Version July 2025
INTRODUCTION —
Symptoms such as diarrhea and abdominal pain are common to both active inflammatory bowel disease (IBD) and disorders of gut-brain interaction (DGBI). Patients with an established diagnosis of IBD (eg, Crohn disease, ulcerative colitis) may have persistent gastrointestinal (GI) symptoms, despite successful IBD therapy that has resulted in quiescent disease characterized by mucosal healing and disease remission. Recognizing that persistent symptoms in patients with IBD may not be due to active disease helps to avoid the risk of adverse effects associated with escalating IBD-focused therapies. Persistent GI symptoms in patients with quiescent IBD were previously referred to as "functional," but this term has been replaced [1]. Persistent GI symptoms are associated with anxiety, depression, lower quality of life, and increased health care utilization [1-3]. Therefore, it is important to identify such GI symptoms in order to choose an effective therapeutic approach.
Persistent GI symptoms occurring in patients with quiescent IBD have been diagnosed as irritable bowel syndrome (IBS), but this is not appropriate since patients with IBD have been excluded from studies that developed diagnostic criteria for IBS. Furthermore, the presence of inflammatory mucosal disease cannot always be excluded. In other words, symptoms in some patients appear to be a hybrid of those generated by an IBS-like condition and those generated by ongoing inflammation or other noninflammatory condition such as bile acid diarrhea or small intestinal bacterial overgrowth [1,4].
This topic will discuss recognizing and managing persistent GI symptoms in patients with IBD in remission. The pathophysiology, clinical manifestations, diagnosis, and management of IBS are discussed separately:
●(See "Pathophysiology of irritable bowel syndrome".)
●(See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)
●(See "Treatment of irritable bowel syndrome in adults".)
The clinical manifestations, diagnosis, and treatment of Crohn disease are discussed separately:
●(See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)
●(See "Overview of the medical management of mild (low risk) Crohn disease in adults".)
●(See "Medical management of moderate to severe Crohn disease in adults".)
The clinical manifestations, diagnosis, and treatment of ulcerative colitis are also discussed separately:
●(See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)
●(See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis".)
●(See "Management of the hospitalized adult patient with severe ulcerative colitis".)
●(See "Management of moderate to severe ulcerative colitis in adults".)
CLINICAL PRESENTATION —
Patients with persistent symptoms in the setting of quiescent IBD typically present with nonacute abdominal pain and altered bowel habits (eg, diarrhea, constipation, or alternating diarrhea and constipation). They may also report abdominal bloating and increased gas production in the form of flatulence or belching. Symptoms are not limited to the small bowel and colon, but can also include heartburn, nausea, and dyspepsia [5]. The characterization of persistent symptoms in patients with inactive IBD shares similarities with the clinical presentation of IBS, which is discussed separately. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on 'Clinical manifestations'.)
EVALUATION
Goals — When a patient with IBD presents with ongoing gastrointestinal symptoms (eg, diarrhea, abdominal pain, bloating), the goal is to determine whether the symptoms are due to active intestinal inflammation, an IBD-related complication (eg, partial small bowel obstruction), another organic disease process, or a noninflammatory process. The gastrointestinal tract can express itself in a limited number of ways that highly overlap for all underlying problems.
Accurate diagnosis of the origin of symptoms in patients with IBD requires the following (see 'Initial steps' below):
●Suspect that symptoms may not be inflammatory in nature, based on the patient’s clinical presentation and pertinent negative findings (eg, absence of bloody stools).
●Assess intestinal inflammatory disease activity by biochemical, endoscopic and/or imaging techniques.
●Exclude another organic disease as the etiology if clinical presentation suggests an alternative diagnosis (eg, celiac disease, infectious colitis) (see 'Differential diagnosis' below).
Initial steps — The initial evaluation for patients with IBD who present with GI symptoms (eg, diarrhea, abdominal pain, and/or constipation) includes performing a history and physical examination. The medical history serves to identify potential organic causes for the symptoms. In general, patients whose symptoms are noninflammatory in nature do not present acutely and do not have any of the following alarm features: bloody stools, fever, unintentional weight loss, nocturnal bowel movements, fecal incontinence, large volume diarrhea (ie, ≥6 watery stools daily), abdominal distension, or abdominal mass. These features suggest active IBD (or another organic etiology) and require further investigation. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on 'Additional evaluation based on the presence of alarm features'.)
