Irritable bowel syndrome and how to avoid them

As William Osler emphasised: “It is much more important to know what sort of a patient has a disease than what sort of a disease a patient has”. Multiple medically unexplained symptoms are a common feature in patients who have IBS, which can lead to multiple referrals to non-gastrointestinal specialists. This may reflect abnormal processing of sensory signals, which is a feature of somatization disorder. This can be easily assessed using the Patient Health Questionnaire-12 somatic symptom (PHQ-12SS) scale, which asks about non-gastrointestinal symptoms such as bodily pains and symptoms. Less than 5% of healthy controls score more than 6 on the PHQ-12SS scale, while 67% of IBS patients do.⁴ High scores predict more visits to the primary care physician and are clinically useful. Low scores are most atypical and should suggest that an alternative diagnosis needs to be excluded. Ignoring this feature results in multiple referrals to non-gastrointestinal specialists and is a very likely cause of the excess of hysterectomies and cholecystectomies seen in IBS patients.⁵

Setting expectations is an important part of any consultation. Patients who meet IBS criteria in the absence of any alarm features have a very high probability that investigations will yield normal results, so it is important to make this clear to the patient before ordering tests. In this setting, when test results turn out to be normal, the soundness of the diagnosis will be apparent to the patient. By contrast, if no prior diagnosis has been made, then a negative test may simply lead to the demand for more tests, an all-too-common feature of many IBS patients’ medical ‘careers’.

While dietary management of IBS has been widely adopted with considerable success, ⁶ encouraging food exclusion does have risks. Patients fail to appreciate that the exclusion phase of the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is only supposed to last 4-8 weeks and followed by a period of systematic reintroduction of foods to confirm apparent intolerance.⁷ Unless supervised by a dietician who understands the composition of different foods this can , this can lead to ever more restricted diets and potentially malnutrition. It is important to recognise the features of those at risk of developing eating disorders, such as self induced vomiting, self perception as fat and food dominating lifeself-induced vomiting, self-perception as fat and food-dominating life, something that can be easily quantified using the SCOFF questionnaire.⁸ A recent survey⁹ identified around 1 in 4 of IBS patients referred for a low FODMAP diet had abnormal SCOFF scores(9). These patients lose weight by excluding more and more foods as they try to link flares of IBS symptoms with particular foods. It is vital to explain to patients that flares should only be attributed to foods if the response can be reproduced on more than one occasion. It is also important to test these foods again after an interval—in many cases double blind, a double-blind challenge later shows these foods do not cause symptoms and that the flare was due to other uncontrolled factors. As previously documented with gluten exclusion, a strong nocebo effect¹⁰ can lead to these beliefs being self-perpetuating, so supervision of such exclusion diets by a dietician is helpful to avoid patients developing a nutritionally inadequate diet.

Taking a careful dietary history is important before any dietary recommendations are made. Many patients already restrict their consumption of dairy products and there is little point in doing a lactose tolerance test on someone who consumes <240ml of milk or its equivalent per day. A randomised, blinded trial showed that this amount of milk could not be distinguished from a lactose-free placebo, even in those with true lactose malabsorption.¹¹ More recent studies demonstrate that symptoms developing after a lactose challenge are dose-dependent: only 3% of those with genetically determined lactose malabsorption developed symptoms with a 10 g lactose challenge, rising to 21.7% of patients challenged with 20 g lactose and 73.3% of patients challenged with 40 g lactose.¹² IBS patients, however, show more symptoms after each dose, regardless of its size, indicating a degree of visceral hypersensitivity. It is also worth noting the strong nocebo effect of challenging IBS patients with foods they believe they are intolerant of¹⁰. Thus, until underlying beliefs have been changed, little progress can be expected.

Bloating is reported as the most troublesome symptom in over 1/3 of patients with IBS-C and M though rather less for those with IBS-D.¹³ It is a condition that is mysterious to many patients and physicians and often leads to unnecessary investigations and considerable irradiation. Two types of bloating need to be recognised. The first involves a sensation of distension without any obvious change in girth and is thought to reflect increased visceral sensitivity.¹⁴ The second is characterised by visible distension that requires loosening of clothes and an increase in abdominal girth, something that usually worsens during the day and remits overnight.¹⁵ Until recently, it was unclear how even a mouthful of food could induce a sudden distension of the abdomen. We now recognise, however, that this very characteristic and diagnostically helpful feature is due to a combination of relaxation of the abdominal wall and lowering of the diaphragm.¹⁶ This neural response can occur within seconds. Bloating thus does not involve any acute change in abdominal contents. As an increasing amount of abdominal fat is a frequent cause of a slow, progressive increase in abdominal distension, recent weight gain should be specifically enquired for in such patients. Ovarian cancer can also present with progressive distension, but in this case, the day-to-day variability characteristic of IBS is lacking.

