Our Recommendations

The authors therefore recommend routine upper GI endoscopy in all patients with IBD with biopsies performed in the upper and lower esophagus and, in particular, those with established or suspected CD with upper GI symptoms. Endoscopy may conveniently be performed at the time of colonoscopy especially in those with concomitant complaints of diarrhea, and may aid in identifying sites of unsuspected CD. Moreover, routine upper GI endoscopy may be considered a comprehensive evaluation tool for determining CD extent in patients with established CD, and allows for differentiation of UC from CD in patients with predominantly colonic involvement with no small bowel or patchy colonic involvement, which are both clear signs of CD. Given the risks associated with PPI use, we recommend stepping down therapy when possible, as well as increased utilization of histamine receptor antagonists (H2RAs), such as ranitidine, and calcium-containing antacids for those with infrequent symptoms, as many patients with IBD are at risk for osteoporosis. In patients with atypical or extraesophageal GERD who lack typical symptoms of pyrosis and regurgitation, we recommend pH testing to avoid giving PPIs to patients without true GERD. Patients who do not have significant acid reflux on pH testing performed while off of PPI may be classified as having functional heartburn or reflux hypersensitivity, based on the presence or absence of symptom correlation to reflux events. Treatment of these patients is largely empiric, with trials of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), or gabapentin. The authors also recommend avoidance of PPI therapy in patients with IBD, given the extensive long-term side effect profile of these agents, and the likely exacerbation of symptoms in these patients ( Fig. 1 ).

Evaluation and management of suspected GERD. EGD, esophagogastroduodenoscopy.

Gastroparesis

Gastroparesis (GP) is a syndrome of delayed gastric emptying in the absence of mechanical obstruction. The cardinal symptoms include nausea and vomiting (N/V), early satiety, postprandial fullness, bloating, and upper abdominal pain. In severe cases, it can result in weight loss and malnutrition. The cause is most frequently idiopathic, although it can also result from diabetes, prior surgery, thyroid disease, neurologic disease, autoimmune disease, medications that retard gastric emptying, or following a viral illness.

Delayed gastric emptying (GE) appears to occur more frequently in patients with CD as compared with UC or healthy controls. One study of children with IBD found that 33% of those with CD had had delayed GE, whereas all of the children with UC had normal GE. After medical management of their CD and nutritional supplementation, significant improvements in GE were seen. Another study involving patients with IBD with moderate or no disease activity, 46% of patients with CD had prolonged GE, as compared with 20% of patients with UC. In the subgroup of patients with CD, only vomiting was associated with delayed GE, whereas pain, nausea, bloating, and early satiety were not.

The mechanism for the delayed GE that occurs in some patients with IBD is unclear. In an animal model of rats with colitis induced via Trinitrobenzenesulfonic acid exposure, gastric emptying was found to be delayed, even in the absence of local gastric inflammation. When these rats had their pelvic nerve sectioned, gastric emptying returned to baseline, suggesting that pelvic afferent nerve hyperactivity may contribute to delayed gastric emptying. Another study showed threefold elevations in postprandial cholecystokinin (CCK) levels in patients with CD versus controls, and postulated that excessive CCK release may contribute to delayed GE. Other potential mechanisms could be loss of the interstitial cells of Cajal, which are lower in density in the small bowel tissue from patients with CD as compared with controls.

Studies have also yielded conflicting results regarding the correlation between disease activity in CD and the presence of delayed GE. A study of 17 children with CD found that GE of solids was significantly slower in those who were malnourished, although liquid emptying was preserved, a phenomenon seen in patients with anorexia. The delay in GE correlated with caloric intake and involvement of the duodenum (57%), but not with disease activity. Still, others have shown that disease activity may be correlated with prolonged GE. Not surprisingly, patients with UC who have had previously undergone IPAA have similar solid-phase GE compared with controls, but those with more than 6 bowel movements (BMs) per day have more rapid emptying of liquids as compared with those who had 6 or fewer BMs per day and those with constipation also have delayed GE.