The medical history also covers travel history, especially to regions where chronic intestinal infections are endemic, changes to diet (eg, becoming vegetarian, changes to fiber intake) and medications for comorbidities (eg, metformin for diabetes).
Physical examination is usually normal in patients with noninflammatory persistent symptoms. However, patients may have mild abdominal tenderness but without abdominal distension. For patients with constipation-predominant symptoms, digital rectal examination may be useful in identifying dyssynergic defecation, particularly if the patient complains of a sense of incomplete evacuation or is requiring digital maneuvers to empty the rectum. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on 'History and physical examination' and "Etiology and evaluation of chronic constipation in adults", section on 'History and physical examination'.)
Initial diagnostic testing includes the following:
●Serum markers – We assess for systemic inflammation by testing for an acute phase reactant such as C-reactive protein (CRP); erythrocyte sedimentation rate (ESR) is an alternative. Elevated CRP or ESR in the absence of other causes (eg, rheumatoid arthritis, infection) typically represents active intestinal inflammation in patients with IBD. However, normal values do not confirm inactive disease because many patients do not have elevated acute phase reactants despite active inflammation. In addition, the results of CRP and ESR determinations may be discrepant due to factors related to the inflammatory process (eg, differences in specific cytokines), and these issues are discussed separately. (See "Acute phase reactants", section on 'Laboratory evaluation'.)
●Stool markers of inflammation – We obtain the stool marker calprotectin or lactoferrin (not as commonly used) to assess for intestinal inflammation [6-8]. A fecal calprotectin value within the reference range (generally <50 mcg/g) indicates that mucosal disease is in remission [9-11]. If the fecal calprotectin value is above the reference range, we evaluate the mucosa for active inflammation with ileocolonoscopy and/or cross-sectional imaging. (See 'Assessment of IBD activity' below.)
The fecal calprotectin threshold indicating quiescent disease has been uncertain. A cutoff value of 150 or 250 mcg/g has been used in epidemiologic studies, but some patients have active disease with calprotectin ranging from 50 to 250 mcg/g. Interpreting the calprotectin value also depends on the extent of IBD. Patients with active disease limited to the small bowel tend to have lower calprotectin levels than patients with active pancolitis.
●Other stool studies – For patients with chronic diarrhea, stool testing for infectious pathogens is individualized and informed by the patient’s risk factors and whether symptom exacerbation is present. In selected patients (eg, those with recent travel to an endemic area, symptoms shared by family members), we obtain stool testing for chronic infectious pathogens (eg, Giardia duodenalis) and for amebiasis by checking serology or antigen testing together with identification of the parasite in the stool. Intestinal amebiasis is discussed separately. (See "Intestinal Entamoeba histolytica amebiasis".)
The approach to evaluating patients with acute or chronic diarrhea is discussed in more detail separately. (See "Approach to the adult with acute diarrhea in resource-abundant settings" and "Approach to the adult with chronic diarrhea in resource-abundant settings".)
Assessment of IBD activity — For patients with symptoms or diagnostic studies suggestive of active IBD (eg, bloody diarrhea, unintentional weight loss, elevated CRP or fecal calprotectin), we assess the degree intestinal inflammation with the following tests (see 'Initial steps' above):
●Endoscopy – We perform ileocolonoscopy with biopsies because endoscopic and histologic evaluation determines the degree and extent of ileocolonic disease activity. Mucosal biopsies may demonstrate active inflammation or may confirm that histologic remission of IBD has been achieved, which supports the concept that symptoms are not related to intestinal inflammation [12]. Flexible sigmoidoscopy may be an alternative to colonoscopy for patients with history of distal colitis.
