IRRITABLE BOWEL SYNDROME Daniel G. Tobin, M.D. Week 17 Educational Objectives: 1. Recognize clinical features consistent with Irritable Bowel Syndrome (IBS) and become familiar with established clinical criteria used to make this diagnosis 2. Learn how to personalize the diagnostic work-up to avoid unnecessary testing 3. Effectively use appropriate treatment options for IBS CASE ONE: Ms. Rome is a 42-year-old woman who presents to your office seeking your help for her abdominal complaints. She reports many years of intermittent crampy lower abdominal discomfort, usually associated with the sensation that she needs to urgently move her bowels but denies any history of actual fecal incontinence. A bowel movement usually leads to the temporary resolution of her symptoms. She tells you that she alternates between weeks of constipation and weeks of diarrhea, during which time she reports that her stools are “filled with mucus.” Her medical history is otherwise only notable for fibromyalgia, but she isn’t taking any medications. She denies any substance use, has no significant family history, and reports that she has a supportive family. She says “my husband thinks I just have an irritable bowel, but I’m worried that something’s really wrong with me. What do you think?” Questions: 1. What is Irritable Bowel Syndrome? What diagnostic criteria are available to make this diagnosis? Are this patient’s symptoms consistent with IBS? Irritable bowel syndrome (IBS) refers to a functional bowel disorder characterized by abdominal discomfort associated with defecation or a change in bowel habits in the absence of another organic cause. This is a clinical diagnosis made on the basis of identifying a symptom complex consistent with IBS and performing an individualized focused evaluation to rule out organic disease (see questions 2 and 3 below). The prevalence of IBS in the United States is thought to be between 9-22% of all adults and accounts for 12% of primary care provider visits and almost 30% of visits to gastroenterologists, with most studies showing a female predominance. The etiology of IBS is unknown, but various hypotheses have been generated including abnormal gut motility, bacterial overgrowth, food allergies, altered visceral sensitivity, infectious triggers, hormonal disruption, and disorders of the serotonin reuptake transport system. Numerous clinical criteria have been created in an attempt to better define the diagnosis. The Manning criteria introduced in 1978 characterized a patient as having symptoms consistent with IBS if they had relief of abdominal pain with bowel movements, looser and more frequent stools with onset of pain, passage of mucus, and a sense of incomplete emptying. This was followed in 1984 by the Kruis criteria (Table 2 of Podovei article) which were more cumbersome and not widely used. In 1992, in an attempt to standardize clinical research protocols, an international working group published a consensus definition of IBS, known as the Rome criteria, which were revised in 1999 (Rome II) and again in 2005(Rome III). The Rome III criteria are defined as: Recurrent abdominal pain or discomfort for at least three days per month in the previous three months with symptom onset in six months prior to diagnosis with two or more of the following: Pain relieved with defecation, and/or Onset associated with a change in frequency of stool, and/or Onset associated with a change in form (appearance) of stool However, the predictive value of any of the diagnostic criteria has been found to be quite variable depending on the prevalence of IBS and organic gastrointestinal disorders in the individual practice setting. As a result, a consensus statement issued by the American Gastroenterological Association in 2002 recommends that a diagnosis of IBS should be based upon the combination of positive clinical symptoms consistent with the condition (as noted in the Rome criteria above) after excluding other conditions with similar clinical presentations in a cost-effective manner. This patient’s symptoms are indeed consistent with the diagnosis of IBS, but we do not yet have adequate data to rule out another gastrointestinal disorder or to make this diagnosis. 