Irritable Bowel Syndrome (IBS) affects 10–20% of the adult U.S. population, is the most common diagnosis made by gastroenterologists, and is one of the top 10 reasons for visits to primary care physicians.Irritable Bowel Syndrome is the most common functional bowel disorder and affects predominantly women (70% of patients).This may be due to the fact that women more easily report their symptoms of abdominal pain,gas,bloating,and altered bowel movements.
It may also be due to hormonal differences between men and women that may affect gut function and alter perception of pain related to abdominal distention.IBS can cause great discomfort, sometimes intermittent or continuous, for many decades in a patient’s life and can have a significantly negative impact on quality of life.
Irritable Bowel Syndrome primarily affects people in the prime of their lives, mostly between the ages of 20 and 40 years. Patient surveys from both the United States and the United Kingdom report an average disease duration of 11 years, with one third of patients having symptoms for much longer. For many patients, symptoms occur frequently and significantly impair emotional, physical, and social well-being. Almost three fourths of patients report symptoms more than once a week and about half report daily symptoms.In a telephone survey of female IBS sufferers in the United States, almost 40% reported pain and discomfort as intolerable without relief. Women with Irritable Bowel Syndrome reported 71% more abdominal surgeries than women without IBS (58% vs 34%). The rates of gallbladder operations, hysterectomies, and appendectomies were twice as high or higher among women with Irritable Bowel Syndrome.Twentyfive percent had been hospitalized overnight due to symptoms. Seventy-eight percent of women had limits on what they ate, 43% had limits on sports and recreational activity, 43% on social activity,40% on vacation or travel,and 28% on sexual activity. Two thirds of women were concerned about restroom availability wherever they went, one third avoided group meetings, and 25% got up earlier for work. Even more frustrating was that only 39% of women were diagnosed with IBS by the first physician they saw; 3% saw eight or more physicians before receiving a diagnosis. Time from onset to diagnosis took an average of 3 years,and patients saw an average of three physicians before getting a diagnosis.
Irritable Bowel Syndrome is a disease that can be caused by many factors. Disturbed bowel motility, visceral hypersensitivity, bacterial overgrowth, and psychological problems can all contribute to causing or exacerbating IBS. There are several important, take-home points in treating Irritable Bowel Syndrome.First,clinicians must take a good history and rule out “red flags.” Celiac sprue, bacterial overgrowth,and microscopic colitis, among many other conditions, can masquerade as IBS. Second, clinicians should provide reassurance and close follow-up at first to make sure the diagnosis is correct. Recall that the Rome III criteria have high specificity in making the diagnosis of Irritable Bowel Syndrome. Third, despite the lack of evidence-based studies,diet plays a role in exacerbating gastrointestinal symptoms and a good dietary history should be taken.Fourth,clinicians should not forget the psychological component of IBS. Many patients with IBS have coexisting depression and anxiety, and patients with severe IBS often have a history of physical and sexual abuse. Lastly, there are only a few newer medications with good data from randomized controlled trials. Given the paucity of specific medicines with positive results in the evidence-based medical literature,treatment is often a trial and error process.However, a combination of dietary and lifestyle changes, relaxation training or psychotherapy, and individualized IBS medicines tailored to each patient’s symptoms usually improves quality of life.
The response of an organism to external stressors is mediated through the integration of the hypothalamic-pituitary-adrenal axis (HPA) and the sympathetic branch of the autonomic nervous system with the host immune system. A recent model for the pathogenesis of IBS proposes altered stress circuits in predisposed individuals, which are triggered by external stressors resulting in the development of gut symptoms.In postinfective Irritable Bowel Syndrome,the persistence of chronic inflammatory mucosal changes and enterochromaffin cell hyperplasia that persists after eradication of the infectious organism are consistent with an inadequate physiologic response to gut inflammation, in particular, an inadequate cortisol or altered sympathetic response. The key interplay between the autonomic nervous system and the HPA axis in regulating gut mucosal immunology has been explored through research looking at how the stress response, which activates both of these systems, may be important in Irritable Bowel Syndrome. Environmental stressors are important in predisposing toward IBS and in perpetuating the symptoms of Irritable Bowel Syndrome. Prior life stressors and a history of childhood abuse predispose toward developing Irritable Bowel Syndrome in later life. Psychiatric illness episodes or anxiety-provoking situations preceded the onset of bowel symptoms in two thirds of Irritable Bowel Syndrome patients being treated in tertiary care centers; in addition, Irritable Bowel Syndrome patients report significantly more negative life events than matched peptic ulcer patients. In addition, psychological traits such as hypochondriasis, anxiety, and depression predispose previously healthy individuals who develop gastroenteritis to go on to develop symptoms of IBS. In fact, a subgroup of IBS patients have an exaggerated endocrine stress response, as shown by a heightened release of adrenocorticotropic hormone and cortisol in response to exogenous corticotropin-releasing factor administration. This exaggerated stress response seems to be associated with mucosal immune activation.