●Imaging – We obtain small bowel imaging for patients with a history of Crohn disease when active small bowel inflammation is suspected (eg, chronic diarrhea, elevated CRP) but when ileocolonoscopy with biopsies does not demonstrate inflammation. Several imaging modalities are available including computed tomography (CT) enterography, magnetic resonance (MR) enterography, capsule endoscopy, or gastrointestinal ultrasound [13]. We prefer MR enterography over CT enterography (although both have high sensitivities) for detecting active small bowel inflammation because MR enterography lacks radiation exposure and provides a detailed characterization of stenotic lesions [14]. In centers where expertise is available, transabdominal gastrointestinal ultrasound is also preferred over CT enterography because it is noninvasive, well-accepted by patients, requires no preparation, and can be performed at the point of care [13]. Ultrasound has a sensitivity similar to that of MR enterography, and it may be repeated in follow-up. (See "Transabdominal ultrasonography of the small and large intestine", section on 'Crohn disease'.)
The endoscopic and imaging evaluation for patients who are suspected of having active IBD is discussed in more detail separately. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults", section on 'Diagnostic evaluation' and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Evaluation'.)
Additional studies — If active IBD or an IBD-related complication is not suspected as the cause of symptoms based upon clinical presentation and initial diagnostic evaluation, we may obtain the following tests to exclude other conditions:
●Serology for celiac disease – Serology for celiac disease (eg, anti-tissue transglutaminase antibody) is obtained if it was not performed during the patient’s initial diagnostic work-up for IBD and if the patient is not following a gluten-restricted diet (see "Diagnosis of celiac disease in adults", section on 'Serologic evaluation').
●Stool testing for fecal elastase – Stool testing for fecal elastase is performed in patients with symptoms suggestive of pancreatic exocrine insufficiency (ie, chronic diarrhea that may be accompanied by steatorrhea, abdominal pain, or unintentional weight loss). (See "Exocrine pancreatic insufficiency".)
●Tests for patients with constipation-predominant symptoms – For patients with constipation-predominant symptoms, we typically obtain a plain abdominal x-ray or, preferably, gastrointestinal ultrasound (if expertise in this technique is available) to assess the stool burden, particularly for patients with ulcerative colitis [15]. If symptoms are suggestive of pelvic floor dyssynergia (eg, a sense of incomplete evacuation, need for digital maneuvers), we perform a digital rectal examination and anorectal manometry. (See "Etiology and evaluation of chronic constipation in adults".)
●Screening for psychologic distress – Psychologic factors such as anxiety, depression, or inadequate coping strategies may influence the expression of gastrointestinal symptoms [16]. Assessment of the patient’s psychologic status may be facilitated by the use of screening questionnaires, and this is discussed separately [17]. (See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis" and "Screening for depression in adults".)
●Tests of uncertain value – Breath testing for specific carbohydrate malabsorption has limited utility in guiding dietary therapy, with the exception of lactose breath testing. Demonstrating normal lactose absorption may help avoid the unnecessary restriction of calcium-rich dairy foods. The diagnosis and management of lactose intolerance are discussed separately. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)
Assessing fructose, sorbitol, or mannitol absorption has little utility in designing dietary approaches because functional symptoms do not correlate well with malabsorption demonstrated on breath testing [18,19].
We do not evaluate for small intestinal bacterial overgrowth (SIBO) using hydrogen breath testing because such testing has not been assessed for sensitivity and specificity in patients with IBD. In addition, the performance characteristics of breath testing in patients with DGBI are limited.
DIFFERENTIAL DIAGNOSIS —
When patients with IBD present with persistent symptoms and active disease has been excluded, the differential diagnosis remains broad. Subsequent evaluation often depends on whether the predominant bowel-related symptom is diarrhea or constipation. Other organic disorders that result in GI symptoms include the following (see 'Additional studies' above):
●Celiac disease – Patients with celiac disease may report nonbloody diarrhea, while signs of malabsorption (eg, iron deficiency anemia) may also be present. However, malabsorption is also common in patients with IBD without celiac disease. (See "Diagnosis of celiac disease in adults" and "Approach to the adult patient with suspected malabsorption".)
●Infectious diarrhea – Patients who travel to endemic areas are at higher risk for chronic infectious diarrhea such as giardiasis or amebiasis. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis" and "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis".)
