Approach to the Patient with Functional Gastrointestinal Disease
James M. Richter
Functional gastrointestinal (GI) disease accounts for a large proportion of the GI complaints seen in office practice, not only in the primary care setting but also in the referral practices of gastroenterologists. The International Working Group consensus definition of functional GI disease refers to “a variable combination of chronic or recurrent GI symptoms not explained by structural or biochemical abnormalities.” Symptoms may be attributed to dysfunction of the pharynx, esophagus, stomach, biliary tree, small and large intestine, or anorectum. Included under the rubric of functional GI disease are two common, often-troubling syndromes: irritable bowel syndrome (IBS) and nonulcer dyspepsia. The former is associated with large-bowel discomfort or pain, disturbed defecation, and distention, often with predominant constipation, diarrhea, or gaseousness. The latter is characterized by upper abdominal discomfort, bloating, distension, and nausea, which is often, but not necessarily, exacerbated or triggered by eating.
The primary care physician needs to be expert in the recognition and management of these conditions not only because they can mimic more serious disease (sometimes leading to unnecessary testing and treatment) but also because they are the source of much worry, functional impairment, and substantial health care expenditures.
IRRITABLE BOWEL SYNDROME
IBS is a functional disturbance of intestinal motility and visceral perception. It accounts for about half of GI complaints seen by physicians. Epidemiologic studies suggest that nearly 20% of adults suffer from some form of the condition, although only a fraction seeks medical attention. Functional bloating, functional constipation, and functional diarrhea are closely allied syndromes that are beginning to be separated from IBS. Older and
lay terms sometimes used synonymously include spastic bowel, mucous colitis, and spastic colitis. Because there are no definitive diagnostic tests, the identification of the condition requires taking a careful history to avoid misdiagnosis.
lay terms sometimes used synonymously include spastic bowel, mucous colitis, and spastic colitis. Because there are no definitive diagnostic tests, the identification of the condition requires taking a careful history to avoid misdiagnosis.
Pathophysiology and Clinical Presentation (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17)
Pathophysiology
Traditional views of IBS pathophysiology emphasized psychosocial dysfunction and disorders of the interaction between the central and peripheral nervous system, the so-called nociceptive errors. However, an increasing body of evidence finds that in many cases, IBS also involves peripheral mechanisms, supporting the view that IBS is not a purely neuropsychosocial phenomenon.
Abnormal motor function is a hallmark of this syndrome, which is capable of producing both diarrhea and constipation. Neurotransmitter imbalance (especially dysfunctional serotonin release) appears to play an important role. The GI tract contains the highest concentration of serotonin-secreting cells, which are capable of stimulating vagal activity and potent motor and secretory responses. The altered motility produces nonpropulsive colonic contractions and abnormal slow-wave myoelectric patterns. When excessive, these contractions may impede propulsion of stool, prolong transit time, and cause constipation. Diarrhea occurs when the increase in contractility is localized to the small bowel and proximal colon. A pressure gradient develops, causing accelerated movement of intestinal contents. Meals normally cause an increase in colonic contractions, but controlled study has shown that patients with irritable colon syndrome have a significantly exaggerated increase in motor response to food. Patients with diarrhea-predominant disease have more jejunal, fast, and high-amplitude contractions postprandially than do healthy individuals, resulting in reduced colonic transit time. In some patients, the diarrhea appears to be responsive to drug therapy that targets serotonin receptors (see later discussion).
Visceral hypersensitivity also plays an important role, particularly in the abdominal pain and anorectal discomfort experienced. Abnormal nociception has been demonstrated in balloon manometry studies of IBS patients, who manifest excessive sensitivity to balloon distention in the ileum, rectosigmoid, and anorectum. In persons who suffer predominantly from diarrhea, there are reduced thresholds for the initiation of reflex motor activity and discomfort; urgency is precipitated at abnormally small volumes of balloon distention. In patients with constipation, the threshold for reflex motor activity is abnormally high, and emptying is delayed. Fecal material collects and hardens, and the bowel becomes distended; pain ensues. Excessive afferent sensory activity and differences in its central processing have also been detected, probably contributing to the nociceptive dysfunction. Serotonergic and noradrenergic neurotransmission are believed to be active in central and peripheral components of IBS pathophysiology and serve as a possible link between the two.
