Professor Humphrey J. O’Connor MD FRCP AGAF, Trinity Academic Gastroenterology Group, Trinity Centre for Health Sciences, Tallaght University Hospital, Tallaght, Dublin 24
email: oconnor_hj@hotmail.com
Introduction
When you think about it, the gut is a marvellous machine! Simply eating food automatically sets the machine in motion and all being well we are blissfully unaware of digestion without pain, wind, or noise. In the lower gut, a feeling of rectal fullness disappears once defaecation is complete. The whole process of digestion critically depends on normal gut-brain contact with continuous crosstalk between the automatic nervous system within the gut, the Enteric Nervous System (ENS), and the Central Nervous System (CNS). If for whatever reason, at brain or gut level, that crosstalk between the ENS and CNS becomes disturbed or dysregulated the end result can be the development of a Disorder of Gut Brain Interaction (DGBI). Irritable Bowel Syndrome (IBS) is the commonist DGBI and perhaps the most troublesome. IBS is defined as a syndrome of recurring abdominal pain at least one day per week in the last three months related to defaecation and associated with a change in bowel habit. Other symptoms of IBS can include excess wind, bloating and a feeling of incomplete rectal emptying.
IBS is very common affecting about 1 in 10 people, causes a significant negative impact on quality of life, social life and work productivity, and is associated with increased medical costs and healthcare utilisation. For unknown reasons, IBS is far commoner in women than men (7 of 10 patients) and women also bear the brunt of the condition with more severe symptoms, more comorbid somatic symptoms and increased need for second line medications. IBS is arbitrarily defined by the predominant disturbance in bowel habit. About 10 to 20% of patients have IBS Diarrhoea, 10 to 20% have IBS Constipation, and the majority of patients are IBS Mixed. The IBS subtype has an important bearing on the choice of treatment options. Nearly 40% of primary care and gastroenterologist visits can be attributed to IBS. Long-term, about a third of patients with IBS improve and symptoms disappear, symptoms remain unchanged in 30 to 50%, but can worsen in about 20%.
Diagnosis
It is important to remember that the majority of IBS patients are diagnosed and managed in primary care. The diagnosis of IBS is primarily based on patients having appropriate symptoms of abdominal pain and altered bowel habit and normal results in a limited number of tests. One of the dilemmas faced by IBS patients is their multiple symptoms, feeling so unwell, and yet all tests are normal. There is no specific test or biomarker for IBS but at the same time doctors and patients do not want to miss a serious or organic disease masquerading as IBS, particularly cancer. Basic tests can be summarised as the four C’s, Complete or full blood count, C reactive protein, Coeliac serology (tTg antibody) and faecal Calprotectin. Thyroid function tests are often added to this list. This set of tests will help exclude inflammatory bowel disease, microscopic colitis, coeliac disease and hyper or hypothyroidism.
The need for invasive tests such as colonoscopy or scans is driven by the presence of “red flag symptoms” such as night waking, weight loss or non-hemorrhoidal rectal bleeding, and patient age. Current guidelines use an age cut-off of 45 or 50 years for colonoscopy but factors such as family history of colorectal cancer or patient worries and wishes should be respected. Another recent concern is the inexplicable and genuine rise in young-onset colorectal cancer, particularly in women, and this phenomenon might also lower the age threshold for colonoscopy.
Long-term follow up of patients positively diagnosed with IBS is reassuring with only rare development of organic disease. Hence, although symptoms might persist and even change over the years, repeat testing should be avoided. Extensive and fruitless investigations only serve to undermine patients confidence in the diagnosis of IBS and in their healthcare provider. The fact that IBS does not increase the risk of colorectal cancer should also be emphasised.