●Lactose malabsorption – Some types of carbohydrate malabsorption (eg, lactose) may be more common in patients with IBD. In a study of 91 patients with Crohn disease, 56 patients with ulcerative colitis and 71 healthy controls, the rates of lactose malabsorption detected by breath hydrogen testing were higher in patients with Crohn disease or ulcerative colitis compared with healthy controls (42 or 40 percent, respectively, versus 18 percent) [20]. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)
●Small intestinal bacterial overgrowth – Patients with Crohn disease who have strictures, fistula, or history of surgical resection may be at increased risk for small intestinal bacterial overgrowth (SIBO). Intestinal hypomotility in the setting of quiescent Crohn disease and a history of prior bowel surgery may be risk factors for SIBO [21,22]. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis".)
●Bile acid diarrhea – Patients with ileal Crohn disease or ileal resection are at risk for bile acid diarrhea. Ileal disease or resection reduces small bowel absorption of bile acids and results in excessive bile acids in the colon, leading to diarrhea. In addition, diarrhea following cholecystectomy is often due to bile acid diarrhea, which is discussed separately. (See "Approach to the adult patient with suspected malabsorption", section on 'Other infrequently performed tests' and "Approach to the adult with chronic diarrhea in resource-abundant settings", section on 'Postcholecystectomy diarrhea'.)
●Pancreatic exocrine insufficiency – Patients with IBD may be at increased risk for pancreatic exocrine insufficiency, and they can present with chronic diarrhea with or without steatorrhea and abdominal pain. In a cross-sectional study including 200 patients with IBD and 100 healthy controls, patients with IBD were more likely to have pancreatic insufficiency based on screening with a fecal elastase test (≤200 mcg/g) compared with healthy controls (odds ratio 10.5, 95% CI 2.5-44.8) [23]. However, fecal elastase values may be falsely low in patients with chronic diarrhea, if this is not corrected for stool water by the laboratory. (See "Chronic pancreatitis: Clinical manifestations and diagnosis in adults".)
●Pelvic floor dyssynergia – Defecatory symptoms including constipation, fecal urgency with overflow diarrhea, and fecal incontinence are more common in patients with IBD in remission than in individuals without IBD [24,25]. The evaluation and management of pelvic floor dyssynergia are discussed separately. (See "Etiology and evaluation of chronic constipation in adults".)
MANAGEMENT
Goals and sequence of therapies — Because the most effective treatment for persistent symptoms in patients with inactive IBD is not well defined and often depends on the specific symptom(s), our treatment approach is based on the following principles (see 'Initial measures' below):
●The goal of therapy is to provide relief of symptom(s).
●Our preference for therapies is based on limited data and clinical experience, and selection among them depends on the specific symptom(s), severity of symptoms, response to prior therapy, risk of adverse effects, and patient preferences.
●Managing persistent symptoms in patients with inactive IBD is similar to the management of patients with IBS or functional dyspepsia (if upper GI symptoms are present). However, much of the supporting evidence is indirect and is extrapolated from studies in patients with disorders of gut-brain interaction (DGBI) but without coexisting IBD.
Initial measures — Establishing a clinician-patient relationship is an important aspect of management of patients with quiescent IBD and persistent GI symptoms. We initially use dietary and lifestyle modification for patients with symptoms rather than begin specific pharmacologic agents. For patients who fail to respond to initial management, we proceed with behavioral therapy or symptom-based pharmacologic therapy. (See 'Subsequent therapy' below.)
Initial measures include the following:
●Low FODMAP diet – For the initial treatment of persistent symptoms (eg, diarrhea, abdominal pain, bloating) in patients with IBD in remission, we begin a diet low in slowly absorbed and indigestible short-chain carbohydrates (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols [FODMAPs]) (table 1). These short-chain carbohydrates are osmotically active in the small intestine and are rapidly fermented in the colon, resulting in symptoms of abdominal pain and bloating. Low FODMAP diet is discussed in more detail separately. (See "Treatment of irritable bowel syndrome in adults", section on 'Low-FODMAP diet'.)
