Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a relapsing bowel disorder in which abdominal pain is associated with defecation or a change in bowel habit. Bloating and distension are often also accompanying symptoms. IBS is defined by symptom-based diagnostic criteria, in the absence of detectable organic causes. The symptoms are not specific for IBS.¹

Previously described as a functional disorder, IBS has been re-classified as a disorder of brain-gut interaction.

The diagnosis of IBS rarely alters over time, but always be prepared to reconsider the diagnosis if the clinical picture changes. IBS has a significant negative impact on quality of life and social functioning in many patients, but it is not associated with the development of serious disease or with excess mortality.²

Epidemiology

• IBS occurs in 10-20% of the population in the UK, but prevalence is thought to be higher than this as many people with the disorder do not seek medical advice.³

• A systematic review of global prevalence showed significant geographical differences (between 1% and 45%).⁴

• It is more common in women than in men, with a ratio of 1.67:1.⁵ Certain subtypes of IBS show different gender variability.

• Peak prevalence is between the ages of 20 and 30.⁶

Aetiology²

• There is no structural lesion, and no single explanation has been found to explain the condition. However, it seems to involve abnormal smooth muscle activity ± visceral hypersensitivity, and abnormal central processing of painful stimuli. The bidirectional communication between the gut and the brain is modulated by the autonomic nervous system. A reduction in parasympathetic activity and an increase in sympathetic activity is seen in many IBS patients.

• IBS is associated with increased levels of psychiatric distress and poor coping strategies.

• Between 20% and 60% of patients with IBS have enhanced visceral perception to various physiological stimuli (eg, balloon distension of the bowel).

• There can be aggregation of the condition in families and a genetic cause has been suspected. Numerous genetic single nucleotide polymorphisms have been described in IBS patients, although a meta-analysis of genes associated with inflammatory mediators found no significant associations for most genes assessed.

• Subclasses of IBS have been identified as follows:⁷

  • Approximately one third of patients have IBS with constipation (IBS-C) = loose stools <25% and hard stools >25% of the time.

  • Approximately one third of patients have IBS with diarrhoea (IBS-D) = loose stools >25% and hard stools <25% of the time.

  • The remainder have IBS-mixed (IBS-M) = both hard and soft stools >25% of the time.

• Colonic transit is abnormal in only 10-20% of patients with IBS-C and IBS-M, and 25-45% of patients with IBS-D. However, transit times do not equate to motility; increased fasting and postprandial activity has been reported in patients with normal transit times.

• Modulation by the immune system may play a part. Increased mast cell activity associated with low-grade mucosal inflammation is sometimes seen in postinfectious IBS. Confocal laser endomicroscopy studies suggest exposure to certain food antigens can disrupt the epithelial barrier in approximately 50% of patients with IBS.

• There is good evidence that bacterial, viral or parasitic infections can trigger IBS. Studies have shown antibiotics can either improve or worsen the condition. Alterations in the gut microbiome have been demonstrated. It is unclear however whether these are involved in IBS aetiology or relate to secondary factors including diet, drugs, or altered physiology including gastrointestinal transit or gastrointestinal water content.

Presentation

The British Gastroenterology guidelines acknowledge the Rome IV criteria as being the definitive source of IBS classification. Rome IV defines IBS as the presence of abdominal pain related to defecation, associated with a change in stool frequency and/or stool form. The Rome IV definition increased the frequency of abdominal pain from at least three days per month, to at least one day per week. It also removed the requirement for pain to be relieved by defecation (as some people reported it made the pain worse) and simply said it had to be 'related to defaecation'.²

The National Institute for Health and Care Excellence (NICE) considered this definition was too restrictive to be of use in clinical practice in primary care and suggests the following:

• Patients must give at least a six-month history of either:

  • Abdominal pain or discomfort.

  • Bloating.

  • Change in bowel habit.

• Consider positively diagnosing IBS only if abdominal pain is either relieved by defecation, or associated with altered bowel frequency or stool form;

  • AND at least two of the following are present:

    • Altered passage of stool (straining, urgency, incomplete evacuation).

    • Abdominal bloating (women >men), distention tension or hardness.

    • Symptoms aggravated by eating.

    • Passage of mucus rectally.

Lethargy, nausea, backache and bladder symptoms may be used to support diagnosis.⁶

Further notes on IBS features

• Most patients have abdominal pain and disordered bowel habit, continuous or intermittent. This may be predominantly diarrhoea, predominantly constipation, or alternating between the two. A 'morning rush' is common: patients feel the urgent need to defecate several times on getting up, during and after breakfast.

• Symptoms are chronic, with remissions interrupted by relapses precipitated by stress or changes in bowel flora produced by antibiotics.

