IBD MANAGEMENT
| ARE THE GI SYMPTOMS IBD OR IBS ?—Ray E. Clouse, MD, Professor of Medicine, Washington University School of Medicine, St. Louis |
| Can functional gastrointestinal (GI) disorders occur with inflammatory bowel disease (IBD)? |
 | Source of functional symptoms: heightened sensorimotor activity arc between central nervous system (CNS) and gut thought to originate in brain (neurologically based and separate from IBD); in patients with functional syndromes, brainstem processing of incoming signals from gut abnormal and can result in altered brainstem response and abnormal motor activity (may be secondary to primary process of visceral hypersensitivity); sensorimotor arc can be triggered by events occurring at gut luminal or mucosal level; also sensitive to psychologic cognitive environment in CNS (ie, emotional system may be responsible for initiating or worsening hypersensitivity process); visceral hypersensitivity also may be due to genetic predispositions or unexplained processes |
| Visceral hypersensitivity: patients may have unexpected reaction to physiologic stimulus without having abnormality at gut level, ie, symptoms in absence of gut disease or symptoms out of proportion to established gut disease; no mechanism identified clinically; physician must use clinical suspicions based on history and physical examination; balloon distention can reproduce symptoms, even though balloon not distended to noxious level for normal population; mucosal inflammation also can trigger process, but there seem to be other triggering factors involved in IBD patients; predicted primarily by psychologic features |
| Conclusion: visceral hypersensitivity key feature of functional syndromes; possible that IBD patients can have this neurologic factor turned on by inflammation but only in certain susceptible situations, possibly marked by psychologic features |
| How are functional GI symptoms recognized in IBD patients? tremendous overlap of functional and IBD symptoms; both sets of symptoms might be triggered by inflammation; patients with irritable bowel syndrome (IBS) can have extraintestinal symptoms that can mimic IBD (eg, joint aches, fatigue, sleep disturbance); most interested in functional dyspepsia (pain syndrome in upper abdomen), functional abdominal pain (not much relation to physiology of bowel), IBS, and functional anorectal disorders |
| Rome criteria for IBS: high rate of symptom overlap with IBD; key features include change in bowel habit linked to pain and chronicity; other features supporting diagnosis of IBS but not required in patients who do not have IBD include urgency, straining, feelings of incomplete evacuation, passage of mucus without mucopus, bloating or abdominal distention; having compatible symptoms first clue patient may have IBD and IBS coexisting; studies show overlap of symptoms may be much more common than previously appreciated; in ulcerative colitis (UC), one third of patients met criteria for IBS, while in Crohn’s disease (CD), nearly half met criteria for IBS; do not bombard patients with escalating anti-IBD medications if evidence disease in remission and symptoms compatible with IBS |
| Clues that patient predisposed to functional syndromes: presence of other non-GI functional syndromes in areas not related to IBD, eg, tinnitus, fibromyalgia, chronic fatigue syndrome, migraine headaches; comorbidities in psychiatric realm, eg, anxiety disorders, affective disorders, somatization disorder; rates of psychiatric diagnoses elevated in patients with CD compared to controls, but not in patients with UC; presence of psychiatric disorders, especially anxiety or depression, helpful clue to functional nature of symptoms; key—symptoms typical of functional syndromes; symptoms out of proportion to objective findings; comorbid functional GI syndromes, non-GI syndromes, and psychiatric disorders |
| Gut-directed therapy: aimed at interrupting sensorimotor activity at gut level or treating mucosal inflammation or eliminating dietary factors; serotonin receptor antagonists (5HT3 antagonists decrease visceral sensation and motility; use in patients with diarrhea-predominant patterns; 5HT4 antagonists decrease visceral sensation but primarily increase motility); alosetron (Lotronex) available for limited use in diarrhea-predominant IBS; cilansetron should be out within 1 yr (next-generation 5HT3 antagonist); tegaserod (5HT3 agonist); prucalopride and cisapride no longer available; alosetron cannot be prescribed safely to IBD patients because of restrictive prescribing pattern; tegaserod useful in patients with constipation-dominant symptoms that persist after resolution or remission of IBD (not intended for patients with obstructive disease) |