Implementation of a FODMAP dietary strategy should be performed by a dietitian with training in gastrointestinal disorders. This involves screening the patient for disordered eating behaviors that may increase the nutritional risk of this approach. If suitable, the diet is individualized and food over-restriction is avoided [26,27]. FODMAP dietary education consists of initially avoiding all high FODMAP foods for two to six weeks. If symptoms improve, gradual reintroduction of foods high in individual FODMAPs determines the tolerated dose of specific FODMAPs [28]. The subsequent diet is then personalized. As an example, for patients with IBS, the long-term, low FODMAP diet is usually less restrictive. If the patient cannot follow major dietary restrictions or if nutritional compromise is a risk, we typically use a "FODMAP gentle" diet in which only common FODMAP-rich foods are restricted. This approach has not been tested in clinical trials [27].
Data have indicated that a low FODMAP diet reduced persistent GI symptoms in patients with quiescent IBD [29-33]. In a meta-analysis of six studies including 319 patients with IBD in remission, a low FODMAP diet resulted in improvement in multiple symptoms: diarrhea (odds ratio [OR] 0.24, 95% CI 0.11-0.52); bloating (OR 0.17, 95% CI 0.06-0.16); and abdominal pain (OR 0.24, 95% CI 0.16-0.35) [30]. In a blinded rechallenge study including 29 patients with quiescent IBD, patients ingesting fructans had lower rates of pain relief compared with those ingesting glucose (62 versus 90 percent), suggesting that FODMAPs were the likely inducer of symptoms [31].
●Mediterranean diet – Use of a Mediterranean diet is an alternative dietary approach. The Mediterranean diet consists mostly of plant foods (eg, wholegrains, fruit, vegetables, and legumes) and olive oil as the major source of fat, while allowing low to moderate intake of fish, dairy, and nuts, and wine consumption with meals [34]. However, studies involving the Mediterranean diet for patients with inactive IBD and persistent symptoms are limited [35]. (See "Healthy diet in adults", section on 'Mediterranean diet' and "Nutrition and dietary management for adults with inflammatory bowel disease", section on 'Other dietary options'.)
●Other diet options – The use of other dietary approaches depends on the patient’s predominant symptom, the underlying disease process, and clinician preference. For example, for patients with constipation-predominant symptoms, we advise an increase in dietary fiber if baseline intake is low (eg, less than 14 grams per 1000 calories). (See "Healthy diet in adults", section on 'Fiber' and "Nutrition and dietary management for adults with inflammatory bowel disease", section on 'Patients in remission'.)
For patients with symptoms that are related to ingesting moderate amounts of lactose-containing foods (eg, bloating, abdominal pain), we advise lactose restriction (if the patient declines a trial of a low FODMAP diet). Both of these dietary approaches are reasonable, while data to support them are limited. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)
Other restrictive diets (eg, gluten-restricted diet, specific carbohydrate diet) may help relieve symptoms, but these have not been studied in randomized controlled trials in adults with IBD and may not meet nutritional requirements due to their restrictive nature [36].
Restriction of fat, alcohol, and caffeine is often advised; however, the effect of these dietary restrictions on persistent symptoms has not been well studied.
Gut-specific hypersensitivity reactions to food proteins is an emerging therapeutic approach for treating DGBI [37], but guidance on how to do this in clinical practice is unclear. Such an approach in patients with persistent symptoms and quiescent IBD has not been studied. (See "History and physical examination in the patient with possible food allergy" and "Food intolerance and food allergy in adults: An overview".)
●Physical activity – Mild to moderate intensity exercise is safe and improves well-being in patients with IBD, but there is no conclusive data suggesting an anti-inflammatory effect [38]. Hence, exercise may have a positive effect on functional GI symptoms, but this aspect has not been directly studied [39]. (See "Exercise prescription and guidance for adults".)
Subsequent therapy — For patients who do not improve with initial measures, we may use behavioral therapy and/or pharmacologic therapies directed at specific symptoms. (See 'Initial measures' above.)
Behavioral therapies — Patients with quiescent IBD and persistent GI symptoms may benefit from behavioral modification, similar to the approach for treating IBS. (See "Treatment of irritable bowel syndrome in adults".)