• Upper gastrointestinal symptoms may include nausea, heartburn, dysphagia, and early satiety.

• Extra-intestinal symptoms such as headaches and migraine, asthma, backache, lethargy, dyspareunia, urinary frequency, and urgency are more commonly reported by patients with IBS. Psychological problems (anxiety and depression) are also more common, although some psychological morbidity appears to be associated with healthcare seeking rather than with IBS per se.

Signs

Abdominal and digital rectal examination can help exclude other diagnoses. Such assessment may confirm the consistency of stool, including rectal impaction. Dyssynergic defecation (paradoxical contraction on rectal examination during straining) or low rectal masses may be identified.

Differential diagnosis

• Colonic cancer.

• Inflammatory bowel disease (IBD): Crohn's disease, ulcerative colitis.

• Bile acid malabsorption.

• Coeliac disease.

• Gastroenteritis - eg, giardiasis.

• Diverticular disease.

• Gut neuroendocrine tumours (NETs) - eg carcinoid.⁸

• Gynaecological problems - eg, pelvic inflammatory disease, endometriosis, ovarian tumours.

• Anxiety ± depression, somatisation and panic disorders.

Investigations⁶

The diagnosis of IBS should be made positively on symptom-based criteria, NOT as a diagnosis of exclusion after ruling out organic disease by exhaustive investigation.

Carefully and sympathetically elicit a history and carry out an appropriately thorough physical examination. Ask about a family history of IBD or colon cancer, at age <50 - as this should lower the threshold for investigation/referral.

All patients meeting the symptomatic criteria for IBS should have the following investigations:

• FBC.

• ESR.

• CRP.

• Antibody testing for coeliac disease - endomysial antibodies (EMAs) or tissue transglutaminase (TTG).

• CA 125 for women with symptoms which could be ovarian cancer.⁹

• Faecal calprotectin for those with symptoms which could be IBD.³

The following tests are NOT required to confirm IBS in those who meet the diagnostic criteria:

• TFTs.

• Ultrasound.

• Colonoscopy/sigmoidoscopy/barium enema.

• Faecal occult blood.

• Faecal ova and parasite tests.

• Hydrogen breath tests.
  

Referral criteria

Refer patients in the event of diagnostic uncertainty, alarm symptoms, or severe resistant symptoms.

An urgent two-week referral is occasionally appropriate if signs and symptoms of cancer are present in line with NICE guidance on recognition and referral for suspected cancer.¹⁰

• Lower bowel investigations - colonoscopy, or sigmoidoscopy ± barium enema. A rectal biopsy may be appropriate (to diagnose IBD).

• Gastroscopy may be appropriate if upper gastrointestinal symptoms predominate.

• Gynaecological referral may help to rule out endometriosis and pelvic infection.

• Consider psychological referral if the main problems are inability to cope with symptoms.

Beware of unnecessary specialist referral and interventions - eg, hysterectomy and cholecystectomy. Referral may prolong anxiety as much as allay it.

Management^{2 6}

Having confidently made the diagnosis, reassurance and explanation are vital, including frank explanation of the likely course of disease. Many patients may have a fear of cancer, but careful and often-repeated explanations of the nature of the disease reduce this.

Lifestyle and physical activity

• Provide information about the condition and self-help, covering lifestyle, physical activity, diet and symptom-targeted medication.

• Encourage patients to identify and make best use of leisure time, and create times in the day for relaxation.

• Assess physical activity levels and give advice on increasing activity if appropriate. There is evidence that increasing physical activity has a positive effect on symptoms.¹¹

Diet

General dietary advice

• Have regular meals - ie avoid long gaps between meals and don't rush them.

• Drink plenty of fluids (at least eight cups per day) but restrict tea/coffee to three cups or so per day.

• Reduce intake of alcohol and fizzy drinks.

• Consider limiting high-fibre foods (eg, wholemeal flour or bran), and resistant starches (often in processed or recooked foods, and fresh fruits - limit to three portions per day).

• For diarrhoea - avoid sorbitol.

• For wind - consider increasing oats and linseeds (one tablespoon/day).

Fibre
Review fibre intake and adjust this in line with symptoms. Those with constipation as a predominant symptom may need to increase fibre intake, whereas those with diarrhoea may find the opposite helpful.

