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CLINICAL GUIDELINES
ACG Clinical Guideline: Management of Irritable Bowel Syndrome
Brian E. Lacy, PhD, MD, FACG \( ^{1} \) , Mark Pimentel, MD, FACG \( ^{2} \) , Darren M. Brenner, MD, FACG \( ^{3} \) , William D. Chey, MD, FACG \( ^{4} \) , Laurie A. Keefer, PhD \( ^{5} \) , Millie D. Long, MDMPH, FACG (GRADE Methodologist) \( ^{6} \) and Baha Moshiree, MD, MSc, FACG \( ^{7} \)
Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterology clinical guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Twenty-five clinically important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodology, we endorse the following: We suggest that a positive diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serologic testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Additional statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.
SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/B755.
INTRODUCTION
Irritable bowel syndrome (IBS) is a chronic, often debilitating, and highly prevalent disorder of gut-brain interaction (previously called functional gastrointestinal [GI] disorders) (1,2). In clinical practice, IBS is characterized by symptoms of recurrent abdominal pain and disordered defecation (1,3). The Rome IV criteria, derived by consensus from a multinational group of experts in the field of disorders of gut-brain interaction, can be used to diagnose IBS for both clinical and research purposes (4). Patients with IBS should report symptoms of abdominal pain at least once weekly (on average) in association with a change in stool frequency, a change in stool form, and/or relief or worsening of abdominal pain related to defecation (Table 1). Although bloating is a commonly reported symptom, its presence is not mandatory to accurately diagnose IBS (4).
IBS is a common source of referrals to gastroenterologists with a prevalence of approximately 4.4%–4.8% in the United States, United Kingdom, and Canada and affects most commonly women and individuals younger than 50 years (5). Symptoms of IBS greatly affect patients' quality of life (6,7), and this marked negative impact
is highlighted by 1 study which reported that a majority of patients would give up 10–15 years of life expectancy for an instant cure for their condition and by another study which found that patients with IBS would accept a median risk of sudden death of 1% if a hypothetical medication could cure their IBS symptoms (8,9).
IBS causes a significant burden to health care systems worldwide. As highlighted in a recent review article, direct medical costs attributed to IBS in the United States, excluding prescription and over-the-counter medications, are estimated to be as high as $1.5–$10 billion per year (10). High levels of health care resource utilization, testing that is often unnecessary or performed too frequently, and significant regional variation in testing and treatment further contribute to substantial direct and indirect costs (11,12).
The management of IBS has been examined in several recent monographs, reviews, and position statements (1,3,4). These publications summarize and review data and provide management recommendations based on meta-analysis and/or expert opinion. However, essential diagnostic and treatment recommendations have not been formally evaluated by the American
\( ^{1} \) Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA; \( ^{2} \) Division of Gastroenterology and Hepatology, Cedars-Sinai, Los Angeles, California, USA; \( ^{3} \) Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois, USA; \( ^{4} \) Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA; \( ^{5} \) Icahn School of Medicine at Mount Sinai, New York, New York, USA; \( ^{6} \) Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA; \( ^{7} \) Division of Gastroenterology and Hepatology, University of North Carolina, College of Medicine, Charlotte, North Carolina, USA. Correspondence: Brian E. Lacy, PhD, MD, FACG. E-mail: Lacy.Brian@mayo.edu. Received April 15, 2020; accepted October 8, 2020
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Lacy et al.
Table 1. Rome IV diagnostic criteria for irritable bowel syndrome (4)
<table><tr><td>Recurrent abdominal pain on average at least 1 d/wk in the last 3 mo, associated with 2 or more of the following criteria</td></tr><tr><td>1. Related to defecation</td></tr><tr><td>2. Associated with a change in the frequency of stool</td></tr><tr><td>3. Associated with a change in the form (appearance) of stool</td></tr><tr><td>These criteria should be fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis.Adapted with permission from Bowel Disorders. Gastroenterology 2016;150:1393–407. ©2016 AGA Institute. Published by Elsevier. All rights reserved.</td></tr></table>
College of Gastroenterology (ACG) using rigorous Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This ACG clinical guideline was developed to provide clinicians with high quality evidence, when available, to support essential clinical questions relevant to the diagnosis and management of IBS (Table 2).
SCOPE OF THE GUIDELINE AND METHODOLOGY
This guideline will focus on key issues related to the diagnosis and management of IBS. Given the complexity of IBS, it is not possible to address all diagnostic and management issues. Clinically relevant questions were developed by a panel of experts who focus their clinical and research efforts on disorders of gut-brain interaction (previously called functional GI disorders). The group formulated 25 key statements that followed the population, intervention, comparator, and outcome format to guide the search for evidence (Table 3). These questions were answered by performing a comprehensive international literature search (see methods below). This guideline focuses primarily on the evaluation and management of patients in North America, as not all diagnostic tools (e.g., 23-seleno-25-homotaurocholic acid [SeHCAT]) and medications for IBS (e.g., pinaverium) are available in North America. Over the past decade the US Food and Drug Administration (FDA) has issued guidelines, suggesting that therapies for IBS symptoms be evaluated with an emphasis on global symptom improvement. As such, when applicable, questions were developed with an emphasis on evaluating global response to IBS symptoms for each therapy. An inherent limitation to this approach is that not all therapies were evaluated in double-blind, randomized, placebo-controlled trials with the primary endpoint being an improvement in global IBS symptoms. Where appropriate, this is mentioned in the text. Finally, it is worth noting that the strength of the recommendation, as described below, is based on an overall review of the literature and does not infer or imply that an individual patient may or may not receive benefits from the specific therapy described.
