Progress Report: Irritable Bowel Syndrome

The authors provide updated diagnostic criteria and a multimodal therapeutic approach to the long-misunderstood digestive disorder known as irritable bowel syndrome, now viewed as a complex interaction of enteric neurochemical abnormalities with psychosocial and environmental factors.

By Rebecca C. Dunphy, MD, and G. Nicholas Verne, MD

 
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder, the hallmark of which is abdominal pain or discomfort associated with a change in defecation or bowel habits. We now know that this clinical condition, which has long been misunderstood and misdiagnosed, may represent a complex interaction of altered neurochemical mediators in the enteric nervous system with psychosocial and environmental influences. With its broad clinical criteria, IBS is one of the most common disorders seen in the primary care setting and is responsible for up to 40% of referrals to gastroenterologists.

In this article, we will review the incidence and prevalence of IBS and the pathophysiologic mechanisms at work in this disease. We will also discuss key diagnostic criteria, patient assessment, and treatment options available to the clinician.
 

INCIDENCE AND PREVALENCE

Recent studies suggest that in the United States the incidence of IBS is 10% and its prevalence 20%. These numbers are dependent on the diagnostic criteria used as well as on the population studied. Approximately 70% of patients who meet the diagnostic criteria for IBS do not seek medical care; the remaining patients account for 12% of primary care visits, for a total of 2.4 to 3.5 million visits per year. Community-based estimates suggest that up to 30% of patients with a gastrointestinal complaint will have IBS. Furthermore, as suggested by the high number of primary care visits for IBS, only a minority of patients will be diagnosed by a gastroenterologist.

Gender, race, and age all play a role in the prevalence of IBS. In Western cultures, women are more commonly affected than men, with recent data indicating that 14% to 24% of women and 5% to 19% of men in the United States and Great Britain have IBS. In India and Sri Lanka, however, IBS is more common among men. The prevalence of the disease appears to be lower in Hispanics compared to whites, but similar between African Americans and whites. Significantly, more than half of all patients with IBS first present to a physician between ages 30 and 50. In patients older than 60, the incidence decreases but prevalence stays about the same.

As with any chronic condition, the cost of IBS is high in terms of both health care dollars and quality of life. It is estimated that the total health care cost for patients with IBS is 50% higher than for patients who do not fit the diagnostic criteria. These patients undergo more surgical procedures (such as hysterectomy, appendectomy, and cholecystectomy) and have a higher rate of work absenteeism and an increased number of physician visits per year. Moreover, these patients have significantly impaired quality of life even when compared with chronic diseases such as diabetes.

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THREE PATHOPHYSIOLOGIC MECHANISMS AT WORK

Irritable bowel syndrome is a disorder in which at least three pathophysiologic mechanisms interact to produce a typical pattern of symptoms: psychosocial interactions, altered motility, and visceral hypersensitivity. Visceral hypersensitivity refers to the finding that patients with IBS have significantly lower pain thresholds to experimentally induced intestinal distension compared to patients without IBS.

In the 1970s and 1980s, IBS was widely regarded as a disorder of gastrointestinal motility. However, no consistent pattern of motility within the gut was found to correlate with patients' symptoms. More recent research has focused on IBS as a disorder of perception resulting from alterations in the enteric nervous system. The hypothesis that patients with IBS have increased pain perception comes from numerous studies in which patients with IBS displayed visceral hypersensitivity. Also, while psychosocial factors play no direct role in the diagnosis of IBS, psychological and socioeconomic factors modify the illness experience and influence the level of pain reporting, number of physician visits, and use of medications.

Irritable bowel syndrome is one of a group of functional bowel diseases that may coexist or overlap in any given population of patients. A functional bowel disease is a disorder in which symptoms attributable to the gastrointestinal tract are present in the absence of any structural or measurable biochemical abnormality. While there is currently no way to measure neurotransmitter levels in the gastrointestinal tract, it is likely that functional bowel disorders have some biochemical etiology such as alterations in serotonin or acetylcholine within the enteric nervous system.

There have been several attempts to outline the symptomatic criteria that define IBS. The first attempt resulted in the Manning criteria (see table above). Further refinements of these criteria led to the Rome I criteria and its recent revision, the Rome II criteria (see table below). As the tables show, IBS is a disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habits. Key elements in the presentation of IBS include abnormal stool frequency (more than three bowel movements per day or less than three bowel movements per week), hard or loose watery stool, feelings of incomplete evacuation or retained stool, bloating or abdominal distension, and the passing of mucus. Subgroup analysis of patients with IBS has demonstrated that approximately 30% of patient who meet the Rome II criteria have diarrhea as their predominant symptom; 30% report that constipation is their most frequent symptom; and 30% alternate between diarrhea and constipation. Knowing the subgroup into which any particular patient falls is critical in terms of outlining a treatment plan.

