Irritable bowel syndrome

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Chapter 9 IRRITABLE BOWEL SYNDROME

• Irritable bowel syndrome (IBS) is a highly prevalent condition affecting 15% of the population.

• IBS is defined by chronic or relapsing abdominal symptoms (pain and/or discomfort) associated with an abnormality of bowel movements (loose or hard, or more or less frequent stools at pain onset) in the absence of structural lesions.

• In the absence of alarm features (e.g. weight loss, vomiting, rectal bleeding) or advanced age, a diagnosis of IBS usually can be made with no additional testing.

• Communicating the diagnosis and explaining the prognosis is key for further treatment.

• A proportion of patients with IBS suffer from concomitant anxiety or depressive disorders.

• Proper dietary assessment and advice may help identify triggers for symptoms.

• Target the dominant symptoms (i.e. abdominal pain, constipation or diarrhoea) when planning symptomatic treatment.

• Low-dose tricyclic antidepressants, psychological interventions or hypnotherapy can be considered in patients with severe symptoms not responding to the conventional therapies.

DEFINITIONS AND CATEGORIES

In less than 50% of patients with chronic or relapsing symptoms such as abdominal pain or discomfort, structural or biochemical abnormalities can be found that explain these symptoms. On the other hand, even if there are structural abnormalities, such as diverticula in the sigmoid colon, these abnormalities may not explain the symptoms in patients presenting for assessment. If there are no abnormalities explaining symptoms, a functional gastrointestinal disorder can be diagnosed.

If there is no structural abnormality to explain the symptoms, and symptoms such as pain or discomfort are associated with changes in bowel habit, irritable bowel syndrome (IBS) can be diagnosed. The most stringent definitions for functional gastrointestinal disorders have been provided by the Rome Committee, an international working party. The Rome III criteria for IBS are summarised in Table 9.1. Essentially, IBS can be diagnosed when structural lesions are absent (or unlikely based upon the clinical presentation) and the patient suffers from chronic or relapsing abdominal discomfort or pain associated with an abnormality of bowel movements (constipation, diarrhoea or alternating diarrhoea and constipation). Bloating is also common.

TABLE 9.1 Diagnostic criteria for irritable bowel syndrome (Rome III)

Recurrent abdominal pain or discomfort for at least 3 months, and symptoms at least 3 days/month associated with two or more of the following:

1. Relief of pain or discomfort with defecation

2. Onset of pain or discomfort associated with a change in bowel frequency

3. Onset of pain or discomfort associated with a change in form (appearance) of stool (loose or hard stools)

Based upon the symptoms, patients with IBS are usually categorised into one of three groups: IBS with predominant diarrhoea (IBS-D) or predominant constipation (IBS-C) or a mixed pattern of diarrhoea and constipation. Alternating refers to changing from diarrhoea to a constipation pattern (IBS-A). There is a group of patients who develop IBS symptoms after an episode of acute infectious diarrhoea, sometimes accompanied by fever, nausea and vomiting. This syndrome is now labelled post-infectious or PI-IBS. Interestingly, post-infectious IBS is usually associated with diarrhoea predominant IBS. Chronic abdominal pain or discomfort in the absence of abnormalities in stool pattern is not IBS, but is called chronic functional abdominal pain.

EPIDEMIOLOGY

The prevalence of IBS ranges from 10% to 20% in Western countries, and it is just as common in India, Japan and China. Only one out of three people who have symptoms of IBS seek medical attention. Generally, those who have more severe symptoms seek medical help. IBS is more prevalent in females. While IBS is not life-threatening, it is remarkable that affected patients have a substantial number of days off work, and thus society has to cope with the burden of IBS too.

PATHOPHYSIOLOGY OF IBS

A number of mechanisms are believed to be involved in the manifestation of IBS. Indeed, there is evidence accumulating that IBS is not one disease, but most likely represents a group of disorders with different pathophysiologies.

Genetic and environment

IBS runs in families. It is reasonable to speculate that specific genetic factors in combination with the exposure to specific environmental factors cause IBS. The environmental influences (e.g. infections or stress) most likely have different effects based upon an array of factors that include genetic predisposition.