Our Recommendations for Gastroparesis

An algorithm for the evaluation and management of suspected GP in patients with IBD is presented in Fig. 2 . We recommend screening for delayed GE by solid-phase gastric emptying scintigraphy using the standardized method by Tougas and colleagues, with a positive test having greater than 10% retention at 4 hours. Drugs that effect gastric motility, such as opioids, PPIs, ondansetron, prokinetics, anticholinergics, and glucagon-like peptide 1 (GLP-1) agonists, should be discontinued for 48 to 72 hours before testing. We recommend against the use of wireless motility capsule, as it is contraindicated in patients with CD given the risk of capsule retention in patients with possible strictures. We also recommend against the use of 13-C breath testing, as its accuracy is contingent on normal small bowel absorption, which may not be the case in many patients with IBD. An upper endoscopy should be performed to exclude upper GI CD, other mucosal disease, celiac sprue, and mechanical obstruction. In patients with CD, MRI enterography should be performed to exclude distal strictures resulting in recurrent partial small bowel obstruction that may mimic symptoms of GP. After GP is diagnosed, potential causes should be screened for and treated.

Evaluation and management of suspected GP.

Initial management of gastroparesis consists of dietary modification with a low-fat, low insoluble fiber diet with small, frequent meals, and use of a liquid multivitamin. Foods that have been found to provoke symptoms include those that are fatty, acidic, spicy, or contain significant roughage. For those unable to tolerate solids, food can be blenderized or liquid nutritional supplements can be used. Antiemetics can be used to treat nausea. Although TCAs are widely used for GP, a multicenter trial of nortriptyline for idiopathic gastroparesis failed to show improvement over placebo. Although macrolides are currently the most potent prokinetics available for treatment of GP, their associated risk of developing C difficile infection with chronic use, risk of diarrhea, and potentially increased risk of sudden cardiac death limit their use in IBD. Moreover, their long-term use is limited by the development of tachyphylaxis. As the only prokinetic approved by the Food and Drug Administration (FDA) for use in GP, metoclopramide is also to be avoided given the risk of irreversible tardive dyskinesia seen in less than 1% and inability to use the drug beyond 3 months, but instead we favor the use of either domperidone, which requires an investigational new drug application through the FDA. Domperidone is a peripheral dopamine 2 (D2) receptor antagonist with effects similar to metoclopramide. It has been shown to be effective in diabetic GP, although more rigorous trials are lacking. Domperidone can cause QT prolongation, and therefore electrocardiograms should be checked at baseline and while on therapy. Bethanechol is a muscarinic agonist that is inexpensive and sometimes used in the management of GP. It increases lower esophageal sphincter (LES) tone and the amplitudes of gastric contractions, but does not accelerate GE. Several newer prokinetics are being studied such as 5-HT ₄ receptor agonists, including prucalopride and velusetrag, as well as ghrelin agonists and newer motilin agonists. Relamorelin is a ghrelin agonist that has been shown to reduce vomiting frequency and accelerate gastric emptying in patients with diabetic GP. When possible, liquid formulations of prokinetics should be used to facilitate absorption. Table 1 summarizes the mechanism, dosing, and side effects of prokinetics. We recommend against the use of gastric electrical stimulators in patients with IBD, as this has not been studied and given risk of theoretic autoimmune-type reaction to the pacer wires or infection risk in patients with IBD. In patients who are losing weight despite treatment for GP, we recommend nutritional supplementation via nasoenteric feeds, jejunostomy, or percutaneous endoscopic gastrojejunostomy (PEG-GJ) tube placement, or if these measures fail, start total parenteral nutrition.