Studies involving patients with IBS suggested that behavioral therapies (eg, cognitive behavioral therapy, gut-directed hypnotherapy, mindfulness therapy) improved GI symptoms and quality of life [40-42]. Clinical trials in patients with IBD have assessed behavioral therapies for treating symptoms and mood disorders, providing coping skills, and improving quality of life [43]. Most therapies improved quality of life and mood disorders in the short term. Therapies that emphasize acceptance and mindfulness appear to perform better than cognitive behavioral therapy. Applying these data to guide management of patients with IBD and persistent GI symptoms is challenging. However, such patients may have symptomatic improvement by treating coexisting mood disorders.
Symptom-based therapies
Patients with diarrhea — Symptomatic treatment with antidiarrheal medications such as loperamide is an option for patients who have diarrhea in the absence of active mucosal inflammation. We do not use loperamide for patients with active inflammatory disease or for those who are hospitalized. The use of loperamide for patients with Crohn disease or ulcerative colitis is discussed separately. (See "Overview of the medical management of mild (low risk) Crohn disease in adults", section on 'Antidiarrheal medications' and "Medical management of low-risk adult patients with mild to moderate ulcerative colitis", section on 'Other therapies'.)
There are several other medications for treating persistent diarrhea in patients with quiescent IBD, based on indirect evidence from studies in patients with diarrhea-predominant IBS. These include tricyclic antidepressants, 5-HT3-receptor antagonists (eg, ondansetron), and rifaximin, but data are limited. The use of pharmacologic agents for patients with diarrhea-predominant IBS is discussed in more detail separately. (See "Treatment of irritable bowel syndrome in adults", section on 'Antispasmodic agents for episodic symptoms' and "Treatment of irritable bowel syndrome in adults", section on 'Tricyclic antidepressants for persistent symptoms'.)
For patients with Crohn disease in remission who have chronic diarrhea, bile acid diarrhea should be suspected. Consensus clinical practice guidelines have suggested performing testing to confirm bile acid malabsorption [44]. (See "Approach to the adult with chronic diarrhea in resource-abundant settings", section on 'Postcholecystectomy diarrhea'.).
The principles of using bile acid-sequestering agents include that there is no optimal dose but that these agents should be initiated at low doses. The dose may be increased at weekly intervals if symptoms do not improve or reduced if constipation develops. For cholestyramine, the initial dose is 4 g daily (which represents one sachet of powder daily). If symptoms persist, the dose is titrated to a maximum of 12 g daily, taken in three divided doses [45,46]. If cholestyramine is poorly tolerated because of side effects (eg, constipation, nausea), an alternative bile acid-sequestering agent, such as colesevelam, can be used. Colesevelam is usually available in capsule form with each capsule containing 625 mg. Initial therapy is three capsules, taken once or twice a day (3.75 g) [45-47]. Published evidence that informs the maximum colesevelam dose is limited but suggests a maximum dose of six capsules daily.
For patients with Crohn disease and extensive ileal involvement or resection resulting in short bowel syndrome, use of bile acid sequestering agents should be avoided. (See "Management of short bowel syndrome in adults", section on 'Other interventions with unclear role'.)
Patients with abdominal pain — Chronic abdominal pain in the absence of active mucosal inflammation or an IBD-related complication can present a management challenge. There are few studies that can guide choosing a specific medication for abdominal pain in this setting, and our approach is similar to the management of patients with IBS. We use antispasmodic medications (eg, dicyclomine, hyoscyamine, peppermint oil) as needed for patients with abdominal pain but without constipation, and for patients with abdominal pain and constipation if the pain persists after successful treatment of constipation [48]. (See 'Patients with constipation' below.)
The use and adverse effects of antispasmodics for patients with IBS is discussed separately. (See "Treatment of irritable bowel syndrome in adults", section on 'Antispasmodic agents for episodic symptoms'.)
For patients who cannot tolerate or do not improve with an antispasmodic agent, a low-dose tricyclic antidepressant (eg, amitriptyline) may result in symptomatic improvement. In a retrospective study including 81 patients with quiescent IBD and persistent symptoms, tricyclic antidepressant therapy was associated with moderate improvement in abdominal pain in 54 patients (67 percent) [49]. (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects".)