An individualized literature search was performed for each population, intervention, comparator, and outcome question which involved searching MEDLINE, EMBASE, PubMed, and the Cochrane Controlled Trials Register from inception to February 1, 2020. The search emphasized randomized, placebo-controlled trials with at least 10 subjects and study length \( \geq \) 4 weeks. Abstracts, case reports, uncontrolled studies, and studies less than 4 weeks in duration were not included. References of articles meeting the search criteria were reviewed for additional relevant studies. Trained GRADE methodologists analyzed the
data to assess the quality of evidence and given strength of recommendation. The quality of evidence was expressed as high (estimate of effect is unlikely to change with new data), moderate, low, or very low (estimate of effect is very uncertain). GRADE uses objective reproducible criteria to determine quality of evidence and risk of bias among relevant studies, including evidence of publication bias, unexplained heterogeneity among studies, directness of the evidence, and precision of the estimate of effect (13). A summary of the quality of evidence for the statements is given in Table 4. The strength of recommendation is given as either strong (most patients should receive the recommended course of action) or conditional (many patients will have this recommended course of action, but different choices may be appropriate for some patients). In the case of conditional recommendations, a greater discussion is warranted, so that each patient can arrive at a decision based on their values and preferences. The strength of recommendation is based on the quality of evidence and risks vs benefits (14).
We used a modified Delphi approach to achieve consensus. Each statement was presented during a monthly phone conference and voted on by all expert authors. Statements were revised and then either presented again on a phone conference or circulated by email. One face-to-face meeting was held. The vote on the final recommendation and quality of evidence for each statement was unanimous. A summary of the recommendations is given in Table 2.
Recommendation
We recommend that serologic testing be performed to rule out celiac disease (CD) in patients with IBS and diarrhea symptoms. Strong recommendation; moderate quality of evidence.
CD is an immune-mediated disease in which foods containing the storage protein gluten lead to enteropathy in genetically susceptible individuals. The clinical presentation of CD is highly variable, ranging from entirely asymptomatic to frank malabsorption. In a meta-analysis of studies conducted in North America, the seroprevalence of CD based on 7 studies including almost 18K subjects was estimated to be 1.4% (95% confidence interval [CI] 0.7%–2.2%), whereas the prevalence of biopsy-proven CD, based on a single study including 200 subjects, was estimated to be 0.5% (15–17). Making a diagnosis of CD is important because untreated persons can develop a myriad of significant downstream consequences including neuropsychiatric disease, other autoimmune diseases, nutritional deficiencies, infertility, as well as GI malignancies (16).
Many patients with CD present with abdominal pain, bloating, and/or altered bowel habits which can be mistaken for IBS (18–21). A recent meta-analysis of 36 eligible studies, including 15,256 persons of which 9,275 fulfilled symptom-based criteria for IBS, was conducted to determine whether patients with IBS symptoms are more likely to test positive for CD (19). The prevalence of positive antidemysial antibodies and/or tissue transglutaminase antibodies was 2.6% (95% CI 1.6%–3.8%) and of biopsy-proven CD was 3.3% (95% CI 2.3%–4.5%) in patients with IBS symptoms (20). Pooled odds ratios (ORs) from the world's literature showed an increased likelihood of positive antiendomysial antibodies and/or tissue transglutaminase antibodies (2.75, 95% CI 1.35–5.61) and biopsy-proven CD (4.48, 95% CI 2.33–4.60) in patients with IBS symptoms compared with controls. Only a small number of included studies were
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Management of Irritable Bowel Syndrome
Table 2. Summary and strength of recommendations
<table><tr><td>1</td><td>We recommend that serologic testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. Strong recommendation; moderate quality of evidence.</td></tr><tr><td>2</td><td>We suggest that fecal calprotectin (or fecal lactoferrin) and C-reactive protein be checked in patients without alarm features and with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. Strong recommendation; moderate quality of evidence for C-reactive protein and fecal calprotectin. Strong recommendation; very low quality of evidence for fecal lactoferrin.</td></tr><tr><td>3</td><td>We recommend against routine stool testing for enteric pathogens in all patients with IBS. Conditional recommendation; low quality of evidence.</td></tr><tr><td>4</td><td>We recommend against routine colonoscopy in patients with IBS symptoms younger than 45 years without warning signs. Conditional recommendation; low quality of evidence.</td></tr><tr><td>5</td><td>We suggest a positive diagnostic strategy as compared to a diagnostic strategy of exclusion for patients with symptoms of IBSs to improve time to initiate appropriate therapy. Consensus recommendation; unable to assess using GRADE methodology.</td></tr><tr><td>6</td><td>We recommend a positive diagnostic strategy as compared to a diagnostic strategy of exclusion for patients with symptoms of IBSs to improve cost-effectiveness. Strong recommendation; high quality of evidence.</td></tr><tr><td>7</td><td>We suggest that categorizing patients based on an accurate IBS subtype improves patient therapy. Consensus recommendation; unable to assess using GRADE methodology.</td></tr><tr><td>8</td><td>We do not recommend testing for food allergies and food sensitivities in all patients with IBS unless there are reproducible symptoms concerning for a food allergy. Consensus recommendation; unable to assess using GRADE methodology.</td></tr><tr><td>9</td><td>We suggest that anorectal physiology testing be performed in patients with IBS and symptoms suggestive of a pelvic floor disorder and/or refractory constipation not responsive to standard medical therapy. Consensus recommendation; unable to assess using GRADE methodology.</td></tr><tr><td>10</td><td>We recommend a limited trial of a low FODMAP diet in patients with IBS to improve global IBS symptoms. Conditional recommendation; very low quality of evidence.</td></tr><tr><td>11</td><td>We suggest that soluble, but not insoluble, fiber be used to treat global IBS symptoms. Strong recommendation; moderate quality of evidence.</td></tr><tr><td>12</td><td>We recommend against the use of antispasmodics for the treatment of global IBS symptoms. Conditional recommendation; low quality of evidence.</td></tr><tr><td>13</td><td>We suggest the use of peppermint to provide relief of global IBS symptoms. Conditional recommendation; low quality of evidence.</td></tr><tr><td>14</td><td>We suggest against probiotics for the treatment of global IBS symptoms. Conditional recommendation; very low quality of evidence.</td></tr></table>