Functional Gastroduodenal Disorders

Functional gastroduodenal disorders are common in patients with IBD, with a prevalence of approximately 30%. Based on the Rome IV criteria, these disorders are categorized into functional dyspepsia, belching disorders, chronic N/V disorders, and rumination syndrome. Functional dyspepsia (FD) is defined as the presence of bothersome epigastric pain or burning, postprandial fullness, or early satiety, in the absence of the structural disease. Symptoms must be present for the past 3 months, with symptom onset at least 6 months before diagnosis. Patients with functional dyspepsia may be further classified as having postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), or both. Patients with PDS have bothersome postprandial fullness or early satiety occurring at least 3 days per week, whereas those with EPS have bothersome epigastric pain or burning occurring at least 1 day per week. Heartburn is not considered a dyspeptic symptom, although it often coexists with FD. Although vomiting may be present in a subset of patients, it is uncommon in FD and its presence suggests another disorder, such as gastric outlet obstruction or GP. In addition to GP and upper GI CD, the differential diagnosis of FD includes GERD, peptic ulcer disease, Helicobacter pylori –associated dyspepsia, eosinophilic gastroenteritis, food allergies, and many others, including medications. Medications that have been implicated include nonsteroidal anti-inflammatory drugs, iron, calcium channel blockers, angiotensin-converting enzyme inhibitors, steroids, and methylxanthines, which include theophylline, pentoxifylline, and caffeine.

Our Recommendations for Functional Dyspepsia

An approach to the evaluation and management of FD is presented in Fig. 3 . We recommend screening for and treating comorbid psychiatric illness, as dyspepsia is frequently associated with major depression and generalized anxiety disorder. Moreover, patients with IBD have higher rates of depression than the general population. Initial management of FD includes testing and treating for H pylori as well as a trial of PPI. In patients who respond to a trial of PPI, we recommend step-down therapy to H2RAs, given the risks of PPI use in patients with IBD. For patients who meet criteria for PDS, a trial of a prokinetic should be considered. TCAs, such as amitriptyline, have been shown to be effective in FD, whereas SSRIs have not been effective. STW 5 is a preparation of 9 herbs that has been shown to be safe and effective for the treatment of FD. A trial of cyproheptadine can be considered, as it has been shown to reduce dyspeptic symptoms in children. Buspirone, a 5-HT _1A agonist, causes fundic relaxation and has been shown to be effective in a small trial.

Evaluation and management of FD.

Diagnosis and Differentiation from Inflammatory Bowel Disease and Small Intestinal Bacterial Overgrowth

Treatment of quiescent IBD by increasing the dose of immunosuppressive agents will likely increase the risk for side effects, including malignancy, infections, and malabsorption. Therefore, how do we identify those patients who present with symptoms due to an FBD versus those with active inflammation or long-term consequences of their IBD? A few recent developments in new biomarkers for the treatment of patients with IBS-D have enhanced our ability to differentiate IBS from non-IBS, IBD. This development of validated biomarkers that can help identify and separate those patients with FBD from those with active inflammation is at its preliminary stages but would be invaluable for clinical care, as it is incorporated into the new ROME IV criteria. Some of these are existing biomarkers, CRP level in serum and fecal calprotectin, which are associated with objective mucosal inflammation in patients with IBD and may have high sensitivity and specificity as a screening tool for IBD in adults and children. These tests could even differentiate IBS-D from microscopic colitis, thus avoiding need for endoscopy in a subset of patients. Other newly developed markers are antibodies against cytolethal distending toxin B, which is produced by all gram-negative bacteria with subsequent development of other antibodies, through a molecular mimicry, to vinculin. Vinculin is a cytoskeletal protein that binds adhesion molecules to actin, thereby supporting the intestinal barrier against injury. High levels of both antibodies have been detected in patients with IBS-D subtype but not in IBD, with a specificity of 92% and a sensitivity of 44%. Although the test does not differentiate celiac disease from IBS, it may be a reliable test for “ruling in” IBS, therefore minimizing use of invasive testing as would be necessary for ruling out IBD. Correct identification of IBS would have huge implications for the treatment and identification of quiescent CD, which would mimic IBS.

