# Irritable Bowel Syndrome: How Far Do You Go in the Workup?



## eric (Jul 8, 1999)

with permissionThe UNC Center for Functional GI http://www.med.unc.edu/ibs& Motility DisordersIrritable Bowel Syndrome:How Far Do You Go in the Workup?Douglas A. Drossman, M.D., FACG, UNC Center for Functional GI & Motility Disorders, Chapel Hill, NCThe diagnostic evaluation of patients with irritable bowel syndrome (IBS) can be challenging for severalreasons. First, there is no biological marker for the disorder. The diagnosis is based primarily on thepresence of a clustered set of symptoms relating to abdominal pain or discomfort and altered bowel habit.Second, it follows that a diagnosis based solely on symptoms can be unsettling; clinicians will strugglewith the possibility of missing another diagnosis. This level of uncertainty may increase the risk ofoverdoing diagnostic studies, though many clinicians believe an extensive diagnostic effort justified: itseeks to satisfy the patient's request to and a specific diagnosis, as well as the physician's personalinterest to "leave no stone unturned." Unfortunately, this approach contributes to the disproportionatelyhigh health care costs for IBS relative to other gastrointestinal disorders as reported in one HealthMaintenance Organization study.1 Finally, developing a diagnostic algorithm for IBS can be challenginggiven the effect of daily and life stress, and other psychosocial factors on IBS.2Currently, the diagnostic evaluation of patients presenting with IBS symptoms has no simple standard; itis based on the art and science of medicine. Several factors can influence the decision making: (1)symptom pattern and severity will influence, for example, whether biopsies are taken for diarrheapredominantsymptoms, or ultrasound or computerized tomography (CT Scans) are done for pain andweight loss,3 (2) features such as older age on initial presentation or a family history of inflammatorybowel disease or colon cancer may lead to a more extensive (e.g., colonoscopic) evaluation, (3) a patient'spain communication style must be appraised in the light of objective screening data; this, for example,will reduce the tendency for physicians merely to order tests based on urgent requests to "do something"(furor medicus"),4 and finally (4), the clinical setting will influence the probability of other medicaldisorders; so primary care physicians more than gastroenterologists will minimize diagnostic studies, treatthe symptoms of IBS and follow the patient expectantly,5 simply because the likelihood of another seriousmedical disease in a primary care setting is far less than in a referral practice.Efforts to consolidate these many influences on diagnostic decision making have occurred by creatingspecific published guidelines obtained by consensus.3,6,7 Most authors agree that an initial diagnosis ofIBS should be fulfilled by: (a) meeting symptom-based diagnostic criteria, such as Rome II6,8 criteria, (obtaining a negative physical examination, and © performing a cost-effective, conservative set ofscreening studies. These usually include a sigmoidoscopy (or colonoscopy for patients older than 50years), a few laboratory tests (e.g., complete blood count, stool for occult blood or ova and parasites), andadditional studies if certain "alarm" features are found: fever, an abnormal physical examination, blood inthe stool, an abnormal complete blood count or elevated sedimentation rate, significant weight loss,nocturnal symptoms that awaken the patient, or a family history of cancer or inflammatory boweldisease.12,13 Several prospective studies now offer evidence that the proper application of suchrecommendations rarely leads to a revision in diagnosis, even for patients observed over many years.6,14,15In one study, the positive predictive value for the diagnosis of IBS using Rome I criteria and excluding"red flags" over 1-year follow-up was 98%.12Of course, the gastroenterologist in referral practice may not be content to accept these probabilitieswithout first excluding those rare conditions overlooked by routine evaluations. So how far should thegastroenterologist go in the workup of patients referred to them who typically present with IBS and havenegative screening studies? One gastroenterologist recently commented to me: 'I order breath hydrogenstudies and blood tests for celiac sprue on all my patients referred with IBS. No doubt this commentreflects the concern that referral gastroenterologists have an obligation to contribute additional expertiseto the diagnostic effort. Recently, the breath H2 test is being requested more actively by physicians andthe public alike, possibly because of media attention to a study claiming a 73% rare of bacterialThe UNC Center for Functional GI http://www.med.unc.edu/ibs& Motility Disordersovergrowth in patients with IBS referred for breath H2 testing, and a 50% improvement with antibiotictreatment.16 However, the design limitations of this study, including a high referral bias, use of anuncontrolled and unblinded treatment protocol, and only a 30% follow-up rate evaluated over a relativelyshort period of time, make it unlikely that clinicians in practice will also obtain such dramatic results. Soalthough this study increases awareness of bacterial overgrowth as an entity that can mimic or exacerbateIBS, clinical experience suggests that the diagnostic yield in general gastrointestinal practice is probablymuch lower than reported, perhaps 10% or less.What about celiac disease? This disorder should always be considered in evaluating IBS because thediarrhea and abdominal discomfort caused by this intestinal disease will specifically respond to a glutenfreediet. There fore, making a diagnosis early may be cost-effective. The prevalence of celiac disease inthe United States is reported to range from 1:250 to 1:1500.17 However, this is influenced by the methodof assessment as well as the probability of the disorder being