Sensorimotor dysfunction

There is sufficient evidence from numerous studies that, at least in a proportion of patients, abnormal gut sensory function is present (increased sensitivity to innocuous stimuli in the gut).

Food intolerance

A proportion of patients report intolerance of specific foods. There is evidence for hypersensitivity but usually not food allergy. However, diets that carefully exclude these nutrients rarely succeed in providing long-lasting relief.

Gastrointestinal flora and bacterial overgrowth

Emerging evidence suggests that, at least in a subgroup of patients, small intestinal bacterial overgrowth may be present. Antibiotic therapy has improved symptoms, especially bloating, more than the placebo, but more data are needed.

Psychological factors

Up to two-thirds of patients with IBS referred to a tertiary centre suffer from depression or anxiety disorders. In addition, it is striking that IBS patients are more likely to report a history of physical or sexual abuse. However, IBS is not simply a psychological disorder.

MANAGEMENT

Even though IBS does not carry any risk for excess mortality, effective management of and treatment for these patients is important since this disorder can cause severe and sometimes disabling symptoms, impairment of quality of life and, if inappropriately treated, may trigger unnecessary costs for diagnostic and therapeutic measures. Establishing the diagnosis is the first step and, for further management, the most important step. IBS can be diagnosed in the majority of patients without any tests, simply based upon the clinical presentation. While a colonoscopy may not find structural lesions that explain the chronic symptoms in the majority of patients, it may still be helpful to reassure the patient or, if the patients are 50 years of age or older, may be a preventive measure with regard to the early detection of colonic polyps and cancer.

Diagnostic tests

For many years, IBS was considered a diagnosis of exclusion. Patients with alarm symptoms or signs (red flags) such as weight loss, fever, rectal bleeding, malnutrition (or laboratory abnormalities such as anaemia, a low albumin level or an elevated white blood count) need to undergo a diagnostic work-up before the diagnosis of IBS can be made. However, current best evidence does not support the routine use of tests in order to exclude organic gastrointestinal disease in patients with typical IBS symptoms without alarm features. Serological testing for coeliac sprue only might be useful (5% with IBS-type symptoms may have coeliac disease). However, alarm features or persistent non-responsive symptoms should prompt a more detailed diagnostic evaluation.

The diagnosis of IBS is based on patient descriptions of common symptoms and, in particular, abdominal pain or discomfort accompanied by changes in stool form or frequency, often associated symptoms such as bloating and distension. A review of the literature shows that, in patients with no alarm symptoms, the Rome criteria have a positive predictive value of approximately 98%, and that additional diagnostic tests have a yield of 2% or less. The diagnostic evaluation ideally should also include a psychosocial assessment specifically addressing any history of sexual or physical abuse because these issues significantly influence management strategies and treatment success.

While the evidence for a comprehensive diagnostic work-up to establish the diagnosis of IBS is poor, it needs to be acknowledged that the response to treatment is frequently disappointing. Even treatments that are considered to be effective only yield a gain over placebo that does not exceed 10%–20%. Thus, a large proportion of patients that are diagnosed on clinical grounds as having IBS ultimately will have further diagnostic measures simply because the symptoms do not respond to therapy or symptoms relapse after a while.

If tests are being considered, a complete blood count, erythrocyte sedimentation rate (or C-reactive protein), serum chemistry and albumin, and stool examination for ova and parasites can be ordered. However, the cost-benefit of these tests is not established. Coeliac disease serological testing (e.g. transglutaminase) should be ruled out by appropriate serological testing and appears to be cost effective. While not necessary from the perspective of establishing the diagnosis of IBS, in patients over 50 years of age, a colonoscopy is recommended due to the increased probability of colon cancer. In younger patients, colonoscopy or sigmoidoscopy with biopsies can be performed, based upon relevant clinical features (e.g. diarrhoea to exclude microscopic colitis).

