INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain and altered bowel habits in the absence of specific and unique organic pathology. Osler coined the term mucous colitis in 1892 when he wrote of a disorder of mucorrhea and abdominal colic with a high incidence in patients with coincident psychopathology. Since that time, the syndrome has been referred to by sundry terms, including spastic, irritable, and nervous colon.

Traditionally, IBS is a diagnosis of exclusion. No specific motility or structural correlates have been consistently demonstrated, so IBS remains a clinically defined illness. Manning and associates established 6 criteria to distinguish IBS from organic bowel disease. Although historically important, these criteria are insensitive (58%), nonspecific (74%), and less reliable in men.

The Manning criteria to distinguish IBS from organic disease are as follows:

• Onset of pain associated with more frequent bowel movements
• Onset of pain associated with looser bowel movements
• Pain relieved by defecation
• Visible abdominal bloating
• Subjective sensation of incomplete evacuation more than 25% of the time
• Mucorrhea more than 25% of the time

More recently, a consensus panel created and then updated the Rome criteria to provide a standardized diagnosis for research and clinical practice.

The Rome III criteria (2006) for the diagnosis of IBS require that patients must have recurrent abdominal pain or discomfort at least 3 days per month during the previous 3 months that is associated with 2 or more of the following:

• Relieved by defecation
• Onset associated with a change in stool frequency
• Onset associated with a change in stool form or appearance

Supporting symptoms include the following:

• Altered stool frequency
• Altered stool form
• Altered stool passage (straining and/or urgency)
• Mucorrhea
• Abdominal bloating or subjective distention

Four bowel patterns may be seen with IBS. These patterns include IBS-D (diarrhea predominant), IBS-C (constipation predominant), IBS-M (mixed diarrhea and constipation), and IBS-A (alternating diarrhea and constipation). The usefulness of these subtypes is debatable. Notably, within 1 year, 75% of patients change subtypes, and 29% switch between constipation-predominant IBS and diarrhea-predominant IBS.

Pathophysiology

Traditional theories regarding pathophysiology may be visualized as a 3-part complex of altered GI motility, visceral hyperalgesia, and psychopathology.

• Altered GI motility includes distinct aberrations in small and large bowel motility.
• • The myoelectric activity of the colon is composed of background slow waves with superimposed spike potentials. Colonic dysmotility in IBS manifests as variations in slow-wave frequency and a blunted, late-peaking, postprandial response of spike potentials. Patients who are prone to diarrhea demonstrate this disparity to a greater degree than patients who are prone to constipation.
  • Small bowel dysmotility manifests in delayed meal transit in patients prone to constipation and in accelerated meal transit in patients prone to diarrhea. In addition, patients exhibit shorter intervals between migratory motor complexes (the predominant interdigestive small bowel motor patterns). 
  • Current theories integrate these widespread motility aberrations and hypothesize a generalized smooth muscle hyperresponsiveness. They describe increased urinary symptoms, including frequency, urgency, nocturia, and hyperresponsiveness to methacholine challenge.
• Visceral hyperalgesia is the second part of the traditional 3-part complex that characterizes IBS.
• • Enhanced perception of normal motility and visceral pain characterizes IBS. Rectosigmoid and small bowel balloon inflation produces pain at lower volumes in patients than in controls. Notably, hypersensitivity appears with rapid but not gradual distention.
  • Patients who are affected describe widened dermatomal distributions of referred pain. 
  • Sensitization of the intestinal afferent nociceptive pathways that synapse in the dorsal horn of the spinal cord provides a unifying mechanism.
• Psychopathology is the third aspect.
• • Associations between psychiatric disturbances and IBS pathogenesis are not clearly defined. 
  • Patients with psychological disturbances relate more frequent and debilitating illness than control populations. 
  • Patients who seek medical care have a higher incidence of panic disorder, major depression, anxiety disorder, and hypochondriasis than control populations. 
  • An Axis I disorder coincides with the onset of GI symptoms in as many as 77% of patients. 
  • A higher prevalence of physical and sexual abuse has been demonstrated in patients with IBS. 
  • Whether psychopathology incites development of IBS or vice versa remains unclear.
• Recently, microscopic inflammation has been documented in some patients. This concept is groundbreaking in that IBS had previously been considered to have no demonstrable pathologic alterations.
• • Both colonic inflammation and small bowel inflammation have been discovered in a subset of patients with IBS as well as in patients with inception of IBS after infectious enteritis (postinfectious IBS). Risk factors for developing postinfectious IBS include female gender, longer duration of illness, the type of pathogen involved, an absence of vomiting during the infectious illness, and young age.
  • Laparoscopic full-thickness jejunal biopsy samples revealed infiltration of lymphocytes into the myenteric plexus and intraepithelial lymphocytes in a subset of patients. Neuronal degeneration of the myenteric plexus was also present in some patients.
  • Patients with postinfectious IBS may have increased numbers of colonic mucosal lymphocytes and enteroendocrine cells.
  • Enteroendocrine cells in postinfectious IBS appear to secrete high levels of serotonin, increasing colonic secretion and possibly leading to diarrhea.
• Recently, small bowel bacterial overgrowth has been heralded as a unifying mechanism for the symptoms of bloating and distention common to patients with IBS. This has led to proposed treatments with probiotics and antibiotics.