PATIENT ASSESSMENT

As with any disorder, a complete history and physical examination are the first steps in assessing the patient with gastrointestinal complaints. Dietary habits, travel history, and medication use may provide clues to other diagnoses whose symptoms mimic those of IBS. Asking the patient about an antecedent event such as a viral gastroenteritis or food-borne illness is important because there is evidence that up to 30% of patients will develop IBS-like symptoms after experiencing Salmonella enteritis. The use of sorbitol in the form of sugar-free candies and gum or ingestion of large amounts of cruciferous vegetables, caffeine, or fructose can lead to symptoms of diarrhea or bloating.

Lactase intolerance is another common condition that can mimic diarrhea-predominant IBS, suggesting that a dairy-free trial should be first-line therapy if the patient cannot tolerate milk and milk products. Medication history is also important because there is mounting evidence that patients who have taken a recent course of antibiotics are up to three times as likely to report symptoms like those seen in IBS. It is thought that antibiotics may alter normal bowel flora or may induce a short-term inflammatory response that induces a hypersensitive state within the colon.

The patient's gender and age, the duration of symptoms, any change in symptoms over time, a family history of gastrointestinal disease, the results of prior diagnostic testing, and the presence of warning symptoms or red flags (see table below) all influence the initial diagnostic work-up. By definition, IBS is a chronic syndrome in which symptoms have been present for at least 12 weeks in the preceding 12 months. In the acute care setting, therefore, evaluation of the patient who presents with abdominal pain, diarrhea, or constipation should initially focus on alarm symptoms that demand immediate attention, such as weight loss, malnutrition, or blood in the stool.

For the IBS patient without alarm symptoms, the initial diagnostic work-up should include a complete blood count, electrolyte levels, a thyroid-stimulating hormone level, stool hemoccult testing, and flexible sigmoidoscopy or colonoscopy. If the patient does have IBS, this limited work-up will not reveal any specific abnormality. Additional tests may be warranted based on the history. For example, if a patient reports a sudden onset of diarrhea and abdominal cramping after camping in an area in which Giardia lamblia is endemic, a stool sample should be sent for Giardia antigen testing. Likewise, if a patient reports the onset of diarrhea after being treated with antibiotics, stool should be sent for Clostridium difficile toxin testing.

The constellation of bloating, diarrhea, and iron deficiency anemia should alert the clinician to the possibility of celiac sprue, which is estimated to occur in 1 out of 200 people in the United States and in 1 out of 30 patients referred for the diagnosis of IBS. If celiac sprue is suspected, the patient should have appropriate serologic studies performed—serum IgG and IgA antigliadin antibody titers and IgA tissue transglutaminase antibody titers—and should be referred to a gastroenterologist for esophagogastroduodenoscopy with small bowel biopsy.

Studies aimed at establishing the long-term outcome of IBS using a similar conservative diagnostic approach demonstrated that virtually all patients had a correct diagnosis at five years' follow-up. Adherence to this strategy should help reassure the primary physician that the correct diagnosis has been made and discourage overuse of medical resources in patients with an otherwise benign clinical syndrome.

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TREATMENT OF IBS

One of the major difficulties in developing a treatment strategy for patients with IBS is the diverse nature of the symptoms that comprise each subgroup—namely diarrhea-predominant, constipation-predominant, and alternating diarrhea and constipation. Furthermore, unlike other chronic disease states, such as diabetes or hypercholesterolemia, no unique target for pharmacotherapy has been discovered in IBS. Finally, there is a wide range of symptom severity within the spectrum of the disease. Symptoms range from mild, infrequent alterations in bowel habits to severe symptoms resulting in a high level of health care utilization, economic disability, and psychological distress.

The diverse nature of IBS suggests that a combination of pharmacologic agents and therapeutic interventions may be necessary to maintain adequate symptomatic relief. These may include fiber therapy, antidiarrheal medications, antispasmodics, tricyclic antidepressants (TCAs), and psychological interventions. Prokinetics, which no longer play a significant role in the treatment of IBS, will also be discussed. Narcotic pain medications are not recommended because of the risk of exacerbating symptoms in patients with constipation-predominant IBS and the risk of physical and psychological dependence.

Fiber therapy. The widespread use of fiber therapy in IBS is based on early studies that demonstrated that patients who consume a diet high in refined foods had a markedly prolonged transit time through the small and large bowel compared with those who had a diet high in fiber. While there have been multiple trials to evaluate the use of fiber in IBS, the results are hard to interpret because of a high placebo response rate and the difficulty of comparing the types of fiber across studies. Most studies support the use of fiber in the range of 20 to 30 grams daily in constipation-predominant IBS patients. Anecdotal evidence suggests that fiber supplementation may also improve symptoms in diarrhea-predominant IBS by acting as a stool-bulking agent, but this remains controversial.

Over-the-counter fiber preparations come in many forms, including psyllium, methylcellulose, and polycarbophil. Calcium polycarbophil is the only fiber preparation that has been demonstrated to make bowel movements more comfortable and to reduce nausea, pain, and bloating compared with placebo in patients with constipation-predominant IBS. Each over-the-counter preparation contains a different amount of dietary fiber and may produce varying degrees of abdominal bloating and flatulence.

