Functional Gastrointestinal Disease

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[edit] Functional Gastrointestinal Disease

Richard I. Rothstein

Functional gastrointestinal diseases consist of varying combinations of chronic or recurrent symptoms with no identifiable physiologic, biochemical, infectious, anatomic, or structural cause. These disorders comprise a large percentage of primary care patient visits and account for about 40% of visits to gastroenterologists. A random survey of the U.S. population revealed that 69% reported having at least one of 20 defined functional gastrointestinal (GI) symptoms during the previous 3 months. With significant overlap, symptoms were attributed to four major regions: esophagus (42%), gastroduodenum (26%), bowel (44%), and anorectum (26%). In general, symptom reporting declined with increasing age, and low socioeconomic status was associated with increased symptom reporting. The rate of physician visits and work or school absenteeism was increased for those having a functional GI disorder.

The functional GI disorders encompass those related to the esophagus (globus, rumination, atypical chest pain), gastroduodenum (nonulcer dyspepsia, aerophagia), bowel (irritable bowel syndrome, chronic constipation, painless diarrhea, bloating/excessive gas, chronic abdominal pain), pancreaticobiliary tree (pancreaticobiliary dyskinesia, pancreatitis), and anorectum (proctalgia fugax, levator syndrome). The unifying pathophysiology for functional GI disorders is probably a primary disorder of gut motility. With no specific gold standard to assist in identification, these disorders require comprehensive histories, physical examinations, and laboratory studies. Diagnostic criteria for functional disorders based on epidemiologic and clinical research have enhanced diagnostic certainty and the ability to make a positive diagnosis rather than a diagnosis of exclusion.

The functional GI diseases share similar biopsychosocial models and a close relationship of psychophysiologic effect. Stress, anxiety, depression, and heightened emotional states affect symptom production and response (Fig. 110-1). The seeking of medical attention for functional symptoms may be prompted by increased frequency or severity of symptoms, reduced coping mechanisms or concomitant illness, or fear of serious illness. Individuals with functional complaints who seek medical attention have significant psychiatric disorders more frequently diagnosed than those who do not seek care. Psychologic factors influence the decision to seek health care, and examining the motivation for an office visit is a key step in evaluation and management.

Figure 110-1 La colique. Honoré Daumier, Paris, 1848.

[edit] IRRITABLE BOWEL SYNDROME

Some physicians use the term irritable bowel syndrome (IBS) to connote all the functional GI disorders, from globus to proctalgia fugax. IBS has provided a general diagnosis for complaints not attributable to organic disease. The sharedsimilarities of the various functional syndromes in pathophysiology and presentation have suggested the concept of the irritable gut or irritable person syndrome, with symptoms arising principally from global physiologic changes that accompany emotional tension. IBS is defined as a functional GI disorder attributed to the intestine and includes chronic or recurrent abdominal pain, altered bowel habit (consistency, frequency, feeling of incomplete evacuation), abdominal bloating with feelings of excessive intestinal gas, and mucus in the stools. These symptoms are continuous or intermittent and should be present for at least 3 months (Box 110-1).

[edit] Epidemiology and Etiology

The syndrome of IBS occurs in 15% to 20% of adults, with a predominance among women in the United States (nearly 2:1) but a reported predominance among men in other parts of the world (e.g., India). In the United States, no difference exists among racial subgroups. Symptoms usually begin in young adulthood and persist throughout life, although intermittently. The childhood GI disorder of recurrent abdominal pain may be equivalent in symptoms and pathophysiology to IBS, and about one third of affected children have IBS in adulthood. Less than half the people with irritable bowel symptoms seek medical attention and become patients with IBS. The overall prevalence of IBS in a population remains stable, although dynamic shifting occurs, with some individuals becoming asymptomatic and others developing symptoms or having a recurrence.

[edit] Pathophysiology

Pain in the lower abdomen, relief of pain on defecation, and passage of scybala (pelletlike stools) implicate irritability of the distal colon as a principal mechanism of IBS. Sigmoid contractions are paradoxically increased in patients with symptoms of constipation, causing increased segmentation and decreased propulsive movement, with resultant scybala and distention. Segmental contractions may be decreased in diarrhea-prone patients, with more rapid intestinal transit time. Abdominal pain in IBS most likely arises from areas of intestinal distention occurring proximal to areas of spasm.

Altered myoelectric activity of the colon, with a higher proportion of slow waves in the frequency range of 2 to 4 cycles per minute, has been reported for patients with IBS. The specificity of this marker has been questioned, however, since it also occurs in psychoneurotic patients who have no bowel symptoms. Small intestinal transit is more rapid in diarrhea-prone IBS patients, whereas it is prolonged in those with constipation and abdominal pain or distention.

An altered sensation of visceral pain may occur in IBS, with a lowered threshold for gut distention. Balloon distention of the lower bowel provokes pain in patients with IBS at volumes that do not usually cause symptoms in controls. Patients with IBS frequently complain of bloating and increased gas; however, studies have shown that IBS patients have abdominal symptoms with the same or lower colonic gas volumes as nonsymptomatic controls. Balloon distention at various sites along the large or small bowel during colonoscopy or during the passage of a small bowel tube resulted in the exact reproduction of right upper quadrant pain in a group of patients initially thought to have gallbladder symptoms. All patients had negative screening tests for gallbladder disease. This possibly explains the return or persistence of symptoms in patients who undergo cholecystectomy for right upper quadrant pain suspected to be biliary in origin, who may have had a silent gallstone but noisy gut.

