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Diagnostic approach to the patient with irritable bowel syndrome
Diagnostic Approach to the Patient with Irritable Bowel Syndrome Max W. Schmulson, MD, Lin Chang, MD
Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder characterized by abdominal pain or discomfort and alterations in bowel habits. In clinical practice, diagnosis is based on positive symptoms known as the Rome criteria and limited diagnostic screen, taking into account warning features suggestive of organic disease. Minimal diagnostic tests are warranted to rule out structural lesions in a cost-effective manner and to convince the patient of the diagnosis of IBS. An initial diagnosis of IBS is safe and rarely needs revision over time. Persistence of symptoms is to be expected and does not justify suspicion of other diagnoses. Only change in the clinical pattern over time justifies additional investigations. Other diagnostic evaluations depend on predominant symptoms, namely constipation, diarrhea, and pain or discomfort. It should be emphasized that although an initial “positive diagnosis” is safe to exclude other diseases with similar symptoms, a common disorder such as IBS may often coexist with other asymptomatic disorders. Am J Med. 1999;107(5A):20S–26S. © 1999 by Excerpta Medica, Inc.
I
rritable bowel syndrome (IBS) is a chronic functional bowel disorder of unknown origin characterized by abdominal pain or discomfort and alterations in bowel habits. It affects up to 20% of the US population, producing considerable costs to society in terms of work lost, consultation, unnecessary tests, and inappropriate management, and even unnecessary surgery.1,2 Diagnosis is based on identifying positive symptoms and warning features suggestive of organic disease and excluding other conditions in a cost-effective manner using minimal diagnostic studies. In this article we review diagnostic approaches to the patient with IBS.
CRITERION-BASED DIAGNOSIS: THE ROME CRITERIA The symptom-based criteria, known as the Rome criteria (see article by Hammer and Talley, this supplement), emphasizes a “positive diagnosis” rather than exhaustive tests to exclude other diseases.3 Although the accuracy and pathophysiologic significance have yet to be reported, the Rome criteria are probably the most reasonable approach for clinical diagnosis and research purposes. Because physical findings and available diagnostic tests lack specificity for clinical use, the diagnosis of IBS involves identifying certain symptoms consistent with the disorder and excluding other medical conditions that may have a similar clinical presentation.4 A validation study of the Rome criteria, after excluding patients with warning features, showed a sensitivity of 63%, a specificity of 100%, and more importantly, a positive predictive value of 100% and a negative predictive value of 76%.5
HISTORY AND PHYSICAL EXAMINATION
From Departamento de Gastroenterologı´a, Instituto Nacional de la Nutricio´n Salvador Zubira´n, Me´xico D.F., Mexico (MWS); and University of California, Los Angeles/CURE Neuroenteric Disease Program, Department of Medicine, UCLA School of Medicine, Los Angeles, California (LC). Requests for reprints should be addressed to Max W. Schmulson, MD, Departamento de Gastroenterologı´a, Instituto Nacional de la Nutricio´n Salvador Zubira´n, Vasco de Quiroga No. 15, Tlalpan C.P. 14000, Me´xico D.F., Mexico. 20S
© 1999 by Excerpta Medica, Inc. All rights reserved.
A detailed history using the established symptom criteria often can exclude most organic diseases that could cause symptoms compatible with IBS. The presence of gastrointestinal bleeding, fever, weight loss, anemia, palpable masses, or other warning features of organic disease should be determined.6 A careful interpretation of the pain and/or discomfort and stool characteristics is the most important step in recognizing IBS.7 Abdominal pain or discomfort should be related to defecation, whereas that associated with exercise, movement, urination, or menstruation may have a different cause. Although a palpable, tender sigmoid colon and discomfort with rectal examination may be present, related to increased visceral sensitivity,8 physical examination is usu0002-9343/99/$20.00 PII S0002-9343(99)00278-8
A Symposium: Diagnostic Approach to IBS/Schmulson and Chang
Table 1. Differential Diagnoses of IBS Inflammatory bowel disease Colorectal carcinoma Constipating medications Gastrointestinal infections (e.g., Giardia, Entamoeba histolytica, Yersinia, Strongyloides) Lactose intolerance Endocrine disorders (hypo- or hyperthyroidism, diabetes) Medications (e.g., laxatives, magnesium-containing antacids) Microscopic colitis Bacterial overgrowth Malabsorption syndromes (e.g., celiac sprue, pancreatic insufficiency) Chronic intestinal idiopathic pseudo-obstruction Endocrine tumors (e.g., gastrinoma, VIPoma)
tively as possible.20 So far, no test has been established as a diagnostic standard for IBS, and there is currently no specific treatment available that relies on the result of any diagnostic procedure; thus, the role of diagnostic procedures in IBS is limited to the identification of patients with structural lesions.20
DIAGNOSTIC EVALUATION
General Clinical Evaluation Care should be taken to avoid unnecessary investigations that are costly and harmful. Minimal diagnostic procedures have been advocated in the initial diagnostic approach to reasonably exclude structural lesions and to convince the patient of the diagnosis of IBS.21 As shown in Figure 1, minimal diagnostic procedures include complete blood count (CBC) and erythrocyte sedimentation rate (ESR), blood chemistries, thyroid panel, and stool for occult blood, ova, and parasites. Most of the initial screening tests are available to the general practitioner.15 Flexible sigmoidoscopy and barium enema or colonoscopy in patients older than 50 years are less accessible to the general practitioner but have a yield of approximately 1%, as they provide more chances of finding structural lesions such as polyps, colon cancer, and colitis.22 Other tests, such as abdominal ultrasonography, do not appear to change a patient’s treatment.23 Follow-up studies extending up to 9 years after the diagnosis of IBS using symptom criteria and limited diagnostic evaluations have found that fewer than 5% of patients had other explanations for their symptoms.5,24 The simple persistence of symptoms does not justify suspicion of another diagnosis. Indeed, such persistence is to be expected, and further investigation only serves to undermine the patient’s confidence in the diagnosis and the physician.7 A more detailed diagnostic evaluation (Figure 1) should be considered for those individuals who present with recent onset of symptoms, particularly in patients older than 50 years, more severe or disabling symptoms, clinical change over time, or a family history of colon cancer particularly at younger age. Psychosocial difficulties will affect reported symptoms, although they do not protect patients from organic conditions. Physicians should consider the best diagnostic approach in patients with such coexisting conditions.4