Irritable Bowel Syndrome Symptoms and Signs
As the Rome III criteria indicate , the key features are abdominal pain or discomfort that is clearly linked to bowel function, either being relieved by defecation or associated with a change in stool form or consistency. These symptoms are not explained by biochemical or structural abnormalities. Symptoms should be present for at least 6 months to clearly distinguish those from other conditions such as infections, which often pass quickly, or progressive diseases such as bowel cancer that are usually diagnosed within 6 months of symptoms onset. Symptoms that are common in IBS but are not part of the Rome III criteria include bloating,abnormal stool form (hard,loose,or both), abnormal stool frequency (< 3 times/week or > 3 times/week), straining at defecation,urgency,feeling of incomplete evacuation,and the passage of mucus per rectum.Most patients experience flares intermittently, with symptoms lasting 2–4 days followed by periods of remission. In women, symptoms can be worse at the time of menstruation and can cycle with the menstrual cycle. One common symptom of Irritable Bowel Syndrome not part of the Rome III criteria is repeated defecation in the morning (morning rush) when stool consistency changes from solid to liquid as the colon contents are evacuated.
One important exception to the Rome III criteria is patients who feel abdominal pain continuously. The diagnosis in this case is likely functional abdominal pain, an unusual, particularly severe condition in which patients respond poorly to treatment and often have severe underlying psychological disturbances. IBS is considered a painful condition and those with painless bowel dysfunction are labeled as having “functional constipation” or “functional diarrhea.”
Irritable Bowel Syndrome Diagnosis
Basic laboratory screening should include compete blood count, thyroid-stimulating hormone, and serologies for celiac disease. All patients should have stool tested for fecal occult blood (FOBT).
The basic indications for colonoscopy in this setting are age 50 or greater, positive FOBT or frank rectal bleeding, and a family history of colon cancer.
Lactose intolerance is very common and has similar symptoms to Irritable Bowel Syndrome. It is seen in 7–20% of Caucasians, as high as 80–95% of Native Americans, 65–75% of Africans and African Americans, and 50% of Hispanics. The prevalence is greater than 90% in some populations in East Asia. The preferred method of testing is a hydrogen breath test. For patients who are lactose intolerant,lactase preparations such as Lactaid,Lactase,and Dairy Ease may help,but many patients still have symptoms and will have to avoid all lactose containing food products.
Although there have been no controlled trials on diet and IBS, certain foods can cause or exacerbate Irritable Bowel Syndrome symptoms and a physicians should not forget to take a dietary history.Once lactose intolerance is excluded, the biggest offenders are sugar-free and carbohydrate-free or low-carbohydrate foods. These foods contain sugar alcohols such as sorbitol, maltitol, and xylitol.They are meant to be indigestible and as such can cause cramping, flatulence, and diarrhea. Sorbitol is even commercially available as a laxative.Diet soft drinks,flavored water, chewing gum, and candies often contain these sugar alcohols. Monosodium glutamate (MSG) can cause symptoms in sensitive individuals and is used as a flavoring in Chinese food and other preparations commonly purchased at the supermarket.Carbonated beverages contribute to gas and bloating, and alcohol can cause gastritis and diarrhea. Caffeine found in coffee, tea, soft drinks, or chocolate can exacerbate abdominal cramps and diarrhea. Other specific diets should be individualized, keeping in mind that there is no evidence-based literature. True food allergies are rare in adults and particular patients in whom there is a high suspicion should be referred to an allergist.