The pathophysiology of IBS involves the enteric nervous system, visceral smooth muscle, and neurohumoral control of gut function. Symptoms arise as the lower gut participates in the total-body response to emotional arousal, as part of the fight-or-flight emergency reactions. Release of neurotransmitters and interchange of information from the central nervous system to the enteric nervous system modulate the activity of the bowel and its irritability. Measured alterations in bowel motility occur in response to such stimuli as eating, stressful interviews, and acute psychologic or physical stress. Measurement of sigmoid motility during hypnosis, using an indwelling transrectal manometric catheter, has provided information about brain-gut emotional relationships, with the ability to isolate an emotion (e.g., hostility, anger, sadness) and its related manometric pattern. The prevalence of psychologic symptoms and psychoneurotic personality traits in patients with IBS is higher than in non-IBS controls and, importantly, higher than in those with IBS who do not seek medical care. Depression, somatization, and frequency of consulting a physician for minor complaints (learned illness behavior) are found more frequently in patients than nonpatients with IBS. These psychologic factors relate to the health care–seeking behavior in patients with IBS and not to the illness itself. Patients presenting to primary care practices may demonstrate less somatization than those referred to gastroenterologists, although mood disturbances are often present in IBS patients visiting primary care settings.

The patient's total dependency needs must be recognized, including attitude toward illness and the sick role. Surveys of IBS patients and matched controls have shown that childhood physical, emotional, and sexual abuse occurred more often in IBS patients and that abuse was not confined to women. Childhood sexual abuse was associated with findings of depression, increased medical visits, and multiple somatic complaints in IBS patients.

[edit] Clinical Presentation and Patient Evaluation

A wide range of symptoms prompts the division of IBS into symptom-predominant subtypes, although it may be best considered as a single entity with variable manifestations. Patients who offer one of the predominant IBS symptoms (pain, constipation, diarrhea) as their chief complaint usually have all three symptoms after rigorous history taking and stool inspection. Dyspepsia, without organic explanation, affects most patients with IBS, and symptoms of esophageal dysfunction occur in 50%. The noncolonic GI symptoms of nausea, vomiting, dysphagia, and early satiety were found more often in IBS patients than in matched controls. In two studies of IBS patients and age-matched controls who were 90% to 100% female and middle aged, anxiety, fatigability, hostile feelings, sadness, and sleep disturbances were reported more often in the IBS group, as were palpitations, hand tremor, and fear of serious disease. Bladder dysfunction symptoms (nocturia, frequency and urgency of micturition, feeling of incomplete bladder emptying) were present more often in the IBS patients, as were the symptoms of back pain, unpleasant taste in the mouth, constant feelings of tiredness, and dyspareunia. This range of symptom reporting represents global physiologic responses and heightened emotional arousal.

The usual patient with IBS has had at least months of symptoms, and many relate a lifelong history of altered bowel habits and abdominal distress. New onset of IBS symptoms in an elderly patient should prompt a thorough examination for organic etiology, although prevalence of functional symptoms may be level throughout all age groups. Patients may describe the initial passage of a formed bowel movement, possibly after straining, with a sense of incomplete evacuation. Subsequent need to defecate results in several looser bowel movements, which may be described as diarrhea. Other patients may relate the passage of pelletlike stools and a changing frequency of bowel habits. IBS patients may report alterations in stool consistency, color, and shape. Patients may have long periods of normal stool habits and no abdominal symptoms, only to develop sudden recurrence of symptoms. Crampy lower abdominal pain, usually on the left, may be worsened or precipitated by eating (gastrocolic reflex); it is relieved, perhaps only transiently, by passage of flatus or stool. Some patients complain of bloating and being full of gas with variable increases in eructation or passage of flatus, although most do not have demonstrable changes in abdominal girth. Occasional patients have abdominal protrusion caused by contraction of the diaphragm and lumbar muscles.

Female patients may relate exacerbations of symptoms to phases of their menstrual cycle, with exacerbation of diarrhea often occurring during menstrual or premenstrual phases. About half of IBS patients may describe episodes of fecal or mucous incontinence, and many complain of stool urgency. Sleep disturbances may relate to exacerbation of symptoms. A history of rectal bleeding, weight loss, fever, and nocturnal diarrhea or pain awakening the patient from sleep is not part of IBS and should prompt investigation for other causes. Although bleeding may result from hemorrhoids or an anal fissure caused by straining from constipation, bleeding is not part of IBS and should always be fully investigated.

The physical examination in patients with IBS is usually normal, although fullness and tenderness may be found during palpation of the left lower quadrant, associated with sigmoid colon spasm and distention. This finding is not specific for IBS and may occur in diverticular disease. The digital rectal examination can help determine stool character. Patients with a chief complaint of diarrhea may have formed, hard scybalous stool in the rectal vault; an empty rectum can be found in constipated patients. A careful bimanual pelvic examination should be done for female patients with lower abdominopelvic pain to check for a possible gynecologic cause of symptoms (Box 110-2).

[edit] Laboratory Studies and Diagnostic Procedures

The range of symptoms of IBS encompasses those found in the organic diseases that form its differential diagnosis. Abdominal pain and altered bowel habit are common symptoms in a variety of GI illnesses, and a review of the disorders that produce symptoms of IBS should always be undertaken. When diarrhea is a predominant symptom, stool samples should be analyzed for fecal leukocytes and ova and parasites to check for infectious or inflammatory colitis. Depending on the specific clinical situation, a stool culture for enteric pathogens and assay for Clostridium difficile toxin may be sent. The stool Giardia antigen immunoassay requires only one sample and has excellent sensitivity and specificity.

In most patients, flexible sigmoidoscopy and stool analysis for occult blood are necessary diagnostic tests. Biopsy of the bowel mucosa to check for microscopic or collagenous colitis or possible mast cell disease may be considered. Young patients with infrequent symptoms and good response to initial treatments do not require endoscopic examination of the lower bowel. Those with diarrhea or who do not improve with initial treatment should undergo this procedure. Reproduction of the patient's usual abdominal pain during air insufflation of the sigmoid and its reduction with removal of the air and endoscope are typically elicited in IBS patients undergoing sigmoidoscopy. Any patient with rectal bleeding requires lower GI endoscopy because hematochezia is not part of IBS, and its source must be determined.

Lactose intolerance should be considered, since it may result in altered bowel habit, bloating, and excess intestinal gas and can be easily identified by the lactose hydrogen breath test or lactose tolerance test. An inexpensive lactose tolerance test involves asking the patient to drink a quart of milk at one sitting and record the ensuing gut symptoms, if any. This usually works better to identify lactose-related symptoms than the dairy-free diets sometimes recommended.