Table 2. (continued)
<table><tr><td>15</td><td>We suggest against PEG products to relieve global IBS symptoms in those with IBS-C. Conditional recommendation; low quality of evidence.</td></tr><tr><td>16</td><td>We recommend the use of chloride channel activators to treat global IBS-C symptoms. Strong recommendations; moderate quality of evidence.</td></tr><tr><td>17</td><td>We recommend the use of guanylate cyclase activators to treat global IBS-C symptoms. Strong recommendation; high quality of evidence.</td></tr><tr><td>18</td><td>We suggest that the 5-HT4 agonist tegaserod be used to treat IBS-C symptoms in women younger than 65 years with ≤1 cardiovascular risk factors who have not adequately responded to secretagogues. Strong/conditional recommendation; low quality of evidence</td></tr><tr><td>19</td><td>We do not suggest the use of bile acid sequestrants to treat global IBS-D symptoms. Conditional recommendation; very low quality of evidence.</td></tr><tr><td>20</td><td>We recommend the use of rifaximin to treat global IBS-D symptoms. Strong recommendation; moderate quality of evidence.</td></tr><tr><td>21</td><td>We recommend that alosetron be used to relieve global IBS-D symptoms in women with severe symptoms who have failed conventional therapy. Conditional recommendation; low quality of evidence.</td></tr><tr><td>22</td><td>We suggest that mixed opioid agonists/antagonists be used to treat global IBS-D symptoms. Conditional recommendation; moderate quality of evidence.</td></tr><tr><td>23</td><td>We recommend that tricyclic antidepressants be used to treat global symptoms of IBS. Strong recommendation; moderate quality of evidence.</td></tr><tr><td>24</td><td>We suggest that gut-directed psychotherapies be used to treat global IBS symptoms. Conditional recommendations; very low quality of evidence.</td></tr><tr><td>25</td><td>Using currently available evidence, we recommend against the use of fecal transplant for the treatment of global IBS symptoms. Strong recommendation; very low quality of evidence.</td></tr></table>
5-HT \( _{4} \) , serotonin type-4 receptor; FOADMAP, fermentable oligosaccharides, disaccharides, monosaccharides, polyols; GRADE, Grading of Recommendations, Assessment, Development, and Evaluation; IBS, irritable bowel syndrome; IBS-C, IBS with constipation; IBS-D, IBS with diarrhea; PEG, polyethylene glycol.
conducted in North America, and these did not identify a difference in the odds of positive serological testing (1.05, 95% CI 0.21–5.15) or biopsy-proven CD (0.93, 95% CI 0.13–6.63) among patients with IBS symptoms vs controls. The increased likelihood of CD among patients with IBS symptoms was greater in studies conducted in secondary or tertiary care and less apparent in population-based studies. The meta-analysis by Irvine et al. (19) also reported the prevalence of CD in different IBS subgroups. The highest prevalence of CD was reported in IBS with diarrhea (IBS-D) (EMA or tTG 5.7%, 95% CI 3.0%–9.1%), followed by IBS with mixed or alternating bowel habits (IBS-M) (3.4%, 95% CI
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Table 3. Population, intervention, comparator, and outcome statements evaluated in the IBS guideline \( ^{a} \)
<table><tr><td>Informal question</td><td>Population</td><td>Intervention</td><td>Comparator</td><td>Outcome</td><td>\( Method^b \)</td></tr><tr><td>Should patients with IBS and diarrhea symptoms be checked for celiac disease?</td><td>Adult patients with IBS and diarrhea</td><td>Serologic tests for celiac disease</td><td>Adult patients without celiac disease</td><td>Prevalence of patients with IBS and celiac disease</td><td>1. Cohort studies2. Case-control studies3. Systematic review4. Meta-analyses</td></tr><tr><td>Can fecal calprotectin, fecal lactoferrin, and/or CRP be used to rule out IBD in patients with IBS and diarrhea symptoms?</td><td>Adults patients with IBS and diarrhea</td><td>Evaluation of CRP, fecal calprotectin, and fecal lactoferrin</td><td>Patients with IBD; healthy controls</td><td>Clinical utility of testing to detect IBD in IBS patients (sensitivity, specificity, and positive and negative predictive value)</td><td>1. Cohort studies2. Systematic review3. Meta-analyses</td></tr><tr><td>Should IBS patients be routinely checked for stool pathogens?</td><td>Adult patients with IBS and diarrhea</td><td>Tests for stool pathogens</td><td>Healthy controls; patients with known Giardia infection</td><td>Prevalence of enteric pathogens in patients with IBS</td><td>1. Population studies2. Cohort studies3. Meta-analyses</td></tr><tr><td>Should patients younger than 45 years routinely undergo colonoscopy for IBS symptoms?</td><td>Adult patients with IBS</td><td>Colonoscopy</td><td>Adults undergoing screening colonoscopy</td><td>Prevalence of abnormal colonoscopic findings in patients with IBS</td><td>1. Prospective trials2. RCT3. Meta-analysis</td></tr><tr><td>Is it more cost-effective to approach patients with suspected IBS using a positive diagnostic strategy as opposed to one of exclusion?</td><td>Adult patients with IBS symptoms</td><td>Cost analysis</td><td>Patients with organic disease; patients without IBS</td><td>Costs of evaluation</td><td>1. Descriptive studies2. Health claims analysis3. Prospective RCT</td></tr><tr><td>Should a low FODMAP diet be used in patients with IBS?</td><td>Adult patients with IBS</td><td>Low FODMAP diet</td><td>Low FODMAP diet or standard diet</td><td>Improvement in global IBS symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Should fiber be used to treat global IBS symptoms?</td><td>Adult patients with IBS</td><td>Soluble or insoluble fiber</td><td>Fiber vs placebo</td><td>Improvement in global IBS symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Should antispasmodics be used to treat global IBS symptoms?</td><td>Adult patients with IBS</td><td>Antispasmodics</td><td>Antispasmodic vs placebo</td><td>Improvement in global IBS symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Does peppermint improve global IBS symptoms?</td><td>Adult patients with IBS</td><td>Peppermint oil (different forms)</td><td>Peppermint oil vs placebo</td><td>Improvement in global IBS symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Should probiotics be used to treat global IBS symptoms?</td><td>Adult patients with IBS</td><td>Probiotics (various formulations)</td><td>Probiotic vs placebo</td><td>Improvement in global IBS symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr></table>
| Lacy et al.
| Lacy et al.

Copyright © 2020 by The American College of Gastroenterology
© 2020 by The American College of Gastroenterology
Society of Gastroenterology 2020;47:1-2.