Serotonin-norepinephrine reuptake inhibitors (eg, duloxetine) may result in symptomatic improvement, but selective serotonin reuptake inhibitors are generally less effective for IBS-related abdominal pain [50]. (See "Treatment of irritable bowel syndrome in adults", section on 'Tricyclic antidepressants for persistent symptoms'.)
Drug therapy directed toward neuropathic pain, such as use of gabapentin at lower doses, is an alternative to antidepressants for chronic abdominal pain [51], but there are few published data. (See "Overview of pharmacologic management of chronic pain in adults", section on 'Antiseizure medications'.)
Patients with constipation — Our approach for patients with quiescent IBD and constipation-predominant symptoms includes adequate intake of fluids and fiber along with at least three mealtimes per day. If dietary intervention is not helpful, polyethylene glycol (PEG) solution is a subsequent option. If radiologic imaging demonstrates marked stool burden, use of a bowel preparation may be an option prior to initiating long-term therapy. Evaluation and management of constipation are discussed separately. (See "Etiology and evaluation of chronic constipation in adults" and "Management of chronic constipation in adults" and "Bowel preparation before colonoscopy in adults".)
Low dietary fiber intake can be addressed by dietary counseling or by initiating a fiber supplement. Psyllium, a slowly fermentable fiber, is a good choice. However, if such a fiber supplement is not well tolerated, a non-fermentable fiber such as sterculia or methylcellulose can be tried, but published data to support this approach are lacking. Wheat bran should be avoided due to its fructan content and its risk of exacerbating abdominal pain and bloating [52]. Because some patients may experience increased bloating and gas with increasing fiber intake, we initiate fiber supplements at a low dose (eg, one teaspoon daily), and then increase the dose every three days (if tolerated) to a target dose of two heaped teaspoons twice daily. Fiber supplementation for functional disorders is discussed separately. (See "Treatment of irritable bowel syndrome in adults".)
The goal for daily fluid intake varies depending on a number of factors including the patient’s activity level and stool output, and this is discussed separately. (See "Maintenance and replacement fluid therapy in adults", section on 'Water balance'.)
For patients with constipation-predominant symptoms that do not improve with dietary intervention, we begin PEG because it is inexpensive, widely available, and has fewer side effects compared with other osmotic laxatives (eg, magnesium hydroxide). The use of osmotic and other laxatives for patients with IBS is discussed separately. (See "Treatment of irritable bowel syndrome in adults", section on 'Medical treatment for constipation-predominant IBS (IBS-C)'.)
We do not use secretagogues (eg, lubiprostone, linaclotide) or prokinetic drugs (eg, the 5-HT4-receptor antagonists) for patients with IBD, and published studies in this patient population are lacking.
Patients with bloating — We use a low FODMAP diet to manage bloating. (See 'Initial measures' above.)
Studies in patients with IBS suggested that bloating may improve by treating underlying constipation. In some patients with abdominal distension, abdominophrenic dyssynergia (ie, the paradoxical flattening of the diaphragm) may be the etiology. We use diaphragmatic breathing exercises for treating abdominophrenic dyssyngeria based on clinical experience, although published studies in patients with IBS or IBD are lacking.
Patients with defection disorders — Pelvic floor physiotherapy and biofeedback therapy may be beneficial in patients with IBD who have pelvic floor dyssynergia and/or fecal incontinence. (See "Etiology and evaluation of chronic constipation in adults".)
Therapies of uncertain benefit — The therapeutic benefit of the following interventions is uncertain in patients with inactive IBD and persistent GI symptoms:
●Complementary and alternative medicine – Complementary and alternative medicine (CAM) remedies (eg, herbal preparations, cannabis) may help relieve IBD-related symptoms such as abdominal pain [38,53]. In a study including 38 patients with Crohn disease in remission, osteopathic treatment was associated with greater improvement in IBS-related symptoms and in fatigue compared with no osteopathic therapy [54]. However, most CAM studies have not specifically addressed persistent GI symptoms in patients with IBD. More data are needed before CAM remedies are routinely used in this setting. (See "Overview of herbal medicine and dietary supplements".)
●Therapies that modify intestinal microbiota – Therapies that modify the intestinal microbiota (eg, antibiotics, probiotics, prebiotics, fecal microbiota transplantation) have mainly been studied in patients with either IBS or active IBD. Probiotics have been assessed for their effect on inflammation in patients with IBD, while they have been more widely studied for functional symptoms. The degree of benefit from probiotics and the most effective species are unclear.