According to Drossman et al17 and Sandler et al,18 less than half of individuals with IBS become patients. Reasons for seeking medical care include symptom severity, fear about serious illness, disability, or psychosocial factors.15 An early confident diagnosis permits tests to be minimized and reassures the patient that there is no lethal disease.19 In this era of managed care, many of the expensive and sophisticated tests available are generally not needed for patients with positive symptom criteria and no features suggestive of organic diseases.4 Furthermore, diagnostic procedures in general are used not only to diagnose a specific disorder but to target treatment as effec-
Predominant Symptom-Based Diagnostic Approach If the initial diagnostic approach is unrevealing, the physician should initiate symptomatic treatment and reassess in 3 to 6 weeks (see Camilleri’s article in this supplement). It has been proposed that additional diagnostic strategies should be based on predominant symptom subgroups, such as constipation, diarrhea, or abdominal pain.21,25 Recent studies have reported pathophysiologic differences in the symptom reporting and perceptual responses among these subgroups and support a symptom-based diagnostic approach.26 –29
VIP ⫽ vasoactive intestinal peptide.
ally unremarkable in IBS and serves primarily to exclude other diagnoses.9 Examination also provides an essential foundation for the physician to reassure the patient.10 Extracolonic symptoms, such as nausea, heartburn, early satiety, loss of appetite, dyspareunia, dysuria, nocturia, urinary urgency, prostatism, lethargy, headache, and back pain, occur frequently in IBS patients. These extraintestinal symptoms often result in the unnecessary involvement of several specialists in the care of IBS patients.8,11–14
DIFFERENTIAL DIAGNOSIS A detailed history often can exclude most organic diseases that can cause symptoms consistent with IBS. The differential diagnoses of IBS are quite small and include inflammatory bowel disease, gastrointestinal infections, lactose intolerance, thyroid disease, endocrine tumors, microscopic colitis, and malabsorption syndromes (Table 1).8,15 It is important to note that the presence of diverticula on a barium enema does not rule out the diagnosis of IBS.16 A common condition such as IBS that affects up to 20% of the population can coexist with organic disease.
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Figure 1. Rome criteria for irritable bowel syndrome.
Compared with patients with diarrhea-predominant IBS, those with constipation-predominant IBS more frequently report musculoskeletal symptoms, dyspepsia-associated symptoms, and alterations in vital functions, such as poor sleep, loss of appetite, and sexual dysfunction.26 In addition, rectal discomfort thresholds are lower in constipation-predominant patients but are relatively normal in diarrhea-predominant patients.27 Motility studies have also demonstrated differences between the IBS subgroups. Patients with constipation-predominant IBS show postprandial rectal relaxation and a blunted gastrocolonic response, whereas patients with diarrheapredominant IBS have an increased rectal tone in response to meal intake and a normal gastrocolonic response.29 Preliminary studies using positron emission tomography (PET) suggest differences in brain activation between constipation and diarrhea groups. In addition, differences in the therapeutic response to medications has been found. Studies have shown that alosetron (Glaxo Wellcome Inc., Research Triangle Park, NC), a new 5-hydroxytryptamine (5-HT3) antagonist compound, is specifically effective in nonconstipated female patients with IBS.30,31 A subgroup of patients with IBS report pain as their most predominant symptom. Lower rectal sensitivity thresholds and higher symptom severity scores have been reported in this subgroup.32,33 Patients with constipation-predominant bowel habit: IBS patients with constipation predominance mainly complain of infrequent bowel movements, hard or lumpy stools, sensation of incomplete evacuation, or ex22S
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cessive straining with no loose or watery stools unless laxatives are taken. Further evaluation is warranted if they do not respond to general treatment measurements (see Camilleri’s article in this supplement). In those with lowfrequency defecation, measurement of colonic transit using radiopaque markers is recommended.34 Patients with colonic inertia usually have prolonged transit time, predominantly in the right colon. In patients with left-side colon delay or normal colonic transit, excessive straining, or sensation of constant rectal fullness, flexible sigmoidoscopy is recommended to rule out structural abnormalities. If this study is negative, functional rectal outlet obstruction should be suspected.6,34 The causes of functional rectal outlet obstruction include anismus (pelvic floor dyssynergia), rectocele, rectal prolapse, and intussusception, and can coexist with IBS. These disorders can be evaluated by several diagnostic tests (Figure 2). Anorectal manometry is helpful in the evaluation of constipation by measuring rectal compliance (accommodation of the rectal wall) and rectal sensation.35 In constipated patients, lower rectal sensory thresholds have been reported,36 although in patients with increased rectal compliance, elevated thresholds may be found.37 Anorectal manometry can also evaluate anal sphincter relaxation, which may be abnormal in constipated patients. Loss of the rectoanal inhibitory reflex (failure of the internal anal sphincter to relax normally during rectal balloon distension) has been used as a diagnostic criterion for Hirschprung’s disease. Anorectal manometry also includes the use of two tests that aid in the diagnosis of functional rectal outlet obstruction, rectal balloon expulVolume 107 (5A)
A Symposium: Diagnostic Approach to IBS/Schmulson and Chang
Figure 2. Constipation-predominant IBS.