The need for additional diagnostic tests such as thyroid stimulating hormone (TSH) may depend on the symptom subtype. For example, for constipation-predominant symptoms, a therapeutic trial of fibre supplementation may be sufficient. The American Gastroenterological Association guidelines recommend that in patients who do not respond to fibre, confirmation of slow colonic transit with a whole gut transit test, or evaluation for obstructed defecation with anorectal motility and balloon expulsion test, might be indicated. In patients with diarrhoea-predominant symptoms, clinical judgment will determine the further diagnostic work-up. In patients with relapsing or chronic loose/watery stools, a lactose/dextrose H₂ breath test for bacterial overgrowth, serology for coeliac sprue or biopsies of the small intestine (for Giardia, small bowel malabsorption) or colon (for microscopic colitis) might be necessary. Small intestine imaging might be required to rule out Crohn’s disease. Other imaging procedures such as computed tomography (CT) or magnetic resonance imaging (MRI) scan may be justified in very selected patients with severe symptoms not responding to therapy, and patients whose symptoms appear to worsen over time. However, none of these can be considered routine diagnostic measures. If clinically indicated, lactose intolerance should be excluded by breath test or an exclusion diet.

Treatment

General measures

The management approach in patients with IBS is summarised in Figure 9.1. It is most important to address the patient’s needs and to match their individual requirements with the management strategy. Ultimately, it must be recognised that a proper clinical assessment and carefully selected diagnostic measures are important to reassure the patient. Thus, theoretically while the decision to use a specific diagnostic test can be based simply upon the clinical presentation (symptoms, age, family history), this decision making should also address the patient’s needs in order to avoid over- or under-treatment.

FIGURE 9.1 Management of patients with irritable bowel syndrome (IBS). After establishing the working diagnosis, the predominant symptom is used to guide therapy. It is of crucial importance to determine and tailor the management approach based upon the primary reason for consultation (i.e. a patient concerned about symptoms may require a different management approach compared with a patient with severe symptoms dramatically impairing quality of life).

5-HT = serotonin; IBS = irritable bowel syndrome.

* e.g. Alosetron, currently available in the USA with strict restrictions due to the risk of ischaemic colitis

# Only if clinical trial data on efficacy and safety are available for the respective plant extract or the combinations available

For a large proportion of patients, explanation of the causes of symptoms, the underlying mechanism and reassurance are probably the most important elements of treatment. Patients with mild or infrequent symptoms that do not affect quality of life may not need any further measures. On the other hand, patients who are anxious, depressed and suffer from the fear that an incurable malignancy is causing the symptoms, require, as an important ‘therapeutic step’, diagnostic work-up to address this concern. In fact, in these patients a colonoscopy might be considered, even if they are below the age of 50 and the risk of malignancy is excessively low, in order to provide reassurance.

General advice to patients should also include dietary recommendations. Foods that trigger symptoms should be identified and systematically avoided. A logbook to document meals and symptoms might be helpful for this purpose. Alternatively, a systematic elimination diet can be attempted. In patients with diarrhoea and bloating, artificial sweeteners sometimes contribute to the manifestation of symptoms. Thus, advice should be given to avoid (at least temporarily) nutrients and sweets with large amounts of artificial sweeteners (including soft drinks, and chewing gum, if used extensively). However, there is currently no diet that has been proven to cure IBS. Removal of foods that have high IgG responses may improve symptoms in a sub-group of patients but remains to be better tested.

IBS is a chronic or relapsing condition. Probably with the exception of fibre, medication should be only used temporarily and doses reduced or drugs discontinued as soon as possible. However, it needs to be acknowledged that a proportion of patients requires long-term maintenance therapy.

Fibre (bulking agent)

Soluble fibre has been shown to affect bowel transit time but trials in IBS have provided conflicting evidence. However, in clinical practice small amounts of fibre or a fibre supplement (e.g. psyllium) are added to the diet. Exposure of these patients to large amounts of fibre should be avoided since excess fibre can cause bloating. However, it needs to be emphasised that it is a common clinical experience that many patients consuming ‘standard doses’ of fibre improve if doses are reduced. Thus, as a general rule fibre should be introduced in very small doses.

Antispasmodics

Use of antispasmodics (e.g. hyoscine, mebeverine) or peppermint oil may help some patients suffering from cramps or diarrhoea.

Anti-constipation agents

In patients with constipation (not responding to fibre), osmotic laxatives can be helpful. Polyethylene glycol (PEG) can be helpful for constipation. Lubiprostone is a chloride channel activator that also improves constipation. The 5-HT₄ agonist, tegaserod, has demonstrated modest superiority over placebo.