2. What additional questions do you need to ask her to guide your evaluation? Are there any specific physical findings for IBS on exam? The appropriate evaluation of a patient suspected to have IBS is based on the patient’s age, the duration and severity of symptoms, the presence of “alarm” symptoms or signs (hematochezia, anemia, fever, weight loss of 10 lbs or more, or strong family history of colon cancer), a family history of gastrointestinal disease, and psychosocial factors. Patients with typical IBS symptoms and no alarm features require few tests beyond the history and exam. A careful history must be performed, and the patient should be asked about the presence of blood in her stools, unintentional weight loss, persistent or recurring fever, gynecologic symptoms, and a family history of colon cancer. She should explain what she means by the terms “diarrhea” and “constipation” and further describe the timing between eating and developing symptoms. Dietary factors should be considered (including the intake of lactose containing foods or “sugar free” products that may have high levels of poorly absorbed carbohydrates such as sorbitol) as should the use of antacids or laxatives that can lead to similar symptoms. A social history should evaluate for associated psychosocial factors such as severe stress or a history of physical or sexual abuse. There are no diagnostic exam findings, but abdominal tenderness may be present. A complete physical exam is important and should look for stigmata consistent with thyroid disease and anemia, the abdomen should be assessed for organomegaly and masses, and a rectal examination should be performed to evaluate for mucosal pathology or the presence of occult blood. CASE ONE CONTINUED: During a careful history and review of systems, your patient denies fevers, unintentional weight loss, excessive fatigue, or blood in her stools. She denies a history of voluminous diarrhea or gastrointestinal symptoms that awaken her from sleep at night. She denies travel outside the United States, and her dietary history is remarkable only for minimal dairy consumption because she “hates the taste of milk.” She also denies any history of physical or sexual abuse, does not report any symptoms concerning for depression, and reports an unremarkable gynecologic history. She takes no medications, no dietary supplements, and does not use laxatives or antacids. No one in her family has a history of colon cancer. On exam her vital signs are within normal limits, and she appears well-nourished without pallor; her cardiovascular, pulmonary, abdominal, gynecologic, and rectal exams are all unremarkable, and guaiac testing is negative for occult blood. 3. What other diagnostic tests (if any) are needed at this point? In the absence of alarm symptoms or signs, few additional tests are warranted. Consider obtaining a CBC and chemistry panel in most patients, but reserve thyroid testing, extensive stool testing (including ova and parasites), and other blood work (such as antibody studies for celiac sprue) for patients with findings that are concerning for a specific alternate diagnosis. A colonoscopy is indicated for patients over the age of 50 (because of the higher pretest probability for colon cancer) or earlier, if a family history for early colon cancer is present, consistent with current guidelines. In younger patients, reserve endoscopic procedures for those with excessive diarrhea, bloody stools or other alarm symptoms. Abdominal radiography, gut motility studies, and rectal biopsies should not be performed unless there is a high suspicion for an alternate diagnosis, at which time these tests would be crucial to either establish the diagnosis or rule it out. CASE ONE CONTINUED: After obtaining a CBC, a basic chemistry panel, and a lipid profile (you ARE a primary care provider after all!) that are all within normal limits, you follow-up with your patient a week later to review the results. In a non-judgmental and empathic manner, you reassure the patient that her symptoms do not appear to be due to a dangerous illness or colon cancer and that she does indeed seem to be suffering from irritable bowel syndrome. You explain that although there is no “cure” for the disorder, it is treatable and that you will work with her to help control her symptoms. You advise her that additional testing is not necessary at this time but should be considered if her symptoms change or if she does not get relief from appropriate therapy. 4. What treatment options are available? A supportive therapeutic relationship, patient education, and appropriate lifestyle modification is the cornerstone of a successful treatment plan. Dietary modification to avoid known trigger foods and to increase the consumption of dietary fiber is recommended. For many patients, avoiding gas-producing foods such as beans, celery, raisins, apricots, and prunes can be helpful. If present, treatment of coexistent psychiatric disease and appropriate support for psychosocial stressors is also of critical importance. The value of a healthy sleep cycle and adequate aerobic exercise should be emphasized as well, particularly if IBS coexists with fibromyalgia or other functional pain disorders. Other nonpharmacologic therapeutic options to consider include hypnosis (small but significant improvement in abdominal discomfort in RCTs) and acupuncture (significant improvement in symptoms, but no better than placebo). Pharmacologic treatment should be directed toward the dominant