| Central modulation effects: aimed at blocking psychologic interface with process or direct interaction with process; antidepressants most effective agents (affect visceral sensitivity); when given in low (subpsychiatric) doses, tricyclic antidepressants (TCAs) effective; rapid onset of effectiveness expected; all functional symptoms may respond; TCAs seem superior to selective serotonin reuptake inhibitors (SSRIs); treat patients for 6 to 24 mo; appears nortriptyline and desipramine have fewest side effects (25-50 mg daily typical, but continue to escalate dose until side effects get in way or until full psychiatric dosing reached in patients with partial responses); if patient does not respond to TCAs, try SSRIs; citalopram (Celexa) and escitalopram (Lexapro) have least interaction with cytochrome P450 system; newer serotonergic agents (eg, duloxetine) should not be considered front-line agents because of their side-effect profile |
| Precautions: monitor examination, laboratory, imaging, and endoscopy in patients with refractory symptoms to make sure inflammatory activity not returning and being confused with functional syndrome; anticholinergic agents, like antispasmodics and TCAs, can be used routinely in IBD patients, but anticholinergic activity can become problematic in patients with severe colonic inflammation |
| UNIQUE ASPECTS OF IBD IN ADOLESCENCE —Robert J. Rothbaum, MD, Professor of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Washington University School of Medicine, St. Louis |
| Onset and appearance: not unusual in childhood; can occur as early as 2 to 3 yr of age; percentage of cases increases with age, peaking at 20 yr of age; disease does not look particularly different in adults vs adolescents; colonoscopic appearance does not predict eventual severity of disease |
| Location of CD: adolescents tend to have CD in ileum and right colon that sometimes stays localized and does not develop to greater extent (localization can persist over years); compared to adults, fewer adolescents have disease limited to ileum; colonic involvement same in adults and adolescents; diffuse small bowel disease relatively unusual in both groups |
| Symptomatology: crampy right lower quadrant pain, often related to meals or defecation; frequent stools, often with visible blood (colitic symptoms) |
| Ulcerative colitis (UC): 30% of adults with UC have proctitis; proctitis in child or adolescent expected to advance to left-sided disease or pancolitis; localized inflammation in rectum unusual in children and adolescents and raises suspicion that patient has another disorder, not simple IBD (eg, solitary rectal ulcer syndrome); most patients with proctitis progress to widespread disease |
| Systemic manifestations of IBD: 10% of adolescents with CD and 12% with UC have painful joints; erythema nervosum or pyoderma gangrenosum less common in adolescents than in adults; liver disease, sclerosing cholangitis, pericholangitis, autoimmune hepatitis less frequent; weight loss primary symptom, particularly in CD (common in adults, less common in adolescents; not affected as much in UC) |
| Growth and maturation: major problem in adolescents with CD; patient may be 16 yr of age but look 11 or 12 yr of age; mechanism not clear; growth chart important tool; patients can have period of lack of weight gain and growth before overt intestinal symptomatology (pediatricians and family practitioners becoming sensitive to this pattern and may begin to evaluate patient for IBD; difficult to treat); CD delays growth and maturation more often than UC; most patients with UC appear healthy and have normal growth and development; CD presenting before puberty more likely to affect growth, development, and maturation than if it presents during or after puberty; corticosteroid use during puberty associated with more growth delay, but delay primarily process of disease; resection of localized disease sometimes becomes therapy of choice in order to get patient to grow (recurrence of disease expected); surgery successful most of time if performed as puberty begins |
| What adolescents worry about (study): flare in disease; life-long illness; CD patients ranked concern about growth and weight gain high, but less important for patients with UC; both groups bothered about taking medication (physicians should try to keep medications to minimum and use what most likely will be effective; avoid anything beyond bid dosing; do not want patient’s activities inhibited by taking medication); missing sports, feeling angry, bleeding (more concern in UC patients), and location of next bathroom also important concerns for adolescent patients (particularly in UC) |