The combination of abnormal motor, sensory, and cortical functioning has the potential to cause the patient much discomfort. For example, increased sensitivity can trigger excessive reflex motor activity, leading to a cycle of anorectal discomfort or pain before a bowel movement, a sense of incomplete evacuation after one, and increased frequency of movements, perhaps as a result of learned behavior or underlying psychopathology.
Psychosocial stress and psychopathology not only result from IBS, but they also may contribute to it. Psychopathology often confounds the management of IBS, which is dependent on coping skills and lifestyle changes. Hypermotility in response to stress has been documented in both healthy persons and patients with IBS, but the latter show a significantly higher frequency of life stress. In addition, there is a high prevalence of psychopathology among IBS patients presenting for care. Somatization, personality disturbances, anxiety, and depression are frequently identified. Such psychopathology appears to be more a predictor of illness behavior than a direct cause of bowel dysfunction. Psychiatric symptoms and poor coping skills usually predate bowel complaints. Disturbances in bowel function can be especially troubling to patients with preexisting psychopathology and more likely to precipitate medical encounters than might similar symptoms in otherwise well-adjusted persons. Hypervigilance is characteristic. This finding has been invoked to explain why only a fraction of patients with IBS ever present for medical care. Patients with IBS who do not consult physicians have been found to be psychologically similar to control subjects.
Intraluminal factors can alter bowel motor function and cause it to behave in an “irritable” manner. Selective malabsorption of certain sugars, such as lactose (the common dairy product sugar as seen in lactase deficiency—see Chapter 64), fructose (the common citrus fruit sugar), and sorbitol (often found in “sugar-free” candy) can be responsible. Sorbitol is a common sweetener in candies and chewing gum and is capable of causing bloating and diarrhea if taken in large amounts, as are milk products in patients with lactose intolerance. Bile acid malabsorption has been detected in up to 10% of patients with diarrhea-predominant IBS. The resulting large quantities of fatty acids descending on the colon can trigger painful rapid contractions, leading to marked discomfort and diarrhea.
Such factors might help to explain the observed onset of IBS-like symptoms in up to 10% of persons with a postinfectious presentation of IBS after recent bacterial or viral gastroenteritis, especially in those with concurrent psychosocial stress. Purported mechanisms include residual inflammation and persistent changes in mucosally active cells, enteric nerves, and the GI microflora—adverse psychological factors are associated with persistent low-grade inflammation. The prognosis for patients with PI-IBS is somewhat better than for those with unselected IBS, but PI-IBS can still take years to resolve. There are no specific treatments for PI-IBS; these should be tailored to the predominant bowel disturbance, which is most frequently diarrhea.
Clinical Presentation and Course
Most patients experience the onset of symptoms well before age 40 years; about one half are younger than 30 years, and one fourth are younger than 20 years. The combination of abdominal pain and diarrhea and/or constipation helps to differentiate IBS from other forms of functional GI disease, in which only one feature is present. In about two thirds of IBS patients, either diarrhea or constipation may predominate.
Abdominal pain or discomfort is almost universal. In two thirds of patients, abdominal pain is reported most often in the left lower quadrant or lower abdomen; one third note upper abdominal pain, and one fourth experience it in multiple sites. The pain is typically achy rather than crampy and is often relieved by a bowel movement or the passage of flatus, and it usually does not disturb sleep. Pain radiation is variable and can extend into the left chest and arm when gas is trapped in the splenic flexure.