Treatment
It is in the treatment of IBS that the word “Personalised” really becomes important. A good doctor-patient relationship is important in all aspects of clinical medicine but is paramount in the management of IBS. Dedicated time is needed in clinic to appreciate what are the patients’ predominant symptoms, concerns and preferences, previous treatments, and possible psychological comorbidities. Equally, time is needed to educate and explain to patients in plain language and diagrams the nature of IBS as a brain-gut disorder and the role of factors such as lifestyle, diet, stress, and gut bacteria etc. For many patients, education and the reassurance of normal test results as outlined above, coupled with lifestyle and dietary interventions are enough to ease symptoms and improve quality of life. Increased exercise, healthy eating habits and reduced intake of alcohol, caffeine, fat and spicy or gas-producing foods have all been shown to have beneficial effects on IBS symptoms.
If medication is needed for mild to moderate IBS, the choice is largely driven by the predominant symptoms. Antispasmodics including mebeverine or alverine, the anticholinergic hyoscine, or peppermint oil have all been shown to have some impact on the pain of IBS and can be used as necessary. Water soluble fibre such as ispaghula or the osmotic laxative polyethylene glycol can help constipation. Loperamide is an effective antidiarrhoeal agent but does not improve overall IBS symptoms and again can be used as necessary.
Dietary Therapy
In a recently published study from the Netherlands on treatment preferences, IBS patients showed a strong preference for dietary intervention (48%) compared with pharmacological therapy (29%) or psychotherapy (23%). Since its introduction from Melbourne Australia over a decade ago, low FODMAP diet (LFD) has become the diet of choice worldwide in the management of IBS. LFD works on the premise that Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols are responsible for IBS symptoms by, among other things, creating an osmotic load in the small bowel and increasing colonic gas production. The upshot of at least ten clinical trials suggests LFD can give effective symptom relief in about 50 – 70% of IBS patients and all IBS subtypes can show response with IBS Diarrhoea most favourable. In practice, patients firstly eliminate FODMAPs for an arbitrary 2-6 weeks to assess response. If symptom response is good foods are gradually reintroduced to ultimately personalise the diet to the minimum numbers of FODMAPs that need to be avoided. Personalised advice from a dietitian and providing written instructions have been shown to increase compliance and success.
LFD comes with a number of caveats. We have very little long-term data on the effects of LFD and concerns have been raised about its nutritional adequacy and the reduction in fibre intake. We are also only beginning to assess combination treatments, for instance, LFD with prebiotics or probiotics, or LFD with psychological treatments.
Probiotics and Antibiotics
The human microbiome, the microorganisms that inhabit the gut, has received enormous attention in recent years with the realisation that a “good” microbiome is essential for health whereas a “disturbed” microbiome might contribute to ill health, including IBS. The fact that by-products of microbiome metabolism might actually interact with the ENS and play a role in brain-gut crosstalk has added further interest. Our colleagues at University College Cork have been to the forefront of this cutting edge research. By putting live microorganisms into the gut, probiotics are designed to improve the microbiome. At least 50 clinical trials have tested the effects of probiotics in IBS. On balance, probiotics have been shown to improve global symptoms as well as bloating and excess wind. However, no solid recommendation can be given at this time on what particular strain or formulation of probiotic is best, or the subtype of IBS most likely to respond.
Ironically, antibiotics which might diminish the microbiome have also shown efficacy in IBS. Clinical trials of Rifaximin, an oral broad-spectrum minimally absorbed antibiotic, have shown good effect particularly in non-constipated IBS. The course of Rifaximin lasts two weeks and can be repeated.
Moderate to Severe IBS
About 20% of IBS patients have really troublesome symptoms poorly responsive to first line treatments and dietary changes and will usually be attending a gastroenterology clinic. Added to their bothersome IBS symptoms many of these patients will have other gastrointestinal symptoms, extra intestinal symptoms apparently emanating from several organ systems, and psychological problems (Figure). In clinical practice, the most commonly reported extraintestinal problems include chronic fatigue, fibromyalgia, poor sleep, low back pain, chronic pelvic pain, dysuria, and dyspareunia (Table 1). A history of anxiety, depression or panic disorder is common enough in this group of patients but the extraintestinal symptoms can occur in the absence of mood disorder. On direct questioning some patients will give a history of unresolved childhood abuse. In this setting IBS is aptly described as a BioPsychoSocial disorder disorder and difficult to judge whether treatment should be directed to the brain or gut or both.