sion and electromyography (EMG). Rectal balloon expulsion is probably the simplest test to rule out anismus.38,39 EMG evaluates the function of the striated muscle of the anal sphincter and can detect paradoxical contraction of the puborectalis muscles during defecation.40 This finding in the setting of an abnormal rectal balloon expulsion test supports the diagnosis of anismus35,40 (Figure 2). Defecography (defecating proctography) in which the rectum and anus are imaged while the patient strains and expels barium inserted into the rectum, is the best available technique to visualize the pelvic floor and rectal wall motions during rectal emptying. It is useful in the diagnosis of rectal prolapse, rectocele, and anismus, which can all present with constipation40 (Figure 2). Patients with diarrhea-predominant bowel habit: Patients with diarrhea-predominant IBS complain of frequent bowel movements, loose or watery stools, and urgency for a bowel movement. CBC, ESR, blood chemistries, and thyroid function tests are helpful in ruling out inflammatory diseases, bleeding from the gastrointestinal tract, and hyperthyroidism.37 There are several stool studies that can be useful in determining the underlying cause of diarrhea. Stool examination should be performed for occult blood, ova, and parasites, and stool white blood cell count can help rule out infectious and inflammatory diseases of the bowel. Stool weight may help clarify the nature of diarrhea. Stool weights ⬎500 g/day are rarely if ever seen in patients with IBS and stool weights ⬍1,000 g/day are evidence against pancreatic cholera syndrome.41,42 Osmotic gap of the stool helps in differentiating osmotic (⬎125 mOsm/kg) from secretory
diarrhea (⬍50 mOsm/kg).43 In carbohydrate malabsorption, the osmotic gap lies between 50 and 125 mOsm/ kg.43 A fecal pH ⬍5.3 indicates carbohydrate malabsorption, whereas higher pH values are observed in generalized malabsorption.44 In cases of osmotic diarrhea, the lactose hydrogen breath test or lactose-free diet should be instituted. Furthermore, lactose malabsorption prevalence in patients with IBS is similar to the general US population.45 The presence of excess stool fat or “steatorrhea” can be assessed qualitatively by means of Sudan stain or quantitatively by direct measurement. Levels ⬎7 g/day suggest fat malabsorption is the result of small intestinal wall alterations, whereas levels ⬎14 g/day are more indicative of pancreatic steatorrhea.44 The D-xylose-absorption test is used as a screening test for small intestinal absorption function. A urinary excretion rate ⬍5 g/5 hours after an ingestion of 25 g of D-xylose is considered abnormal and suggests that the diarrhea is the result of small intestinal disease rather than pancreatic insufficiency.46 Other tests can be performed to exclude structural diseases and infections that may present with diarrhea. Flexible sigmoidoscopy or colonoscopy with mucosal biopsies allow the exclusion of neoplasms, inflammatory bowel disease, and microscopic or collagenous colitis. Radiographic examination of the small intestine (small bowel follow-through) is useful in evaluating such intestinal disorders as celiac sprue, lymphoma, and Crohn’s disease. Abnormal findings, such as excess luminal fluid and irregular mucosal surface, will guide in the diagnosis of malabsorption.47 Upper endoscopy with biopsy specimens from the distal duodenum or proximal jejunum
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Figure 3. Diarrhea-predominant IBS.
are helpful in ruling out Crohn’s disease, celiac sprue, Whipple’s disease, intestinal lymphoma, and infections. If bacterial overgrowth is suspected, an aspirate of small intestinal contents can be sent for aerobic and anaerobic bacterial culture. More than 105 organisms/mL is diagnostic for bacterial overgrowth.48,49 Giardia lamblia infection can be diagnosed by small bowel biopsies and aspirate, and stool for ova and parasites.49 Finally, acquired immunodeficiency syndrome (AIDS) should be considered in patients with promiscuous sexual activity, history of intravenous drug abuse, or blood transfusions. Analy-
sis of laxatives in stool or urine should be done in diarrhea patients with unknown causes to rule out factitious diarrhea50 (Figure 3). Patients with pain/discomfort-predominant IBS: A subgroup of patients complain mainly of abdominal pain. The latter may be associated with symptoms such as bloating, gas, and abdominal distention. Breath tests are used to rule out lactose malabsorption and bacterial overgrowth.51 Small bowel follow-through is indicated to investigate mechanical obstruction, chronic intestinal idio-
Figure 4. Pain/discomfort-predominant IBS. 24S
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pathic pseudo-obstruction, or inflammatory diseases.47 Chronic pancreatitis can be assessed by abdominal x-rays, abdominal ultrasound, or computerized tomography. Unexplained abdominal pain is an indication for antroduodenal manometry to investigate small intestinal motor disorders and to differentiate intestinal myopathies from neuropathies52 (Figure 4).
10.
11. 12.
Psychological Assessment It is known that stressful life events, such as history of physical or sexual abuse, death, divorce, or other major traumas, frequently precede the onset of IBS symptoms.53 Psychiatric diagnosis and other psychosocial difficulties are more common in IBS patients than other groups.54 Subjects with IBS who seek medical attention have a high frequency of psychosocial disturbances, which influences the clinical outcome.55 Thus, an assessment of behavioral and psychological disease is essential in the cost-effective evaluation of patients with IBS.6
13.