In general, IBS patients should be instructed to start fiber therapy once a day, using the recommended dose for the chosen preparation, and increase their intake as tolerated to three times a day. Abdominal distension, flatulence, and bloating should be carefully monitored because these side effects of fiber therapy can be confused with an exacerbation of the underlying disorder. Counseling the patient on dietary sources of fiber is also appropriate, but it is rare that a patient will be able to maintain adequate fiber intake through diet alone.

Antidiarrheal medications. Nearly one-third of patients with IBS present with diarrhea as the predominant symptom, while another one-third will alternate between diarrhea and constipation. For those patients with diarrhea, loperamide is considered first-line therapy. An opioid that does not affect the central nervous system, loperamide slows transit time through the colon and increases intestinal water resorption. The standard dose is 2 mg after each loose stool up to 16 mg daily. For those patients who report postprandial diarrhea or who avoid social situations because of chronic diarrhea, the use of loperamide before a meal or a social event may improve symptoms significantly.

Cholestyramine, a bile acid-binding resin, has also been used to treat diarrhea in a subset of patients with IBS. Although not a first-line agent, cholestyramine may be of benefit in patients with excessive bile secretion and those with proven bile salt malabsorption.

Antispasmodics. Although all of these agents may have mixed actions, antispasmodics can be classified into three general categories: antimuscarinics, smooth muscle relaxants, and calcium channel blockers. The most commonly prescribed drugs are dicyclomine and hyoscyamine. They are used for acute exacerbations of pain but appear to lose efficacy in chronic therapy. Librax, a combination of the benzodiazepine chlordiazepoxide and the antimuscarinic drug clinidium, should be avoided due to the addictive potential of benzodiazepines.

One potential complication with anticholinergic preparations is decreased gastrointestinal motility. These drugs should be avoided in constipation-predominant patients and used with caution in those who experience alternating constipation and diarrhea. Also, as with any anticholinergic preparation, these drugs should be used with caution in the elderly. In the emergency department, they may best be used as "bridge" medications pending further evaluation by a primary care physician or gastroenterologist.

Tricyclic antidepressants. The recognition that pain perception plays a role in the pathophysiology of IBS led to an interest in drugs that target pain pathways. The use of TCAs in this setting is appropriate on at least two levels. First, the association of functional gastrointestinal disease with psychosomatic disorders is well known. Secondly, TCAs are playing an increasingly larger role in the treatment of chronic pain syndromes; approximately 30% of prescriptions for TCAs are written for painful conditions.

A recent five-year retrospective trial of TCAs in patients who met at least two of the six Manning criteria found complete resolution of symptoms in 61% of patients and improvement of symptoms in 89%. These patients tend to respond to TCA doses that are much lower than those used in depression, suggesting that the benefit of TCAs is not dependent on the treatment of an underlying psychiatric disorder (see table below). As with antispasmodics, these agents are best used in the emergency department as bridge medications pending follow-up with a primary care physician or gastroenterologist, and they should only be used in patients with severe or refractory pain.

Prokinetics. Prokinetic medications have no established role in the treatment of IBS and essentially no role in treating patients who present with acute symptoms in the emergency department. Cisapride, a mixed serotonin agonist/antagonist, was thought to be of some benefit in the treatment of constipation-predominant IBS; it was believed to decrease intestinal transit time and increase the number of days when stool was passed. However, recent data that looked at the efficacy of cisapride over a 12-week period did not show any benefit over placebo. Unfortunately, cisapride's adverse effects include a prolonged QT interval, which can lead to fatal heart arrhythmias. Although the majority of adverse events were reported in patients taking drugs that may interact with cisapride or in patients with underlying cardiac conditions, continuing reports of fatal heart arrhythmias led to the withdrawal of cisapride from the U.S. market in July 2000.

Psychological interventions. While psychiatric disturbances are more likely to be seen in patients with IBS who consult physicians, not all of these patients necessarily need a referral to a psychiatrist. In general, patients with mild symptoms that are infrequent and not debilitating do not need a referral. The vast majority of patients with IBS who seek medical care will fall into this category, and they can be treated with reassurance, dietary modifications, and education.

In patients with moderately debilitating symptoms that disrupt daily activities and are linked to stressful events, symptoms may be controlled with fiber, antispasmodics, and TCAs, but more intensive psychological therapy is warranted. Patients with severe intractable symptoms usually have an underlying psychiatric disease, which they may not acknowledge. These patients are usually unresponsive to psychotherapy and may need referral to a pain management clinic rather than to a psychiatrist or psychologist.
 

KEY STEPS

There are several key steps to follow in evaluating and treating patients with IBS. The first step is to recognize the diagnostic criteria as outlined by the Rome II committee. The second step is to realize that in the absence of alarm symptoms, a limited symptom-directed evaluation is both cost effective and medically sound. The third step is to know which therapies are effective in thse patients—namely fiber, antispasmodics, antidiarrheals, and TCAs and which medications to avoid, such as narcotics. Finally, it is of utmost importance to provide follow-up care for the patient, whether it be with a primary care physician, gastroenterologist, or psychiatrist. If the clinician follows these key steps, IBS can be accurately diagnosed and well managed in the acute care setting.

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