Most bowel infections should be transient and symptoms will not be present for 6 months in order to meet the Rome III criteria. Broad-spectrum antibiotics lead to transient diarrhea in 10% of cases which, if severe and persistent, should lead to consideration of testing for Clostridium difficile toxin or sigmoidoscopy to exclude pseudomembranous colitis. Chronic giardiasis can last for months and manifest with bloating,abdominal pain,and diarrhea.Stool enzyme-linked immunosorbent assay testing for Giardia antigen is the most sensitive (90–100%) and specific (95–100%) method to test for Giardia and should be considered in patients who have histories of exposure to poor sanitary conditions.
Celiac disease occurs in about 1 in 250 people in the United States. It can be identified through blood analysis of immunoglobulin A (IgA) level, anti-endomysial antibody, and anti-transglutaminase antibody. IgA level should be checked,because IgA deficiency is more common in patients with celiac disease. Patients who are antibody positive or in whom there is a high suspicion should undergo upper endoscopy and biopsy. Genetic testing is helpful in certain cases. More than 99% of patients with celiac disease have HLA DQ2, DQ8, or both, compared with about 40% of the general population. Thus, celiac disease is highly unlikely in patients without these haplotypes. The treatment of celiac disease is a strict gluten-free diet.
The key diagnostic test in tropical sprue is small intestinal mucosal biopsy,which is usually obtained at esophagogastroduodenoscopy. Gross findings at endoscopy include flattening of duodenal folds and so-called scalloping.The latter finding was originally thought to be pathognomonic of celiac disease but also occurs in tropical sprue and other small bowel diseases. The major histologic findings are shortened,blunted villi and elongated crypts with increased inflammatory cells in the lamina propria. These histologic changes are similar but not identical to those occurring in patients with untreated celiac disease. Most authorities recommend tetracycline (250 mg orally, four times daily) plus folic acid (5 mg/day) for 3–6 months for the treatment of tropical sprue.Even on this regimen,relapses or reinfection occur in up to 20% of patients living in the tropics.
Small Bowel Bacterial Overgrowth
Small bowel bacterial overgrowth is characterized by nutrient malabsorption associated with an increased number or type of bacteria in the upper gastrointestinal tract. Affected patients can have abdominal pain, watery diarrhea, dyspepsia, and weight loss. The most frequent presenting symptoms in one series of 100 adult patients were diarrhea, weight loss,bloating,and excess flatulence.A [14C]-D-xylose breath test is helpful in making the diagnosis. Xylose is a pentose sugar that is catabolized by gram-negative aerobes, which are invariably part of the microflora implicated in bacterial overgrowth. Bacterial action on the sugar releases the radioactive isotope 14CO2, which, after absorption, is detectable in breath samples.Breath hydrogen testing is performed by administering a test dose of carbohydrate (usually lactose or glucose), which, in patients with bacterial overgrowth,is associated with a rise in breath hydrogen levels.It is possible to have no rise in hydrogen production during a lactulose breath hydrogen test if hydrogen is converted to methane or hydrogen sulfide by hydrogen consumptive microbes. Concurrent testing with methane may enhance sensitivity.
Inflammatory Bowel Disease
Crohn disease and ulcerative colitis are fairly easy to distinguish from IBS with modern diagnostic testing. Most patients with inflammatory bowel disease present with weight loss,bleeding,and abdominal pain.Laboratory studies often reveal anemia, increased sedimentation rate, and sometimes leukocytosis. Colonoscopy in patients with colitis reveals inflammation, erythema, exudates, and sometimes ulcerations. Pathologic examination shows chronic changes in the mucosa. Subtle Crohn disease of the small bowel is almost always found by computed tomographic enterography or capsule endoscopy in cases that are difficult to diagnose.