14.
15.
16. 17.
CONCLUSIONS The clinical diagnosis of IBS is based on identifying symptom criteria with a “positive diagnosis” and excluding organic disease with minimal diagnostic evaluation. Clinicians should feel secure with the diagnosis of IBS if made properly, because it is rarely associated with other explanations for their symptoms. Additional diagnostic studies are based on symptom predominance, such as constipation, diarrhea, and abdominal pain/discomfort.
18.
19.
20.
REFERENCES 1. Sandler RS. Epidemiology of irritable bowel syndrome in the United States. Gastroenterology. 1990;99:409 – 415. 2. Mitchell CM, Drossman DA. Survey of the AGA membership relating to patients with functional gastrointestinal disorders. Gastroenterology. 1987;92:1282–1284. 3. Drossman DA, Thompson GW, Talley NJ, Funch-Jensen P, Janssens J, Whitehead WE. Identification of subgroups of functional gastrointestinal disorders. Gastroenterology Int. 1990;3:159 –172. 4. American Gastroenterological Association Medical Position Statement. Irritable bowel syndrome. Gastroenterology. 1997;112:2118 –2119. 5. Vanner S, Glenn D, Paterson W. Diagnosing irritable bowel syndrome: predictive values of Rome criteria. Gastroenterology. 1997;112:A47. Abstract. 6. Lembo T, Mayer EA. Irritable bowel syndrome. In: Brandt LJ, ed. Clinical Practice of Gastroenterology: Current Medicine. Philadelphia: Current Medicine, 1997:19 –29. 7. Thompson GW. Functional bowel disorders and functional abdominal pain. In: Drossman DA, Richter J, Talley NJ, Thompson GW, Corazziari E, Whitehead WE, eds. The Functional Gastrointestinal Disorders. Boston: Little, Brown, 1994;115–174. 8. Whorwell PJ, McCallum M, Creed FH, Roberts CT. Noncolonic features of irritable bowel syndrome. Gut. 1986;27: 37– 40. 9. American Gastroenterological Association Patient Care
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Committee. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology. 1997; 112:2120 –2137. Thompson GW. Gastrointestinal symptoms in the irritable bowel compared with peptic ulcer and inflammatory bowel disease. Gut. 1984;25:1089 –1092. Hart J. Fibrositis (fibromyalgia): a common non-entity. Drugs. 1988;35:320 –327. Maxton DG, Whorwell PJ. Use of medical resources and attitudes to health care of patients with “chronic abdominal pain.” Br J Med Econ. 1992;2:75–79. Fass R, Fullerton S, Naliboff B, Hirsh T, Mayer EA. Sexual dysfunction in patients with irritable bowel syndrome and non-ulcer dyspepsia. Digestion. 1998;59:79 – 85. Fass R, Fullerton S, Diehl DL, Mayer EA. Sleep disturbance (SD) in patients with functional bowel disorders (FBD). Gastroenterology. 1995;108:A596. Coremans G, Dapoigny M, Muller-Lissner SA, et al. Working team report. Diagnostic procedures in irritable bowel syndrome. Digestion. 1995;56:76 – 84. Thompson GW. Do colonic diverticula cause symptoms? Am J Gastroenterol. 1986;81:613– 614. Drossman DA, McKee DC, Sandler RS, et al. Psychosocial factors in the irritable bowel syndrome. A multivariate study of patients and nonpatients with irritable bowel syndrome. Gastroenterology. 1988;95:701–708. Sandler RS, Drossman DA, Nathan HP, McKee DC. Symptom complaints and health care seeking behavior in subjects with bowel dysfunction. Gastroenterology. 1984;87: 314 –318. Thompson GW. Pathogenesis and management of the irritable bowel syndrome. In: Champion MC, Orr WC, eds. Evolving Concepts in Gastrointestinal Motility. Oxford: Blackwell Science, 1996;200 –220. Holtmann G. Treatment strategies for functional gastrointestinal disorders. In: Goebell H, Holtmann G, Talley NJ, eds. Functional Dyspepsia and Irritable Bowel Syndrome. Dordrecht: Kluwer Academic Publishers, 1997;217–223. Camilleri M, Prather CM. The irritable bowel syndrome: mechanisms and a practical approach to management. Ann Intern Med. 1992;116:1001–1008. McIntosh DG, Thompson GW, Patel DG. Is rectal biopsy necessary in irritable bowel syndrome? Am J Gastroenterol. 1992;87:1407–1409. Francis CY, Duffy JN, Whorwell PJ, Martin DF. Does routine abdominal ultrasound enhance diagnostic accuracy in irritable bowel syndrome? Am J Gastroenterol. 1996;91: 1348 –1350. Svendsen JH, Munck LK, Andersen JR. Irritable bowel syndrome: prognosis and diagnostic safety. A 5-year follow-up study. Scand J Gastroenterol. 1985;20:415– 418. Drossman DA, Thompson WG. The irritable bowel syndrome: review and a graduated multicomponent treatment approach. Ann Intern Med. 1992;116:1009 –1016. Schmulson M, Lee OY, Chang L, Naliboff B, Mayer EA. Symptom differences in moderate to severe IBS patients based on predominant bowel habit. Am J Gastroenterol. 1999;in press. Schmulson M, Chang L, Naliboff B, Lee OY, Mayer EA. Correlation of symptom criteria with perception thresholds during rectosigmoid distension in irritable bowel syndrome patients. Am J Gastroenterol. 1999;in press. Munakata J, Silverman DHS, Naliboff B, Berman S, Mayer EA. Evidence for cortical visceral autonomic dysregulation THE AMERICAN JOURNAL OF MEDICINE威
