Irritable Bowel Syndrome - Current evidence based management principles

Depending on the diagnostic criteria employed, irritable bowel syndrome (IBS) affects approximately 11% of the population globally and is estimated to affect 10 to 20% of the Western population. In Western countries, women are two to three times more likely to develop IBS than men, although males represent 70-80% of patients with IBS in the Indian subcontinent.

IBS is a chronic, relapsing and often life-long disorder. It is characterised by the presence of abdominal pain associated with defaecation, or a change in bowel habit together with disordered defaecation (constipation or diarrhoea or both), and the sensation of abdominal distension. The onset of idiopathic IBS symptoms is usually in teenage years or young adulthood. IBS is also known as a functional gastrointestinal disorder which means that it occurs in the absence of any known structural pathology.

The chronic nature of the condition and its severity has a significant impact on a patient's quality of life and healthcare utilisation. Criteria have been devised to guide clinicians and researchers in making a diagnosis.

How Is IBS Diagnosed?

Historically, IBS has been a diagnosis of exclusion where multiple diagnostic procedures were often performed in order to exclude an organic disorder. Organic disease is the term used to describe any health condition in which there is an observable and measurable disease process (e.g. inflammation or tissue damage). The term is used in contrast to functional disorders, such as IBS, in which no such disease process is visible through standard diagnostic testing.

Although a new blood test has recently shown promise as a possible biomarker for IBS, there is currently no established biochemical, histopathological or radiological diagnostic test for the condition. Until a definitive diagnostic test for the condition is identified, the diagnosis of IBS relies primarily on symptom assessment.

Over the last two decades, an international panel of experts have met in Rome, Italy to publish refined criteria for IBS. The initial criteria were established in 1990 (Rome I) and were simplified with updates in 1999 and 2006. Current Rome III guidelines (2006)11 are used for clinical diagnosis. ROME III criteria (2006) for IBS. 
In addition to these criteria, warning symptoms or "red flags," such as age over 50 years, a short history of symptoms, nocturnal symptoms, weight loss, rectal bleeding, anaemia, and the presence of markers for inflammation or infections, should be excluded.  When any of these warning symptoms are present, a more extensive evaluation is warranted to exclude other conditions such as celiac sprue, colonic polyps or cancer, parasites, endocrinopathy, bacterial overgrowth, or carbohydrate maldigestion.

The 2009 American College of Gastroenterology (ACG) evidence-based position statement on the management of IBS does not recommend laboratory testing or diagnostic imaging in patients younger than 50 years with typical IBS symptoms and without “alarm features.” IBS patients are further sub-grouped on the basis of differences in the predominant bowel pattern as:

• Diarrhoea-predominant (IBS-D)
• Constipation-predominant (IBS-C)
• A mixture of both diarrhoea and constipation (IBS-M)
• Un-subtyped IBS in patients with an insufficient abnormality of stool consistency to meet the criteria for IBS C, D or M

It has been reported that approximately one third of patients have IBS-D, one third have IBS-C, and the remainder have IBS-M or un-subtyped IBS. The division of IBS patients into subtypes is useful for clinical practice and symptomatic treatment, but it is common for IBS patients to switch from one subtype to another over time. These patients are known as “alternators.” More than 75% of IBS patients change to either of the other 2 subtypes at least once over a 1-year period. Controversy remains about the value and validation of symptom-based criteria. In general, these studies report a modest specificity of 70%, which is improved to 90% with consideration of red flag signs and symptoms.

What Are the Symptoms of IBS?

IBS is characterised by abdominal pain, altered bowel habits, and abdominal distension. The symptoms of IBS are usually long term, occurring daily or on an episodic basis.

Abdominal pain is frequently diffuse. Acute episodes of sharp pain are often superimposed on a more constant dull ache. Meals times may precipitate pain and defication commonly improves pain but may not fully relieve it.

Constipation variably results in hard, narrow stools, painful or infrequent defecation. The use of to laxatives does not help.

Diarrhoea usually is described as small volumes of loose stool, with evacuation preceded by urgency or frequent defaecation.

Postprandial urgency is common, as is alternation between constipation and diarrhoea. Patients frequently report increased amounts of bloating and gas. Characteristically, one feature predominates in a single patient, but significant variability exists among patients.

What Causes IBS?

The pathophysiology of IBS includes a complex of:

• Altered gastrointestinal (GI) motility
• Visceral hyperalgesia
• Psychopathology
• Microscopic inflammation
• Small bowel bacterial overgrowth

A unifying mechanism has not been determined. For the first time, recent studies have documented microscopic inflammation in some patients with IBS. This concept is groundbreaking in that, until now, IBS has been considered to have no demonstrable tissue or organ pathology.

Altered GI motility

Altered GI motility includes distinct aberrations in small and large bowel motility. Small bowel dysmotility manifests in delayed meal transit in patients prone to constipation and in accelerated meal transit in patients prone to diarrhoea.

Visceral hyperalgesia

IBS is characterised by enhanced perception of normal GI motility and visceral pain. Rectosigmoid and small bowel balloon inflation produces pain at lower volumes in IBS patients than in controls.