A complete blood cell count (CBC) is recommended to check for anemia or inflammation. Tests for thyroid disease, carcinoid, or other systemic disease are usually not done unless specific clinical indicators are present in the history or physical examination. Depending on the situation, barium enema studies or colonoscopy may be done to examine the proximal colon and ileocecal region. Localized pain and other features may dictate an ultrasound study of the gallbladder, liver, and pancreas; computed tomography (CT) scan of these organs; or imaging studies of the colon, as in suspected diverticulitis. Small bowel radiography may be done in patients with periumbilical pain and other symptoms possibly related to Crohn's disease. Some patients with constipation, especially those with laxative abuse or dependency, benefit from study of colonic transit, and those who complain of fecal incontinence may be studied with anorectal manometry. Dyspeptic patients may require upper GI radiography or endoscopy. Patients with unexplained diarrhea should have a stool sample alkalinized to check for phenolphthalein from surreptitious laxative abuse; a few drops of sodium hydroxide on a small stool smear results in a red color change if the laxative is present. Laxative abuse was the cause in about one third of patients who came to a tertiary medical center because of chronic diarrhea.

At present the minimal workup for IBS should include the history and physical examination of the stools, CBC, and in most patients, flexible sigmoidoscopy. Tests for lactose intolerance should be considered. Other possible tests should be reserved for specific clinical indicators based on patient age or should be done later if subsequent clinical information suggests alternative etiologies (Box 110-3).

[edit] Differential Diagnosis

The symptoms of IBS are not specific for it. Abdominal distress with altered bowel habit may result from many conditions affecting the GI tract. Complaints of diarrhea should prompt a search for lactose intolerance, an extremely common condition that can result in loosening of bowels, increased bowel frequency, increased intestinal gas and passage of flatus, and feelings of bloating. The amount of lactose load determines symptoms, and patients should look for a relationship between dietary intake and gut symptoms. Prevalence of lactose intolerance ranges from about 6% in white Americans to 75% to 90% in groups of Native Americans, African-Americans, and Asian-Americans. No relationship exists between lactose intolerance and IBS, and since both occur with relative frequency, they will affect some individuals concomitantly. Tests for lactase deficiency should be done, and if confirmed, most patients are easily managed with lactase supplements without altering dairy intake. Other patients may need to reduce the total intake of lactose-containing foods.

Giardiasis, sprue, Crohn's disease, bacterial overgrowth, and other small bowel disorders should be considered. Food intolerance, different from true food allergy, can cause abdominal pain and diarrhea in patients who are often atopic. Food diaries to record intake and symptoms may assist in discovering food relationships. The history taking should include possible sorbitol ingestion from sugarless gums, candies, or soft drinks, since many adults have sorbitol intolerance because of excessive intake and may experience abdominal pain, cramping, bloating, and altered bowel habit.

Abdominal symptoms arising from peptic ulcer disease or gallbladder disease are not generally accompanied by altered bowel habit and should not usually be confused with IBS. Upper GI radiography or abdominal ultrasound should be reserved for patients with an unclear clinical picture. Inflammatory bowel disease, and less often, infectious colitis, may give rise to symptoms simulating IBS. The common feature of hematochezia in ulcerative colitis separates it from IBS, which lacks rectal bleeding. Collagenous colitis, microscopic colitis, and eosinophilic gastroenteritis are unusual disorders with features overlapping those of IBS, with chronic diarrhea and abdominal discomfort predominating. Symptoms of diarrhea, abdominal pain, urinary frequency, headache, flushing, hives, and dermatographia are seen in some patients with mast cell–mediated disease, and increased numbers of mast cells may be found in colonic or terminal ileal mucosal biopsies. Lower abdominal pain may arise from pelvic processes (e.g., ovarian cysts, pelvic inflammatory disease, endometriosis) and can be investigated with pelvic examination, ultrasound, or CT scan.

Constipation may result from anatomic obstruction (e.g., bowel malignancy), a medication side effect, or sigmoid spasm in diverticulosis. It may be part of idiopathic pseudoobstruction, Hirschsprung's disease, or a sequela of laxative abuse. Sigmoidoscopy allows screening for luminally obstructing processes, the presence of diverticulosis, or melanosis coli (resulting from laxative abuse). Since the pathophysiology of colonic diverticulosis involves sigmoid spasm and segmentation, some patients with diverticulosis have symptoms similar to those of IBS patients, and the two disorders may coexist. The majority of patients with diverticulosis are asymptomatic. Patients with constipation and abdominal symptoms since infancy should be considered for anorectal manometry to determine the presence of reflex internal sphincter relaxation, which is absent in Hirschsprung's disease.

The physician must avoid extensive, expensive, repetitive, or hazardous workups in approaching an IBS diagnosis as a diagnosis of exclusion. Using a strict definition for IBS and following a limited workup, investigators have shown that a positive diagnosis can be made with excellent reliability. Positive historic features favoring the functional diagnosis of IBS include (1) pain eased by a bowel movement, (2) looser stools and more frequent bowel movements at onset of pain and abdominal distention, (3) scybala, (4) diarrhea alternating with constipation, (5) passage of mucus, and (6) absence of weight loss. A normal screening CBC and flexible sigmoidoscopy confirm the diagnosis. Rectal bleeding, fever, anemia, evidence of malnutrition, and other atypical features in presentation or laboratory findings are not part of the IBS and should prompt investigation into the differential diagnosis (Table 110-1).

Table 110-1 Differential Diagnosis of IBS

[edit] Management

The physician-patient relationship is important in caring for patients with IBS. A willingness to provide ongoing care, with appropriate consultation as indicated, is prerequisite for successful management. Many patients search for an explanation of their symptoms and might be shunted around a primary care physician as multiple specialists do extensive medical investigations or invasive surgery.