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in irritable bowel syndrome. Neurogastroenterol Motil. 1998;10:362. Abstract. Schmulson M, Lee OY, Olivas T, et al. Effect of food intake on rectosigmoid motor and perceptual responses in IBS patients with different bowel habit. Gastroenterology 1999; 116:A1078. Abstract. Northcutt AR, Camilleri M, Mayer EA, et al. Alosetron, a 5-HT3-receptor antagonist, is effective in the treatment of female irritable bowel syndrome patients. Gastroenterology. 1998;114:812. Abstract. Mangel AW, Camilleri M, Chey WY, et al. Treatment of female IBS patients with Alosetron, a potent and selective 5HT3-receptor antagonist. Gastroenterology. 1999;116: A1036. Abstract. Whitehead WE, Diamant N, Meyer K, et al. Pain thresholds measured by the barostat predict the severity of clinical pain in patients with irritable bowel syndrome. Gastroenterology. 1998;114:859. Abstract. Lembo T, Naliboff B, Munakata J, et al. Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome. Am J Gastroenterol. 1999;94:1320 – 1326. Wald A. Evaluation and management of constipation. Clin Persp Gastroenterol. 1998;1:106 –115. Mertz H. Constipation. Curr Opin Gastroenterol. 1997;13: 5–10. Schmulson M, Lee OY, Chang L, Naliboff B, Munakata J, Mayer EA. Differences in viscerosensory processing between IBS patients with constipation and diarrhea. Am J Gastroenterol. 1998;93:1699. Abstract. Lee OY, Schmulson M, Mayer EA. Functional GI disorders. Clin Cornerst. 1999;1:57– 68. Kuijpers HC, Bleijenberg G. The spastic pelvic floor syndrome: a cause of constipation. Dis Colon Rectum. 1985;28:669 – 672. Fleshman J, Dreznik Z, Cohen E, Fry R, Kodner I. Balloon expulsion test facilitates diagnosis of pelvic floor obstruction due to nonrelaxing puborectalis muscle. Dis Colon Rectum. 1992;35:1019 –1025. Wald A. Anal sphincter and pelvic floor dysfunction. In: Fisher RS, Krevsky B, eds. AGA-Motor Disorders of the Gastrointestinal Tract. What’s New and What to Do. New York: Academy Professional Information Services, 1993; 115–120. Goy JA, Eastwood MA, Mitchell WD, Pritchard JL, Smith AN. Fecal characteristics contrasted in the irritable bowel
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syndrome and diverticular disease. Am J Clin Nutr. 1976; 29:1480 –1484. Pimparkar BD, Tulsky EG, Kalser MH, Bockus HL. Correlation of radioactive and chemical fecal fat determinations in the malabsorption syndrome. Studies in normal man and in functional disorders of the gastrointestinal tract. Am J Med. 1961;30:910 –926. Eherer AJ, Fordtram JS. Fecal osmotic gap and pH in experimental diarrhea of various causes. Gastroenterology. 1992;103:545–551. Fine KD, Fordtram JS. The effect of diarrhea on fecal fat excretion. Gastroenterology. 1992;102:1936 –1939. Hamm LR, Sorrells SC, Harding JP, et al. Additional investigations fail to alter diagnosis of irritable bowel syndrome in subjects fulfilling the Rome criteria. Am J Gastroenterol. 1999;94:1279 –1282. Haeney MR, Culank LS, Montgomery RD, Sammons HG. Evaluation of xylose as measured in blood and urine. A one-hour blood xylose screening test for malabsorption. Gastroenterology. 1978;75:393– 400. Ott DJ, Chen YM, Gelfand DW, Van Swearingen F, Munitz HA. Detailed per-oral small bowel examination vs. enteroclysis. Radiology. 1985;155:29 –31. Rubin CE, Dobbins WO. Peroral biopsy of the small intestine. Gastroenterology. 1965;49:676 – 697. Perera DR, Weinstein WM, Rubin CE. Small intestine biopsy. Hum Pathol. 1975;6:157–217. Anonymous. AGA Technical review on the evaluation and management of chronic diarrhea. Gastroenterology. 1999; 116:1464 –1486. Solomons NW. Evaluation of carbohydrate absorption: the hydrogen breath test in clinical practice. Clin Nutr. 1984;3: 71–78. Byrne KG. Antroduodenal manometry: an evaluation of an emerging methodology. Dig Dis. 1997;15:53– 63. Drossman DA, Creed FH, Fava GA. Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology Int. 1995;8:47–90. Palmer RL, Stonehill E, Crisp AH, Waller SL, Misiewicz JJ. Psychological characteristics of patients with the irritable bowel syndrome. Postgrad Med J. 1974;50:416 – 419. Whitehead WE, Crowell MD, Heller BR, Robinson JC, Horn S. Modeling and reinforcement of the sick role during childhood predicts adult illness behaviour. Psychosom Med. 1994;6:541–550.