Frequency

United States

Population-based studies estimate the prevalence of IBS at 10-20% and the incidence of IBS at 1-2% per year. Of people with IBS, approximately 10-20% seek medical care. An estimated 20-50% of gastroenterology referrals relate to this symptom complex.

International

Incidence is markedly different among countries.

Mortality/Morbidity

• This is a chronic relapsing condition. Physicians must be forthcoming with patients because knowledge may help allay undue fears as their disease waxes and wanes. IBS does not increase mortality or the risk of inflammatory bowel disease or cancer.
• The principal associated physical morbidities include abdominal pain and lifestyle modifications secondary to altered bowel habits.
• Work absenteeism resulting in lost wages is more frequent in patients with IBS.

Race

• American and European cultures demonstrate similar frequencies of IBS across racial and ethnic lines. However, within the United States, survey questionnaires indicate a lower prevalence in Hispanics in Texas and Asians in California.
• Populations of Asia and Africa may have a lower prevalence.
• The role of different cultural influences and varying health care–seeking behaviors is unclear.

Sex

In Western countries, women are 2-3 times more likely to develop IBS than men, although males represent 70-80% of patients with IBS in the Indian subcontinent. Women seek health care more often, but the IBS-specific influence of this occurrence remains unknown. Other factors, such as a probably greater incidence of abuse in women, may confound interpretation of this statistic.

Age

• Patients often retrospectively note the onset of abdominal pain and altered bowel habits in childhood.
• Approximately 50% of people with IBS report symptoms beginning before they were aged 35 years.
• The development of symptoms in people older than 40 years does not exclude IBS but should prompt a closer search for an underlying organic etiology.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

A meticulous history is the key to diagnosis. The Rome criteria provide the construct upon which questions are based (see Background). Symptoms consistent with IBS include the following:

• Altered bowel habits
• • Constipation variably results in complaints of hard stools of narrow caliber, painful or infrequent defecation, and intractability to laxatives.
  • Diarrhea usually is described as small volumes of loose stool, with evacuation preceded by urgency or frequent defecation.
  • Postprandial urgency is common.
  • Alternating habits are common. Characteristically, one feature predominates in a single patient, but significant variability exists among patients.
• Abdominal pain
• • Descriptions are protean. Pain frequently is diffuse without radiation. Common sites of pain include the lower abdomen, specifically the left lower quadrant.
  • Acute episodes of sharp pain are often superimposed on a more constant dull ache.
  • Meals may precipitate pain, and defecation commonly improves pain. Defecation may not fully relieve pain.
  • Pain from presumed gas pockets in the splenic flexure may masquerade as anterior chest pain or left upper quadrant abdominal pain. This splenic flexure syndrome is demonstrable by balloon inflation in the splenic flexure and should be considered in the differential of chest or left upper quadrant abdominal pain.
• Abdominal distention
• • Patients frequently report increased amounts of bloating and gas. Quantitative measurements fail to support this claim.
  • People with IBS may manifest increasing abdominal circumference throughout the day, as assessed by CT scan. They may also demonstrate intolerance to otherwise normal amounts of abdominal distention.
• Clear or white mucorrhea of a noninflammatory etiology is commonly reported.
• Noncolonic and extraintestinal symptoms
• • Epidemiologic associations with dyspepsia, heartburn, nausea, vomiting, sexual dysfunction (including dyspareunia and poor libido), and urinary frequency and urgency have been noted.
  • Symptoms may worsen in the perimenstrual period.
  • Fibromyalgia is a common comorbidity.
• Stressor-related symptoms
• • These symptoms may be revealed with careful questioning.
  • Emphasize avoidance of stressors.
• Inconsistent symptoms must alert the physician to the possibility of an organic pathology. Symptoms not consistent with IBS include the following:
• • Onset in middle age or older
  • Acute symptoms: IBS is defined by chronicity.
  • Progressive symptoms
  • Nocturnal symptoms
  • Anorexia or weight loss
  • Fever
  • Rectal bleeding
  • Painless diarrhea
  • Steatorrhea
  • Lactose and/or fructose intolerance
  • Gluten intolerance

Physical

• The patient has an overall healthy appearance.
• The patient may be tense or anxious.
• The patient may present with sigmoid tenderness or a palpable sigmoid cord.

Causes

Causes remain poorly defined, but they are being avidly researched.

• Postulated etiologies
• • Abnormal transit profiles and an enhanced perception of normal motility may exist.
  • Local histamine sensitization of the afferent neuron causing earlier depolarization may occur.
• Causes related to enteric infection (See Pathophysiology for more detail.)
• • Colonic muscle hyperreactivity and neural and immunologic alterations of the colon and small bowel may persist after gastroenteritis.
  • Psychological comorbidity independently predisposes the patient to the development of postinfectious IBS.
  • Psychological illness may create a proinflammatory cytokine milieu, leading to IBS through an undefined mechanism after acute infection.
• Central neurohormonal mechanisms
• • Abnormal glutamate activation of N-methyl-D-aspartate (NMDA) receptors, activation of nitric oxide synthetase, activation of neurokinin receptors, and induction of calcitonin gene-related peptide have been observed.
  • The limbic system mediation of emotion and autonomic response enhances bowel motility and reduces gastric motility to a greater degree in patients who are affected than in controls. Limbic system abnormalities, as demonstrated by positron emission tomography, have been described in patients with IBS and in those with major depression.
  • The hypothalamic-pituitary axis may be intimately involved in the origin. Motility disturbances correspond to an increase in hypothalamic corticotropin-releasing factor (CRF) production in response to stress. CRF antagonists eliminate these changes.
• As discussed in Pathophysiology, Pimental and colleagues have proposed that small bowel bacterial overgrowth provides a unifying mechanism for the common symptoms of bloating and gaseous distention in patients with IBS.
• Bloating and distention may also occur from intolerance to dietary fats. Reflex-mediated small bowel gas clearance is more impaired by lipids (fat) ingestion in patients with IBS versus patients without IBS.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Infectious colitis
Medication adverse effects
Secretory diarrhea
Lactose intolerance
Fructose intolerance
VIPoma
Gastrinoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• A comprehensive history, a physical examination, and tailored laboratory and radiographic studies can establish a diagnosis of IBS in most patients.
• Lab studies may include the following:
• • CBC count with differential to screen for anemia, inflammation, and infection
  • A comprehensive metabolic panel to evaluate for metabolic disorders and to rule out dehydration/electrolyte abnormalities in patients with diarrhea
• Gastrointestinal bleeding should be ruled out. A hemoccult test may be useful.
• Microbiologic studies to consider include the following stool examinations:
• • Ova and parasites: Consider obtaining specimens for Giardia antigen as well.
  • Enteric pathogens
  • Leukocytes
  • Clostridium difficile toxin
• The following selected studies are directed by history:
• • Breath testing: Screen for lactose and/or fructose intolerance.
  • Thyroid function tests: Screen for hyperthyroidism or hypothyroidism.
  • Serum calcium: Screen for hyperparathyroidism.
  • Erythrocyte sedimentation rate or C-reactive protein: This is a nonspecific screening test for inflammation.
  • Serologies or small bowel biopsy for celiac disease: Consider, especially in diarrhea-predominant IBS.
• H2 breath test to exclude bacterial overgrowth may be considered in patients with diarrhea.

