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Irritable Bowel Syndrome and Other FunctionalGastrointestinal Disorders

Ilkay Simsek, MD

Abstract: Irritable bowel syndrome is one of several highlyprevalent functional gastrointestinal disorders (FGID) displayingsymptoms of gastrointestinal dysmotility and visceral hypersensi-tivity. Substantial overlap of symptoms and comorbidities occurnot only between irritable bowel syndrome and other FGID butalso with gastrointestinal disorders that are not related to motility(eg, celiac disease and lactose intolerance) and to somatic conditions(eg, fibromyalgia and chronic fatigue syndrome). Pathogenic

mechanisms common among FGIDs may include alternations inintestinal and colonic microflora. Evidence is also emerging of aninterplay between gut immune cells/activity and alternations inmotility, secretion, and sensation. The role of cytokine activity andinflammation is important in this regard. As recommended byRome III, diagnostic testing should be guided by the patients age,primary symptom characteristics, and other clinical and laboratoryfeatures. The high prevalence of coexisting conditions suggests theneed to routinely assess patients for related disorders. Treatmentshould be based on an individualized evaluation, explanation, andreassurance.

Key Words: irritable, bowel, functional, gastrointestinal, IBS

(J Clin Gastroenterol 2011;45:S86S88)

Irritable bowel syndrome (IBS) is one of several highlyprevalent, multisymptom functional gastrointestinal dis-orders (FGID) that have a wide clinical spectrum andwhich are associated with symptoms of gastrointestinaldysmotility and visceral hypersensitivity.1 Significant over-lap of symptoms and comorbidities are frequently identifiednot only between IBS and other FGID [including func-tional abdominal pain, functional abdominal bloating,functional constipation, functional dyspepsia (FD), andgastroesophageal reflux disease], but also with gastrointest-inal disorders that are not related to motility (such as celiacdisease and lactose intolerance), and to somatic conditions(such as fibromyalgia and chronic fatigue syndrome).19

Reflecting on whether IBS affects the entire gastrointestinalsystem, this study considers other related conditions andputatively common pathogenic mechanisms. One clinicalimplication of coexisting conditions is the need to routinelyassess patients for related disorders.

DIAGNOSING FUNCTIONAL ESOPHAGEAL AND

GASTRODUODENAL DISORDERS

It is important to understand the different diagnosticcriteria for the various functional esophageal and gastro-duodenal disorders and for this it is necessary to refer to thecurrent diagnostic criteria as recommended by the 2006Rome III process.1,10 Functional esophageal disordersinclude functional heartburn, functional chest pain of eso-

phageal origin, functional dysphagia, and globus. Func-tional heartburn is defined as episodic retrosternal burningin the absence of gastroesophageal reflux disease, histo-pathology-based motility disorders, or structural disorders.Symptoms are related to acid reflux events in the absence ofabnormal esophageal acid exposure. In western populationsheartburn occurs in 20% to 40% individuals irrespective ofsex and age.5 All of the following must be met to meet thediagnostic criteria for functional heartburn: burning retro-sternal discomfort or pain; absence of evidence that thegastroesophageal acid reflux is the cause of the symptom;absence of a histopathology-based motility disorder. Aswith all functional esophageal disorders, these criteria mustbe fulfilled for 3 months with symptom onset at least 6

months before diagnosis. The diagnostic criteria for func-tional chest pain of esophageal origin must include all ofthe following: midline chest pain or discomfort that is notof burning quality; the absence of evidence that gastro-esophageal reflux is the cause of symptom; and the absenceof histopathology-based esophageal motility disorders.10

The diagnostic criteria for functional dysphagia are asfollows: sense of solid and/or liquid foods sticking; lodgingor passing abnormally through the esophagus; the absenceof evidence that gastroesophageal reflux is the cause ofsymptom; and the absence of histopathology-based eso-phageal motility disorders.10 The diagnostic criteria forglobus are the persistant or intermittent, nonpainful sensa-tion of a lump or foreign body in the throat; occurence of

the sensation between meals; absence of dysphagia orodynophagia; absence of evidence that gastroesophagealreflux is the cause of the symptom; and the absence ofhistopathology-based esophageal motility disorders.10

Functional gastroduodenal disorders include FD (ie,postprandial distress syndrome (PDS) and epigastric painsyndrome), belching disorders (ie, aerophagia and unspe-cied excessive belching), nausea and vomiting disorders (ie,chronic nausea, functional vomiting, and cyclic vomitingsyndrome), and rumination syndrome. It is useful to notethat FD is a heterogeneous disorder associated with diversepathophysiological mechanisms. PDS must include 1 ormore of following: bothersome postprandial fulness, earlysatiation, epigastric pain, epigastric burning, and no

evidence of structural disease that is likely to explain thesymptoms (including upper gastrointestinal endoscopy).Diagnostic criteria for PDS include one or both of theCopyright r 2011 by Lippincott Williams & Wilkins

From the Dokuz Eylul University, Medicine Faculty, Department ofGastroenterology, Izmir, Turkey.

