g), Osmotic Laxative Yes H2 Breath Test Celiac panel Antidiarrheal Yes Abdominal X-ray (KUB During Pain) Antispasmodic + Antidepressant No Camilleri & Prather. 1992 Additional Tests Therapeutic Trial Constipation Diarrhea Pain/Gas/Bloat Symptom Features
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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