The initial encounters should provide adequate time for exploration of symptoms and explanation of GI function and dysfunction. Some patients are able to correlate the onset or recurrence of symptoms with critical or stressful life events. Many IBS patients demonstrate excessive somatic focusing and more health-related fears, a common feature of patients in referral practices. They complain of more nongastrointestinal symptoms and more frequently utilize health care services than their IBS counterparts who tolerate their symptoms without consulting a physician. This illness behavior may be based on familial factors, such as learning a sick role, being reinforced for symptoms, or even undergoing physical or sexual abuse. A significant minority of patients meet the criteria for a psychiatric illness (e.g., depression, anxiety, somatoform disorder, posttraumatic stress disorder), which should be recognized and managed. IBS patients in primary care practices may demonstrate less chronic somatization than those in referral gastroenterology practices, although mood disorders are common in IBS patients at primary care sites.

A positive diagnosis of IBS must be established beginning with the first encounter if it appears to be the reason for the patient's symptoms. Confidence minimizes the desire for more testing “to be sure no other hidden disease exists” to explain the symptoms. Scheduling return visits demonstrates an ongoing interest, and follow-up encounters enable the assessment of changes in clinical features and response to treatment. As the clinical course progresses, less frequent and shorter appointments are needed as the patient responds to treatment and gains an understanding of the disease.

The impact of irritable bowel symptoms on the quality of a patient's life is often underrecognized or insufficiently explored. In a group of patients, two thirds of whom were female with a mean age of 45 and mean duration of symptoms of 7 years, the reported areas impacting quality of life were activities and schedules, diet and nutrition, lack of social support and interpersonal relationships, and mood changes. Patients were concerned about not being taken seriously, being told “it's in your head,” undergoing many tests without adequate explanation, and a perceived lack of physician concern for their symptoms. Many of these issues are easily avoided through adequate patient education and empathic listening. Failure to attend to these issues contributes to “doctor shopping” and alternative health care venues.

Management of IBS may involve dietary, pharmacologic, and psychologic intervention (Box 110-4). The intermittent nature of IBS directs intervention to symptomatic relapses and to strategies for management of its chronic forms. Patients with IBS have a marked placebo response rate, and many interventions appear successful, at least initially. Patients need to be reassured that the disorder is benign, waxes and wanes, has an excellent prognosis, and is not related to colon cancer. Although most patients respond to reassurance and supportive therapy, along with symptom-specific medical treatment, some require frequent telephone or office contact. The dependency issues in these patients are related to their more common psychopathology, especially neuroticism and hypochondriasis. When psychiatric disease is identified in IBS patients, appropriate referral is indicated.

Specific dietary recommendations involve lactose avoidance for IBS patients who also have lactase deficiency, or they may use lactase supplements when eating foods containing dairy products. Yogurt and aged cheeses may be better tolerated because lactose is diminished by the microbial action in those products. Specific foods that trigger symptoms should be avoided. For some patients with either constipation or diarrhea, bulking the stools with fiber may be helpful through increased bran in the diet. A significant number of patients are intolerant of excessive bran, however, and develop bloating and increased intestinal gas. The fiber supplements of hydrophilic colloid (psyllium, methylcellulose) may be better tolerated and can be ingested as liquids, tablets, or even cookies. Patients with constipation and those taking fiber supplements should be encouraged to drink at least 2 quarts of fluid each day. Bland or restrictive diets do not generally benefit the IBS patient and may be harmful over time.

Although patients with an initial complaint of constipation, diarrhea, or abdominal pain have all three identified after careful questioning and physical examination, medication therapy should focus on the chief complaint. Patients with abdominal cramps or spastic abdominal pain may obtain benefit from anticholinergic agents, which function to diminish sigmoid contractility and decrease intestinal distention occurring proximally. Hyoscyamine and dicyclomine are frequently prescribed for this effect, and patients need to be aware of the side effects of dry mouth, dizziness, and possible blurred vision. Anticholinergics coupled with minor tranquilizers (e.g., phenobarbital, chlordiazepoxide) may be of benefit for patients with anxiety, although controlled trials demonstrating clinical efficacy are lacking. The natural antispasmodic peppermint oil may be of benefit; its encapsulation allows dissolution distal to the stomach to avoid the possible side effect of pyrosis, caused by lowering of esophageal sphincter tone if the oil is released at a higher level. Tricyclic antidepressants can help manage symptoms of abdominal pain, perhaps because of their anticholinergic effect and central effects.

Diarrhea may be controlled with diphenoxylate or loperamide; the latter is particularly useful with concomitant fecal incontinence. Some patients benefit from stool bulking to solidify their looser stools; calcium supplements are potentially useful, as are cholestyramine and cholestipol. Although diarrhea may not be fully controlled with these measures, urgency and frequency may be reduced. Some patients with diarrhea may also benefit from treatment with the tricyclic antidepressants. Long-term use of paregoric or codeine is not recommended. The new 5HT₃ antagonist, Alosetron, has been shown to be of benefit in diarrhea-predominant women with IBS.

Constipation in IBS usually responds to bulking agents, increased fluids, and exercise. Stool softeners (dioctyl sodium sulfosuccinate) are of occasional benefit, but patients should be counseled to avoid long-term use of laxatives. Infrequently a patient may require treatment with lactulose or polyethylene glycol and electrolytes (colonoscopy prep solution) to enhance colonic transit. Initial use of enemas may help wean a patient from laxative use.

For patients with intestinal gas or bloating, specific food avoidance (e.g., leguminous vegetables, beans) may be of benefit. The yeast-derived enzyme food supplement Beano, marketed to diminish intestinal gas production, is not likely to offer benefit, nor will simethicone products, whose target is gas bubble dissolution in the upper GI tract. Activated charcoal capsules taken with meals can reduce intestinal fermentation and gas production, although patients should be advised that charcoal will darken their stools.

Psychotherapy, behavioral therapy, and hypnotherapy offer alternative approaches or can assist in management of the IBS patient. Compared with continued medical therapy, dynamically oriented short-term psychotherapy is more likely to reduce abdominal pain and bowel dysfunction. Patients refractory to at least six different therapeutic regimens over a year or more had significantly improved symptoms of abdominal pain and bowel irregularity after hypnosis compared with medically treated controls. The improvement persisted in long-term follow-up and in patients who underwent group hypnotherapy. Behavioral therapies such as biofeedback have met with mixed success and may be considered.