Constipation is a prominent complaint, characterized by small, hard, infrequent stools and an empty rectal ampulla. Prolonged retention of stool allows the full absorption of intestinal water content. About one third of patients report mucous stools, pellet-like stools, and/or excessive flatus. A constipationpredominant form of IBS occurs in about one third of patients, more commonly in men.
Diarrhea characteristically alternates with constipation; in about 10% of patients, diarrhea is the sole manifestation. The diarrhea is typically small in volume, associated with visible
amounts of mucus, and may follow a hard movement by a few hours. There may be urgency. In about one third of patients, a diarrhea-predominant form of IBS is noted, more frequently in women.
amounts of mucus, and may follow a hard movement by a few hours. There may be urgency. In about one third of patients, a diarrhea-predominant form of IBS is noted, more frequently in women.
Dyspepsia and excessive eructation are also reported, supporting the view of a process that involves the entire GI tract. Weight loss is rare. Intercurrent infectious gastroenteritis may trigger an exacerbation. Fifty percent of patients consider their symptoms to be related to stress, whereas one third deny it. Two thirds manifest symptoms of anxiety or depression. Rectal bleeding is absent unless there is coincident hemorrhoidal disease.
Chronicity is the rule, with little change in symptoms over time, except for waxing and waning. Duration is measured in years. There is no evidence of significant morbidity or mortality. Severity waxes and wanes, but the constellation of symptoms remains remarkably constant. In natural history studies, about 50% of patients are unchanged at 1 year, about 30% to 35% are improved (10% symptom-free), and 15% to 20% are worse. The symptom-free period is usually less than a few months. One third of employed IBS patients lose time from work. At 2 years of follow-up, a similar pattern is found. Persons with symptoms triggered by a major life stress enjoy long symptom-free periods after the acute problem abates, whereas those with continuous intestinal complaints in response to daily living rarely became asymptomatic.
Clinical Criteria for Diagnosis of IBS
The lack of an objective laboratory marker for IBS necessitates clinical criteria for diagnosis. The two most widely used and best-validated sets of criteria are those specified by Manning et al. in the late 1970s and the subsequently developed Rome Diagnostic Criteria (Table 74-1). These symptom-based criteria have been largely validated and are widely used for suggesting the diagnosis of IBS.
Although the sensitivity and specificity of the Manning criteria have, for the most part, been confirmed, there are some questions regarding the discriminating value of individual items. Consequently, the Rome Diagnostic Criteria were developed to overcome some of the shortcomings of the Manning criteria and are often used for patient selection in clinical studies.
TABLE 74-1 Diagnostic Criteria for IBS | ||||||||||||||||||||||||
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Some clinical situations require ruling out organic pathology that might resemble and be mistaken for IBS (see later discussion). Detailed history taking and careful physical examination, combined with selective parsimonious testing and a few diagnostic trials of therapeutic measures, will usually provide the best combination of completeness and cost efficacy.
Subgroups
Based on clinical presentation, subgroups are designated: IBS with diarrhea predominant, IBS with constipation predominant, and IBS with mixed bowel habits.
Differential Diagnosis and Overall Approach to Workup
Colon cancer, inflammatory bowel disease, celiac sprue, and ovarian cancer are the principal “must-not-miss” conditions that may mimic the presentation of IBS. Concern about such etiologies often precipitates the patient’s coming for evaluation. A detailed initial history and careful physical examination supplemented by a few simple laboratory studies (e.g., complete blood count) can address the diagnostic criteria for IBS and check for warning signs of more serious disease, helping to differentiate the IBS patient from one who needs more extensive workup for a mimicking must-not-miss condition. Colonoscopy and other expensive testing are not required for diagnosis unless symptoms and signs of worrisome pathology are elicited. Prospective studies with up to 30 years of follow-up for such an approach to IBS workup have shown only a 1% rate of missing the mustnot-miss conditions.
Alarm Symptoms.