Gut
With greater understanding of the ENS over the past decade, the pharmaceutical industry has developed targeted oral treatments that act at gut level to help difficult IBS constipation or diarrhoea. Prucalopride (Resolor), linaclotide, plecanatide and lubiprostone are all prosecretory agents which have been shown to ease the symptoms of IBS Constipation. At present prucalopride is the only one of these medications available on prescription and perhaps the availability of the other agents is delayed for pharmacoeconomic reasons with linaclotide available on a named patient basis. Eluxadoline, a opioid receptor agonist, has proven efficacy in the management of IBS diarrhoea but again is not available on prescription in Ireland.
In difficult IBS Diarrhoea, it is worth remembering idiopathic bile acid diarrhoea (BAD) as a possible contributor to urgent watery stools and a real risk of faecal incontinence. In idiopathic BAD, increased bile synthesis seems to overpower absorptive capacity in the ileum, with consequent excess colonic bile acids which increase colonic motility, water secretion and mucosal permeability. Diagnostic tests are available for BAD but sometimes an easier alternative is a treatment trial of a bile acid binder medication such as cholestyramine or colesevelam. A favourable response to these medications is tantamount to a positive diagnostic test.
Brain
Faced with difficult poorly responsive IBS, gastroenterologists have increasingly turned to treatment with low dose psychotropic agents, originally developed to treat psychological or psychiatric disorders. Before prescribing, open discussion is needed to reassure the patient that he or she is not being stigmatised with IBS as a psychiatric disorder and to explain potential medication benefits and risks. Sedation is the most common side effect but unwanted weight gain should also be mentioned. Low dose amitriptyline or nortriptyline are particularly useful in the management of IBS diarrhoea or IBS mixed. 10mg at bedtime also helps poor sleep and responders usually feel clinical benefit within a week or two. Nortriptyline may be less sedating than amitriptyline. Patients should be asked to promptly report side effects and a planned follow up contact at two weeks is very beneficial for a good trusted doctor-patient relationship in the long-term. If a patient has not responded to 10mg of amitriptyline or nortriptyline after two weeks and has not had any side effects, continue 10mg for longer rather than increase the dose as cumulative benefit can occur over time. Increased dose potentially invites more side effects but on occasion the dose can escalate to 50mg daily. If a patient is doing well, treatment should continue for six to twelve months on the premise that a longer course might reduce the chance of symptom recurrence when the medication is slowly withdrawn. Tricyclic antidepressants tend to be avoided in patients with IBS constipation and a treatment trial of a low dose selective serotonin reuptake inhibitor, escitalopram at 5 to 10mg, is an alternative choice in that setting. Other related agents include mirtazapine 15mg at night for IBS Diarrhoea and functional dyspepsia and low dose duloxetine 30mg for abdominal pain and IBS Constipation.
Psychotherapy
A variety of different psychological treatments are effective in the management of IBS including cognitive behavioural therapy, gut-directed hypnotherapy, relaxation therapy, multicomponent psychological therapy and dynamic psychotherapy. Younger patients more often prefer psychotherapy than older patients and at least one study has shown gut-directed hypnotherapy worked best in young female IBS patients with associated anxiety. The practical difficulty in psychological therapies is limited availability, high costs, and the difficulty of weekly appointments. Some of those difficulties may be overcome by mobile Apps such as Nerva which delivers a self-administered gut-directed hypnotherapy programme at home. In an ideal world, the clinic setting for difficult IBS would combine the services of a gastroenterologist, a specialist dietitian, and gastrointestinal psychotherapist.
Conclusions
IBS is a common, often troublesome DGBI that creates a multiplicity of symptoms both within and outside the gut. IBS disimproves quality of life and increases healthcare seeking. The burden of IBS falls very much on women more than men. Management of IBS calls for a personalised doctor-patient relationship that can deliver empathy, explanation, a measured diagnostic workup, and effective safe therapy mindful of the patients condition and preferences. In essence, optimum care of IBS patients requires an effective holistic approach that truly combines the science and art of medicine.
References on request