The future management of IBS may include therapies directed at neuroendocrine manipulation (e.g., leuprolide, 5HT-receptor antagonists) or prokinetic motility stimulation, but further clinical evaluation is needed. No one management strategy works for all patients. Directing therapy at the initial or chief complaint should effect symptom relief and may permit identification and modification of stressful situations. Patients need to be educated about the relationship of IBS symptoms to diet and stress. Although most patients with IBS can be managed completely in a primary care practice, referral to a gastroenterologist should occur when endoscopic examination is anticipated, when the patient fails to respond to initial therapies, for second opinions, and for periodic follow-up assessments. The primary care physician serves a critical role as health adviser and counselor for the patient with IBS, and the most important tool of management is the ongoing, supportive physician-patient relationship.

[edit] GLOBUS

The sensation of a lump or ball in the throat that occurs independently of the act of swallowing is called globus. Typically this sensation is present all the time and seems to interfere with swallowing and breathing. Often the onset may follow a swallowing event in which the patient believes a food item may have gotten stuck or caused irritation, such as a fishbone or seed. Many individuals with globus sensation relate significant stress or anxiety as a precipitant to symptom onset. Globus can be a common complaint; it was experienced by about one third of patients with IBS, was present in 18% of a control group of women in a gynecology clinic, and accounted for 4% of new otolaryngologic clinic appointments. In younger patients, globus was three times more prevalent in women than men, but after age 50 the prevalence is equal.

Although its pathophysiology is not understood, globus sensation is presumably caused by cricopharyngeal spasm, which may occur during heightened emotional arousal. A tense individual may become aware of the previously subconscious act of swallowing; coupled with anxiety-related reduction of saliva, this may result in further tension and spasm. Manometric studies to document increased cricopharyngeal tone have been contradictory. In about one fourth of globus patients, abnormal gastroesophageal reflux may be present, although the nature of its association or its relationship to symptoms is not clear.

Globus should be differentiated from true dysphagia, which may be high, with difficulties in initiating a swallow, or may be low, with the typical symptom of food or pills lodging substernally in the esophagus. A careful history allows separation of globus from dysphagia, the latter occurring only with swallow attempts (Table 110-2). If high or low dysphagia is suspected, investigation should identify an anatomic obstruction or motility disorder. Barium radiography, laryngoscopy, upper GI endoscopy, esophageal manometry, and other specialized tests may identify oropharyngeal or cricopharyngeal disorders, esophageal stenosis from ring or stricture, or possible motility disorder. The workup for globus may involve cineradiography to evaluate the swallowing function and to provide reassurance. Globus sensation may occur in some patients with reflux esophagitis.

Table 110-2 Comparison of Globus and Dysphagia

Management of the globus sensation requires adequate explanation of the mechanism of symptom production and reassurance. Some patients with gastroesophageal reflux disease (GERD) may benefit from acid suppression or prokinetic agents. Treatment of globus sensation is often difficult, and recurrence is common. Determining stressful trigger events and providing supportive therapy may be helpful. Some patients benefit from treatment with antidepressants, behavioral therapy, or psychotherapy.

[edit] RUMINATION

Rumination, also called merycism, involves painless regurgitation of swallowed food into the mouth. The regurgitated food is rechewed and reswallowed; this behavior does not upset the individual, who considers the regurgitated material pleasant tasting. The process is involuntary, usually begins shortly after meals, lasts about a half hour, and decreases as the regurgitant material changes its taste from increased acidity. In contrast to vomiting, rumination is not associated with nausea. In contrast to GERD, patients have no pain. The motility of the esophagus and stomach is normal in ruminators. The habit begins in childhood, sometimes persisting into adulthood. Although this behavior is unusual, within certain families it may be fully acceptable, with familial ruminators developing in several generations. Rumination appears to be a learned behavior and is upsetting to the patient only when it results in social embarrassment. It is important to distinguish rumination from vomiting or GERD to avoid unnecessary treatments. Some ruminant patients respond to behavioral therapies.

[edit] ATYPICAL CHEST PAIN

Patients with chest pain are regularly evaluated in primary care practices and emergency departments. Diagnosing possible coronary artery disease is the first step in the evaluation of chest pain, resulting in about 600,000 coronary arteriograms annually in the United States. With up to one third of these examinations having normal results, about 200,000 new cases of noncardiac chest pain are diagnosed each year. The number is actually higher, since younger patients or those without classic anginal symptoms do not undergo catheterization. Within this group of noncardiac chest pain patients, about one third have an esophageal cause of the pain after investigation, with GERD a more common finding than esophageal dysmotility or spasm. Noncardiac chest pain assumes the exclusion of valvular heart disease and pericarditis; disorders of the lung or pleura (tumor, pleurisy) and chest wall conditions of musculoskeletal origin (costochondritis) are part of the differential diagnosis.

The term chest pain of unknown origin (CPUO) is used to describe a chest pain syndrome without a discernible cause. The pain is often atypical for classic angina. Patients with CPUO have a high prevalence of anxiety disorders, depression, somatization, and perceived vulnerability to serious heart disease. High levels of neuroticism and poor coping strategies are found in some CPUO patients, with less symptom improvement, more frequent pain episodes, and greater social maladjustment. Patients with CPUO may have a lower threshold to visceral sensation and may interpret normal physiologic events as uncomfortable. Studies incorporating balloon inflation in the esophagus show that CPUO patients experience chest discomfort at significantly smaller balloon volumes than do asymptomatic volunteers. The pathophysiology of CPUO may parallel that for IBS, with a lowered threshold to visceral stimulation (sensing distention above an area of spasm), induction of abnormal motility during acutely stressful stimulation, a close relationship with emotional arousal, and similar psychometric profiles for personality characteristics. About one third of CPUO patients have panic disorder, with features of tachycardia, sweating, dyspnea, dizziness, hot flashes, nausea, choking, trembling, depersonalization, paresthesias, fear of dying, or fear of “going crazy.”