| Taking history: take indirect approach when talking about patient’s symptoms, eg, how much time are you spending at home? are you going to the mall? are you going to the movies? are you staying overnight at a friend’s house? if not doing any of these things, patient probably having fairly active symptoms |
| Concerns ranked by physicians (study): flare 13th (adolescents ranked it first); lifelong disease 24th (patients ranked it second); taking medication 80th (patients ranked it third); both groups worried about stomachaches and cramps interfering with activity; height in patients with CD eighth (patients ranked it fourth) |
| Concerns of parents: parents and school-age children agreed on severity of disease, type and frequency of symptoms, and quality-of-life parameters, except for social functioning (children thought they were doing better socially) |
| Cognition: younger children view illness as being caused by events outside body (illness often viewed as punishment); adolescents come to understand physiologic processes, define illness in terms of functioning, begin having conceptualization of prevention (not well developed) |
| Office visit: make transfer of education from parent to child; get information from adolescent without too much invasion of privacy; deal with issues of dependence, independence, and overprotection; parents have been managing illness and must now relinquish control, knowing adolescents will make mistakes and misjudgments that might lead to flare in disease and additional problems; increase time of office visit to allow involvement of parent and adolescent together, and adolescent alone |
| Goals of therapy: control symptoms; sustain good nutrition; provide emotional support |
| Treatment: to achieve goals, must avoid corticosteroids and use immunosuppressants early; patients usually tolerate first course of prednisone well but not subsequent courses because medication changes patient’s appearance (ie, round face, acne problems, flushed cheeks); keep medication regimens simple; ask patients how regularly and how much of their medication they are taking (may take holiday from medication if doing well; may be more adherent close to physician visits); do not add more medication if they have not been taking their current medication; expect and accept nonadherence; start teaching patient about their medication at ≈12 yr of age; discuss treatment options; expect some incorrect decisions; give patient time and counseling |
| DYSPLASIA IN ULCERATIVE COLITIS —Bret Lashner, MD, Director, Center for Inflammatory Bowel Disease, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland |
| Case: 62-yr-old man with UC for 7 yr; symptoms well controlled on sulfasalazine; surveillance colonoscopy found distorted vascular pattern throughout colon and some polypoid lesions, mostly in descending and sigmoid colon, that were relatively large and somewhat irregular in shape; irregularly shaped polyps that looked like they could have been inflammatory contained low-grade dysplasia |
| Low-grade dysplasia and flat mucosa (study): 46 patients with UC; 11 had immediate colectomy (2 patients had cancer in colectomy specimen); of remaining 35 patients elected for continued surveillance, 14 progressed to high-grade dysplasia or cancer (7 had cancer); rate of progression 53% in 5 yr, 80% at 10 yr; colectomy indicated in patients with confirmed low-grade dysplasia in flat mucosa |
| Chromoendoscopy: allows clinician to find dysplasia more often; dysplasia and dysplasia-associated lesion or mass (DALM) patchy and difficult to differentiate endoscopically from granular mucosa; in study, dysplasia detection rate 38% in chromoendoscopy group vs 12% in standard group |
| Dysplasia-associated lesion or mass: speaker’s study of 27 patients with UC who underwent polypectomy; 15 were young (<50 yr of age; polyps not expected), and, of these, 5 developed cancer, 3 had high-grade dysplasia, and 2 developed additional low-grade dysplasia on follow-up; other 12 patients older and mostly had disease distant from polyp (polypectomy realistic treatment); be concerned about young patients with polyps or patients with polyps in area of colitis |
| p53 mutations and surveillance colonoscopies: most patients with sporadic adenomas do not have p53 abnormalities, while patients with cancers do; most patients with UC who have dysplasia or DALM also have p53 mutation; speaker’s study found that of 95 patients who had surveillance colonoscopies, 37 p53 positive and, of these, 73% developed dysplasia or cancer during course of surveillance; of those p53 negative, only 14% developed dysplasia or cancer; patients who are p53 positive 4.5 times more likely to develop cancer or dysplasia than those who are not; p53-positive patients have worse prognosis |
