GI Consult: Irritable Bowel Syndrome

Two specialists discuss the pathophysiology, clinical characteristics, and management of this common ailment.

By Christine L. Frissora, MD, and Lucinda A. Harris, MD

1. What is irritable bowel syndrome?

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder. It accounts for 12% of all visits to primary care physicians and affects 15% of the population in the U.S. Like other functional disorders, IBS does not lead to cancer, nor is there an organic or infectious component; in fact, the involved anatomic structures are grossly normal. The situation is much like that of a light bulb that will not illuminate even though it is structurally sound. Likewise, IBS appears to be caused by an anomaly of the circuitry, specifically an abnormal communication between the central nervous system (CNS) and the enteric nervous system (ENS) mediated by serotonin. It should be noted, however, that there is a small subset of patients who have what is called postinfectious IBS, a disorder thought to be caused by an infectious process.

2. What is serotonin and what role does it play in IBS?

Serotonin, or 5-hydroxytryptamine (5-HT), is a peptide that is found throughout the body. Approximately 96% of serotonin is located in the gastrointestinal tract, 2% in platelets, and 2% in the CNS. More than 20 types of serotonin receptors at various locations in the human body have been described, but the receptors that seem to be most important in the gastrointestinal tract in general and in IBS in particular are the 5-HT3 and 5-HT4 receptors.

Because the structure of the receptor determines the function of the peptide, serotonin has slightly different functions when paired with each different receptor. Generally, these receptors are involved in controlling the motility of and secretions in the gut and the perception of abdominal pain. Typically, 5-HT3 and 5-HT4 receptor agonists promote motility and the antagonists decrease motility. Although the exact mechanism is not known, these receptors do not function properly in IBS.

3. What are the clinical features of IBS?

Symptoms of IBS normally appear in late adolescence or early adulthood. The disorder is twice as likely to occur in women. In most patients with IBS, a particular symptom or pattern of symptoms will predominate. The predominant symptom in IBS can be pain or bloating, diarrhea, or constipation, or it may alternate between diarrhea and constipation. Patients with IBS have abdominal discomfort, which is normally relieved by defecation or associated with a change in stool frequency or consistency.

Stress and certain foods often trigger and exacerbate symptoms of IBS. Dairy products, fatty food, alcohol, caffeine, lactose, sorbitol, and fructose have all been known to produce and aggravate symptoms of IBS. Other influences such as lack of sleep, decreased fluid intake, and a sedentary lifestyle can also affect the severity of symptoms.

In a given patient, the dominant symptom usually remains constant. Studies have shown that 75% of patients have the same set of symptoms over a five-year period. If the dominant symptom changes, a new, separate disorder may have occurred and a reevaluation may be necessary.

4. How is IBS diagnosed?

Irritable bowel syndrome is no longer a diagnosis made only by exclusion. In the 1990s, a group of gastroenterologists and health professionals formed a committee in Rome, Italy, to develop clinical criteria that would enable physicians to make a reliable and focused diagnosis of irritable bowel syndrome. The criteria devised by the Rome II committee define IBS as abdominal pain or discomfort lasting twelve weeks—consecutive or nonconsecutive—in the year before treatment is sought and that is associated with two of the following: pain relieved by defecation; pain associated with a change in frequency of the stool; or pain associated with a change in the form of the stool.

In addition to a focused history and physical examination, the Rome committee recommended that the following laboratory tests be performed: complete blood count; erythrocyte sedimentation rate (ESR); chemistry panel, including liver function tests; and stool studies that include measurement of stool guaiac, ova and parasites, stool culture, and fecal leukocytes. A flexible sigmoidoscopy is also suggested, and for some patients, colonoscopy is recommended.

Because thyroid disease is common in many young adults, measurements of thyroid-stimulating hormone and thyroxine may be necessary: hypothyroidism often occurs with constipation and, conversely, hyperthyroidism often accompanies diarrhea. Culture of a stool sample for Clostridium difficile should also be considered if clinically indicated, particularly in patients who have undergone antibiotic therapy, recent hospitalization, or a surgical procedure. Colonoscopy and flexible sigmoidoscopy can also be useful in the diagnosis of IBS; the appropriate technique will be determined by the clinical characteristics of each patient (see Question 6).

5. Are there any "red flags" to look for in the history and on physical and laboratory evaluations that can be used to rule out IBS?