The American College of Gastroenterology 2020;47:1-2.
The American Journal of Gastroenterology
Table 3. (continued)
<table><tr><td>Informal question</td><td>Population</td><td>Intervention</td><td>Comparator</td><td>Outcome</td><td>\( Method^b \)</td></tr><tr><td>Should polyethylene glycol products be used to treat IBS-C symptoms?</td><td>Adult patients with IBS</td><td>PEG</td><td>PEG vs placebo, lactulose or tegaserod</td><td>Improvement in IBS-C symptoms</td><td>1. RCT2. Systematic reviews</td></tr><tr><td>Should chloride channel activators be used to treat IBS-C symptoms?</td><td>Adult patients with IBS</td><td>Lubiprostone</td><td>Lubiprostone vs placebo</td><td>Improvement in IBS-C symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Should GC-C agonists be used to treat IBS-C symptoms?</td><td>Adult patients with IBS</td><td>Linaclotide; plecanatide</td><td>Linaclotide or plecanatide vs placebo</td><td>Improvement in IBS-C symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Should 5-HT4agonists be used in women younger than 65 years to treat IBS-C symptoms?</td><td>Women with IBS</td><td>Tegaserod</td><td>Tegaserod vs placebo</td><td>Improvement in IBS-C symptoms</td><td>1. RCT2. Systematic review3. Meta-analyses</td></tr><tr><td>Should bile acid sequestrants be used to treat IBS-D symptoms?</td><td>Adult patients with IBS</td><td>Colestipol and colesevelam</td><td>Open-label trials; no placebo-controlled studies</td><td>Improvement in IBS-D symptoms</td><td>1. Open-label trials2. Reviews</td></tr><tr><td>Should rifaximin be used to treat global IBS-D symptoms?</td><td>Adult patients with IBS-D</td><td>Rifaximin</td><td>Rifaximin vs placebo</td><td>Improvement in global IBS-D symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Should alosetron be used in women with IBS-D and severe symptoms?</td><td>Women with IBS and diarrhea</td><td>Alosetron</td><td>Alosetron vs placebo</td><td>Improvement in IBS-D symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Should opioid agonists/mixed antagonists be used to treat IBS-D symptoms?</td><td>Adult patients with IBS</td><td>Eluxadoline</td><td>Eluxadoline vs placebo</td><td>Improvement in IBS-D symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Should tricyclic antidepressants be used to treat global IBS symptoms?</td><td>Adult patients with IBS</td><td>Various TCAs</td><td>TCA vs placebo</td><td>Improvement in global IBS symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr><tr><td>Can psychotherapy be used to treat global IBS symptoms?</td><td>Adult patients with IBS</td><td>Various gut-directed psychotherapy (cognitive-behavior therapy, mindfulness, and hypnosis)</td><td>Psychotherapy vs standard care or education or medical therapy</td><td>Improvement in global IBS symptoms</td><td>1. RCT2. Systematic reviews3. Meta-analyses</td></tr></table>
Management of Irritable Bowel Syndrome

Lacy et al.
Table 3. (continued)
<table><tr><td>Informal question</td><td>Population</td><td>Intervention</td><td>Comparator</td><td>Outcome</td><td>Method*</td></tr><tr><td>Should fecal transplant be performed? Adult patients with IBS to treat IBS symptoms?</td><td>Adult patients with IBS</td><td>Fecal transplant</td><td>Donor vs patient stool; different methods of transplant</td><td>Improvement in global IBS symptoms. 1 RCT2. SYSTEMATIC review3. Meta-analyses</td><td></td></tr><tr><td>5-H, 5-retorhin type-4 receptor; CRP, C-reactive protein; FODMAP, fermentable oligosaccharides; disaccharides, oligosaccharides, polysaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, Oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides,
5-H, 5-retorhin type-4 receptor; CRP, C-reactive protein; FODMAP, fermentable oligosaccharides; disaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, Oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides, oligosaccharides,
1.4%–6.2%); the lowest prevalence was reported in IBS with constipation (IBS-C) (2.1%, 95% CI 0.9%–3.8%).
In summary, it is recommended that patients who fulfill symptom-based criteria for IBS with diarrhea symptoms be screened for CD, given available evidence supports increased odds of CD among patients with IBS symptoms; the significant potential consequences of missing the diagnosis of CD; the availability of highly effective treatment; and the apparent cost-effectiveness of an early diagnosis (22,23). The limited data from North America are recognized. Based on the available data, the greatest yield of screening would be expected in patients with IBS-D (24). The ACG clinical guideline on CD recommends serological screening with immunoglobulin A (IgA) tissue transglutaminase and a quantitative IgA level. If upper endoscopy is performed, 6 biopsies from the duodenum, including the duodenal bulb, should be obtained for histological review (15).
Recommendation
We suggest that either fecal calprotectin \( ^{1} \) or fecal lactoferrin \( ^{2} \) and C-reactive protein \( ^{1} \) be checked in patients without alarm features and with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease.
\( ^{1} \) Strong recommendation; moderate quality of evidence (CRP, fecal calprotectin).
\( ^{2} \) Strong recommendation; very low quality of evidence (fecal lactoferrin).
A major shortfall in making the diagnosis of IBS is the absence of biomarkers (25). It can be difficult to distinguish IBS-D from inflammatory bowel disease (IBD); symptoms alone cannot always accurately distinguish the 2 disorders (26). The pretest probability of IBD in IBS is reported to be \(< 0.5\% - 1.2\%\) (27,28). In the absence of alarm symptoms, the prevalence of IBD in patients with IBS is low; however, after 5 years of symptoms, the incidence is 2.6–5 times higher than in controls (21,29).
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are the 2 serologic tests most commonly used to exclude IBD in patients with IBS-D, although both are nonspecific (30–32). A comprehensive meta-analysis evaluated serologic markers in 2,145 subjects identified as IBD, IBS, or healthy controls and found that an elevated ESR could not discriminate between patient groups, although a CRP ≤0.5 mg/dL yielded a 1% probability of IBD with good accuracy (33). The rapid turnaround time for CRP makes it appealing because fecal inflammatory testing is often not widely available.