Imaging Studies

• The following selected studies are directed by history:
• • Upper GI barium study with small bowel follow-through: Screen for tumor, inflammation, obstruction, and Crohn disease.
  • Double-contrast barium enema: Screen for neoplasm and inflammation.
  • Gallbladder ultrasonography: Consider this test if the patient has recurrent dyspepsia or characteristic postprandial pain.
  • Abdominal CT scan: Screen for tumors, obstruction, and pancreatic disease.

Other Tests

• Direct a lactose-free diet for 1 week in conjunction with lactase supplements. Improvement incriminates lactose intolerance, although the patient's clinical history and response to a trial may be unreliable. Some gastroenterologists therefore recommend a formal hydrogen breath test. Fructose intolerance must also be considered.
• Direct a 48-hour fast. Persistent diarrhea suggests a secretory etiology.
• Anal manometry may reveal spastic response to rectal distention or other problems.

Procedures

• Endoscopy directed for many patients includes flexible sigmoidoscopy to determine inflammation or distal obstruction.
• The following selected studies are directed by history:
• • Esophagogastroduodenoscopy with possible biopsy - Indicated for a patient with persistent dyspepsia or if weight loss or symptoms suggest malabsorption or if celiac disease is a concern
  • Colonoscopy - Indicated for patients with warning signs such as bleeding; anemia; chronic diarrhea; older age; history of colon polyps; cancer in the patient or first-degree relatives; or constitutional symptoms such as weight loss or anorexia. A screening colonoscopy should be performed according to published guidelines.

Histologic Findings

New research suggests that neuronal degeneration and myenteric plexus lymphocytosis may exist in the proximal jejunum. Additionally, colonic lymphocytosis and enteroendocrine cell hyperplasia has been demonstrated in some patients.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Successful management relies on a strong patient-physician relationship.
• Reassure the patient that the absence of an organic pathology indicates a normal life expectancy.
• Emphasize the expected chronicity of symptoms with periodic exacerbations.
• Teach the patient to acknowledge stressors and to use avoidance techniques.

Consultations

• Consider psychiatric referral. Evidence supports improvement in GI symptoms with successful treatment of psychiatric comorbidities.

Diet

• Fiber supplementation may improve symptoms of constipation and diarrhea. Individualize the treatment because few patients experience exacerbated bloating and distention with high-fiber diets. Polycarbophil compounds (eg, Citrucel, FiberCon) may produce less flatulence than psyllium compounds (eg, Metamucil).
• The data regarding the effectiveness of fiber are controversial because 40-70% of patients improve with placebo.
• Judicious water intake in patients who predominantly experience constipation is recommended.
• Caffeine avoidance may limit anxiety and symptom exacerbation.
• Legume avoidance may decrease abdominal bloating.
• Lactose and/or fructose should be limited or avoided in patients with these contributing disorders. Take care to supplement calcium in patients limiting lactose intake.

Activity

No limitation is recommended.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The selection of pharmacologic treatment remains symptom directed.

