Answers

Short answers

1 Irritable bowel syndrome with predominance of diarrhoea.

2 The Rome III criteria encourage clinicians to make a positive diagnosis of irritable bowel syndrome on the basis of validated symptom criteria rather than make a diagnosis of exclusion. Tests recommended by National Institute for Health and Clinical Excellence (NICE) guidelines are a full blood count, erythrocyte sedimentation rate or plasma viscosity, C reactive protein, and antibody tests for coeliac disease (endomysial antibodies or anti-tissue transglutaminase).

3 The presence of alarm signs warrants further evaluation. Such signs include rectal bleeding, short history of symptoms, documented weight loss, nocturnal symptoms, male sex, family history of colon cancer, recent use of antibiotics, and age greater than 50 years.

4 Treatment relies on a strong doctor-patient relationship and pharmacotherapy aimed at symptom control. New drugs include lubiprostone, a selective C₂ chloride channel activator, for the treatment of irritable bowel syndrome with constipation, and alosetron, a 5HT₃ antagonist, for the treatment of irritable bowel syndrome with diarrhoea.

Long answers
1 Diagnosis
Irritable bowel syndrome is defined as a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit; features of disordered defecation are also present.¹ The prevalence is 9-12% in the Western world,² and most studies show a female predominance.^{2 3} Even though altered rectal perception has been proposed to be a biological marker of the syndrome,⁴ the diagnosis still relies on diagnostic criteria.

The new Rome III criteria categorise patients with irritable bowel syndrome exclusively on their stool form.^{5 6} This change is based on studies showing that most patients have a normal stool frequency, and that straining, urgency, and incomplete bowel emptying may be present regardless of stool form. The Rome III committee advised that researchers and practitioners use the Bristol stool form scale to divide patients into one of four subgroups—irritable bowel syndrome with constipation, with diarrhoea, with a mixed subtype, and without a subtype; constipation is defined as hard or lumpy stools, and diarrhoea as loose, mushy, or watery stools.

2 Further investigations
The diagnosis is not always straightforward for several reasons—irritable bowel syndrome has no consistent biological marker, so clinicians have to rely on symptoms to make the diagnosis; the symptoms are often difficult to measure objectively; and many organic conditions can masquerade as irritable bowel syndrome. The last fact is the most troubling to clinicians and patients, many of whom are worried that alternative diagnoses have been overlooked (such as colon cancer, inflammatory bowel disease, microscopic colitis, infectious colitis, small intestinal bacterial overgrowth, coeliac disease, and surreptitious laxative abuse). This uncertainty often prompts clinicians to approach irritable bowel syndrome as a diagnosis of exclusion, by performing tests to exclude alternative aetiologies.

However, the Rome III criteria encourage clinicians to make a positive diagnosis on the basis of validated symptom criteria and emphasise that irritable bowel syndrome is not a diagnosis of exclusion.¹ This recommendation is based on extensive evidence that diagnostic tests have a low yield in patients who fulfil the Rome criteria but lack alarm signs or symptoms. One study showed that Rome criteria symptoms have a positive predictive value of 98% for diagnosing irritable bowel syndrome.³ In other words, 98% of patients with Rome criteria symptoms have the syndrome, rather than an underlying organic condition, after undergoing standard evaluations.

The irritable bowel syndrome task force of the American College of Gastroenterology recommends that, in young patients without alarm features, irritable bowel syndrome can be diagnosed clinically and additional investigations such as laboratory tests are not needed.⁷ However, in practice, most clinicians would order a full blood count, C reactive protein, erythrocyte sedimentation rate, and serological testing for coeliac disease, particularly in patients with diarrhoea predominant or mixed diarrhoea-constipation disease, according to national guidance from NICE.⁸ A study from Leeds found that only 3.3% of patients with irritable bowel syndrome in general practice in the United Kingdom did not have irritable bowel syndrome but had coeliac disease.⁹

3 Alarm symptoms
Symptoms that are common in irritable bowel syndrome but not part of the diagnostic criteria include bloating, abnormal stool form (hard or loose), abnormal stool frequency, straining at defecation, urgency, feeling of incomplete evacuation, and the passage of mucus per rectum.¹⁰ Most patients have intermittent symptoms, with flares lasting two to four days followed by periods of remission.

Alarm features in irritable bowel syndrome that warrant further investigation include:

• Age >50 years
  
• Documented weight loss
  
• Male sex
  
• Anaemia
  
• Recent antibiotic use
  
• Short history of symptoms
  
• Nocturnal symptoms
  
• Family history of colon cancer
  
• Rectal bleeding.
  

4 New treatments in irritable bowel syndrome
These new agents are potentially toxic, so most gastroenterologists would ensure other conditions are excluded before starting treatment.

Serotonin affects gastrointestinal motility, secretion, and visceral sensitivity, all of which are altered in patients with irritable bowel syndrome. Drugs designed to target key serotonin receptors in the gastrointestinal tract, including 5-HT₃ receptor antagonists (such as alosetron) and 5-HT₄ receptor agonists¹¹ (such as tegaserod, recently withdrawn), improve many symptoms of irritable bowel syndrome.

Alosetron was significantly better than placebo at improving individual symptoms (such as bowel urgency and abdominal pain) of irritable bowel syndrome with diarrhoea, as well as a global symptom score (irritable bowel syndrome global improvement scale).The most commonly reported adverse effects during clinical trials were constipation (alosetron 29% v placebo 6%), abdominal pain or discomfort (7% v 4%), and nausea (6% v 5%).¹² Constipation generally occurred as single episodes during the first month of treatment and resolved either on its own or after an interruption in treatment.¹³ Ischaemic colitis and serious complications related to constipation were reported. Alosetron has a restricted indication for women with severe irritable bowel syndrome with diarrhoea who have not responded to conventional treatment and in whom anatomical and biochemical abnormalities have been excluded.

Lubiprostone (a prostaglandin E1 derivative bicyclic fatty acid) acts as a chloride channel opener, increasing intestinal fluid secretion and thereby softening stools, promoting bowel movement, and decreasing bloating and abdominal pain.¹⁴

Patient outcome

The patient was reassured and given an explanation of the pathophysiology of irritable bowel syndrome. She was started on loperamide to reduce her stool frequency and was taught how to titrate the dose herself. A full blood count, thyroid function test, serological tests for coeliac disease (tissue transglutaminase), and inflammatory markers were performed after the initial consultation. At review six weeks later, her blood tests were found to be normal. At this time she was less troubled by her symptoms and much less anxious about her condition. The ability to titrate her dose of loperamide herself allowed her to increase her social engagement.

Cite this as: BMJ 2009;339:b3369