The results of the most recent meta-analyses of the benefits of soluble and insoluble fibre for IBS contradict each other. A Cochrane review found no benefit for either.¹² Another review, however, found a benefit for soluble fibre, as ispaghula.¹³

Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs)

There has been interest in the role of FODMAPs in causing symptoms of IBS. Foods high in FODMAPs, such as apples, cherries, peaches, nectarines, artificial sweeteners, most lactose-containing foods, legumes, and many green vegetables (broccoli, Brussels sprouts, cabbage, and peas) may have fermentation and osmotic effects, increasing symptoms. Diets low in FODMAPs have therefore been advocated in helping symptoms. There is evidence to support this approach.^{14 15 16} Up to 86% of people with IBS are said to report an improvement in symptoms, specifically bloating, abdominal pain, flatus and altered bowel habit, when using a low-FODMAP diet.¹⁷ However, some potential limitations and concerns have been raised, including nutritional adequacy, cost, and difficulty in teaching the diet and maintaining it. Most of these concerns can be addressed by involving a skilled nutritionist, who can clearly explain to the patient the different phases of the diet and ensure nutritional adequacy and compliance.¹⁸

Dietician
For those who find diet plays a significant role in their symptoms, referral to a dietician may be helpful for advice.

Probiotics
There is some evidence for probiotics being helpful in alleviating symptoms of IBS. Multi-strain probiotic supplements seem better than mono-strain supplements, but further studies are needed to make more specific recommendations about optimal regimes and products.¹⁹ NICE guidelines suggest if used, they should be taken for four weeks at the dose recommended by the manufacturer, while monitoring the effect.

Pharmacological treatments

• There is a high rate of placebo effect in IBS, even when the patient knows they are taking a placebo.²⁰

• Pharmacological options should target the individual symptoms, such as diarrhoea, abdominal spasm, bloating or constipation.

• Loperamide is the medication of choice for diarrhoea.

• Antispasmodics should be used as required for abdominal pain and spasms. A number of options are used, including alverine, mebeverine and peppermint oil.²¹

• Laxatives may be used as required for constipation. Linaclotide has recently been added to recommendations, to be considered when other laxatives have not worked and constipation has been present for 12 months. Patients should be followed up after three months. Avoid lactulose.

• Antidepressants have been shown to be of benefit, as in other chronic pain conditions. Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been shown convincingly to be effective, although studies have not been done in primary care. NICE guidelines advocate the use of an SSRI only if a low-dose TCA has not been effective. Treatment should be started at a low dose (for example, 10 mg amitriptyline) and increased if necessary to no more than 30 mg.

• Antibiotics have been shown to have a variable effect in IBS. The non-absorbable antibiotic rifaximin is an efficacious second-line drug for IBS with diarrhoea in secondary care, More research is needed.²

• 5-hydroxytryptamine 3 receptor antagonists are efficacious second-line drugs for IBS with diarrhoea in secondary care. Alosetron and ramosetron are unavailable in the UK; ondansetron titrated from a dose of 4 mg once a day to a maximum of 8 mg three times a day is a reasonable alternative (unlicensed use).

• Tegaserod (a 5-HT4 partial agonist) is an effective second-line secondary care treatment for those with constipation, but is unavailable in the UK.

• Lubiprostone, a chloride channel activator, is an emerging secondary care second-line treatment for constipation, but is unavailable in the UK.

• Eluxadoline, a mixed opioid receptor drug, will be available routinely under the NHS for the treatment of patients with irritable bowel syndrome and diarrhoea (IBS-D) from within secondary care. Eluxadoline acts by binding to specific receptors in the digestive system and slowing down the passage of food through the gut, relieving stomach cramps and the urgent need to open the bowels. Treatment should not be continued beyond four weeks, if there is no clinical response. It may be given along with existing therapies for IBS-D, including antispasmodics or hypnotherapy. It is contra-indicated in patients with prior sphincter of Oddi problems or cholecystectomy, alcohol dependence, pancreatitis or severe liver impairment.

Other therapies

• Psychological therapy is recommended by NICE. Cognitive behavioural therapy, hypnotherapy and/or psychological therapy should be considered for people with IBS who do not respond to pharmacological treatments after 12 months and who develop a continuing symptom profile (described as refractory IBS).

• NICE guidance advises against the use of acupuncture or reflexology for IBS.

• There is some evidence that herbal remedies may be of benefit. A systematic review found some support for a number of preparations but concluded that further research was needed.²²

Prognosis²³

• Symptoms fluctuate over many years. More than 50% will continue to have symptoms after seven years.

• People with a long history of IBS are less likely to improve.

• Ongoing stress may hinder recovery.

• IBS is not associated with the long-term development of any serious disease, although individuals with IBS are more likely to undergo certain surgical operations (eg, hysterectomy or cholecystectomy) than controls. Those with IBS have been shown to have an increased risk of cholecystectomy which is not due to an increased risk of gallstones.²⁴ It appears to be related to abdominal pain, increased awareness of gallstones and inappropriate surgical indications.

• The postinfective subgroup appears to have a better prognosis, with symptoms resolving in many within 5-6 years.²⁵