Two fecal-derived markers of intestinal inflammation, fecal lactoferrin (FL) (34,35) and fecal calprotectin (fCal) (33,36–39), are both diagnostically useful and perhaps superior to serologic tests (e.g., ESR and CRP) based on their diagnostic accuracy in discriminating IBD from IBS (40–43) (see Supplemental Table 1, Supplementary Digital Content, http://links.lww.com/AJG/B755). At all cutoffs for fCal, the negative predictive value (NPV) as a screening tool is superior to CRP and ESR (38). One meta-analysis comparing fCal with endoscopy showed a sensitivity and specificity of fCal for IBD of 93% (CI 85%–97%) and 96% (79%–99%), respectively (36). FL enzyme-linked immunosorbent assay has a lower sensitivity but higher specificity for active IBD vs IBS of 67%–86% and 96%–100%, respectively, with a positive predictive value and an NPV of 92%–100% and 80%–87%, respectively (35). A meta-analysis of 7 eligible small studies in adults and pediatric patients who underwent FL testing showed a pooled accuracy of
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Table 4. Summary of quality of evidence
<table><tr><td>Recommendation</td><td>Quality of evidence</td></tr><tr><td>Strong: The strength of recommendation is given as strong if most patients should receive the recommended course of action</td><td>High—the estimate of effect is unlikely to change with new data</td></tr><tr><td>Conditional: The strength of recommendation is given as conditional if many patients should have this recommended course of action, but different choices may be appropriate for some patients</td><td>Moderate; low; very low—estimate of effect is very uncertain</td></tr></table>
88% (standard error = 0.01), sensitivity of 78%, and specificity of 94% for differentiating IBD (active and inactive) from IBS (43). At all cutoffs for fCal, the NPV as a screening tool is superior to CRP and ESR (38). Fecal rapid tests are available for both FL and fCal. Rapid testing may be even more accurate than enzyme-linked immunosorbent assay for both fecal tests, although they are not widely available (44). Importantly, significant heterogeneity is seen between cutoff values for both FL and fCal with higher levels of FL being more predictive of IBS and thus less helpful in distinguishing between the 2 diseases as compared to fCal (33).
In summary, fCal and FL are safe, noninvasive, generally available, and can identify IBD with good accuracy (45). Of the serologic testing available, CRP has the highest utility for distinguishing IBD from IBS. Although not directly tested, the combination of CRP with fecal testing—preferably fCal—may provide even greater discrimination. Although these tests are often used clinically to rule out IBD in patients with IBS, it is important to note that neither are biomarkers for ruling in IBS.
Recommendation
We recommend against routine stool testing for enteric pathogens in all patients with IBS.
Conditional recommendation; low quality of evidence.
IBS can arise within months following a variety of GI infections, including bacterial (Campylobacter jejuni and Salmonella), viral (Norwalk), and parasitic (Cryptosporidium spp. or Giardia [Giardia duodenalis or Giardia lamblia]) infections with an OR of
3.51 (95% CI 2.05–6.00) (46–48). The estimated pooled prevalence of postinfection IBS is 11% (95% CI 8.2–15.8), 4.2 times higher in individuals exposed to any of these pathogens as compared to nonexposed individuals. It is worth noting that this prevalence rate seems higher than recently published data (5) because of differences in how patients were defined and categorized. Postinfection IBS is more commonly seen in women, those exposed to antibiotics, and when there is a history of anxiety or depression (49). Although bacterial and viral gastroenteritides are acute and associated with alarm symptoms, parasitic infections range from asymptomatic to self-limited to chronic symptoms of bloating, diarrhea, and abdominal pain–similar to IBS. Of patients with a parasitic cause of enteritis, 41.9% develop IBS vs 13.8% of patients who had a bacterial infection (49). Giardia infection (Giardiasis) is the most common such pathogen in the United States; there are approximately 20,000 reported cases per year, although rates have been decreasing since 2012 (5.8 per 100,000 population) (50). The relative risk of developing IBS, using Rome III criteria, after Giardiasis is 3.4 (95% CI 2.9–3.9), with several studies reporting a prevalence of any parasitic infection in IBS as low as <2% (48,51,52). Based on a longitudinal cohort study using health insurance data, the 1-year incidence of IBS is higher in persons with Giardiasis (incidence ratio = 37.7/1,000 person-years) vs those without a previous Giardia infection (4.4/1,000 person-years) (53).
Animal studies show a cause-and-effect relationship among IBS symptoms and the development of visceral hypersensitivity (demonstrated by luminal balloon distension of the jejunum and rectum), activation of nociceptive signaling pathways, increased intraepithelial lymphocytes and mast cells within the jejunum, and disruption of the intestinal barrier after Giardiasis (54). Exposure to Giardia is also associated with the development of food intolerances up to 3 years after infection (55). Giardiasis is reportable to the Centers for Disease Control and Prevention which recommends screening for patients with acute diarrhea lasting >3 days (56).
Since testing for stool ova and parasites in general is widely available and inexpensive, community gastroenterologists and primary care physicians commonly order them as compared to IBS experts, despite lack of evidence demonstrating a change in diagnosis or outcome (57). However, in patients with risk factors for Giardiasis (Table 5), testing is indicated and should be performed through fecal immunoassays or polymerase chain reaction, tests which have sensitivities of 82%–100% and
Table 5. Centers for Disease Control and Prevention listing of risk factors for development of Giardia infection
<table><tr><td>Risk factors for Giardiasis</td></tr><tr><td>Children in childcare settings, in particular, diaper-aged children</td></tr><tr><td>Close contacts of people with Giardiasis (for example, people living in the same household) or people who care for those sick with Giardiasis</td></tr><tr><td>People who drink water or use ice made from places where Giardia may live (for example, untreated or improperly treated water from lakes, streams, or wells)</td></tr><tr><td>Backpackers, hikers, and campers who drink unsafe water or who do not practice good hygiene (for example, proper handwashing)</td></tr><tr><td>People who swallow water while swimming and playing in recreational water</td></tr><tr><td>People exposed to human feces through sexual contact</td></tr><tr><td>International travelers where Giardia may live, especially in lakes, rivers, springs, ponds, and streams</td></tr><tr><td>Modified from Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED). 2015 [Public Domain].</td></tr></table>
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Lacy et al.