Volume 107 (5A)
Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder characterized by abdominal pain or discomfort and alterations in bowel habits. In clinical practice, diagnosis is based on positive symptoms known as the Rome criteria and limited diagnostic screen, taking into account warning features suggestive of organic disease. Minimal diagnostic tests are warranted to rule out structural lesions in a cost-effective manner and to convince the patient of the diagnosis of IBS. An initial diagnosis of IBS is safe and rarely needs revision over time. Persistence of symptoms is to be expected and does not justify suspicion of other diagnoses. Only change in the clinical pattern over time justifies additional investigations. Other diagnostic evaluations depend on predominant symptoms, namely constipation, diarrhea, and pain or discomfort. It should be emphasized that although an initial “positive diagnosis” is safe to exclude other diseases with similar symptoms, a common disorder such as IBS may often coexist with other asymptomatic disorders. Am J Med. 1999;107(5A):20S–26S. © 1999 by Excerpta Medica, Inc.
I
rritable bowel syndrome (IBS) is a chronic functional bowel disorder of unknown origin characterized by abdominal pain or discomfort and alterations in bowel habits. It affects up to 20% of the US population, producing considerable costs to society in terms of work lost, consultation, unnecessary tests, and inappropriate management, and even unnecessary surgery.1,2 Diagnosis is based on identifying positive symptoms and warning features suggestive of organic disease and excluding other conditions in a cost-effective manner using minimal diagnostic studies. In this article we review diagnostic approaches to the patient with IBS.
CRITERION-BASED DIAGNOSIS: THE ROME CRITERIA The symptom-based criteria, known as the Rome criteria (see article by Hammer and Talley, this supplement), emphasizes a “positive diagnosis” rather than exhaustive tests to exclude other diseases.3 Although the accuracy and pathophysiologic significance have yet to be reported, the Rome criteria are probably the most reasonable approach for clinical diagnosis and research purposes. Because physical findings and available diagnostic tests lack specificity for clinical use, the diagnosis of IBS involves identifying certain symptoms consistent with the disorder and excluding other medical conditions that may have a similar clinical presentation.4 A validation study of the Rome criteria, after excluding patients with warning features, showed a sensitivity of 63%, a specificity of 100%, and more importantly, a positive predictive value of 100% and a negative predictive value of 76%.5
HISTORY AND PHYSICAL EXAMINATION
From Departamento de Gastroenterologı´a, Instituto Nacional de la Nutricio´n Salvador Zubira´n, Me´xico D.F., Mexico (MWS); and University of California, Los Angeles/CURE Neuroenteric Disease Program, Department of Medicine, UCLA School of Medicine, Los Angeles, California (LC). Requests for reprints should be addressed to Max W. Schmulson, MD, Departamento de Gastroenterologı´a, Instituto Nacional de la Nutricio´n Salvador Zubira´n, Vasco de Quiroga No. 15, Tlalpan C.P. 14000, Me´xico D.F., Mexico. 20S
© 1999 by Excerpta Medica, Inc. All rights reserved.
A detailed history using the established symptom criteria often can exclude most organic diseases that could cause symptoms compatible with IBS. The presence of gastrointestinal bleeding, fever, weight loss, anemia, palpable masses, or other warning features of organic disease should be determined.6 A careful interpretation of the pain and/or discomfort and stool characteristics is the most important step in recognizing IBS.7 Abdominal pain or discomfort should be related to defecation, whereas that associated with exercise, movement, urination, or menstruation may have a different cause. Although a palpable, tender sigmoid colon and discomfort with rectal examination may be present, related to increased visceral sensitivity,8 physical examination is usu0002-9343/99/$20.00 PII S0002-9343(99)00278-8
A Symposium: Diagnostic Approach to IBS/Schmulson and Chang
Table 1. Differential Diagnoses of IBS Inflammatory bowel disease Colorectal carcinoma Constipating medications Gastrointestinal infections (e.g., Giardia, Entamoeba histolytica, Yersinia, Strongyloides) Lactose intolerance Endocrine disorders (hypo- or hyperthyroidism, diabetes) Medications (e.g., laxatives, magnesium-containing antacids) Microscopic colitis Bacterial overgrowth Malabsorption syndromes (e.g., celiac sprue, pancreatic insufficiency) Chronic intestinal idiopathic pseudo-obstruction Endocrine tumors (e.g., gastrinoma, VIPoma)
tively as possible.20 So far, no test has been established as a diagnostic standard for IBS, and there is currently no specific treatment available that relies on the result of any diagnostic procedure; thus, the role of diagnostic procedures in IBS is limited to the identification of patients with structural lesions.20
DIAGNOSTIC EVALUATION
General Clinical Evaluation Care should be taken to avoid unnecessary investigations that are costly and harmful. Minimal diagnostic procedures have been advocated in the initial diagnostic approach to reasonably exclude structural lesions and to convince the patient of the diagnosis of IBS.21 As shown in Figure 1, minimal diagnostic procedures include complete blood count (CBC) and erythrocyte sedimentation rate (ESR), blood chemistries, thyroid panel, and stool for occult blood, ova, and parasites. Most of the initial screening tests are available to the general practitioner.15 Flexible sigmoidoscopy and barium enema or colonoscopy in patients older than 50 years are less accessible to the general practitioner but have a yield of approximately 1%, as they provide more chances of finding structural lesions such as polyps, colon cancer, and colitis.22 Other tests, such as abdominal ultrasonography, do not appear to change a patient’s treatment.23 Follow-up studies extending up to 9 years after the diagnosis of IBS using symptom criteria and limited diagnostic evaluations have found that fewer than 5% of patients had other explanations for their symptoms.5,24 The simple persistence of symptoms does not justify suspicion of another diagnosis. Indeed, such persistence is to be expected, and further investigation only serves to undermine the patient’s confidence in the diagnosis and the physician.7 A more detailed diagnostic evaluation (Figure 1) should be considered for those individuals who present with recent onset of symptoms, particularly in patients older than 50 years, more severe or disabling symptoms, clinical change over time, or a family history of colon cancer particularly at younger age. Psychosocial difficulties will affect reported symptoms, although they do not protect patients from organic conditions. Physicians should consider the best diagnostic approach in patients with such coexisting conditions.4
According to Drossman et al17 and Sandler et al,18 less than half of individuals with IBS become patients. Reasons for seeking medical care include symptom severity, fear about serious illness, disability, or psychosocial factors.15 An early confident diagnosis permits tests to be minimized and reassures the patient that there is no lethal disease.19 In this era of managed care, many of the expensive and sophisticated tests available are generally not needed for patients with positive symptom criteria and no features suggestive of organic diseases.4 Furthermore, diagnostic procedures in general are used not only to diagnose a specific disorder but to target treatment as effec-
Predominant Symptom-Based Diagnostic Approach If the initial diagnostic approach is unrevealing, the physician should initiate symptomatic treatment and reassess in 3 to 6 weeks (see Camilleri’s article in this supplement). It has been proposed that additional diagnostic strategies should be based on predominant symptom subgroups, such as constipation, diarrhea, or abdominal pain.21,25 Recent studies have reported pathophysiologic differences in the symptom reporting and perceptual responses among these subgroups and support a symptom-based diagnostic approach.26 –29
VIP ⫽ vasoactive intestinal peptide.