Supported by Abbott Products Operations AG, Hegenheimermattweg127, 4123 Allschwil, Switzerland.

Conflict of Interest: The author is a speaker for Solvay and Abbott andreceived sponsorships for organizing scientific events from Solvayand Abbott.

Reprints: I

lkay Simsek, MD, Dokuz Eylul University, MedicineFaculty, Department of Gastroenterology, Izmir, Turkey (e-mail:ilkay.simsek@deu.edu.tr).

PRESENTATION

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following: bothersome postprandial fullness, occuring afterordinary-sized meals, at least several times per week; earlysatiation that prevents finishing a regular meal, at leastseveral times per week. Supportive criteria including upperabdominal bloating or postprandial nausea or excessivebelching can be present; epigastric pain syndrome may co-

exist. The following must be present for the diagnosis ofepigastric pain syndrome: pain or burning localized to theepigastrium at least of moderate severity, at least once perweek; pain is intermittent; not generalized or localized toother abdominal or chest regions; not relieved by defecationor passage of flatus; not fullfilling criteria for gall bladder orsphincter of oddi disorders. Supportive criteria include: thepain may be of a burning quality, but without a retrosternalcomponent; the pain is commonly induced or relieved byingestion of meal, but may occur while fasting; and PDSmay coexist.

Interestingly, studies have shown duodenal involve-ment in the pathophysiology of FD. Patients with FD haveshown duodenal hypersensitivity to acid, increased duode-

nal acid exposure, and abnormal responses to duodenallipids or released cholecystokinin. Evidence also suggeststhe involvement of duodenal immune activation in FD.Furthermore, alterations in the number of duodenal eosino-phils or intraepithelial lymphocytes have been reported in asubset of patients with FD, particularly those with post-infectious FD.11 Meanwhile, the overlap between FD andIBS was highlighted in an important recent systematicreview and meta-analysis. Individuals with dyspepsia werefound to have an 8-fold increase in prevalence of IBScompared with the general population, suggesting thatdyspeptic patients should be assessed routinely for IBS.9

Among 18,173 individuals included in the analysis, thedegree of overlap between the 2 conditions varied from

15% to 42%, depending on diagnostic criteria used foreach.

Regarding belching disorders, the diagnosis of aero-phagia must include all of the following: troublesome repe-titive belching at least several times a week; air swallowingthat is objectively observed or measured. For unspecifiedexcessive belching: troublesome, repetitive belching at leastseveral times a week; no evidence that excessive air swallow-ing underlies the symptom. Chronic nausea must include:bothersome nausea occuring at least several times per week;not usually associated with vomiting; absence of abnormali-ties at upper endoscopy or metabolic disease that explainsnausea. Functional vomiting must include: on average 1 ormore episodes; absence of criteria for an eating disorder,

rumination or major psychiatric disease to DSM-IV; andabsence of self-induced vomiting and chronic cannabioiduse. There must also be an absence of abnormalities in thecentral nervous system or metabolic diseases to explainrecurrent vomiting. Cyclic vomiting syndrome must in-clude: stereotypical episodes of vomiting regarding onset(acute) and duration (

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pain in IBS. Intestinal mast cell infiltration is thought toparticipate to abdominal pain in IBS. It is thought thatintestinal mast cell infiltration may perturb nerve functionleading to symptom perception. In a recent study, mucosalmast cell mediators from IBS patients were found to exciterat nociceptive visceral sensory nerves.24 Findings of an

earlier clinical study suggested that colonic mast cell in-filtration and mediator release in proximity to mucosalinnervation may contribute to abdominal pain perceptionin IBS patients (diagnosed according to Rome II criteria).25

In summary, as recommended by Rome III, diagnostictesting should be guided by the patients age, primarysymptom characteristics, and other clinical and laboratoryfeatures. Treatment of functional bowel disorders is basedon an individualized evaluation, explanation, and reassur-ance. Symptoms of IBS have traditionally been linked todisturbed gastrointestinal motility, visceral hypersensitivity,and psychological distress. However, growing evidencesuggests that alternations in intestinal and colonic micro-flora play a role in IBS. Particularly, important in this

regard are the observations that infectious gastroenteritissignificantly increases the risk of developing IBS and thatquantitave and qualitative changes in gut flora have beennoted in IBS patients. Evidence exists for interplay betweengut immune cells/activity and alternations in motility,secretion, and sensation. The pathophysiological linksbetween IBS and other FGID continue to be exploredand the role of cytokine activity and inflammation areemerging areas of research in IBS.

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