If excessive amounts of bile acids enter the colon, they activate the bile acid receptor TGR5 resulting in increased colonic permeability, stimulation of water and mucus secretion and inhibition of apical anion exchange.¹⁷ Colonic motility is also directly stimulated via TGR5 receptors on enteric nerves causing frequent loose stools associated with a sensation of urgency, often accompanied by nocturnal diarrhoea. A recent meta-analysis indicates that almost one in four IBS patients meeting the criteria for IBS with diarrhoea have bile acid malabsorption.¹⁸ The most sensitive and specific test for bile acid malabsorption remains the 7-day retention of Selenium-75-labelled homocholic acid taurine (75SeHCAT). If retention at 7 days is <5%, the test predicts a 100% response to colestyramine, while 5–10% retention predicts a response of around 37%.6 Since the 75SeHCAT test is not available worldwide, alternative blood tests have been suggested, as has the simpler therapeutic trial of colestyramine; however, such trials are less reliable as they are influenced by many other uncontrolled factors like diet and emotion. Alternative assessments include measuring serum levels of 7-alpha-hydroxy-4-cholesten-3-one (C4), which is a key intermediary in bile acid synthesis from cholesterol, faecal bile acids and serum FGF19, which is a signalling molecule that normally provides negative feedback to inhibit bile acid synthesis; however, these tests are only available routinely in a few laboratories, though this may change in the future.¹⁷

All new cases meeting the Rome III criteria for IBS-D should have, as a minimum, a full blood count, serological test for coeliac disease and a faecal calprotectin measurement to exclude inflammatory bowel disease (IBD). An ileocolonoscopy should be performed for those with abnormal results or for other reasons, such as a family history of IBD or weight loss. If symptoms are chronic and unchanged since a previous normal colonoscopy, this need not be repeated unless there is evidence of systemic inflammation (raised CRP levels or platelet count) or elevated faecal calprotectin. Referred patients probably have a greater risk of having Crohn’s disease. Indeed, a large study in Canada suggested that 8.6% of patients referred to secondary care who met the Rome III criteria turned out to have Crohn’s disease.¹⁹ Community studies indicate that patients who have colonic Crohn’s disease can have symptoms for many years prior to diagnosis²⁰ and are often labelled as having IBS since they lack the key alarm features of rectal bleeding and weight loss. Faecal calprotectin has high sensitivity and specificity for IBD,²¹ as may a full blood count showing an elevated platelet count or microcytosis.²²

Although the pain in patients with IBS is often described as extremely severe and opiates are undoubtedly effective, most clinicians strongly advise against their use because receptor desensitisation occurs rapidly, leading to rapid dose escalation. High doses of opiates are associated with troublesome side effects, including nausea and vomiting, as well as profound constipation and drug dependence.²³ While IBS symptoms are usually intermittent, opiate use is constant. In a subgroup of susceptible patients who often have psychological comorbidities, opiate use may result in ‘narcotic bowel syndrome’, in which the opiates appear to actually aggravate the pain. Opiate withdrawal is difficult owing to psychological dependence but can result in marked remission of pain. An opiate withdrawal programme aided by centrally acting neuromodulators, including tricyclic antidepressants and clonidine have been recommended.²⁴

By contrast, peripherally acting μ-opioid receptor antagonists such as loperamide are effective in controlling diarrhoea and urgency and do not run the risk of causing dependency. However, loperamide has no effect on pain or bloating, and being widely available, most patients will have already tried and failed it before consulting a medical practitioner. More recently eluxadoline, a peripherally acting μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, has also been shown to be moderately effective in IBS-D, though because of a 0.4% risk of pancreatitis and 0.5% incidence of sphincter of Oddi spasm, it should not be given to patients with cholelithiasis, prior cholecystectomy or alcoholism.²⁵

The pain in patients with IBS is poorly localized but may, in some cases, be right upper quadrant pain, which can be confused with biliary pain. Patients with IBS have approximately double the prevalence of cholecystectomy, suggesting misdiagnosis is common.²⁶ Relief on defecation may help distinguish the two. The pattern of pain is also helpful: biliary pain is typically very episodic with weeks of freedom, whereas IBS pain is associated with only a few days free from pain before the next flare occurs. Of those with gallstones who undergo laparoscopic cholecystectomy, outcomes are worse for those with pre-existing IBS, particularly those with loose bowel movements at the onset of their abdominal pain.²⁷ This may, in part, reflect the increase in faecal bile acids which occur after cholecystectomy.²⁸

IBS patients also have an increased risk of appendectomy, hysterectomy and back surgery, often with no benefit to the symptoms.²⁹ Paying careful attention to the Rome criteria, especially relief on defecation or association of pain with changes in bowel habit, should help distinguish IBS from other causes of lower abdominal pain. Likewise, multiple somatic complaints should also point towards a diagnosis of IBS⁴ rather than a specific surgically remediable cause. Once abdominal surgery has been performed, there is a very real risk of developing adhesions, further confusing the diagnosis and hindering management.

Amitriptyline has been widely used as an adjunct for pain relief for a range of conditions such as backache, neuralgia, migraine and IBS, but it is only just recently that a large trial showed benefit in unselected IBS patients consulting in primary care.³⁰ The study used tritrated dosing from 10-30mg taken before sleep to reduce the incidence of side effects like drowsiness. The benefit was significant at both 3 and 6 months, with a slightly greater difference from placebo at 6 months, making the point that the effect does take time to develop. The most common mistake is to use the much higher doses recommended for depression (150-300mg), which often lead to lethargy, tiredness and sleepiness during the day, which is unacceptable to most patients. When allowed to self-titrate, around 1/3rd of patients used just 10mg, with 1/3rd taking 20mg and the remainder 30mg. Some patients can even manage on 5mg or 10mg alternate nights. IBS patients are hypersensitive to many stimuli, including drug side effects, so using the lowest dose possible is often necessary.