The diagnostic investigation for a patient with chest pain involves a careful history and physical examination (checking for chest wall tenderness), an electrocardiogram (ECG), and a chest radiograph. Echocardiography may be indicated, and treadmill exercise tolerance testing evaluates for a possible cardiac origin of symptoms. Some patients need referral to cardiologists for assessment and coronary catheterization. Microvascular angina (syndrome X) may be diagnosed during atrially paced coronary catheterization, as may coronary spasm during ergonovine stimulation. When coronary disease is ruled out as the cause of chest pain, or if the pain is accompanied by esophageal symptoms initially (e.g., dysphagia, reflux), esophageal investigation should be performed. Upper GI radiography or endoscopy provides information on possible GERD. Endoscopy allows acquisition of esophageal biopsies for histologic evidence of reflux esophagitis, even when the endoscopic view is normal. Referral to a GI motility laboratory for ambulatory 24-hour pH probe testing allows quantification of esophageal acid exposure and correlation of reflux events to symptoms. Stationary or ambulatory esophageal motility testing may reveal a baseline dysmotility associated with the chest pain (e.g., achalasia, diffuse spasm, nutcracker esophagus), and provocative testing with edrophonium or balloon inflation may implicate a probable esophageal cause for symptoms.

The differential diagnosis for CPUO includes the disorders just reviewed with consideration of peptic ulcer disease, biliopancreatic disease, IBS, upper GI malignancy, and panic disorder.

Management of patients with CPUO begins with the reassurance that none of the determinable disorders that cause its symptoms has been found. Patients should be educated about the possible mechanisms of pain production and assessed for psychologic disease. They should know that the prognosis in CPUO is excellent, with no increased risk of mortality. Patients with reflux-type symptoms or evidence of increased esophageal acid exposure may benefit from acid suppression or prokinetic medications. If esophageal motility changes are evident on manometric studies or by clinical suspicion, nitrates, calcium channel blockers, or anticholinergics should be tried. Some patients may respond to low-dose anxiolytics or to antidepressant therapies. Behavioral therapies may also be of benefit for some patients with CPUO.

[edit] AEROPHAGIA

Aerophagia means excessive air swallowing followed by belching. Normal individuals swallow approximately 2 to 3 ml of air with each swallow, accumulate air in the gastric fundus as a bubble, and intermittently eructate (burp). After a meal or the ingestion of carbonated beverages, large amounts of gas may be belched from the stomach, and depending on the norms of a society, burping may be socially appropriate and expected or inappropriate and discouraged.

Patients with aerophagia complain of excessive stomach gas and feel bloated after meals. They may have abdominal pain or dyspepsia in addition to distention. Eructating seems to offer relief of symptoms, and the patient complains of constant need to belch, which can be accompanied by some regurgitation. Individuals with aerophagia may believe that their gas results from poor digestion or fermentation. Although these two mechanisms account for production of gas in the colon, gas in the stomach is primarily derived from swallowed air and has a composition similar to that of room air. Anxiety increases the frequency of swallowing and may contribute to the excess ingestion of air.

Patients with aerophagia should be observed during the initial visit for repetitive air swallowing, which usually precedes a belch. The mechanism of air intake into the esophagus and stomach, with forced expulsion, can be easily explained by making the person aware of the activity. Attention during eating often reveals excessive air intake, with slurping of some foods or high intake of carbonated drinks.

The symptoms of bloating, abdominal distention, pain, and eructation may be found in other GI conditions, such as peptic ulcer disease, giardiasis, and IBS. Some of these symptoms may be seen in patients with GERD, gallbladder disease, and gastroparesis. Bloating, distention, and abdominal pain with increased flatus but not excessive eructation are characteristic of lactose intolerance and some malabsorptive diseases. In select patients, barium radiography, abdominal ultrasound, upper GI endoscopy, and tests of lactase deficiency may be indicated. Most patients require minimal workup, especially if active air swallowing is witnessed during the initial encounter.

Patients with aerophagia should be educated about the origin of their symptoms. Pointing out each air-swallowing event, as observed during the office visit, can demonstrate the mechanism and frequency of aerophagia to the patient. An explanation of the mechanism of esophageal speech taught to patients with laryngectomies is often helpful in understanding air intake and belching. The physician's demonstration of air swallowing and belching can be effective. Patients must be more aware of the frequency of their maladaptive behavior, and this awareness often reduces the frequency of air swallowing. Simethicone, with an ability to coalesce smaller air bubbles into larger ones, does not reduce total ingested air but does offer significant placebo effect. Again, reassurance and education provide impressive benefit in managing patients with aerophagia.

[edit] PANCREATICOBILIARY DYSKINESIA

Dysfunction of the sphincter of Oddi can result in biliary and pancreatic disorders. Biliary dyskinesia results in elevated common duct pressure because of increased sphincteric resistance to bile flow, either from sphincter stenosis, hypertonicity (spasm), or dyssynergic motility. Sphincter stenosis may occur from passage of a stone, with resultant papillitis and fibrosis. Dysfunction of the sphincter from spasm or abnormal contractile activity has been variously termed tachyoddia, sphincterismus, and dyssynergia. Abdominal pain is presumed to develop when elevated bile duct pressure is transmitted to liver ductules. Cholecystectomy removes the capacitor for bile storage, with more direct pressure changes exerted on the proximal biliary tract, and biliary dyskinesia should be considered in the evaluation of the postcholecystectomy syndrome. Sphincter of Oddi dysfunction has also been implicated in the pathophysiology of pancreatitis and pancreatic pain.

Pancreaticobiliary dyskinesia most often affects women and is usually seen after cholecystectomy. Other functional GI disorders are frequently found in patients with biliary dyskinetic syndromes, including IBS, esophageal dysmotility, and gastroparesis. Dyskinetic patients have more neuropsychiatric complaints and increased somatization scoring on psychometric testing than controls, as well as increased incidence of temporomandibular joint syndrome and hysterectomy.