specificities of 91.5%–100% (40,58). Since Giardiasis has the highest prevalence in developing countries, it is reasonable to perform testing in these areas. In addition, in the appropriate clinical setting (e.g., travel to endemic areas, poor water quality, camping, and daycare exposure), testing is warranted. As testing for bacterial and viral infections with subsequent treatment does not prevent development of IBS, and in fact antibiotic exposure may be a risk factor for postinfection IBS, we do not recommend routinely testing for these agents in patients with chronic IBS symptoms (49). In summary, given a lack of clear evidence from the existing literature, we do not recommend routine testing for enteric pathogens, including Giardia, in all patients with IBS, except those with a high pretest probability and definite risk factors for Giardia exposure.
Recommendation
We recommend against routine colonoscopy in patients with IBS symptoms younger than 45 years without warning signs.
Conditional recommendation; low quality of evidence.
The high prevalence of IBS greatly influences IBS patient care. An important aspect is the health and economic burden of unnecessary testing. Colonoscopy is a common test used to confirm the absence of pathology that might be responsible for a patient's intestinal symptoms, such as IBD, microscopic colitis, or colon cancer. This test imposes a significant burden to the patient because of lost work hours, morbidity from the preparation, sedation-related effects, and direct financial costs. This impact is further heightened because many primary care providers directly request a colonoscopy before GI consultation. Colonoscopy is thus one of the most frequent and most expensive tests used during the evaluation of IBS symptoms. However, the evidence to support performing a colonoscopy in younger patients without warning signs, as described below, is poor.
First, it is important to consider key patient features in the decision to conduct a colonoscopy—these are referred to as “alarm features” and include hematochezia, melena, unintentional weight loss, older age of onset of symptoms, family history of IBD, colon cancer, or other significant GI disease. When present, there is a greater sense of concern about identifying a pathologic process that could account for the patients’ symptoms (59). However, alarm features in patients with IBS have a low predictive value (60).
Second, colon cancer screening is a special consideration in patients with IBS. It is important that patients are up-to-date with colon cancer screening independent from their presenting IBS complaints. In other words, if a patient believed to have IBS presents to clinic with symptoms of IBS-D at the age of 52 years having never had a colonoscopy for colon cancer screening, the colonoscopy should be based on the age of the person and considered independent of IBS symptoms. Not uncommonly, the colonoscopy is normal. In a large US study, the rate of colon polyps was lower in patients with IBS compared with healthy controls (61). The reason for this is unclear but was independent of age.
Third, colonoscopy has been recommended in patients with IBS symptoms and without warning signs because it has been suggested that pain during colonoscopy could be an adjunct to the diagnosis of IBS (62). This stems from the theory that IBS symptoms represent visceral hyperalgesia (63), a concept supported by higher levels of reported pain in patients with IBS compared with
non-IBS subjects during balloon inflation of the rectosigmoid colon (64). One study found that subjects with IBS exhibited pain during colonoscopy that replicated their IBS pain (62). This was confirmed by others (65) and led investigators to suggest that pain during colonoscopy could be an “adjunct” to the diagnosis of IBS (62,65). However, this has never been proven in large scale, and controlled trials and the presence of multiple confounders (variation in sedation protocols, quality of prep, skill of endoscopist, and use of \( CO_{2} \) or not) (66) make this theory untenable.
Fourth, clinicians express concern about missing important pathology in patients with IBS symptoms. Several studies have investigated this issue. Chey et al. determined that the most common lesions identified in patients with IBS during colonoscopy were hemorrhoids, diverticulosis, and polyps (61). However, polyps were found in only 7.7% of cases in patients with IBS compared with 26.1% in non-IBS patients (P < 0.0001). This remained significant even after controlling for age and other factors. In a more recent study of 559 subjects who met Rome III IBS criteria, alarm features had a higher rate of discoverable disease, and yet, even among the 136 subjects with no alarm features, Crohn's disease was found in 7.4% of subjects and celiac in 2.9% (59). This second study may speak to both the poor specificity of the Rome criteria, which has a positive likelihood ratio of only 3.35 (40), and the geographic prevalence of diseases such as IBD and CD when studies are conducted in northern populations. Finally, in the largest study to date from Japan of 4,528 subjects undergoing colonoscopy, 5 colonic neoplasms were identified in the 203 Rome positive IBS subjects (67). However, all were detected in subjects older than 50 years. None were seen in the subjects with IBS younger than 49 years.
Finally, 1 common indication that is used to justify colonoscopy in a patient suspected of having IBS-D is to “rule out microscopic colitis.” This may be a special case among women older than 60 years where there is a higher risk of new-onset microscopic colitis. However, there are limited data here. Making things more complicated, a recent meta-analysis identified limitations of the Rome criteria since 32.5% of patients with microscopic colitis would meet Rome criteria for IBS-D while others would meet Rome criteria for functional diarrhea (67,68).
In summary, based on current evidence, in the absence of alarm features, there seems to be no justification for routine colonoscopy in subjects with IBS younger than 45 years (although beyond the scope of this manuscript, the change in screening to age 45 is controversial, and the reader is referred to recent society guidelines and publications for a comprehensive review of this topic). In patients older than 45 years, a recent negative colonoscopy for colon cancer screening or for other investigative purposes should mitigate the need for another colonoscopy for IBS symptoms in the absence of new alarm features. In patients considered to be at high risk of microscopic colitis (older age [>60], female gender, and more intense diarrhea), there may be mounting evidence to support the use of colonoscopy.
Recommendation
We suggest a positive diagnostic strategy as compared to a diagnostic strategy of exclusion for patients with symptoms of IBS to improve time to initiate appropriate therapy.
Consensus recommendation; unable to assess using GRADE methodology.