Another possibly distinct (but not mutually exclusive) entity coexisting with IBD and IBS may be small intestinal bacterial overgrowth (SIBO) defined as clinical or laboratory evidence of malabsorption due to an increased population of small bowel bacteria. The clinical presentation of a patient with SIBO can be similar to IBS, IBD, celiac disease, carbohydrate malabsorption, and even partial mechanical obstruction. These symptoms include abdominal fullness, bloating, upper periumbilical or epigastric abdominal pain, diarrhea, weight loss, and/or nausea with vomiting and weight loss. The presence of bacteria in the small bowel results in intestinal fermentation with production of gases, production of metabolites in addition to degradation of carbohydrates, production of short-chain fatty acids altering motility and leading to symptoms in IBS (4%–54%), and possibly UC (15%) and CD (28%). These rates depend on the method of diagnosis used: breath testing or duodenal/jejunal aspirates and cultures. IBD itself is a risk factor for having a positive = jejunal aspirate. This “gold standard” is both invasive and costly with limitations depending on type of method for cultures obtained. Hydrogen breath testing by both lactulose and glucose breath testing methods is an alternative to obtaining aspirates in patients with suspected SIBO and rely on high levels of methane and hydrogen. However, both lactulose (an osmotic laxative) and glucose have been shown to accelerate intestinal transit and especially in patients with diarrhea (IBD or IBS) could result in false-positive findings due to rapid arrival of substrate to the right colon. We do not advocate breath testing in patients with symptoms of diarrhea and known IBD. A recent North American Consensus Meeting has made an effort to standardize testing for SIBO, noting jejunal cultures of ≥10 ³ coliforms/mL colonic bacteria and not ≥10 ⁵ as the new standard SIBO definition with further standardizing of breath testing.

Our Recommendations

Given the complexity and overlap of IBS, IBD, and SIBO, we first advocate dietary measures with 2 diets found to be most effective in patients with IBD and IBS: Low FODMAP diet and less consistently, a gluten-free diet ( Fig. 4 ). Two probiotics most studied in patients with IBD and IBS, Bifidobacterium infantis and the combination probiotic VSL#3, are advocated as first-line treatments; however, one should note that probiotics treat only pain and bloating but not fecal urgency or frequency. These therapies may be followed by treatments for concomitant IBS-D targeting serotonin (alosetron), opiate agonists (eluxadoline), and nonsystemically absorbed antibiotics (rifaximin), which are now the 3 FDA-approved treatments for IBS-D. Incorporating use of antidepressants, such as the TCAs especially in patients with IBD with frequent comorbidities, such as anxiety and depression, also may be helpful to treat the visceral hypersensitivity, and as tricyclics are less likely to cause more diarrhea. In patients found to have significant weight loss with suspected small bowel dysmotility causing SIBO, or in those with normal transit and imaging excluding a stricture as the cause of continued symptoms, empiric treatment of SIBO with a nonsystemic antibiotic such as rifaximin versus other antibiotics should be started, although trials of rifaximin in exclusively patients with SIBO do not exist in well-designed studies. If the patient continues to decline, however, without evidence of an inflammatory cause, jejunal aspirates should be done with cultures added for possible fungal overgrowth. Checking for micronutrient deficiencies is also important, as patients with SIBO often have high or normal folate and vitamin K levels, as they are produced by bacteria.

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related posts:

The First Endoscopy in Suspected Inflammatory Bowel Disease Capsule Endoscopy and Deep Enteroscopy in Inflammatory Bowel Disease Role of Histologic Inflammation in the Natural History of Ulcerative Colitis Endoscopic Evaluation and Management of the Postoperative Crohn’s Disease Patient The Gastroenterologist’s Role in Management of Perianal Fistula Dilation of Strictures in Patients with Inflammatory Bowel Disease

Stay updated, free articles. Join our Telegram channel

Join