Antidiarrhoeals

From randomised trials, it can be concluded that loperamide improves diarrhoea but not pain. Cholestyramine may help some cases. Alosetron, a 5-HT₃ receptor antagonist, is not available in many countries and its use has been restricted because of the potential risk of ischaemic colitis. However, in clinical trials its superiority was clearly demonstrated over placebo and the antispasmodic mebeverine.

Alternative therapies

In IBS, acupuncture is no better than placebo. Psychological interventions are controversial and there are many issues in relation to study design. However, psychological interventions are probably efficacious. Traditional Chinese herbal remedies/treatments have been found in one controlled trial to be superior to placebo, but further trials are needed to confirm this finding and it cannot be concluded that all traditional Chinese medicines are efficacious.

Alterations of enteric flora may play a role in irritable bowel syndrome. There is emerging evidence that bacterial overgrowth exists in a subgroup of patients. These patients are usually characterised by bloating and abdominal distension. While antibiotic treatment or probiotics appear to improve symptoms, little is known about the long-term outcome.

In patients with pain that does not respond to the above-mentioned measures, low-dose tricyclic antidepressants can be recommended, which appear to be beneficial in a subset of patients.

Long-term prognosis

The life expectancy of patients with IBS is normal. Many patients improve over time and will become asymptomatic. However, it needs to be acknowledged that, in a proportion of patients, all the above-mentioned measures fail. Multimodal therapeutic approaches involving pain specialists and clinical psychologists can sometime improve the situation in these patients.

Perspective

IBS is a syndrome most likely due to various underlying pathophysiologies. There is no treatment that cures this condition. The high prevalence of this condition and the resulting implications for the healthcare system are significant. Better understanding of the pathophysiology will hopefully provide the opportunity to develop more effective treatments that ultimately will lead to cure.

SUMMARY

Irritable bowel syndrome (IBS) is a highly prevalent condition affecting 15% of the population. IBS is defined by chronic or relapsing abdominal symptoms (abdominal pain and/or discomfort) associated with an abnormality of bowel movements (diarrhoea and/or constipation) in the absence of structural lesions. In younger patients (<50 y), if there are no alarm symptoms (e.g. weight loss, per anal blood loss), the diagnosis can usually be made with no additional testing. Communicating the diagnosis and explaining the implications for the prognosis and future management is key for optimal treatment. Based upon the severity of symptoms and the severity of impairment of quality of life, no further therapeutic measures may be required in a subgroup of patients once the diagnosis has been established. A large proportion of patients with IBS suffer from concomitant anxiety or depression. Thus there is frequently the fear of an underlying catastrophic disease as the cause of the symptoms. In this context, further diagnostic measures may need to be done to reassure the patient. Proper dietary assessment and advice can sometimes help identify triggers for symptoms. Pharmacotherapy targets the dominant symptoms but is not disease modifying. Low doses of tricyclic antidepressants may be used in subjects not responding to standard therapy.

FURTHER READING

American Gastroenterological Association. Medical position statement: irritable bowel syndrome. Gastroenterology. 2002;123:2105-2107.

Bueno L, de Ponti F, Fried M, et al. Serotonergic and non-serotonergic targets in the pharmacotherapy of visceral hypersensitivity. Neurogastroenterol Motil. 2007;19(1 Suppl):89-119.

Halvorson HA, Schlett CD, Riddle MS. Postinfectious irritable bowel syndrome—a meta-analysis. Am J Gastroenterol. 2006;101:1894-1899. quiz 942

Heading R, Bardhan K, Hollerbach S, et al. Systematic review: the safety and tolerability of pharmacological agents for treatment of irritable bowel syndrome—a European perspective. Aliment Pharmacol Ther. 2006;24:207-236.

Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130:1480-1491.

Mayer EA, Tillisch K, Bradesi S. Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease. Aliment Pharmacol Ther. 2006;24:919-933.

Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome—etiology, prevalence and consequences. Eur J Clin Nutr. 2006;60:667-672.

Park JM, Choi MG, Park JA, et al. Serotonin transporter gene polymorphism and irritable bowel syndrome. Neurogastroenterol Motil. 2006;18:995-1000.

Riordan SM, Kim R. Bacterial overgrowth as a cause of irritable bowel syndrome. Curr Opin Gastroenterol. 2006;22:669-673.

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