symptom and are helpful for some (but not all) patients. Options include the following: Bulking Agents: available over the counter, including various types of fiber including psyllium (also known as ispaghula husk) , methylcellulose, and calcium polycarbophil; have been advocated to provide bulk to the stool by increasing water content, thereby improving stool frequency and ease of passage. Thirteen RCTs have evaluated the efficacy of these agents and found that there is no convincing evidence that they are more effective than placebo at relieving IBS symptoms, but the placebo effect itself can dramatically improve symptoms. They are generally inexpensive compared with other medications and, when used as directed, are quite safe and thus often recommended as first line therapy despite the lack of evidence that they are efficacious compared with placebo. Side effects can include bloating, increased flatulence, and abdominal discomfort although these symptoms are usually mild. Some bulking agents have been associated with esophageal and bowel obstruction if taken in large quantities without adequate water, and patients must be cautioned to use them as directed. Antidiarrheal agents: Agents such as loperamide can be useful for patients with diarrhea-prominent IBS. However, RCTs have failed to show an improvement in abdominal discomfort or global symptoms of IBS when compared with placebo. Antispasmodic agents: these agents decrease intestinal smooth muscle contraction and may be beneficial in patients with postprandial abdominal pain, gas, bloating, and fecal urgency, which are symptoms often presumed to be secondary to spasm. However, only three controlled trials have evaluated antispasmodic agents available in the United States (dicyclomine and hyoscyamine, both anticholinergic/antimuscarinic agents). Two of these studies showed no improvement in symptoms compared with placebo and the third did show a significant improvement in IBS symptoms with high doses of dicyclomine (40 mg four times a day). Unfortunately, high doses of dicyclomine are associated with atropine-like side effects and can exacerbate constipation, which often limits the use of this agent at therapeutic doses. If prescribed, these medications should be given on a prn basis. Antidepressants: Tricyclic antidepressants (TCAs) in low doses can be effective for chronic pain conditions such as fibromyalgia, headaches, and neuropathic pain independent of their mood altering properties and have been used successfully to help control the symptoms of IBS. The mechanism of action is not known, but proposed actions include increased endogenous endorphin release, enhancement of descending inhibitory pain pathways via blockade of norepinephine reuptake, and blockade of the pain neuromodulator serotonin. In addition, tricyclic agents also slow intestinal transit time due to their anticholinergic effects and can help reduce the frequency of diarrhea. Although the efficacy of these agents has been found to be variable in the literature, numerous RCTs and a large meta-analysis have all found TCAs to be more effective than placebo at improving abdominal discomfort. Of note, patients may need to take these medications for weeks before an adequate response is seen. The use of antidepressants other than TCAs is not currently supported in the literature. 5-hydroxytryptamine (serotonin) 3 receptor antagonists: Alosetron (lotronex) is a 5-HT3 receptor antagonist which is marketed for women with severe diarrhea-predominant IBS who have failed conventional therapies. This agent is felt to work by decreasing colonic transit and mediating afferent nerve activity. However, the drug is associated with ischemic colitis and serious complications related to severe constipation, and at one point the FDA removed it from the market in the United States. However, it has since been reintroduced under tight control by the FDA and only physicians enrolled in GlaxoSmithKline's “Prescribing Program for Lotronex” may prescribe this medication. Program stickers must be affixed to all prescriptions; no phone, fax, or computerized prescriptions are permitted with this program. 5-hydroxytryptamine (serotonin) 4 receptor agonists: The agent tegaserod (Zelnorm) improves colonic transit time and visceral hypersensitivity and has been found to be efficacious for the treatment of constipation-predominant IBS in women. However, tegaserod was removed from the market by the FDA in March of 2007 because of cardiovascular side effects. Primary References: 1. Podovei M and Kuo B. Irritable Bowel Syndrome: A practical review. Southern Medical Journal. 2006; 99(11): 1235-1242. 2. Longstreth GF et al. Functional Bowel Disorders. Gastroenterology. 2006; 130(5): 1480-1491. Additional Reference: 3. Drossman DA et al. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002; 123(6): 2108-2131.