ally unremarkable in IBS and serves primarily to exclude other diagnoses.9 Examination also provides an essential foundation for the physician to reassure the patient.10 Extracolonic symptoms, such as nausea, heartburn, early satiety, loss of appetite, dyspareunia, dysuria, nocturia, urinary urgency, prostatism, lethargy, headache, and back pain, occur frequently in IBS patients. These extraintestinal symptoms often result in the unnecessary involvement of several specialists in the care of IBS patients.8,11–14
DIFFERENTIAL DIAGNOSIS A detailed history often can exclude most organic diseases that can cause symptoms consistent with IBS. The differential diagnoses of IBS are quite small and include inflammatory bowel disease, gastrointestinal infections, lactose intolerance, thyroid disease, endocrine tumors, microscopic colitis, and malabsorption syndromes (Table 1).8,15 It is important to note that the presence of diverticula on a barium enema does not rule out the diagnosis of IBS.16 A common condition such as IBS that affects up to 20% of the population can coexist with organic disease.
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Figure 1. Rome criteria for irritable bowel syndrome.
Compared with patients with diarrhea-predominant IBS, those with constipation-predominant IBS more frequently report musculoskeletal symptoms, dyspepsia-associated symptoms, and alterations in vital functions, such as poor sleep, loss of appetite, and sexual dysfunction.26 In addition, rectal discomfort thresholds are lower in constipation-predominant patients but are relatively normal in diarrhea-predominant patients.27 Motility studies have also demonstrated differences between the IBS subgroups. Patients with constipation-predominant IBS show postprandial rectal relaxation and a blunted gastrocolonic response, whereas patients with diarrheapredominant IBS have an increased rectal tone in response to meal intake and a normal gastrocolonic response.29 Preliminary studies using positron emission tomography (PET) suggest differences in brain activation between constipation and diarrhea groups. In addition, differences in the therapeutic response to medications has been found. Studies have shown that alosetron (Glaxo Wellcome Inc., Research Triangle Park, NC), a new 5-hydroxytryptamine (5-HT3) antagonist compound, is specifically effective in nonconstipated female patients with IBS.30,31 A subgroup of patients with IBS report pain as their most predominant symptom. Lower rectal sensitivity thresholds and higher symptom severity scores have been reported in this subgroup.32,33 Patients with constipation-predominant bowel habit: IBS patients with constipation predominance mainly complain of infrequent bowel movements, hard or lumpy stools, sensation of incomplete evacuation, or ex22S
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cessive straining with no loose or watery stools unless laxatives are taken. Further evaluation is warranted if they do not respond to general treatment measurements (see Camilleri’s article in this supplement). In those with lowfrequency defecation, measurement of colonic transit using radiopaque markers is recommended.34 Patients with colonic inertia usually have prolonged transit time, predominantly in the right colon. In patients with left-side colon delay or normal colonic transit, excessive straining, or sensation of constant rectal fullness, flexible sigmoidoscopy is recommended to rule out structural abnormalities. If this study is negative, functional rectal outlet obstruction should be suspected.6,34 The causes of functional rectal outlet obstruction include anismus (pelvic floor dyssynergia), rectocele, rectal prolapse, and intussusception, and can coexist with IBS. These disorders can be evaluated by several diagnostic tests (Figure 2). Anorectal manometry is helpful in the evaluation of constipation by measuring rectal compliance (accommodation of the rectal wall) and rectal sensation.35 In constipated patients, lower rectal sensory thresholds have been reported,36 although in patients with increased rectal compliance, elevated thresholds may be found.37 Anorectal manometry can also evaluate anal sphincter relaxation, which may be abnormal in constipated patients. Loss of the rectoanal inhibitory reflex (failure of the internal anal sphincter to relax normally during rectal balloon distension) has been used as a diagnostic criterion for Hirschprung’s disease. Anorectal manometry also includes the use of two tests that aid in the diagnosis of functional rectal outlet obstruction, rectal balloon expulVolume 107 (5A)
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Figure 2. Constipation-predominant IBS.