Collagenous and lymphocytic colitis are more difficult to distinguish from IBS because patients present with chronic watery diarrhea and often no weight loss. In addition, these forms of colitis have completely normal endoscopic appearances. Collagenous colitis has two main histologic components: increased subepithelial collagen deposition and colitis with increased intraepithelial lymphocytes. The female-tomale ratio is 9:1, and most patients present in the sixth or seventh decades of life. Treatments range from sulfasalazine or mesalamine and diphenoxylate hydrochloride–atropine sulfate (Lomotil) to bismuth, budesonide, and prednisone for refractory disease. Lymphocytic colitis has features similar to collagenous colitis, including age at onset and clinical presentation, but it has almost equal incidence in men and women and no subepithelial collagen deposition on pathologic section. However, intraepithelial lymphocytes are increased. The frequency of celiac disease is increased in lymphocytic colitis and ranges from 9% to 27%. Celiac disease should be excluded in all patients with lymphocytic colitis,particularly if diarrhea does not respond to conventional therapy. Treatment is similar to that of collagenous colitis with the exception of a gluten-free diet for those who have celiac disease
Irritable Bowel Syndrome Treatment
Current treatment options for IBS are limited and include dietary modification, fiber supplements, pharmacologic agents, and psychotherapy.
found in whole grains, fruits, nuts, seeds, and vegetables and also in the form of fiber supplements containing psyllium (Metamucil), guar gum (Benefiber), calcium polycarbophil (FiberCon), and methylcellulose (Citrucel) helps to regulate bowel movements and improve stool consistency. Although it may help individual patients and is used commonly for patients with IBS-mixed disease or alternators, there is no high-quality evidence-based literature supporting the benefits of fiber in treating IBS.
Loperamide (Imodium) and diphenoxylate hydrochloride– atropine sulfate (Lomotil) decrease diarrhea but they have no effect on bloating or abdominal pain. Cholestyramine resin binds bile salts and slows down diarrhea but similarly has no effect on abdominal pain or bloating. These agents can be helpful for IBS in combination with other antispasmotics or can be used to provide as-needed therapy for diarrhea.
Enemas and Suppositories
Among patients who need these agents for intractable constipation, the majority will use them only occasionally. The safest suppository to use is a glycerin suppository because it is not a stimulant laxative and has no lasting ill effects on the gut.Fleets,tap water,or mineral oil enemas can be used occasionally for refractory constipation but insertion of air that comes with the enema fluid will only exacerbate bloating and abdominal pain.
Various laxatives are available for the constipation component of IBS. They include the stimulant laxatives (senna, bisacodyl, cascara) and the osmotic laxatives (polyethylene glycol,lactulose,sorbitol).The stimulant laxatives may cause permanent damage to the myenteric plexus but studies are conflicting. In any case, they do exacerbate abdominal cramps and bloating when used chronically. Abdominal cramps and excess gas and bloating are seen with the osmotic laxative but MiraLax was deemed effective for chronic constipation in one long-term study.
There is only minimal evidence-based literature that antispasmotics are effective in treating the pain component of IBS. Antispasmotics relax the smooth muscle of the gut and include dicyclomine hydrochloride (Bentyl), hyoscyamine sulfate (Levsin), scopolamine and phenobarbital (Donnatal), and clidinium bromide with chlordiazepoxide (Librax).These medicines are usually given before meals to inhibit abdominal pain and immediate,uncontrolled bowel movements.
Tricyclic antidepressants, such as amitriptyline hydrochloride (Elavil) and nortriptyline hydrochloride (Pamelor),prescribed at low doses, are beneficial in patients with and without diagnosed depression and anxiety because their benefit derives more from pain reduction than depression.There is some evidence-based literature favoring amitriptyline in treating visceral hypersensitivity. Side effects of both antispasmotics and tricyclics include dry mouth, dry eyes, and fatigue.Weight gain is a side effect particular to tricyclics.
Selective Serotonin Reuptake Inhibitors (SSRIs)
More recently, citalopram hydrobromide (Celexa) has been tested in patients with IBS. One study found that this SSRI, which is commonly used for depression, was effective in patients with IBS. Citalopram significantly improved symptoms of abdominal pain and bloating and improved quality of life and overall well-being. Fluoxetine hydrochloride (Prozac), an SSRI commonly used in the treatment of depression, is also effective in treating IBS. In a recent study in patients with IBS-C, fluoxetine decreased abdominal discomfort and bloating and increased bowel movements.