Features that should lead the clinician to consider other diagnoses include older age, family history of colon cancer or inflammatory bowel disease (IBD), or a history of being awakened in the night by the need to have bowel movements. Surgical history should also be considered. For example, a patient who has undergone cholecystectomy may have-instead of IBS-bile salt diarrhea, which can be treated with cholestyramine. Likewise, fever, palpable abdominal masses, or guaiac positive stool are not features of IBS and could indicate IBD or a malignant process. Similarly, anemia, increased ESR, and abnormal results on metabolic or liver function tests are usually not seen in IBS.

6. Is colonoscopy necessary for every patient suspected of having IBS?

Whether to perform sigmoidoscopy or colonoscopy depends on the age, symptoms, and family history of the patient. The American College of Physicians recommends that routine colon cancer screening should begin at age 50. Some patients with a family history of IBD, colon cancer, or severe symptoms of IBS may require colonoscopy at a younger age. If a diagnosis of microscopic or collagenous colitis is suspected, a biopsy will be necessary during colonoscopy because the mucosa will appear normal. If flexible sigmoidoscopy is performed for a patient who has IBS in which diarrhea is the predominant symptom, then a biopsy will be necessary to rule out ulcerative colitis. In some patients, ulcerative colitis is not grossly obvious and can be confirmed only by microscopic examination.

When sigmoidoscopy or colonoscopy is performed, stool specimens can be obtained for culturing and to determine the presence of C. difficile antigen or ova and parasites. In patients with a family history of sprue or stomach cancer, upper endoscopy may be indicated, depending on the clinical symptoms.

7. Can a patient have both IBS and IBD?

Patients and physicians alike can confuse IBS and IBD, and distinguishing the symptoms of IBS from a flare up of IBD can be clinically challenging. Crohn's disease and ulcerative colitis are two types of IBD. Some symptoms of IBD, such as gas and pain, can be similar to those of IBS. Patients with ulcerative colitis usually have fever and bloody diarrhea; those with Crohn's disease can have pain, diarrhea or constipation, perianal disease, strictures, or fistula. It is also known, however, that patients with IBD can have IBS as well.

8. What is the approach to treatment in patients with IBS?

For patients with mild disease, all that may be needed is education about the disease, reassurance from the physician, and lifestyle and dietary modification.

Many patients may have previously been given an erroneous diagnosis, or their physician may have even dismissed their symptoms as psychosomatic. It is therefore important to explain to all patients the actual physiologic causes and processes of IBS-including the role of serotonin and the interaction between the ENS and CNS-and reassure them that the disorder won't lead to cancer or IBD.

Patients with IBS should also understand that the disorder is chronic and its severity varies in response to several influences, including diet, stress, lifestyle, and medications such as antibiotics or other drugs meant for other conditions.

In addition to the dietary triggers mentioned earlier, dairy products can produce and exacerbate symptoms. Women who must limit the dairy content in their diet should be encouraged to take calcium supplements. Women who have constipation may benefit from calcium combined with magnesium, whereas those who have diarrhea may do better with calcium carbonate. Stress may be relieved through regular exercise and a proper and consistent amount of rest. Stretching exercises and yoga in particular can be very beneficial for some patients.

9. What role does dietary fiber have in the treatment of IBS?

Dietary fiber is often advocated in the treatment of diarrhea, because it is believed to absorb excess water from the stool. In practice, however, dietary fiber has proved ineffective for that purpose, but studies have shown that it has a role in the treatment of constipation-predominant IBS. Soluble fiber helps reduce colonic transit time, thereby relieving constipation. Dietary fiber provides ancillary benefits as well, including the lowering of serum cholesterol levels, improving glucose control in diabetic patients, and perhaps preventing certain cancers by reducing the number of free radicals in the gastrointestinal tract.

Patients with mild, constipation-predominant IBS must be careful to limit the amount of crude, insoluble fiber in their diet. Found in the bran layers of wheat and other grains and in cruciferous vegetables, insoluble fiber generates gas and bloating, which are the products of carbohydrate fermentation that occurs when the fiber reaches colonic bacteria in the large intestine. Soluble fiber, however, which is found in fruits, vegetables, oats, barley, legumes, and seaweed, produces less gas and is therefore the type that patients with constipation-predominant IBS are encouraged to include in their diet.

Soluble fiber may also be derived from over-the-counter supplements. Those that contain calcium polycarbophil are often better tolerated than psyllium-based compounds, which can produce more gas.