sion and electromyography (EMG). Rectal balloon expulsion is probably the simplest test to rule out anismus.38,39 EMG evaluates the function of the striated muscle of the anal sphincter and can detect paradoxical contraction of the puborectalis muscles during defecation.40 This finding in the setting of an abnormal rectal balloon expulsion test supports the diagnosis of anismus35,40 (Figure 2). Defecography (defecating proctography) in which the rectum and anus are imaged while the patient strains and expels barium inserted into the rectum, is the best available technique to visualize the pelvic floor and rectal wall motions during rectal emptying. It is useful in the diagnosis of rectal prolapse, rectocele, and anismus, which can all present with constipation40 (Figure 2). Patients with diarrhea-predominant bowel habit: Patients with diarrhea-predominant IBS complain of frequent bowel movements, loose or watery stools, and urgency for a bowel movement. CBC, ESR, blood chemistries, and thyroid function tests are helpful in ruling out inflammatory diseases, bleeding from the gastrointestinal tract, and hyperthyroidism.37 There are several stool studies that can be useful in determining the underlying cause of diarrhea. Stool examination should be performed for occult blood, ova, and parasites, and stool white blood cell count can help rule out infectious and inflammatory diseases of the bowel. Stool weight may help clarify the nature of diarrhea. Stool weights ⬎500 g/day are rarely if ever seen in patients with IBS and stool weights ⬍1,000 g/day are evidence against pancreatic cholera syndrome.41,42 Osmotic gap of the stool helps in differentiating osmotic (⬎125 mOsm/kg) from secretory
diarrhea (⬍50 mOsm/kg).43 In carbohydrate malabsorption, the osmotic gap lies between 50 and 125 mOsm/ kg.43 A fecal pH ⬍5.3 indicates carbohydrate malabsorption, whereas higher pH values are observed in generalized malabsorption.44 In cases of osmotic diarrhea, the lactose hydrogen breath test or lactose-free diet should be instituted. Furthermore, lactose malabsorption prevalence in patients with IBS is similar to the general US population.45 The presence of excess stool fat or “steatorrhea” can be assessed qualitatively by means of Sudan stain or quantitatively by direct measurement. Levels ⬎7 g/day suggest fat malabsorption is the result of small intestinal wall alterations, whereas levels ⬎14 g/day are more indicative of pancreatic steatorrhea.44 The D-xylose-absorption test is used as a screening test for small intestinal absorption function. A urinary excretion rate ⬍5 g/5 hours after an ingestion of 25 g of D-xylose is considered abnormal and suggests that the diarrhea is the result of small intestinal disease rather than pancreatic insufficiency.46 Other tests can be performed to exclude structural diseases and infections that may present with diarrhea. Flexible sigmoidoscopy or colonoscopy with mucosal biopsies allow the exclusion of neoplasms, inflammatory bowel disease, and microscopic or collagenous colitis. Radiographic examination of the small intestine (small bowel follow-through) is useful in evaluating such intestinal disorders as celiac sprue, lymphoma, and Crohn’s disease. Abnormal findings, such as excess luminal fluid and irregular mucosal surface, will guide in the diagnosis of malabsorption.47 Upper endoscopy with biopsy specimens from the distal duodenum or proximal jejunum
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Figure 3. Diarrhea-predominant IBS.
are helpful in ruling out Crohn’s disease, celiac sprue, Whipple’s disease, intestinal lymphoma, and infections. If bacterial overgrowth is suspected, an aspirate of small intestinal contents can be sent for aerobic and anaerobic bacterial culture. More than 105 organisms/mL is diagnostic for bacterial overgrowth.48,49 Giardia lamblia infection can be diagnosed by small bowel biopsies and aspirate, and stool for ova and parasites.49 Finally, acquired immunodeficiency syndrome (AIDS) should be considered in patients with promiscuous sexual activity, history of intravenous drug abuse, or blood transfusions. Analy-
sis of laxatives in stool or urine should be done in diarrhea patients with unknown causes to rule out factitious diarrhea50 (Figure 3). Patients with pain/discomfort-predominant IBS: A subgroup of patients complain mainly of abdominal pain. The latter may be associated with symptoms such as bloating, gas, and abdominal distention. Breath tests are used to rule out lactose malabsorption and bacterial overgrowth.51 Small bowel follow-through is indicated to investigate mechanical obstruction, chronic intestinal idio-
Figure 4. Pain/discomfort-predominant IBS. 24S
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pathic pseudo-obstruction, or inflammatory diseases.47 Chronic pancreatitis can be assessed by abdominal x-rays, abdominal ultrasound, or computerized tomography. Unexplained abdominal pain is an indication for antroduodenal manometry to investigate small intestinal motor disorders and to differentiate intestinal myopathies from neuropathies52 (Figure 4).
10.
11. 12.
Psychological Assessment It is known that stressful life events, such as history of physical or sexual abuse, death, divorce, or other major traumas, frequently precede the onset of IBS symptoms.53 Psychiatric diagnosis and other psychosocial difficulties are more common in IBS patients than other groups.54 Subjects with IBS who seek medical attention have a high frequency of psychosocial disturbances, which influences the clinical outcome.55 Thus, an assessment of behavioral and psychological disease is essential in the cost-effective evaluation of patients with IBS.6
13.
14.
15.
16. 17.
CONCLUSIONS The clinical diagnosis of IBS is based on identifying symptom criteria with a “positive diagnosis” and excluding organic disease with minimal diagnostic evaluation. Clinicians should feel secure with the diagnosis of IBS if made properly, because it is rarely associated with other explanations for their symptoms. Additional diagnostic studies are based on symptom predominance, such as constipation, diarrhea, and abdominal pain/discomfort.
18.
19.
20.
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