Newer Medical Therapies for IBS
Two newer medical therapies for inflammatory bowel disease focus on the serotonin receptor in the gut. Alosetron (Lotronex) is a 5-HT3 antagonist approved for use in women with severe IBS-D who have failed conventional therapy. Alosetron slows colonic transit, decreases rectal urgency, and decreases abdominal pain.The drug was launched in February of 2000 and temporarily withdrawn from the market in November ofthat year due to isolated reports of constipation and ischemic colitis. There were 3 deaths and 77 hospitalizations. Public outcry resulted in approval by the U.S. Food and Drug Administration (FDA) to allow the reintroduction of alosetron on a limited basis, and the drug was reintroduced in November 2002 under a new risk-management program. Restrictions on the use of alosetron include updated warnings in the complete Prescribing Information; including a Medication Guide for patients that explains what to do if they become constipated or have signs of ischemic colitis; a lower starting dose than previously approved; and a prescribing program for physicians to be enrolled in, based on self-attestation of qualifications and acceptance of certain responsibilities in prescribing alosetron. There is significant evidence-based literature to recommend use of alosetron in women with severe IBS-D,and it is an important drug in the IBS armamentarium. Studies show a statistically significant increase in global improvement in IBS symptoms, adequate relief of IBS pain and discomfort,and improvement in bowel symptoms.
Tegaserod maleate (Zelnorm) is a partial 5-HT4 receptor agonist. It stimulates the peristaltic reflex, increases velocity of propulsion through the colon, reduces the firing rate of rectal afferent nerves, alters chloride secretion in the intestine, and reduces visceral sensitivity. Tegaserod normalizes bowel function and relieves abdominal pain and discomfort in IBS patients. It is indicated for IBS-C in women and chronic constipation in men and women. On March 30, 2007, Novartis announced it was complying with a request from the FDA to suspend U.S. marketing and sales of tegaserod due to an analysis of clinical trial data identifying a small but statistically significant imbalance in the number of cardiovascular ischemic events in patients taking tegaserod.The data showed that events occurred in 13 out of 11,614 patients treated with tegaserod (0.11%), compared with one case in 7031 placebo-treated patients (0.01%).These events included heart attack,stroke,and unstable angina.The cardiovascular ischemic events occurred in patients who had preexisting cardiovascular disease or cardiovascular risk factors, or both. No causal relationship has been demonstrated between tegaserod and these events, and on July 27, 2007, tegaserod again become available through a special FDA IND program restricted to gastroenterologists prescribing this medication for female patients younger than 55 years with IBS-C or chronic constipation. High-quality, evidence-based literature supports the efficacy of tegaserod in IBS.In several randomized-controlled trials, tegaserod was superior to placebo for relief of abdominal discomfort or pain,bloating,and constipation.Patients taking tegaserod had a statistically significant increase in stool frequency and consistency. In one study, a response to tegaserod was observed within the first treatment week. In addition, tegaserod produced greater satisfaction, work productivity, and improved quality of life than placebo (P < 0.05).
Lubiprostone (Amitiza) is specific chloride channel-2 activator that enhances intestinal fluid secretion to facilitate increased motility. It is currently indicated for the treatment of chronic constipation and has recently been approved for IBS-C. Lubiprostone increases weekly spontaneous bowel movements, and a significant number of patients respond within 24 hours.It is the only medicine for constipation with an indication for patients 65 years of age and older. There is one high-quality study published on lubiprostone in chronic constipation and the rest of the data is in abstract form only. The main side effect is nausea, which can be alleviated by taking the medicine with food.
Rifaximin (Xifaxan) is a nonsystemic (< 0.4%) semisynthetic antibiotic whose spectrum includes most gram-positive and gram-negative bacteria, both aerobes and anaerobes. In one questionnaire study in patients with IBS, there was a statistically significant improvement in overall symptoms and less bloating (P = 0.020) over placebo.There was no difference in pain,diarrhea,or constipation.The dosage of rifaximin used in this study (400 mg orally, three times daily for 10 days) is higher than that approved by the FDA for traveler’s diarrhea.
In a recent study, Bifidobacterium infantis 35624 was shown to alleviate abdominal pain and bloating and bowel movement difficulty. Another probiotic, which contains eight different strains of bacteria including lactobacillus and bifidobacteria, alleviated flatulence and slowed down stools in IBS patients.
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