10. When is pharmacotherapy necessary?

Patients with moderate IBS can benefit from drug therapy directed at either pain and bloating, diarrhea, or constipation, depending on which symptom predominates. Before beginning such therapy, however, patients should keep a symptom diary, in which they can track the progress of their symptoms and the relationship of those symptoms to diet, activity, and stress. From the information collected in the diary, the physician and patient can then determine the predominant symptom to treat and the appropriate regimen to begin.

The available agents currently given for the treatment of the bloating and pain that accompany moderate IBS are, as a rule, minimally effective. Over-the-counter drugs that contain simethicone may be helpful in eliminating gas in the upper gastrointestinal tract, but they are mostly ineffective in treating flatulence and bloating. Activated charcoal is sometimes recommended to relieve gas in the lower tract, but it too is not very effective. In addition, it turns stools black and can even cause constipation.

Anticholinergic/antispasmodic drugs may have a role in treating severe intestinal spasm, but they also produce drowsiness, urinary retention, and dry mouth, adverse effects that limit the medications' acceptance among patients. Examples include hyoscyamine, dicyclomine, methscopolamine bromide, and clidinium/chlordiazepoxide. Selective serotonin reuptake inhibitors (SSRIs) can relieve pain and bloating, but these drugs should be reserved for patients with moderate to severe IBS.

In the treatment of diarrhea, agents such as diphenoxylate, loperamide, and cholestyramine have all been used with varying success. Through their anticholinergic effects, tricyclic antidepressant agents, such as amitriptyline and desipramine, can be helpful in treating diarrhea. When given in low doses, they may also help relieve the abdominal pain of IBS, but these drugs also produce drowsiness and weight gain, which limits their usefulness and acceptance. Currently under investigation are antibiotics such as ciprofloxacin, metronidazole, and doxycycline, which can treat postinfectious IBS, a disorder believed to be caused by alterations in intestinal microflora.

In addition to dietary or supplementary soluble fiber, the standard treatment for constipation has included laxatives, usually milk of magnesia or lactulose. Polyethylene glycol agents are often more effective, however, and produce less bloating than does lactulose.

The latest advance in the treatment of moderate constipation-predominant IBS are the neuroenteric modulator agents, which affect the 5-HT3 and 5-HT4 serotoninergic receptors. Variants are targeted specifically at either diarrhea or constipation, but all neuroenteric modulator agents can also control the pain and bloating that often accompany these symptoms. Tegaserod, expected to be released in 2001, is a 5-HT4 partial agonist that increases intestinal motility and is meant for the treatment of constipation-predominant IBS. Alosetron, a 5-HT3 antagonist intended for the treatment of diarrhea-predominant IBS, was removed from the market because it was found to cause constipation and possibly ischemic colitis.

It is important to know which neuroenteric modulator agents treat diarrhea and which treat constipation; they are not dietary supplements, and patients who take them must be monitored more closely.

11. What are the options for patients with severe IBS?

Along with the pharmacotherapy described above, patients with severe IBS-and even those with moderate IBS-may try short-term psychotherapy, which may consist of cognitive or relaxation therapy or hypnosis. For such patients it is important to establish realistic treatment goals that require their understanding, participation, and cooperation with the physician. They should be made aware that because a cure is not likely, their attention should be focused on health, not illness, with an aim toward controlling the symptoms and improving overall functioning. Physicians should also be aware that a high proportion of patients with severe IBS have been victims of child or sexual abuse.

When stronger pharmacologic agents for the treatment of pain are necessary, the SSRIs and tricyclic antidepressants, mentioned earlier, can be tried. The SSRIs, which include citalopram, sertraline, fluoxetine, and paroxetine, are given when pain and bloating or constipation predominates, whereas the tricyclic agents are given when diarrhea is the predominant symptom.

Until recently, SSRI therapy was usually administered empirically, but research has begun to confirm some of the benefits of these drugs in the treatment of severe IBS. In one study, for example, citalopram was associated with increased pain tolerance and decreased sensitivity to rectal distension. To allay any fears of addiction or mind-altering effects, physicians should explain to their patients that the drugs only inhibit the sensation of intestinal pain and are neither addictive nor psychotropic. For all patients given antidepressant drugs or neuroenteric modulators, monitoring and follow-up are essential.

As with any chronic illness, severe IBS can be complicated by anxiety or depression, for which a longer period of psychotherapy or admission to a pain management clinic may be beneficial.