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Management of Irritable Bowel Syndrome
The role of a careful clinical history, focused on key symptoms of abdominal pain and altered bowel habits in the absence of alarm features, and their duration (>6 months), coupled with a physical examination and minimal diagnostic testing, is sufficient to confidently diagnose a patient with IBS (1,3,4). Providers are often uncomfortable, however, with a positive diagnostic strategy or a symptom-based diagnosis of IBS. Although a validated definition does not exist, a positive diagnostic strategy involves a careful history, physical examination, and the use of a standard definition to make a diagnosis, with limited diagnostic tests.
Justification for a positive diagnosis of IBS, as compared to a diagnosis of exclusion, is based on consensus and data from existing studies (described below) which show a low diagnostic yield of additional workup in suspected IBS without alarm features, and a minimal impact on patient outcomes or satisfaction. Indeed, extensive testing is unlikely to uncover new information and, despite best intentions, does not actually reassure a patient of their IBS diagnosis. In a retrospective evaluation of nearly 500 patients with IBS aged between 18 and 49 years undergoing a “peace of mind” colonoscopy, the procedure had no impact on patient reassurance, quality of life, or psychological symptoms (69).
A systematic review and meta-analysis of more than 1,000 patients compared a range of diagnostic approaches including the symptom-based Rome III criteria to diagnose IBS and noted that the symptom-based Rome criteria performed quite modestly (69.6% sensitivity and 82.0% specificity). Minor clinical enhancements to the criteria increased its overall specificity—high somatization, no nocturnal passage of stool plus high level of somatization, hospital anxiety and depression score >8 plus normal hemoglobin and CRP. Overall, the accuracy of the Rome III criteria plus clinical and laboratory enhancements increased to 95% specificity among patients referred for endoscopy for lower GI symptoms (70).
In another study, 300 primary care patients believed by their doctors to have IBS and no alarm signs were randomized to either a diagnostic strategy of exclusion, which included invasive testing such as sigmoidoscopy with biopsies, stool cultures, and simple laboratory studies (complete blood count and CRP) or to a positive diagnostic strategy which included only a complete blood count and CRP. Regardless of randomization, none of the patients meeting Rome III criteria at baseline were reclassified at 1 year with IBD, colorectal cancer, or CD. Both diagnostic approaches performed similarly in terms of symptoms, quality of life, and patient satisfaction. A positive diagnostic strategy was determined to be noninferior to a diagnosis of exclusion (71).
Not only is a positive diagnostic strategy noninferior to a diagnosis of exclusion, it can substantially shorten time to appropriate therapy. A physician who provides a confident, positive diagnosis of IBS made with minimal investigation is more likely to reduce time to initiation of therapy by engaging patients in shared decision-making. Furthermore, if a primary care physician is able to provide a confident, positive diagnosis without referring a patient to a gastroenterologist, health care costs, and potentially time to initiation of therapy could also be reduced (72). In a large study of positively diagnosed vs undiagnosed IBS-D patients, positively diagnosed patients were much more likely to have already encountered evidence-based therapies and were more likely to have received an effective prescription medication (vs dietary modifications or over-the-counter antidiarrheal agents). Many had also received a referral for brain-gut psychotherapy (73). Although not studied, the same is likely true for the other IBS subtypes.
Finally, a positive diagnosis could lead to improved patient education and reassurance, including knowledge around the
multifactorial nature of IBS, thereby increasing patient acceptance of the diagnosis and early adoption of effective therapies. Despite relatively low quality of evidence supporting the specific outcome of improved time to appropriate treatment, we recommend delaying diagnostic workup when possible and treating patients with IBS empirically, as this can often apprise health care providers to the next steps in care while minimizing unnecessary testing.
Recommendation
We recommend a positive diagnostic strategy as compared to a diagnostic strategy of exclusion for patients with symptoms of IBS to improve cost-effectiveness.
Strong recommendation; high quality of evidence.
Justification for a positive diagnosis of IBS as opposed to a diagnosis of exclusion is based on consensus and data from studies (discussed below) which show a low diagnostic yield of additional diagnostic studies in patients with IBS symptoms without alarm features and a minimal impact on patient outcomes or satisfaction. Unfortunately, in a large survey of community and academic gastroenterologists, more than 70% of community-based providers believed IBS to be a diagnosis of exclusion. These providers ordered nearly twice the number tests per patient and consumed $400 more per patient than those who used a positive diagnostic strategy. Although this difference may not initially seem significant, in a highly prevalent condition such as IBS, the cost difference is substantial (57).
In an elegant Australian language analysis study of provider notes, it was determined that providing IBS patients with a clear, confident, positive diagnosis translated into less demand for additional diagnostic workup. Use of qualifying “exclusion” language around diagnosis, such as “may be suffering from” or “it’s possible that,” “fits the picture of…,” or “working impression is…,” when compared with clear, positive diagnostic language such as “she has,” “she is suffering from,” “she is diagnosed with,” or “I have diagnosed her with” led to more studies, endoscopies, and repeat consultations, driving up the cost of care. Similarly, patients who were diagnosed in the medical record with IBS were unaware of their diagnosis, in contrast to patients with “organic” diseases (74).
In a retrospective employer-based health care claims study of patients with IBS-D, which considered the cost of care within the first 2 years after diagnosis, nearly 80% of health care costs were associated with a diagnosis of exclusion approach, including diagnostic testing, laboratory and radiology services, hospitalizations, and emergency department visits. Only about 20% of patient costs could be related to treatment specifically, including office visits and prescription medications (75). The same was previously shown in patients with IBS-C (76). Both studies show the high costs associated with considering IBS as a diagnosis of exclusion, rather than leveraging symptom-based criteria, particularly in patients younger than 50 years without alarm features. In a large national database study of patients with IBS, colonoscopy was the most frequently conducted test with half of all patients younger than 50 years undergoing at least one (12).
High quality evidence for a positive diagnostic approach comes from a study that conducted a head-to-head, randomized comparison of a positive diagnostic strategy vs an exclusion strategy in >300 patients seen in a primary care setting (71). Patients were followed over 1 year with the primary outcome of quality of life. Not only was noninferiority of the positive strategy
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demonstrated, overall health care costs were almost 40% lower in the positive diagnostic group (\$5,075 vs \$3,160 annually), with no differences between groups in terms of GI symptoms or patient satisfaction. There were no cases of IBD, CD, or cancer discovered through either diagnostic strategy, further underscoring the cost-effectiveness of a positive one (71).