| Conclusion: p53 mutation associated with cancer or dysplasia; p53 mutation precedes cancer or dysplasia; colorectal cancers that are p53 positive have high mortality; low-grade dysplasia and flat mucosa should warrant colectomy; patients with DALM have bad prognosis and should be considered for colectomy |
Educational Objectives
| The goal of this program is to educate the listener about inflammatory bowel disease (IBD). After hearing and assimilating this program, the clinician will be better able to: |
| 1. Review the current thinking on IBD and how it can coexist with functional syndromes. |
| 2. List clues that help distinguish IBD from functional gastrointestinal symptoms. |
| 3. Rank in order the top 4 concerns adolescent patients have about their inflammatory bowel disease. |
| 4. Explain how to take a history from the adolescent patient with IBD. |
| 5. Discuss the relationship of the p53 mutation to dysplasia and cancer. |
Discussed on This Program
Alosetron HCl [Lotronex] Azathioprine (AZA) [Imuran] Cilansetron (investigational) Cisapride [Propulsid] Citalopram HBr [Celexa] Desipramine HCl [Norpramin] Duloxetine [Cymbalta] (investigational) Infliximab [Remicade] Methotrexate (amethopterin; MTX) [Methotrexate LPF, Rheumatrex Dose Pack, Trexall] Nortriptyline HCl [Aventyl HCl, Aventyl HCl Pulvules, Pamelor] Prucalopride (investigational) Sulfasalazine [Azulfidine, Azulfidine EN-tabs] Tegaserod maleate [Zelnorm] Trazodone HCl [Desyrel, Desyrel Dividose]
Programs of Related Interest
Camilleri M, Olden KW: Irritable bowel syndrome update. Audio-Digest Gastroenterology 18:07(Jul 1), 2004; Derezin M et al: Issues in gastroenterology. Audio-Digest Family Practice 52:47(Dec 21), 2004; Dietz DW et al: Inflammatory bowel disease. Audio-Digest General Surgery 52:06(Mar 21), 2005; Stollman N, Abreu MT: Advances in gastroenterology. Audio-Digest Internal Medicine 50:11(Jun 7), 2003.
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Suggested Reading
Creed F et al: Outcome in severe irritable bowel syndrome with and without accompanying depressive, panic and neurasthenic disorders. Br J Psychiatry 186:507, 2005; Engelsgjerd M et al: Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis. Gastroenterology 117:1288, 1999; Ginsburg PM et al: Managing Functional Disturbances in Patients with Inflammatory Bowel Disease. Curr Treat Options Gastroenterol 8:211, 2005; Izquierdo S et al: Has the identification of rectal hypersensitivity any implication in the clinical outcome of irritable bowel syndrome? Rev Esp Enferm Dig 97:223, 2005; Kiesslich R et al: Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology 124:880, 2003; Lashner BA et al: Evaluation of the usefulness of testing for p53 mutations in colorectal cancer surveillance for ulcerative colitis. Am J Gastroenterol 94:456, 1999; Otaka M et al: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther 21 Suppl 2:42, 2005; Patel SM et al: The placebo effect in irritable bowel syndrome trials: a meta-analysis. Neurogastroenterol Motil 17:332, 2005; Rubin PH et al: Colonoscopic polypectomy in chronic colitis: conservative management after endoscopic resection of dysplastic polyps. Gastroenterology 117:1295, 1999; Stephenson JJ et al: Effectiveness of tegaserod therapy on GI-related resource utilization in a managed care population. Am J Manag Care 11:S35, 2005; Talley NJ: Environmental versus genetic risk factors for irritable bowel syndrome: clinical and therapeutic implications. Rev Gastroenterol Disord 5:82, 2005; Ullman T et al: Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis. Gastroenterology 125:1311, 2003.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, Dr. Lashner reports being on the Speakers’ Bureau of Proctor & Gamble Pharmaceutical, AstraZeneca Pharmaceuticals LP, Salix Pharmaceuticals, Inc., and Centocor, Inc.
Drs. Clouse and Rothbaum were recorded September 18, 2004, in St. Louis, Missouri, at Inflammatory Bowel Disease, sponsored by Washington University School of Medicine, St. Louis, Division of Gastroenterology, Section of Colon & Rectal Surgery, Digestive Disease Research Core Center; Dr. Lashner, on September 9, 2004, in Cleveland, at the 40th Annual Gastroenterology Update, sponsored by the Cleveland Clinic Department of Gastroenterology and Hepatology in joint sponsorship with the American College of Gastroenterology. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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