The nonabsorbed antibiotic rifaximin (<0.4%) is a broad-spectrum antibiotic specific for enteric pathogens (ie, gram-positive, gram-negative, aerobic and anaerobic) of the GI tract. Rifaximin is a structural analog. It binds to a beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis. It is indicated for Escherichia coli (enterotoxigenic and enteroaggregative strains) associated with travelers' diarrhea. Rifaximin has been studied in patients with IBS and is believed to improve the symptoms of bloating, diarrhea, abdominal pain, and constipation.

Drug Category: Anticholinergics

Are antispasmodics that inhibit intestinal smooth-muscle depolarization at the muscarinic receptor.

Drug Category: Antidiarrheals

Are nonabsorbable synthetic opioids. They prolong GI transit time and decrease secretion via peripheral µ-opioid receptors. They reduce visceral nociception via afferent pathway inhibition.

Drug Category: Tricyclic antidepressants

Provide antidepressive and analgesic properties. Various agents have efficacy; much research has concentrated on imipramine and amitriptyline (off-label use).

Drug Category: Prokinetics

Are promotility agents, proposed for use with constipation-predominant symptoms. Unfortunately, cisapride availability is restricted in the United States, and other motility agents, such as metoclopramide, domperidone, and erythromycin, have not yielded consistent benefits in patients with IBS.

Tegaserod marketing was temporarily withdrawn from the US market in March 2007; however, as of July 27, 2007, restricted use of tegaserod is now permitted via a treatment investigational new drug (IND) protocol. The treatment IND protocol will allow tegaserod treatment of irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease.
 
Earlier in 2007, tegaserod marketing was suspended because of a meta-analysis of safety data pooled from 29 clinical trials that involved more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, myocardial infarction, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients, and placebo was taken by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Serious and life-threatening cardiovascular adverse effects occurred in 13 patients (0.1%) treated with tegaserod; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication. 
 
For more information, see the FDA MedWatch Product Safety Alert.

Drug Category: Serotonin (5-HT3) receptor antagonists

Inhibit activation of nonselective cation channels, which modulate the enteric nervous system.

Drug Category: Chloride-channel activator

These agents enhance chloride-rich intestinal fluid secretions without altering sodium and potassium concentrations in the serum.

Drug Category: Bulk-forming laxatives

May use these agents as fiber supplementation to improve symptoms of constipation and diarrhea. Use is controversial. These products are made of natural and semisynthetic hydrophilic polysaccharides and cellulose derivatives that dissolve or swell in the intestinal fluid, forming emollient gels that facilitate passage of intestinal contents and stimulate peristalsis.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Frequent physician visits enhance the patient-physician relationship, especially in patients who were recently diagnosed. Visits become less frequent as patients are educated and reassured.

In/Out Patient Meds

• Pharmacologic management is an adjunct to psychological support and dietary modifications and should be directed at symptoms.

Deterrence/Prevention

• Deterrence depends on patient avoidance of stressors and on development of coping mechanisms.
• No specific modalities completely prevent IBS.

Complications

• No increased risk of developing an organic pathology exists.

Prognosis

• IBS is a chronic relapsing disorder characterized by recurrent symptoms of variable severity; however, life expectancy remains similar to that of the general population.

Patient Education

• Patient education remains the cornerstone of successful treatment.
• Teach the patient to acknowledge stressors and to develop avoidance techniques.
• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center and Muscle Disorders Center. Also, see eMedicine's patient education articles Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Chronic Pain.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider the possibility of coexistent organic pathology, especially in patients with atypical symptoms, is a potential pitfall.
• Failure to recognize suicidal ideation and/or depression would be detrimental. A recent study has suggested that patients with IBS may have suicidal ideation and/or suicide attempts strictly as a result of their bowel symptoms. Clinical alertness to depression and hopelessness is mandatory. This is underscored by another study that revealed that physicians may trivialize patient complaints that relate to functional bowel disorders.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Aug 8, 2007