A variety of factors may predispose certain patients to excessive diagnostic testing, as shown in a large US claims database of more than 200,000 patients with IBS in which patients who were older than 50 years, female, with multiple comorbidities, and had more office visits, emergency department visits, and hospitalizations. Patients who had 3 or more diagnostic tests/procedures comprised 40% of the overall sample, with patients with IBS-C driving the most costs (77). Similar variability in diagnostic practices is seen regionally, and across health settings and provider types, high variability is associated with unnecessary costs to the US health system (12).
In summary, a positive diagnostic strategy should be used in an effort to minimize unnecessary testing and reduce health care costs.
Recommendation
We suggest that categorizing patients based on an accurate IBS subtype improves patient therapy.
Consensus recommendation; unable to assess using GRADE methodology.
Although the primary symptom of IBS is recurrent abdominal pain, identification of the patients' predominant stool form on days in which stools are perceived to be abnormal is critical to the proper selection of diagnostic studies and treatments. Current

Figure 1. Bristol Stool Form Scale (English for the United States). Reprinted with permission from the Rome Foundation. ©2000 Rome Foundation. All Rights Reserved.
pharmacological therapies usually target diarrhea and constipation subtypes, although IBS is characterized by 4 distinct subtypes: IBS-D, IBS-C, IBS-M, and those without a significant pattern of abnormal stool (IBS-U). More than half of patients with IBS change predominant subtype over a 1-year period; therefore, clarification of subtype should be performed routinely (78). Diarrhea-predominant IBS patients are more likely to report pain and urgency with each bowel movement, whereas constipation-predominant patients report substantially more symptoms and impaired functioning in between bowel movements; thus, treatment of abdominal pain symptoms may also differ between patient subtypes (79).
To accurately categorize a patient with IBS by subtype, we recommend the following:
1. Predominant stool consistency can be determined based on the Bristol Stool Form Scale (BSFS) (80) (Figure 1).
2. Determine patient's primary stool consistency only on the days s/he reports abnormal bowel movements. This determination should be made when patient is off of therapy(ies) that could affect bowel pattern. Daily diaries should be performed for 2 weeks for the most accurate assessment.
3. Once the pattern of stool consistency is determined, subtype decisions can be made according to the Rome IV criteria (4): a. IBS-C: >25% of bowel movements associated with BSFS 1 or 2 with BSFS 6 or 7 occurring less than 25%.
b. IBS-D: >25% of bowel movements associated with BSFS 6 or 7 with less than 25% of bowel movements with BSFS 1 or 2.
c. IBS-M: >25% of bowel movements associated with BSFS 1 or 2 and >25% of bowel movements associated with BSFS 6 or 7.
d. IBS-U: cannot be determined.
In summary, most therapeutic agents used to treat IBS symptoms were developed with an emphasis on 1 specific IBS subtype; therefore, although not studied prospectively, assigning the wrong subtype to a patient could result in a treatment approach that actually worsens symptoms. Currently, there are no approved medications for the treatment of IBS-M or IBS-U; this is an important gap to be addressed in future research.
Recommendation
We do not recommend testing for food allergies and food sensitivities in all patients with IBS unless there are reproducible symptoms concerning for a food allergy.
Consensus recommendation; unable to assess using GRADE methodology.
Up to 20% of the population report adverse reactions to food (81,82). Reported symptoms are nonspecific and include abdominal pain, nausea, bloating, and diarrhea. Interestingly, when rechallenged with the offending food, only 2%–3% develop recurrent symptoms (81,83). Patients with IBS are more likely than the general population to report adverse reactions to food, with prevalence rates as high as 50% (84–86). Although the default interpretation of reactions to foods is that of an allergic reaction, this is unlikely in IBS. Food allergies are an immune-mediated event and are classified as an IgE response, a non-IgE response, or a mixed (IgE and non-IgE) response (87). Symptoms of a food allergy occur reproducibly and rapidly (usually within
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Management of Irritable Bowel Syndrome
Table 6. Clinical symptoms, rectal examination findings, and anorectal physiologic testing suggestive of a pelvic floor disorder \( ^{a} \)
<table><tr><td>Testing</td><td>Findings</td></tr><tr><td>Rectal examination findings on inspection</td><td>Dermatitis/perianal erythemaRectal prolapseGaping anusHemorrhoidsFistula or fissureRectal scarAnorectal mass</td></tr><tr><td>Digital rectal examination findings suggesting dyssynergic defecation</td><td>Impaired sensory perception of stool (perineal sensation testing)Rectal distension and stool impaction Contraction of the diaphragm, abdomen, and rectum during push maneuvers (abdominal pressure and rectal examination must be performed simultaneously)Abnormal relaxation of external anal sphincter and puborectalis muscles (or no relaxation with Valsalva maneuver)</td></tr><tr><td>Anorectal physiology findings suggesting pelvic floor disorders</td><td>Uncoordinated abdominal, rectoanal, and pelvic floor musclesRectal hyporesponsivityParadoxical increase in sphincter pressure/purobectalis muscle pressure during relaxation or simulated evacuationProlonged balloon expulsion timeInadequate anal relaxation during push maneuversInadequate abdominorectal propulsive forces</td></tr></table>
\( ^{a} \) Many of these symptoms and examination findings are seen in all subtypes of irritable bowel syndrome and are not specific to pelvic floor dyssynergia.
minutes) on exposure to a given food and are absent during avoidance (87). For IgE-mediated food allergies, sensitization with development of specific IgE antibodies to a food allergen needs to occur (e.g., peanuts). Non-IgE food allergies are mediated by T cells, usually confined to childhood, and include food protein-induced enterocolitis syndrome and food protein-induced enterocolitis. Mixed IgE- and non-IgE-mediated food allergies include cow's milk protein allergy, eosinophilic esophagitis, and eosinophilic gastroenteritis.
Food allergies are uncommon and occur in only 1%–3% of adults (88,89). They are more likely to occur in atopic individuals, but are not more likely to occur in patients with IBS (90,91). The most common

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