Most patients with biliary dyskinesia report a recurrence of the same pain that led to gallbladder removal. The pain is usually episodic, located in the epigastrium or right upper abdominal quadrant, and may radiate to the back or flank. The pain in some patients is more chronic, with variations in intensity. Pancreatic dyskinesia may produce chronic or intermittent pancreatic-type pain, epigastric in location with radiation to the back. Initial diagnostic studies to define pancreaticobiliary dyskinesia include screening for elevations in liver function tests or in amylase and lipase during or after pain episodes and ultrasound for a dilated common bile duct or pancreatic duct. Referral for endoscopic retrograde cholangiopancreatography (ERCP) allows definition of ductal anatomy and bile duct drainage time, and some specialists can perform sphincter of Oddi manometry along with ERCP to determine ductal pressures and sphincteric function. Diagnosis of pancreaticobiliary dyskinesia is based on the history of classic symptoms, with elevated liver or pancreatic enzymes, dilated biliary or pancreatic ducts, and often delayed ductal drainage at ERCP. Sphincter of Oddi manometry has become a gold standard to demonstrate elevated ductal pressures and dysfunction of sphincter motility. The differential diagnosis includes other disorders of the biliopancreatic ducts (e.g., stones, strictures, tumors). Patients with postcholecystectomy pain should be reevaluated for possible IBS or peptic diathesis.

Management of pancreaticobiliary dyskinesia includes pharmacologic agents that lower sphincteric tone (calcium channel blockers, nitrates, anticholinergics). Pancreatic enzyme supplementation may lessen pancreatic pain by suppressing pancreatic exocrine secretion and decreasing ductal pressure. Endoscopic sphincterotomy and surgical sphincteroplasty are effective in reducing or alleviating symptoms in selected patients with elevated sphincter of Oddi pressures determined by manometry. Patients with pancreaticobiliary dyskinesia should benefit from the behavioral and supportive therapies found useful in the other functional disorders.

[edit] CHRONIC ABDOMINAL PAIN

Chronic functional abdominal pain is defined as pain persisting at least 6 months for which no defined cause is discernible after extensive review of the history, physical examination, and laboratory testing. The majority of patients with this syndrome are women, and many had chronic abdominal pain as children. The true prevalence is not known, but patients with this disorder are frequent users of the health care system, often for multiple chronic pain syndromes (see Chapters 14 and 107 ).

Pain is usually reported to be present constantly and not related to positional changes, diet, eating, or defecation. The patient may have fixed beliefs about the cause of the pain that do not correlate with anatomic or physiologic processes. Increased symptom reporting is usually associated with heightened stress and emotional arousal. Many patients with chronic pain have experienced sexual or physical abuse in childhood. Some individuals manifest depression, and somatoform disorders are often present.

The physical examination usually elicits pain with palpation of the abdomen but without focality. Patients asked to demonstrate the area of pain with one finger often rub the entire abdomen with the whole hand. Multiple surgical scars are often present. The laboratory evaluation should be directed at symptoms suggestive of particular organ systems, and often patients are extensively studied. It is important to review prior studies and avoid unnecessary repetition.

The differential diagnosis is extensive; however, features of the history and laboratory should guide the appropriate workup (Table 110-3).

Table 110-3 Differential Diagnosis of Chronic Abdominal Pain

Management of patients with chronic pain is best accomplished with a multidisciplinary team approach including the primary care physician and referral specialists. Some institutions have a pain clinic with a coordinated program of analgesic, behavioral, psychologic, and medical management. The physician should establish an ongoing relationship with the patient and provide reassurance. Goals should focus on minimizing the impact of the illness on the patient and family and not on curing the illness. The patient must be an active participant in the treatment process. Various pharmacologic agents have been used in managing chronic abdominal pain, including opiate analgesics, tricyclic antidepressants, and anxiolytics. Psychologic treatments have encompassed behavioral therapy, psychotherapy, and hypnotherapy. Chemical or surgical nerve destruction has been successful in some patients with intractable chronic abdominalpain, and transcutaneous electrical nerve stimulation (TENS) and acupuncture have helped others. Relaxation training and biofeedback techniques are useful adjuncts in comprehensive multidisciplinary treatment.

[edit] CHRONIC CONSTIPATION AND LAXATIVE ABUSE

Chronic constipation is a common disorder that can lead to chronic laxative abuse and resultant colonic dysmotility. Constipation in IBS often alternates with diarrhea and is associated with abdominal pain, whereas chronic functional constipation may be painless and constant. Some patients with lifelong symptoms may defecate once weekly or even less frequently. Individuals with chronic constipation often begin their symptoms in childhood, related to improper toilet training, lack of bathroom privacy, or embarrassment. With suppression of the normal urge to defecate the rectum fills with stool and becomes capacious. Subsequent stool passage may be painful due to hardness or volume of the feces or because of an associated anal fissure or inflamed hemorrhoid. This prompts further stool holding and leads to reduced rectal sensation of the urge to defecate. The capacious rectum affects normal anorectal reflex relaxation of the internal sphincter, requiring ever-increasing volumes of rectal contents to trigger this initial defecatory event. Some children and elderly patients may develop encopresis, described as involuntary fecal incontinence resulting from overflow of looser stool past a full rectum. Encopresis in childhood is usually accompanied by behavioral or personality changes and may be secondary to significant family psychopathology. Occasionally, elderly patients have an associated stercoral ulcer of the rectum.

Constipation in adult patients is usually related to dysfunction of the colon in one of three patterns: pancolonic inertia, sigmoid spasm, or anorectal dysmotility. Pancolonic inertia may result from neuropathic illnesses, medication side effects, or laxative abuse. Sigmoid spasm is a mechanism for diminished bowel transit in IBS or diverticulosis, resulting from paradoxic hypermotility of the left colon and excessive segmental contractions. Anorectal dysmotility may result from rectal distention and diminished rectal sensitivity or from failed relaxation of the internal sphincter with megacolon in Hirschsprung's disease. Hirschsprung's disease involves congenital absence of ganglion cells in a segment of bowel wall, with resultant chronic segmental contraction and failure of relaxation of the anal sphincter. The colon dilates above the hypertonic segment with ensuing megacolon. The affected segment varies in length and usually produces symptoms in childhood or adolescence, although some individuals with short-segment involvement might not show symptoms until adulthood. Treatment involves surgical resection of the aganglionic segment.