present in the population under study. Withregard to the method of assessment, in a study set in Olmstead County,18 the reported prevalence was1:4600, and the cases were identified by clinical and pathologic criteria. In contrast, when blood tests areused for diarrhea, the prevalence is at 1:250 or even higher,19 and in one recent study, the prevalence forwomen was 1:125 compared with males at 1:250.20 So, when clinically suspected, primary care physiciansand specialists may now obtain anti-gliadin and anti-endomysial IgA antibody serologies. These arereasonably effective screening tests, given that the sensitivities and positive predictive values range from90%-l00%.17 However, in populations in which the prevalence of this disorder is low, many positiveserologic tests will be false positives. Therefore, because the gold standard of diagnosis requires upperendoscopy with duodenal biopsy, endoscopy is almost always needed for confirmation of the diagnosis.Recently there is considerable research being done to reduce the cost of unneeded diagnostic studies. Theuse of simple "Red Flags" or "Alarm Signs" based on the medical history or simple screenings and bloodtests are examples. There are also more sensitive tests of intestinal inflammation (Calprotectin) that canbe recommended from the stool and can exclude inflammatory bowel disease (ref - Tribble).Is it possible that some simple and inexpensive tests will emerge to accurately diagnose IBS? I do notthink that IBS can by diagnosed by ordering tests, either to make a unitary diagnosis, or by default byexcluding other disorders. There is evidence that IBS is a heterogeneous disorder in which differentphysiologic sub groups contribute to the clinical expression of the syndrome. For example, there is asubgroup of patients, called "post-infectious IBS' who appear to respond to an enteric infection such ascawpylobactor jejuni with an increased inflammatory cell response.22 This is associated with activatingenterochromaffin cells to produce 5HT, and CD3 cells to produce cytokines, which in turn leads toenhanced motility and lowered visceral sensation thresholds.22,23 But microscopic inflammation cannot bea diagnostic marker for IBS because it does nor typically produce pain in those who have it. All patientswith active celiac disease have microscopic inflammation, but a large proportion do not have abdominalpain, and patients with ulcerative colitis who also have microscopic inflammation when compared withpatients with IBS seem to have higher pain thresholds.24 In individuals with these disorders, there may becentral nervous system counter-regulatory measures responding to the peripheral pain/inflammatoryprocesses that increase pain thresholds.With regard to IBS, the gut-related effects of microscopic inflammation may be only one component of adysfunctional brain-gut system. In addition, and often in response to stress, there may be a failure toactivate pain inhibition systems that lead to the perception of pain and produce other symptoms that typifythis disorder.25 In one prospective study of postinfectious IBS, it was found that those who retained theirsymptoms 3 months after an enteric infection had not only increased inflammation in the intestinal lining,but also had increased psychosocial distress at the time of the infection. Furthermore, lowered visceralpain thresholds and increased motility were present after the infection regardless of whether or not thepatients retained their symptoms.26 Therefore, the microscopic inflammation and its physiologic effects onmotility and sensation contribute to, but are not always sufficient for, the clinical expression of IBS pain.The UNC Center for Functional GI http://www.med.unc.edu/ibs& Motility DisordersAt least for postinfectious IBS, this provides some evidence that psychologic distress alters brain painregulatory pathways to amplify incoming visceral signals leading to the full clinical expression of thissyndrome.27,28 Recent studies using brain imaging29,30 may help us to understand the physiologicmechanisms that modulate these central nervous system responses to pain, and in the process, identify thesubgroup with IBS that are more amenable to psychologic and psychopharmacological treatments.As we continue to develop the means to assess the pathophysiological determinants of IBS symptoms, wewill identify subgroups that will change our diagnostic assessment. This may even lead us to redefinewhat we mean by IBS. Postinfectious IBS and patients having concurrent psychosocial disturbances(among others to be determined) characterize subgroups that will be more responsive to more specifictreatments. For the present, we must still make a diagnosis of IBS based on established guidelines,including symptom-based (e.g., Rome) criteria. We must also remain vigilant to identifying other relevantdisorders like celiac disease that may mimic or exacerbate IBS, and will use clinical judgment (e.g.,ordering anti-endomysial antibodies for patients with predominant diarrhea), rather than routinelyordering tests in all IBS patients just to exclude other disease. With careful appraisal of the historical andlaboratory data and good clinical judgment, a positive diagnosis of IBS can be made in a cost-effectivemanner and with confidence.References1. Levy R Von Korff M, Whitehead WE, Stang P, Saunders K, Jhingran P, Barghout V, Feld AD. Costs of care forirritable bowel syndrome patients in a health maintenance organization. Am J Gastoenterol 2001;96:3122-3129.2. Drossman DA, Creed Fit Olden KW, Svedlund J, Toner BB, Whitehead WE. Psychosocial aspects of thefunctional gastrointestinal disorders. In: Drossman DA, Corazziari E, Talley NJ, Thompson WG, Whitehead WE,eds. Rome II. The functional gastrointestinal disorders: diagnosis, pathophysiology and treatment; A multinationalconsensus. 2nd ad. McLean, VA: Degnon and Associates. 2000:157-245.


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