Antibiotics, such as rifaximin, may improve gastrointestinal symptoms in patients with IBD and functional symptoms, presumably by treating underlying small intestinal bacterial overgrowth [22]. However, no data are available to guide antibiotic therapy in this setting. (See "Small intestinal bacterial overgrowth: Management".)
Treatment with prebiotics or fecal microbiota transplantation has been directed toward mucosal inflammation in patients with IBD, but their effect on persistent GI symptoms in patients with quiescent IBD has not been well studied. Prebiotics are mostly FODMAPs (eg, fructo-oligosaccharides, inulin). Thus, use of prebiotics in patients with Crohn disease may exacerbate symptoms, particularly abdominal pain, bloating, and flatulence [55]. (See "Treatment of irritable bowel syndrome in adults", section on 'Other therapies'.)
Therapies to avoid — We do not use nonsteroidal anti-inflammatory drugs (NSAIDs) for treating persistent GI symptoms in patients with quiescent IBD, because NSAIDs increase the risk of gastric and small bowel ulceration. (See "NSAIDs (including aspirin): Pathogenesis and risk factors for gastroduodenal toxicity".)
Opioids should be avoided for patients with quiescent IBD and persistent symptoms because of the potential adverse effects and risks (opioid-induced constipation, narcotic bowel syndrome, opioid-induced hyperalgesia, and opioid dependence) [56]. (See "Use of opioids in the management of chronic pain in adults".)
Patients with chronic abdominal pain that is not improving with dietary and symptom-based therapy may benefit from consultation with a pain management specialist.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Irritable bowel syndrome" and "Society guideline links: Ulcerative colitis in adults" and "Society guideline links: Crohn disease in adults".)
SUMMARY AND RECOMMENDATIONS
●Background – For some patients with inflammatory bowel disease (IBD), symptoms such as diarrhea and abdominal pain may persist despite healing of intestinal inflammation. Recognizing that persistent symptoms in patients with IBD may not be due to active inflammation helps to avoid the risk of adverse effects associated with escalating inflammation-focused therapies. (See 'Introduction' above.)
●Evaluation – Evaluation of persistent gastrointestinal (GI) symptoms in patients with IBD requires the following steps (see 'Goals' above):
•Suspect that symptoms may be unrelated to intestinal inflammation, based on the patient's clinical presentation, pertinent negative findings (eg, absence of bloody stools or fever), and prior history of IBD in remission (minimally or no active mucosal inflammation).
•Assess for active intestinal inflammation or an IBD-related complication as the etiology of symptoms. The evaluation may include biochemical tests (serum CRP, fecal calprotectin), endoscopic examination of the ileum and colon with biopsies, and cross-sectional imaging of the small intestine (eg, MR enterography, intestinal ultrasound [if available]). (See 'Assessment of IBD activity' above.)
•Evaluate for other organic diseases if clinical presentation suggests an alternative diagnosis (eg, celiac disease, infectious colitis).
●Differential diagnosis – For patients with persistent gastrointestinal symptoms despite inactive IBD, the differential diagnosis remains broad and includes alternative causes (eg, celiac disease) and coexisting conditions (eg, bile acid diarrhea, lactose malabsorption. (See 'Differential diagnosis' above.)
●Management – For patients with IBD in remission and persistent GI symptoms, we suggest implementing a diet that is low in FODMAPs in consultation with a dietitian (Grade 2B). Guidance from a dietician helps avoid unnecessary dietary restriction and helps to maintain a nutritionally adequate diet. (See 'Initial measures' above and "Treatment of irritable bowel syndrome in adults", section on 'Low-FODMAP diet'.)
For patients who do not have adequate relief of symptoms with initial measures, behavioral therapies may be of benefit, particularly when symptoms occur in association with mood disorders. For patients with persistent or severe symptoms, we use pharmacologic therapies directed at specific symptoms. (See 'Subsequent therapy' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff thank Dr. Richard MacDermott for his contributions as author to prior versions of this topic review.