Psychopathology

Associations between psychiatric disturbances and IBS pathogenesis are not clearly defined. Patients with psychological disturbances relate more frequent and debilitating illness than control patients. Patients who seek medical care have a higher incidence of panic disorder, major depression, anxiety disorder, and hypochondriasis than control populations.

Small bowel bacterial overgrowth

It has been proposed that small bowel bacterial overgrowth provides a unifying mechanism for the common symptoms of bloating and gaseous distention in patients with IBS. The intestinal microflora have been shown to differ in patients with IBS versus controls. 

Microscopic inflammation

Microscopic inflammation has been documented in some patients. 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 gastroenteritis (post-infectious IBS ). Risk factors for developing post-infectious IBS include longer duration of illness, the type of pathogen involved, smoking, female gender, an absence of vomiting during the infectious illness, and young age.

How Is IBS Treated?

In discussing therapies for IBS, it is helpful to understand the concept of “global symptom improvement,” which is one of the points emphasised by the Rome Committee in its recommendations for the design of IBS treatment trials. Essentially, global symptom improvement is the measure of whether an IBS patient ends up feeling better holistically. While targeting individual IBS symptoms may be desirable, global symptom improvement is viewed as the most fundamental measure of a therapy for IBS.

Pharmacologic therapies

The selection of pharmacologic treatment remains symptom - directed. Agents used for management of symptoms in IBS include:

• Anticholinergics
• Antidiarrhoeals
• Tricyclic antidepressants
• Prokinetics
• Bulk-forming laxatives
• Antibiotics
• Serotonin receptor antagonists
• Probiotics

Anticholinergics. Anticholinergic agents are antispasmodics that inhibit intestinal smooth muscle. These agents help relieve symptoms of intestinal spasms in IBS. A Cochrane systematic review found that several antispasmodics, including peppermint oil, pinaverium, trimebutine, and cimetropium/dicyclomine, significantly outperformed placebo at improving IBS symptom and global assessment scores.

Antidiarrhoeals. These agents are nonabsorbable synthetic opioids. They prolong GI transit time and reduce visceral pain perception. Diphenoxylate hydrochloride 2.5mg with atropine sulfate 0.025 mg (Lomotil) and loperamide (Imodium) both act by inhibiting GI motility. The 2009 ACG position statement on management of IBS noted that the antidiarrhoeal agent, loperamide, effectively reduced stool frequency and improved stool consistency, but it did not relieve pain, bloating, or other global IBS symptoms.

Tricyclic antidepressants. Tricyclic antidepressants have both antidepressive and analgesic properties. Agents such as imipramine and amitriptyline are efficacious in treating symptoms of IBS. The use of tricyclic antidepressants in IBS is "off label" (meaning that they are being lawfully prescribed for a condition not specifically approved by the Therapeutic Goods Administration (TGA)). Imipramine (Tofranil) and amitriptyline (Endep) both increase the pain threshold in the GI tract and thus provide a visceral analgesic effect. Both drugs prolong GI transit time, reduce abdominal pain, mucorrhea, and stool frequency. These agents increase global well-being variably in studies. Both drugs are effective in IBS at doses that are subtherapeutic for antidepressive actions, suggesting an independent mechanism of their action in IBS.

Serotonin (5-HT3) receptor antagonists. Alosetron controls IBS symptomsthrough its potent and selective antagonism of serotonin 5-HT receptors. These receptors are located extensively throughout the GI tract, and their stimulation causes hypersensitivity and hyperactivity of the intestines. This agent is currently approved only for women with severe chronic diarrhoea-predominant IBS who have not responded to conventional therapy.

Probiotics. 

Data from both animal models and studies conducted in humans suggest that probiotics may be of benefit in IBS. Changes in the composition of GI intestinal flora have been demonstrated in patients with IBS. Murine studies have demonstrated a reduction in visceral hypersensitivity, and attenuation of postinfectious muscle hypercontractility following administration of probiotics. 

Further randomised controlled trials are required to determine the most efficacious species, or combinations of species, of probiotics in the treatment of IBS, but overall, these products are safe to trial.

Antibiotics. Antibiotics may play a role in the treatment of IBS by preventing the overgrowth of intestinal bacteria. 

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

Bulk-forming laxatives. As fiber supplements, these products may improve symptoms of constipation and diarrhoea, but their use in IBS is controversial. Methylcellulose (Citrucel) and psyllium (Metamucil) promote bowel evacuation by forming a viscous liquid and enhancing intestinal motility. There are concerns that insoluble fiber may exacerbate symptoms in some sufferers.

Psychological therapies

An increase in psychological morbidity has been observed in patients with IBS, including anxiety, mood disorder, and neuroticism. Such observations have prompted investigators to evaluate various psychological therapies in IBS. A systematic review and meta-analysis in this field has been conducted recently. The most robust evidence for any benefit of psychological therapy was observed with cognitive behavioral therapy. Hypnotherapy, multicomponent psychotherapy and dynamic psychotherapy also appeared to be superior to control therapy, but the total number of studies was small for the latter three therapies.

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