The diagnostic evaluation in chronic constipation involves a complete history and physical examination, with attention to signs of possible metabolic or neurologic illness. The digital rectal examination may reveal a fecal impaction in the rectum and defines the anal sphincter. Patients with Hirschsprung's disease have large amounts of stool in the colon but none palpable with the examining finger, whereas patients with functional constipation but not IBS usually have abundant stool felt in the rectum by digital examination. Anoscopy is important to search for an anal fissure if painful defecation is present. Flexible sigmoidoscopy permits screening for left-sided colonic lesions associated with obstruction (e.g., neoplasia, stricture, myochosis [spastic, thickened bowel wall] with diverticulosis). Endoscopy can reveal melanosis coli, a brown pigment found in the colonic wall in patients who chronically ingest anthroquinone laxatives (e.g., senna, cascara, aloe). Barium enema examination depicts form and function of the colon, and plain radiographs are helpful to quantify stool content and distention of bowel loops.

The most important examination in chronically constipated patients may be the marker study of colonic transit. Patients ingest a gelatin capsule containing 20 plastic opaque 1-mm rings, and the progress of these markers is documented with plain abdominal films over the next 5 days. Patients must not take laxatives and should supplement their diets with 30 g of fiber daily, beginning 3 days before swallowing the marker capsule and throughout the radiographic study. The location of the markers at the end of 5 days directs further investigation and management: for pancolonic inertia if the markers are scattered throughout the colon, for sigmoid spasm or obstruction if markers pile up at the left colon, and for possible Hirschsprung's disease if markers make it to the rectum but do not exit by the end of the study. If Hirschsprung's disease is suspected, anorectal manometry is done to investigate sphincter function. Often, all markers are gone from the intestine by day 5, indicating normal colonic function, and patients attribute an improvement in their symptoms to fiber supplements. Fiber then becomes a basis for treatment.

The differential diagnosis for constipation is broad, but the usual chronic nature of functional constipation allows it to be distinguished from metabolic, neurologic, or anatomic causes. Appropriate evaluation screens for these other etiologies.

The management of chronic constipation begins with educating the patient about the physiology of defecation and the pathophysiology of constipation. Bowel retraining should be instituted, with encouragement to visit the toilet after a meal, taking advantage of the gastrocolic reflex, and regular exercise to help stimulate colonic transit. Judicious use of laxatives initially may assist in regularizing the bowel habit, but long-term use is prohibited. High intake of supplemental fiber (e.g., bran, hydrophylic colloid) is safe and effective and should be accompanied by generous intake of fluids. Dried fruits and fiber-rich fruit juices are excellent adjuncts. Stool softeners or glycerin suppositories are of occasional benefit. Some patients require initial and periodic enemas to help empty the lower bowel, but chronic enema therapy should not be necessary. Long-term management may include daily lactulose, a nonabsorbed carbohydrate fermented by colonic bacteria that results in increased stool fluidity and colonic output. A rare patient may require intermittent use of colonoscopic prep solutions (polyethylene glycol with electrolytes), with small daily amounts effecting increased stool output. All treatment regimens need to be individualized, and response depends on duration of symptoms, antecedent laxative abuse, and general activity status.

[edit] LEVATOR SYNDROME

The levator syndrome is characterized by a dull ache or firm pressure felt higher in the rectum than the anal location of proctalgia. More women than men experience this discomfort, usually in middle age. Unlike the fleeting pain inproctalgia fugax, patients with levator syndrome, also called coccygodynia, experience pain for hours to days. The pain is most often constant or rhythmic and may be likened to sitting on a ball or feeling like a ball (or corncob) was inside the rectum. Precipitants include defecation, sexual intercourse, sitting for long periods, and stress or anxiety. The pathophysiology probably involves spasm of the pelvic floor muscles.

Digital rectal examination in levator syndrome demonstrates tender rectal muscles. Palpation of the coccyx may reveal tenderness or excessive mobility from traumatic injury, suggesting an alternative diagnosis. As with proctalgia, patients with levator syndrome should undergo flexible sigmoidoscopy to screen for other anorectal diseases. Careful pelvic and prostate examinations need to be conducted, and ultrasound or CT scan of the pelvis may be warranted.

Management of levator syndrome and proctalgia fugax has included digital puborectal muscle massage, sitz baths, electrogalvanic stimulation, and biofeedback training utilizing electromyography. Medications that may help control symptoms include muscle relaxants, nonsteroidal antiinflammatory drugs, and calcium channel blockers.

[edit] ADDITIONAL READINGS

• TP Almy, RI Rothstein: Irritable bowel syndrome: classification and pathogenesis. Annu Rev Med 1987; 38:257.
• M Camilleri, CM Prather: The irritable bowel syndrome: mechanisms and a practical approach to management. Ann Intern Med 1992; 116:1001.
• DA Drossman, WG Thompson: The irritable bowel syndrome: review and a graduated multicomponent treatment approach. Ann Intern Med 1992; 116:1009.
• DA Drossman,et al.: Identification of subgroups of functional gastrointestinal disorders. Gastroenterol Int 1990; 3:159.
• RB Lynn, LS Frieman: Current concepts: irritable bowel syndrome. N Engl J Med 1993; 329:1940.
• NJ Talley, SF Philips: Non-ulcer dyspepsia: potential causes and pathophysiology. Ann Intern Med 1988; 108:865.
• WG Thompson, H Pigeon-Reesor: The irritable bowel syndrome. Semin Gastrointest Dis 1990; 1:57.
• WE Whitehead, MD Crowell, MM Schuster: Functional disorders of the anus and rectum. Semin Gastrointest Dis 1990; 1:74.
• J Zighelboim, NJ Talley: What are functional bowel disorders?. Gastroenterology 1993; 104:1196.