Attention to the so-called alarm symptoms (weight loss, evidence of GI blood loss, anemia, fever, frequent nocturnal symptoms, positive family history of colon cancer, onset after age 50 years, sudden change in symptoms) helps to screen for the mustnot-miss conditions. Persons with IBS-like symptoms manifesting one of the alarm “symptoms” should not be labeled as having IBS until more extensive testing is conducted (see later discussion and also Chapters 58, 64, and 65).
When Constipation Predominates.
In this setting, it may be necessary to rule out a malignancy and Crohn disease, particularly in patients older than the age of 40 years who have an alarm symptom such as weight loss or a family history of colon cancer. In such patients, one needs to consider colonoscopy (see Chapter 65). In young persons, a stool test for occult blood and a complete blood count (for microcytic anemia) should suffice. The absence of evidence for GI blood loss helps to exclude organic disease. A test of thyroid-stimulating hormone is indicated to rule out hypothyroidism, which also may present as constipation. Patients taking diuretics should have serum potassium checked because hypokalemia may reduce bowel contractility and produce an ileus. A clinical trial of increased dietary fiber or an osmotic laxative (psyllium) complements the diagnostic assessment.
When Diarrhea Predominates.
Here, it is important to be sure that there are no symptoms suggestive of celiac sprue, inflammatory disease, and other important causes of chronic diarrhea (see Chapter 64). Once completed, a dietary review can be helpful, especially for evidence of intolerance to lactose or sorbitol. A check of blood sugar is needed to rule out diabetes mellitus (which may present as diarrhea due to diabetic gastroenteropathy; see Chapter 102), as is a check of the stool for ova and parasites. A diagnostic trial of eliminating sorbitol-containing candies and restricting lactose-containing milk products (yogurt containing live cultures is relatively lactose-free) helps to rule out contributions from intraluminal factors. A lactose hydrogen breath test is an
alternative means of testing for lactose intolerance. A trial of the bile acid-binding resin cholestyramine serves as a simple test for bile acid malabsorption.
alternative means of testing for lactose intolerance. A trial of the bile acid-binding resin cholestyramine serves as a simple test for bile acid malabsorption.
If diarrhea persists undiagnosed, a colonoscopy with or without mucosal biopsy might be reasonable to exclude inflammatory bowel disease and collagenous and lymphocytic forms of colitis (see Chapter 64). Because the clinical presentation can be mimicked by celiac sprue, testing for antiendomysial and/or tissue transglutaminase antibodies (see Chapter 64) is indicated when the possibility cannot be ruled out clinically; sensitivity is greater than 90% for these immunoglobulin A antibodies (see Chapter 64).
When Abdominal Pain, Distention, and Bloating Predominate.
In this setting, intermittent bowel obstruction, inflammatory bowel disease, celiac sprue, and pelvic pathology (especially ovarian carcinoma and endometriosis) require consideration. A plain film of the abdomen during an attack of severe pain should suffice to rule out obstruction. A complete blood count also helps to check for significant underlying bowel pathology. A negative serum determination for antiendomysial antibodies eliminates concern for celiac disease, especially when there is concurrent anemia. Transvaginal ultrasound is indicated when symptoms are of new onset or of increased frequency (almost daily) or severity, especially if they are accompanied by urinary tract or pelvic complaints (see Chapter 58). Such bloating and discomfort may also occur with lactose, fructose, or sorbitol intolerance, which can be tested for as detailed.
Psychological Assessment
Because underlying psychopathology is common in patients with IBS, therapy often requires identifying and addressing the patient’s psychological difficulties. In the context of conducting a thorough workup, the clinician needs sensitively to elicit details of the patient’s life situation, aspirations, accomplishments, frustrations, and losses. Concerns, fears, expectations, and responses to previous life stresses can also be very informative, as can the mental status of the patient on examination. Anxiety disorders are commonly identified (see Chapter 226), but depression (see Chapter 227) and somatization (see Chapter 230) often go unrecognized.
